Association of high post-transplant soluble CD30 serum levels with chronic allograft nephropathy.

PubMed

Grenzi, Patricia C; Campos, Érika F; Tedesco-Silva, Hélio; Felipe, Claudia R; Franco, Marcello F; Soares, Maria Fernanda; Medina-Pestana, José Osmar; Gerbase-Delima, Maria

2013-12-01

The purpose of this study was to evaluate the association of post-transplant soluble CD30 (sCD30) levels, isolated or in combination with of anti-HLA class II antibodies and of serum creatinine levels, with kidney graft loss due to chronic allograft nephropathy (CAN), and type of lesions in graft biopsies for cause. The study comprised 511 first kidney graft recipients, transplanted at a single center, with a graft functioning for at least 2.8 years. A single blood sample was collected from each patient. sCD30 levels were determined by ELISA, and HLA antibodies by Luminex assay. The minimum follow-up after testing was 9.3 years. High sCD30 levels, set at sCD30 ≥ 34.15 ng/mL, the presence of HLA class II antibodies, and serum creatinine ≥ 1.9 mg/dL were independently associated with CAN-graft loss (P values <0.0001, 0.05, <0.0001, respectively), and the combined hazard ratio for CAN-graft loss was 20.2. Analyses of 166 biopsies for cause showed that high sCD30 levels and creatinine were independently associated with interstitial lesions. Post-transplant sCD30 serum levels, especially in conjunction with information regarding HLA class II antibodies and serum creatinine levels, provide valuable information regarding graft outcome and could be useful for the management of kidney transplant recipients. © 2013.

[Influence of pre-transplant serum level of soluble CD30 on the long-term survival rates of kidney transplant recipients and grafts].

PubMed

Chen, Jiang-hua; Lü, Rong; Chen, Ying; Wu, Jian-yong; He, Qiang; Huang, Hong-feng; Qu, Li-hui

2005-06-15

To investigate the influence of pre-transplant sCD30 level on the long-term survival rates of kidney transplant recipients and grafts among Chinese. A retrospective cohort of 707 patients undergoing cadaver renal transplants between Dec.1998 and Aug 2003, 467 males and 240 females, aged 40 +/- 11, with their blood samples preserved was studied. The plasma levels of sCD30 were determined by ELISA. The 5-year graft survival/functional rates of the high sCD30 group were 77.7% +/- 3.5%/85.0% +/- 3.2%, significantly lower than those of the low and intermediate groups, 84.7% +/- 2.1%/98.9% +/- 1.1% and 88.1% +/- 2.9%/95.1% +/- 1.6% respectively (all P < 0.05). The 5-year recipient survival rate of the intermediate sCD30 group was 92.4% +/- 1.6%, higher than those of the low and high sCD30 groups, 84.7% +/- 3.9% and 87.1% +/- 2.7% respectively with a significant difference between the intermediate and high sCD30 groups (P = 0.032). Pre-transplant serum level of sCD30 reflects the immune status. Recipients with high sCD30 are prone to rejection while those with low sCD30 are prone to infections.

HIERARCHICAL ORGANIZATION OF OSTEOBLASTS REVEALS THE SIGNIFICANT ROLE OF CD166 IN HEMATOPOIETIC STEM CELL MAINTANANCE AND FUNCTION

PubMed Central

Chitteti, Brahmananda R.; Cheng, Ying-Hua; Kacena, Melissa A.; Srour, Edward F.

2013-01-01

The role of osteoblasts (OB) in maintaining hematopoietic stem cells (HSC) in their niche is well elucidated, but the exact definition, both phenotypically and hierarchically of OB responsible for these functions is not clearly known. We previously demonstrated that OB maturational status influences HSC function whereby immature OB with high Runx2 expression promote hematopoietic expansion. Here, we show that Activated Leukocyte Cell Adhesion Molecule (ALCAM) or CD166 expression on OB is directly correlated with Runx2 expression and high hematopoiesis enhancing activity (HEA). Fractionation of OB with lineage markers: Sca1, osteopontin (OPN), CD166, CD44, and CD90 revealed that Lin-Sca1-OPN+CD166+ cells (CD166+) and their subpopulations fractionated with CD44 and CD90 expressed high levels of Runx2 and low levels of osteocalcin (OC) demonstrating the relatively immature status of these cells. Conversely, the majority of the Lin-Sca1-OPN+CD166− cells (CD166−) expressed high OC levels suggesting that CD166− OB are more mature. In vitro hematopoietic potential of LSK cells co-cultured for 7 days with fresh OB or OB pre-cultured for 1, 2, or 3 weeks declined precipitously with increasing culture duration concomitant with loss of CD166 expression. Importantly, LSK cells co-cultured with CD166+CD44+CD90+ OB maintained their in vivo repopulating potential through primary and secondary transplantation, suggesting that robust HEA activity is best mediated by immature CD166+ OB with high Runx2 and low OC expression. These studies begin to define the hierarchical organization of osteoblastic cells and provide a more refined definition of OB that can mediate HEA. PMID:23369988

Germination, Physiological Responses and Gene Expression of Tall Fescue (Festuca arundinacea Schreb.) Growing under Pb and Cd

PubMed Central

Lou, Yanhong; Zhao, Peng; Wang, Deling; Amombo, Erick; Sun, Xin; Wang, Hui; Zhuge, Yuping

2017-01-01

Cadmium (Cd) and lead (Pb) are recognized as the most toxic metal ions due to their detrimental effects not only to plants, but also to humans. The objective of this study was to investigate the effects of Cd and Pb treatments on seed germination, plant growth, and physiological response in tall fescue (Festuca arundinacea Schreb.). We employed six treatments: CK (nutrient solution as control), T1 (1000 mg L-1 Pb), T2 (50 mg L-1 Cd), T3 (150 mg L-1 Cd), T4 (1000 mg L-1 Pb+50 mg L-1 Cd), T5 (1000 mg L-1 Pb+150 mg L-1 Cd). Antagonistic and synergistic actions were observed in tall fescue under Pb and Cd combined treatments. Under low Cd, plants exhibited higher relative germination rate, germ length, VSGR, catalase (CAT) and peroxidase (POD) activities. Additionally, in the shoots, the gene expression level of Cu/Zn SOD, FeSOD, POD, GPX, translocation factors, MDA, EL, and soluble protein contents were reduced under Pb stress. Conversely, under high Cd level, there was a decline in NRT, Pb content in shoots, Pb translocation factors, CAT activity; and an increase in VSGR, Pb content in roots, gene expression level of Cu/ZnSOD and POD in tall fescue exposed to Pb2+ regimes. On the other hand, tall fescue plants treated with low Cd exhibited lower relative germination rate, germination index, germ length, NRT, Cd content in roots. On the other hand there was higher Cd content, Cd translocation factor, CAT and POD activities, and gene expression level of Cu/Zn SOD, FeSOD, POD, GPX under Pb treatment compared with single Cd2+ treatment in the shoots. However, after high Cd exposure, plants displayed lower NRT, Cd content, CAT activity, and exhibited higher Cd contents, Cd translocation factor, MDA content, gene expression level of Cu/ZnSOD and GPX with the presence of Pb2+ relative to single Cd2+ treatment. These findings lead to a conclusion that the presence of low Cd level impacted positively towards tall fescue growth under Pb stress, while high level of Cd impacted negatively. In summary, antioxidant enzymes responded to Cd and Pb interaction at an early stage of exposure, and their gene expression profiles provided more details of the activation of those systems. PMID:28046098

Germination, Physiological Responses and Gene Expression of Tall Fescue (Festuca arundinacea Schreb.) Growing under Pb and Cd.

PubMed

Lou, Yanhong; Zhao, Peng; Wang, Deling; Amombo, Erick; Sun, Xin; Wang, Hui; Zhuge, Yuping

2017-01-01

Cadmium (Cd) and lead (Pb) are recognized as the most toxic metal ions due to their detrimental effects not only to plants, but also to humans. The objective of this study was to investigate the effects of Cd and Pb treatments on seed germination, plant growth, and physiological response in tall fescue (Festuca arundinacea Schreb.). We employed six treatments: CK (nutrient solution as control), T1 (1000 mg L-1 Pb), T2 (50 mg L-1 Cd), T3 (150 mg L-1 Cd), T4 (1000 mg L-1 Pb+50 mg L-1 Cd), T5 (1000 mg L-1 Pb+150 mg L-1 Cd). Antagonistic and synergistic actions were observed in tall fescue under Pb and Cd combined treatments. Under low Cd, plants exhibited higher relative germination rate, germ length, VSGR, catalase (CAT) and peroxidase (POD) activities. Additionally, in the shoots, the gene expression level of Cu/Zn SOD, FeSOD, POD, GPX, translocation factors, MDA, EL, and soluble protein contents were reduced under Pb stress. Conversely, under high Cd level, there was a decline in NRT, Pb content in shoots, Pb translocation factors, CAT activity; and an increase in VSGR, Pb content in roots, gene expression level of Cu/ZnSOD and POD in tall fescue exposed to Pb2+ regimes. On the other hand, tall fescue plants treated with low Cd exhibited lower relative germination rate, germination index, germ length, NRT, Cd content in roots. On the other hand there was higher Cd content, Cd translocation factor, CAT and POD activities, and gene expression level of Cu/Zn SOD, FeSOD, POD, GPX under Pb treatment compared with single Cd2+ treatment in the shoots. However, after high Cd exposure, plants displayed lower NRT, Cd content, CAT activity, and exhibited higher Cd contents, Cd translocation factor, MDA content, gene expression level of Cu/ZnSOD and GPX with the presence of Pb2+ relative to single Cd2+ treatment. These findings lead to a conclusion that the presence of low Cd level impacted positively towards tall fescue growth under Pb stress, while high level of Cd impacted negatively. In summary, antioxidant enzymes responded to Cd and Pb interaction at an early stage of exposure, and their gene expression profiles provided more details of the activation of those systems.

Calcium Deficiency Triggers Phloem Remobilization of Cadmium in a Hyperaccumulating Species1

PubMed Central

Tian, Shengke; Xie, Ruohan; Wang, Haixin; Hu, Yan; Ge, Jun; Liao, Xingcheng; Gao, Xiaoyu; Brown, Patrick; Lin, Xianyong; Lu, Lingli

2016-01-01

Understanding cadmium (Cd) accumulation in plants is critical for the development of plant-based strategies for soil remediation and crop safety. Sedum alfredii is a nonbrassica plant species known to hyperaccumulate Cd. The characteristics of Cd uptake, distribution, and retranslocation affected by the Ca status were investigated at cellular levels in S. alfredii. Low Ca supply significantly increased Cd contents in shoots of S. alfredii, particularly in the young leaves. Micro x-ray fluorescence images confirmed that sequestration of Cd was greatly enhanced in the young leaves under Ca deficiency stress, with a significant amount of Cd localized in mesophyll cells, compared to the young leaves supplied with high Ca levels. Cd influx into protoplasts isolated from young leaves was significantly inhibited by the addition of Ca channel inhibitors, but not by pre-exposure to Ca deficiency. In stems, the Cd signal in vascular systems under low Ca levels was 10-fold higher than in those treated with higher Ca levels. A detailed investigation of vascular bundles revealed that an extremely high Cd signal induced by low Ca supply occurred in the phloem tissues, but not in the xylem tissues. Transfer of Cd pretreated plants to nutrient solutions at different Ca levels confirmed that a much higher amount of Cd was reallocated to the new growth tissues under low Ca stress compared to plants supplied with sufficient Ca. These results suggest that Ca deficiency triggered a highly efficient phloem remobilization of Cd in S. alfredii and subsequently enhanced Cd accumulation in its young leaves. PMID:27789737

Serosal Cavities Contain Two Populations of Innate-like integrin α4highCD4+ T Cells, Integrin α4β1+α6β1+α4β7- and α4β1+α6β1-α4β7+ Cells.

PubMed

Yang, Jeong In; Park, Chanho; Kho, Inseong; Lee, Sujin; Suh, Kyung-Suk; Kim, Tae Jin

2017-12-01

We previously reported peritoneal innate-like integrin α4 (CD49d) high CD4 + T cells that provided help for B-1a cells. Here we analyzed the expression of various integrin chains on the peritoneal and pleural integrin α4 high CD4 + T cells and investigated the functional heterogeneity of the subpopulations based on the integrin expression. Pleural cavity contained a lower ratio of integrin α4 high CD4 + T cells to integrin α4 low CD4 + T cells than peritoneal cavity, but the pleural integrin α4 high CD4 + T cells have the same characteristics of the peritoneal integrin α4 high CD4 + T cells. Most of integrin α4 high CD4 + T cells were integrin β1 high β7 - , but a minor population of integrin α4 high CD4 + T cells was integrin β1 + β7 + . Interestingly, the integrin α4 high β1 high β7 - CD4 + T cells expressed high levels of integrin α4β1 and α6β1, whereas integrin α4 high β1 + β7 + CD4 + T cells expressed high levels of integrin α4β1 and α4β7, suggesting an alternative expression of integrin α6β1 or α4β7 in combination with α4β1 in respective major and minor populations of integrin α4 high CD4 + T cells. The minor population, integrin α4 high β1 + β7 + CD4 + T cells, were different from the integrin α4 high β1 high β7 - CD4 + T cells in that they secreted a smaller amount of Th1 cytokines upon stimulation and expressed lower levels of Th1-related chemokine receptors CCR5 and CXCR3 than the integrin α4 high β 1 high β 7 - CD4 + T cells. In summary, the innate-like integrin α4 high CD4 + T cells could be divided into 2 populations, integrin α4β1 + α6β1 + α4β7 - and α4β1 + α6β1 - α4β7 + cells. The functional significance of serosal integrin α4β7 + CD4 + T cells needed to be investigated especially in view of mucosal immunity.

The differential effect of genetic variation on soluble CD14 levels in human plasma and milk.

PubMed

Guerra, Stefano; Carla Lohman, I; LeVan, Tricia D; Wright, Anne L; Martinez, Fernando D; Halonen, Marilyn

2004-09-01

The protein CD14 is a pattern recognition receptor for bacterial lipopolysaccharide (LPS). Whether genetic variation has the same influence on soluble CD14 (sCD14) levels in human plasma and milk remains to be determined. We measured sCD14 levels in plasma during pregnancy (n = 196) and in milk in the postpartum (n = 152) for women genotyped for the single nucleotide polymorphisms (SNPs) at positions -1619, -550, and -159 from the transcription start site of the CD14 gene. Plasma- and milk-sCD14 levels differed significantly both by CD14/-1619 and CD14/-550 genotypes and by haplotypes. Most interestingly, sCD14 levels were regulated differentially by the same genetic variants in plasma and milk, with the CD14/-550T allele and the corresponding are ATC haplotype associated with high sCD14 in milk but low sCD14 in plasma. A correlation between sCD14 levels in plasma and milk was absent (r = 0.091, P = NS). Our findings suggest the existence of cell-specific regulation mechanisms of CD14 gene expression.

Post-transplant soluble CD30 levels are associated with early subclinical rejection in kidney transplantation.

PubMed

Grenzi, Patricia C; Campos, Érika F; Silva, Hélio T; Felipe, Claudia R; Franco, Marcelo F; Soares, Maria F; Medina-Pestana, José O; Gerbase-DeLima, Maria

2015-03-01

Several studies have shown association of high pre- or post-transplant levels of soluble CD30 (sCD30) with acute rejection and poor late kidney transplant outcome. Our goal was to investigate whether sCD30 levels at month-3 post-transplant are associated with subclinical rejection, presence of CD30(+) cells within the graft, and expression of immune response genes in peripheral blood mononuclear cells. The study comprised 118 adult first kidney graft recipients, transplanted at a single center, receiving tacrolimus in low concentration. All were submitted to a protocol biopsy at month-3. Subclinical rejection was identified in 10 biopsies and sCD30 levels ≥ 61.88 ng/mL (P = 0.004), younger recipient age (P = 0.030) and non-Caucasian ethnicity (P = 0.011) were independently associated with this outcome. Rare CD30(+) cells were present in only two biopsies. There was a correlation between sCD30 levels and CD30 gene expression in peripheral blood mononuclear cells (r = 0.385, P = 0.043). These results show that high sCD30 levels are independent predictors of graft dysfunction and may contribute to patient selection protocols by indicating those who could benefit from a more thorough evaluation. Copyright © 2015 Elsevier B.V. All rights reserved.

Pre- and post-transplant monitoring of soluble CD30 levels as predictor of acute renal allograft rejection.

PubMed

Wang, Dong; Wu, Guo-Jun; Wu, Wei-Zhen; Yang, Shun-Liang; Chen, Jin-Hua; Wang, He; Lin, Wen-Hong; Wang, Qing-Hua; Zeng, Zhang-Xin; Tan, Jian-Ming

2007-06-01

Identification of renal graft candidates at high risk of impending acute rejection (AR) and graft loss may be helpful for patient-tailored immunosuppressive regimens and renal graft survival. To investigate the feasibility with soluble CD30 (sCD30) as predictor of AR, sCD30 levels of 70 patients were detected on day 0 pre-transplant and day 1, 3, 5, 7, 10, 14, 21, and 30 post-transplant. AR episodes in 6 months were recorded and then patients were divided into Group AR (n=11) and Group UC (n=59). Results showed that the patients had higher pre-transplant sCD30 levels than healthy people. A significant decrease of sCD30 was observed on the first day post-transplant and continued until day 14 post-transplant. Soluble CD30 presented a stable level from day 14 to 30 post-transplant. Pre-transplant sCD30 levels of Group AR were much higher than those of Group UC (P<0.001). Patients of Group AR also had higher sCD30 levels than those of Group UC on day 1, 3, 5, 7, 10 and 14 (P<0.001). The sCD30 level presented a significantly delayed decrease in the patients of Group AR. Statistical results showed that the highest value of area under ROC curve (0.95) was obtained on day 5 post-transplant, suggesting that sCD30 levels on day 5 are of high predictive value. Therefore, sCD30 level may be a good marker of increased alloreactivity and of significant predictive value. It's necessary to monitor the variation of sCD30 in the early period post-transplant.

CD32-Expressing CD4 T Cells Are Phenotypically Diverse and Can Contain Proviral HIV DNA.

PubMed

Martin, Genevieve E; Pace, Matthew; Thornhill, John P; Phetsouphanh, Chansavath; Meyerowitz, Jodi; Gossez, Morgane; Brown, Helen; Olejniczak, Natalia; Lwanga, Julianne; Ramjee, Gita; Kaleebu, Pontiano; Porter, Kholoud; Willberg, Christian B; Klenerman, Paul; Nwokolo, Nneka; Fox, Julie; Fidler, Sarah; Frater, John

2018-01-01

Efforts to both characterize and eradicate the HIV reservoir have been limited by the rarity of latently infected cells and the absence of a specific denoting biomarker. CD32a (FcγRIIa) has been proposed to be a marker for an enriched CD4 T cell HIV reservoir, but this finding remains controversial. Here, we explore the expression of CD32 on CD3 + CD4 + cells in participants from two primary HIV infection studies and identify at least three distinct phenotypes (CD32 low , CD32 + CD14 + , and CD32 high ). Of note, CD4 negative enrichment kits remove the majority of CD4 + CD32 + T cells, potentially skewing subsequent analyses if used. CD32 high CD4 T cells had higher levels of HLA-DR and HIV co-receptor expression than other subsets, compatible with their being more susceptible to infection. Surprisingly, they also expressed high levels of CD20, TCRαβ, IgD, and IgM (but not IgG), markers for both T cells and naïve B cells. Compared with other populations, CD32 low cells had a more differentiated memory phenotype and high levels of immune checkpoint receptors, programmed death receptor-1 (PD-1), Tim-3, and TIGIT. Within all three CD3 + CD4 + CD32 + phenotypes, cells could be identified in infected participants, which contained HIV DNA. CD32 expression on CD4 T cells did not correlate with HIV DNA or cell-associated HIV RNA (both surrogate measures of overall reservoir size) or predict time to rebound viremia following treatment interruption, suggesting that it is not a dominant biomarker for HIV persistence. Our data suggest that while CD32 + T cells can be infected with HIV, CD32 is not a specific marker of the reservoir although it might identify a population of HIV enriched cells in certain situations.

Different thresholds of T cell activation regulate FIV infection of CD4{sup +}CD25{sup +} and CD4{sup +}CD25{sup -} cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joshi, Anjali; Garg, Himanshu; Tompkins, Mary B.

2005-05-10

Cellular activation plays an important role in retroviral replication. Previously, we have shown that CD4{sup +}CD25{sup +} T cells by the virtue of their partially activated phenotype represent ideal candidates for a productive feline immunodeficiency virus (FIV) infection. In the present study, we extended our previous observations with regard to FIV replication in CD4{sup +}CD25{sup +} and CD4{sup +}CD25{sup -} cells under different stimulation conditions. Both CD4{sup +}CD25{sup +} and CD4{sup +}CD25{sup -} cells remain latently infected in the absence of IL-2 or concanvalinA (ConA), respectively; harboring a replication competent provirus capable of reactivation several days post-infection. While CD4{sup +}CD25{supmore » +} cells require low levels of exogenous IL-2 and virus inputs for an efficient FIV replication, CD4{sup +}CD25{sup -} T cells can only be productively infected in the presence of either high concentrations of IL-2 or high virus titers, even in the absence of mitogenic stimulation. Interestingly, while high virus input activates CD4{sup +}CD25{sup -} cells to replicate FIV, it induces apoptosis in a high percentage of CD4{sup +}CD25{sup +} T cells. High IL-2 concentrations but not high virus inputs lead to surface upregulation of CD25 and significant cellular proliferation in CD4{sup +}CD25{sup -} cells. These results suggest that CD4{sup +}CD25{sup +} and CD4{sup +}CD25{sup -} T cells have different activation requirements which can be modulated by both viral and cytokine stimuli to reach threshold activation levels in order to harbor a productive FIV infection. This holds implications in vivo for CD4{sup +}CD25{sup +} and CD4{sup +}CD25{sup -} cells to serve as potential reservoirs of a productive and latent FIV infection.« less

Relation between pretransplant serum levels of soluble CD30 and acute rejection during the first 6 months after a kidney transplant.

PubMed

Shooshtarizadeh, Tina; Mohammadali, Ali; Ossareh, Shahrzad; Ataipour, Yousef

2013-06-01

The immunologic status of kidney allograft recipients affects transplant outcome. High levels of pretransplant serum soluble CD30 correlate with an increased risk of acute rejection. Studies show conflicting results. We evaluated the relation between pretransplant serum sCD30 levels with the risk of posttransplant acute kidney rejection in renal transplant recipients. This prospective cohort study was performed between March 2010 and March 2011 on 77 kidney transplant recipients (53 men [68.8%], 24 women [31.2%]; mean age, 41 ± 14 y). Serum samples were collected 24 hours before transplant and analyzed for soluble CD30 levels by enzyme-linked immunosorbent assay. Patients were followed for 6 months after transplant. Acute biopsy-proven rejection episodes were recorded, serum creatinine levels were measured, and glomerular filtration rates were calculated at the first and sixth months after transplant. Preoperative serum soluble CD30 levels were compared in patients with and without rejection. The mean pretransplant serum soluble CD30 level was 92.1 ± 47.3 ng/mL. At 6 months' follow-up, 10 patients experienced acute rejection. Mean pretransplant soluble CD30 levels were 128.5 ± 84 ng/mL versus 86.7 ± 37 ng/mL in patients with and without acute rejection episodes (P = .008). At 100 ng/mL, the sensitivity, specificity, and positive and negative predictive values of pretransplant serum soluble CD30 level to predict acute rejection were 70%, 73.6%, 29.1%, and 94.3%. We showed a significant relation between pretransplant serum soluble CD30 levels and acute allograft rejection. High pretransplant levels of serum soluble CD30 can be a risk factor for kidney transplant rejection, and its high negative predictive value at various cutoffs make it useful to find candidates with a low risk of acute rejection after transplant.

High variation of individual soluble serum CD30 levels of pre-transplantation patients: sCD30 a feasible marker for prediction of kidney allograft rejection?

PubMed

Altermann, Wolfgang; Schlaf, Gerald; Rothhoff, Anita; Seliger, Barbara

2007-10-01

Previous studies have suggested that the pre-transplant levels of the soluble CD30 molecule (sCD30) represent a non-invasive tool which can be used as a biomarker for the prediction of kidney allograft rejections. In order to evaluate the feasibility of sCD30 for pre-transplantation monitoring the sera of potential kidney recipients (n = 652) were collected four times in a 3 months interval. Serum from healthy blood donors (n = 203) served as controls. The sCD30 concentrations of all samples were determined using a commercially available ELISA. This strategy allowed the detection of possible variations of individual sCD30 levels over time. Heterogeneous sCD30 concentrations were found in the samples obtained from individual putative kidney transplant recipients when quarterly measured over 1 year. Total 95% of serum samples obtained from healthy controls exhibited sCD30 values <30 U/ml, whereas most recipients displayed higher serum levels (>30 U/ml). Total 524 patients (80.4%) constantly exhibited serum concentrations of <100 U/ml during the period investigated, whereas 109 patients (16.7%) showed variations by exceeding the proposed 'cut off' of 100 U/ml for one to three times. The frequency of samples exhibiting sCD30 values >100 U/ml was significantly lower than that previously reported. The high degree of variation does not allow the stratification of patients into high and low immunological risk groups based on a single sCD30 value > 100 U/ml. Due to the heterogeneity of sCD30 levels during time course and the high values of SD, its implementation as a pre-transplant marker cannot be justified to generate special provisions for the organ allocation to patients with single sCD30 values > 100 U/ml.

Soluble CD30 serum levels before and after treatment with alpha-interferon in patients with chronic hepatitis C.

PubMed

Di Cesare, Enrico; Spadaro, Aldo; Ajello, Antonino; Ferraù, Oscar; Alessi, Nunziata; Luigiano, Carmelo; Melluso, Rossana; Freni, Maria A

2005-01-01

It has been suggested that soluble CD30 (sCD30) serum levels in chronic hepatitis C are correlated with the activity of the disease and with the outcome of interferon (IFN) treatment. In this study, sCD30 serum levels in 25 patients with chronic hepatitis C, before and after treatment with IFN-2alpha, were measured. A total of 20 healthy subjects were used as controls. High sCD30 levels in serum were found in 36% of patients and in 5% of controls. In patients with sCD30 levels above or within the normal range, no significant differences in age, gender, serum transaminases and histology activity index were found. In relation to IFN treatment, only responder patients had serum sCD30 higher than controls, although the difference between responders and non-responders was not significant. No changes from baseline values were observed after treatment. Although high, sCD30 serum levels in chronic hepatitis C are not correlated with the disease activity, are not affected by IFN treatment and are not predictors of response to IFN treatment.

The effects of deep level traps on the electrical properties of semi-insulating CdZnTe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zha, Gangqiang; Yang, Jian; Xu, Lingyan

2014-01-28

Deep level traps have considerable effects on the electrical properties and radiation detection performance of high resistivity CdZnTe. A deep-trap model for high resistivity CdZnTe was proposed in this paper. The high resistivity mechanism and the electrical properties were analyzed based on this model. High resistivity CdZnTe with high trap ionization energy E{sub t} can withstand high bias voltages. The leakage current is dependent on both the deep traps and the shallow impurities. The performance of a CdZnTe radiation detector will deteriorate at low temperatures, and the way in which sub-bandgap light excitation could improve the low temperature performance canmore » be explained using the deep trap model.« less

Implications of infiltrating immune cells within bone marrow of patients with diffuse large B-cell lymphoma.

PubMed

Jeong, Juhyeon; Oh, Eun Ji; Yang, Woo Ick; Kim, Soo Jeong; Yoon, Sun Och

2017-06-01

The implications of infiltrating immune cells, especially T cells and macrophages, in the bone marrow (BM) microenvironment of patients with diffuse large B-cell lymphoma (DLBCL) have rarely been studied. We aimed to investigate the significance of infiltrating immune cells in the BM microenvironment as a prognostic factor for DLBCL patients. Using the initial pretreatment BM biopsy obtained from 198 DLBCL patients, we semiquantitatively evaluated CD3+ T cells, CD8+ T cells, and CD163+ macrophages that infiltrate into the paratrabecular and interstitial areas of BM by immunohistochemistry and analyzed their clinicopathological and prognostic implications. Levels of infiltrating CD3+ T cells, CD8+ T cells, and CD163+ macrophages were significantly higher in BM with DLBCL involvement (BMI-positive group) than in that without DLBCL involvement (BMI-negative group). Infiltration of CD8+ T cells significantly increased in cases with advanced Ann Arbor stage, elevated lactate dehydrogenase level, extranodal site involvement ≥2 sites, higher Eastern Cooperative Oncology Group performance status, and higher International Prognostic Index (IPI) risk. High levels of CD3+ T cells were significantly associated with age ≤60, and high levels of CD163+ macrophages were associated with advanced Ann Arbor stage and higher IPI risk. High infiltration of CD8+ T cells was significantly related to inferior overall and recurrence-free survival rate, even in the BMI-negative group. High infiltration of CD8+ T cells within the pretreatment BM was related to poor prognosis, and might be a useful prognostic factor of DLBCL patients. Therefore, evaluation of CD8+ T cells is helpful for predicting prognosis in initial pretreatment BM biopsy of DLBCL patients. Copyright © 2017 Elsevier Inc. All rights reserved.

PD-1(HIGH) Follicular CD4 T Helper Cell Subsets Residing in Lymph Node Germinal Centers Correlate with B Cell Maturation and IgG Production in Rhesus Macaques.

PubMed

Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A; Veazey, Ronald S

2014-01-01

CD4+ T follicular helper (TFH) cells guide development and maturation of B cells and are crucial for effective antibody responses. Here we found rhesus macaque TFH cells, defined as CXCR5+CD4 T cells, contain two major populations: PD-1(INT) and PD-1(HIGH) cells. Of these, PD-1(HIGH)CD4+ T cells highly co-express ICOS but little CCR7, and reside in lymph node germinal centers (GCs), but not in blood. These cells secrete IL-21 and express transcriptional factor Bcl-6 at higher levels than CXCR5+PD-1(INT)CD4+ T cells. In addition, the frequency of PD-1(HIGH)CD4+ T cells is low in lymph nodes of newborns, but increases with age. Levels of PD-1(HIGH)CD4+ T cells correlate with mature B cells in lymph nodes, and PD-1 blockade in PD-1(HIGH)CD4+ T and B cell co-cultures significantly inhibits IgG production. In summary, PD-1(HIGH)CD4+ T cells residing in GC represent a specific TFH subset that contributes to maturation of B cells and IgG production.

Microbial activity and community diversity in a variable charge soil as affected by cadmium exposure levels and time*

PubMed Central

Shentu, Jia-li; He, Zhen-li; Yang, Xiao-e; Li, Ting-qiang

2008-01-01

Effects of cadmium (Cd) on microbial biomass, activity and community diversity were assessed in a representative variable charge soil (Typic Aquult) using an incubation study. Cadmium was added as Cd(NO3)2 to reach a concentration range of 0~16 mg Cd/kg soil. Soil extractable Cd generally increased with Cd loading rate, but decreased with incubation time. Soil microbial biomass was enhanced at low Cd levels (0.5~1 mg/kg), but was inhibited consistently with increasing Cd rate. The ratio of microbial biomass C/N varied with Cd treatment levels, decreasing at low Cd rate (<0.7 mg/kg available Cd), but increasing progressively with Cd loading. Soil respiration was restrained at low Cd loading (<1 mg/kg), and enhanced at higher Cd levels. Soil microbial metabolic quotient (MMQ) was generally greater at high Cd loading (1~16 mg/kg). However, the MMQ is also affected by other factors. Cd contamination reduces species diversity of soil microbial communities and their ability to metabolize different C substrates. Soils with higher levels of Cd contamination showed decreases in indicator phospholipids fatty acids (PLFAs) for Gram-negative bacteria and actinomycetes, while the indicator PLFAs for Gram-positive bacteria and fungi increased with increasing levels of Cd contamination. PMID:18357628

High pre-transplant soluble CD30 levels are predictive of the grade of rejection.

PubMed

Rajakariar, Ravindra; Jivanji, Naina; Varagunam, Mira; Rafiq, Mohammad; Gupta, Arun; Sheaff, Michael; Sinnott, Paul; Yaqoob, M M

2005-08-01

In renal transplantation, serum soluble CD30 (sCD30) levels in graft recipients are associated with increased rejection and graft loss. We investigated whether pre-transplant sCD30 concentrations are predictive of the grade of rejection. Pre-transplant sera of 51 patients with tubulointerstitial rejection (TIR), 16 patients with vascular rejection (VR) and an age-matched control group of 41 patients with no rejection (NR) were analyzed for sCD30. The transplant biopsies were immunostained for C4d. The median sCD30 level was significantly elevated in the group with VR (248 Units (U)/mL, range: 92-802) when compared with TIR (103 U/mL, range: 36-309, p<0.001) and NR (179 U/mL, range: 70-343, p<0.03). Moreover, patients with TIR had significantly lower sCD30 levels compared to NR. Based on C4d staining, a TH2 driven process, the median sCD30 levels were significantly raised in C4d+ patients compared with C4d- group (177 U/mL vs. 120 U/mL, p<0.05). sCD30 levels measured at time of transplantation correlate with the grade of rejection. High pre-transplant levels are associated with antibody-mediated rejection which carries a poorer prognosis. sCD30 could be another tool to assess immunological risk prior to transplantation and enable a patient centered approach to immunosuppression.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, De-Ju; Xu, Yan-Ming; Du, Ji-Ying

Highlights: • Normal human bronchial epithelial cells (BEAS-2B) were dosed with cadmium (Cd). • A low level (2 μM) of Cd treatment for 36 h elicited negligible cytotoxicity. • High levels (20 or 30 μM) of Cd treatment for 36 h induced cell death. • High levels of Cd can upregulate the protein levels of eIF5A1 and NF-κB p65. • We suggest that eIF5A1 level is possibly modulated by NF-κB. - Abstract: Cadmium (Cd) and Cd compounds are widely-distributed in the environment and well-known carcinogens. Here, we report that in CdCl{sub 2}-exposed human bronchial epithelial cells (BEAS-2B), the level ofmore » p53 is dramatically decreased in a time- and dose-dependent manner, suggesting that the observed Cd-induced cytotoxicity is not likely due to the pro-apoptotic function of p53. Therefore, this prompted us to further study the responsive pro-apoptotic factors by proteomic approaches. Interestingly, we identified that high levels (20 or 30 μM) of Cd can significantly upregulate the protein levels of eukaryotic translation initiation factor 5A1 (eIF5A1) and redox-sensitive transcription factor NF-κB p65. Moreover, there is an enhanced NF-κB nuclear translocation as well as chromatin-binding in Cd-treated BEAS-2B cells. We also show that small interfering RNA-specific knockdown of eIF5A1 in Cd-exposed cells attenuated the Cd cytotoxicity, indicating the potential role of eIF5A1 in Cd cytotoxicity. As eIF5A1 is reported to be related with cell apoptosis but little is known about its transcriptional control, we hypothesize that NF-κB might likely modulate eIF5A1 gene expression. Notably, by bioinformatic analysis, several potential NF-κB binding sites on the upstream promoter region of eIF5A1 gene can be found. Subsequent chromatin immunoprecipitation assay revealed that indeed there is enhanced NF-κB binding on eIF5A1 promoter region of Cd-treated BEAS-2B cells. Taken together, our findings suggest for the first time a regulatory mechanism for the pro-apoptotic protein eIF5A1 in which its level is possibly modulated by NF-κB in human lung cells.« less

Changes in serum levels of lipopolysaccharides and CD26 in patients with Crohn's disease

PubMed Central

Kotze, Paulo Gustavo; Martinez, Carlos Augusto Real; Camargo, Michel Gardere; Guadagnini, Dioze; Calixto, Antonio Ramos; Vasques, Ana Carolina Junqueira; Ayrizono, Maria de Lourdes Setsuko; Geloneze, Bruno; Pareja, José Carlos; Saad, Mario José; Coy, Claudio Saddy Rodrigues

2017-01-01

Background/Aims Lipopolysaccharide (LPS) is a molecule formed by lipids and polysaccharides and is the major cell wall component of gram-negative bacteria. High LPS levels are known to block CD26 expression by activating Toll-like receptor 4. The aim of this study was to correlate the serum levels of LPS and CD26 in Crohn's disease (CD) patients with serum levels of C-reactive protein (CRP), interleukins, CD activity index, and tumor necrosis factor-α (TNF-α). Methods Serum samples were collected from 27 individuals (10 with active CD, 10 with inactive CD, and 7 controls) and the levels of LPS, CD26, TNF-α, interleukin-1β (IL-1β), IL-6, IL-17, and CRP were determined by enzyme-linked immunosorbent assay. The levels of LPS and CD26 were then tested for correlation with TNF-α, IL-1β, IL-6, IL-17, and CRP. Results Serum levels of LPS were significantly elevated in the active CD group (P=0.003). Levels of IL-1β (P=0.002), IL-6 (P=0.003), and IL-17 (P<0.001) were lower in the CD groups. Serum TNF-α levels were increased in the active CD group. The CRP levels were elevated in the CD groups when compared to controls (P<0.001). The CD26 levels were lower in the CD groups than in the control group (P<0.001). Among the variables analyzed, there was a correlation between LPS and CRP (r=−0.53, P=0.016) in the CD groups. Conclusions Individuals with CD exhibited higher serum levels of LPS varying from a 2- to 6-fold increase depending on disease activity, when compared with healthy controls. CD26 levels were lower in the CD groups. Both LPS and CD26 correlated with disease severity and serve as potential CD biomarkers. PMID:28670232

Cutaneous CD30+ cells in children with atopic dermatitis.

PubMed

Cavagni, G; Caffarelli, C; Facchetti, F; Brugnoni, D; Notarangelo, L D; Tosoni, C; Altobelli, R

2000-03-01

CD30 expression can be considered a marker of Th2 cells. We investigated the presence of CD30+ cells in the lesional skin of children with atopic dermatitis (AD). We also analyzed the possible relationship between CD30+ cells and serum soluble CD 30 (sCD30) levels, and IgE, soluble interleukin-2 (IL-2) receptor (sIL-2R) or soluble CD23 (sCD23) levels in the blood, and clinical score. Ten eczematous children (4 males, 6 females; median age: 4 years and 5 months; range: 11 months to 14 years), 9 sex- and age-matched control children and an adult control group were studied. A clinical score (SCORAD index), was given to eczematous lesions. Blood was taken for the determination of IgE, sCD30, sIL-2R and sCD23 levels. Punch biopsies of lesional skin were stained with hematoxylin and eosin or incubated with anti-CD30 monoclonal antibodies. Skin prick tests (SPTs) were also performed. In the biopsy specimens, CD30 expression was observed in high proportions of infiltrating cells. In children with AD, total serum IgE, sCD30, sIL-2R, sCD23 and eosinophils were significantly elevated compared to controls. CD30+ cells were not associated with serum IgE, sCD30, sIL-2R, sCD23, or SPT results, score of inflammatory cells in lesional skin or clinical score. Children with AD who had high total IgE and specific IgE antibodies did not differ from those with normal total IgE and negative specific IgE in respect of age, clinical score, number of CD30+ cells, sCD30, sIL-2R and sCD23 levels, score of inflammatory cells in skin or clinical score. Our results showed remarkable numbers of CD30+ cells in the lesional skin and high sCD30 in the serum of children with AD. CD30+ cells did not correlate with systemic markers of IgE reaction. Copyright 2000 S. Karger AG, Basel

Plasma-soluble CD30 in childhood tuberculosis: effects of disease severity, nutritional status, and vitamin A therapy.

PubMed

Hanekom, W A; Hussey, G D; Hughes, E J; Potgieter, S; Yogev, R; Check, I J

1999-03-01

Plasma-soluble CD30 (sCD30) is the result of proteolytic splicing from the membrane-bound form of CD30, a putative marker of type 2 cytokine-producing cells. We measured sCD30 levels in children with tuberculosis, a disease characterized by prominent type 1 lymphocyte cytokine responses. We postulated that disease severity and nutritional status would alter cytokine responses and therefore sCD30 levels. Samples from South African children enrolled prospectively at the time of diagnosis of tuberculosis were analyzed. (Patients were originally enrolled in a randomized, double-blind placebo-controlled study of the effects of oral vitamin A supplementation on prognosis of tuberculosis.) Plasma samples collected at the time of diagnosis and 6 and 12 weeks later (during antituberculosis therapy) were analyzed. sCD30 levels were measured by enzyme immunoassay. The 91 children included in the study demonstrated high levels of sCD30 at diagnosis (median, 98 U/liter; range, 11 to 1,569 U/liter). Although there was a trend toward higher sCD30 levels in more severe disease (e.g., culture-positive disease or miliary disease), this was not statistically significant. Significantly higher sCD30 levels were demonstrated in the presence of nutritional compromise: the sCD30 level was higher in patients with a weight below the third percentile for age, in those with clinical signs of kwashiorkor, and in those with a low hemoglobin content. There was minimal change in the sCD30 level after 12 weeks of therapy, even though patients improved clinically. However, changes in sCD30 after 12 weeks differed significantly when 46 patients (51%) who received vitamin A were compared with those who had received a placebo. Vitamin A-supplemented children demonstrated a mean (+/- standard error of the mean) decrease in sCD30 by a factor of 0.99 +/- 0.02 over 12 weeks, whereas a factor increase of 1.05 +/- 0.02 was demonstrated in the placebo group (P = 0.02). We conclude that children with tuberculosis had high sCD30 levels, which may reflect the presence of a type 2 cytokine response. Nutritional compromise was associated with higher sCD30 levels. Vitamin A therapy resulted in modulation of sCD30 levels over time.

Plasma-Soluble CD30 in Childhood Tuberculosis: Effects of Disease Severity, Nutritional Status, and Vitamin A Therapy

PubMed Central

Hanekom, W. A.; Hussey, G. D.; Hughes, E. J.; Potgieter, S.; Yogev, R.; Check, I. J.

1999-01-01

Plasma-soluble CD30 (sCD30) is the result of proteolytic splicing from the membrane-bound form of CD30, a putative marker of type 2 cytokine-producing cells. We measured sCD30 levels in children with tuberculosis, a disease characterized by prominent type 1 lymphocyte cytokine responses. We postulated that disease severity and nutritional status would alter cytokine responses and therefore sCD30 levels. Samples from South African children enrolled prospectively at the time of diagnosis of tuberculosis were analyzed. (Patients were originally enrolled in a randomized, double-blind placebo-controlled study of the effects of oral vitamin A supplementation on prognosis of tuberculosis.) Plasma samples collected at the time of diagnosis and 6 and 12 weeks later (during antituberculosis therapy) were analyzed. sCD30 levels were measured by enzyme immunoassay. The 91 children included in the study demonstrated high levels of sCD30 at diagnosis (median, 98 U/liter; range, 11 to 1,569 U/liter). Although there was a trend toward higher sCD30 levels in more severe disease (e.g., culture-positive disease or miliary disease), this was not statistically significant. Significantly higher sCD30 levels were demonstrated in the presence of nutritional compromise: the sCD30 level was higher in patients with a weight below the third percentile for age, in those with clinical signs of kwashiorkor, and in those with a low hemoglobin content. There was minimal change in the sCD30 level after 12 weeks of therapy, even though patients improved clinically. However, changes in sCD30 after 12 weeks differed significantly when 46 patients (51%) who received vitamin A were compared with those who had received a placebo. Vitamin A-supplemented children demonstrated a mean (± standard error of the mean) decrease in sCD30 by a factor of 0.99 ± 0.02 over 12 weeks, whereas a factor increase of 1.05 ± 0.02 was demonstrated in the placebo group (P = 0.02). We conclude that children with tuberculosis had high sCD30 levels, which may reflect the presence of a type 2 cytokine response. Nutritional compromise was associated with higher sCD30 levels. Vitamin A therapy resulted in modulation of sCD30 levels over time. PMID:10066655

A reevaluation of CD22 expression in human lung cancer.

PubMed

Pop, Laurentiu M; Barman, Stephen; Shao, Chunli; Poe, Jonathan C; Venturi, Guglielmo M; Shelton, John M; Pop, Iliodora V; Gerber, David E; Girard, Luc; Liu, Xiao-yun; Behrens, Carmen; Rodriguez-Canales, Jaime; Liu, Hui; Wistuba, Ignacio I; Richardson, James A; Minna, John D; Tedder, Thomas F; Vitetta, Ellen S

2014-01-01

CD22 is a transmembrane glycoprotein expressed by mature B cells. It inhibits signal transduction by the B-cell receptor and its coreceptor CD19. Recent reports indicate that most human lung cancer cells and cell lines express CD22, making it an important new therapeutic target for lung cancer. The objective of our studies was to independently validate these results with the goal of testing the efficacy of our CD22 immunotoxins on lung cancer cell lines. As determined by quantitative real-time PCR analysis, we found that levels of CD22 mRNA in a panel of human lung cancer cell lines were 200 to 60,000-fold lower than those observed in the human CD22(+) Burkitt lymphoma cells, Daudi. Using flow cytometry with a panel of CD22 monoclonal antibodies and Western blot analyses, we could not detect surface or intracellular expression of CD22 protein in a panel of lung cancer cell lines. In addition, the in vitro proliferation of the lung tumor cell lines was not affected by either CD22 antibodies or our highly potent anti-CD22 immunotoxin. In contrast, CD22(+) Daudi cells expressed high levels of CD22 mRNA and protein, and were sensitive to our CD22 immunotoxin. Importantly, primary non-small cell lung cancers from more than 250 patient specimens did not express detectable levels of CD22 protein as assessed by immunohistochemistry. We conclude that CD22 is not expressed at measurable levels on the surface of lung cancer cells, and that these cells cannot be killed by anti-CD22 immunotoxins.

Genetic Diversity, Rather than Cultivar Type, Determines Relative Grain Cd Accumulation in Hybrid Rice

PubMed Central

Sun, Liang; Xu, Xiaxu; Jiang, Youru; Zhu, Qihong; Yang, Fei; Zhou, Jieqiang; Yang, Yuanzhu; Huang, Zhiyuan; Li, Aihong; Chen, Lianghui; Tang, Wenbang; Zhang, Guoyu; Wang, Jiurong; Xiao, Guoying; Huang, Daoyou; Chen, Caiyan

2016-01-01

Cadmium (Cd) is a toxic element, and rice is known to be a leading source of dietary Cd for people who consume rice as their main caloric resource. Hybrid rice has dominated rice production in southern China and has been adopted worldwide. The characteristics of high yield heterosis of rice hybrids makes the public think intuitively that the hybrid rice accumulates more Cd in grain than do inbred cultivars. A detailed understanding of the genetic basis of grain Cd accumulation in hybrids and developing Cd-safe rice are one of the top priorities for hybrid rice breeders at present. In this study, we investigated genetic diversity and grain Cd levels in 617 elite rice hybrids collected from the middle and lower Yangtze River Valley in China and 68 inbred cultivars from around the world. We found that there are large variations in grain Cd accumulation in both the hybrids and their inbred counterparts. However, we found grain Cd levels in the rice hybrids to be similar to the levels in indica rice inbreds, suggesting that the hybrids do not accumulate more Cd than do the inbred rice cultivars. Further analysis revealed that the high heritability of Cd accumulation in the grain and the single indica population structure increases the risk of Cd over-accumulation in hybrid rice. The genetic effects of Cd-related QTLs, which have been identified in related Cd-QTL mapping studies, were also determined in the hybrid rice population. Four QTLs were identified as being associated with the variation in grain Cd levels; three of these loci exhibited obvious indica-japonica differentiations. Our study will provide a better understanding of grain Cd accumulations in hybrid rice, and pave the way toward effective breeding for high-yielding, low grain-Cd hybrids in the future. PMID:27708659

Dose-dependent modulation of CD8 and functional avidity as a result of peptide encounter

PubMed Central

Kroger, Charles J; Alexander-Miller, Martha A

2007-01-01

The generation of an optimal CD8+ cytotoxic T lymphocyte (CTL) response is critical for the clearance of many intracellular pathogens. Previous studies suggest that one contributor to an optimal immune response is the presence of CD8+ cells exhibiting high functional avidity. In this regard, CD8 expression has been shown to contribute to peptide sensitivity. Here, we investigated the ability of naive splenocytes to modulate CD8 expression according to the concentration of stimulatory peptide antigen. Our results showed that the level of CD8 expressed was inversely correlated with the amount of peptide used for the primary stimulation, with higher concentrations of antigen resulting in lower expression of both CD8α and CD8β. Importantly the ensuing CD8low and CD8high CTL populations were not the result of the selective outgrowth of naive CD8+ T-cell subpopulations expressing distinct levels of CD8. Subsequent encounter with peptide antigen resulted in continued modulation of both the absolute level and the isoform of CD8 expressed and in the functional avidity of the responding cells. We propose that CD8 cell surface expression is not a static property, but can be modulated to ‘fine tune’ the sensitivity of responding CTL to a defined concentration of antigen. PMID:17484768

Minimally Activated CD8 Autoreactive T Cells Specific for IRBP Express a High Level of Foxp3 and Are Functionally Suppressive

PubMed Central

Peng, Yong; Shao, Hui; Ke, Yan; Zhang, Ping; Han, Gencheng; Kaplan, Henry J.; Sun, Deming

2008-01-01

Purpose Results in previous reports have demonstrated that immunization of the EAU-prone B6 mouse activates both CD4 and CD8 IRBP-specific T cells. The purpose of this study was to investigate structural and functional differences between CD4 and CD8 autoreactive T cells activated by the uveitogenic peptide. Methods Purified CD4 and CD8 isolated from B6 mice immunized with an uveitogenic peptide, interphotoreceptor retin-oid-binding protein (IRBP)1-20, were stimulated in vitro with various doses of immunizing peptide. The activated T cells were determined for cytokine production, expression of Foxp3, and suppressor activity. Results CD4 autoreactive T cells underwent full activation when stimulated with high or medium concentrations of immunizing peptide, whereas a high dose of antigenic peptide resulted in only modest activation of CD8 autoreactive T cells. When stimulated by a low dose (<0.1 μg/mL) of antigen or by of a high dose of antigen and a small amount of TGF-β1, the minimally activated CD8 T cells expressed a high level of Foxp3 and gained suppressor function. Conclusions Minimally activated CD8 autoreactive T cells can be functionally suppressive and may neutralize the tissue-damaging effect of the CD4 autoreactive T cells. PMID:17460277

CD133 expression in osteosarcoma and derivation of CD133⁺ cells.

PubMed

Li, Ji; Zhong, Xiao-Yan; Li, Zong-Yu; Cai, Jin-Fang; Zou, Lin; Li, Jian-Min; Yang, Tao; Liu, Wei

2013-02-01

Cluster of differentiation 133 (CD133) is recognized as a stem cell marker for normal and cancerous tissues. Using cell culture and real‑time fluorescent polymerase chain reaction, CD133 expression was analyzed in osteosarcoma tissue and Saos‑2 cell lines. In addition, cancer stem cell‑related gene expression in the Saos‑2 cell line was determined to explore the mechanisms underlying tumorigenesis and high drug resistance in osteosarcoma. CD133+ cells were found to be widely distributed in various types of osteosarcoma tissue. Following cell culture, cells entered the G2/M and S cell cycle stages from G0/G1. Levels of CD133+ cells decreased to normal levels rapidly over the course of cell culture. Colony forming efficiency was higher in the CD133+ compared with the CD133‑ subpopulation of Saos‑2 cells. Expression levels of stem cell‑related genes, including multidrug resistance protein 1 (MDR1) and sex determining region Y‑box 2 (Sox2) in the CD133+ subpopulation of cells were found to be significantly higher compared with the CD133‑ subpopulation. These observations indicate that CD133+ Saos‑2 cells exhibit stem cell characteristics, including low abundance, quiescence and a high potential to undergo differentiation, as well as expression of key stem cell regulatory and drug resistance genes, which may cause osteosarcoma and high drug resistance.

CD147 (Basigin/Emmprin) identifies FoxP3+CD45RO+CTLA4+-activated human regulatory T cells.

PubMed

Solstad, Therese; Bains, Simer Jit; Landskron, Johannes; Aandahl, Einar Martin; Thiede, Bernd; Taskén, Kjetil; Torgersen, Knut Martin

2011-11-10

Human CD4(+)FoxP3(+) T cells are functionally and phenotypically heterogeneous providing plasticity to immune activation and regulation. To better understand the functional dynamics within this subset, we first used a combined strategy of subcellular fractionation and proteomics to describe differences at the protein level between highly purified human CD4(+)CD25(+) and CD4(+)CD25(-) T-cell populations. This identified a set of membrane proteins highly expressed on the cell surface of human regulatory T cells (Tregs), including CD71, CD95, CD147, and CD148. CD147 (Basigin or Emmprin) divided CD4(+)CD25(+) cells into distinct subsets. Furthermore, CD147, CD25, FoxP3, and in particular CTLA-4 expression correlated. Phenotypical and functional analyses suggested that CD147 marks the switch between resting (CD45RA(+)) and activated (CD45RO(+)) subsets within the FoxP3(+) T-cell population. Sorting of regulatory T cells into CD147(-) and CD147(+) populations demonstrated that CD147 identifies an activated and highly suppressive CD45RO(+) Treg subset. When analyzing CD4(+) T cells for their cytokine producing potential, CD147 levels grouped the FoxP3(+) subset into 3 categories with different ability to produce IL-2, TNF-α, IFN-γ, and IL-17. Together, this suggests that CD147 is a direct marker for activated Tregs within the CD4(+)FoxP3(+) subset and may provide means to manipulate cells important for immune homeostasis.

The role of anxiety in cortisol stress response and cortisol recovery in boys with oppositional defiant disorder/conduct disorder.

PubMed

Schoorl, Jantiene; Rijn, Sophie van; Wied, Minet de; van Goozen, Stephanie; Swaab, Hanna

2016-11-01

Children with antisocial and aggressive behaviors have been found to show abnormal neurobiological responses to stress, specifically impaired cortisol stress reactivity. The role of individual characteristics, such as comorbid anxiety, in the stress response is far less studied. Furthermore, this study extended previous studies in that not only baseline and reactivity to a psychosocial stressor were examined, but also recovery from a stressor. These three phases of cortisol could be impacted differentially in boys with oppositional defiant disorder/conduct disorder (ODD/CD) with (+ANX) and without anxiety (-ANX). The results revealed that cortisol patterns in response to psychosocial stress were different for boys with ODD/CD+ANX (n=32), ODD/CD-ANX (n=22) and non-clinical controls (NC) (n=34), with age range of 7.8-12.9 years. The ODD/CD-ANX group showed lower overall cortisol levels than the NC group. When considering the three phases of cortisol separately, the ODD/CD-ANX group had lower baseline cortisol levels relative to the other groups, whereas the ODD/CD+ANX showed an impaired cortisol recovery response. Within those with ODD/CD, callous-unemotional traits were predictive of high baseline cortisol levels. Also, anxiety predicted high baseline and recovery cortisol levels, whereas a high number of CD symptoms predicted reduced cortisol stress reactivity. These results clearly indicate that comorbid anxiety is an important factor in explaining differences in stress response profiles in boys with ODD/CD; although boys with CD/ODD are generally characterized by an impaired cortisol stress response, we found that those with comorbid anxiety showed impaired cortisol recovery, whereas those without anxiety showed reduced baseline cortisol levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemokine Receptor Expression on Normal Blood CD56+ NK-Cells Elucidates Cell Partners That Comigrate during the Innate and Adaptive Immune Responses and Identifies a Transitional NK-Cell Population

PubMed Central

Queirós, Maria Luís; Gonçalves, Marta; Fonseca, Sónia; Moura, João

2015-01-01

Studies of chemokine receptors (CKR) in natural killer- (NK-) cells have already been published, but only a few gave detailed information on its differential expression on blood NK-cell subsets. We report on the expression of the inflammatory and homeostatic CKR on normal blood CD56+low CD16+ and CD56+high  CD16−/+low NK-cells. Conventional CD56+low and CD56+high NK-cells present in the normal PB do express CKR for inflammatory cytokines, although with different patterns CD56+low NK-cells are mainly CXCR1/CXCR2+ and CXCR3/CCR5−/+, whereas mostly CD56+high NK-cells are CXCR1/CXCR2− and CXCR3/CCR5+. Both NK-cell subsets have variable CXCR4 expression and are CCR4− and CCR6−. The CKR repertoire of the CD56+low NK-cells approaches to that of neutrophils, whereas the CKR repertoire of the CD56+high NK-cells mimics that of Th1+ T cells, suggesting that these cells are prepared to migrate into inflamed tissues at different phases of the immune response. In addition, we describe a subpopulation of NK-cells with intermediate levels of CD56 expression, which we named CD56+int NK-cells. These NK-cells are CXCR3/CCR5+, they have intermediate levels of expression of CD16, CD62L, CD94, and CD122, and they are CD57− and CD158a−. In view of their phenotypic features, we hypothesize that they correspond to a transitional stage, between the well-known CD56+high and CD56+low NK-cells populations. PMID:26543875

High levels of the soluble form of CD30 molecule in rheumatoid arthritis (RA) are expression of CD30+ T cell involvement in the inflamed joints.

PubMed Central

Gerli, R; Muscat, C; Bistoni, O; Falini, B; Tomassini, C; Agea, E; Tognellini, R; Biagini, P; Bertotto, A

1995-01-01

The CD30 is a surface molecule expressed by Th2-type lymphokine-producing T cells upon activation. CD30-expressing activated T cells release a soluble form of the molecule, which can be detectable both in vitro and in vivo. In the present study, high levels of soluble CD30 were found in peripheral blood and synovial fluid from patients with RA. However, CD30+ CD3+ cells, either CD4+ or CD8+, were significantly present in synovial fluid, but not in peripheral blood, of RA patients. Serum values of soluble CD30 were higher in active than inactive RA patients and directly correlated with rheumatoid factor serum titres. These data strongly support an involvement of CD30+ T cells in the immune processes of rheumatoid synovitis, and may suggest a relationship between Th2-type cytokine-secreting T cells and the pathological response in RA. PMID:8536371

Soluble CD30 levels in recipients undergoing heart transplantation do not predict post-transplant outcome.

PubMed

Ypsilantis, Efthymios; Key, Timothy; Bradley, J Andrew; Morgan, C Helen; Tsui, Stephen; Parameshwar, Jayan; Taylor, Craig J

2009-11-01

The pre-transplant serum level of soluble CD30 (sCD30), a proteolytic derivative of the lymphocyte surface receptor CD30, has been suggested as a biomarker for immunologic risk after organ transplantation. Pre-transplant serum sCD30 levels were determined in 200 consecutive adult heart transplant recipients undertaken at a single center. Transplant outcome (acute rejection in the first 12 months and patient survival up to 5 years post-transplant) was determined. Patients treated with a left ventricular assist device (LVAD) prior to transplantation (n = 28) had higher levels of sCD30 (median 64 U/ml, range 12 to 112 U/ml) than those (n = 172) with no LVAD (median 36 U/ml, range 1 to 158 U/ml, p < 0.0001). Recipients were categorized according to whether sCD30 levels were "low" (lower quartile, <24 U/ml, n = 50), "intermediate" (24 to 58 U/ml, n = 100) or "high" (upper quartile, >58 U/ml, n = 50). Neither acute rejection nor recipient survival differed according to sCD30 level, with values (mean +/- SEM) of 0.30 +/- 0.04, 0.23 +/- 0.03 and 0.30 +/- 0.05 acute rejection episodes per 100 days in the low, intermediate and high groups, respectively, with recipient survival rates at 1 year of 77.7%, 84.9% and 86% and at 5 years of 73.6%, 67.9% and 75.8%, respectively. Pre-transplant serum sCD30 level does not predict acute allograft rejection or recipient survival after heart transplantation, although sCD30 levels are increased by LVAD, possibly as a result of biomaterial-host immune interaction.

A Re-evaluation of CD22 Expression by Human Lung Cancer

PubMed Central

Pop, Laurentiu M.; Barman, Stephen; Shao, Chunli; Poe, Jonathan C.; Venturi, Guglielmo M.; Shelton, John M.; Pop, Iliodora V.; Gerber, David E.; Girard, Luc; Liu, Xiao-yun; Behrens, Carmen; Rodriguez-Canales, Jaime; Liu, Hui; Wistuba, Ignacio I.; Richardson, James A.; Minna, John D.; Tedder, Thomas F.; Vitetta, Ellen S.

2014-01-01

CD22 is a transmembrane glycoprotein expressed by mature B cells. It inhibits signal transduction by the B cell receptor and its co-receptor CD19. Recently it was reported that most human lung cancer cells and cell lines express CD22 making it an important new lung cancer therapeutic target (Can Res 72:5556, 2012). The objective of our studies was to independently validate these results with the goal of testing the efficacy of our CD22 immunotoxins on lung cancer cell lines. As determined by qRT-PCR analysis, we found that levels of CD22 mRNA in a panel of human lung cancer cell lines were 200–60,000- fold lower than those observed in the human CD22+ Burkitt’s lymphoma cells, Daudi. Using flow cytometry with a panel of CD22 monoclonal antibodies and Western blot analyses, we could not detect surface or intracellular expression of CD22 protein in a panel of lung cancer cell lines. In addition, the in vitro proliferation of the lung tumor cell lines was not affected by CD22 antibodies or our highly potent anti-CD22 immunotoxin. By contrast, CD22+ Daudi cells expressed high levels of CD22 mRNA and protein and were sensitive to our CD22 immunotoxin. Importantly, primary non-small cell lung cancers from over 250 patient specimens did not express detectable levels of CD22 protein as assessed by immunohistochemistry. We conclude that CD22 is not expressed at measurable levels on the surface of lung cancer cells and that these cells can not be killed by anti-CD22 immunotoxins. PMID:24395821

Biomonitoring potential of five sympatric Tillandsia species for evaluating urban metal pollution (Cd, Hg and Pb)

NASA Astrophysics Data System (ADS)

Sánchez-Chardi, Alejandro

2016-04-01

The present study quantifies non essential heavy metals highly toxic for biological systems (Pb, Hg and Cd) in five autochthonous epiphytic plants from Tillandsia genus (T. recurvata, T. meridionalis, T. duratii, T. tricholepis, T. loliacea) according to different traffic levels (reference, low, medium and high polluted sites) in Asunción (Paraguay). The three metals increased in polluted sites following Pb (till 62.99 ppm in T. tricholepis) > Cd (till 1.35 ppm in T. recurvata) > Hg (till 0.36 ppm in T. recurvata) and Pb and Cd levels were directly related to traffic flow. Although the species showed similar bioaccumulation pattern (namely, higher levels of metals in polluted sites), enrichment factors (maximum EF values 37.00, 18.16, and 11.90 for Pb, Hg, and Cd, respectively) reported T. tricholepis as the most relevant bioindicator due to its wide distribution and abundance in study sites, low metal content in control site and high metal contents in polluted sites, and significant correlations with traffic density of Pb and Cd. This study emphasizes the necessity of biomonitoring air pollution in areas out of air monitoring control such as Asunción, where the high levels of metal pollution especially Pb, may represent an increment of risk for the human population inhabiting this urban area.

Soluble CD40L Is a Useful Marker to Predict Future Strokes in Patients With Minor Stroke and Transient Ischemic Attack.

PubMed

Li, Jiejie; Wang, Yilong; Lin, Jinxi; Wang, David; Wang, Anxin; Zhao, Xingquan; Liu, Liping; Wang, Chunxue; Wang, Yongjun

2015-07-01

Elevated soluble CD40 ligand (sCD40L) was shown to be related to cardiovascular events, but the role of sCD40L in predicting recurrent stroke remains unclear. Baseline sCD40L levels were measured in 3044 consecutive patients with acute minor stroke and transient ischemic attack, who had previously been enrolled in the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial. Cox proportional-hazards model was used to assess the association of sCD40L with recurrent stroke. Patients in the top tertile of sCD40L levels had increased risk of recurrent stroke comparing with those in the bottom tertile, after adjusted for conventional confounding factors (hazard ratio, 1.49; 95% confidence interval, 1.11-2.00; P=0.008). The patients with elevated levels of both sCD40L and high-sensitive C-reactive protein also had increased risk of recurrent stroke (hazard ratio, 1.81; 95% confidence interval, 1.23-2.68; P=0.003). Elevated sCD40L levels independently predict recurrent stroke in patients with minor stroke and transient ischemic attack. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589. © 2015 American Heart Association, Inc.

Identification of patients at risk of acute rejection by pretransplantation and posttransplantation monitoring of soluble CD30 levels in kidney transplantation.

PubMed

Sengul, Sule; Keven, Kenan; Gormez, Ulku; Kutlay, Sim; Erturk, Sehsuvar; Erbay, Bulent

2006-04-27

In this study, we investigated the impact of pre- and posttransplantation sCD30 monitoring on early (<6 months) acute rejection (AR) risk and analyzed the effect of different immunosuppressive regimens on posttransplantation sCD30 levels in kidney recipients. Fifty patients receiving kidney allograft and 10 healthy donors were included in this retrospective cohort study. Eight patients developed biopsy-proven AR (19%). In pretransplantation samples, patients showed a significantly higher sCD30 than healthy controls. The pretransplantation and posttransplantation (day-15) sCD30 levels were significantly elevated in rejecting patients compared to non-rejecting patients. No significant differences among immunosuppressive regimens were found in posttransplantation sCD30 levels. High pretransplantation and posttransplantation (day 15) sCD30 levels are associated with increased risk of early AR, and sCD30 can be another tool to evaluate immunological risk prior to kidney transplantation. There was no difference in immunosuppressive regimens used in this study on posttransplantation sCD30 levels at the first month.

Activation of CD11b+ Kupffer Cells/Macrophages as a Common Cause for Exacerbation of TNF/Fas-Ligand-Dependent Hepatitis in Hypercholesterolemic Mice

PubMed Central

Nakashima, Hiroyuki; Ogawa, Yoshiko; Shono, Satoshi; Kinoshita, Manabu; Nakashima, Masahiro; Sato, Atsushi; Ikarashi, Masami; Seki, Shuhji

2013-01-01

We have reported that the mouse hepatic injury induced by either α-galactosylceramide (α-GalCer) or bacterial DNA motifs (CpG-ODN) is mediated by the TNF/NKT cell/Fas-ligand (FasL) pathway. In addition, F4/80+ Kupffer cells can be subclassified into CD68+ subset with a phagocytosing capacity and CD11b+ subset with a TNF-producing capacity. CD11b+ subset increase if mice are fed high-fat and cholesterol diet (HFCD). The present study examined how a HFCD affects the function of NKT cells and F4/80+ CD11b+ subset and these hepatitis models. After the C57BL/6 mice received a HFCD, high-cholesterol diet (HCD), high-fat diet (HFD) and control diet (CD) for four weeks, the HFCD mice increased surface CD1d and intracellular TLR-9 expression by the CD11b+ population compared to CD mice. Hepatic injury induced either by α-GalCer or CpG-ODN was more severe in HCD and HFCD mice compared to CD mice, which was in proportion to the serum TNF levels. In addition, liver cholesterol levels but not serum cholesterol levels nor liver triglyceride levels were involved in the aggravation of hepatitis. The FasL expression of NKT cells induced by both reagents was upregulated in HFCD mice. Furthermore, the liver mononuclear cells and purified F4/80+ CD11b+ subset from HFCD mice stimulated with either reagent in vitro produced a larger amount of TNF than did those from CD mice. Intracellular TNF production in F4/80+ CD11b+ cells was confirmed. The increased number of F4/80+ CD11b+ Kupffer cells/macrophages by HFCD and their enhanced TNF production thus play a pivotal role in TNF/NKT cell/FasL dependent hepatic injury. PMID:23372642

Activation of CD11b+ Kupffer cells/macrophages as a common cause for exacerbation of TNF/Fas-ligand-dependent hepatitis in hypercholesterolemic mice.

PubMed

Nakashima, Hiroyuki; Ogawa, Yoshiko; Shono, Satoshi; Kinoshita, Manabu; Nakashima, Masahiro; Sato, Atsushi; Ikarashi, Masami; Seki, Shuhji

2013-01-01

We have reported that the mouse hepatic injury induced by either α-galactosylceramide (α-GalCer) or bacterial DNA motifs (CpG-ODN) is mediated by the TNF/NKT cell/Fas-ligand (FasL) pathway. In addition, F4/80(+) Kupffer cells can be subclassified into CD68(+) subset with a phagocytosing capacity and CD11b(+) subset with a TNF-producing capacity. CD11b(+) subset increase if mice are fed high-fat and cholesterol diet (HFCD). The present study examined how a HFCD affects the function of NKT cells and F4/80(+) CD11b(+) subset and these hepatitis models. After the C57BL/6 mice received a HFCD, high-cholesterol diet (HCD), high-fat diet (HFD) and control diet (CD) for four weeks, the HFCD mice increased surface CD1d and intracellular TLR-9 expression by the CD11b(+) population compared to CD mice. Hepatic injury induced either by α-GalCer or CpG-ODN was more severe in HCD and HFCD mice compared to CD mice, which was in proportion to the serum TNF levels. In addition, liver cholesterol levels but not serum cholesterol levels nor liver triglyceride levels were involved in the aggravation of hepatitis. The FasL expression of NKT cells induced by both reagents was upregulated in HFCD mice. Furthermore, the liver mononuclear cells and purified F4/80(+) CD11b(+) subset from HFCD mice stimulated with either reagent in vitro produced a larger amount of TNF than did those from CD mice. Intracellular TNF production in F4/80(+) CD11b(+) cells was confirmed. The increased number of F4/80(+) CD11b(+) Kupffer cells/macrophages by HFCD and their enhanced TNF production thus play a pivotal role in TNF/NKT cell/FasL dependent hepatic injury.

Kidney graft recipients with pretransplantation HLA CLASS I antibodies and high soluble CD30 are at high risk for graft loss.

PubMed

Rodríguez, Libia M; París, Sara C; Arbeláez, Mario; Cotes, José M; Süsal, Caner; Torres, Yolanda; García, Luís F

2007-08-01

In the present study, we investigated whether pretransplantation HLA class I and class II antibodies and pretransplantation levels of soluble CD30 (sCD30) and IgA anti-Fab autoantibodies are predictive of kidney allograft survival. Pretransplantation sera of 504 deceased-donor kidney recipients were tested for IgG HLA class I and class II antibodies, sCD30, and IgA anti-Fab levels using the CTS 4 ELISA kit. Kidney graft survival was estimated by Kaplan-Meier method and multivariate Cox regression. Regardless of the presence of HLA class II antibodies, recipients with high HLA class I reactivity had lower 1-year graft survival than recipients with low reactivity (p < 0.01). Recipients with high sCD30 had lower 5-year graft survival rate than those with low sCD30 (p < 0.01). The sCD30 effect was observed in presensitized and nonsensitized recipients, demonstrated a synergistic effect with HLA class I antibodies (p < 0.001), and appeared to be neutralized in recipients with no HLA class II mismatches. IgA anti-Fab did not influence kidney graft survival. Our results indicate that high pretransplantation sCD30 levels and HLA class I positivity increase the risk of kidney graft loss regardless of other factors. Consequently, such determinations should be routinely performed to estimate recipients' risks of graft rejection before transplantation.

RANK Expression and Osteoclastogenesis in Human Monocytes in Peripheral Blood from Rheumatoid Arthritis Patients.

PubMed

Nanke, Yuki; Kobashigawa, Tsuyoshi; Yago, Toru; Kawamoto, Manabu; Yamanaka, Hisashi; Kotake, Shigeru

2016-01-01

Rheumatoid arthritis (RA) appears as inflammation of synovial tissue and joint destruction. Receptor activator of NF- κ B (RANK) is a member of the TNF receptor superfamily and a receptor for the RANK ligand (RANKL). In this study, we examined the expression of RANK high and CCR6 on CD14 + monocytes from patients with RA and healthy volunteers. Peripheral blood samples were obtained from both the RA patients and the healthy volunteers. Osteoclastogenesis from monocytes was induced by RANKL and M-CSF in vitro . To study the expression of RANK high and CCR6 on CD14 + monocytes, two-color flow cytometry was performed. Levels of expression of RANK on monocytes were significantly correlated with the level of osteoclastogenesis in the healthy volunteers. The expression of RANK high on CD14 + monocyte in RA patients without treatment was elevated and that in those receiving treatment was decreased. In addition, the high-level expression of RANK on CD14 + monocytes was correlated with the high-level expression of CCR6 in healthy volunteers. Monocytes expressing both RANK and CCR6 differentiate into osteoclasts. The expression of CD14 + RANK high in untreated RA patients was elevated. RANK and CCR6 expressed on monocytes may be novel targets for the regulation of bone resorption in RA and osteoporosis.

Cadmium accumulation in different rice cultivars and screening for pollution-safe cultivars of rice.

PubMed

Yu, Hui; Wang, Junli; Fang, Wei; Yuan, Jiangang; Yang, Zhongyi

2006-11-01

Large areas of contaminated land are being used for agricultural production in some countries due to the high demand for food. To minimize the influx of pollutants to the human food chain through consumption of agricultural products, we propose the concept of pollution-safe cultivars (PSCs), i.e. cultivars whose edible parts accumulate a specific pollutant at a level low enough for safe consumption, even when grown in contaminated soil. We tested the feasibility of the PSC concept by growing 43 cultivars of paddy rice (Oryza sativa L., including 20 normal and 23 hybrid cultivars) under a high (75.69-77.55 mg kg(-1)) and a low (1.75-1.85 mg kg(-1)) cadmium (Cd) exposure. These pot experiments took place in the spring and summer of 2004. At the low level of Cd exposure, 30 out of the 43 tested cultivars were found to be Cd-PSCs. Grain Cd concentrations were highly correlated (p<0.01) between the two experiments, suggesting that Cd accumulation in rice grain is genotype-dependent and that the selection of PSCs is possible, at least at a certain level of soil contamination. No Cd-PSCs were found under the high level of Cd exposure. Yield was enhanced in some cultivars and depressed in others in response to elevated soil Cd, indicating that farmers cannot rely on yield depression as an indicator of toxicity of the grains. It is therefore important and feasible to screen for PSCs and to establish PSC breeding programs to effectively and efficiently reduce the risk of human exposure to soil pollutants, such as Cd, through crop consumption.

Predicting renal graft failure by sCD30 levels and de novo HLA antibodies at 1year post-transplantation.

PubMed

Wang, Dong; Wu, Guojun; Chen, Jinhua; Yu, Ziqiang; Wu, Weizhen; Yang, Shunliang; Tan, Jianming

2012-06-01

HLA antibodies and sCD30 levels were detected in the serum sampled from 620 renal graft recipients at 1 year post-transplantation, which were followed up for 5 years. Six-year graft and patient survivals were 81.6% and 91.0%. HLA antibodies were detected in 45 recipients (7.3%), of whom there were 14 cases with class I antibodies, 26 cases with class II, and 5 cases with both class I and II. Much more graft loss was record in recipients with HLA antibodies than those without antibodies (60% vs. 15.1%, p<0.001). Significantly higher sCD30 levels were recorded in recipients suffering graft loss than the others (73.9±48.8 U/mL vs. 37.3±14.6 U/mL, p<0.001). Compared with those with high sCD30 levels, recipients with low sCD30 levels (<50 U/mL) had much better 6-year graft survival (92.4% vs. 46.6%, p<0.001). Further statistical analysis showed that detrimental effect of de novo HLA antibodies and high sCD30 on graft survival was not only independent but also additive. Therefore, post-transplantation monitoring of HLA antibodies and sCD30 levels is necessary and recipients with elevated sCD30 level and/or de novo HLA antibody should be paid more attention in order to achieve better graft survival. Copyright © 2012 Elsevier B.V. All rights reserved.

Persistent high plasma levels of sCD163 and sCD14 in adult patients with measles virus infection.

PubMed

Mascia, Claudia; Pozzetto, Irene; Kertusha, Blerta; Marocco, Raffaella; Del Borgo, Cosmo; Tieghi, Tiziana; Vita, Serena; Savinelli, Stefano; Iannetta, Marco; Vullo, Vincenzo; Lichtner, Miriam; Mastroianni, Claudio Maria

2018-01-01

Measles is an infectious disease that represents a serious public health problem worldwide, being associated with increased susceptibility to secondary infections, especially in the respiratory and gastrointestinal tracts. The aim of this study was to evaluate sCD163 and sCD14 levels in measles virus (MV) infected patients, as markers of immune activation, in order to better understand their role in the pathogenesis of the disease. TNF-α plasma levels were also evaluated. sCD163, sCD14 and TNF-α were measured by ELISA in plasma samples of 27 MV infected patients and 27 healthy donors (HD) included as controls. At the time of hospital admission, sCD163 and sCD14 levels were significantly higher in MV infected patients than in HD, while a decrease in TNF-α levels were found even if without statistical significance. sCD163 and sCD14 levels were significantly decreased after two months from acute infection compared to hospital admission although they remained significantly higher compared to HD. TNF-α levels increased significantly during the follow-up period. Considering clinical parameters, sCD163 levels positively correlated with aspartate aminotransferase, white blood cell count and neutrophils rate, while negatively correlated with the lymphocyte percentage. sCD14 levels positively correlated with the neutrophil and lymphocyte percentages. These results indicate that, despite the resolution of symptoms, an important macrophage/monocyte activation persists in measles patients, even after two months from infection.

Measurement of soluble CD59 in CSF in demyelinating disease: Evidence for an intrathecal source of soluble CD59.

PubMed

Zelek, Wioleta M; Watkins, Lewis M; Howell, Owain W; Evans, Rhian; Loveless, Sam; Robertson, Neil P; Beenes, Marijke; Willems, Loek; Brandwijk, Ricardo; Morgan, B Paul

2018-02-01

CD59, a broadly expressed glycosylphosphatidylinositol-anchored protein, is the principal cell inhibitor of complement membrane attack on cells. In the demyelinating disorders, multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), elevated complement protein levels, including soluble CD59 (sCD59), were reported in cerebrospinal fluid (CSF). We compared sCD59 levels in CSF and matched plasma in controls and patients with MS, NMOSD and clinically isolated syndrome (CIS) and investigated the source of CSF sCD59 and whether it was microparticle associated. sCD59 was quantified using enzyme-linked immunosorbent assay (ELISA; Hycult; HK374-02). Patient and control CSF was subjected to western blotting to characterise anti-CD59-reactive materials. CD59 was localised by immunostaining and in situ hybridisation. CSF sCD59 levels were double those in plasma (CSF, 30.2 ng/mL; plasma, 16.3 ng/mL). Plasma but not CSF sCD59 levels differentiated MS from NMOSD, MS from CIS and NMOSD/CIS from controls. Elimination of microparticles confirmed that CSF sCD59 was not membrane anchored. CSF levels of sCD59 are not a biomarker of demyelinating diseases. High levels of sCD59 in CSF relative to plasma suggest an intrathecal source; CD59 expression in brain parenchyma was low, but expression was strong on choroid plexus (CP) epithelium, immediately adjacent the CSF, suggesting that this is the likely source.

Early elevation of soluble CD14 may help identify trauma patients at high risk for infection.

PubMed

Carrillo, E H; Gordon, L; Goode, E; Davis, E; Polk, H C

2001-05-01

Elevated levels of soluble CD14 (sCD14) have been implicated in both gram-positive and gram-negative sepsis, and it has been associated with high mortality in trauma patients who become infected. Eleven healthy volunteers and 25 adult trauma patients with multiple injuries and a mean Injury Severity Score of 32 participated. Whole blood was obtained at intervals. Immunohistochemistry was used to quantify membrane CD14 (mCD14), by flow cytometry and plasma levels of sCD14 by enzyme-linked immunosorbent assay. Analysis of variance and Student's T test with Mann-Whitney posttest were used to determine significance at p < 0.05. On posttrauma day 1, sCD14 was significantly different in the plasma of infected patients compared with normal controls (7.16 +/- 1.87 microg/mL vs. 4.4 +/- 0.92 microg/mL, p < 0.01), but not significantly different from noninfected patients. The percentage of monocytes expressing mCD14 in trauma patients did not differentiate them from normal controls; however, mCD14 receptor density did demonstrate significance in septic trauma patients (n = 15) versus normal controls on posttrauma day 3 (p = 0.0065). On the basis of our data, mCD14 did not differentiate infected and noninfected trauma patients, although trauma in general reduced mCD14 and elevated sCD14. Interestingly, 100% of patients who exceeded plasma levels of 8 microg/mL of sCD14 on day 1 after injury developed infections. Therefore, early high expressers of sCD14 may be at higher risk for infectious complications after trauma.

Soluble CD30 serum level in HCV-positive chronic active hepatitis: A surrogate marker of disease activity?

PubMed

Foschi, F G; Gramenzi, A; Castelli, E; Cursaro, C; Pagani, S; Margotti, M; D'Errico, A; Andreone, P; Stefanini, G F; Bernardi, M

2000-06-01

In the present study, high levels of CD30s, a glycoprotein preferentially expressed and released by T lymphocytes producing Th(2)-type cytokines, were seen in the sera of patients with chronic hepatitis C, and a correlation with histological activity of the disease was found. CD30s levels were assayed in the sera of 29 HCV RNA-positive patients with histologically proven chronic active hepatitis and in 30 healthy blood donors. Thirteen of 29 (45%) HCV patients had CD30s serum levels above the normal range (>20 U/ml). Mean CD30s serum levels were significantly higher in HCV patients than in controls (P<0.0005). A positive correlation was found between serum CD30s levels and both the histological activity index (r=0.59, P=0.001) and ALT serum levels (r=0.5; P=0.006). The raised CD30s level found in more severe HCV liver disease indirectly suggests activation and expansion of Th(2)cells. CD30s levels could represent a useful surrogate marker of activity in chronic HCV infections. Copyright 2000 Academic Press.

The effect of angiotensin-2 receptor blocker valsartan on circulating level of endothelial progenitor cells in diabetic patients with asymptomatic coronary artery disease.

PubMed

Berezin, Alexander E; Kremzer, Alexander A; Martovitskaya, Yulia V; Samura, Tatyana A

2015-01-01

Decreased circulating endothelial progenitor cells (EPCs) are considered as strong and robust biomarkers for the prediction of cardiovascular outcomes in diabetic populations. The perspectives for modulating EPCs levels in T2DM with known coronary artery disease (CAD) with different drugs, affected mechanisms of improving mobilization of EPCs from tissue, are not still understood. To evaluate an effect of angiotensin-2 receptor blocker valsartan on circulating level of EPCs in diabetic patients with asymptomatic CAD. The study population was structured retrospectively after determining the CAD by contrast-enhanced spiral computed tomography angiography in 126 asymptomatic subjects. All subjects were distributed into two cohorts depending on daily doses of valsartan given. Low (80-160 mg daily orally) and high doses (240-320 mg daily orally) of valsartan were used and they were adjusted depending on achieving BP level less than 140/80 mmHg. The change from baseline in CD34(+) subset cells (frequencies and absolute values) was not significantly different between treatment cohorts. We found a significant increase of circulating level of CD14(+)CD309(+) cells in two patient cohorts. But more prominent change of CD14(+)CD309(+) cells was verified in subjects who were given valsartan in high daily doses when compared with persons who were included into cohort with low daily doses of the drug (1.96% versus 2.59%, respectively; P<0.05). Therefore, both frequencies and absolute values in CD14(+)CD309(+)Tie(2+) were increased significantly in patients who were treated with high doses of valsartan only. We found positive influence of angiotensin-2 receptor blocker valsartan in escalation doses on bone marrow-derived EPCs phenotyped as CD14(+)CD309(+) and CD14(+)CD309(+)Tie(2+) in T2DM patients with known asymptomatic CAD. Copyright © 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Soluble CD163 is an indicator of liver inflammation and fibrosis in patients chronically infected with the hepatitis B virus.

PubMed

Dultz, G; Gerber, L; Farnik, H; Berger, A; Vermehren, J; Pleli, T; Zeuzem, S; Piiper, A; Kronenberger, B; Waidmann, O

2015-04-01

Soluble CD163 (sCD163), a marker for macrophage activation, was found to be associated with the severity of liver cirrhosis. The aim of the current study was to investigate whether serum sCD163 levels correlate with liver inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection. In a retrospective cohort study, serum sCD163 levels were assessed by ELISA together with clinical and laboratory data in 186 patients with chronic HBV infection and 15 healthy controls. The relation between parameters for liver fibrosis and necroinflammation and sCD163 levels was analysed. Additionally, sCD163 was quantified in a subset of follow-up serum samples after initiation of antiviral treatment. sCD163 levels differed among phases of chronic HBV infection (P < 0.0001), and sCD163 concentrations were associated with inflammatory activity and fibrosis in the liver. sCD163 levels ≥ 1961 ng/l had a high specificity in the identification of subjects with substantial fibrosis (F ≥ 2). sCD163 concentrations decreased significantly after initiation of antiviral treatment. The correlation of sCD163 levels with necroinflammation and fibrosis and the sCD163 decline under treatment indicates that macrophage activation plays a role in HBV-related liver pathogenesis. © 2014 John Wiley & Sons Ltd.

IL-4 and IL-13 mediated down-regulation of CD8 expression levels can dampen anti-viral CD8⁺ T cell avidity following HIV-1 recombinant pox viral vaccination.

PubMed

Wijesundara, Danushka K; Jackson, Ronald J; Tscharke, David C; Ranasinghe, Charani

2013-09-23

We have shown that mucosal HIV-1 recombinant pox viral vaccination can induce high, avidity HIV-specific CD8(+) T cells with reduced interleukin (IL)-4 and IL-13 expression compared to, systemic vaccine delivery. In the current study how these cytokines act to regulate anti-viral CD8(+) T, cell avidity following HIV-1 recombinant pox viral prime-boost vaccination was investigated. Out of a panel of T cell avidity markers tested, only CD8 expression levels were found to be enhanced on, KdGag197-205 (HIV)-specific CD8(+) T cells obtained from IL-13(-/-), IL-4(-/-) and signal transducer and, activator of transcription of 6 (STAT6)(-/-) mice compared to wild-type (WT) controls following, vaccination. Elevated CD8 expression levels in this instance also correlated with polyfunctionality, (interferon (IFN)-γ, tumour necorsis factor (TNF)-α and IL-2 production) and the avidity of HIVspecific CD8(+) T cells. Furthermore, mucosal vaccination and vaccination with the novel adjuvanted IL-13 inhibitor (i.e. IL-13Rα2) vaccines significantly enhanced CD8 expression levels on HIV-specific CD8(+), T cells, which correlated with avidity. Using anti-CD8 antibodies that blocked CD8 availability on CD8(+), T cells, it was established that CD8 played an important role in increasing HIV-specific CD8(+) T cell avidity and polyfunctionality in IL-4(-/-), IL-13(-/-) and STAT6(-/-) mice compared to WT controls, following vaccination. Collectively, our data demonstrate that IL-4 and IL-13 dampen CD8 expression levels on anti-viral CD8(+) T cells, which can down-regulate anti-viral CD8(+) T cell avidity and, polyfunctionality following HIV-1 recombinant pox viral vaccination. These findings can be exploited to, design more efficacious vaccines not only against HIV-1, but many chronic infections where high, avidity CD8(+) T cells help protection. Copyright © 2013 Elsevier Ltd. All rights reserved.

Antigen sensitivity of CD22-specific chimeric T cell receptors is modulated by target epitope distance from the cell membrane

PubMed Central

James, Scott E.; Greenberg, Philip D.; Jensen, Michael C.; Lin, Yukang; Wang, Jinjuan; Till, Brian G.; Raubitschek, Andrew A.; Forman, Stephen J.; Press, Oliver W.

2008-01-01

We have targeted CD22 as a novel tumor-associated antigen for recognition by human CTL genetically modified to express chimeric T cell receptors (cTCR) recognizing this surface molecule. CD22-specifc cTCR targeting different epitopes of the CD22 molecule promoted efficient lysis of target cells expressing high levels of CD22 with a maximum lytic potential that appeared to decrease as the distance of the target epitope from the target cell membrane increased. Targeting membrane-distal CD22 epitopes with cTCR+ CTL revealed defects in both degranulation and lytic granule targeting. CD22-specific cTCR+ CTL exhibited lower levels of maximum lysis and lower antigen sensitivity than CTL targeting CD20, which has a shorter extracellular domain than CD22. This diminished sensitivity was not a result of reduced avidity of antigen engagement, but instead reflected weaker signaling per triggered cTCR molecule when targeting membrane-distal epitopes of CD22. Both of these parameters were restored by targeting a ligand expressing the same epitope but constructed as a truncated CD22 molecule to approximate the length of a TCR:pMHC complex. The reduced sensitivity of CD22-specific cTCR+ CTL for antigen-induced triggering of effector functions has potential therapeutic applications, as such cells selectively lysed B cell lymphoma lines expressing high levels of CD22 but demonstrated minimal activity against autologous normal B cells, which express lower levels of CD22. Thus, our results demonstrate that cTCR signal strength – and consequently antigen sensitivity – can be modulated by differential choice of target epitopes with respect to distance from the cell membrane, allowing discrimination between targets with disparate antigen density. PMID:18453625

Antigen sensitivity of CD22-specific chimeric TCR is modulated by target epitope distance from the cell membrane.

PubMed

James, Scott E; Greenberg, Philip D; Jensen, Michael C; Lin, Yukang; Wang, Jinjuan; Till, Brian G; Raubitschek, Andrew A; Forman, Stephen J; Press, Oliver W

2008-05-15

We have targeted CD22 as a novel tumor-associated Ag for recognition by human CTL genetically modified to express chimeric TCR (cTCR) recognizing this surface molecule. CD22-specific cTCR targeting different epitopes of the CD22 molecule promoted efficient lysis of target cells expressing high levels of CD22 with a maximum lytic potential that appeared to decrease as the distance of the target epitope from the target cell membrane increased. Targeting membrane-distal CD22 epitopes with cTCR(+) CTL revealed defects in both degranulation and lytic granule targeting. CD22-specific cTCR(+) CTL exhibited lower levels of maximum lysis and lower Ag sensitivity than CTL targeting CD20, which has a shorter extracellular domain than CD22. This diminished sensitivity was not a result of reduced avidity of Ag engagement, but instead reflected weaker signaling per triggered cTCR molecule when targeting membrane-distal epitopes of CD22. Both of these parameters were restored by targeting a ligand expressing the same epitope, but constructed as a truncated CD22 molecule to approximate the length of a TCR:peptide-MHC complex. The reduced sensitivity of CD22-specific cTCR(+) CTL for Ag-induced triggering of effector functions has potential therapeutic applications, because such cells selectively lysed B cell lymphoma lines expressing high levels of CD22, but demonstrated minimal activity against autologous normal B cells, which express lower levels of CD22. Thus, our results demonstrate that cTCR signal strength, and consequently Ag sensitivity, can be modulated by differential choice of target epitopes with respect to distance from the cell membrane, allowing discrimination between targets with disparate Ag density.

Trigger-happy resident memory CD4+ T cells inhabit the human lungs.

PubMed

Oja, A E; Piet, B; Helbig, C; Stark, R; van der Zwan, D; Blaauwgeers, H; Remmerswaal, E B M; Amsen, D; Jonkers, R E; Moerland, P D; Nolte, M A; van Lier, R A W; Hombrink, P

2018-05-01

Resident memory T cells (T RM ) reside in the lung epithelium and mediate protective immunity against respiratory pathogens. Although lung CD8 + T RM have been extensively characterized, the properties of CD4 + T RM remain unclear. Here we determined the transcriptional signature of CD4 + T RM , identified by the expression of CD103, retrieved from human lung resection material. Various tissue homing molecules were specifically upregulated on CD4 + T RM , whereas expression of tissue egress and lymph node homing molecules were low. CD103 + T RM expressed low levels of T-bet, only a small portion expressed Eomesodermin (Eomes), and although the mRNA levels for Hobit were increased, protein expression was absent. On the other hand, the CD103 + T RM showed a Notch signature. CD4 + CD103 + T RM constitutively expressed high transcript levels of numerous cytotoxic mediators that was functionally reflected by a fast recall response, magnitude of cytokine production, and a high degree of polyfunctionality. Interestingly, the superior cytokine production appears to be because of an accessible interferon-γ (IFNγ) locus and was partially because of rapid translation of preformed mRNA. Our studies provide a molecular understanding of the maintenance and potential function of CD4 + T RM in the human lung. Understanding the specific properties of CD4 + T RM is required to rationally improve vaccine design.

Very high levels of soluble CD30 recognize the patients with classical Hodgkin's lymphoma retaining a very poor prognosis.

PubMed

Visco, Carlo; Nadali, Gianpaolo; Vassilakopoulos, Theodoros P; Bonfante, Valeria; Viviani, Simonetta; Gianni, Alessandro M; Federico, Massimo; Luminari, Stefano; Peethambaram, Prema; Witzig, Thomas E; Pangalis, Gerassimos; Cabanillas, Fernando; Medeiros, L Jeffrey; Sarris, Andreas H; Pizzolo, Giovanni

2006-11-01

To evaluate the prognostic role of pretreatment serum levels of soluble CD30 (sCD30) in patients with advanced stage classical Hodgkin's lymphoma (cHL) treated with adriamycin, bleomycin, vinblastine, and dacarbazine or equivalent regimens. We identified 321 previously untreated patients with cHL who presented to the participating centers between 1985 and 2002, and had serum samples available for the determination of sCD30 levels. With a median follow-up of 72 months, the actuarial 5-year overall survival was 82%, and failure-free survival (FFS) was 71%. The median serum level of sCD30 was 65 U/mL (range: 1-2230), and was significantly higher (P < 0.0001) when compared with a group of 113 healthy controls (4 U/mL, range: 0-20). Increasing level of sCD30 was associated with a continuous worsening of FFS and OS, and patients with sCD30 >or=200 U/mL had a 5-year FFS of 39%. With multivariate analysis, sCD30, Ann Arbor stage, and lactic acid dehydrogenase were significant independent factors in terms of FFS. The association of the above-mentioned three independent prognostic variables could discriminate 22% of patients with 5-year FFS of 40%. Our data confirm the independent prognostic role of sCD30 in identifying the patients with high risk of treatment failure, and show that its association with other variables can recognize patients with FFS considerably lower than 50%.

Doping dependent crystal structures and optoelectronic properties of n-type CdSe:Ga nanowries.

PubMed

Hu, Zhizhong; Zhang, Xiujuan; Xie, Chao; Wu, Chunyan; Zhang, Xiaozhen; Bian, Liang; Wu, Yiming; Wang, Li; Zhang, Yuping; Jie, Jiansheng

2011-11-01

Although CdSe nanostructures possess excellent electrical and optical properties, efforts to make nano-optoelectronic devices from CdSe nanostructures have been hampered by the lack of efficient methods to rationally control their structural and electrical characteristics. Here, we report CdSe nanowires (NWs) with doping dependent crystal structures and optoelectronic properties by using gallium (Ga) as the efficient n-type dopant via a simple thermal co-evaporation method. The phase change of CdSe NWs from wurtzite to zinc blende with increased doping level is observed. Systematical measurements on the transport properties of the CdSe:Ga NWs reveal that the NW conductivity could be tuned in a wide range of near nine orders of magnitude by adjusting the Ga doping level and a high electron concentration up to 4.5 × 10(19) cm(-3) is obtained. Moreover, high-performance top-gate field-effect transistors are constructed based on the individual CdSe:Ga NWs by using high-κ HfO(2) as the gate dielectric. The great potential of the CdSe:Ga NWs as high-sensitive photodetectors and nanoscale light emitters is also exploited, revealing the promising applications of the CdSe:Ga NWs in new-generation nano-optoelectronics.

Lead and cadmium in the blood of nine species of seabirds, Marion Island, South Africa.

PubMed

Summers, Carly F; Bowerman, William W; Parsons, Nola; Chao, Wayne Y; Bridges, William C

2014-10-01

Levels of lead (Pb) and cadmium (Cd) were investigated as potential stressors in nine species of breeding seabirds on Marion Island, South Africa. The majority of blood Pb levels (95 %) were below background exposure levels. Species was a significant factor in ranked means analysis for mean blood Pb levels. Fewer individual blood Cd levels (<60 %) were within background exposure levels and species was not significant. Elevated levels of Cd have been documented in other seabird species without apparent outward effects, which suggests that seabirds may be adapted to high cadmium environments, particularly from their diets. Overall, the results suggest Pb and Cd are not primary causes for concern in these seabirds.

Cushing`s disease: Fibrinogen and D-dimer levels fail to normalize despite early postoperative remission - a prospective, controlled study.

PubMed

Witek, Przemysław; Zieliński, Grzegorz; Szamotulska, Katarzyna; Witek, Joanna; Kamiński, Grzegorz

2016-01-01

Effective transsphenoidal surgery (TSS) for Cushing`s disease (CD) normalizes cortisol levels and reduces complications of hypercortisolism. However, there is evidence of increased cardiovascular morbidity even after successful surgery. A prospective, controlled study on the dynamics of fibrinogen and D-dimer levels with a six-month follow-up after an effective TSS for CD. Forty patients with CD and forty healthy age- and sex-matched subjects were included. We assessed ACTH, urinary and serum cortisol, and fibrinogen and D-dimer levels before TSS and during follow-up. Baseline BMI (P < 0.001), fibrinogen (P = 0.002), and D-dimer (P = 0.001) levels in CD patients were significantly higher than those in healthy controls. High fibrinogen levels in the CD group were independent of BMI, and were positively associated with hsCRP (rS = 0.61, P < 0.001) and arterial hypertension (P = 0.029). After the six-month follow-up we confirmed a sustained difference between the remission group and controls in fibrinogen and D-dimer levels (P = 0.001 and P = 0.017, respectively). Despite early biochemical remission of CD the levels of fibrinogen and D-dimer failed to decrease. This probably contributes to the high risk of thrombotic events and indicates the need for a close follow-up for signs of thromboembolic and cardiovascular complications in patients with early CD remission. (Endokrynol Pol 2016; 67 (3): 283-291).

No simple answers for the Finnish and Russian Karelia allergy contrast: Methylation of CD14 gene.

PubMed

Khoo, Siew-Kim; Mäkelä, Mika; Chandler, David; Schultz, En Nee; Jamieson, Sarra E; Goldblatt, Jack; Haahtela, Tari; LeSouëf, Peter; Zhang, Guicheng

2016-11-01

Finnish and Russian Karelian children have a highly contrasting occurrence of asthma and allergy. In these two environments, we studied associations between total serum immunoglobulin E (IgE) with methylation levels in cluster of differentiation 14 (CD14). Five hundred Finnish and Russian Karelian children were included in four groups: Finnish children with high IgE (n = 126) and low IgE (n = 124) as well as Russian children with high IgE (n = 125) and low IgE (n = 125). DNA was extracted from whole blood cells and pyrosequenced. Three CpG sites were selected in the promoter region of CD14. Methylation levels in two of the three CpG sites were higher in the Finnish compared to Russian Karelian children. In the promoter area of CD14, the Finnish compared to Russian children with low IgE had a significant (p < 0.0001) increase in methylation levels at the Amp5Site 2. Likewise, the Finnish compared to Russian children with high IgE had a significant (p = 0.003) increase in methylation levels at the Amp5Site 3. In Russian children with low vs. high IgE, there were significant differences in methylation levels, but this was not the case on the Finnish side. In the regression analysis, adding the methylation variation of CD14 to the model did not explain the higher asthma and allergy risk in the Finnish children. The methylation levels in the promoter region of CD14 gene were higher in the Finnish compared to Russian Karelian children. However, the methylation variation of this candidate gene did not explain the asthma and allergy contrast between these two areas. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Delineating CD4 dependency of HIV-1: Adaptation to infect low level CD4 expressing target cells widens cellular tropism but severely impacts on envelope functionality

PubMed Central

Beauparlant, David; Rusert, Peter; Magnus, Carsten; Weber, Jacqueline; Uhr, Therese; Clapham, Paul R.; Metzner, Karin J.

2017-01-01

A hallmark of HIV-1 infection is the continuously declining number of the virus’ predominant target cells, activated CD4+ T cells. With diminishing CD4+ T cell levels, the capacity to utilize alternate cell types and receptors, including cells that express low CD4 receptor levels such as macrophages, thus becomes crucial. To explore evolutionary paths that allow HIV-1 to acquire a wider host cell range by infecting cells with lower CD4 levels, we dissected the evolution of the envelope-CD4 interaction under in vitro culture conditions that mimicked the decline of CD4high target cells, using a prototypic subtype B, R5-tropic strain. Adaptation to CD4low targets proved to severely alter envelope functions including trimer opening as indicated by a higher affinity to CD4 and loss in shielding against neutralizing antibodies. We observed a strikingly decreased infectivity on CD4high target cells, but sustained infectivity on CD4low targets, including macrophages. Intriguingly, the adaptation to CD4low targets altered the kinetic of the entry process, leading to rapid CD4 engagement and an extended transition time between CD4 and CCR5 binding during entry. This phenotype was also observed for certain central nervous system (CNS) derived macrophage-tropic viruses, highlighting that the functional perturbation we defined upon in vitro adaptation to CD4low targets occurs in vivo. Collectively, our findings suggest that CD4low adapted envelopes may exhibit severe deficiencies in entry fitness and shielding early in their evolution. Considering this, adaptation to CD4low targets may preferentially occur in a sheltered and immune-privileged environment such as the CNS to allow fitness restoring compensatory mutations to occur. PMID:28264054

Immunological alterations in individuals exposed to metal(loid)s in the Panasqueira mining area, Central Portugal.

PubMed

Coelho, Patrícia; García-Lestón, Julia; Costa, Solange; Costa, Carla; Silva, Susana; Fuchs, Dietmar; Geisler, Simon; Dall'Armi, Valentina; Zoffoli, Roberto; Bonassi, Stefano; Pásaro, Eduardo; Laffon, Blanca; Teixeira, João Paulo

2014-03-15

Environmental studies performed in Panasqueira mine area (central Portugal) identified high concentrations of several metal(loid)s in environmental media, and individuals environmentally and occupationally exposed showed higher levels of As, Cr, Mg, Mn, Mo, Pb and Zn in blood, urine, hair and nails when compared to unexposed controls. To evaluate the presence of immunological alterations attributable to environmental contamination, we quantified neopterin, kynurenine, tryptophan, and nitrite concentrations in plasma, and analysed the percentage of several lymphocytes subsets, namely CD3(+), CD4(+) and CD8(+) T-cells, CD19(+) B-cells, and CD16(+)56(+) natural killer (NK) cells in a group of individuals previously tested for metal(loid) levels in different biological matrices. The environmentally exposed group had significantly lower levels of %CD8(+) and higher CD4(+)/CD8(+) ratios, whereas the occupationally exposed individuals showed significant decreases in %CD3(+) and %CD4(+), and significant increases in %CD16(+)56(+), when compared to controls. Analysed biomarkers were found to be influenced by age, particularly neopterin, kynurenine and kynurenine to tryptophan ratio (Kyn/Trp) with significantly higher levels in older individuals, and %CD3(+), %CD8(+) and %CD19(+) with significantly lower values in older individuals. Males environmentally exposed showed significantly lower values of %CD19(+) when compared to control females. The concentration of Pb in toenails was associated to the level of neopterin, kynurenine and Kyn/Trp ratio (all direct), and the concentration of Mn in blood to the level of %CD8(+), %CD19(+) (both inverse) and CD4(+)/CD8(+) ratio (direct). Overall our results show that the metal(loid) contamination in Panasqueira mine area induced immunotoxic effects in exposed populations, possibly increasing susceptibility to diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

Plasma soluble cluster of differentiation 147 levels are increased in breast cancer patients and associated with lymph node metastasis and chemoresistance.

PubMed

Kuang, Y H; Liu, Y J; Tang, L L; Wang, S M; Yan, G J; Liao, L Q

2018-05-25

Cluster of differentiation 147 (CD147) contributes to breast cancer invasion, metastasis, and multidrug resistance. Recent studies have shown that peripheral soluble CD147 (sCD147) is increased in hepatocellular tumour and multiple myeloma patients and correlated with disease severity. The primary aim of our study was to assess the level, as well as the biological and clinical significance of sCD147 in breast cancer. We tested plasma sCD147 levels in 308 breast cancer patients by enzyme-linked immunosorbent assay between February 2014 and February 2017. A subset of 165 cases of benign breast diseases was included as a control group at the same period. We analysed the clinical significance of plasma sCD147 with relevance to clinicopathological factors of breast cancer patients. Plasma sCD147 levels were significantly higher in patients with primary breast cancer than those with benign breast diseases (P=0.001), in patients with locally advanced breast cancer (T3-T4 tumour) than those in early breast cancer (T1-T2 tumour; P=0.001), in patients with lymph node metastasis than in those without (P<0.001), and in patients with high recurrence risk than those with medium recurrence risk (P<0.001). Plasma sCD147 levels were also significantly higher in the chemotherapy-resistant group than in the chemotherapy-sensitive group (P=0.040). Plasma sCD147 was an independent predictor for lymph node metastasis in breast cancer patients (P=0.001). This is the first study to demonstrate that plasma sCD147 levels are elevated in breast cancer patients. Soluble CD147 is also associated with tumour size, lymph node metastasis, high recurrent risk, and chemoresistance. Our findings support that plasma sCD147 is an independent predictive factor for lymph node metastasis.

Declining metal levels at Foundry Cove (Hudson River, New York): response to localized dredging of contaminated sediments.

PubMed

Mackie, Joshua A; Natali, Susan M; Levinton, Jeffrey S; Sañudo-Wilhelmy, Sergio A

2007-09-01

This study examines the effectiveness of remediating a well-recognized case of heavy metal pollution at Foundry Cove (FC), Hudson River, New York. This tidal freshwater marsh was polluted with battery-factory wastes (1953-1979) and dredged in 1994-1995. Eight years after remediation, dissolved and particulate metals (Cd, Co, Cu, Pb, Ni, and Ag) were found to be lower than levels in the lower Hudson near New York City. Levels of metals (Co, Ni, Cd) on suspended particles were comparatively high. Concentrations of surface sediment Cd throughout the marsh system remain high, but have decreased both in the dredged and undredged areas: Cd was 2.4-230mg/kg dw of sediment in 2005 vs. 109-1500mg/kg in the same area in 1983. The rate of tidal export of Cd from FC has decreased by >300-fold, suggesting that dredging successfully stemmed a major source of Cd to the Hudson River.

Tumor evasion of the immune system by converting CD4+CD25- T cells into CD4+CD25+ T regulatory cells: role of tumor-derived TGF-beta.

PubMed

Liu, Victoria C; Wong, Larry Y; Jang, Thomas; Shah, Ali H; Park, Irwin; Yang, Ximing; Zhang, Qiang; Lonning, Scott; Teicher, Beverly A; Lee, Chung

2007-03-01

CD4+CD25+ T regulatory (T(reg)) cells were initially described for their ability to suppress autoimmune diseases in animal models. An emerging interest is the potential role of T(reg) cells in cancer development and progression because they have been shown to suppress antitumor immunity. In this study, CD4+CD25- T cells cultured in conditioned medium (CM) derived from tumor cells, RENCA or TRAMP-C2, possess similar characteristics as those of naturally occurring T(reg) cells, including expression of Foxp3, a crucial transcription factor of T(reg) cells, production of low levels of IL-2, high levels of IL-10 and TGF-beta, and the ability to suppress CD4+CD25- T cell proliferation. Further investigation revealed a critical role of tumor-derived TGF-beta in converting CD4+CD25- T cells into T(reg) cells because a neutralizing Ab against TGF-beta, 1D11, completely abrogated the induction of T(reg) cells. CM from a nontumorigenic cell line, NRP-152, or irradiated tumor cells did not convert CD4+CD25- T cells to T(reg) cells because they produce low levels of TGF-beta in CM. Finally, we observed a reduced tumor burden in animals receiving 1D11. The reduction in tumor burden correlated with a decrease in tumor-derived TGF-beta. Treatment of 1D11 also reduced the conversion of CD4+ T cells into T(reg) cells and subsequent T(reg) cell-mediated suppression of antitumor immunity. In summary, we have demonstrated that tumor cells directly convert CD4+CD25- T cells to T(reg) cells through production of high levels of TGF-beta, suggesting a possible mechanism through which tumor cells evade the immune system.

Pre-transplant soluble CD30 level as a predictor of not only acute rejection and graft loss but pneumonia in renal transplant recipients.

PubMed

Wang, Dong; Wu, Wei-Zhen; Chen, Jin-Hua; Yang, Shun-Liang; Wang, Qing-Hua; Zeng, Zhang-Xin; Tan, Jian-Ming

2010-02-01

Pre-transplant sera of 586 renal graft recipients were tested to investigate whether soluble CD30 (sCD30) is a useful predictor of some severe clinical episodes post-transplant. Correlation analysis showed sCD30 level was significantly correlated with acute rejection (AR) (r=0.242, P<0.001), graft loss (r=0.162, P<0.001), and pneumonia (r=-0.147, P<0.001). Higher sCD30 levels were observed in patients with AR than the others (180.0+/-89.1 vs. 135.3+/-72.7U/ml, P<0.001). And patients with pneumonia had significantly lower pre-transplant sCD30 level than the others (123.2+/-75.5 vs. 150.7+/-79.6U/ml, P=0.003). Based on statistical results, 120 and 240U/ml were selected as the optimal couple of cut-off value to divide patients into three groups: Group High (H), Group Intermedial (I) and Group Low (L). The lowest AR rate of 17.4% was observed in Group L (P<0.001). Significant difference of AR rate was also observed between Group I (29.2%) and H (42.9%) (P<0.001). There were much more patients suffering pneumonia in Group L (P=0.001). Significantly lower 5-year patient survival rate (79.4%) was observed in Group H (P=0.016). These data showed that elevated pre-transplant sCD30 level of renal allograft recipients may reflect an immune state detrimental for renal allograft survival. But sCD30 level lower than <120U/ml may be associated with a high risk of pneumonia. Pre-transplant sCD30 level is an independent predictor of acute rejection, lung infection, even graft survival. Suitable immunosuppression protocol should be selected according to pre-transplant sCD30 level in an attempt to promote patient and graft survival. Copyright 2010 Elsevier B.V. All rights reserved.

Transport Properties of ZnSe- ITO Hetero Junction

NASA Astrophysics Data System (ADS)

Ichibakase, Tsuyoshi

In this report, ITO(Indium Tin Oxide) was used on the glass substrates as the transparent electrode, and ZnSe layer was prepared by the vacuum deposition on this ITO. Then, the electrical characteristics of this sample were investigated by mans of the electric current transport analysis. The sample that ZnSe was prepared as 3.4 μm in case of ITO-ZnSe sample, has high density level at the junction surface. The ITO-ZnSe junction has two type of diffusion current. However, the ITO-ZnSe sample that ZnSe layer was prepared as 0.1 μm can be assumed as the ohmic contact, and ITO-ZnSe(0.1μm) -CdTe sample shows the avalanche breakdown, and it is considered that the avalanche breakdown occurs in CdTe layer. It is difficult to occur the avalanche breakdown, if ZnSe-CdTe junction has high-density level and CdTe layer has high-density defect. Hence, the ZnSe-CdTe sample that CdTe layer was prepared on ITO-ZnSe(0.1μm) substrate has not high-density level at the junction surface, and the CdTe layer with little lattice imperfection can be prepared. It found that ITO-ZnSe(0.1μm) substrate is available for the II-VI compounds semiconductor device through above analysis result.

Cadmium Accumulation Characteristics in Turnip Landraces from China and Assessment of Their Phytoremediation Potential for Contaminated Soils.

PubMed

Li, Xiong; Zhang, Xiaoming; Yang, Ya; Li, Boqun; Wu, Yuansheng; Sun, Hang; Yang, Yongping

2016-01-01

Heavy metal (HM) pollution is a global environmental problem that threatens ecosystem and human health. Cadmium (Cd) pollution is the most prominent HM pollution type because of its high toxicity, strong migration, and the large polluted area globally. Phytoremediation of contaminated soil is frequently practiced because of its cost-effectiveness and operability and because it has no associated secondary pollution. High-accumulation plants, including those identified as hyperaccumulators, play an important role in phytoremediation. Therefore, screening of plants to identify hyperaccumulators is important for continued phytoremediation. In the present study, we investigated the Cd tolerance and accumulation capabilities of 18 turnip landraces from China under a soil experiment with known Cd level. The results indicated that turnip has a high capacity for Cd accumulation. Furthermore, significant differences in Cd tolerance and accumulation characteristics were found among different landraces when they grew at 50 mg kg -1 (dry weight) Cd concentration. Among the studied landraces, five turnip landraces met the requirements of Cd hyperaccumulators and three landraces were identified as potential candidates. However, the total Cd content accumulated by individual plant of different turnip landraces was dependent on both the Cd accumulation capacity and plant biomass. Compared with some reported Cd hyperaccumulators, turnip not only shows a high Cd-accumulation capacity but also has rapid growth and a wide distribution area. These advantages indicate that turnip may have considerable potential for phytoremediation of Cd-contaminated soil. Furthermore, the study also indicates that it is not advisable to consume turnip cultivated in an environment that exceeds safe Cd levels.

Cadmium transfer and detoxification mechanisms in a soil-mulberry-silkworm system: phytoremediation potential.

PubMed

Zhou, Lingyun; Zhao, Ye; Wang, Shuifeng

2015-11-01

Phytoremediation has been proven to be an environmentally sound alternative for the recovery of contaminated soils, and the economic profit that comes along with the process might stimulate its field use. This study investigated cadmium (Cd) transfer and detoxification mechanisms in a soil-mulberry-silkworm system to estimate the suitability of the mulberry and silkworm as an alternative method for the remediation of Cd-polluted soil; it also explored the underlying mechanisms regulating the trophic transfer of Cd. The results show that both the mulberry and silkworm have high Cd tolerance. The transfer factor suggests that the mulberry has high potential for Cd extraction from polluted soil. The subcellular distribution and chemical forms of Cd in mulberry leaves show that cell wall deposition and vacuolar compartmentalization play important role in Cd tolerance. In the presence of increasing Cd concentrations in silkworm food, detoxification mechanisms (excretion and homeostasis) were activated so that excess Cd was excreted in fecal balls, and metallothionein levels in the mid-gut, the posterior of the silk gland, and the fat body of silkworms were enhanced. And, the Cd concentrations in silk are at a low level, ranging from 0.02 to 0.21 mg kg(-1). Therefore, these mechanisms of detoxification can regulate Cd trophic transfer, and mulberry planting and silkworm breeding has high phytoremediation potential for Cd-contaminated soil.

The serum level of soluble CD26/dipeptidyl peptidase 4 increases in response to acute hyperglycemia after an oral glucose load in healthy subjects: association with high-molecular weight adiponectin and hepatic enzymes.

PubMed

Aso, Yoshimasa; Terasawa, Tomoko; Kato, Kanako; Jojima, Teruo; Suzuki, Kunihiro; Iijima, Toshie; Kawagoe, Yoshiaki; Mikami, Shigeru; Kubota, Yoshiro; Inukai, Toshihiko; Kasai, Kikuo

2013-11-01

A soluble form of CD26/dipeptidyl peptidase 4 (sCD26/DPP4) is found in serum and it has DPP4 enzymatic activity. We investigated whether the serum level of sCD26/DPP4 was influenced by the oral glucose tolerance test (OGTT) in healthy subjects. The serum sCD26/DPP4 level increased significantly from 824.5 ng/mL (interquartile range, from 699.0 to 1050 ng/mL) at baseline to a peak of 985.0 ng/mL (interquartile range, from 796.5 to 1215 ng/mL) during the OGTT (P < 0.0001). The peak sCD26/DPP4 level correlated positively with the baseline age and body mass index, and fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), alanine aminotransferase, and γ-glutamyl transpeptidase (GGT) levels whereas it correlated negatively with high-density lipoprotein (HDL) cholesterol and the serum levels of total and high-molecular weight (HMW) adiponectin. Stepwise regression analysis was done with forward selection of variables, including age, FPG, HOMA-IR, TG, HDL cholesterol, uric acid, GGT, C-reactive protein, and HMW adiponectin. In a model that explained 57.5% of the variation of the peak sCD26/DPP4 level, GGT (β = 0.382, P = 0.007) and HOMA-IR (β = 0.307, P = 0.034) were independent determinants of the peak serum level of sCD26/DPP4. Serum HMW adiponectin decreased significantly from 4.43 μg/mL (interquartile range, from 2.80 to 6.65 μg/mL) at baseline to 4.17 μg/mL (interquartile range, from 2.48 to 6.96 μg/mL) 120 minutes after the oral glucose load (P < 0.0001). The baseline serum level of sCD26/DPP4 showed a significant negative correlation with the percent change of HMW adiponectin during the OGTT. In conclusion, the serum level of sCD26/DPP4 increased acutely after an oral glucose load in apparently healthy subjects. The abrupt increase of serum sCD26/DPP4 after a glucose load may be a marker of insulin resistance that could come from liver or muscle. Copyright © 2013 Mosby, Inc. All rights reserved.

Cord blood-derived CD34+ hematopoietic cells with low mitochondrial mass are enriched in hematopoietic repopulating stem cell function.

PubMed

Romero-Moya, Damia; Bueno, Clara; Montes, Rosa; Navarro-Montero, Oscar; Iborra, Francisco J; López, Luis Carlos; Martin, Miguel; Menendez, Pablo

2013-07-01

The homeostasis of the hematopoietic stem/progenitor cell pool relies on a fine-tuned balance between self-renewal, differentiation and proliferation. Recent studies have proposed that mitochondria regulate these processes. Although recent work has contributed to understanding the role of mitochondria during stem cell differentiation, it remains unclear whether the mitochondrial content/function affects human hematopoietic stem versus progenitor function. We found that mitochondrial mass correlates strongly with mitochondrial membrane potential in CD34(+) hematopoietic stem/progenitor cells. We, therefore, sorted cord blood CD34(+) cells on the basis of their mitochondrial mass and analyzed the in vitro homeostasis and clonogenic potential as well as the in vivo repopulating potential of CD34(+) cells with high (CD34(+) Mito(High)) versus low (CD34(+) Mito(Low)) mitochondrial mass. The CD34(+) Mito(Low) fraction contained 6-fold more CD34(+)CD38(-) primitive cells and was enriched in hematopoietic stem cell function, as demonstrated by its significantly greater hematopoietic reconstitution potential in immuno-deficient mice. In contrast, the CD34(+) Mito(High) fraction was more enriched in hematopoietic progenitor function with higher in vitro clonogenic capacity. In vitro differentiation of CD34(+) Mito(Low) cells was significantly delayed as compared to that of CD34(+) Mito(High) cells. The eventual complete differentiation of CD34(+) Mito(Low) cells, which coincided with a robust expansion of the CD34(-) differentiated progeny, was accompanied by mitochondrial adaptation, as shown by significant increases in ATP production and expression of the mitochondrial genes ND1 and COX2. In conclusion, cord blood CD34(+) cells with low levels of mitochondrial mass are enriched in hematopoietic repopulating stem cell function whereas high levels of mitochondrial mass identify hematopoietic progenitors. A mitochondrial response underlies hematopoietic stem/progenitor cell differentiation and proliferation of lineage-committed CD34(-) cells.

Soluble CD14, α-and β-defensins in breast milk: association with the emergence of allergy in a high-risk population.

PubMed

Savilahti, Emma M; Kukkonen, Anna K; Kuitunen, Mikael; Savilahti, Erkki

2015-04-01

As innate immunity factors in breast milk (BM) modulate infants' immune responses, we investigated whether soluble CD14 (sCD14) and defensin levels in BM are associated with the emergence of allergy in childhood. The randomly selected group of 260 mother-child pairs belonged to a randomized, double-blind placebo-controlled trial where 1223 mothers with fetuses at high risk for allergy received for the 4 last wk of pregnancy a mixture of probiotics, or placebo; after birth, the child received the treatment for 6 mo. Children were followed for the emergence of sensitization and allergic symptoms for 5 yr. IgE-mediated allergic disorder was diagnosed in 80 children by the age of 5 yr. Levels of sCD14, human neutrophil peptide (HNP) 1-3 and β-defensin 2 (HBD2) in colostrum and in BM 3 mo post-partum were measured with ELISA. BM sCD14 levels decreased from 0 to 3 mo. HNP1-3 and HBD2 were detected in colostrum, but not in BM 3 mo post-partum. High sCD14 levels in BM 3 mo post-partum were associated with children developing an IgE-mediated allergic disorder by the age of 5 yr. BM HNP1-3, HBD2 or sCD14 levels were not associated with probiotics treatment. Our results suggest that sCD14 in BM influences the emergence of allergy in children with atopic heredity. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Reduced soluble CD14 levels in amniotic fluid and breast milk are associated with the subsequent development of atopy, eczema, or both.

PubMed

Jones, Catherine A; Holloway, Judith A; Popplewell, Eleanor J; Diaper, Norma D; Holloway, John W; Vance, Gillian H s; Warner, Jill A; Warner, John O

2002-05-01

Exposure to various microbial products in early life reduces the risk of atopy. Such exposure induces downregulation of T(H)2 allergy-biased responses by means of pattern recognition molecules, such as CD14, an LPS receptor. We sought to determine whether infant and maternal levels of soluble CD14 (sCD14) are associated with the atopic outcomes of infants. Levels of sCD14 in plasma, amniotic fluid, and breast milk were measured with a specific ELISA in different cohorts. Expression of toll-like receptors in the fetal gut was examined by using RT-PCR. Soluble CD14 levels increased during fetal development and postnatally, attaining adult levels by around 4 months of age, with an overshoot of adult levels from 6 months of age. There was no difference in plasma sCD14 levels at birth of children with a high compared with those with a low risk of development of atopy. Amniotic fluid sCD14 levels at midgestation (16-17 weeks) were significantly lower when the child was subsequently atopic (P <.05). Soluble CD14 levels in breast milk collected 3 months postpartum were significantly lower in children with eczema at 6 months of age, irrespective of whether they were atopic (P =.003). Transcripts for toll-like receptor 4, which would enable transmembrane signaling for LPS/sCD14 complexes, were expressed within fetal gut and skin. Exposure to reduced levels of sCD14 in the fetal and neonatal gastrointestinal tract is associated with the development of atopy, eczema, or both. Thus the exogenous supply of sCD14 might influence immunologic reactivity both locally and systemically in early life and thereby influence disease outcome.

Low baseline levels of NK cells may predict a positive response to ipilimumab in melanoma therapy.

PubMed

Tietze, Julia K; Angelova, Daniela; Heppt, Markus V; Ruzicka, Thomas; Berking, Carola

2017-07-01

The introduction of immune checkpoint blockade (ICB) has been a breakthrough in the therapy of metastatic melanoma. The influence of ICB on T-cell populations has been studied extensively, but little is known about the effect on NK cells. In this study, we analysed the relative and absolute amounts of NK cells and of the subpopulations of CD56 dim and CD56 bright NK cells among the peripheral blood mononuclear cells (PBMCs) of 32 patients with metastatic melanoma before and under treatment with ipilimumab or pembrolizumab by flow cytometry. In 15 (47%) patients, an abnormal low amount of NK cells was found at baseline. Analysis of the subpopulations showed also low or normal baseline levels for CD56 dim NK cells, whereas the baseline levels of CD56 bright NK cells were either normal or abnormally high. The relative and absolute amounts of NK cells and of CD56 dim and CD56 bright NK cell subpopulations in patients with a normal baseline did not change under treatment. However, patients with a low baseline of NK cells and CD56 dim NK cells showed a significant increase in these immune cell subsets, but the amounts remained to be lower than the normal baseline. The amount of CD56 bright NK cells was unaffected by treatment. The baseline levels of NK cells were correlated with the number of metastatic organs. Their proportion increased, whereas the expression of NKG2D decreased significantly when more than one organ was affected by metastases. Low baseline levels of NK cells and CD56 dim NK cells as well as normal baseline levels of CD56 bright NK cells correlated significantly with a positive response to ipilimumab but not to pembrolizumab. Survival curves of patients with low amounts of CD56 dim NK cells treated with ipilimumab showed a trend to longer survival. Normal baseline levels of CD56 bright NK cells were significantly correlated with longer survival as compared to patients with high baseline levels. In conclusion, analysis of the amounts of total NK cells and of CD56 dim and CD56 bright NK cells subpopulations at baseline may help to predict the outcome of treatment with ipilimumab. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

40 CFR Appendix F to Part 60 - Quality Assurance Procedures

Code of Federal Regulations, 2013 CFR

2013-07-01

... plus the 2.5 percent error confidence coefficient of a series of tests divided by the mean of the RM...-level) CD or the daily high-level CD exceeds two times the limits of the applicable PS's in appendix B... result exceeds four times the applicable drift specification in appendix B during any CD check, the CEMS...

40 CFR Appendix F to Part 60 - Quality Assurance Procedures

Code of Federal Regulations, 2010 CFR

2010-07-01

... plus the 2.5 percent error confidence coefficient of a series of tests divided by the mean of the RM...-level) CD or the daily high-level CD exceeds two times the limits of the applicable PS's in appendix B... result exceeds four times the applicable drift specification in appendix B during any CD check, the CEMS...

40 CFR Appendix F to Part 60 - Quality Assurance Procedures

Code of Federal Regulations, 2011 CFR

2011-07-01

... plus the 2.5 percent error confidence coefficient of a series of tests divided by the mean of the RM...-level) CD or the daily high-level CD exceeds two times the limits of the applicable PS's in appendix B... result exceeds four times the applicable drift specification in appendix B during any CD check, the CEMS...

Cadmium tolerance and accumulation of Elsholtzia argyi origining from a zinc/lead mining site - a hydroponics experiment.

PubMed

Li, Siliang; Wang, Fengping; Ru, Mei; Ni, Wuzhong

2014-01-01

In this study, a hydroponics experiment was conducted to investigate the characteristics of Cd tolerance and accumulation of Elsholtzia argyi natively growing on the soil with high levels of heavy metals in a Zn/Pb mining site. Seedlings of E. argyi grown for 4 weeks and then were treated with 0(CK), 5,10,15, 20, 25, 30, 40, 50,100 umM Cd for 21 days. Each treatment had three replications. No visual toxic symptoms on shoots of E. argyi were observed at Cd level < or = 50 muM. The results indicated that the dry biomass of each tissue and the whole plants of the treatments with < or =40 umM cadmium were similar to that of the control, implying that E. argyi was a cadmium tolerant plant. The results also showed that the shoot Cd concentration significantly (P < 0.05) increased with the increase in the Cd level in nutrient solution. The shoot Cd concentration of the treatment with 40 umM Cd was as high as 237.9 mg kg(-1), which was higher than 100 mg kg(-1), normally used as the threshold concentration for identifying the Cd hyperaccumulating plant. It could be concluded that E. argyi was a Cd tolerant and accumulating plant species.

Contradictory intrahepatic immune responses activated in high-load hepatitis C virus livers compared with low-load livers.

PubMed

Ishibashi, Mariko; Yamaguchi, Hiromi; Hirotani, Yukari; Sakurada, Akihisa; Endo, Toshihide; Sugitani, Masahiko; Takayama, Tadatoshi; Makishima, Makoto; Esumi, Mariko

2018-04-01

We found a HLA class II histocompatibility antigen gene, DQ alpha 1 chain (HLA-DQA1), that was expressed more than 9-fold higher in high-load hepatitis C virus (HCV) livers than low-load HCV livers using transcriptomics of chronic HCV-infected livers. To further investigate this finding, we examined which cells were positive for HLA-DQA1 and what liver immune responses were different between HCV-high and -low livers. HLA-DQA1-positive cells were significantly increased in the HCV-high group, and most positive cells were identified as non-parenchymal sinusoid cells and lymphocytic infiltrates in the portal area. Parenchymal hepatocytes were negative for HLA-DQA1. HLA-DQA1-positive cells in the liver sinusoid were positive for CD68 (macrophages or Kupffer cells); those in the lymphocytic infiltrates were positive for CD20 (B cells) or CD3 (T cells). mRNA levels of antigen-presenting cell (APC) markers such as CD68 and CD11c were significantly upregulated in the HCV-high group and were correlated with HLA-DQA mRNA levels. CD8B mRNA (CD8 + T cells) was upregulated in both HCV-positive livers compared with HCV-negative livers, whereas CD154 mRNA (CD4 + T helper cell) was upregulated in the HCV-high group compared with the HCV-low group. The immune regulatory molecules FOXP3 mRNA (regulatory T cell, T reg) and programmed cell death ligand-1 (PD-L1) mRNA were significantly increased in the HCV-high group. HCV-high livers had two molecular immune responses: increased APC numbers and adaptive immunity and the induction of immune tolerance. The local hepatic imbalance of contradictory immune responses might be responsible for high HCV loads.

Increased CD4+CD45RA-FoxP3low cells alter the balance between Treg and Th17 cells in colitis mice.

PubMed

Ma, Ya-Hui; Zhang, Jie; Chen, Xue; Xie, You-Fu; Pang, Yan-Hua; Liu, Xin-Juan

2016-11-14

To investigate the role of regulatory T cell (Treg) subsets in the balance between Treg and T helper 17 (Th17) cells in various tissues from mice with dextran sulfate sodium-induced colitis. Treg cells, Treg cell subsets, Th17 cells, and CD4 + CD25 + FoxP3 + IL-17 + cells from the lamina propria of colon (LPC) and other ulcerative colitis (UC) mouse tissues were evaluated by flow cytometry. Forkhead box protein 3 (FoxP3), interleukin 17A (IL-17A), and RORC mRNA levels were assessed by real-time PCR, while interleukin-10 (IL-10) and IL-17A levels were detected with a Cytometric Beads Array. In peripheral blood monocytes (PBMC), mesenteric lymph node (MLN), lamina propria of jejunum (LPJ) and LPC from UC mice, Treg cell numbers were increased ( P < 0.05), and FoxP3 and IL-10 mRNA levels were decreased. Th17 cell numbers were also increased in PBMC and LPC, as were IL-17A levels in PBMC, LPJ, and serum. The number of FrI subset cells (CD4 + CD45RA + FoxP3 low ) was increased in the spleen, MLN, LPJ, and LPC. FrII subset cells (CD4 + CD45RA - FoxP3 high ) were decreased among PBMC, MLN, LPJ, and LPC, but the number of FrIII cells (CD4 + CD45RA - FoxP3 low ) and CD4 + CD25 + FoxP3 + IL-17A + cells was increased. FoxP3 mRNA levels in CD4 + CD45RA - FoxP3 low cells decreased in PBMC, MLN, LPJ, and LPC in UC mice, while IL-17A and RORC mRNA increased. In UC mice the distribution of Treg, Th17 cells, CD4 + CD45RA - FoxP3 high , and CD4 + CD45RA - FoxP3 low cells was higher in LPC relative to other tissues. Increased numbers of CD4 + CD45RA - FoxP3 low cells may cause an imbalance between Treg and Th17 cells that is mainly localized to the LPC rather than secondary lymphoid tissues.

Increased CD4+CD45RA-FoxP3low cells alter the balance between Treg and Th17 cells in colitis mice

PubMed Central

Ma, Ya-Hui; Zhang, Jie; Chen, Xue; Xie, You-Fu; Pang, Yan-Hua; Liu, Xin-Juan

2016-01-01

AIM To investigate the role of regulatory T cell (Treg) subsets in the balance between Treg and T helper 17 (Th17) cells in various tissues from mice with dextran sulfate sodium-induced colitis. METHODS Treg cells, Treg cell subsets, Th17 cells, and CD4+CD25+FoxP3+IL-17+ cells from the lamina propria of colon (LPC) and other ulcerative colitis (UC) mouse tissues were evaluated by flow cytometry. Forkhead box protein 3 (FoxP3), interleukin 17A (IL-17A), and RORC mRNA levels were assessed by real-time PCR, while interleukin-10 (IL-10) and IL-17A levels were detected with a Cytometric Beads Array. RESULTS In peripheral blood monocytes (PBMC), mesenteric lymph node (MLN), lamina propria of jejunum (LPJ) and LPC from UC mice, Treg cell numbers were increased (P < 0.05), and FoxP3 and IL-10 mRNA levels were decreased. Th17 cell numbers were also increased in PBMC and LPC, as were IL-17A levels in PBMC, LPJ, and serum. The number of FrI subset cells (CD4+CD45RA+FoxP3low) was increased in the spleen, MLN, LPJ, and LPC. FrII subset cells (CD4+CD45RA-FoxP3high) were decreased among PBMC, MLN, LPJ, and LPC, but the number of FrIII cells (CD4+CD45RA-FoxP3low) and CD4+CD25+FoxP3+IL-17A+ cells was increased. FoxP3 mRNA levels in CD4+CD45RA-FoxP3low cells decreased in PBMC, MLN, LPJ, and LPC in UC mice, while IL-17A and RORC mRNA increased. In UC mice the distribution of Treg, Th17 cells, CD4+CD45RA-FoxP3high, and CD4+CD45RA-FoxP3low cells was higher in LPC relative to other tissues. CONCLUSION Increased numbers of CD4+CD45RA-FoxP3low cells may cause an imbalance between Treg and Th17 cells that is mainly localized to the LPC rather than secondary lymphoid tissues. PMID:27895423

Alteration of circulating natural autoantibodies to CD25-derived peptide antigens and FOXP3 in non-small cell lung cancer.

PubMed

Zhao, Huan; Zhang, Xuan; Han, Zhifeng; Xie, Wenjing; Yang, Wei; Wei, Jun

2018-06-29

Natural autoantibody is a key component for immune surveillance function. Regulatory T (Treg) cells play indispensable roles in promoting tumorigenesis via immune escape mechanisms. Both CD25 and FOXP3 are specific markers for Treg cells and their natural autoantibodies may be involved in anticancer activities. This work was designed to develop an in-house enzyme-linked immunosorbent assay (ELISA) to examine plasma natural IgG against CD25 and FOXP3 in non-small cell lung cancer (NSCLC). Compared with control subjects, NSCLC patients had significantly higher levels of plasma IgG for CD25a (Z = -8.05, P < 0.001) and FOXP3 (Z = -4.17, P < 0.001), lower levels for CD25b (Z = -3.58, P < 0.001), and a trend toward lower levels for CD25c (Z = -1.70, P = 0.09). Interestingly, the anti-CD25b IgG assay had a sensitivity of 25.0% against a specificity of 95.0% in an early stage patients (T 1 N 0 M 0 ) who showed the lowest anti-CD25b IgG levels among 4 subgroups classified based on staging information. Kaplan-Meier survival analysis showed that patients with high anti-FOXP3 IgG levels had shorter survival than those with low anti-FOXP3 IgG levels (χ 2  = 3.75, P = 0.05). In conclusion, anti-CD25b IgG may be a promising biomarker in terms of screening individuals at high risk of lung cancer.

Serum soluble CD163 levels in patients with influenza-associated encephalopathy.

PubMed

Hasegawa, Shunji; Matsushige, Takeshi; Inoue, Hirofumi; Takahara, Midori; Kajimoto, Madoka; Momonaka, Hiroshi; Ishida, Chiemi; Tanaka, Saya; Morishima, Tsuneo; Ichiyama, Takashi

2013-08-01

Influenza-associated encephalopathy (IE) is a serious complication during influenza viral infection. Common clinical symptoms of IE include seizures and progressive coma with high-grade fever. We previously reported that hypercytokinemia and monocyte/macrophage activation may play an important role in the pathogenesis of IE. CD163 is a scavenger receptor for hemoglobin-haptoglobin complexes and is expressed by monocytes/macrophages. Proteolytic cleavage of monocyte-bound CD163 by matrix metalloproteinases releases soluble CD163 (sCD163). However, there have been no reports regarding serum sCD163 levels in IE patients. We measured serum levels of sCD163 as a marker of monocyte/macrophage activation in IE patients with poor outcomes, those without neurological sequelae, influenza patients without IE, and control subjects. Serum sCD163 levels were significantly higher in IE patients with poor outcomes than in those without neurological sequelae. In particular, sCD163 levels in cases of death were significantly higher than those in other cases. Our results suggest that monocyte/macrophage activation is related to the pathogenesis of severe IE. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Panel reactive HLA antibodies, soluble CD30 levels, and acute rejection six months following renal transplant.

PubMed

Domingues, Elizabeth M F L; Matuck, Teresa; Graciano, Miguel L; Souza, Edison; Rioja, Suzimar; Falci, Mônica C; Monteiro de Carvalho, Deise B; Porto, Luís Cristóvão

2010-01-01

Specific anti-human leukocyte antigen antibodies (HLA) in the post-transplant period may be present with acute rejection episodes (ARE), and high soluble CD30 (sCD30) serum levels may be a risk factor for ARE and graft loss. HLA cross-matching, panel reactive antibodies (PRA), and sCD30 levels were determined prior to transplantation in 72 patients. Soluble CD30 levels and PRA were re-assessed at day 7, 14, 21, and 28, and monthly up to the sixth.   Twenty-four subjects had a positive PRA and 17 experienced ARE. Nine of 17 ARE subjects demonstrated positive PRA and 16 had HLA mismatches. Positive PRA was more frequent in ARE subjects (p = 0.03). Eight subjects with ARE had donor-specific antibodies (DSA) in serum samples pre-transplantation, two subjects developed DSA. Three subjects without ARE had positive PRA only in post-transplantation samples. Soluble CD30 levels were higher in pre-transplant samples and ARE subjects than non-ARE subjects (p = 0.03). Post-transplant sCD30 levels were elevated in subjects who experienced rejection and were significantly higher at seven d (p = 0.0004) and six months (p = 0.03). Higher sCD30 levels following transplant were associated with ARE. Elevated sCD30 levels may represent a risk factor for acute rejection. © 2009 John Wiley & Sons A/S.

Higher Frequency of Circulating PD-1high CXCR5+CD4+ Tfh Cells in Patients with Chronic Schistosomiasis

PubMed Central

Zhang, Yumei; Jiang, Yanyan; Wang, Yanjuan; Liu, Hua; Shen, Yujuan; Yuan, Zhongying; Hu, Yuan; Xu, Yuxin; Cao, Jianping

2015-01-01

The current knowledge of immunological responses to schistosomiasis is insufficient for the development of vaccine and therapies. The role of T follicular helper (Tfh) cells in schistosome infections is not fully defined. The frequency of circulating Tfh cells and serum cytokine levels were analyzed in 11 patients with chronic schistosomiasis and 10 healthy controls (HC), who reside in an endemic area for Schistosomiasis japonicum. Significantly higher frequencies of circulating CXCR5+ CD4+ Tfh cells and higher expression levels of ICOS and PD-1 in CXCR5+ CD4+ Tfh cells were observed in patients with chronic schistosomiasis compared to HC. The levels of IL-21 in serum and the expression of IL-21 mRNA were higher in chronic schistosomiasis patients than in HC. Moreover, the frequency of circulating PD-1high CXCR5+ CD4+ Tfh cells positively correlated with the levels of IL-21 in serum from patients with chronic schistosomiasis. A positive correlation was also found between the frequency of PD-1high CXCR5+ CD4+ Tfh cells and the levels of soluble egg antigen (SEA)-specific antibodies in serum samples from the patient group. Our study is the first regarding Tfh cells in chronic human schistosomiasis and the finding indicate that PD-1high CXCR5+ CD4+Tfh cells might play an important role in the production of specific antibodies in schistosomiasis. This study contributes to the understanding of immune response to schistosomiasis and may provide helpful support in vaccine development. PMID:26221072

Higher Frequency of Circulating PD-1(high) CXCR5(+)CD4(+) Tfh Cells in Patients with Chronic Schistosomiasis.

PubMed

Zhang, Yumei; Jiang, Yanyan; Wang, Yanjuan; Liu, Hua; Shen, Yujuan; Yuan, Zhongying; Hu, Yuan; Xu, Yuxin; Cao, Jianping

2015-01-01

The current knowledge of immunological responses to schistosomiasis is insufficient for the development of vaccine and therapies. The role of T follicular helper (Tfh) cells in schistosome infections is not fully defined. The frequency of circulating Tfh cells and serum cytokine levels were analyzed in 11 patients with chronic schistosomiasis and 10 healthy controls (HC), who reside in an endemic area for Schistosomiasis japonicum. Significantly higher frequencies of circulating CXCR5(+) CD4(+) Tfh cells and higher expression levels of ICOS and PD-1 in CXCR5(+) CD4(+) Tfh cells were observed in patients with chronic schistosomiasis compared to HC. The levels of IL-21 in serum and the expression of IL-21 mRNA were higher in chronic schistosomiasis patients than in HC. Moreover, the frequency of circulating PD-1(high) CXCR5(+) CD4(+) Tfh cells positively correlated with the levels of IL-21 in serum from patients with chronic schistosomiasis. A positive correlation was also found between the frequency of PD-1(high) CXCR5(+) CD4(+) Tfh cells and the levels of soluble egg antigen (SEA)-specific antibodies in serum samples from the patient group. Our study is the first regarding Tfh cells in chronic human schistosomiasis and the finding indicate that PD-1(high) CXCR5(+) CD4(+)Tfh cells might play an important role in the production of specific antibodies in schistosomiasis. This study contributes to the understanding of immune response to schistosomiasis and may provide helpful support in vaccine development.

Bioaccessibility and Human Exposure Assessment of Cadmium and Arsenic in Pakchoi Genotypes Grown in Co-Contaminated Soils

PubMed Central

Wei, Yanyan; Zheng, Xiaoman; Shohag, Md. Jahidul Islam; Gu, Minghua

2017-01-01

In many countries cadmium (Cd) and arsenic (As) commonly coexist in soils contaminated by mining activities, and can easily enter the human body via consumption of leafy vegetables, like the popularly consumed pakchoi (Brassica chinensis L.), causing major health concerns. In the present study, bioaccessibility and human exposure of Cd and As were assessed in twenty genotypes of pakchoi cultured at two different levels of co-contamination to identify low health risk genotypes. The bioaccessibilities of Cd and As represent a fraction of the total metals content could be bioaccessible for human, in the present study, significant differences in pakchoi Cd and As bioaccessibility were observed among all tested genotypes and co-contaminated levels. Cd and As bioaccessibility of pakchoi were in the ranges of 24.0–87.6% and 20.1–82.5%, respectively, for in the high level co-contaminated soils, which was significantly higher than for low level co-contaminated soils with 7.9–71.8% for Cd bioaccessibility and 16.1–59.0% for As bioaccessibility. The values of bioaccessible established daily intakes (BEDI) and the total bioaccessible target hazard quotients (TBTHQ) of Cd and As were also considerably higher in high level co-contaminated soils than in low level co-contaminated soils. Two genotypes (Meiguanqinggengcai and Zhenqing60F1) contained relatively low concentrations and bioaccessible Cd and As and, their BEDI and TBTHQ for Cd and As ranged below the tolerable limits set by the FAO/WHO (BEDI of Cd < 0.83 μg kg−1 bw day−1, BEDI of As < 3 μg kg−1 bw day−1) and United States Environmental Protection Agency (TBTHQ for Cd and As < 1), this applied for both levels of co-contaminated soils for adults and children. Consequently, these findings suggest identification of safe genotypes in leafy vegetable with low health risk via genotypic screening and breeding methods could be a useful strategy to ensure the safety of food crops grown in those Cd and As co-contaminated fields due to mining activities. PMID:28850097

Bioaccessibility and Human Exposure Assessment of Cadmium and Arsenic in Pakchoi Genotypes Grown in Co-Contaminated Soils.

PubMed

Wei, Yanyan; Zheng, Xiaoman; Shohag, Md Jahidul Islam; Gu, Minghua

2017-08-29

In many countries cadmium (Cd) and arsenic (As) commonly coexist in soils contaminated by mining activities, and can easily enter the human body via consumption of leafy vegetables, like the popularly consumed pakchoi ( Brassica chinensis L.), causing major health concerns. In the present study, bioaccessibility and human exposure of Cd and As were assessed in twenty genotypes of pakchoi cultured at two different levels of co-contamination to identify low health risk genotypes. The bioaccessibilities of Cd and As represent a fraction of the total metals content could be bioaccessible for human, in the present study, significant differences in pakchoi Cd and As bioaccessibility were observed among all tested genotypes and co-contaminated levels. Cd and As bioaccessibility of pakchoi were in the ranges of 24.0-87.6% and 20.1-82.5%, respectively, for in the high level co-contaminated soils, which was significantly higher than for low level co-contaminated soils with 7.9-71.8% for Cd bioaccessibility and 16.1-59.0% for As bioaccessibility. The values of bioaccessible established daily intakes (BEDI) and the total bioaccessible target hazard quotients (TBTHQ) of Cd and As were also considerably higher in high level co-contaminated soils than in low level co-contaminated soils. Two genotypes (Meiguanqinggengcai and Zhenqing60F1) contained relatively low concentrations and bioaccessible Cd and As and, their BEDI and TBTHQ for Cd and As ranged below the tolerable limits set by the FAO/WHO (BEDI of Cd < 0.83 μg kg -1 bw day -1 , BEDI of As < 3 μg kg -1 bw day -1 ) and United States Environmental Protection Agency (TBTHQ for Cd and As < 1), this applied for both levels of co-contaminated soils for adults and children. Consequently, these findings suggest identification of safe genotypes in leafy vegetable with low health risk via genotypic screening and breeding methods could be a useful strategy to ensure the safety of food crops grown in those Cd and As co-contaminated fields due to mining activities.

Differential Susceptibility of Germ and Leydig Cells to Cadmium-Mediated Toxicity: Impact on Testis Structure, Adiponectin Levels, and Steroidogenesis

PubMed Central

Cupertino, Marli C.; Neves, Ana C.; Oliveira, Juraci A.

2017-01-01

This study investigated the relationship between germ and Leydig cell death, testosterone, and adiponectin levels in cadmium-mediated acute toxicity. Cadmium chloride was administered in a single dose to five groups of rats: G1 (0.9% NaCl) and G2 to G5 (0.67, 0.74, 0.86, and 1.1 mg Cd/kg). After 7 days, the animals were euthanized, and the testosterone and testes were analyzed. Dose-dependent Cd accumulation in the testes was identified. At 0.86 and 1.1 mg/kg, animals exhibited marked inflammatory infiltrate and disorganization of the seminiferous epithelium. While Leydig cells were morphologically resistant to Cd toxicity, massive germ cell death and DNA oxidation and fragmentation were observed. Although numerical density of Leydig cells was unchanged, testosterone levels were significantly impaired in animals exposed to 0.86 and 1.1 mg Cd/kg, occurring in parallel with the reduction in total adiponectins and the increase in high-molecular weight adiponectin levels. Our findings indicated that Leydig and germ cells exhibit differential microstructural resistance to Cd toxicity. While germ cells are a primary target of Cd-induced toxicity, Leydig cells remain resistant to death even when exposed to high doses of Cd. Despite morphological resistance, steroidogenesis was drastically impaired by Cd exposure, an event potentially related to the imbalance in adiponectin production. PMID:29422988

Increased Prevalence of Luminal Narrowing and Stricturing Identified by Enterography in Pediatric Crohn Disease Patients with Elevated Granulocyte-Macrophage Colony Stimulating Factor Auto-antibodies

PubMed Central

Dykes, Dana M.H.; Towbin, Alexander J.; Bonkowski, Erin; Chalk, Claudia; Bezold, Ramona; Lake, Kathleen; Kim, Mi-Ok; Heubi, James E.; Trapnell, Bruce C.; Podberesky, Daniel J.; Denson, Lee A.

2013-01-01

Background Crohn disease (CD) patients with elevated Granulocyte-Macrophage Colony-Stimulating Factor auto-antibodies (GM-CSF Ab) are more likely to develop stricturing behavior requiring surgery. Computed Tomography or Magnetic Resonance Enterography (CTE or MRE) may detect luminal narrowing (LN) prior to stricture development. Objective To determine whether CD patients with elevated GM-CSF Ab (≥ 1.6 mcg/mL) have a higher prevalence of LN and stricturing on CTE or MRE. Methods A single center, cross-sectional study of 153 pediatric CD patients and controls undergoing CTE or MRE. A novel scoring system evaluated for disease activity, presence of LN, stricture, intra-abdominal abscess, or fistulae Ouutcomes were compared with respect to antibody status using Fisher's exact test, logistic regression, and the unpaired t-test. Results GM-CSF Ab were elevated in CD patients (n=114) with a median (IQR) GM-CSF Ab level of 2.3 mcg/mL (0.5, 6.6) compared with healthy and disease controls, p=0.001. Ileal disease location was more common in CD patients with high GM-CSF Ab, p<0.001. Luminal narrowing increased from 39% in CD patients with low GM-CSF Ab to 71% in those with high levels (p=0.004). High GM-CSF Ab remained significantly associated with LN in a multivariate logistic model. Stricturing increased from 4% in CD patients with low GM-CSF Ab to 19% in those with high GM-CSF Ab (p=0.03). Conclusions Pediatric CD patients with high GM-CSF Ab levels have a higher prevalence of LN on CTE or MRE. Further study will be needed to determine whether medical therapy will reduce progression to stricturing behavior in these patients. PMID:23893081

Intestinal double-positive CD4+CD8+ T cells are highly activated memory cells with an increased capacity to produce cytokines.

PubMed

Pahar, Bapi; Lackner, Andrew A; Veazey, Ronald S

2006-03-01

Peripheral blood and intestinal CD4+CD8+ double-positive (DP) T cells have been described in several species including humans, but their function and immunophenotypic characteristics are still not clearly understood. Here we demonstrate that DP T cells are abundant in the intestinal lamina propria of normal rhesus macaques (Macaca mulatta). Moreover, DP T cells have a memory phenotype and are capable of producing different and/or higher levels of cytokines and chemokines in response to mitogen stimulation compared to CD4+ single-positive T cells. Intestinal DP T cells are also highly activated and have higher expression of CCR5, which makes them preferred targets for simian immunodeficiency virus/HIV infection. Increased levels of CD69, CD25 and HLA-DR, and lower CD62L expression were found on intestinal DP T cells populations compared to CD4+ single-positive T cells. Collectively, these findings demonstrate that intestinal and peripheral blood DP T cells are effector cells and may be important in regulating immune responses, which distinguishes them from the immature DP cells found in the thymus. Finally, these intestinal DP T cells may be important target cells for HIV infection and replication due to their activation, memory phenotype and high expression of CCR5.

Low levels of SIV infection in sooty mangabey central-memory CD4+ T-cells is associated with limited CCR5 expression

PubMed Central

Paiardini, Mirko; Cervasi, Barbara; Reyes-Aviles, Elane; Micci, Luca; Ortiz, Alexandra M.; Chahroudi, Ann; Vinton, Carol; Gordon, Shari N.; Bosinger, Steven E.; Francella, Nicholas; Hallberg, Paul L.; Schlub, Timothy; Chan, Ming Liang; Riddick, Nadeene E.; Collman, Ronald G.; Apetrei, Cristian; Pandrea, Ivona; Else, James; Munch, Jan; Kirchhoff, Frank; Davenport, Miles P.; Brenchley, Jason M.; Silvestri, Guido

2011-01-01

Naturally SIV-infected sooty mangabeys (SMs) do not progress to AIDS despite high-level virus replication. We previously showed that the fraction of CD4+CCR5+ T-cells is lower in SMs compared to humans and macaques. Here we found that, after in vitro stimulation, SM CD4+ T-cells fail to up-regulate CCR5, and that this phenomenon is more pronounced in CD4+ central-memory T-cells (TCM). CD4+ T-cell activation was similarly uncoupled from CCR5 expression in SMs in vivo during (i) acute SIV infection and (ii) following antibody-mediated CD4+ T-cell depletion. Remarkably, CD4+ TCM of SMs that express low levels of CCR5 demonstrated reduced susceptibility to SIV infection both in vivo and in vitro when compared to CD4+ TCM of RMs. These data suggest that low CCR5 expression on SM CD4+ T-cells favors the preservation of CD4+ T-cell homeostasis and promotes an AIDS-free status by protecting CD4+ TCM from direct virus infection. PMID:21706028

Delineation of behavioral phenotypes in genetic syndromes: characteristics of autism spectrum disorder, affect and hyperactivity.

PubMed

Oliver, Chris; Berg, Katy; Moss, Jo; Arron, Kate; Burbidge, Cheryl

2011-08-01

We investigated autism spectrum disorder (ASD) symptomatology, hyperactivity and affect in seven genetic syndromes; Angelman (AS; n = 104), Cri du Chat (CdCS; 58), Cornelia de Lange (CdLS; 101), Fragile X (FXS; 191), Prader-Willi (PWS; 189), Smith-Magenis (SMS; 42) and Lowe (LS; 56) syndromes (age range 4-51). ASD symptomatology was heightened in CdLS and FXS. High levels of impulsivity were seen in SMS, AS, CdCS, FXS and adults with CdLS. Negative affect was prominent in adults with CdLS, while positive affect was prominent in adults with AS and FXS. Heightened levels of overactivity and impulsivity were identified in FXS, AS and SMS while low levels were identified in PWS. These findings confirm and extend previously reported behavioral phenotypes.

Antitumor action of lymphokin-activated cells of patients with soft tissue sarcomas and melanomas in dependence on expression of MHC classes I and II antigenes.

PubMed

Berezhnaya, N M; Vinnichuk, U D; Belova, O B; Baranovich, V V

2006-09-01

To study expression of major histocompatibility complex (MHC) classes and antigens and CD25, CD71, Ki-67, CD54, CD56, CD11b, PCNA on lymphocytes and tumor cells and antitumor action of lymphocytes activated with IL-2. Tumor explants (soft tissue sarcoma, n = 20, melanoma, n = 25) were co-cultivated in diffusion chambers with autologous lymphocytes; antitumor action was evaluated by morphologic patterns of explant's growth. Expression of CD25, CD71, Ki-67, CD54, CD56, CD11b, PCNA was evaluated by the method of indirect fluorescence using respective monoclonal antibodies. The highest antitumor action of lymphocytes toward soft tissue sarcoma and melanoma cells is observed if tumor cells are expressing MHC class I antigens. In the cases of soft tissue sarcoma no correlation between the level of antitumor activity of lymphocytes and expression of CD25, CD71, Ki-67, CD54, CD56, CD11b, PCNA has been found, whilst in the case of melanoma it is associated with the high level of CD11b expression. There is a direct correlation between sensitivity of soft tissue sarcoma and melanoma cells to action of lymphokin-activated killer cells and the level of MHC class I antigens.

Infliximab induces clonal expansion of γδ-T cells in Crohn's disease: a predictor of lymphoma risk?

PubMed

Kelsen, Jens; Dige, Anders; Schwindt, Heinrich; D'Amore, Francesco; Pedersen, Finn S; Agnholt, Jørgen; Christensen, Lisbet A; Dahlerup, Jens F; Hvas, Christian L

2011-03-31

Concominant with the widespread use of combined immunotherapy in the management of Crohn's disease (CD), the incidence of hepato-splenic gamma-delta (γδ)-T cell lymphoma has increased sharply in CD patients. Malignant transformation of lymphocytes is believed to be a multistep process resulting in the selection of malignant γδ-T cell clones. We hypothesised that repeated infusion of anti-TNF-α agents may induce clonal selection and that concurrent treatment with immunomodulators further predisposes patients to γδ-T cell expansion. We investigated dynamic changes in the γδ-T cells of patient with CD following treatment with infliximab (Remicade®; n=20) or adalimumab (Humira®; n=26) using flow cytometry. In patients with a high γδ-T cell level, the γδ-T cells were assessed for clonality. Of these 46 CD patients, 35 had a γδ-T cells level (mean 1.6%) comparable to healthy individuals (mean 2.2%), and 11 CD patients (24%) exhibited an increased level of γδ-T cells (5-15%). In the 18 patients also receiving thiopurines or methotrexate, the average baseline γδ-T cell level was 4.4%. In three male CD patients with a high baseline value, the γδ-T cell population increased dramatically following infliximab therapy. A fourth male patient also on infliximab monotherapy presented with 20% γδ-T cells, which increased to 25% shortly after treatment and was 36% between infusions. Clonality studies revealed an oligoclonal γδ-T cell pattern with dominant γδ-T cell clones. In support of our clinical findings, in vitro experiments showed a dose-dependent proliferative effect of anti-TNF-α agents on γδ-T cells. CD patients treated with immunomodulators had constitutively high levels of γδ-T cells. Infliximab exacerbated clonal γδ-T cell expansion in vivo and induced γδ-T cell proliferation in vitro. Overall, young, male CD patients with high baseline γδ-T cell levels may be at an increased risk of developing malignant γδ-T cell lymphomas following treatment with anti-TNF-α agents.

Assessment of potential soybean cadmium excluder cultivars at different concentrations of Cd in soils.

PubMed

Zhi, Yang; He, Kangxin; Sun, Ting; Zhu, Yongqiang; Zhou, Qixing

2015-09-01

The selection of cadmium-excluding cultivars has been used to minimize the transfer of cadmium into the human food chain. In this experiment, five Chinese soybean plants were grown in three soils with different concentrations of Cd (0.15, 0.75 and 1.12mg/kg). Variations in uptake, enrichment, and translocation of Cd among these soybean cultivars were studied. The results indicated that the concentration of Cd in seeds that grew at 1.12mg/kg Cd in soils exceeded the permitted maximum levels in soybeans. Therefore, our results indicated that even some soybean cultivars grown on soils with permitted levels of Cd might accumulate higher concentrations of Cd in seeds that are hazardous to human health. The seeds of these five cultivars were further assessed for interactions between Cd and other mineral nutrient elements such as Ca, Cu, Fe, Mg, Mn and Zn. High Cd concentration in soil was found to inhibit the uptake of Mn. Furthermore, Fe and Zn accumulations were found to be enhanced in the seeds of all of the five soybean cultivars in response to high Cd concentration. Cultivar Tiefeng 31 was found to fit the criteria for a Cd-excluding cultivar under different concentrations of Cd in soils. Copyright © 2015. Published by Elsevier B.V.

Genotype variations in cadmium and lead accumulations of leafy lettuce (Lactuca sativa L.) and screening for pollution-safe cultivars for food safety.

PubMed

Zhang, Kun; Yuan, Jiangang; Kong, Wei; Yang, Zhongyi

2013-06-01

Heavy-metals in polluted soils can accumulate in plants and threaten crop safety. To evaluate the risk of heavy-metal pollution in leafy lettuce (Lactuca sativa L.), two pot experiments were conducted to investigate Cd and Pb accumulation and transfer potential in 28 cultivars of lettuce and to screen for low-Cd and low-Pb accumulative cultivars. In the three treatments, 5.2-fold, 4.8-fold and 4.8-fold differences in the shoot Cd concentration were observed between the cultivars with the highest and the lowest Cd concentrations, respectively. This genotype variation was sufficiently large to identify low-Cd accumulative genotypes to reduce Cd contamination in food. Cadmium accumulation in the low-Cd accumulative genotypes was significantly positively correlated with Pb accumulation. At the cultivar level, Cd and Pb accumulation in lettuce was stable and genotype-dependent. High Pb soil levels did not affect shoot Cd accumulation in lettuce. Lettuce was concluded to be at high risk for Cd pollution and low risk for Pb pollution. Among the tested cultivars, cvs. SJGT, YLGC, N518, and KR17 had the lowest Cd and Pb accumulation abilities in shoots and are thus important parental material for breeding pollution-safe cultivars to minimize Cd and Pb accumulation.

The pan-B cell marker CD22 is expressed on gastrointestinal eosinophils and negatively regulates tissue eosinophilia¶

PubMed Central

Wen, Ting; Mingler, Melissa K.; Blanchard, Carine; Wahl, Benjamin; Pabst, Oliver; Rothenberg, Marc E.

2011-01-01

CD22 is currently recognized as a B cell-specific Siglec and has been exploited therapeutically with humanized anti-CD22 monoclonal antibody having been used against B cell leukemia. Herein, tissue-specific eosinophil mRNA microarray analysis identified that CD22 transcript levels of murine gastrointestinal (GI) eosinophils are 10-fold higher than those of lung eosinophils. In order to confirm the mRNA data at the protein level, we developed a FACS-based protocol designed to phenotype live GI eosinophils isolated from the murine lamina propria. Indeed, we found that jejunum eosinophils expressed remarkably high levels of surface CD22, similar to levels found in B cells across multiple mouse strains. In contrast, CD22 was undetectable on eosinophils from the colon, blood, thymus, spleen, uterus, peritoneal cavity and allergen-challenged lung. Eosinophils isolated from newborn mice did not express CD22 but subsequently upregulated CD22 expression to adult levels within the first 10 days after birth. The GI lamina propria from CD22 gene-targeted mice harbored more eosinophils than wild-type control mice, while the GI eosinophil turnover rate was unaltered in the absence of CD22. Our findings identify a novel expression pattern and tissue eosinophilia-regulating function for the “B cell-specific” inhibitory molecule CD22 on GI eosinophils. PMID:22190185

The pan-B cell marker CD22 is expressed on gastrointestinal eosinophils and negatively regulates tissue eosinophilia.

PubMed

Wen, Ting; Mingler, Melissa K; Blanchard, Carine; Wahl, Benjamin; Pabst, Oliver; Rothenberg, Marc E

2012-02-01

CD22 is currently recognized as a B cell-specific Siglec and has been exploited therapeutically with humanized anti-CD22 mAb having been used against B cell leukemia. In this study, tissue-specific eosinophil mRNA microarray analysis identified that CD22 transcript levels of murine gastrointestinal (GI) eosinophils are 10-fold higher than those of lung eosinophils. To confirm the mRNA data at the protein level, we developed a FACS-based protocol designed to phenotype live GI eosinophils isolated from the murine lamina propria. Indeed, we found that jejunum eosinophils expressed remarkably high levels of surface CD22, similar to levels found in B cells across multiple mouse strains. In contrast, CD22 was undetectable on eosinophils from the colon, blood, thymus, spleen, uterus, peritoneal cavity, and allergen-challenged lung. Eosinophils isolated from newborn mice did not express CD22 but subsequently upregulated CD22 expression to adult levels within the first 10 d after birth. The GI lamina propria from CD22 gene-targeted mice harbored more eosinophils than wild type control mice, whereas the GI eosinophil turnover rate was unaltered in the absence of CD22. Our findings identify a novel expression pattern and tissue eosinophilia-regulating function for the "B cell-specific" inhibitory molecule CD22 on GI eosinophils.

Availability of activated CD4+ T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys.

PubMed

Klatt, Nichole R; Villinger, Francois; Bostik, Pavel; Gordon, Shari N; Pereira, Lara; Engram, Jessica C; Mayne, Ann; Dunham, Richard M; Lawson, Benton; Ratcliffe, Sarah J; Sodora, Donald L; Else, James; Reimann, Keith; Staprans, Silvija I; Haase, Ashley T; Estes, Jacob D; Silvestri, Guido; Ansari, Aftab A

2008-06-01

Naturally SIV-infected sooty mangabeys (SMs) remain asymptomatic despite high virus replication. Elucidating the mechanisms underlying AIDS resistance of SIV-infected SMs may provide crucial information to better understand AIDS pathogenesis. In this study, we assessed the determinants of set-point viremia in naturally SIV-infected SMs, i.e., immune control of SIV replication versus target cell limitation. We depleted CD4+ T cells in 6 naturally SIV-infected SMs by treating with humanized anti-CD4 mAb (Cdr-OKT4A-huIgG1). CD4+ T cells were depleted almost completely in blood and BM and at variable levels in mucosal tissues and LNs. No marked depletion of CD14+ monocytes was observed. Importantly, CD4+ T cell depletion was associated with a rapid, significant decline in viral load, which returned to baseline level at day 30-45, coincident with an increased fraction of proliferating and activated CD4+ T cells. Throughout the study, virus replication correlated with the level of proliferating CD4+ T cells. CD4+ T cell depletion did not induce any changes in the fraction of Tregs or the level of SIV-specific CD8+ T cells. Our results suggest that the availability of activated CD4+ T cells, rather than immune control of SIV replication, is the main determinant of set-point viral load during natural SIV infection of SMs.

High susceptibility to liver injury in IL-27 p28 conditional knockout mice involves intrinsic interferon-γ dysregulation of CD4+ T cells.

PubMed

Zhang, Song; Liang, Ruifang; Luo, Wei; Liu, Chang; Wu, Xiaoli; Gao, Yanan; Hao, Jianlei; Cao, Guangchao; Chen, Xi; Wei, Jun; Xia, Siyuan; Li, Zheng; Wen, Ti; Wu, Yunyun; Zhou, Xinglong; Wang, Puyue; Zhao, Liqing; Wu, Zhengzhou; Xiong, Sidong; Gao, Xiaoming; Gao, Xiang; Chen, Yongyan; Ge, Qing; Tian, Zhigang; Yin, Zhinan

2013-04-01

Interleukin (IL)-27, a newly discovered IL-12 family cytokine, is composed of p28 and EBI3. In this study, CD11c-p28(f/f) conditional knockout mice were generated to delete p28 specifically in dendritic cells (DCs). We demonstrated that in the absence of DC-derived p28, these mice were highly susceptible to both low and higher concentrations of concanavalin A (ConA) (5 mg/kg or 10 mg/kg), with extremely early and steady high levels of interferon-γ (IFN-γ) in sera. Neutralizing IFN-γ prevented ConA-induced liver damage in these mice, indicating a critical role of IFN-γ in this pathological process. Interestingly, the main source of the increased IFN-γ in CD11c-p28(f/f) mice was CD4+ T cells, but not natural killer T (NKT) cells. Depletion of CD4+ , but not NK1.1+ , cells completely abolished liver damage, whereas transferring CD4+ T cells from CD11c-p28(f/f) mice, but not from wild-type mice or CD11c-p28(f/f) -IFN-γ(-/-) double knockout mice to CD4(-/-) mice, restored the increased liver damage. Further studies defined higher levels of IFN-γ and T-bet messenger RNA in naïve CD4+ T cells from CD11c-p28(f/f) mice, and these CD4+ T cells were highly responsive to both low and higher concentrations of anti-CD3, indicating a programmed functional alternation of CD4+ T cells. We provide a unique model for studying the pathology of CD4+ T cell-mediated liver injury and reveal a novel function of DC-derived p28 on ConA-induced fulminant hepatitis through regulation of the intrinsic ability for IFN-γ production by CD4+ T cells. Copyright © 2012 American Association for the Study of Liver Diseases.

Exogenous proline mediates alleviation of cadmium stress by promoting photosynthetic activity, water status and antioxidative enzymes activities of young date palm (Phoenix dactylifera L.).

PubMed

Zouari, M; Ben Ahmed, Ch; Zorrig, W; Elloumi, N; Rabhi, M; Delmail, D; Ben Rouina, B; Labrousse, P; Ben Abdallah, F

2016-06-01

The ability of exogenous compatible solutes, such as proline, to counteract cadmium (Cd) inhibitory effects in young date palm plants (Phoenix dactylifera L. cv Deglet Nour) was investigated. Two-year-old date palm plants were subjected for five months at different Cd stress levels (0, 10 and 30 mg CdCl2 kg(-1) soil) whether supplied or not with exogenous proline (20mM) added through the irrigation water. Different levels of Cd stress altered plant growth, gas exchanges and chlorophyll content as well as water status, but at different extent among them. In contrast, an increase of antioxidant enzymes activities of Cd-treated plants in association with high amounts of proline content, hydrogen peroxide (H2O2), thiobarbituric acid reactive substances (TBARS) and electrolyte leakage (EL) were observed. Interestingly, exogenous proline mitigated the adverse effects of Cd on young date palm. Indeed, it alleviated the oxidative damage induced by Cd accumulation and established better levels of plant growth, water status and photosynthetic activity. Moreover, proline-treated plants showed high antioxidant enzymes activities (superoxide dismutase, catalase and glutathione peroxydase) in roots and leaves as compared to Cd-treated plants. Copyright © 2016 Elsevier Inc. All rights reserved.

Sequence variations and two levels of MCT1 and CD147 expression in red blood cells and gluteus muscle of horses.

PubMed

Koho, N M; Mykkänen, A K; Reeben, M; Raekallio, M R; Ilves, M; Pösö, A R

2012-01-01

MCT1-CD147 complex is the prime lactate transporter in mammalian plasma membranes. In equine red blood cells (RBCs), activity of the complex and expression of MCT1 and CD147 is bimodal; high in 70% and low in 30%. We studied whether sequence variations contribute to the bimodal expression of MCT1 and CD147. Samples of blood and cremaster muscle were collected in connection of castration from 24 horses. Additional gluteus muscle samples were collected from 15 Standardbreds of which seven were known to express low amounts of CD147 in RBCs. The cDNA of MCT1 and CD147 together with a promoter region of CD147 was sequenced. The amounts of MCT1 and CD147 expressed in RBC and muscle membranes were measured by Western blot and mRNA levels in muscles by qPCR. MCT1 and CD147 were expressed in 20 castrates, and in four only were traces found. Sequence variations found in MCT1 were not linked to MCT1 expression. In CD147 linked heterozygous single nucleotide polymorphisms (SNPs) 389A>G (Met(125)Val) and 990C>T (3'-UTR) were associated to low expression of CD147. Also a mutation 168A>G (Ile(51)Val) in CD147 was associated to low MCT1 and CD147 expression. Low MCT1 and CD147 mRNA levels in gluteus were found in Standardbreds with low CD147 expression in RBCs. The results suggest that sequence variations affect the expression level of CD147, but do not explain its bimodality. The levels of MCT1 and CD147 mRNA correlated with the expression of CD147 and suggest that bimodality of their expression is regulated at transcriptional level. Copyright © 2011 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mijal, Renee S., E-mail: rmijal@epi.msu.edu; Holzman, Claudia B.

The heavy metal cadmium (Cd) is long-lived in the body and low-level cumulative exposure, even among non-smokers, has been associated with changes in renal function and bone metabolism. Women are more susceptible to the adverse effects of Cd and have higher body burdens. Due to increased dietary absorption of Cd in menstruating women and the long half-life of the metal, reproductive age exposures are likely important contributors to overall body burden and disease risk. We examined blood Cd levels in women of reproductive age in the US and assessed variation by race/ethnicity. Blood Cd concentrations were compared among female NHANESmore » participants aged 20-44, who were neither pregnant nor breastfeeding. Sample size varied primarily based on inclusion/exclusion of smokers (n=1734-3121). Mean Cd concentrations, distributions and odds ratios were calculated using SUDAAN. For logistic regression Cd was modeled as high (the upper 10% of the distribution) vs. the remainder. Overall, Mexican Americans had lower Cd levels than other groups due to a lower smoking prevalence, smoking being an important source of exposure. Among never-smokers, Mexican Americans had 1.77 (95% CI: 1.06-2.96) times the odds of high Cd as compared to non-Hispanic Whites after controlling for age and low iron (ferritin). For non-Hispanic Blacks, the odds were 2.96 (CI: 1.96-4.47) times those of non-Hispanic Whites in adjusted models. Adjustment for relevant reproductive factors or exposure to environmental tobacco smoke had no effect. In this nationally representative sample, non-smoking Mexican American and non-Hispanic Black women were more likely to have high Cd than non-Hispanic White women. Additional research is required to determine the underlying causes of these differences.« less

Potential of Pteris vittata L. for phytoremediation of sites co-contaminated with cadmium and arsenic: the tolerance and accumulation.

PubMed

Xiao, Xiyuan; Chen, Tongbin; An, Zhizhuang; Lei, Mei; Huang, Zechun; Liao, Xiaoyong; Liu, Yingru

2008-01-01

Field investigation and greenhouse experiments were conducted to study the tolerance of Pteris vittata L. (Chinese brake) to cadmium (Cd) and its feasibility for remediating sites co-contaminated with Cd and arsenic (As). The results showed that P. vittata could survive in pot soils spiked with 80 mg/kg of Cd and tolerated as great as 301 mg/kg of total Cd and 26.8 mg/kg of diethyltriaminepenta acetic acid (DTPA)-extractable Cd under field conditions. The highest concentration of Cd in fronds was 186 mg/kg under a total soil concentration of 920 mg As/kg and 98.6 mg Cd/kg in the field, whereas just 2.6 mg/kg under greenhouse conditions. Ecotypes of P. vittata were differentiated in tolerance and accumulation of Cd, and some of them could not only tolerate high concentrations of soil Cd, but also accumulated high concentrations of Cd in their fronds. Arsenic uptake and transportation by P. vittata was not inhibited at lower levels (< or = 20 mg/kg) of Cd addition. Compared to the treatment without addition of Cd, the frond As concentration was increased by 103.8% at 20 mg Cd/kg, with the highest level of 6434 mg/kg. The results suggested that the Cd-tolerant ecotype of P. vittata extracted effectively As and Cd from the site co-contaminated with Cd and As, and might be used to remediate and revegetate this type of site.

Psychological stress is associated with altered levels of myeloid-derived suppressor cells in breast cancer patients.

PubMed

Mundy-Bosse, Bethany L; Thornton, Lisa M; Yang, Hae-Chung; Andersen, Barbara L; Carson, William E

2011-01-01

Our group has shown in a randomized clinical trial that psychological intervention to reduce stress in patients with stages II and III breast cancer led to enhanced immune function, fewer recurrences and improved overall survival. We hypothesized that patients with high levels of stress would have alterations in myeloid-derived suppressor cells (MDSC) compared to patients with lower stress. PBMC from 16 patients with high stress (n = 8) or with low stress (n = 8) after surgery as measured by the Impact of Event Scale (IES) questionnaire were evaluated for the presence of MDSC. Patients with higher IES scores had significantly elevated salivary cortisol levels (P = 0.013; 13 μg/dl vs. 9.74 μg/dl). Levels of IL-1Rα were also significantly elevated in the higher IES group (45.09 pg/ml vs. 97.16 pg/ml; P = 0.010). IP 10, G-CSF, and IL-6 were all higher in the high stress group although not to a significant degree. Flow cytometric analysis for CD33+/HLA-DR-neg/CD15+/CD11b+ MDSC revealed increased MDSC in patients with lower IES scores (P = 0.009). CD11b+/CD15+ cells constituted 9.4% of the CD33+/HLA DR-neg cell population in patients with high IES, vs. 27.3% in patients with low IES scores. Additional analyzes of the number of stressful events that affected the patients in addition to their cancer diagnosis revealed that this type of stress measure correlated with elevated levels of MDSC (P = 0.064). These data indicate the existence of a complex relationship between stress and immune function in breast cancer patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Psychological Stress is Associated with Altered Levels of Myeloid-Derived Suppressor cells in Breast Cancer Patients

PubMed Central

Mundy-Bosse, Bethany L.; Thornton, Lisa M.; Yang, Hae-Chung; Andersen, Barbara L.; Carson, William E.

2011-01-01

Our group has shown in a randomized clinical trial that psychological intervention to reduce stress in patients with stage II and III breast cancer led to enhanced immune function, fewer recurrences and improved overall survival. We hypothesized that patients with high levels of stress would have alterations in myeloid-derived suppressor cells (MDSC) compared to patients with lower stress. PBMC from 16 patients with high stress (n = 8) or with low stress (n = 8) after surgery as measured by the Impact of Event Scale (IES) questionnaire were evaluated for the presence of MDSC. Patients with higher IES scores had significantly elevated salivary cortisol levels (P = 0.013; 13 µg/dl vs. 9.74 µg/dl). Levels of IL-1Rα were also significantly elevated in the higher IES group (45.09 pg/mL vs. 97.16 pg/mL; P = 0.010). IP 10, G-CSF, and IL-6 were all higher in the high stress group although not to a significant degree. Flow cytometric analysis for CD33+/HLA-DR-neg/CD15+/CD11b+ MDSC revealed increased MDSC in patients with lower IES scores (P = 0.009). CD11b+/CD15+ cells constituted 9.4% of the CD33+/HLA DR-neg cell population in patients with high IES, versus 27.3% in patients with low IES scores. Additional analyses of the number of stressful events that affected the patients in addition to their cancer diagnosis revealed that this type of stress measure correlated with elevated levels of MDSC (P = .064). These data indicate the existence of a complex relationship between stress and immune function in breast cancer patients. PMID:21600570

High Aminopeptidase N/CD13 Levels Characterize Human Amniotic Mesenchymal Stem Cells and Drive Their Increased Adipogenic Potential in Obese Women

PubMed Central

Iaffaldano, Laura; Nardelli, Carmela; Raia, Maddalena; Mariotti, Elisabetta; Ferrigno, Maddalena; Quaglia, Filomena; Labruna, Giuseppe; Capobianco, Valentina; Capone, Angela; Maruotti, Giuseppe Maria; Pastore, Lucio; Di Noto, Rosa; Martinelli, Pasquale; Del Vecchio, Luigi

2013-01-01

Maternal obesity is associated to increased fetal risk of obesity and other metabolic diseases. Human amniotic mesenchymal stem cells (hA-MSCs) have not been characterized in obese women. The aim of this study was to isolate and compare hA-MSC immunophenotypes from obese (Ob-) and normal weight control (Co-) women, to identify alterations possibly predisposing the fetus to obesity. We enrolled 16 Ob- and 7 Co-women at delivery (mean/SEM prepregnancy body mass index: 40.3/1.8 and 22.4/1.0 kg/m2, respectively), and 32 not pregnant women. hA-MSCs were phenotyped by flow cytometry; several maternal and newborn clinical and biochemical parameters were also measured. The expression of membrane antigen CD13 was higher on Ob-hA-MSCs than on Co-hA-MSCs (P=0.005). Also, serum levels of CD13 at delivery were higher in Ob- versus Co-pregnant women and correlated with CD13 antigen expression on Ob-hA-MSCs (r2=0.84, P<0.0001). Adipogenesis induction experiments revealed that Ob-hA-MSCs had a higher adipogenic potential than Co-hA-MSCs as witnessed by higher peroxisome proliferator-activated receptor gamma and aP2 mRNA levels (P=0.05 and P=0.05, respectively), at postinduction day 14 associated with increased CD13 mRNA levels from baseline to day 4 postinduction (P<0.05). Adipogenesis was similar in the two sets of hA-MSCs after CD13 silencing, whereas it was increased in Co-hA-MSCs after CD13 overexpression. CD13 expression was high also in Ob-h-MSCs from umbilical cords or visceral adipose tissue of not pregnant women. In conclusion, antigen CD13, by influencing the adipogenic potential of hA-MSCs, could be an in utero risk factor for obesity. Our data strengthen the hypothesis that high levels of serum and MSC CD13 are obesity markers. PMID:23488598

Fibrocytes in the fibrotic lung: altered phenotype detected by flow cytometry.

PubMed

Reese, Charles; Lee, Rebecca; Bonner, Michael; Perry, Beth; Heywood, Jonathan; Silver, Richard M; Tourkina, Elena; Visconti, Richard P; Hoffman, Stanley

2014-01-01

Fibrocytes are bone marrow hematopoietic-derived cells that also express a mesenchymal cell marker (commonly collagen I) and participate in fibrotic diseases of multiple organs. Given their origin, they or their precursors must be circulating cells before recruitment into target tissues. While most previous studies focused on circulating fibrocytes, here we focus on the fibrocyte phenotype in fibrotic tissue. The study's relevance to human disease is heightened by use of a model in which bleomycin is delivered systemically, recapitulating several features of human scleroderma including multi-organ fibrosis not observed when bleomycin is delivered directly into the lungs. Using flow cytometry, we find in the fibrotic lung a large population of CD45(high) fibrocytes (called Region I) rarely found in vehicle-treated control mice. A second population of CD45+ fibrocytes (called Region II) is observed in both control and fibrotic lung. The level of CD45 in circulating fibrocytes is far lower than in either Region I or II lung fibrocytes. The chemokine receptors CXCR4 and CCR5 are expressed at higher levels in Region I than in Region II and are present at very low levels in all other lung cells including CD45+/collagen I- leucocytes. The collagen chaperone HSP47 is present at similar high levels in both Regions I and II, but at a higher level in fibrotic lung than in control lung. There is also a major population of HSP47(high)/CD45- cells in fibrotic lung not present in control lung. CD44 is present at higher levels in Region I than in Region II and at much lower levels in all other cells including CD45+/collagen I- leucocytes. When lung fibrosis is inhibited by restoring caveolin-1 activity using a caveolin-1 scaffolding domain peptide (CSD), a strong correlation is observed between fibrocyte number and fibrosis score. In summary, the distinctive phenotype of fibrotic lung fibrocytes suggests that fibrocyte differentiation occurs primarily within the target organ.

Fibrocytes in the fibrotic lung: altered phenotype detected by flow cytometry

PubMed Central

Reese, Charles; Lee, Rebecca; Bonner, Michael; Perry, Beth; Heywood, Jonathan; Silver, Richard M.; Tourkina, Elena; Visconti, Richard P.; Hoffman, Stanley

2014-01-01

Fibrocytes are bone marrow hematopoietic-derived cells that also express a mesenchymal cell marker (commonly collagen I) and participate in fibrotic diseases of multiple organs. Given their origin, they or their precursors must be circulating cells before recruitment into target tissues. While most previous studies focused on circulating fibrocytes, here we focus on the fibrocyte phenotype in fibrotic tissue. The study's relevance to human disease is heightened by use of a model in which bleomycin is delivered systemically, recapitulating several features of human scleroderma including multi-organ fibrosis not observed when bleomycin is delivered directly into the lungs. Using flow cytometry, we find in the fibrotic lung a large population of CD45high fibrocytes (called Region I) rarely found in vehicle-treated control mice. A second population of CD45+ fibrocytes (called Region II) is observed in both control and fibrotic lung. The level of CD45 in circulating fibrocytes is far lower than in either Region I or II lung fibrocytes. The chemokine receptors CXCR4 and CCR5 are expressed at higher levels in Region I than in Region II and are present at very low levels in all other lung cells including CD45+/collagen I- leucocytes. The collagen chaperone HSP47 is present at similar high levels in both Regions I and II, but at a higher level in fibrotic lung than in control lung. There is also a major population of HSP47high/CD45- cells in fibrotic lung not present in control lung. CD44 is present at higher levels in Region I than in Region II and at much lower levels in all other cells including CD45+/collagen I- leucocytes. When lung fibrosis is inhibited by restoring caveolin-1 activity using a caveolin-1 scaffolding domain peptide (CSD), a strong correlation is observed between fibrocyte number and fibrosis score. In summary, the distinctive phenotype of fibrotic lung fibrocytes suggests that fibrocyte differentiation occurs primarily within the target organ. PMID:24999331

High PD-L1/CD86 MFI ratio and IL-10 secretion characterize human regulatory dendritic cells generated for clinical testing in organ transplantation.

PubMed

Zahorchak, Alan F; Macedo, Camila; Hamm, David E; Butterfield, Lisa H; Metes, Diana M; Thomson, Angus W

2018-01-01

Human regulatory dendritic cells (DCreg) were generated from CD14 immunobead-purified or elutriated monocytes in the presence of vitamin D3 and IL-10. They exhibited similar, low levels of costimulatory CD80 and CD86, but comparatively high levels of co-inhibitory programed death ligand-1 (PD-L1) and IL-10 production compared to control immature DC (iDC). Following Toll-like receptor 4 ligation, unlike control iDC, DCreg resisted phenotypic and functional maturation and further upregulated PD-L1:CD86 expression. Whereas LPS-stimulated control iDC (mature DC; matDC) secreted pro-inflammatory tumor necrosis factor but no IL-10, the converse was observed for LPS-stimulated DCreg. DCreg weakly stimulated naïve and memory allogeneic CD4 + and CD8 + T cell proliferation and IFNγ, IL-17A and perforin/granzyme B production in MLR. Their stimulatory function was enhanced however, by blocking PD-1 ligation. High-throughput T cell receptor (TCR) sequencing revealed that, among circulating T cell subsets, memory CD8 + T cells contained the most alloreactive TCR clonotypes and that, while matDC expanded these alloreactive memory CD8 TCR clonotypes, DCreg induced more attenuated responses. These findings demonstrate the feasibility of generating highly-purified GMP-grade DCreg for systemic infusion, their influence on the alloreactive T cell response, and a key mechanistic role of the PD1 pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Interaction effects of metals and salinity on biodegradation of a complex hydrocarbon waste.

PubMed

Amatya, Prasanna L; Hettiaratchi, Joseph Patrick A; Joshi, Ramesh C

2006-02-01

The presence of high levels of salts because of produced brine water disposal at flare pits and the presence of metals at sufficient concentrations to impact microbial activity are of concern to bioremediation of flare pit waste in the upstream oil and gas industry. Two slurry-phase biotreatment experiments based on three-level factorial statistical experimental design were conducted with a flare pit waste. The experiments separately studied the primary effect of cadmium [Cd(II)] and interaction effect between Cd(II) and salinity and the primary effect of zinc [Zn(II)] and interaction effect between Zn(II) and salinity on hydrocarbon biodegradation. The results showed 42-52.5% hydrocarbon removal in slurries spiked with Cd and 47-62.5% in the slurries spiked with Zn. The analysis of variance showed that the primary effects of Cd and Cd-salinity interaction were statistically significant on hydrocarbon degradation. The primary effects of Zn and the Zn-salinity interaction were statistically insignificant, whereas the quadratic effect of Zn was highly significant on hydrocarbon degradation. The study on effects of metallic chloro-complexes showed that the total aqueous concentration of Cd or Zn does not give a reliable indication of overall toxicity to the microbial activity in the presence of high salinity levels.

Different T-bet expression patterns characterize particular reactive lymphoid tissue lesions.

PubMed

Jöhrens, K; Anagnostopoulos, I; Dürkop, H; Stein, H

2006-03-01

To investigate T-bet expression profiles in various lymphoid tissue diseases caused by intracellular pathogens and to compare them in disorders without an infective aetiology. Murine and in vitro experiments have shown that the expression/induction of T-bet, the master regulator of Th1 differentiation, can be achieved by obligate intracellular pathogens and high interferon (IFN)-gamma levels. Lymph node biopsies were analysed immunohistochemically employing single and double labelling for T-bet and CD20, CD4, CD8 and CD30 detection. In disorders associated with high IFN-gamma levels and intracellular pathogens (infectious mononucleosis, HIV-associated lymphadenopathy, cat-scratch disease, and toxoplasmic lymphadenitis), T-bet-expressing CD4 cells were accompanied by significant numbers of T-bet-positive CD8 and B cells. A similar profile was also found in histiocytic necrotizing (Kikuchi) lymphadenitis, a disease of unknown cause. In contrast, T-bet expression in disorders without an infective aetiology was observed in only a small portion of lymphocytes. Increased T-bet expression does not only identify intracellular infections in lymphoid tissue associated with high IFN-gamma levels, but also implies that, under these conditions, it becomes induced in B cells, which apparently support the Th1 response. T-bet expression in Kikuchi lymphadenitis underscores the hypothesis that it is caused by an intracellular microorganism.

Sex Differences in Arm Muscle Fatigability With Cognitive Demand in Older Adults.

PubMed

Pereira, Hugo M; Spears, Vincent C; Schlinder-Delap, Bonnie; Yoon, Tejin; Harkins, April; Nielson, Kristy A; Hoeger Bement, Marie; Hunter, Sandra K

2015-08-01

Muscle fatigability can increase when a stressful, cognitively demanding task is imposed during a low-force fatiguing contraction with the arm muscles, especially in women. Whether this occurs among older adults (>60 years) is currently unknown. We aimed to determine if higher cognitive demands, stratified by sex, increased fatigability in older adults (>60 years). Secondarily, we assessed if varying cognitive demand resulted in decreased steadiness and was explained by anxiety or cortisol levels. Seventeen older women (70±6 years) and 13 older men (71±5 years) performed a sustained, isometric, fatiguing contraction at 20% of maximal voluntary contraction until task failure during three sessions: high cognitive demand (high CD=mental subtraction by 13); low cognitive demand (low CD=mental subtraction by 1); and control (no subtraction). Fatigability was greater when high and low CD were performed during the fatiguing contraction for the women but not for the men. In women, time to failure with high CD was 16±8 minutes and with low CD was 17±4 minutes, both of which were shorter than time to failure in control contractions (21±7 minutes; high CD mean difference: 5 minutes [95% confidence interval {CI}, 0.78-9.89], p=0.02; low CD mean difference: 4 minutes [95% CI, 0.57-7.31], p=0.03). However, in men, no differences were detected in time to failure with cognitive demand (control: 13±5 minutes; high CD mean difference: -0.09 minutes [95% CI, -2.8 to 2.7], p=1.00; low CD mean difference: 0.75 minutes [95% CI, -1.1 to 2.6], p=0.85). Steadiness decreased (force fluctuations increased) more during high CD than control. Elevated anxiety, mean arterial pressure, and salivary cortisol levels in both men and women did not explain the greater fatigability during high CD. Older women but not men showed marked increases in fatigability when low or high CD was imposed during sustained static contractions with the elbow flexor muscles and contrasts with previous findings for the lower limb. Steadiness decreased in both sexes when high CD was imposed. Older women are susceptible to greater fatigability of the upper limb with heightened mental activity during sustained postural contractions, which are the foundation of many work-related tasks.

Residual Endotoxin Contaminations in Recombinant Proteins Are Sufficient to Activate Human CD1c+ Dendritic Cells

PubMed Central

Schwarz, Harald; Schmittner, Maria; Duschl, Albert; Horejs-Hoeck, Jutta

2014-01-01

Many commercially available recombinant proteins are produced in Escherichia coli, and most suppliers guarantee contamination levels of less than 1 endotoxin unit (EU). When we analysed commercially available proteins for their endotoxin content, we found contamination levels in the same range as generally stated in the data sheets, but also some that were higher. To analyse whether these low levels of contamination have an effect on immune cells, we stimulated the monocytic cell line THP-1, primary human monocytes, in vitro differentiated human monocyte-derived dendritic cells, and primary human CD1c+ dendritic cells (DCs) with very low concentrations of lipopolysaccharide (LPS; ranging from 0.002–2 ng/ml). We show that CD1c+ DCs especially can be activated by minimal amounts of LPS, equivalent to the levels of endotoxin contamination we detected in some commercially available proteins. Notably, the enhanced endotoxin sensitivity of CD1c+ DCs was closely correlated with high CD14 expression levels observed in CD1c+ DCs that had been maintained in cell culture medium for 24 hours. When working with cells that are particularly sensitive to LPS, even low endotoxin contamination may generate erroneous data. We therefore recommend that recombinant proteins be thoroughly screened for endotoxin contamination using the limulus amebocyte lysate test, fluorescence-based assays, or a luciferase based NF-κB reporter assay involving highly LPS-sensitive cells overexpressing TLR4, MD-2 and CD14. PMID:25478795

Spatial distribution and ecological risk assessment of heavy metal on surface sediment in west part of Java Sea

NASA Astrophysics Data System (ADS)

Effendi, Hefni; Wardiatno, Yusli; Kawaroe, Mujizat; Mursalin; Fauzia Lestari, Dea

2017-01-01

The surface sediments were identified from west part of Java Sea to evaluate spatial distribution and ecological risk potential of heavy metals (Hg, As, Cd, Cr, Cu, Pb, Zn and Ni). The samples were taken from surface sediment (<0.5 m) in 26 m up to 80 m water depth with Eikman grab. The average material composition on sediment samples were clay (9.86%), sand (8.57%) and mud sand (81.57%). The analysis showed that Pb (11.2%), Cd (49.7%), and Ni (59.5%) exceeded of Probably Effect Level (PEL). Base on ecological risk analysis, {{Cd }}≤ft( {E_r^i:300.64} \\right) and {{Cr }}≤ft( {E_r^i:0.02} \\right) were categorized to high risk and low risk criteria. The ecological risk potential sequences of this study were Cd>Hg>Pb>Ni>Cu>As>Zn>Cr. Furthermore, the result of multivariate statistical analysis shows that correlation among heavy metals (As/Ni, Cd/Ni, and Cu/Zn) and heavy metals with Risk Index (Cd/Ri and Ni/Ri) had positive correlation in significance level p<0.05. Total variance of analysis factor was 80.04% and developed into 3 factors (eigenvalues >1). On the cluster analysis, Cd, Ni, Pb were identified as fairly high contaminations level (cluster 1), Hg as moderate contamination level (cluster 2) and Cu, Zn, Cr with lower contamination level (cluster 3).

Comparative analysis of proteomic changes in contrasting flax cultivars upon cadmium exposure.

PubMed

Hradilová, Jana; Rehulka, Pavel; Rehulková, Helena; Vrbová, Miroslava; Griga, Miroslav; Brzobohatý, Bretislav

2010-01-01

Cadmium (Cd) is classified as a serious pollutant due to its high toxicity, high carcinogenicity, and widespread presence in the environment. Phytoremediation represents an effective low-cost approach for removing pollutants from contaminated soils, and a crop with significant phytoremediation potential is flax. However, significant differences in Cd accumulation and tolerance were previously found among commercial flax cultivars. Notably, cv. Jitka showed substantially higher tolerance to elevated Cd levels in soil and plant tissues than cv. Tábor. Here, significant changes in the expression of 14 proteins (related to disease/defense, metabolism, protein destination and storage, signal transduction, energy and cell structure) were detected by image and mass spectrometric analysis of two-dimensionally separated proteins extracted from Cd-treated cell suspension cultures derived from these contrasting cultivars. Further, two proteins, ferritin and glutamine synthetase (a key enzyme in glutathione biosynthesis), were only up-regulated by Cd in cv. Jitka, indicating that Cd tolerance mechanisms in this cultivar may include maintenance of low Cd levels at sensitive sites by ferritin and low-molecular weight thiol peptides binding Cd. The identified changes could facilitate marker-assisted breeding for Cd tolerance and the development of transgenic flax lines with enhanced Cd tolerance and accumulation capacities for phytoremediating Cd-contaminated soils.

Resistance mechanisms and their difference between the root and leaf of Microsorum pteropus - A novel potential aquatic cadmium hyperaccumulator.

PubMed

Lan, Xin-Yu; Yang, Bin; Yan, Yun-Yun; Li, Xin-Yuan; Xu, Fu-Liu

2018-03-01

Microsorum pteropus (M. pteropus), an aquatic Polypodiaceae fern, was identified as a novel potential cadmium (Cd) hyperaccumulator in our previous study. This study reveals the Cd-resistance mechanisms and their difference between the root and leaf of M. pteropus based on analyses of photosynthesis, antioxidant systems and gene expression. A high level of Cd at 500μM was used to treat the samples to test the effects of this compound. Superoxide dismutase (SOD), peroxidase (POD), malondialdehyde (MDA) and flavonoids were used as indicators for antioxidant system changes. Five chlorophyll fluorescent parameters including the maximal photochemical efficiency of photosystem II (F v /F m ), effective quantum yield of photosystem II (Y(II)), photochemical quenching (qP), nonphotochemical quenching (qN) and electron transport rate (ETR) were measured to determine the photosynthetic changes. RNA-sequencing analysis was used to study the changes in gene expression. The results showed that after exposure to high levels of Cd, the concentrations of enzymatic oxidants (SOD and POD) were significantly increased, while the MDA levels were significantly decreased. There were no significant changes for the chlorophyll fluorescent parameters during Cd stress, which indicates that M. pteropus is highly effective at protecting itself. Certain functional genes, including photosystem genes and secondary metabolites, had significantly altered levels of expression. Different Cd-resistance mechanisms were found between the root and leaf tissues of M. pteropus. The root tissues of M. pteropus resist Cd damage using antioxidants, while its leaf tissues mainly protect themselves using photosystem self-protection. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhancing tonoplast Cd/H antiport activity increases Cd, Zn, and Mn tolerance, and impacts root/shoot Cd partitioning in Nicotiana tabacum L.

USDA-ARS?s Scientific Manuscript database

Sequestration mechanisms that prevent high concentrations of free metal ions from persisting in metabolically active compartments of cells are thought to be central in tolerance of plants to high levels of divalent cation metals. Expression of "AtCAX2" or "AtCAX4", which encode divalent cation/proto...

MYCN and HDAC5 transcriptionally repress CD9 to trigger invasion and metastasis in neuroblastoma

PubMed Central

Fabian, Johannes; Opitz, Desirée; Althoff, Kristina; Lodrini, Marco; Hero, Barbara; Volland, Ruth; Beckers, Anneleen; de Preter, Katleen; Decock, Anneleen; Patil, Nitin; Abba, Mohammed; Kopp-Schneider, Annette; Astrahantseff, Kathy; Wünschel, Jasmin; Pfeil, Sebastian; Ercu, Maria; Künkele, Annette; Hu, Jamie; Thole, Theresa; Schweizer, Leonille; Mechtersheimer, Gunhild; Carter, Daniel; Cheung, Belamy B.; Popanda, Odilia; von Deimling, Andreas; Koster, Jan; Versteeg, Rogier; Schwab, Manfred; Marshall, Glenn M.; Speleman, Frank; Erb, Ulrike; Zoeller, Margot; Allgayer, Heike; Simon, Thorsten; Fischer, Matthias; Kulozik, Andreas E.; Eggert, Angelika; Witt, Olaf; Schulte, Johannes H.; Deubzer, Hedwig E.

2016-01-01

The systemic and resistant nature of metastatic neuroblastoma renders it largely incurable with current multimodal treatment. Clinical progression stems mainly from the increasing burden of metastatic colonization. Therapeutically inhibiting the migration-invasion-metastasis cascade would be of great benefit, but the mechanisms driving this cycle are as yet poorly understood. In-depth transcriptome analyses and ChIP-qPCR identified the cell surface glycoprotein, CD9, as a major downstream player and direct target of the recently described GRHL1 tumor suppressor. CD9 is known to block or facilitate cancer cell motility and metastasis dependent upon entity. High-level CD9 expression in primary neuroblastomas correlated with patient survival and established markers for favorable disease. Low-level CD9 expression was an independent risk factor for adverse outcome. MYCN and HDAC5 colocalized to the CD9 promoter and repressed transcription. CD9 expression diminished with progressive tumor development in the TH-MYCN transgenic mouse model for neuroblastoma, and CD9 expression in neuroblastic tumors was far below that in ganglia from wildtype mice. Primary neuroblastomas lacking MYCN amplifications displayed differential CD9 promoter methylation in methyl-CpG-binding domain sequencing analyses, and high-level methylation was associated with advanced stage disease, supporting epigenetic regulation. Inducing CD9 expression in a SH-EP cell model inhibited migration and invasion in Boyden chamber assays. Enforced CD9 expression in neuroblastoma cells transplanted onto chicken chorioallantoic membranes strongly reduced metastasis to embryonic bone marrow. Combined treatment of neuroblastoma cells with HDAC/DNA methyltransferase inhibitors synergistically induced CD9 expression despite hypoxic, metabolic or cytotoxic stress. Our results show CD9 is a critical and indirectly druggable suppressor of the invasion-metastasis cycle in neuroblastoma. PMID:27572323

MYCN and HDAC5 transcriptionally repress CD9 to trigger invasion and metastasis in neuroblastoma.

PubMed

Fabian, Johannes; Opitz, Desirée; Althoff, Kristina; Lodrini, Marco; Hero, Barbara; Volland, Ruth; Beckers, Anneleen; de Preter, Katleen; Decock, Anneleen; Patil, Nitin; Abba, Mohammed; Kopp-Schneider, Annette; Astrahantseff, Kathy; Wünschel, Jasmin; Pfeil, Sebastian; Ercu, Maria; Künkele, Annette; Hu, Jamie; Thole, Theresa; Schweizer, Leonille; Mechtersheimer, Gunhild; Carter, Daniel; Cheung, Belamy B; Popanda, Odilia; von Deimling, Andreas; Koster, Jan; Versteeg, Rogier; Schwab, Manfred; Marshall, Glenn M; Speleman, Frank; Erb, Ulrike; Zoeller, Margot; Allgayer, Heike; Simon, Thorsten; Fischer, Matthias; Kulozik, Andreas E; Eggert, Angelika; Witt, Olaf; Schulte, Johannes H; Deubzer, Hedwig E

2016-10-11

The systemic and resistant nature of metastatic neuroblastoma renders it largely incurable with current multimodal treatment. Clinical progression stems mainly from the increasing burden of metastatic colonization. Therapeutically inhibiting the migration-invasion-metastasis cascade would be of great benefit, but the mechanisms driving this cycle are as yet poorly understood. In-depth transcriptome analyses and ChIP-qPCR identified the cell surface glycoprotein, CD9, as a major downstream player and direct target of the recently described GRHL1 tumor suppressor. CD9 is known to block or facilitate cancer cell motility and metastasis dependent upon entity. High-level CD9 expression in primary neuroblastomas correlated with patient survival and established markers for favorable disease. Low-level CD9 expression was an independent risk factor for adverse outcome. MYCN and HDAC5 colocalized to the CD9 promoter and repressed transcription. CD9 expression diminished with progressive tumor development in the TH-MYCN transgenic mouse model for neuroblastoma, and CD9 expression in neuroblastic tumors was far below that in ganglia from wildtype mice. Primary neuroblastomas lacking MYCN amplifications displayed differential CD9 promoter methylation in methyl-CpG-binding domain sequencing analyses, and high-level methylation was associated with advanced stage disease, supporting epigenetic regulation. Inducing CD9 expression in a SH-EP cell model inhibited migration and invasion in Boyden chamber assays. Enforced CD9 expression in neuroblastoma cells transplanted onto chicken chorioallantoic membranes strongly reduced metastasis to embryonic bone marrow. Combined treatment of neuroblastoma cells with HDAC/DNA methyltransferase inhibitors synergistically induced CD9 expression despite hypoxic, metabolic or cytotoxic stress. Our results show CD9 is a critical and indirectly druggable suppressor of the invasion-metastasis cycle in neuroblastoma.

FoxP3+ CD25+ CD8+ T-Cell Induction during Primary Simian Immunodeficiency Virus Infection in Cynomolgus Macaques Correlates with Low CD4+ T-Cell Activation and High Viral Load▿

PubMed Central

Karlsson, Ingrid; Malleret, Benoît; Brochard, Patricia; Delache, Benoît; Calvo, Julien; Le Grand, Roger; Vaslin, Bruno

2007-01-01

The early immune response fails to prevent the establishment of chronic human immunodeficiency virus (HIV) infection but may influence viremia during primary infection, thereby possibly affecting long-term disease progression. CD25+ FoxP3+ regulatory T cells may contribute to HIV/simian immunodeficiency virus (SIV) pathogenesis by suppressing efficient antiviral responses during primary infection, favoring high levels of viral replication and the establishment of chronic infection. In contrast, they may decrease immune activation during chronic infection. CD4+ regulatory T cells have been studied in the most detail, but CD8+ CD25+ FoxP3+ T cells also have regulatory properties. We monitored the dynamics of CD25+ FoxP3+ T cells during primary and chronic SIVmac251 infection in cynomolgus macaques. The number of peripheral CD4+ CD25+ FoxP3+ T cells paralleled that of memory CD4+ T cells, with a rapid decline during primary infection followed by a rebound to levels just below baseline and gradual depletion during the course of infection. No change in the proportion of CD25+ FoxP3+ T cells was observed in peripheral lymph nodes. A small number of CD4+ CD25+ FoxP3+ T cells at set point was associated with a high plasma viral load. In contrast, peripheral CD8+ CD25+ FoxP3+ T cells were induced a few days after peak plasma viral load during primary infection. The number of these cells was positively correlated with viral load and negatively correlated with CD4+ T-cell activation, SIV antigen-specific proliferative responses during primary infection, and plasma viral load at set point, with large numbers of CD8+ CD25+ FoxP3+ T cells being indicative of a poor prognosis. PMID:17898053

Equine CD4+ CD25high T cells exhibit regulatory activity by close contact and cytokine-dependent mechanisms in vitro

PubMed Central

Hamza, Eman; Gerber, Vinzenz; Steinbach, Falko; Marti, Eliane

2011-01-01

Horses are particularly prone to allergic and autoimmune diseases, but little information about equine regulatory T cells (Treg) is currently available. The aim of this study therefore was to investigate the existence of CD4+ Treg cells in horses, determine their suppressive function as well as their mechanism of action. Freshly isolated peripheral blood mononuclear cells (PBMC) from healthy horses were examined for CD4, CD25 and forkhead box P3 (FoxP3) expression. We show that equine FoxP3 is expressed constitutively by a population of CD4+ CD25+ T cells, mainly in the CD4+ CD25high subpopulation. Proliferation of CD4+ CD25− sorted cells stimulated with irradiated allogenic PBMC was significantly suppressed in co-culture with CD4+ CD25high sorted cells in a dose-dependent manner. The mechanism of suppression by the CD4+ CD25high cell population is mediated by close contact as well as interleukin (IL)-10 and transforming growth factor-β1 (TGF-β1) and probably other factors. In addition, we studied the in vitro induction of CD4+ Treg and their characteristics compared to those of freshly isolated CD4+ Treg cells. Upon stimulation with a combination of concanavalin A, TGF-β1 and IL-2, CD4+ CD25+ T cells which express FoxP3 and have suppressive capability were induced from CD4+ CD25− cells. The induced CD4+ CD25high express higher levels of IL-10 and TGF-β1 mRNA compared to the freshly isolated ones. Thus, in horses as in man, the circulating CD4+ CD25high subpopulation contains natural Treg cells and functional Treg can be induced in vitro upon appropriate stimulation. Our study provides the first evidence of the regulatory function of CD4+ CD25+ cells in horses and offers insights into ex vivo manipulation of Treg cells. PMID:21977999

Functional impairment of cytomegalovirus specific CD8 T cells predicts high-level replication after renal transplantation.

PubMed

Mattes, F M; Vargas, A; Kopycinski, J; Hainsworth, E G; Sweny, P; Nebbia, G; Bazeos, A; Lowdell, M; Klenerman, P; Phillips, R E; Griffiths, P D; Emery, V C

2008-05-01

Human cytomegalovirus (HCMV) remains an important cause of morbidity after allotransplantation, causing a range of direct effects including hepatitis, pneumonitis, enteritis and retinitis. A dominant risk factor for HCMV disease is high level viral replication in blood but it remains unexplained why only a subset of patients develop such diseases. In this detailed study of 25 renal transplant recipients, we show that functional impairment of HCMV specific CD8 T cells in the production of interferon gamma was associated with a 14-fold increased risk of progression to high level replication. The CD8 T-cell impairment persisted during the period of high level replication and was more prominent in patients above 40 years of age (odds ratio = 1.37, p = 0.01) and was also evident in dialysis patients. Threshold levels of functional impairment were associated with an increased risk of future HCMV replication and there was a direct relationship between the functional capacity of HCMV ppUL83 CD8 T cells and HCMV load (R(2)= 0.83). These results help to explain why a subset of seropositive individuals develop HCMV replication and are at risk of end-organ disease and may facilitate the early identification of individuals who would benefit from targeted anti-HCMV therapy after renal transplantation.

Decrease of peritoneal inflammatory CD4(+), CD8(+), CD19(+) lymphocytes and apoptosis of eosinophils in a murine Taenia crassiceps infection.

PubMed

Zepeda, Nadia; Solano, Sandra; Copitin, Natalia; Fernández, Ana María; Hernández, Lilián; Tato, Patricia; Molinari, José L

2010-10-01

After an intraperitoneal infection of mice with Taenia crassiceps metacestodes, peritoneal inflammatory cells labeled with fluoresceinated MoAb anti-mouse were analyzed by flow cytometry. Apoptosis was studied by annexin A/PI, TUNEL assays, DNA laddering, caspase-3 activity, and electron microscopy. An important continuous decrease of CD4+, CD8+ and CD19+ lymphocytes, and an increase of eosinophils and macrophages throughout the observation time were found. Apoptosis of eosinophils was quantified during the observation period with a peak at 6 days post-infection (67.27%). In an additional experiment at 12 days post-infection using TUNEL staining, a high level of apoptosis of eosinophil (92.3%) and a significant decrease of CD4+, CD8+, and CD19+ lymphocytes were confirmed. Caspase-3 activity in peritoneal fluid, peritoneal cells' DNA fragmentation, and apoptosis of eosinophils and monocytes were found. The dramatic decrease of peritoneal inflammatory T and B cells and the high level of apoptosis of inflammatory eosinophils induced in mice by infection with T. crassiceps cysticerci may be important factors of the immunosuppression observed in cysticercosis.

CD151-mediated adhesion is crucial to osteosarcoma pulmonary metastasis

PubMed Central

Sun, Mengxiong; Zhou, Chenghao; Chen, Jian; Yin, Fei; Wang, Hongsheng; Lin, Binhui; Zuo, Dongqing; Li, Suoyuan; Feng, Lijin; Duan, Zhenfeng; Cai, Zhengdong; Hua, Yingqi

2016-01-01

CD151, a tetraspanin family protein involved in cell-cell and cell-extracellular matrix interaction, is differentially expressed in osteosarcoma cell membranes. Thus, this study aimed to investigate the role of CD151 in osteosarcoma metastasis. We analyzed CD151 expression in patient tissue samples using immunohistochemistry. CD151 expression was also silenced with shRNA in osteosarcoma cells of high metastatic potential, and cell adhesion, migration and invasion were evaluated in vitro and pulmonary metastasis was investigated in vivo. Mediators of cell signaling pathways were also examined following suppression of CD151 expression. Overall survival for patients with low versus high CD151 expression level was 94 vs. 41 months (p=0.0451). CD151 expression in osteosarcoma cells with high metastatic potential was significantly higher than in those with low metastatic potential (p<0.001). shRNA-mediated silencing of CD151 did not influence cell viability or proliferation; however, cell adhesion, migration and invasion were all inhibited (all p<0.001). In mice inoculated with shRNA-transduced osteosarcoma cells, the number and size of lung metastatic lesions were reduced compared to the mice inoculated with control-shRNA transduced cells (p<0.001). In addition, CD151 knockdown significantly reduced Akt, p38, and p65 phosphorylation as well as focal adhesion kinase, integrin β1, p70s6, and p-mTOR levels. Taken together, CD151 induced osteosarcoma metastasis likely by regulating cell function through adhesion signaling. Further studies are necessary to fully explore the diagnostic and prognostic value of determining CD151 expression in osteosarcoma patients. PMID:27556355

System analysis of the regulation of the immune response by CD147 and FOXC1 in cancer cell lines

PubMed Central

Kong, Ling-Min; Wei, Ding; Xu, Jing; Wang, Zi-Ling; Bian, Huijie; Chen, Zhi-Nan

2018-01-01

CD147, encoded by BSG, is a highly glycosylated transmembrane protein that belongs to the immunological superfamily and expressed on the surface of many types of cancer cells. While CD147 is best known as a potent inducer of extracellular matrix metalloproteinases, it can also function as a key mediator of inflammatory and immune responses. To systematically elucidate the function of CD147 in cancer cells, we performed an analysis of genome-wide profiling across the Cancer Cell Line Encyclopedia (CCLE). We showed that CD147 mRNA expression was much higher than that of most other genes in cancer cell lines. CD147 varied widely across these cell lines, with the highest levels in the ovary (COLO704) and stomach (SNU668), intermediate levels in the lung (RERFLCKJ, NCIH596 and NCIH1651) and lowest levels in hematopoietic and lymphoid tissue (UT7, HEL9217, HEL and MHHCALL3) and the kidney (A704 and SLR20). Genome-wide analyses showed that CD147 expression was significantly negatively correlated with immune-related genes. Our findings implicated CD147 as a novel regulator of immune-related genes and suggest its important role as a master regulator of immune-related responses in cancer cell lines. We also found a high correlation between the expression of CD147 and FOXC1, and proved that CD147 was a direct transcriptional target of FOXC1. Our findings demonstrate that FOXC1 is a novel regulator of CD147 and confirms its role as a master regulator of the immune response. PMID:29560120

CD30 Expression by B and T Cells: A Frequent Finding in Angioimmunoblastic T-Cell Lymphoma and Peripheral T-Cell Lymphoma-Not Otherwise Specified.

PubMed

Onaindia, Arantza; Martínez, Nerea; Montes-Moreno, Santiago; Almaraz, Carmen; Rodríguez-Pinilla, Socorro M; Cereceda, Laura; Revert, Jose B; Ortega, César; Tardio, Antoni; González, Lucía; García, Sonia; Camacho, Francisca I; González-Vela, Carmen; Piris, Miguel A

2016-03-01

CD30 expression in peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL) is currently of great interest because therapy targeting CD30 is of clinical benefit, but the clinical and therapeutic relevance of CD30 expression in these neoplasms still remains uncertain. The aim of this study was to better quantify CD30 expression in AITL and PTCL-not otherwise specified (NOS). The secondary objective was to determine whether CD30 cells exhibit a B-cell or a T-cell phenotype. Gene expression profiling was studied in a series of 37 PTCL cases demonstrating a continuous spectrum of TNFRSF8 expression. This prompted us to study CD30 immunohistochemical (IHC) expression and mRNA levels by reverse transcription polymerase chain reaction (RT-PCR) in a different series of 51 cases (43 AITLs and 8 PTCL-NOSs) in routine samples. Double stainings with PAX5/CD30, CD3/CD30, and LEF1/CD30 were performed to study the phenotype of CD30 cells. Most (90%) of the cases showed some level of CD30 expression by IHC (1% to 95%); these levels were high (>50% of tumoral cells) in 14% of cases. CD30 expression was not detected in 10% of the cases. Quantitative RT-PCR results largely confirmed these findings, demonstrating a moderately strong correlation between global CD30 IHC and mRNA levels (r=0.65, P=1.75e-7). Forty-four of the positive cases (98%) contained CD30-positive B cells (PAX5), whereas atypical CD30-positive T cells were detected in 42 cases (93%). In conclusion, our data show that most AITL and PTCL-NOS cases express CD30, exhibiting very variable levels of CD30 expression that may be measured by IHC or RT-PCR techniques.

CD8 apoptosis may be a predictor of T cell number normalization after immune reconstitution in HIV

PubMed Central

Lewis, Dorothy E; Gross, Kimber L; Diez, Martine M; Martinez, Maria L; Lukefahr, Helen N; Kozinetz, Claudia A; Arduino, Roberto C

2007-01-01

Background As part of the Houston Vanguard study, a subset of 10 patients randomized to receive IL-2 therapy were compared to 4 patients randomized to not receive IL-2, for markers of T cell activation and death during the first three cycles of IL-2. All patients were treated with combination antiretroviral therapy (ART) and were virally suppressed. The purpose of the study was to examine the role of CD8+ T cell death in responses to ART and IL-2 therapy. Methods Lymphocytes were examined at Day 0, 5 and 30 days during three cycles of IL-2 therapy. CD25, CD38, HLA-DR expression and annexin (cell death) were examined on CD4 and CD8 subpopulations. Follow up studies examined CD4 levels and CD4:CD8 reconstitution after 6 years using both univariant and multivariate analyses. Results Human lymphocytes responded to IL-2 therapy by upregulation of CD25 on CD4+ T cells, leading to an increase in CD4 cell counts. CD8+ T cells did not increase CD25 expression, but upregulated activation antigens (CD38 and DR) and had increased death. At baseline, 7 of the 14 patients had high CD8+ T cell apoptosis (mean 17.0% ± 6.0). We did an exploratory analysis of immune status after six years, and found that baseline CD8+ T cell apoptosis was correlated with CD4 cell count gain beginning two years post enrollment. Patients with low levels of CD8+ T cell apoptosis at baseline (mean 2.2% ± 2.1) had significantly higher CD4 cell counts and more normalized CD4:CD8 ratios than patients with high CD8+ T cell apoptosis (mean CD4 cell counts 1,209 ± 164 vs 754 ± 320 cells/mm3; CD4:CD8 ratios 1.55 vs. 0.70, respectively). Conclusion We postulate that CD8+ T cell apoptosis may reflect inherent activation status, which continues in some patients even though viral replication is suppressed which influences the ability of CD4+ T cells to rebound. Levels of CD8+ T cell apoptosis may therefore be an independent predictor of immune status, which should be shown in a prospective study. PMID:17263884

CD8 apoptosis may be a predictor of T cell number normalization after immune reconstitution in HIV.

PubMed

Lewis, Dorothy E; Gross, Kimber L; Diez, Martine M; Martinez, Maria L; Lukefahr, Helen N; Kozinetz, Claudia A; Arduino, Roberto C

2007-01-30

As part of the Houston Vanguard study, a subset of 10 patients randomized to receive IL-2 therapy were compared to 4 patients randomized to not receive IL-2, for markers of T cell activation and death during the first three cycles of IL-2. All patients were treated with combination antiretroviral therapy (ART) and were virally suppressed. The purpose of the study was to examine the role of CD8(+) T cell death in responses to ART and IL-2 therapy. Lymphocytes were examined at Day 0, 5 and 30 days during three cycles of IL-2 therapy. CD25, CD38, HLA-DR expression and annexin (cell death) were examined on CD4 and CD8 subpopulations. Follow up studies examined CD4 levels and CD4:CD8 reconstitution after 6 years using both univariant and multivariate analyses. Human lymphocytes responded to IL-2 therapy by upregulation of CD25 on CD4(+) T cells, leading to an increase in CD4 cell counts. CD8(+) T cells did not increase CD25 expression, but upregulated activation antigens (CD38 and DR) and had increased death. At baseline, 7 of the 14 patients had high CD8+ T cell apoptosis (mean 17.0% +/- 6.0). We did an exploratory analysis of immune status after six years, and found that baseline CD8+ T cell apoptosis was correlated with CD4 cell count gain beginning two years post enrollment. Patients with low levels of CD8(+) T cell apoptosis at baseline (mean 2.2% +/- 2.1) had significantly higher CD4 cell counts and more normalized CD4:CD8 ratios than patients with high CD8(+) T cell apoptosis (mean CD4 cell counts 1,209 +/- 164 vs 754 +/- 320 cells/mm(3); CD4:CD8 ratios 1.55 vs. 0.70, respectively). We postulate that CD8(+) T cell apoptosis may reflect inherent activation status, which continues in some patients even though viral replication is suppressed which influences the ability of CD4(+) T cells to rebound. Levels of CD8(+) T cell apoptosis may therefore be an independent predictor of immune status, which should be shown in a prospective study.

Properties of human blood monocytes. I. CD91 expression and log orthogonal light scatter provide a robust method to identify monocytes that is more accurate than CD14 expression.

PubMed

Hudig, Dorothy; Hunter, Kenneth W; Diamond, W John; Redelman, Doug

2014-03-01

This study was designed to improve identification of human blood monocytes by using antibodies to molecules that occur consistently on all stages of monocyte development and differentiation. We examined blood samples from 200 healthy adults without clinically diagnosed immunological abnormalities by flow cytometry (FCM) with multiple combinations of antibodies and with a hematology analyzer (Beckman LH750). CD91 (α2 -macroglobulin receptor) was expressed only by monocytes and to a consistent level among subjects [mean median fluorescence intensity (MFI) = 16.2 ± 3.2]. Notably, only 85.7 ± 5.82% of the CD91(+) monocytes expressed high levels of the classical monocyte marker CD14, with some CD91(+) CD16(+) cells having negligible CD14, indicating that substantial FCM under-counts will occur when monocytes are identified by high CD14. CD33 (receptor for sialyl conjugates) was co-expressed with CD91 on monocytes but CD33 expression varied by nearly ten-fold among subjects (mean MFI = 17.4 ± 7.7). In comparison to FCM analyses, the hematology analyzer systematically over-counted monocytes and eosinophils while lymphocyte and neutrophil differential values generally agreed with FCM methods. CD91 is a better marker to identify monocytes than CD14 or CD33. Furthermore, FCM (with anti-CD91) identifies monocytes better than a currently used clinical CBC instrument. Use of anti-CD91 together with anti-CD14 and anti-CD16 supports the identification of the diagnostically significant monocyte populations with variable expression of CD14 and CD16. Copyright © 2013 Clinical Cytometry Society.

CD15s/CD62E Interaction Mediates the Adhesion of Non-Small Cell Lung Cancer Cells on Brain Endothelial Cells: Implications for Cerebral Metastasis

PubMed Central

Jassam, Samah A.; Maherally, Zaynah; Ashkan, Keyoumars; Roncaroli, Federico; Fillmore, Helen L.; Pilkington, Geoffrey J.

2017-01-01

Expression of the cell adhesion molecule (CAM), Sialyl Lewis X (CD15s) correlates with cancer metastasis, while expression of E-selectin (CD62E) is stimulated by TNF-α. CD15s/CD62E interaction plays a key role in the homing process of circulating leukocytes. We investigated the heterophilic interaction of CD15s and CD62E in brain metastasis-related cancer cell adhesion. CD15s and CD62E were characterised in human brain endothelium (hCMEC/D3), primary non-small cell lung cancer (NSCLC) (COR-L105 and A549) and metastatic NSCLC (SEBTA-001 and NCI-H1299) using immunocytochemistry, Western blotting, flow cytometry and immunohistochemistry in human brain tissue sections. TNF-α (25 pg/mL) stimulated extracellular expression of CD62E while adhesion assays, under both static and physiological flow live-cell conditions, explored the effect of CD15s-mAb immunoblocking on adhesion of cancer cell–brain endothelium. CD15s was faintly expressed on hCMEC/D3, while high levels were observed on primary NSCLC cells with expression highest on metastatic NSCLC cells (p < 0.001). CD62E was highly expressed on hCMEC/D3 cells activated with TNF-α, with lower levels on primary and metastatic NSCLC cells. CD15s and CD62E were expressed on lung metastatic brain biopsies. CD15s/CD62E interaction was localised at adhesion sites of cancer cell–brain endothelium. CD15s immunoblocking significantly decreased cancer cell adhesion to brain endothelium under static and shear stress conditions (p < 0.001), highlighting the role of CD15s–CD62E interaction in brain metastasis. PMID:28698503

CD15s/CD62E Interaction Mediates the Adhesion of Non-Small Cell Lung Cancer Cells on Brain Endothelial Cells: Implications for Cerebral Metastasis.

PubMed

Jassam, Samah A; Maherally, Zaynah; Smith, James R; Ashkan, Keyoumars; Roncaroli, Federico; Fillmore, Helen L; Pilkington, Geoffrey J

2017-07-10

Expression of the cell adhesion molecule (CAM), Sialyl Lewis X (CD15s) correlates with cancer metastasis, while expression of E-selectin (CD62E) is stimulated by TNF-α. CD15s/CD62E interaction plays a key role in the homing process of circulating leukocytes. We investigated the heterophilic interaction of CD15s and CD62E in brain metastasis-related cancer cell adhesion. CD15s and CD62E were characterised in human brain endothelium (hCMEC/D3), primary non-small cell lung cancer (NSCLC) (COR-L105 and A549) and metastatic NSCLC (SEBTA-001 and NCI-H1299) using immunocytochemistry, Western blotting, flow cytometry and immunohistochemistry in human brain tissue sections. TNF-α (25 pg/mL) stimulated extracellular expression of CD62E while adhesion assays, under both static and physiological flow live-cell conditions, explored the effect of CD15s-mAb immunoblocking on adhesion of cancer cell-brain endothelium. CD15s was faintly expressed on hCMEC/D3, while high levels were observed on primary NSCLC cells with expression highest on metastatic NSCLC cells ( p < 0.001). CD62E was highly expressed on hCMEC/D3 cells activated with TNF-α, with lower levels on primary and metastatic NSCLC cells. CD15s and CD62E were expressed on lung metastatic brain biopsies. CD15s/CD62E interaction was localised at adhesion sites of cancer cell-brain endothelium. CD15s immunoblocking significantly decreased cancer cell adhesion to brain endothelium under static and shear stress conditions ( p < 0.001), highlighting the role of CD15s-CD62E interaction in brain metastasis.

Characterization of a CD44/CD122int memory CD8 T cell subset generated under sterile inflammatory conditions.

PubMed

Mbitikon-Kobo, Florentin-Martial; Vocanson, Marc; Michallet, Marie-Cécile; Tomkowiak, Martine; Cottalorda, Anne; Angelov, Georgi S; Coupet, Charles-Antoine; Djebali, Sophia; Marçais, Antoine; Dubois, Bertrand; Bonnefoy-Bérard, Nathalie; Nicolas, Jean-François; Arpin, Christophe; Marvel, Jacqueline

2009-03-15

Most memory CD8 T cell subsets that have been hitherto defined are generated in response to infectious pathogens. In this study, we have characterized the CD8 T cells that survive priming conditions, devoid of pathogen-derived danger signals. In both a TCR-transgenic model and a model of contact hypersensitivity, we show that the priming of naive CD8 T cells under sterile inflammatory conditions generates memory. The corresponding memory CD8 T cells can be identified by their intermediate expression levels of CD44 and CD122. We also show that CD44/122(int) memory CD8 T cells spontaneously develop in wild type mice and that they display intermediate levels of several other memory traits including functional (IFN-gamma secretion capacity, CCL5 messenger stores), phenotypic, and molecular (T-bet and eomesodermin expression levels) features. We finally show that they correspond to an early differentiation stage and can further differentiate in CD44/122(high) memory T cells. Altogether, our results identify a new memory CD8 T cell subset that is generated under sterile inflammatory conditions and involved in the recall contact hypersensitivity reactions that are responsible for allergic contact dermatitis.

The Glucotoxicity Protecting Effect of Ezetimibe in Pancreatic Beta Cells via Inhibition of CD36.

PubMed

Yoon, Ji Sung; Moon, Jun Sung; Kim, Yong-Woon; Won, Kyu Chang; Lee, Hyoung Woo

2016-04-01

Inhibition of CD36, a fatty acid transporter, has been reported to prevent glucotoxicity and ameliorate high glucose induced beta cell dysfunction. Ezetimibe is a selective cholesterol absorption inhibitor that blocks Niemann Pick C1-like 1 protein, but may exert its effect through suppression of CD36. We attempted to clarify the beneficial effect of ezetimibe on insulin secreting cells and to determine whether this effect is related to change of CD36 expression. mRNA expression of insulin and CD36, intracellular peroxide level and glucose stimulated insulin secretion (GSIS) under normal (5.6 mM) or high glucose (30 mM) condition in INS-1 cells and primary rat islet cells were compared. Changes of the aforementioned factors with treatment with ezetimibe (20 μM) under normal or high glucose condition were also assessed. mRNA expression of insulin was decreased with high glucose, which was reversed by ezetimibe in both INS-1 cells and primary rat islets. CD36 mRNA expression was increased with high glucose, but decreased by ezetimibe in INS-1 cells and primary rat islets. Three-day treatment with high glucose resulted in an increase in intracellular peroxide level; however, it was decreased by treatment with ezetimibe. Decrease in GSIS by three-day treatment with high glucose was reversed by ezetimibe. Palmitate uptake following exposure to high glucose conditions for three days was significantly elevated, which was reversed by ezetimibe in INS-1 cells. Ezetimibe may prevent glucotoxicity in pancreatic β-cells through a decrease in fatty acid influx via inhibition of CD36.

The Glucotoxicity Protecting Effect of Ezetimibe in Pancreatic Beta Cells via Inhibition of CD36

PubMed Central

2016-01-01

Inhibition of CD36, a fatty acid transporter, has been reported to prevent glucotoxicity and ameliorate high glucose induced beta cell dysfunction. Ezetimibe is a selective cholesterol absorption inhibitor that blocks Niemann Pick C1-like 1 protein, but may exert its effect through suppression of CD36. We attempted to clarify the beneficial effect of ezetimibe on insulin secreting cells and to determine whether this effect is related to change of CD36 expression. mRNA expression of insulin and CD36, intracellular peroxide level and glucose stimulated insulin secretion (GSIS) under normal (5.6 mM) or high glucose (30 mM) condition in INS-1 cells and primary rat islet cells were compared. Changes of the aforementioned factors with treatment with ezetimibe (20 μM) under normal or high glucose condition were also assessed. mRNA expression of insulin was decreased with high glucose, which was reversed by ezetimibe in both INS-1 cells and primary rat islets. CD36 mRNA expression was increased with high glucose, but decreased by ezetimibe in INS-1 cells and primary rat islets. Three-day treatment with high glucose resulted in an increase in intracellular peroxide level; however, it was decreased by treatment with ezetimibe. Decrease in GSIS by three-day treatment with high glucose was reversed by ezetimibe. Palmitate uptake following exposure to high glucose conditions for three days was significantly elevated, which was reversed by ezetimibe in INS-1 cells. Ezetimibe may prevent glucotoxicity in pancreatic β-cells through a decrease in fatty acid influx via inhibition of CD36. PMID:27051238

Availability of activated CD4+ T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys

PubMed Central

Klatt, Nichole R.; Villinger, Francois; Bostik, Pavel; Gordon, Shari N.; Pereira, Lara; Engram, Jessica C.; Mayne, Ann; Dunham, Richard M.; Lawson, Benton; Ratcliffe, Sarah J.; Sodora, Donald L.; Else, James; Reimann, Keith; Staprans, Silvija I.; Haase, Ashley T.; Estes, Jacob D.; Silvestri, Guido; Ansari, Aftab A.

2008-01-01

Naturally SIV-infected sooty mangabeys (SMs) remain asymptomatic despite high virus replication. Elucidating the mechanisms underlying AIDS resistance of SIV-infected SMs may provide crucial information to better understand AIDS pathogenesis. In this study, we assessed the determinants of set-point viremia in naturally SIV-infected SMs, i.e., immune control of SIV replication versus target cell limitation. We depleted CD4+ T cells in 6 naturally SIV-infected SMs by treating with humanized anti-CD4 mAb (Cdr-OKT4A-huIgG1). CD4+ T cells were depleted almost completely in blood and BM and at variable levels in mucosal tissues and LNs. No marked depletion of CD14+ monocytes was observed. Importantly, CD4+ T cell depletion was associated with a rapid, significant decline in viral load, which returned to baseline level at day 30–45, coincident with an increased fraction of proliferating and activated CD4+ T cells. Throughout the study, virus replication correlated with the level of proliferating CD4+ T cells. CD4+ T cell depletion did not induce any changes in the fraction of Tregs or the level of SIV-specific CD8+ T cells. Our results suggest that the availability of activated CD4+ T cells, rather than immune control of SIV replication, is the main determinant of set-point viral load during natural SIV infection of SMs. PMID:18497876

Tumor-Associated Macrophages Associate with Cerebrospinal Fluid Interleukin-10 and Survival in Primary Central Nervous System Lymphoma (PCNSL).

PubMed

Sasayama, Takashi; Tanaka, Kazuhiro; Mizowaki, Takashi; Nagashima, Hiroaki; Nakamizo, Satoshi; Tanaka, Hirotomo; Nishihara, Masamitsu; Mizukawa, Katsu; Hirose, Takanori; Itoh, Tomoo; Kohmura, Eiji

2016-07-01

Increased tumor-associated macrophages (TAMs) have been reported to be associated with poor prognosis in various tumors; however, the importance of TAMs in primary central nervous system lymphoma (PCNSL) has not been clarified. In 47 patients with PCNSL who were treated with high-dose methotrexate (MTX) and radiotherapy, the relationships between the infiltration levels of TAMs and the clinicopathological parameters were analyzed. Univariate analysis of the Cox proportional hazards model using continuous scales revealed that increased CD68 positive (+) TAMs was significantly associated with inferior progression-free survival (PFS) (P = 0.04), and trends were observed for the increased CD163(+)  TAMs and having shorter PFS (P = 0.05). However, increased TAMs were not associated with overall survival. Because TAMs are known to produce various cytokines, we examined the relationships between cerebrospinal fluid (CSF) cytokines and TAMs. CSF interleukin-6 (IL-6) and soluble IL-2 receptor were not correlated with the infiltration rate of TAMs; however, CSF IL-10 level was correlated with infiltration levels of CD68 and CD163(+)  TAMs. We also confirmed the expression of IL-10 in CD68(+)  and CD163(+)  TAMs by double immunostaining analysis. Our results indicate that a high level of IL-10 in CSF may be positively associated with the infiltration level of TAMs in PCNSLs. © 2015 International Society of Neuropathology.

Root and shoot transcriptome analysis of two ecotypes of Noccaea caerulescens uncovers the role of NcNramp1 in Cd hyperaccumulation

USDA-ARS?s Scientific Manuscript database

The Zn/Cd hyperaccumulator, Noccaea caerulescens, has been studied extensively for its ability to accumulate Zn and Cd in its leaves to extremely high levels. Previous studies have indicated that the Zn and Cd hyperaccumulation trait exhibited by this species involves different transport and toleran...

[Regulatory B cells activated by CpG-ODN combined with anti-CD40 monoclonal antibody inhibit CD4(+)T cell proliferation].

PubMed

Wang, Keng; Tao, Lei; Su, Jianbing; Zhang, Yueyang; Zou, Binhua; Wang, Yiyuan; Li, Xiaojuan

2016-09-01

Objective To observe the immunosuppressive function of regulatory B cells (Bregs) in vitro after activated by CpG oligodeoxynucleotide (CpG-ODN) and anti-CD40 mAb. Methods Mice splenic CD5(+)CD1d(high)B cells and CD5(-)CD1d(low)B cells were sorted by flow cytometry. These B cells were first stimulated with CpG-ODN combined with anti-CD40 mAb for 24 hours, and then co-cultured with purified CD4(+)T cells. The interleukin 10 (IL-10) expression in the activated Bregs and other B cell subset, as well as the proliferation and interferon γ (IFN-γ) expression in the CD4(+) T cells activated by anti-CD3 mAb plus anti-CD28 mAb were determined by flow cytometry. Results CD5(+)CD1d(high) B cells activated by CpG-ODN plus anti-CD40 mAb blocked the up-regulated CD4(+)T proliferation and significantly reduced the IFN-γ level. At the same time, activated CD5(-)CD1d(low)B cells showed no inhibitory effect on CD4(+)T cells. Further study revealed that IL-10 expression in the CD5(+)CD1d(high) B cells were much higher than that in the CD5(-)CD1d(low)B cells after stimulated with CpG-ODN combined with anti-CD40 mAb for 24 hours. Conclusion CD5(+)CD1d(high) B cells activated by CpG-ODN combined with anti-CD40 mAb have immune inhibitory effects on CD4(+)T cell activation in vitro , which possibly due to IL-10 secretion.

Potent neutralizing anti-CD1d antibody reduces lung cytokine release in primate asthma model.

PubMed

Nambiar, Jonathan; Clarke, Adam W; Shim, Doris; Mabon, David; Tian, Chen; Windloch, Karolina; Buhmann, Chris; Corazon, Beau; Lindgren, Matilda; Pollard, Matthew; Domagala, Teresa; Poulton, Lynn; Doyle, Anthony G

2015-01-01

CD1d is a receptor on antigen-presenting cells involved in triggering cell populations, particularly natural killer T (NKT) cells, to release high levels of cytokines. NKT cells are implicated in asthma pathology and blockade of the CD1d/NKT cell pathway may have therapeutic potential. We developed a potent anti-human CD1d antibody (NIB.2) that possesses high affinity for human and cynomolgus macaque CD1d (KD ∼100 pM) and strong neutralizing activity in human primary cell-based assays (IC50 typically <100 pM). By epitope mapping experiments, we showed that NIB.2 binds to CD1d in close proximity to the interface of CD1d and the Type 1 NKT cell receptor β-chain. Together with data showing that NIB.2 inhibited stimulation via CD1d loaded with different glycolipids, this supports a mechanism whereby NIB.2 inhibits NKT cell activation by inhibiting Type 1 NKT cell receptor β-chain interactions with CD1d, independent of the lipid antigen in the CD1d antigen-binding cleft. The strong in vitro potency of NIB.2 was reflected in vivo in an Ascaris suum cynomolgus macaque asthma model. Compared with vehicle control, NIB.2 treatment significantly reduced bronchoalveolar lavage (BAL) levels of Ascaris-induced cytokines IL-5, IL-8 and IL-1 receptor antagonist, and significantly reduced baseline levels of GM-CSF, IL-6, IL-15, IL-12/23p40, MIP-1α, MIP-1β, and VEGF. At a cellular population level NIB.2 also reduced numbers of BAL lymphocytes and macrophages, and blood eosinophils and basophils. We demonstrate that anti-CD1d antibody blockade of the CD1d/NKT pathway modulates inflammatory parameters in vivo in a primate inflammation model, with therapeutic potential for diseases where the local cytokine milieu is critical.

Potent neutralizing anti-CD1d antibody reduces lung cytokine release in primate asthma model

PubMed Central

Nambiar, Jonathan; Clarke, Adam W; Shim, Doris; Mabon, David; Tian, Chen; Windloch, Karolina; Buhmann, Chris; Corazon, Beau; Lindgren, Matilda; Pollard, Matthew; Domagala, Teresa; Poulton, Lynn; Doyle, Anthony G

2015-01-01

CD1d is a receptor on antigen-presenting cells involved in triggering cell populations, particularly natural killer T (NKT) cells, to release high levels of cytokines. NKT cells are implicated in asthma pathology and blockade of the CD1d/NKT cell pathway may have therapeutic potential. We developed a potent anti-human CD1d antibody (NIB.2) that possesses high affinity for human and cynomolgus macaque CD1d (KD ∼100 pM) and strong neutralizing activity in human primary cell-based assays (IC50 typically <100 pM). By epitope mapping experiments, we showed that NIB.2 binds to CD1d in close proximity to the interface of CD1d and the Type 1 NKT cell receptor β-chain. Together with data showing that NIB.2 inhibited stimulation via CD1d loaded with different glycolipids, this supports a mechanism whereby NIB.2 inhibits NKT cell activation by inhibiting Type 1 NKT cell receptor β-chain interactions with CD1d, independent of the lipid antigen in the CD1d antigen-binding cleft. The strong in vitro potency of NIB.2 was reflected in vivo in an Ascaris suum cynomolgus macaque asthma model. Compared with vehicle control, NIB.2 treatment significantly reduced bronchoalveolar lavage (BAL) levels of Ascaris-induced cytokines IL-5, IL-8 and IL-1 receptor antagonist, and significantly reduced baseline levels of GM-CSF, IL-6, IL-15, IL-12/23p40, MIP-1α, MIP-1β, and VEGF. At a cellular population level NIB.2 also reduced numbers of BAL lymphocytes and macrophages, and blood eosinophils and basophils. We demonstrate that anti-CD1d antibody blockade of the CD1d/NKT pathway modulates inflammatory parameters in vivo in a primate inflammation model, with therapeutic potential for diseases where the local cytokine milieu is critical. PMID:25751125

PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing.

PubMed

Akhmetzyanova, Ilseyar; Drabczyk, Malgorzata; Neff, C Preston; Gibbert, Kathrin; Dietze, Kirsten K; Werner, Tanja; Liu, Jia; Chen, Lieping; Lang, Karl S; Palmer, Brent E; Dittmer, Ulf; Zelinskyy, Gennadiy

2015-10-01

Cytotoxic CD8+ T Lymphocytes (CTL) efficiently control acute virus infections but can become exhausted when a chronic infection develops. Signaling of the inhibitory receptor PD-1 is an important mechanism for the development of virus-specific CD8+ T cell dysfunction. However, it has recently been shown that during the initial phase of infection virus-specific CD8+ T cells express high levels of PD-1, but are fully competent in producing cytokines and killing virus-infected target cells. To better understand the role of the PD-1 signaling pathway in CD8+ T cell cytotoxicity during acute viral infections we analyzed the expression of the ligand on retrovirus-infected cells targeted by CTLs. We observed increased levels of PD-L1 expression after infection of cells with the murine Friend retrovirus (FV) or with HIV. In FV infected mice, virus-specific CTLs efficiently eliminated infected target cells that expressed low levels of PD-L1 or that were deficient for PD-L1 but the population of PD-L1high cells escaped elimination and formed a reservoir for chronic FV replication. Infected cells with high PD-L1 expression mediated a negative feedback on CD8+ T cells and inhibited their expansion and cytotoxic functions. These findings provide evidence for a novel immune escape mechanism during acute retroviral infection based on PD-L1 expression levels on virus infected target cells.

Co-Expression of Putative Cancer Stem Cell Markers CD44 and CD133 in Prostate Carcinomas.

PubMed

Kalantari, Elham; Asgari, Mojgan; Nikpanah, Seyedehmoozhan; Salarieh, Naghme; Asadi Lari, Mohammad Hossein; Madjd, Zahra

2017-10-01

Cancer stem cells (CSCs) are the main players of prostate tumorigenesis thus; characterization of CSCs can pave the way for understanding the early detection, drug resistance, metastasis and relapse. The current study was conducted to evaluate the expression level and clinical significance of the potential CSC markers CD44 and CD133 in a series of prostate tissues. One hundred and forty eight prostate tissues composed of prostate cancer (PCa), high-grade prostatic intraepithelial neoplasia (HGPIN), and benign prostate hyperplasia (BPH) were immunostained for the putative CSC markers CD44 and CD133. Subsequently, the correlation between the expression of these markers and the clinicopathological variables was examined. A higher level of CD44 expression was observed in 42% of PCa, 57% of HGPIN, and 42% BPH tissues. In the case of CD133 expression PCa, HGPIN, and BPH samples demonstrated high immunoreactivity in 46%, 43%, and 42% of cells, respectively. Statistical analysis showed an inverse significant correlation between CD44 expression with Gleason score of PCa (P = 0.02), while no significant correlation was observed between CD133 expression and clinicopathological parameters. A significant reciprocal correlation was observed between the expression of two putative CSC markers CD44 and CD133 in PCa specimens while not indicating clinical significance. Further clinical investigation is required to consider these markers as targets of new therapeutic strategies for PCa.

Identification and Characterization of Cells with Cancer Stem Cell Properties in Human Primary Lung Cancer Cell Lines

PubMed Central

Suo, Zhenhe; Munthe, Else; Solberg, Steinar; Ma, Liwei; Wang, Mengyu; Westerdaal, Nomdo Anton Christiaan; Kvalheim, Gunnar; Gaudernack, Gustav

2013-01-01

Lung cancer (LC) with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs) within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs) from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC), large cell carcinoma (LCC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). We identified a small population of cells strongly positive for CD44 (CD44high) and a main population which was either weakly positive or negative for CD44 (CD44low/−). Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44highCD90+ sub-population. Moreover, these CD44highCD90+ cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44highCD90+ population a good candidate for the lung CSCs. Both CD44highCD90+ and CD44highCD90− cells in the PLCCL derived from SCC formed spheroids, whereas the CD44low/− cells were lacking this potential. These results indicate that CD44highCD90+ sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44high sub-population. PMID:23469181

Higher B-cell activating factor levels at birth are positively associated with maternal dairy farm exposure and negatively related to allergy development.

PubMed

Lundell, Anna-Carin; Hesselmar, Bill; Nordström, Inger; Adlerberth, Ingegerd; Wold, Agnes E; Rudin, Anna

2015-10-01

A high proportion of circulating immature/naive CD5(+) B cells during early infancy is a risk factor for allergy development. B-cell activating factor (BAFF) is an important cytokine for B-cell maturation. We sought to investigate whether BAFF levels are related to environmental exposures during pregnancy and early childhood and whether BAFF levels are associated with postnatal B-cell maturation and allergic disease. In the FARMFLORA study, including both farming and nonfarming families, we measured BAFF levels in plasma from mothers and their children at birth and at 1, 4, 18, and 36 months of age. Infants' blood samples were also analyzed for B-cell numbers and proportions of CD5(+) and CD27(+) B cells. Allergic disease was clinically evaluated at 18 and 36 months of age. Circulating BAFF levels were maximal at birth, and farmers' children had higher BAFF levels than nonfarmers' children. Higher BAFF levels at birth were positively associated with proportions of CD27(+) memory B cells among farmers' children and inversely related to proportions of CD5(+) immature/naive B cells among nonfarmers' children. Children with allergic disease at 18 months of age had lower cord blood BAFF levels than nonallergic children. At birth, girls had higher BAFF levels and lower proportions of CD5(+) B cells than boys. Farm exposure during pregnancy appears to induce BAFF production in the newborn child, and high neonatal BAFF levels were associated with more accelerated postnatal B-cell maturation, which lend further strength to the role of B cells in the hygiene hypothesis. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Elevated pretransplantation soluble CD30 is associated with decreased early allograft function after human lung transplantation.

PubMed

Shah, Ashish S; Leffell, M Sue; Lucas, Donna; Zachary, Andrea A

2009-02-01

Early allograft function after lung transplantation is variable. Clinical criteria have limited predictive value for early graft function. Recipient immunologic state before LTx may affect early lung function. We investigated the association between pretransplantation soluble CD30 (sCD30), a marker of Th2-type T-cell activation, and early clinical parameters of allograft function. Between September 2002 and January 2007, a total of 80 transplantations were performed at Johns Hopkins Hospital. Of the patients, 43 had a pretransplantation sCD30 level determined. Pre- and postoperative patient variables were collected, and patients were stratified into two groups: sCD30 <20 (low sCD30) and >20 (high sCD30). High sCD30 (n = 26) and low sCD30 (n = 17) groups were similar in age, gender, and ischemia time. In the high sCD30 group, a higher percentage of patients had pulmonary fibrosis and a lower percentage had emphysema. Oxygenation at 48 hours was significantly worse in the high sCD30 group as compared with the low sCD30 (p = 0.003). Moreover, prolonged intubation and 90-day mortality were greater in the high sCD30 group. This represents the first report of the use of sCD30 as a marker for early allograft function in human lung transplanation. Increased pretransplantation recipient sCD30 appears to be associated with decreased early post-transplantation gas exchange, prolonged intubation, and early mortality.

Cadmium phytoextraction from loam soil in tropical southern China by Sorghum bicolor.

PubMed

Wang, Xu; Chen, Can; Wang, Jianlong

2017-06-03

The cadmium (Cd) uptake characteristics by Sorghum bicolor cv. Nengsi 2# and Cowley from the acidic sandy loam soil (pH = 6.1) during the entire growth period (100 days) were investigated in pot outdoors in a tropical district of southern China, Hainan Island. The Cd-spiked levels in soil were set as 3 and 15 mg/kg. Correspondingly, the available Cd levels in soil extracted by Mehlich III solution were 2.71 and 9.41 mg/kg, respectively. Basically, two varieties in a full growth period (100 days) did not show a significant difference in their growth and Cd uptake. Under high Cd stress, the plant growth was inhibited and its biomass weight and height decreased by 38.7-51.5% and 27.6-28.5%, respectively. However, S. bicolor showed higher bioaccumulation capability of Cd from soil to plant [bioconcentration factor (BCF)>4], and higher transfer capability of Cd from roots to shoots [translocation factor (TF)>1] under high Cd stress; Cd contents in the roots, stems, and leaves of S. bicolor reached 43.79-46.07, 63.28-70.60, and 63.10-66.06 mg/kg, respectively. S. bicolor exhibited the potential phytoextraction capability for low or moderate Cd-contamination in acidic sandy loam soil.

Regulation by CD45 of the tyrosine phosphorylation of high affinity IgE receptor beta- and gamma-chains.

PubMed

Adamczewski, M; Numerof, R P; Koretzky, G A; Kinet, J P

1995-04-01

Previous studies using tyrosine phosphatase inhibitors have implicated tyrosine phosphatases in the signal transduction pathway initiated by aggregation of Fc epsilon RI, the high affinity receptor for IgE. To define more precisely a role for the tyrosine phosphatase CD45 in Fc epsilon RI-mediated signaling, we have transfected the three subunits of Fc epsilon RI into wild-type Jurkat and a CD45-deficient Jurkat derivative. Here we demonstrate that CD45 is necessary for the initiation of calcium flux through the transfected Fc epsilon RI. In contrast to the effect of phosphatase inhibitors, the tyrosine phosphorylation levels of beta and gamma after aggregation of Fc epsilon RI are surprisingly reduced, relative to wild-type Jurkat, in the CD45-deficient cells. After reconstitution of the CD45-deficient cells with a chimeric molecule containing the cytoplasmic phosphatase domains of CD45, both the base line and activation-induced tyrosine phosphorylation levels are increased. By examining Lck autophosphorylation, we find that Fc epsilon RI aggregation induces an increase in Lck enzymatic activity only in wild-type Jurkat and the CD45-deficient Jurkat reconstituted with chimeric CD45. This regulation of src-family tyrosine kinase activity may be the means by which CD45 controls aggregation-induced receptor phosphorylation.

Importance of N-Glycosylation on CD147 for Its Biological Functions

PubMed Central

Bai, Yang; Huang, Wan; Ma, Li-Tian; Jiang, Jian-Li; Chen, Zhi-Nan

2014-01-01

Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various tumors, is a potential target for cancer diagnosis and therapy. A significant biochemical property of CD147 is its high level of glycosylation. Studies on the structure and function of CD147 glycosylation provide valuable clues to the development of targeted therapies for cancer. Here, we review current understanding of the glycosylation characteristics of CD147 and the glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we discuss proteins regulating CD147 glycosylation and the biological functions of CD147 glycosylation. PMID:24739808

Increased endothelial and macrophage markers are associated with disease severity and mortality in scrub typhus.

PubMed

Otterdal, Kari; Janardhanan, Jeshina; Astrup, Elisabeth; Ueland, Thor; Prakash, John A J; Lekva, Tove; Abraham, O C; Thomas, Kurien; Damås, Jan Kristian; Mathews, Prasad; Mathai, Dilip; Aukrust, Pål; Varghese, George M

2014-11-01

Scrub typhus is endemic in the Asia-Pacific region. Mortality is high even with treatment, and further knowledge of the immune response during this infection is needed. This study was aimed at comparing plasma levels of monocyte/macrophage and endothelial related inflammatory markers in patients and controls in South India and to explore a possible correlation to disease severity and clinical outcome. Plasma levels of ALCAM, VCAM-1, sCD163, sCD14, YKL-40 and MIF were measured in scrub typhus patients (n = 129), healthy controls (n = 31) and in infectious disease controls (n = 31), both in the acute phase and after recovery, by enzyme immunoassays. Patients had markedly elevated levels of all mediators in the acute phase, differing from both healthy and infectious disease controls. During follow-up levels of ALCAM, VCAM-1, sCD14 and YKL-40 remained elevated compared to levels in healthy controls. High plasma ALCAM, VCAM-1, sCD163, sCD14, and MIF, and in particular YKL-40 were all associated with disease severity and ALCAM, sCD163, MIF and especially YKL-40, were associated with mortality. Our findings show that scrub typhus is characterized by elevated levels of monocyte/macrophage and endothelial related markers. These inflammatory markers, and in particular YKL-40, may contribute to disease severity and clinical outcome. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Evidence for Breakdown of Vibrational Motion in ^110Cd

NASA Astrophysics Data System (ADS)

Bangay, Jack; Garrett, Paul; Bianco, Laura; Leach, Kyle; Finlay, Paul; Green, Katie; Phillips, Andrew; Rand, Evan; Svensson, Carl; Sumithrarachchi, Chandana; Wong, James

2009-10-01

^110Cd has long been considered an excellent example of a vibrational nucleus. However, recent work with other even-even Cadmium isotopes show a breakdown of vibrational motion at the 2 and 3-phonon level, suggesting the need for more precise measurements on ^110Cd. The structure of ^110Cd is studied with the (n,n^'γ) reaction performed at the University of Kentucky, as well as with the high statistics β-decay of ^110In performed at the TRIUMF-ISAC facility using the 8π spectrometer. Excitation funcions and angular distributions from the (n,n^'γ) reaction provide us with spectroscopic information on the level scheme, including level lifetimes and spins. This data is complemented by the γγ coincidences measured in the ^110In β-decay that allows the observation of, or stringent limit on, weak, low-energy branches between levels at high excitation energy. Details of the analysis to date, including candidates for the full octupole-quadrupole coupled quintuplet, will be presented.

Costimulation through the CD137/4-1BB pathway protects human melanoma tumor-infiltrating lymphocytes from activation-induced cell death and enhances antitumor effector function.

PubMed

Hernandez-Chacon, Jessica Ann; Li, Yufeng; Wu, Richard C; Bernatchez, Chantale; Wang, Yijun; Weber, Jeffrey S; Hwu, Patrick; Radvanyi, Laszlo G

2011-04-01

Adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) with high-dose interleukin-2 is a promising form of immunotherapy for stage IV melanoma having clinical response rates of 50% or more. One of the major problems preventing further success of this therapy is that the current protocols used to highly expand TIL for infusion drive CD8(+) T cells to differentiate into effector cells losing key costimulatory molecules such as CD28 and CD27. This has been associated with a lack of persistence in vivo for reasons not entirely clear. In this study, we demonstrate that while human melanoma CD8(+) TIL lost CD27 and CD28 expression during the rapid expansion for ACT, they gained expression of the alternative costimulatory molecule CD137/4-1BB, and to a lesser extent CD134/OX40. Postrapid expansion protocol (REP) TIL were found to be highly sensitive to activation-induced cell death when reactivated through the T-cell receptor with low levels of OKT3 antibody. However, coligation of 4-1BB using 2 different agonistic anti-4-1BB antibodies potently prevented activation-induced cell death of post-REP CD8(+) TIL, including those specific for melanoma antigen recognized by T cells, and facilitated even further cell expansion. This was correlated with increased levels of bcl-2 and bcl-xL together with decreased bim expression. 4-1BB costimulated post-REP TIL also expressed increased levels of the cytolytic granule proteins and exhibited enhanced cytotoxic T-cell activity against melanoma cells. Lastly, post-REP CD8(+) TIL were protected from cell death by anti-4-1BB ligation when exposed to human leukocyte antigen-matched melanoma cells. Our results indicate that 4-1BB costimulation may significantly improve TIL survival during melanoma ACT and boost antitumor cytolytic activity.

Co-stimulation through the CD137/4-1BB pathway protects human melanoma tumor-infiltrating lymphocytes from activation-induced cell death and enhances anti-tumor effector function

PubMed Central

Hernandez-Chacon, Jessica Ann; Li, Yufeng; Wu, Richard C.; Bernatchez, Chantale; Wang, Yijun; Weber, Jeffrey; Hwu, Patrick; Radvanyi, Laszlo

2011-01-01

Adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) with high-dose IL-2 is a promising form of immunotherapy for Stage IV melanoma having clinical response rates of 50% or more. One of the major problems preventing further success of this therapy is that the current protocols used to highly expand TIL for infusion drive CD8+ T cells to differentiate into effector cells losing key co-stimulatory molecules such as CD28 and CD27. This has been associated with a lack of persistence in vivo for reasons not entirely clear. In this study, we demonstrate that while human melanoma CD8+ TIL lost CD27 and CD28 expression during the rapid expansion for ACT, they gained expression of the alternative co-stimulatory molecule CD137/4-1BB, and to a lesser extent CD134/OX40. Post-REP TIL were found to be highly sensitive to activation-induced cell death (AICD) when re-activated through the TCR with low levels of OKT3 antibody. However, co-ligation of 4-1BB using two different agonistic anti-4-1BB antibodies potently prevented AICD of post-REP CD8+ TIL, including those specific for MART-1, and facilitated even further cell expansion. This was correlated with increased levels of bcl-2 and bcl-xL together with decreased bim expression. 4-1BB-co-stimulated post-REP TIL also expressed increased levels of the cytolytic granule proteins and exhibited enhanced CTL activity against melanoma cells. Lastly, post-REP CD8+ TIL were protected from cell death by anti-4-1BB ligation when exposed to HLA-matched melanoma cells. Our results indicate that 4-1BB co-stimulation may significantly improve TIL survival during melanoma ACT and boost anti-tumor cytolytic activity. PMID:21389874

Self-Catalyzed CdTe Wires.

PubMed

Baines, Tom; Papageorgiou, Giorgos; Hutter, Oliver S; Bowen, Leon; Durose, Ken; Major, Jonathan D

2018-04-25

CdTe wires have been fabricated via a catalyst free method using the industrially scalable physical vapor deposition technique close space sublimation. Wire growth was shown to be highly dependent on surface roughness and deposition pressure, with only low roughness surfaces being capable of producing wires. Growth of wires is highly (111) oriented and is inferred to occur via a vapor-solid-solid growth mechanism, wherein a CdTe seed particle acts to template the growth. Such seed particles are visible as wire caps and have been characterized via energy dispersive X-ray analysis to establish they are single phase CdTe, hence validating the self-catalysation route. Cathodoluminescence analysis demonstrates that CdTe wires exhibited a much lower level of recombination when compared to a planar CdTe film, which is highly beneficial for semiconductor applications.

Discordance in CD4+T-Cell Levels and Viral Loads with Co-Occurrence of Elevated Peripheral TNF-α and IL-4 in Newly Diagnosed HIV-TB Co-Infected Cases

PubMed Central

Benjamin, Ronald; Banerjee, Atoshi; Sunder, Sharada Ramaseri; Gaddam, Sumanlatha; Valluri, Vijaya Lakshmi; Banerjee, Sharmistha

2013-01-01

Background Cytokines are the hallmark of immune response to different pathogens and often dictate the disease outcome. HIV infection and tuberculosis (TB) are more destructive when confronted together than either alone. Clinical data related to the immune status of HIV-TB patients before the initiation of any drug therapy is not well documented. This study aimed to collect the baseline information pertaining to the immune status of HIV-TB co-infected patients and correlate the same with CD4+T cell levels and viral loads at the time of diagnosis prior to any drug therapy. Methodology/Principal Findings We analyzed the cytokines, CD4+T cell levels and viral loads to determine the immune environment in HIV-TB co-infection. The study involved four categories namely, Healthy controls (n = 57), TB infected (n = 57), HIV infected (n = 59) and HIV-TB co-infected (n = 57) patients. The multi-partite comparison and correlation between cytokines, CD4+T-cell levels and viral loads prior to drug therapy, showed an altered TH1 and TH2 response, as indicated by the cytokine profiles and skewed IFN-γ/IL-10 ratio. Inadequate CD4+T cell counts in HIV-TB patients did not correlate with high viral loads and vice-versa. When compared to HIV category, 34% of HIV-TB patients had concurrent high plasma levels of IL-4 and TNF-α at the time of diagnosis. TB relapse was observed in 5 of these HIV-TB co-infected patients who also displayed high IFN-γ/IL-10 ratio. Conclusion/Significance With these studies, we infer (i) CD4+T-cell levels as baseline criteria to report the disease progression in terms of viral load in HIV-TB co-infected patients can be misleading and (ii) co-occurrence of high TNF-α and IL-4 levels along with a high ratio of IFN-γ/IL-10, prior to drug therapy, may increase the susceptibility of HIV-TB co-infected patients to hyper-inflammation and TB relapse. PMID:23936398

Effects of systemic carbidopa on dopamine synthesis in rat hypothalamus and striatum

NASA Technical Reports Server (NTRS)

Kaakkola, S.; Tuomainen, P.; Wurtman, R. J.; Maennistoe, P. T.

1991-01-01

Significant concentrations of carbidopa (CD) were found in rat hypothalamus, striatum, and in striatal microdialysis efflux after intraperitoneal administration of the drug. Efflux levels peaked one hour after administration of 100 mg/kg at 0.37 microg/kg or about 2 percent of serum levels. Concurrent CD levels in hypothalamus and striatum were about 2.5 percent and 1.5 percent, respectively, of corresponding serum levels. Levels of dopamine and its principal metabolites in striatal efflux were unaffected. The removal of the brain blood by saline perfusion decreased the striatal and hypothalamic CD concentrations only by 33 percent and 16 percent, respectively. In other rats receiving both CD and levodopa (LD), brain L-dopa, dopamine, and 3,4-dihydroxyphenvlacetic acid (DOPAC) levels after one hour tended to be proportionate to LD dose. When the LD dose remained constant, increasing the CD dose dose-dependently enhanced L-dopa levels in the hypothalamus and striatum. However, dopamine levels did not increase but, in contrast, decreased dose-dependently (although significantly only in the hypothalamus). CD also caused dose-dependent decrease in striatal 3-O-methyldopa (3-OMD) and in striatal and hypothalamic homovanillic acid (HVA), when the LD dose was 50 mg/kg. We conclude that, at doses exceedimg 50 mg/kg, sufficient quantities of CD enter the brain to inhibit dopamine formation, especially in the hypothalamus. Moreover, high doses of LD/CD, both of which are themselves catechols, can inhibit the O-methylation of brain catecholamines formed from the LD.

Effects of systemic carbidopa on dopamine synthesis in rat hypothalamus and striatum

NASA Technical Reports Server (NTRS)

Kaakkola, S.; Tuomainen, P.; Wurtman, R. J.; Mannisto, P. T.

1992-01-01

Significant concentrations of carbidopa (CD) were found in rat hypothalamus, striatum, and in striatal microdialysis efflux after intraperitoneal administration of the drug. Efflux levels peaked one hour after administration of 100 mg/kg at 0.37 micrograms/ml, or about 2% of serum levels. Concurrent CD levels in hypothalamus and striatum were about 2.5% and 1.5%, respectively, of corresponding serum levels. Levels of dopamine and its principal metabolites in striatal efflux were unaffected. The removal of the brain blood by saline perfusion decreased the striatal and hypothalamic CD concentrations only by 33% and 16%, respectively. In other rats receiving both CD and levodopa (LD), brain L-dopa, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels after one hour tended to be proportionate to LD dose. When the LD dose remained constant, increasing the CD dose dose-dependently enhanced L-dopa levels in the hypothalamus and striatum. However dopamine levels did not increase but, in contrast, decreased dose-dependently (although significantly only in the hypothalamus). CD also caused dose-dependent decrease in striatal 3-O-methyldopa (3-OMD) and in striatal and hypothalamic homovanillic acid (HVA), when the LD dose was 50 mg/kg. We conclude that, at doses exceeding 50 mg/kg, sufficient quantities of CD enter the brain to inhibit dopamine formation, especially in the hypothalamus. Moreover, high doses of LD/CD, both of which are themselves catechols, can inhibit the O-methylation of brain catecholamines formed from the LD.

CD28-Negative CD4+ and CD8+ T Cells in Antiretroviral Therapy–Naive HIV-Infected Adults Enrolled in Adult Clinical Trials Group Studies

PubMed Central

Tassiopoulos, Katherine; Landay, Alan; Collier, Ann C.; Connick, Elizabeth; Deeks, Steven G.; Hunt, Peter; Lewis, Dorothy E.; Wilson, Cara; Bosch, Ronald

2012-01-01

Background Individuals infected with human immunodeficiency virus (HIV) have higher risk than HIV-negative individuals for diseases associated with aging. T-cell senescence, characterized by expansion of cells lacking the costimulatory molecule CD28, has been hypothesized to mediate these risks. Methods We measured the percentage of CD28−CD4+ and CD8+ T cells from HIV-infected treatment-naive adults from 5 Adult Clinical Trials Group (ACTG) antiretroviral therapy (ART) studies and the ALLRT (ACTG Longitudinal Linked Randomized Trials) cohort, and from 48 HIV-negative adults. Pretreatment and 96-week posttreatment %CD28− cells were assessed using linear regression for associations with age, sex, race/ethnicity, CD4 count, HIV RNA, ART regimen, and hepatitis C virus (HCV) infection. Results In total, 1291 chronically HIV-infected adults were studied. Pretreatment, lower CD4 count was associated with higher %CD28−CD4+ and %CD28−CD8+ cells. For CD8+ cells, younger age and HCV infection were associated with a lower %CD28−. ART reduced %CD28− levels at week 96 among virally suppressed individuals. Older age was strongly predictive of higher %CD28−CD8+. Compared to HIV-uninfected individuals, HIV-infected individuals maintained significantly higher %CD28−. Conclusions Effective ART reduced the proportion of CD28− T cells. However, levels remained abnormally high and closer to levels in older HIV-uninfected individuals. This finding may inform future research of increased rates of age-associated disease in HIV-infected adults. PMID:22448010

CD147 blockade as a potential and novel treatment of graft rejection

PubMed Central

Luan, Jing; Zhao, Yu; Zhang, Yang; Miao, Jinlin; Li, Jia; Chen, Zhi-Nan; Zhu, Ping

2017-01-01

Cluster of differentiation (CD)147 is highly involved in the T cell activation process. High CD147 expression is observed on the surfaces of activated T cells, particularly CD4+ T cells. In organ transplantation, it is important to prevent graft rejection resulting from the excessive activation of T cells, particularly CD4+ T cells, which exhibit a key role in amplifying the immune response. The present study aimed to investigate the effects of CD147 blockade in vitro and in vivo and used a transplant rejection system to assess the feasibility of utilizing CD147 antibody-based immunosuppressant drugs for the treatment of graft rejection. The effects of CD147 antibodies were evaluated on lymphocyte proliferation stimulated by phytohemagglutinin or CD3/CD28 magnetic beads and in a one-way mixed lymphocyte reaction (MLR) system in vitro. For the in vivo analysis, an allogeneic skin transplantation mouse model was used. CD147 antibodies were effective against lymphocytes, particularly CD4+T lymphocytes, and were additionally effective in the one-way MLR system. In the allogeneic skin transplantation mouse model, the survival of transplanted skin was extended in the CD147 antibody-treated group. Furthermore, the level of inflammatory cell infiltration in transplanted skin was reduced. CD147 blockade decreased the serum levels of interleukin (IL)-17 and the proportions of peripheral blood CD4+ and CD8+ memory T cells. The data demonstrated that CD147 blockade suppressed skin graft rejection, primarily by suppressing CD4+T and memory T cell proliferation, indicating that CD147 exhibits great potential as a target of immunosuppressant drugs. PMID:28849101

CD147 blockade as a potential and novel treatment of graft rejection.

PubMed

Luan, Jing; Zhao, Yu; Zhang, Yang; Miao, Jinlin; Li, Jia; Chen, Zhi-Nan; Zhu, Ping

2017-10-01

Cluster of differentiation (CD)147 is highly involved in the T cell activation process. High CD147 expression is observed on the surfaces of activated T cells, particularly CD4+ T cells. In organ transplantation, it is important to prevent graft rejection resulting from the excessive activation of T cells, particularly CD4+ T cells, which exhibit a key role in amplifying the immune response. The present study aimed to investigate the effects of CD147 blockade in vitro and in vivo and used a transplant rejection system to assess the feasibility of utilizing CD147 antibody‑based immunosuppressant drugs for the treatment of graft rejection. The effects of CD147 antibodies were evaluated on lymphocyte proliferation stimulated by phytohemagglutinin or CD3/CD28 magnetic beads and in a one‑way mixed lymphocyte reaction (MLR) system in vitro. For the in vivo analysis, an allogeneic skin transplantation mouse model was used. CD147 antibodies were effective against lymphocytes, particularly CD4+T lymphocytes, and were additionally effective in the one‑way MLR system. In the allogeneic skin transplantation mouse model, the survival of transplanted skin was extended in the CD147 antibody‑treated group. Furthermore, the level of inflammatory cell infiltration in transplanted skin was reduced. CD147 blockade decreased the serum levels of interleukin (IL)‑17 and the proportions of peripheral blood CD4+ and CD8+ memory T cells. The data demonstrated that CD147 blockade suppressed skin graft rejection, primarily by suppressing CD4+T and memory T cell proliferation, indicating that CD147 exhibits great potential as a target of immunosuppressant drugs.

Endotoxin levels correlate positively with a sedentary lifestyle and negatively with highly trained subjects

PubMed Central

2010-01-01

Introduction A sedentary lifestyle increases the risk of developing cardiovascular disease, obesity, and diabetes. This phenomenon is supported by recent studies suggesting a chronic, low-grade inflammation status. Endotoxin derived from gut flora may be key to the development of inflammation by stimulating the secretion of inflammatory factors. This study aimed to examine plasma inflammatory markers and endotoxin levels in individuals with a sedentary lifestyle and/or in highly trained subjects at rest. Methods: Fourteen male subjects (sedentary lifestyle n = 7; highly trained subjects n = 7) were recruited. Blood samples were collected after an overnight fast (~12 h). The plasmatic endotoxin, plasminogen activator inhibitor type-1 (PAI-1), monocyte chemotactic protein-1 (MCP1), ICAM/CD54, VCAM/CD106 and lipid profile levels were determined. Results Endotoxinemia was lower in the highly trained subject group relative to the sedentary subjects (p < 0.002). In addition, we observed a positive correlation between endotoxin and PAI-1 (r = 0.85, p < 0.0001), endotoxin and total cholesterol (r = 0.65; p < 0.01), endotoxin and LDL-c (r = 0.55; p < 0.049) and endotoxin and TG levels (r = 0.90; p < 0.0001). The plasma levels of MCP-1, ICAM/CD54 and VCAM/CD106 did not differ. Conclusion These results indicate that a lifestyle associated with high-intensity and high-volume exercise induces favorable changes in chronic low-grade inflammation markers and may reduce the risk for diseases such as obesity, diabetes and cardiovascular diseases. PMID:20684772

Endotoxin levels correlate positively with a sedentary lifestyle and negatively with highly trained subjects.

PubMed

Lira, Fabio S; Rosa, Jose C; Pimentel, Gustavo D; Souza, Hélio A; Caperuto, Erico C; Carnevali, Luiz C; Seelaender, Marília; Damaso, Ana R; Oyama, Lila M; de Mello, Marco T; Santos, Ronaldo V

2010-08-04

A sedentary lifestyle increases the risk of developing cardiovascular disease, obesity, and diabetes. This phenomenon is supported by recent studies suggesting a chronic, low-grade inflammation status. Endotoxin derived from gut flora may be key to the development of inflammation by stimulating the secretion of inflammatory factors. This study aimed to examine plasma inflammatory markers and endotoxin levels in individuals with a sedentary lifestyle and/or in highly trained subjects at rest. Fourteen male subjects (sedentary lifestyle n = 7; highly trained subjects n = 7) were recruited. Blood samples were collected after an overnight fast (approximately 12 h). The plasmatic endotoxin, plasminogen activator inhibitor type-1 (PAI-1), monocyte chemotactic protein-1 (MCP1), ICAM/CD54, VCAM/CD106 and lipid profile levels were determined. Endotoxinemia was lower in the highly trained subject group relative to the sedentary subjects (p < 0.002). In addition, we observed a positive correlation between endotoxin and PAI-1 (r = 0.85, p < 0.0001), endotoxin and total cholesterol (r = 0.65; p < 0.01), endotoxin and LDL-c (r = 0.55; p < 0.049) and endotoxin and TG levels (r = 0.90; p < 0.0001). The plasma levels of MCP-1, ICAM/CD54 and VCAM/CD106 did not differ. These results indicate that a lifestyle associated with high-intensity and high-volume exercise induces favorable changes in chronic low-grade inflammation markers and may reduce the risk for diseases such as obesity, diabetes and cardiovascular diseases.

Distribution and ecological risk assessment of cadmium in water and sediment in Longjiang River, China: Implication on water quality management after pollution accident.

PubMed

Zhao, Xue-Min; Yao, Ling-Ai; Ma, Qian-Li; Zhou, Guang-Jie; Wang, Li; Fang, Qiao-Li; Xu, Zhen-Cheng

2018-03-01

In early January 2012, the Longjiang River was subjected to a serious cadmium (Cd) pollution accident, which led to negatively environmental and social impacts. A series of measures of emergency treatment were subsequently taken to reduce water Cd level. However, little information was available about the change of Cd level in environmental matrices and long-term effect of this pollution accident to aquatic ecosystem. Thus, this study investigated the distribution of Cd in water and sediment of this river for two years since pollution accident, as well as assessed its ecological risk to aquatic ecosystem of Longjiang River. The results showed that it was efficient for taking emergency treatment measures to decrease water Cd concentration to below the threshold value of national drinking water quality standard of China. There was high risk (HQ > 1) to aquatic ecosystem in some of reaches between February and July 2012, but low or no risk (HQ < 1) between December 2012 to December 2013. Cd concentration in sediment in polluted reaches increased after pollution accident and emergency treatments in 2012, but decreased in 2013. During flood period, the sediment containing high concentration of Cd in Longjiang River was migrated to downstream Liujiang River. Cd content in sediment was reduced to background level after two years of the pollution accident occurrence. The study provides basic information about Cd levels in different media after pollution accident, which is helpful in evaluating the effectiveness of emergency treatments and the variation of ecological risk, as well as in conducting water management and conservation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

PubMed Central

Saison, J; Ferry, T; Demaret, J; Maucort Boulch, D; Venet, F; Perpoint, T; Ader, F; Icard, V; Chidiac, C; Monneret, G

2014-01-01

The mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (Tregs) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4+ T cell count (> or < 500/mm3). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4+ lymphocytes, including Treg subsets, and CD8+ T cells was performed. Percentages of activated CD4+ T cells, Tregs, effector Tregs and terminal effector Tregs were found to be significantly elevated in iIR. Neither the percentage of activated CD8+ T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4+ T cell count and percentage of Tregs were the only two parameters associated independently with iIR [odds ratio (OR) = 2·339, P = 0·001, and OR = 0·803, P = 0·041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4+ and CD8+ T cells, Treg percentages and very low-level viraemia. Causative interactions between Tregs and CD4+ T cells should now be explored prospectively in a large patients cohort. PMID:24460818

CXCR5+CD8+ T cells present elevated capacity in mediating cytotoxicity toward autologous tumor cells through interleukin 10 in diffuse large B-cell lymphoma.

PubMed

Tang, Jiahong; Zha, Jie; Guo, Xutao; Shi, Pengcheng; Xu, Bing

2017-09-01

Diffuse large B-cell lymphoma (DLBCL) is a common and aggressive subtype of non-Hodgkin's lymphomas, with limited treatment options in refractory and relapsed patients. Growing evidence supports the notion that CD8 + T cell immunity could be utilized to eliminate B cell lymphomas. CXCR5 + CD8 + T cell is a novel cell subtype and share CXCR5 expression with CD19 + tumor cells. In this study, we investigated the frequency and function of existing CXCR5 + CD8 + T cells in DLBCL patients. We found that DLBCL patients as a group demonstrated significantly higher level of CXCR5 + CD8 + T cells than healthy individuals, with huge variability in each patient. Using anti-CD3/CD28-stimulated CD8 + T cells as effector (E) cells and autologous CD19 + tumor cells as target (T) cells, at high E:T ratio, no difference between the intensities of CXCR5 + CD8 + T cell- and CXCR5 - CD8 + T cell-mediated cytotoxicity were observed. However, at intermediate and low E:T ratios, the CXCR5 + CD8 + T cells presented stronger cytotoxicity than CXCR5 - CD8 + T cells. The expressions of granzyme A, granzyme B, and perforin were significantly higher in CXCR5 + CD8 + T cells than in CXCR5 - CD8 + T cells, with no significant difference in the level of degranulation. Tumor cells in DLBCL were known to secrete high level of interleukin 10 (IL-10). We therefore blocked the IL-10/IL-10R pathway, and found that the expressions of granzyme A, granzyme B, and perforin by CXCR5 + CD8 + T cells were significantly elevated. Together, these results suggest that CXCR5 + CD8 + T cells are potential candidates of CD8 + T cell-based immunotherapies, could mediate elimination of autologous tumor cells in DLBCL patients, but are also susceptible to IL-10-mediated suppression. Copyright © 2017. Published by Elsevier B.V.

Post-transplant monitoring of soluble CD30 level as predictor of graft outcome: a single center experience from China.

PubMed

Wang, Dong; Wu, Weizhen; Yang, Shunliang; Wang, Qinghua; Tan, Jianming

2012-12-01

There are no reliable parameters for post-transplantation immunological monitoring, which might enable recipient-tailored immunosuppressive therapy. 250 renal graft recipients were enrolled and detected for sCD30 level pre-transplantation, and on days 5 and 14, and on months 1, 3, 6, 12, 24, 36, 48 and 60 post-transplantation. Analysis was performed on correlation between sCD30 level and acute rejection, lung infection, or graft loss respectively. sCD30 levels descended to a nadir with a mean of 10.2 ± 3.8 U/mL on day 30 post-transplantation, then rose gradually, and approached 21.8 ± 10.1 U/mL on month 3, 34.2 ± 16.5 U/mL on month 6, and 42.9 ± 29.5 U/mL on month 12, then presented a stable level. Recipients with AR had significantly higher sCD30 levels than those without AR on days 5 and 14 post-transplantation. Recipients with pneumonia had significantly lower sCD30 levels within 3 months post-transplantation than those without pneumonia. Significantly higher sCD30 levels were recorded in recipients who suffered graft loss than those with normal graft function on days 5 and 14, and on months 6, 12, and 24. High sCD30 level (≥ 48.3 U/mL) at month 12 post-transplantation has an obvious detrimental effect on renal graft survival (p=0.000, HR=9.075). Serum sCD30 level might reflect immune state of renal graft recipients. Post-transplantation sequential monitoring of sCD30 level is necessary, which might not only identify recipients at the risk of acute rejection and graft loss, but also chosen as an independent predictor of pneumonia in renal transplant recipients. Copyright © 2012 Elsevier B.V. All rights reserved.

Understanding and mitigating the toxicity of cadmium to the anaerobic fermentation of waste activated sludge.

PubMed

Xu, Qiuxiang; Li, Xiaoming; Ding, Rongrong; Wang, Dongbo; Liu, Yiwen; Wang, Qilin; Zhao, Jianwei; Chen, Fei; Zeng, Guangming; Yang, Qi; Li, Hailong

2017-11-01

Cadmium (Cd) is present in significant levels in waste activated sludge, but its potential toxicities on anaerobic fermentation of sludge remain largely unknown. This work therefore aims to provide such support. Experimental results showed that the impact of Cd on short-chain fatty acids (SCFA) production from sludge anaerobic fermentation was dose-dependent. The presence of environmentally relevant level of Cd (e.g., 0.1 mg/g VSS) enhanced SCFA production by 10.6%, but 10 mg/g VSS of Cd caused 68.1% of inhibition. Mechanism exploration revealed that although all levels of Cd did not cause extra leakage of intracellular substrates, 0.1 mg/g VSS Cd increased the contents of both soluble and loosely-bound extracellular polymeric substances (EPS), thereby benefitting sludge solubilization. On the contrary, 10 mg/g VSS Cd decreased the levels of all EPS layers, which reduced the content of soluble substrates. It was also found that 0.1 mg/g VSS Cd benefited both the hydrolysis and acidogenesis but 10 mg/g VSS Cd inhibited all the hydrolysis, acidogenesis, and methanogenesis processes. Further investigations with microbial community and enzyme analysis showed that the pertinent presence of Cd enhanced the activities of protease, acetate kinase, and oxaloacetate transcarboxylase whereas 10 mg/g VSS Cd decreased the microbial diversity, the abundances of functional microbes, and the activities of key enzymes. Finally, one strategy that could effectively mitigate the adverse impact of high Cd levels on SCFA production was proposed and examined. This work provides insights into Cd-present sludge fermentation systems, and the findings obtained may guide engineers to manipulate sludge treatment systems in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Infliximab Induces Clonal Expansion of γδ-T Cells in Crohn's Disease: A Predictor of Lymphoma Risk?

PubMed Central

Kelsen, Jens; Dige, Anders; Schwindt, Heinrich; D'Amore, Francesco; Pedersen, Finn S.; Agnholt, Jørgen; Christensen, Lisbet A.; Dahlerup, Jens F.; Hvas, Christian L.

2011-01-01

Background Concominant with the widespread use of combined immunotherapy in the management of Crohn's disease (CD), the incidence of hepato-splenic gamma-delta (γδ)-T cell lymphoma has increased sharply in CD patients. Malignant transformation of lymphocytes is believed to be a multistep process resulting in the selection of malignant γδ-T cell clones. We hypothesised that repeated infusion of anti-TNF-α agents may induce clonal selection and that concurrent treatment with immunomodulators further predisposes patients to γδ-T cell expansion. Methodology/Principal Findings We investigated dynamic changes in the γδ-T cells of patient with CD following treatment with infliximab (Remicade®; n = 20) or adalimumab (Humira®; n = 26) using flow cytometry. In patients with a high γδ-T cell level, the γδ-T cells were assessed for clonality. Of these 46 CD patients, 35 had a γδ-T cells level (mean 1.6%) comparable to healthy individuals (mean 2.2%), and 11 CD patients (24%) exhibited an increased level of γδ-T cells (5–15%). In the 18 patients also receiving thiopurines or methotrexate, the average baseline γδ-T cell level was 4.4%. In three male CD patients with a high baseline value, the γδ-T cell population increased dramatically following infliximab therapy. A fourth male patient also on infliximab monotherapy presented with 20% γδ-T cells, which increased to 25% shortly after treatment and was 36% between infusions. Clonality studies revealed an oligoclonal γδ-T cell pattern with dominant γδ-T cell clones. In support of our clinical findings, in vitro experiments showed a dose-dependent proliferative effect of anti-TNF-α agents on γδ-T cells. Conclusion/Significance CD patients treated with immunomodulators had constitutively high levels of γδ-T cells. Infliximab exacerbated clonal γδ-T cell expansion in vivo and induced γδ-T cell proliferation in vitro. Overall, young, male CD patients with high baseline γδ-T cell levels may be at an increased risk of developing malignant γδ-T cell lymphomas following treatment with anti-TNF-α agents. PMID:21483853

Serum level of CD26 predicts time to first treatment in early B-chronic lymphocytic leukemia.

PubMed

Molica, Stefano; Digiesi, Giovanna; Mirabelli, Rosanna; Cutrona, Giovanna; Antenucci, Anna; Molica, Matteo; Giannarelli, Diana; Sperduti, Isabella; Morabito, Fortunato; Neri, Antonino; Baldini, Luca; Ferrarini, Manlio

2009-09-01

We analyzed the correlation between well-established biological parameters of prognostic relevance in B-cell chronic lymphocytic leukemia (CLL) [i.e. mutational status of the immunoglobulin heavy chain variable region (IgV(H)), ZAP-70- and CD38-expression] and serum levels of CD26 (dipeptidyl peptidase IV, DPP IV) by evaluating the impact of these variables on the time to first treatment (TFT) in a series of 69 previously untreated Binet stage A B-cell CLL patients. By using a commercial ELISA we found that with exception of a borderline significance for ZAP-70 (P = 0.07) and CD38 (P = 0.08), circulating levels of CD26 did not correlate with either Rai substages (P = 0.520) or other biomarker [beta2-microglobulin (P = 0.933), LDH (P = 0.101), mutational status of IgV(H) (P = 0.320)]. Maximally selected log-rank statistic plots identified a CD26 serum concentration of 371 ng/mL as the best cut-off. This threshold allowed the identification of two subsets of patients with CD26 serum levels higher and lower that 371 ng/mL respectively, whose clinical outcome was different with respect to TFT (i.e. 46% and 71% at 5 yr respectively; P = 0.005). Along with higher serum levels of CD26, the univariate Cox proportional hazard model identified absence of mutation in IgV(H) (P < 0.0001) as predictor of shorter TFT. As in multivariate analysis all these parameters maintained their discriminating power (mutational status of IgV(H,)P < 0.0001; soluble CD26, P = 0.02) their combined effect on clinical outcome was assessed. When three groups were considered: (1) Low-risk group (n = 31), patients with concordant IgVH(mut) and low level of soluble CD26; (2) intermediate risk group (n = 26), patients with discordant pattern; (3) high-risk group (n = 12), patients with concordant IgVH(unmut) and high level of soluble CD26, differences in the TFT were statistically significant, with a TFT at 5 yr of respectively 88%, 51% and 43% (P < 0.0001). Our results indicate that in early B-cell CLL biological profile including among other parameters soluble CD26 may provide a useful insight into the complex interrelationship of prognostic variables. Furthermore, CD26 along with mutational status of IgV(H) can be adequately used to predict clinical behavior of patients with low risk disease.

Different strategies of cadmium detoxification in the submerged macrophyte Ceratophyllum demersum L.

PubMed

Andresen, Elisa; Mattusch, Jürgen; Wellenreuther, Gerd; Thomas, George; Arroyo Abad, Uriel; Küpper, Hendrik

2013-10-01

The heavy metal cadmium (Cd) is highly toxic to plants. To understand the mechanisms of tolerance and resistance to Cd, we treated the rootless, submerged macrophyte Ceratophyllum demersum L. with sub-micromolar concentrations of Cd under environmentally relevant conditions. X-ray fluorescence measurements revealed changing distribution patterns of Cd and Zn at non-toxic (0.2 nM, 2 nM), moderately toxic (20 nM) and highly toxic (200 nM) levels of Cd. Increasing Cd concentrations led to enhanced sequestration of Cd into non-photosynthetic tissues like epidermis and vein. At toxic Cd concentrations, Zn was redistributed and mainly found in the vein. Cd treatment induced the synthesis of phytochelatins (PCs) in the plants, with a threshold of induction already at 20 nM Cd for PC3. In comparison, in plants treated with Cu, elevated PC levels were detected only at the highest concentrations (100-200 nM Cu). Our results show that also non-accumulators like C. demersum store toxic metals in tissues where the heavy metal interferes least with metabolic pathways, but remaining toxicity interferes with micronutrient distribution. Furthermore, we found that the induction of phytochelatins is not proportional to metal concentration, but has a distinct threshold, specific for each PC species. Finally we could show that 20 nM Cd, which was previously regarded as non-toxic to most plants, already induces detoxifying mechanisms.

Analysis cluster of differentiation 4 number and c-reactive protein concentration in patient with human immunodeficiency virus with or without lung tuberculosis

NASA Astrophysics Data System (ADS)

Nur, M. J.; Kuhuwael, F.; Katu, S.; Mubin, H.; Halim, R.

2018-03-01

HIV infected patients characterized by decrease CD4 cell count, where lower CD4 count, has higher infection risk. In HIV patients with Lung, Tuberculosis co-infection showed increase CRP level concomitant with disease severity. This study attempts to analyze TB incidence in HIV cases by looking at CD4 cell count and CRP levels in HIV-infected subjects. For analyzing the CD4 cell count and CRP levels in HIV patient with and without Lung Tuberculosis co-infection in Wahidin Sudirohusodo Hospital. Conducted observational study with cross-sectional design on HIV subjects withand without Lung Tuberculosis co-infection in Wahidin Sudirohusodo Hospital from September 2016 to June 2017. Patients divided into HIV group without TB co-infection, and with TB co-infection. Each group will be assessed CRP levels, which considered low <5 mg/L and high >5 mg/L, whereas CD4 cell count, considered low <200 cell/mm3 and normal >200 cell/mm3. Results are considered significant if p-value<0.05. There were a significantly higher CRP levels (p<0.02) and lower CD4 counts (p<0.02) in HIV with TB co-infection and no significant relationship between CRP levels with aCD4 count in both groups.

Role for granulocyte colony-stimulating factor in the generation of human T regulatory type 1 cells.

PubMed

Rutella, Sergio; Pierelli, Luca; Bonanno, Giuseppina; Sica, Simona; Ameglio, Franco; Capoluongo, Ettore; Mariotti, Andrea; Scambia, Giovanni; d'Onofrio, Giuseppe; Leone, Giuseppe

2002-10-01

Granulocyte colony-stimulating factor (G-CSF) may affect T-cell homeostasis by multiple mechanisms, inducing polarization of cytokine secretion, inhibition of T-cell proliferation, and enhancement of T-cell apoptosis. We analyzed the production of interleukin-10 (IL-10) and transforming growth factor-beta1 (TGF-beta1) by T cells from healthy volunteer donors treated with recombinant human G-CSF. Highly purified CD4(+) T cells obtained before and after G-CSF administration (pre-G and post-G, respectively) were activated using the allogeneic mixed leukocyte reaction. Post-G CD4(+) T cells produced high levels of IL-10 but undetectable levels of IL-2 and IL-4, whereas the level of TGF-beta1 release was comparable to that of pre-G CD4(+) T cells. Notably, post-G CD4(+) T cells proliferated poorly in response to alloantigens and to recall antigens and suppressed the proliferation of autologous CD4(+) T cells in a cell contact-independent and an antigen-nonspecific manner. TGF-beta1 and IL-10 were not dispensable for post-G CD4(+) T cells to mediate suppression, as shown by neutralization studies. Compared with pre-G CD4(+) T cells, alloantigen-activated post-G CD4(+) T cells preferentially expressed markers associated with memory T cells, in conjunction with reduced levels of CD28 and CD62L. Collectively, these data demonstrate that CD4(+) T cells exposed to G-CSF in vivo acquire the properties of T regulatory (Tr) cells once triggered in vitro through the T-cell receptor, including a peculiar cytokine production profile (IL-10(++)TGF-beta1(+)IL-2(low/-)IL-4(low/-)), an intrinsic low proliferative capacity, and a contact-independent suppression of antigen-driven proliferation. Tr cells generated ex vivo after exposure to G-CSF might be clinically relevant for transplantation medicine and for the treatment of human immune-mediated diseases.

Serum levels of soluble CD30 are increased in ulcerative colitis (UC) but not in Crohn's disease (CD)

PubMed Central

Giacomelli, R; Passacantando, A; Parzanese, I; Vernia, P; Klidara, N; Cucinelli, F; Lattanzio, R; Santori, E; Cipriani, P; Caprilli, R; Tonietti, G

1998-01-01

Imbalance in Th1 and Th2 subsets and their derived cytokines seems to be involved in the immune abnormalities underlying UC and CD. CD30 is a member of the tumour necrosis factor/nerve growth receptor superfamily expressed on T cells producing Th2 cytokines and released as a soluble form. In this study high levels of soluble CD30 were found in sera of UC patients independently of disease activity. Furthermore, increased titres of soluble CD30 molecule were shown, in the same patients, by mitogen-stimulated cultures of peripheral blood mononuclear cells. Our data seem to indicate that an activation of Th2 immune response is involved in the pathogenesis of UC, but not of CD. Furthermore, this finding indicates that serum soluble CD30 measurement may be helpful for differentiating these two forms of inflammatory bowel disease. PMID:9528894

Effects of high-intensity interval versus mild-intensity endurance training on metabolic phenotype and corticosterone response in rats fed a high-fat or control diet

PubMed Central

Shen, Youqing; Huang, Guoyuan; McCormick, Bryan P.; Song, Tao

2017-01-01

The aim of the present study was to compare the effects of high-intensity interval training (HI) to mild-intensity endurance training (ME), combined with a high-fat diet (HFD) or control diet (CD) on metabolic phenotype and corticosterone levels in rats. Fifty-three rats were randomized to 6 groups according to diet and training regimen as follows: CD and sedentary (CS, n = 11), CD and ME (CME, n = 8), CD and HI (CHI, n = 8), HFD and sedentary (HS, n = 10), HFD and ME (HME, n = 8), and HFD and HI (HHI, n = 8). All exercise groups were trained for 10 weeks and had matched running distances. Dietary intake, body composition, blood metabolites, and corticosterone levels were measured. Histological lipid droplets were observed in the livers. The HFD led to hyperglycemia, hyperlipidemia and higher body fat (all, P < 0.01, η2 > 0.06), as well as higher corticosterone levels (P < 0.01, η2 = 0.09) compared with the CD groups. Exercise training improved fat weight, glucose, and lipid profiles, and reduced corticosterone levels (P < 0.01, η2 = 0.123). Furthermore, body and fat weight, serum glucose and triglycerides, lipid content in the liver, and corticosterone levels (P < 0.05) were lower with HI training compared to ME training. Reductions in HFD-induced body weight gain, blood glucose and lipid profiles, and corticosterone levels, as well as improvements in QUICKI were better with HHI compared to HME. Correlation analyses revealed that corticosterone levels were significantly associated with phenotype variables (P < 0.01). Corticosterone level was inversely correlated with QUICKI (r = −0.38, P < 0.01). Altogether, these results indicate that HFD may elicit an exacerbated basal serum corticosterone level and thus producing a metabolic imbalance. Compared with ME training, HI training contributes to greater improvements in metabolic and corticosterone responses, leading to a greater reduction in susceptibility to HFD-induced disorders. PMID:28727846

Effects of high-intensity interval versus mild-intensity endurance training on metabolic phenotype and corticosterone response in rats fed a high-fat or control diet.

PubMed

Shen, Youqing; Huang, Guoyuan; McCormick, Bryan P; Song, Tao; Xu, Xiangfeng

2017-01-01

The aim of the present study was to compare the effects of high-intensity interval training (HI) to mild-intensity endurance training (ME), combined with a high-fat diet (HFD) or control diet (CD) on metabolic phenotype and corticosterone levels in rats. Fifty-three rats were randomized to 6 groups according to diet and training regimen as follows: CD and sedentary (CS, n = 11), CD and ME (CME, n = 8), CD and HI (CHI, n = 8), HFD and sedentary (HS, n = 10), HFD and ME (HME, n = 8), and HFD and HI (HHI, n = 8). All exercise groups were trained for 10 weeks and had matched running distances. Dietary intake, body composition, blood metabolites, and corticosterone levels were measured. Histological lipid droplets were observed in the livers. The HFD led to hyperglycemia, hyperlipidemia and higher body fat (all, P < 0.01, η2 > 0.06), as well as higher corticosterone levels (P < 0.01, η2 = 0.09) compared with the CD groups. Exercise training improved fat weight, glucose, and lipid profiles, and reduced corticosterone levels (P < 0.01, η2 = 0.123). Furthermore, body and fat weight, serum glucose and triglycerides, lipid content in the liver, and corticosterone levels (P < 0.05) were lower with HI training compared to ME training. Reductions in HFD-induced body weight gain, blood glucose and lipid profiles, and corticosterone levels, as well as improvements in QUICKI were better with HHI compared to HME. Correlation analyses revealed that corticosterone levels were significantly associated with phenotype variables (P < 0.01). Corticosterone level was inversely correlated with QUICKI (r = -0.38, P < 0.01). Altogether, these results indicate that HFD may elicit an exacerbated basal serum corticosterone level and thus producing a metabolic imbalance. Compared with ME training, HI training contributes to greater improvements in metabolic and corticosterone responses, leading to a greater reduction in susceptibility to HFD-induced disorders.

Soluble CD30 and Hepatocyte growth factor as predictive markers of antibody-mediated rejection of the kidney allograft.

PubMed

Pavlova, Yelena; Viklicky, Ondrej; Slatinska, Janka; Bürgelova, Marcela; Süsal, Caner; Skibova, Jelena; Honsová, Eva; Striz, Ilja; Kolesar, Libor; Slavcev, Antonij

2011-07-01

Our retrospective study was aimed to assess the relevance of pre- and post-transplant measurements of serum concentrations of the soluble CD30 molecule (soluble CD30, sCD30) and the cytokine Hepatocyte growth factor (HGF) for prediction of the risk for development of antibody-mediated rejection (AMR) in kidney transplant patients. Evaluation of sCD30, HGF levels and the presence of HLA-specific antibodies in a cohort of 205 patients was performed before, 2weeks and 6months after transplantation. Patients were followed up for kidney graft function and survival for two years. We found a tendency of higher incidence of AMR in retransplanted patients with elevated pre-transplant sCD30 (≥100U/ml) (p=0.051), however no such correlation was observed in first-transplant patients. Kidney recipients with simultaneously high sCD30 and HLA-specific antibodies (sCD30+/Ab+) before transplantation had significantly lower AMR-free survival compared to the other patient groups (p<0.001). HGF concentrations were not associated with the incidence of AMR at any time point of measurement, nevertheless, the combined analysis HGF and sCD30 showed increased incidence of AMR in recipients with elevated pretransplant sCD30 and low HGF levels. the predictive value of pretransplant sCD30 for the development of antibody-mediated rejection after transplantation is significantly potentiated by the co-presence of HLA specific antibodies. The role of HGF as a rejection-protective factor in patients with high pretransplant HGF levels would need further investigation. Copyright © 2011 Elsevier B.V. All rights reserved.

Association of elevated pretransplant sCD30 levels with graft loss in 206 patients treated with modern immunosuppressive therapies after renal transplantation.

PubMed

Heinemann, Falko M; Rebmann, Vera; Witzke, Oliver; Philipp, Thomas; Broelsch, Christoph E; Grosse-Wilde, Hans

2007-03-27

Recent reports suggest that high pretransplant serum levels of soluble CD30 (sCD30) are a risk factor for rejections after kidney transplantation. The aim of our study was to elucidate the predictive value of pretransplant sCD30 levels for kidney transplantation outcome in a single-center patient cohort that has been treated with modern immunosuppressive therapies after transplantation. We retrospectively analyzed sCD30 in multiple pretransplant sera from 206 patients, of whom 174 were transplanted with a cadaveric kidney and 32 patients received an allograft from a living donor. Renal function after transplantation was estimated by measuring serum creatinine and by rejection diagnosis. We could demonstrate a statistically significant association between increased pretransplant sCD30 values and graft failures (P=0.005). Receiver operating curve analysis revealed a cutoff value of 124 U/mL pretransplant sCD30. A multivariate analysis confirmed pretransplant sCD30 values >124 U/mL (P=0.011) and rejection episodes (P<0.0001) as independent risk factors for graft loss. Our study revealed a strong correlation between pretransplant sCD30 levels and the incidence of graft failure, but we could not confirm that the development of rejection episodes is correlated with pretransplant sCD30 values.

Growth of CdZnTe Crystals for Radiation Detector Applications by Directional Solidification

NASA Technical Reports Server (NTRS)

Su, Ching-Hua

2014-01-01

Advances in Cadmium Zinc Telluride (Cd(sub 1-x)Zn(sub x)Te) growth techniques are needed for the production of large-scale arrays of gamma and x-ray astronomy. The research objective is to develop crystal growth recipes and techniques to obtain large, high quality CdZnTe single crystal with reduced defects, such as charge trapping, twinning, and tellurium precipitates, which degrade the performance of CdZnTe and, at the same time, to increase the yield of usable material from the CdZnTe ingot. A low gravity material experiment, "Crystal Growth of Ternary Compound Semiconductors in Low Gravity Environment", will be performed in the Material Science Research Rack (MSRR) on International Space Station (ISS). One section of the flight experiment is the melt growth of CdZnTe ternary compounds. This talk will focus on the ground-based studies on the growth of Cd(sub 0.80)Zn(sub 0.20)Te crystals for radiation detector applications by directional solidification. In this investigation, we have improved the properties that are most critical for the detector applications (electrical properties and crystalline quality): a) Electrical resistivity: use high purity starting materials (with reproducible impurity levels) and controlled Cd over pressure during growth to reproducibly balance the impurity levels and Cd vacancy concentration b) Crystalline quality: use ultra-clean growth ampoule (no wetting after growth), optimized thermal profile and ampoule design, as well as a technique for supercool reduction to growth large single crystal with high crystalline quality

Post-transplant HLA class II antibodies and high soluble CD30 levels are independently associated with poor kidney graft survival.

PubMed

Langan, L L; Park, L P; Hughes, T L; Irish, A; Luxton, G; Witt, C S; Christiansen, F T

2007-04-01

HLA-specific antibodies (HSA) and soluble CD30 (sCD30) were measured in 208 renal transplant recipients with functioning grafts at least 1 year after transplantation (median 8.2 years) to investigate the predictive value of HSA and sCD30 on subsequent graft outcome. HSA (class I and class II) were detected by both ELISA LAT-M and Luminex LabScreen assays. Data on graft outcome was collected with a median follow-up time of 3.5 years after antibody and sCD30 measurement. Recipients with post-transplant HLA class II antibodies had particularly poor graft outcome with a hazard ratio (HR) of 7.8 (p < 0.0001) when detected by ELISA, and a HR of 6.0 (p < 0.0001) when detected by Luminex. A high post-transplant sCD30 level >or=100 U/mL was associated with increased risk of subsequent graft failure (HR 2.7, p = 0.03). sCD30 and HSA had an independent and additive association with graft outcome. Recipients with HLA class II antibody and high sCD30 had the highest risk of subsequent graft failure (HR 43.4, p < 0.0001 and HR 18.1, p = 0.0008 for ELISA and Luminex, respectively). These data show that detection of HSA and serum sCD30 measured at least 1-year post-transplant provides valuable and predictive information regarding subsequent graft outcome.

The Immune Pathogenesis of Immune Reconstitution Inflammatory Syndrome Associated with Highly Active Antiretroviral Therapy in AIDS

PubMed Central

Zhou, Huaying; He, Yan; Chen, Zi; He, Bo; He, Mei

2014-01-01

Abstract The present study investigated the immunological pathogenesis of immune reconstitution inflammatory syndrome (IRIS) in acquired immunodeficiency syndrome (AIDS) patients undergoing highly active antiretroviral therapy (HAART). A total of 238 patients with AIDS who received initial HAART were included in this prospective cohort study. Blood samples were collected immediately, at baseline, at week 12, and at week 24 after initial HAART and at the onset of IRIS. Lymphocyte subsets, Th1 and Th2 cytokines, and interleukin (IL)-7 levels were measured by flow cytometry or ELISA. Among the 238 patients with AIDS who received HAART, 47 patients developed IRIS. The percentages of CD4+ and CD8+ naive, memory, and activated cells exhibited no significant differences between AIDS patients with and without IRIS 24 weeks after initial HAART. The percentage of CD4+CD25+Foxp3+ regulatory T cells was lower in IRIS patients than in non-IRIS patients before HAART, 12 weeks after HAART, 24 weeks after HAART, and at the onset of IRIS. IL-2 and interferon (IFN)-γ levels were significantly higher at week 4 and at the onset of IRIS in IRIS patients than in non-IRIS patients. In contrast, IL-4 and IL-10 levels were significantly lower at week 4 and at the onset of IRIS in IRIS patients than in non-IRIS patients. Plasma IL-7 decreased gradually with the progression of HAART. The level of IL-7 was higher in IRIS patients than in non-IRIS patients at all follow-up time points. An imbalance of Th1/Th2 cytokines, a consistently low CD+CD25+Fox3+ percentage, and a high IL-7 level may be crucial in the pathogenesis of IRIS in AIDS patients who had received HAART. PMID:25131160

Active RNA replication of hepatitis C virus downregulates CD81 expression.

PubMed

Ke, Po-Yuan; Chen, Steve S-L

2013-01-01

So far how hepatitis C virus (HCV) replication modulates subsequent virus growth and propagation still remains largely unknown. Here we determine the impact of HCV replication status on the consequential virus growth by comparing normal and high levels of HCV RNA expression. We first engineered a full-length, HCV genotype 2a JFH1 genome containing a blasticidin-resistant cassette inserted at amino acid residue of 420 in nonstructural (NS) protein 5A, which allowed selection of human hepatoma Huh7 cells stably-expressing HCV. Short-term establishment of HCV stable cells attained a highly-replicating status, judged by higher expressions of viral RNA and protein as well as higher titer of viral infectivity as opposed to cells harboring the same genome without selection. Interestingly, maintenance of highly-replicating HCV stable cells led to decreased susceptibility to HCV pseudotyped particle (HCVpp) infection and downregulated cell surface level of CD81, a critical HCV entry (co)receptor. The decreased CD81 cell surface expression occurred through reduced total expression and cytoplasmic retention of CD81 within an endoplasmic reticulum -associated compartment. Moreover, productive viral RNA replication in cells harboring a JFH1 subgenomic replicon containing a similar blasticidin resistance gene cassette in NS5A and in cells robustly replicating full-length infectious genome also reduced permissiveness to HCVpp infection through decreasing the surface expression of CD81. The downregulation of CD81 surface level in HCV RNA highly-replicating cells thus interfered with reinfection and led to attenuated viral amplification. These findings together indicate that the HCV RNA replication status plays a crucial determinant in HCV growth by modulating the expression and intracellular localization of CD81.

Active RNA Replication of Hepatitis C Virus Downregulates CD81 Expression

PubMed Central

Ke, Po-Yuan; Chen, Steve S.-L.

2013-01-01

So far how hepatitis C virus (HCV) replication modulates subsequent virus growth and propagation still remains largely unknown. Here we determine the impact of HCV replication status on the consequential virus growth by comparing normal and high levels of HCV RNA expression. We first engineered a full-length, HCV genotype 2a JFH1 genome containing a blasticidin-resistant cassette inserted at amino acid residue of 420 in nonstructural (NS) protein 5A, which allowed selection of human hepatoma Huh7 cells stably-expressing HCV. Short-term establishment of HCV stable cells attained a highly-replicating status, judged by higher expressions of viral RNA and protein as well as higher titer of viral infectivity as opposed to cells harboring the same genome without selection. Interestingly, maintenance of highly-replicating HCV stable cells led to decreased susceptibility to HCV pseudotyped particle (HCVpp) infection and downregulated cell surface level of CD81, a critical HCV entry (co)receptor. The decreased CD81 cell surface expression occurred through reduced total expression and cytoplasmic retention of CD81 within an endoplasmic reticulum -associated compartment. Moreover, productive viral RNA replication in cells harboring a JFH1 subgenomic replicon containing a similar blasticidin resistance gene cassette in NS5A and in cells robustly replicating full-length infectious genome also reduced permissiveness to HCVpp infection through decreasing the surface expression of CD81. The downregulation of CD81 surface level in HCV RNA highly-replicating cells thus interfered with reinfection and led to attenuated viral amplification. These findings together indicate that the HCV RNA replication status plays a crucial determinant in HCV growth by modulating the expression and intracellular localization of CD81. PMID:23349980

Prognostic significance of lactate/proton symporters MCT1, MCT4, and their chaperone CD147 expressions in urothelial carcinoma of the bladder.

PubMed

Choi, Jung-Woo; Kim, Younghye; Lee, Ju-Han; Kim, Young-Sik

2014-07-01

To investigate the prognostic significance of lactate/proton monocarboxylate transporters MCT1, MCT4, and their chaperone CD147 expressions in urothelial carcinoma of the bladder (UCB). We examined the expressions of MCT1, MCT4, and CD147 proteins in a total of 360 cases of UCB by immunohistochemistry. The immunohistochemical expressions were quantified using an ImageJ-based analysis program. MCT1, MCT4, and CD147 expressions were increased in 130 (36.1%), 168 (46.7%), and 228 (63.3%) UCB cases, respectively. Most tumor cells showed diffuse membranous staining, whereas normal urothelial cells showed negative or weak staining. High levels of MCT1 expression correlated with high World Health Organization grade (P<.001), advanced tumor node metastasis (TNM) stage (P<.001), nonpapillary growth type (P<.001), and lymphatic tumor invasion (P=.010), whereas high levels of MCT4 expression did not significantly correlate with any of these variables. High CD147 expression was associated with high World Health Organization grade (P<.001), advanced tumor node metastatis stage (P<.001), and nonpapillary growth type (P=.003). Univariate analyses revealed that high MCT1 (P<.001) and CD147 (P=.029) expressions were associated with poor overall survival and that high MCT4 expression was correlated with poor recurrence-free survival (P=.036). Multivariate analyses revealed that high MCT1 and MCT4 expressions were independent prognostic factors for poor overall survival and poor recurrence-free survival, respectively, in UCB patients. Our results indicate that increased MCT1, MCT4, and CD147 expressions have prognostic implications in UCB and suggest their roles in urothelial cancer metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

Short-Term Clinical Disease Progression in HIV-Infected Patients Receiving Combination Antiretroviral Therapy: Results from the TREAT Asia HIV Observational Database

PubMed Central

Srasuebkul, Preeyaporn; Lim, Poh Lian; Lee, Man Po; Kumarasamy, Nagalingeswaran; Zhou, Jialun; Sirisanthana, Thira; Li, Patrick C. K.; Kamarulzaman, Adeeba; Oka, Shinichi; Phanuphak, Praphan; Vonthanak, Saphonn; Merati, Tuti P.; Chen, Yi-Ming A.; Sungkanuparph, Somnuek; Tau, Goa; Zhang, Fujie; Lee, Christopher K. C.; Ditangco, Rossana; Pujari, Sanjay; Choi, Jun Y.; Smith, Jeffery; Law, Matthew G.

2009-01-01

Objective The aim of our study was to develop, on the basis of simple clinical data, predictive short-term risk equations for AIDS or death in Asian patients infected with human immunodeficiency virus (HIV) who were included in the TREAT Asia HIV Observational Database. Methods Inclusion criteria were highly active antiretroviral therapy initiation and completion of required laboratory tests. Predictors of short-term AIDS or death were assessed using Poisson regression. Three different models were developed: a clinical model, a CD4 cell count model, and a CD4 cell count and HIV RNA level model. We separated patients into low-risk, high-risk, and very high-risk groups according to the key risk factors Identified. Results In the clinical model, patients with severe anemia or a body mass index (BMI; calculated as the weight in kilograms divided by the square of the height in meters) ≤18 were at very high risk, and patients who were aged <40 years or were male and had mild anemia were at high risk. In the CD4 cell count model, patients with a CD4 cell count <50 cells/µL, severe anemia, or a BMI ≤18 were at very high risk, and patients who had a CD4 cell count of 51–200 cells/µL, were aged <40 years, or were male and had mild anemia were at high risk. In the CD4 cell count and HIV RNA level model, patients with a CD4 cell count <50 cells/µL, a detectable viral load, severe anemia, or a BMI ≤18 were at very high risk, and patients with a CD4 cell count of 51–200 cells/µL and mild anemia were at high risk. The incidence of new AIDS or death in the clinical model was 1.3, 4.9, and 15.6 events per 100 person-years in the low-risk, high-risk, and very high-risk groups, respectively. In the CD4 cell count model the respective incidences were 0.9, 2.7, and 16.02 events per 100 person-years; in the CD4 cell count and HIV RNA level model, the respective incidences were 0.8, 1.8, and 6.2 events per 100 person-years. Conclusions These models are simple enough for widespread use in busy clinics and should allow clinicians to identify patients who are at high risk of AIDS or death in Asia and the Pacific region and in resource-poor settings. PMID:19226231

High levels of interleukin-8, soluble CD4 and soluble CD8 in bullous pemphigoid blister fluid. The relationship between local cytokine production and lesional T-cell activities.

PubMed

Sun, C C; Wu, J; Wong, T T; Wang, L F; Chuan, M T

2000-12-01

Bullous pemphigoid (BP) is an inflammatory subepidermal blistering disease associated with autoantibodies that recognize hemidesmosomal proteins. In addition to autoantibodies, the cell-mediated immune reaction is considered to play an important part in blister formation. Objectives To investigate some T-cell activation markers and inflammatory cytokines in the blister fluid and sera of patients with BP. We measured soluble CD4 (sCD4) and soluble CD8 (sCD8), which have been, respectively, associated with CD4 and CD8 T-cell activation. Enzyme-linked immunosorbent assays were also used to quantify the production of the leucocyte chemoattractant interleukin (IL) -8 and of the cytokines IL-1alpha, IL-1beta, IL-6, IL-10 and tumour necrosis factor-alpha in the blister fluid and sera of 11 patients with BP. The mean +/- SD level of sCD4 in patients' blisters (42.4 +/- 25.0 units mL-1) was significantly elevated (P < 0.005) compared with that in their sera (11.2 +/- 8.9) and that in the suction blisters of 10 healthy people (11.4 +/- 5.4; P < 0.005). Mean +/- SD IL-8 concentrations in BP blisters (4683.6 +/- 3878.1 pg mL-1) were much higher than those in their sera (17.1 +/- 18.9; P < 0.001), and were very significantly elevated (P < 0.005) in comparison with those in suction blisters of healthy persons (512 +/- 292). sCD4 levels in BP blisters were inversely related to IL-10 levels (P = 0. 03, r2 = 0.85), IL-8 levels were positively related to sCD8 levels (P = 0.01, r2 = 0.54), and IL-1beta levels were positively related to sCD8 concentrations (P < 0.005, r2 = 0.65). The correlations suggest that there is a delicately orchestrated network of cytokines and cell-mediated immunity operating in BP blisters.

High levels of circulating VEGFR2+ Bone marrow-derived progenitor cells correlate with metastatic disease in patients with pediatric solid malignancies.

PubMed

Taylor, Melissa; Rössler, Jochen; Geoerger, Birgit; Laplanche, Agnès; Hartmann, Olivier; Vassal, Gilles; Farace, Françoise

2009-07-15

Pediatric solid malignancies display important angiogenic potential, and blocking tumor angiogenesis represents a new therapeutic approach for these patients. Recent studies have evidenced rare circulating cells with endothelial features contributing to tumor neovascularization and have shown the pivotal role of bone marrow-derived (BMD) progenitor cells in metastatic disease progression. We measured these cells in patients with pediatric solid malignancies as a prerequisite to clinical trials with antiangiogenic therapy. Peripheral blood was drawn from 45 patients with localized (n = 23) or metastatic (n = 22) disease, and 20 healthy subjects. Subsets of circulating vascular endothelial growth factor receptor (VEGFR)2+-BMD progenitor cells, defined as CD45-CD34+VEGFR2(KDR)+7AAD- and CD45(dim)CD34+VEGFR2+7AAD- events, were measured in progenitor-enriched fractions by flow cytometry. Mature circulating endothelial cells (CEC) were measured in whole blood as CD31+CD146+CD45-7AAD- viable events. Data were correlated with VEGF and sVEGFR2 plasma levels. The CD45-CD34+VEGFR2(KDR)+7AAD- subset represented <0.003% of circulating BMD progenitor cells (< or =0.05 cells/mL). However, the median level (range) of the CD45(dim)CD34+VEGFR2+7AAD- subset was higher in patients compared with healthy subjects, 1.5% (0%-10.3%) versus 0.3% (0%-1.6%) of circulating BMD progenitors (P < 0.0001), and differed significantly between patients with localized and metastatic disease, 0.7% (0%-8.6%) versus 2.9% (0.6%-10.3%) of circulating BMD progenitors (P < 0.001). Median CEC value was 7 cells/mL (0-152 cells/mL) and similar in all groups. Unlike VEGFR2+-BMD progenitors, neither CECs, VEGF, or sVEGFR2 plasma levels correlated with disease status. High levels of circulating VEGFR2+-BMD progenitor cells correlated with metastatic disease. Our study provides novel insights for angiogenesis mechanisms in pediatric solid malignancies for which antiangiogenic targeting of VEGFR2+-BMD progenitors could be of interest.

CD133(+)/CD44(+)/Oct4(+)/Nestin(+) stem-like cells isolated from Panc-1 cell line may contribute to multi-resistance and metastasis of pancreatic cancer.

PubMed

Wang, Dongqing; Zhu, Haitao; Zhu, Ying; Liu, Yanfang; Shen, Huiling; Yin, Ruigen; Zhang, Zhijian; Su, Zhaoliang

2013-05-01

Pancreatic cancer is an aggressive malignant disease. Owing to the lack of early symptoms, accompanied by extensive metastasis and high resistance to chemotherapy, pancreatic adenocarcinoma becomes the fourth leading cause of cancer-related deaths. In this study, we identified a subpopulation of cells isolated from the Panc-1 cell line and named pancreatic cancer stem-like cells. These Panc-1 stem-like cells expressed high levels of CD133/CD44/Oct4/Nestin. Compared to Panc-1 cells, Panc-1 stem-like cells were resistant to gemcitabine and expressed high levels of MDR1; furthermore, Panc-1 stem-like cells have high anti-apoptotic, but weak proliferative potential. These results indicated that Panc-1 stem-like cells, as a novel group, may be a potential major cause of pancreatic cancer multidrug resistance and extensive metastasis. Copyright © 2012 Elsevier GmbH. All rights reserved.

Autoimmune Lymphoproliferative Syndrome-FAS Patients Have an Abnormal Regulatory T Cell (Treg) Phenotype but Display Normal Natural Treg-Suppressive Function on T Cell Proliferation.

PubMed

Mazerolles, Fabienne; Stolzenberg, Marie-Claude; Pelle, Olivier; Picard, Capucine; Neven, Benedicte; Fischer, Alain; Magerus-Chatinet, Aude; Rieux-Laucat, Frederic

2018-01-01

Autoimmune lymphoproliferative syndrome (ALPS) with FAS mutation (ALPS-FAS) is a nonmalignant, noninfectious, lymphoproliferative disease with autoimmunity. Given the central role of natural regulatory T cells (nTregs) in the control of lymphoproliferation and autoimmunity, we assessed nTreg-suppressive function in 16 patients with ALPS-FAS. The proportion of CD25 high CD127 low Tregs was lower in ALPS-FAS patients than in healthy controls. This subset was correlated with a reduced CD25 expression in CD3 + CD4 + T cells from ALPS patients and thus an abnormally low proportion of CD25 high FOXP3 + Helios + T cells. The ALPS patients also displayed a high proportion of naïve Treg (FOXP3 low CD45RA + ) and an unusual subpopulation (CD4 + CD127 low CD15s + CD45RA + ). Despite this abnormal phenotype, the CD25 high CD127 low Tregs' suppressive function was unaffected. Furthermore, conventional T cells from FAS -mutated patients showed normal levels of sensitivity to Treg suppression. An abnormal Treg phenotype is observed in circulating lymphocytes of ALPS patients. However, these Tregs displayed a normal suppressive function on T effector proliferation in vitro . This is suggesting that lymphoproliferation observed in ALPS patients does not result from Tregs functional defect or T effector cells insensitivity to Tregs suppression.

Transcriptional network profile on synovial fluid T cells in psoriatic arthritis.

PubMed

Fiocco, Ugo; Martini, Veronica; Accordi, Benedetta; Caso, Francesco; Costa, Luisa; Oliviero, Francesca; Scanu, Anna; Facco, Monica; Boso, Daniele; Gatto, Mariele; Felicetti, Mara; Frallonardo, Paola; Ramonda, Roberta; Piva, Lucia; Zambello, Renato; Agostini, Carlo; Scarpa, Raffaele; Basso, Giuseppe; Semenzato, Gianpietro; Dayer, Jean-Michel; Punzi, Leonardo; Doria, Andrea

2015-09-01

The objective of the study was to quantify the transcriptional profile, as the main T cell lineage-transcription factors on synovial fluid (SF) T cells, in relation to SF cytokines and T cell frequencies (%) of psoriatic arthritis (PsA) patients. Reverse phase protein array was employed to identify interleukin (IL)-23Rp19-, FOXP3- and related orphan receptor gamma T (RORγt)- protein and Janus associated tyrosine kinases 1 (JAK1), signal transducer and activator and transcription 1 (STAT1), STAT3 and STAT5 phosphoproteins in total T cell lysates from SF of PsA patients. IL-1β, IL-2, IL-6, IL-21 and interferon (INF)-γ were measured using a multiplex bead immunoassay in SF from PsA patients and peripheral blood (PB) from healthy controls (HC). Frequencies of CD4(+)CD25(-), CD4(+)CD25(high) FOXP3(+) and CD4(+)CD25(high) CD127(low) Treg, and either mean fluorescence intensity (MFI) of FOXP3(+) on CD4(+) Treg or MFI of classic IL-6 receptor (IL-6R) α expression on CD4(+)CD25(-) helper/effector T cells (Th/eff) and Treg cells, were quantified in SF of PsA patients and in PB from HC by flow cytometry (FC). In PsA SF samples, IL-2, IL-21 and IFN-γ were not detectable, whereas IL-6 and IL-1β levels were higher than in SF of non-inflammatory osteoarthritis patients. Higher levels of IL-23R-, FOXP3- and RORγt proteins and JAK1, STAT1, STAT3 and STAT5 were found in total T cells from SF of PsA patients compared with PB from HC. Direct correlations between JAK1 Y1022/Y1023 and STAT5 Y694, and STAT3 Y705 and IL6, were found in SF of PsA patients. Increased proportion of CD4(+)CD25(high) FOXP3(+) and CD4(+)CD25(high) CD127(low) Treg cells and brighter MFI of IL-6Rα were observed both on CD4(+)CD25(high)- and CD4(+)CD25(-) T cells in PsA SF. The study showed a distinctive JAK1/STAT3/STAT5 transcriptional network on T cells in the joint microenvironment, outlining the interplay of IL-6, IL-23, IL-1β and γC cytokines in the polarization and plasticity of Th17 and Treg cells, which might participate in the perpetuation of joint inflammation in PsA patients.

Effects of highly active antiretroviral therapy on thymical reconstitution of CD4 T lymphocytes in vertically HIV-infected children.

PubMed

Correa, Rafael; Muñoz-Fernández, Angeles

2002-05-24

CD4 T-cell percentages, viral load and thymic function measured as T-cell receptor rearrangement excision circle (TREC) levels were determined every 2-3 months in six treated HIV-infected children for 4 years. All children experienced a marked increase in CD4 cell count after therapy, accompanied by a concomitantly marked increase in TREC levels. In children, the decrease in viral load caused by antiviral therapy leads to an increase in CD4 T cells, mainly because of a recovery in the thymic production of new T cells.

HIV-1 disease progression during highly active antiretroviral therapy: an application using population-level data in British Columbia: 1996-2011.

PubMed

Nosyk, Bohdan; Min, Jeong; Lima, Viviane D; Yip, Benita; Hogg, Robert S; Montaner, Julio S G

2013-08-15

Accurately estimating rates of disease progression is of central importance in developing mathematical models used to project outcomes and guide resource allocation decisions. Our objective was to specify a multivariate regression model to estimate changes in disease progression among individuals on highly active antiretroviral treatment in British Columbia, Canada, 1996-2011. We used population-level data on disease progression and antiretroviral treatment utilization from the BC HIV Drug Treatment Program. Disease progression was captured using longitudinal CD4 and plasma viral load testing data, linked with data on antiretroviral treatment. The study outcome was categorized into (CD4 count ≥ 500, 500-350, 350-200, <200 cells/mm, and mortality). A 5-state continuous-time Markov model was used to estimate covariate-specific probabilities of CD4 progression, focusing on temporal changes during the study period. A total of 210,083 CD4 measurements among 7421 individuals with HIV/AIDS were included in the study. Results of the multivariate model suggested that current highly active antiretroviral treatment at baseline, lower baseline CD4 (<200 cells/mm), and extended durations of elevated plasma viral load were each associated with accelerated progression. Immunological improvement was accelerated significantly from 2004 onward, with 23% and 46% increases in the probability of CD4 improvement from the fourth CD4 stratum (CD4 < 200) in 2004-2008 and 2008-2011, respectively. Our results demonstrate the impact of innovations in antiretroviral treatment and treatment delivery at the population level. These results can be used to estimate a transition probability matrix flexible to changes in the observed mix of clients in different clinical stages and treatment regimens over time.

Association between tuberculosis and atopy: role of the CD14-159C/T polymorphism.

PubMed

Baççioğlu Kavut, A; Kalpaklioğlu, F; Birben, E; Ayaslioğlu, E

2012-01-01

The development of allergic hypersensitivity depends on both genetic and environmental factors. Different amounts of microbial products could affect patients with atopy and different genotypes. We aimed to evaluate the role of varying degrees of exposure to infection by Mycobacterium tuberculosis (tuberculosis) in atopic patients and analyze the association with genetic factors. We performed CD14-159C/T genotyping in atopic patients (n=118) and healthy individuals (n=62) and recorded the following variables: rural lifestyle, exposure to persons with tuberculosis, bacille Calmette-Guerin (BCG) vaccination, tuberculin skin test (TST), skin prick test, and phenotypes of atopy. Blood samples were analyzed for soluble-CD14 (sCD14), interferon (IFN) y, total immunoglobulin (Ig) E, and eosinophil levels. A score was used to identify the likelihood of exposure to tuberculosis. Almost all the study participants had had a BCG vaccination, and half had a positive TST result. No differences were observed between atopic patients with high/low tuberculosis scores and CD14 genotypes in terms of atopic phenotypes, allergen sensitization, and levels of total IgE, sCD14, and IFN-y. However, the frequency of asthma was higher in atopic patients with a high tuberculosis score and was not associated with CD14 genotypes. Eosinophil counts in blood were higher in atopic patients with a high tuberculosis score and CC+CT genotypes. These results suggest that the C allele of the CD14-159C/T polymorphism has a marked effect on eosinophil levels in atopic patients with increased exposure to tuberculosis. In addition, the degree of exposure to tuberculosis in atopic patients may modify the development of asthma.

CD71(high) population represents primitive erythroblasts derived from mouse embryonic stem cells.

PubMed

Chao, Ruihua; Gong, Xueping; Wang, Libo; Wang, Pengxiang; Wang, Yuan

2015-01-01

The CD71/Ter119 combination has been widely used to reflect dynamic maturation of erythrocytes in vivo. However, because CD71 is expressed on all proliferating cells, it is unclear whether it can be utilized as an erythrocyte-specific marker during differentiation of embryonic stem cells (ESCs). In this study, we revealed that a population expressing high level of CD71 (CD71(high)) during mouse ESC differentiation represented an in vitro counterpart of yolk sac-derived primitive erythroblasts (EryPs) isolated at 8.5days post coitum. In addition, these CD71(high) cells went through "maturational globin switching" and enucleated during terminal differentiation in vitro that were similar to the yolk sac-derived EryPs in vivo. We further demonstrated that the formation of CD71(high) population was regulated differentially by key factors including Scl, HoxB4, Eaf1, and Klf1. Taken together, our study provides a technical advance that allows efficient segregation of EryPs from differentiated ESCs in vitro for further understanding molecular regulation during primitive erythropoiesis. Copyright © 2014. Published by Elsevier B.V.

CD59 Underlines the Antiatherosclerotic Effects of C-Phycocyanin on Mice

PubMed Central

Chu, Xian-Ming; Xu, Ying-Jie; Yang, Fan; Lv, Cong-Yi; Nie, Shu-min

2013-01-01

The effects of C-phycocyanin (C-PC) on atherosclerosis and the regulatory effects of CD59 gene on anti-atherosclerotic roles of C-PC were investigated. Apolipoprotein E knockout (ApoE(−/−)) mice were randomly divided into four groups: control group, C-PC treatment group, CD59 transfection group and C-PC+CD59 synergy group. The mice were fed with high-fat-diet and treated with drug intervention at the same time. Results showed the atherosclerotic mouse model was successfully established. CD59 was over-expressed in blood and tissue cells. Single CD59 or C-PC could reduce blood lipid levels and promote the expression of anti-apoptotic Bcl-2 but inhibit pro-apoptotic Fas proteins in endothelial cells. The expression levels of cell cycle protein D1 (Cyclin D1) and mRNA levels of cyclin dependent protein kinase 4 (CDK4) in smooth muscle cells were restrained by CD59 and C-PC. CD59 or C-PC alone could inhibit the formation of atherosclerotic plaque by suppressing MMP-2 protein expression. In addition, C-PC could promote CD59 expression. So both CD59 and C-PC could inhibit the progress of atherosclerosis, and the anti-atherosclerotic effects of C-PC might be fulfilled by promoting CD59 expression, preventing smooth muscle cell proliferation and the apoptosis of endothelial cells, reducing blood fat levels, and at last inhibiting the development of atherosclerosis. PMID:24319687

Health Risk Assessment of Dietary Cadmium Intake: Do Current Guidelines Indicate How Much is Safe?

PubMed

Satarug, Soisungwan; Vesey, David A; Gobe, Glenda C

2017-03-01

Cadmium (Cd), a food-chain contaminant, is a significant health hazard. The kidney is one of the primary sites of injury after chronic Cd exposure. Kidney-based risk assessment establishes the urinary Cd threshold at 5.24 μg/g creatinine, and tolerable dietary intake of Cd at 62 μg/day per 70-kg person. However, cohort studies show that dietary Cd intake below a threshold limit and that tolerable levels may increase the risk of death from cancer, cardiovascular disease, and Alzheimer's disease. We evaluated if the current tolerable dietary Cd intake guideline and urinary Cd threshold limit provide sufficient health protection. Staple foods constitute 40-60% of total dietary Cd intake by average consumers. Diets high in shellfish, crustaceans, mollusks, spinach, and offal add to dietary Cd sources. Modeling studies predict the current tolerable dietary intake corresponding to urinary Cd of 0.70-1.85 μg/g creatinine in men and 0.95-3.07 μg/g creatinine in women. Urinary Cd levels of < 1 μg/g creatinine were associated with progressive kidney dysfunction and peripheral vascular disease. A urinary Cd of 0.37 μg/g creatinine was associated with breast cancer, whereas dietary Cd of 16-31.5 μg/day was associated with 25-94% increase in risk of estrogen receptor-positive breast cancer. Modeling shows that dietary intake levels for Cd exceed the levels associated with kidney damage and many other adverse outcomes. Thus, the threshold level of urinary Cd should be re-evaluated. A more restrictive dietary intake guideline would afford enhanced health protection from this pervasive toxic metal. Citation: Satarug S, Vesey DA, Gobe GC. 2017. Health risk assessment of dietary cadmium intake: do current guidelines indicate how much is safe? Environ Health Perspect 125:284-288; http://dx.doi.org/10.1289/EHP108.

Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury.

PubMed

Hasan, Djo; Blankman, Paul; Nieman, Gary F

2017-09-01

Severe pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release. High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high ATP levels despite the conversion to adenosine. Above a certain level, extracellular ATP molecules act as danger-associated molecular patterns (DAMPs) and activate the pro-inflammatory response of the innate immunity through purinergic receptors on the surface of the immune cells. This results in lung tissue inflammation, capillary leakage, interstitial and alveolar oedema and lung injury reducing the production of surfactant by the damaged AT II cells and deactivating the surfactant function by the concomitant extravasated serum proteins through capillary leakage followed by a substantial increase in alveolar surface tension and alveolar collapse. The resulting inhomogeneous ventilation of the lungs is an important mechanism in the development of ventilation-induced lung injury. The high levels of extracellular ATP and the upregulation of ecto-enzymes and soluble enzymes that hydrolyse ATP to adenosine (CD39 and CD73) increase the extracellular adenosine levels that inhibit the innate and adaptive immune responses rendering the host susceptible to infection by invading microorganisms. Moreover, high levels of extracellular adenosine increase the expression, the production and the activation of pro-fibrotic proteins (such as TGF-β, α-SMA, etc.) followed by the establishment of lung fibrosis.

Posttransplant soluble CD30 as a predictor of acute renal allograft rejection.

PubMed

Kamali, Koosha; Abbasi, Mohammad Amin; Farokhi, Babak; Abbasi, Ata; Fallah, Parvane; Seifee, Mohammad Hasan; Ghadimi, Naime; Rezaie, Alireza R

2009-12-01

Recent results have indicated that high prerenal and postrenal transplant soluble CD30 levels may be associated with an increased acute rejection and graft loss. The aim of this study was to evaluate the feasibility of using serum sCD30 as a marker for predicting acute graft rejection. In this prospective study,we analyzed clinical data of 80 patients, whose pretransplant and posttransplant serum levels of sCD30 were detected by enzyme-linked immunoassay. Eight patients developed acute rejection, 7 patients showed delayed graft function, and 65 recipients experienced an uncomplicated course group. The patients were followed for 12 months, and there were no deaths. Preoperative sCD30 levels of 3 groups were 96.2 -/+ 32.5, 80.2 -/+ 28.3, and 76.8 -/+ 29.8 U/mL (P = .28). After transplant, a significant decrease in the sCD30 level was detected in 3 groups on day 14 posttransplant (P < .001), while sCD30 levels of acute rejection group remained significantly higher than delayed graft function and nonrejecting patients (28.3 -/+ 5.2, 22.1 -/+ 3.2, and 19.8 -/+ 4.7 U/mL) (P = .02). Positive panel reactive antibody was not statistically different among groups (P = .05). Also, hemodialysis did not affect sCD30 levels (P = .05). Receiver operating characteristic curve demonstrated that the sCD30 level on day 14 posttransplant could discriminate patients who subsequently suffered acute allograft rejection (area under receiver operating characteristic curve, 0.95). According to receiver operating characteristic curve, 20 U/mL may be the optimal operational cutoff level to predict impending graft rejection (specificity 93.8%, sensitivity 83.3%). Measurement of the soluble CD30 level on day 14 after transplant might offer a noninvasive means for recognizing patients at risk of acute graft rejection during the early posttransplant period.

Screening of a new cadmium hyperaccumulator, Galinsoga parviflora, from winter farmland weeds using the artificially high soil cadmium concentration method.

PubMed

Lin, Lijin; Jin, Qian; Liu, Yingjie; Ning, Bo; Liao, Ming'an; Luo, Li

2014-11-01

A new method, the artificially high soil cadmium (Cd) concentration method, was used to screen for Cd hyperaccumulators among winter farmland weeds. Galinsoga parviflora was the most promising remedial plant among 5 Cd accumulators or hyperaccumulators. In Cd concentration gradient experiments, as soil Cd concentration increased, root and shoot biomass decreased, and their Cd contents increased. In additional concentration gradient experiments, superoxide dismutase and peroxidase activities increased with soil Cd concentrations up to 75 mg kg(-1) , while expression of their isoenzymes strengthened. Catalase (CAT) activity declined and CAT isoenzyme expression weakened at soil Cd concentrations less than 50 mg kg(-1) . The maxima of Cd contents in shoots and roots were 137.63 mg kg(-1) and 105.70 mg kg(-1) , respectively, at 100 mg kg(-1) Cd in soil. The root and shoot bioconcentration factors exceeded 1.0, as did the translocation factor. In a field experiment, total extraction of Cd by shoots was 1.35 mg m(-2) to 1.43 mg m(-2) at soil Cd levels of 2.04 mg kg(-1) to 2.89 mg kg(-1) . Therefore, the artificially high soil Cd concentration method was effective for screening Cd hyperaccumulators. Galinsoga parviflora is a Cd hyperaccumulator that could be used to efficiently remediate Cd-contaminated farmland soil. © 2014 SETAC.

Response of Bacterioplankton Communities to Cadmium Exposure in Coastal Water Microcosms with High Temporal Variability

PubMed Central

Wang, Kai; Xiong, Jinbo; Chen, Xinxin; Zheng, Jialai; Hu, Changju; Yang, Yina; Zhu, Jianlin

2014-01-01

Multiple anthropogenic disturbances to bacterial diversity have been investigated in coastal ecosystems, in which temporal variability in the bacterioplankton community has been considered a ubiquitous process. However, far less is known about the temporal dynamics of a bacterioplankton community responding to pollution disturbances such as toxic metals. We used coastal water microcosms perturbed with 0, 10, 100, and 1,000 μg liter−1 of cadmium (Cd) for 2 weeks to investigate temporal variability, Cd-induced patterns, and their interaction in the coastal bacterioplankton community and to reveal whether the bacterial community structure would reflect the Cd gradient in a temporally varying system. Our results showed that the bacterioplankton community structure shifted along the Cd gradient consistently after a 4-day incubation, although it exhibited some resistance to Cd at low concentration (10 μg liter−1). A process akin to an arms race between temporal variability and Cd exposure was observed, and the temporal variability overwhelmed Cd-induced patterns in the bacterial community. The temporal succession of the bacterial community was correlated with pH, dissolved oxygen, NO3−-N, NO2−-N, PO43−-P, dissolved organic carbon, and chlorophyll a, and each of these parameters contributed more to community variance than Cd did. However, elevated Cd levels did decrease the temporal turnover rate of community. Furthermore, key taxa, affiliated to the families Flavobacteriaceae, Rhodobacteraceae, Erythrobacteraceae, Piscirickettsiaceae, and Alteromonadaceae, showed a high frequency of being associated with Cd levels during 2 weeks. This study provides direct evidence that specific Cd-induced patterns in bacterioplankton communities exist in highly varying manipulated coastal systems. Future investigations on an ecosystem scale across longer temporal scales are needed to validate the observed pattern. PMID:25326310

Identification, characterization and isolation of a common progenitor for osteoclasts, macrophages and dendritic cells from murine bone marrow and periphery

PubMed Central

Jacome-Galarza, Christian E.; Lee, Sun-Kyeong; Lorenzo, Joseph A.; LeonardoAguila, Hector

2012-01-01

Osteoclasts are specialized bone resorbing cells that derive from monocyte precursors. We have identified three populations of cells with high osteoclastogenic potential in murine bone marrow, which expressed the phenotype: B220−CD3−CD11b−/low CD115+ and either CD117hi, CD117intermediate or CD117low. We have evaluated these populations for their ability to also generate macrophages and dendritic cells. At a single cell level, the population expressing higher CD117 levels was able to generate bone-resorbing osteoclasts, phagocytic macrophages and antigen-presenting dendritic cells in vitro with efficiencies of over 90 percent, indicating that there exists a common developmental pathway for these cell types. Cells with osteoclastogenic potential also exist in blood and peripheral hematopoietic organs. Their functional meaning and/or their relationship with bone marrow progenitors is not well established. Hence, we characterized murine peripheral cell populations for their ability to form osteoclasts, macrophages and dendritic cells in vitro. The spleen and peripheral blood monocyte progenitors share phenotypic markers with bone marrow progenitors, but differ in their expression of CD11b, which was low in bone marrow but high in periphery. We propose that circulating monocyte progenitors are derived from a common bone marrow osteoclasts/macrophage/dendritic cell progenitor (OcMDC), which we have now characterized at a clonal level. However, the lineage relationship between the bone marrow and peripheral monocyte progenitors has yet to be defined. PMID:23165930

Combined dyslipidemia in childhood.

PubMed

Kavey, Rae-Ellen W

2015-01-01

Combined dyslipidemia (CD) is now the predominant dyslipidemic pattern in childhood, characterized by moderate-to-severe elevation in triglycerides and non-high-density lipoprotein cholesterol (non-HDL-C), minimal elevation in low-density lipoprotein cholesterol (LDL-C), and reduced HDL-C. Nuclear magnetic resonance spectroscopy shows that the CD pattern is represented at the lipid subpopulation level as an increase in small, dense LDL and in overall LDL particle number plus a reduction in total HDL-C and large HDL particles, a highly atherogenic pattern. In youth, CD occurs almost exclusively with obesity and is highly prevalent, seen in more than 40% of obese adolescents. CD in childhood predicts pathologic evidence of atherosclerosis and vascular dysfunction in adolescence and young adulthood, and early clinical cardiovascular events in adult life. There is a tight connection between CD, visceral adiposity, insulin resistance, nonalcoholic fatty liver disease, and the metabolic syndrome, suggesting an integrated pathophysiological response to excessive weight gain. Weight loss, changes in dietary composition, and increases in physical activity have all been shown to improve CD significantly in children and adolescents in short-term studies. Most importantly, even small amounts of weight loss are associated with significant decreases in triglyceride levels and increases in HDL-C levels with improvement in lipid subpopulations. Diet change focused on limitation of simple carbohydrate intake with specific elimination of all sugar-sweetened beverages is very effective. Evidence-based recommendations for initiating diet and activity change are provided. Rarely, drug therapy is needed, and the evidence for drug treatment of CD in childhood is reviewed. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

High dose of plasmid IL-15 inhibits immune responses in an influenza non-human primates immunogenicity model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yin Jiangmei; Dai Anlan; Laddy, Dominick J.

2009-10-10

Interleukin (IL)-15, is a cytokine that is important for the maintenance of long-lasting, high-avidity T cell response to invading pathogens and has, therefore, been used in vaccine and therapeutic platforms as an adjuvant. In addition to pure protein delivery, plasmids encoding the IL-15 gene have been utilized. However, it is critical to determine the appropriate dose to maximize the adjuvanting effects. We immunized rhesus macaques with different doses of IL-15 expressing plasmid in an influenza non-human primate immunogenicity model. We found that co-immunization of rhesus macaques with a Flu DNA-based vaccine and low doses of plasmid encoding macaque IL-15 enhancedmore » the production of IFN-gamma (0.5 mg) and the proliferation of CD4{sup +} and CD8{sup +} T cells, as well as T{sub CM} levels in proliferating CD8{sup +} T cells (0.25 mg). Whereas, high doses of IL-15 (4 mg) decrease the production of IFN-gamma and the proliferation of CD4{sup +} and CD8{sup +} T cells and T{sub CM} levels in the proliferating CD4{sup +} and CD8{sup +} T cells. In addition, the data of hemagglutination inhibition (HI) antibody titer suggest that although not significantly different, there appears to be a slight increase in antibodies at lower doses of IL-15. Importantly, however, the higher doses of IL-15 decrease the antibody levels significantly. This study demonstrates the importance of optimizing DNA-based cytokine adjuvants.« less

Early post-transplant immune monitoring can predict long-term kidney graft survival: soluble CD30 levels, anti-HLA antibodies and IgA-anti-Fab autoantibodies.

PubMed

Amirzargar, Mohammad Ali; Amirzargar, Aliakbar; Basiri, Abbas; Hajilooi, Mehrdad; Roshanaei, Ghodratollah; Rajabi, Gholamreza; Mohammadiazar, Sina; Solgi, Ghasem

2014-01-01

This study aimed to investigate the predictive power of anti-HLA antibodies, sCD30 levels and IgA-anti-Fab autoantibody before and early after transplantation in relation to long-term kidney allograft survival. Pre- and post-transplant sera samples of 59 living-unrelated donor kidney recipients were tested for above risk factors by enzyme-linked immunoabsorbent assay. 15 out of 59 cases experienced rejection episodes (failure group). Pre- and post-transplant high sCD30 levels were significantly associated with graft failure (P=0.02 and P=0.004) and decreased 4 year graft survival (P = 0.009 and P = 0.001). Higher frequency of post-transplant HLA class-II antibody in the absence of class-I antibody was observed in failure group (P=0.007). Patients with post-transplant HLA class-I and class-II antibodies either alone or in combination showed significant lower 4 year graft survival. Recipients with high sCD30 levels in the presence of HLA class-I or class-II antibodies within 2 weeks post-transplant had poor graft survival (P = 0.004 and P = 0.002, respectively). High levels of post-transplant IgA-anti-Fab antibody was more frequent in functioning-graft patients (P = 0.00001), correlated with decreased serum creatinine levels (P = 0.01) and associated with improved graft survival (P = 0.008). Our findings indicate the deleterious effect of early post-transplant HLA antibodies and increased sCD30 levels dependently and protective effect of IgA-anti-Fab antibodies on long-term renal graft outcomes. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Regulated expression of telomerase activity in human T lymphocyte development and activation

PubMed Central

1996-01-01

Telomerase, a ribonucleoprotein that is capable of synthesizing telomeric repeats, is expressed in germline and malignant cells, and is absent in most normal human somatic cells. The selective expression of telomerase has thus been proposed to be a basis for the immortality of the germline and of malignant cells. In the present study, telomerase activity was analyzed in normal human T lymphocytes. It was found that telomerase is expressed at a high level in thymocyte subpopulations, at an intermediate level in tonsil T lymphocytes, and at a low to undetectable level in peripheral blood T lymphocytes. Moreover, telomerase activity is highly inducible in peripheral T lymphocytes by activation through CD3 with or without CD28 costimulation, or by stimulation with phorbol myristate acetate (PMA)/ionomycin. The induction of telomerase by anti-CD3 plus anti-CD28 (anti-CD3/CD28) stimulation required RNA and protein synthesis, and was blocked by herbimycin A, an inhibitor of S pi protein tyrosine kinases. The immunosuppressive drug cyclosporin A selectively inhibited telomerase induction by PMA/ionomycin and by anti-CD3, but not by anti-CD3/CD28. Although telomerase activity in peripheral T lymphocytes was activation dependent and correlated with cell proliferation, it was not cell cycle phase restricted. These results indicate that the expression of telomerase in normal human T lymphocytes is both developmentally regulated and activation induced. Telomerase may thus play a permissive role in T cell development and in determining the capacity of lymphoid cells for cell division and clonal expansion. PMID:8676067

Impact of pyrene and cadmium co-contamination on prokaryotic community in coastal sediment microcosms.

PubMed

Ding, Qifang; Huang, Xiaolin; Hu, Hanjing; Hong, Man; Zhang, Demin; Wang, Kai

2017-12-01

Acute ecological impacts of co-contamination of polycyclic aromatic hydrocarbons (PAHs) and heavy metals on diversity and composition of coastal benthic prokaryotes were unclear. We took pyrene (Pyr) and cadmium (Cd) as the representatives and mimicked an eight-week exposure of moderate and high levels of Pyr, Cd and their mixtures. 16S rRNA amplicon sequencing was used to investigate interaction of the contaminants in temporal succession of prokaryotes. Generally, concentrations of Pyr and HCl-extractable Cd in the sediments were stable over time. Effects and interaction of Pyr and Cd on prokaryotic α-diversity were temporally- and dose-dependent with a decreasing trend in richness and Shannon index under various contamination regimes, particularly in the single-Cd contaminated groups at the early stage. Temporal variability and Pyr-induced pattern in prokaryotic composition were observed. However, Pyr and Cd showed a persistent interaction in prokaryotic composition after 7 days, altering successional trajectories of communities. The communities under Pyr contamination regardless of Cd could be at a developing stage for an active PAH-degrading community with appearance of a pioneer Cycloclasticus phylotype, persistently showing a strong correlation with Pyr level. The associations of phylotypes and Cd level were short-lived and weak, corresponding to the overall resistance of prokaryotic composition to Cd. In the high-throughput sequencing era, using microcosm experiment, we renewed the knowledge about how prokaryotes vary in terms of α-diversity, composition and specific taxa in response to co-contamination of model contaminants at a temporal scale. Copyright © 2017 Elsevier Ltd. All rights reserved.

CD25 is expressed by canine cutaneous mast cell tumors but not by cutaneous connective tissue mast cells.

PubMed

Meyer, A; Gruber, A D; Klopfleisch, R

2012-11-01

Canine cutaneous mast cell tumors (MCT) of different histological grades have distinct biological behaviors. However, little is known about underlying molecular mechanisms that lead to tumor development and increasing malignancy with higher tumor grade. Recent studies have identified the interleukin-2 receptor (IL-2R) subunits CD25 and CD2 as markers that distinguish nonneoplastic from neoplastic mast cells in human systemic mastocytosis. In this study, their potential as a marker for canine MCT and their possible impact on MCT carcinogenesis were evaluated. mRNA expression levels of both genes were compared between grade 1 (n = 12) and grade 3 (n = 8) MCT, and protein expression levels of CD25 were compared in 90 MCT of different tumor grades. mRNA expression levels of both CD25 and CD2 were upregulated in grade 3 MCT. In contrast, CD25 protein was expressed by fewer tumor cells and at decreased levels in grade 3 tumors, while most grade 1 MCT had strong CD25 protein expression. Moreover, CD25 was not expressed by nonneoplastic, resting cutaneous mast cells, while few presumably activated mast cells in tissue samples from dogs with allergic dermatitis had weak CD25 expression. Taken together, these findings suggest that CD25 may play a critical role in early MCT development and may be a stimulatory factor in grade 1 MCT, while grade 3 MCT seem to be less dependent on CD25. Because of the low number of CD25-positive tumor cells in high-grade tumors, the usefulness of CD25 as a tumor marker is, however, questionable.

Association of CD30 transcripts with Th1 responses and proinflammatory cytokines in patients with end-stage renal disease.

PubMed

Velásquez, Sonia Y; Opelz, Gerhard; Rojas, Mauricio; Süsal, Caner; Alvarez, Cristiam M

2016-05-01

High serum sCD30 levels are associated with inflammatory disorders and poor outcome in renal transplantation. The contribution to these phenomena of transcripts and proteins related to CD30-activation and -cleavage is unknown. We assessed in peripheral blood of end-stage renal disease patients (ESRDP) transcripts of CD30-activation proteins CD30 and CD30L, CD30-cleavage proteins ADAM10 and ADAM17, and Th1- and Th2-type immunity-related factors t-bet and GATA3. Additionally, we evaluated the same transcripts and release of sCD30 and 32 cytokines after allogeneic and polyclonal T-cell activation. In peripheral blood, ESRDP showed increased levels of t-bet and GATA3 transcripts compared to healthy controls (HC) (both P<0.01) whereas levels of CD30, CD30L, ADAM10 and ADAM17 transcripts were similar. Polyclonal and allogeneic stimulation induced higher levels of CD30 transcripts in ESRDP than in HC (both P<0.001). Principal component analysis (PCA) in allogeneic cultures of ESRDP identified two correlation clusters, one consisting of sCD30, the Th-1 cytokine IFN-γ, MIP-1α, RANTES, sIL-2Rα, MIP-1β, TNF-β, MDC, GM-CSF and IL-5, and another one consisting of CD30 and t-bet transcripts, IL-13 and proinflammatory proteins IP-10, IL-8, IL-1Rα and MCP-1. Reflecting an activated immune state, ESRDP exhibited after allostimulation upregulation of CD30 transcripts in T cells, which was associated with Th1 and proinflammatory responses. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Limited CD4+ T cell proliferation leads to preservation of CD4+ T cell counts in SIV-infected sooty mangabeys.

PubMed

Chan, Ming Liang; Petravic, Janka; Ortiz, Alexandra M; Engram, Jessica; Paiardini, Mirko; Cromer, Deborah; Silvestri, Guido; Davenport, Miles P

2010-12-22

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections result in chronic virus replication and progressive depletion of CD4+ T cells, leading to immunodeficiency and death. In contrast, 'natural hosts' of SIV experience persistent infection with high virus replication but no severe CD4+ T cell depletion, and remain AIDS-free. One important difference between pathogenic and non-pathogenic infections is the level of activation and proliferation of CD4+ T cells. We analysed the relationship between CD4+ T cell number and proliferation in HIV, pathogenic SIV in macaques, and non-pathogenic SIV in sooty mangabeys (SMs) and mandrills. We found that CD4+ T cell proliferation was negatively correlated with CD4+ T cell number, suggesting that animals respond to the loss of CD4+ T cells by increasing the proliferation of remaining cells. However, the level of proliferation seen in pathogenic infections (SIV in rhesus macaques and HIV) was much greater than in non-pathogenic infections (SMs and mandrills). We then used a modelling approach to understand how the host proliferative response to CD4+ T cell depletion may impact the outcome of infection. This modelling demonstrates that the rapid proliferation of CD4+ T cells in humans and macaques associated with low CD4+ T cell levels can act to 'fuel the fire' of infection by providing more proliferating cells for infection. Natural host species, on the other hand, have limited proliferation of CD4+ T cells at low CD4+ T cell levels, which allows them to restrict the number of proliferating cells susceptible to infection.

Limited CD4+ T cell proliferation leads to preservation of CD4+ T cell counts in SIV-infected sooty mangabeys

PubMed Central

Chan, Ming Liang; Petravic, Janka; Ortiz, Alexandra M.; Engram, Jessica; Paiardini, Mirko; Cromer, Deborah; Silvestri, Guido; Davenport, Miles P.

2010-01-01

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections result in chronic virus replication and progressive depletion of CD4+ T cells, leading to immunodeficiency and death. In contrast, ‘natural hosts’ of SIV experience persistent infection with high virus replication but no severe CD4+ T cell depletion, and remain AIDS-free. One important difference between pathogenic and non-pathogenic infections is the level of activation and proliferation of CD4+ T cells. We analysed the relationship between CD4+ T cell number and proliferation in HIV, pathogenic SIV in macaques, and non-pathogenic SIV in sooty mangabeys (SMs) and mandrills. We found that CD4+ T cell proliferation was negatively correlated with CD4+ T cell number, suggesting that animals respond to the loss of CD4+ T cells by increasing the proliferation of remaining cells. However, the level of proliferation seen in pathogenic infections (SIV in rhesus macaques and HIV) was much greater than in non-pathogenic infections (SMs and mandrills). We then used a modelling approach to understand how the host proliferative response to CD4+ T cell depletion may impact the outcome of infection. This modelling demonstrates that the rapid proliferation of CD4+ T cells in humans and macaques associated with low CD4+ T cell levels can act to ‘fuel the fire’ of infection by providing more proliferating cells for infection. Natural host species, on the other hand, have limited proliferation of CD4+ T cells at low CD4+ T cell levels, which allows them to restrict the number of proliferating cells susceptible to infection. PMID:20591864

Cadmium inhibits lysine acetylation and succinylation inducing testicular injury of mouse during development.

PubMed

Yang, Qiangzhen; Li, Peifei; Wen, Yi; Li, Sisi; Chen, Jun; Liu, Xurui; Wang, Lirui; Li, Xinhong

2018-07-01

The toxic effects of cadmium (Cd) in the reproductive system have been confirmed, and lysine acetylation and succinylation play important roles in spermatogenesis. However, little attention determined whether Cd could affect lysine acylation and how it might have an impact on the reproductive system. Therefore, with the goal of contributing to this subject, we have examined the effects of Cd on lysine acetylation and succinylation of proteins in the germ cells of male mice testes during different developmental stages. We adopted intraperitoneal injection of cadmium chloride (1.2 mg/kg body weight) in mice once every 5 days from postnatal day 5-60. The results showed that Cd could restrict GAPDH activity, ATP and cAMP levels of germ cells to inhibit lysine acetylation and succinylation in the testes, inducing reproductive injuries. Cd also restricts acetylation of histone H4K5 and H4K12, which could result in failure of spermiogenesis. Remarkably, polarized acetylation occurs in meiosis, and high-level acetylation occurs earlier than high-level succinylation during spermatogenesis. Moreover, Cd has a limited effect on body weight but reduces the weight of the testis and litter size. Our research may provide a new way to reveal the mechanisms of Cd reproductive toxicity related to lysine acetylation and succinylation. Copyright © 2018. Published by Elsevier B.V.

Association between 25(OH)D Level, Ultraviolet Exposure, Geographical Location, and Inflammatory Bowel Disease Activity: A Systematic Review and Meta-Analysis

PubMed Central

Lu, Chao; Yang, Jun; Yu, Weilai; Li, Dejian; Xiang, Zun; Lin, Yiming; Yu, Chaohui

2015-01-01

Background There is no consensus on the vitamin D levels and inflammatory bowel disease (IBD). Aim To conduct a systematic review and meta-analysis to analyze the relationship between IBD and 25(OH)D, sun exposure, and latitude, and to determine whether vitamin D deficiency affects the severity of IBD. Methods We searched the PubMed, EBSCO, and ClinicalTrials.gov databases to identify all studies that assessed the association between 25(OH)D, sun exposure, latitude, and IBD through November 1, 2014, without language restrictions. Studies that compared 25(OH)D levels between IBD patients and controls were selected for inclusion in the meta-analysis. We calculated pooled standardized mean differences (SMDs) and odds ratios (ORs). Results Thirteen case-control studies investigating CD and 25(OH)D levels were included, and eight studies part of above studies also investigated the relationship between UC and 25(OH)D. Both CD patients (SMD: 0.26 nmol/L, 95% confidence interval [CI]: 0.09–0.42 nmol/L) and UC patients (SMD: 0.5 nmol/L, 95% CI: 0.15–0.85 nmol/L) had lower levels of 25(OH)D than controls. In addition, CD patients and UC patients were 1.95 times (OR, 1.95; 95% CI, 1.48–2.57) and 2.02 times (OR, 2.02; 95% CI, 1.13–3.60) more likely to be 25(OH)D deficient than controls. We also included 10 studies investigating the relationship between CD activity and vitamin D. Results showed that patients with active CD (CD Activity Index≥150) were more likely to have low vitamin D levels. In addition, whether low sun exposure and high latitude were related to a high morbidity of CD need to be provided more evidence. Conclusion Our study shows that IBD patients have lower vitamin D levels. For active CD patients, vitamin D levels were low. These findings suggest that vitamin D may play an important role in the development of IBD, although a direct association could not be determined in our study. PMID:26172950

Platelets Toll-like receptor-4 in Crohns disease.

PubMed

Schmid, Werner; Novacek, Gottfried; Vogelsang, Harald; Papay, Pavol; Primas, Christian; Eser, Alexander; Panzer, Simon

2017-02-01

Platelets are activated in Crohn's disease (CD) and interplay with leukocytes. Engagement of Toll-like receptor-4 (TLR-4), which is expressed in human platelets, may be involved in crosstalks between platelets and leukocytes leading to their mutual activation for host defense. Human neutrophil peptides (HNPs), lipoprotein binding peptides, and sCD14 were determined by enzyme-linked immunosorbent assays in 42 patients with active CD, in 43 patients with CD in remission, and in 30 healthy individuals. Neutrophil-platelet aggregates and binding of the TLR-4 monoclonal antibody to platelets were determined by flow cytometry. Levels of HNPs were higher in patients with CD than in controls (P = 0.0003 vs. active CD and P = 0.01 vs. CD in remission). Likewise, neutrophils with adhering platelets were higher in patients with active CD than in controls (P = 0.004). Binding of the TLR-4 antibody in patients with active CD was similar to that in controls, while patients in remission had significantly higher binding capacities (P = 0.59 and P = 0.003). Incubation of plasma from patients with active disease or patients in remission with platelets from healthy controls confirmed lower binding of the TLR-4 antibody in the presence of plasma from active diseased patients compared to controls (P = 0.039), possibly due to high levels of lipopolysaccharides, as suggested by high levels of sCD14 and lipoprotein binding protein. Our study indicates involvement of platelet TLR-4 in enhancing the secretion of antimicrobial peptides from neutrophils. While platelet aggregation can be due to a variety of mechanisms in inflammatory disease, the mutual activation of platelets and neutrophils may augment host defense. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

Anti-CD3 Antibody Treatment Induces Hypoglycemia and Super Tolerance to Glucose Challenge in Mice through Enhancing Glucose Consumption by Activated Lymphocytes

PubMed Central

Chernatynskaya, Anna V.; Looney, Benjamin; Wan, Suigui; Clare-Salzler, Michael J.

2014-01-01

Anti-CD3 antibody has been employed for various immune-mediated disorders. However, whether anti-CD3 administration leads to rapid metabolic alternation has not been well investigated. In the current study, we studied how anti-CD3 treatment affected blood glucose levels in mice. We found that anti-CD3 treatment induced immediate reduction of blood glucose after administration. Furthermore, a single dose of anti-CD3 treatment corrected hyperglycemia in all nonobese diabetic mice with recently diagnosed diabetes. This glucose-lowering effect was not attributable to major T cell produced cytokines. Of interest, when tested in a normal strain of mice (C57BL/6), the serum levels of C-peptide in anti-CD3 treated animals were significantly lower than control mice. Paradoxically, anti-CD3 treated animals were highly tolerant to exogenous glucose challenge. Additionally, we found that anti-CD3 treatment significantly induced activation of T and B cells in vitro and in vivo. Further studies demonstrated that anti-CD3 treatment lowered the glucose levels in T cell culture media and increased the intracellular transportation of 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2 deoxyglucose (2-NBDG) particularly in activated T and B cells. In addition, injection of anti-CD3 antibodies induced enhanced levels of Glut1 expression in spleen cells. This study suggests that anti-CD3 therapy-induced hypoglycemia likely results from increased glucose transportation and consumption by the activated lymphocytes. PMID:24741590

Extended diagnostic criteria for plasmacytoid dendritic cell leukaemia.

PubMed

Garnache-Ottou, Francine; Feuillard, Jean; Ferrand, Christophe; Biichle, Sabeha; Trimoreau, Franck; Seilles, Estelle; Salaun, Véronique; Garand, Richard; Lepelley, Pascale; Maynadié, Marc; Kuhlein, Emilienne; Deconinck, Eric; Daliphard, Sylvie; Chaperot, Laurence; Beseggio, Lucille; Foisseaud, Vincent; Macintyre, Elizabeth; Bene, Marie-Christine; Saas, Philippe; Jacob, Marie-Christine

2009-06-01

The diagnosis of plasmacytoid dendritic cell leukaemia (pDCL) is based on the immunophenotypic profile: CD4(+) CD56(+) lineage(neg) CD45RA(+)/RO(neg) CD11c(neg) CD116(low) CD123(+) CD34(neg) CD36(+) HLA-DR(+). Several studies have reported pDCL cases that do not express this exact profile or expressing some lineage antigens that could thus be misdiagnosed. This study aimed to validate pDCL-specific markers for diagnosis by flow-cytometry or quantitative reverse transcription polymerase chain reaction on bone marrow samples. Expression of markers previously found in normal pDC was analysed in 16 pDCL, four pDCL presenting an atypical phenotype (apDCL) and 113 non-pDC - lymphoid or myeloid - acute leukaemia. CD123 was expressed at significantly higher levels in pDCL and apDCL. BDCA-2 was expressed on 12/16 pDCL and on 2/4 apDCL, but was never detected in the 113 non-pDC acute leukaemia cases. BDCA-4 expression was found on 13/16 pDCL, but also in 12% of non-pDC acute leukaemia. High levels of LILRA4 and TCL1A transcripts distinguished pDCL and apDCL from all other acute leukaemia (except B-cell acute lymphoblastic leukaemia for TCL1A). We thus propose a diagnosis strategy, scoring first the CD4(+) CD56(+/-) MPO(neg) cCD3(neg) cCD79a(neg) CD11c(neg) profile and then the CD123(high), BDCA-2 and BDCA-4 expression. Atypical pDCL can be also identified this way and non-pDC acute leukaemia excluded: this scoring strategy is useful for diagnosing pDCL and apDCL.

STAT3 as a promising chemoresistance biomarker associated with the CD44+/high/CD24-/low/ALDH+ BCSCs-like subset of the triple-negative breast cancer (TNBC) cell line.

PubMed

Moreira, Milene Pereira; da Conceição Braga, Letícia; Cassali, Geovanni Dantas; Silva, Luciana Maria

2018-02-15

The cancer stem cell (CSC) concept is currently employed to explain the mechanism of multidrug resistance that is implicated in the reduced efficacy of many chemotherapeutic agents, consequently leading to metastatic spread and disease relapse. We searched for potential predictive markers of doxorubicin (DOX) resistance in breast cancer stem cells (BCSCs) of the BT-549 human triple-negative breast cancer (TNBC) cell line classified as a claudin-low subtype. In this study, we show that BT-549 presents a BCSCs-like subset determined by a CD44 +/high /CD24 -/low /ALDH1 + phenotype. The CD44 +/high /CD24 -/low /ALDH + BCSCs-like subset presented the downregulation of a majority of the genes analyzed (64 genes), and only 3 genes were upregulated after DOX treatment. Among the upregulated genes, MAPK3, PRKCZ and STAT3, STAT3 presented a higher level of upregulation in the DOX-treated CD44 +/high /CD24 -/low /ALDH + BCSCs-like subset. The identification of biomarkers that predict antitumor responses is at the top of cancer research priorities. STAT3 was highlighted as a molecular signature in the CD44 +/high /CD24 -/low /ALDH1 + BCSCs-like subset obtained from the TNBC BT-549 cell line related to DOX resistance. A majority of the evaluated genes in the EGF pathway appear to be not associated with DOX resistance, as observed in the CD44 +/high /CD24 -/low /ALDH1 + BCSCs-like subset. Copyright © 2018 Elsevier Inc. All rights reserved.

Posttransplant sCD30 as a predictor of kidney graft outcome.

PubMed

Süsal, Caner; Döhler, Bernd; Sadeghi, Mahmoud; Salmela, Kaija T; Weimer, Rolf; Zeier, Martin; Opelz, Gerhard

2011-06-27

Reliable markers for assessing the biological effect of immunosuppressive drugs and identification of transplant recipients at risk of developing rejection are not available. In a prospective multicenter study, we investigated whether posttransplant measurement of the T-cell activation marker soluble CD30 (sCD30) can be used for estimating the risk of graft loss in kidney transplant recipients. Pre- and posttransplant sera of 2322 adult deceased-donor kidney recipients were tested for serum sCD30 content using a commercial enzyme-linked immunosorbent assay. sCD30 decreased posttransplant and reached a nadir on day 30. Patients with a high sCD30 of more than or equal to 40 U/mL on day 30 showed a subsequent graft survival rate after 3 years of 78.3±4.1%, significantly lower than the 90.3±1.0% rate in recipients with a low sCD30 on day 30 of less than 40 U/mL (log-rank P<0.001; Cox hazard ratio 2.02, P<0.001). Although an association was found between pre- and posttransplant sCD30 levels, patients with high sCD30 on posttransplant day 30 demonstrated significantly lower 3-year graft survival irrespective of the pretransplant level. Our data suggest that posttransplant measurement of sCD30 on day 30 is a predictor of subsequent graft loss in kidney transplant recipients and that sCD30 may potentially serve as an indicator for adjustment of immunosuppressive medication.

Rapid Perturbation in Viremia Levels Drives Increases in Functional Avidity of HIV-specific CD8 T Cells

PubMed Central

Viganò, Selena; Bellutti Enders, Felicitas; Miconnet, Isabelle; Cellerai, Cristina; Savoye, Anne-Laure; Rozot, Virginie; Perreau, Matthieu; Faouzi, Mohamed; Ohmiti, Khalid; Cavassini, Matthias; Bart, Pierre-Alexandre; Pantaleo, Giuseppe; Harari, Alexandre

2013-01-01

The factors determining the functional avidity and its relationship with the broad heterogeneity of antiviral T cell responses remain partially understood. We investigated HIV-specific CD8 T cell responses in 85 patients with primary HIV infection (PHI) or chronic (progressive and non-progressive) infection. The functional avidity of HIV-specific CD8 T cells was not different between patients with progressive and non-progressive chronic infection. However, it was significantly lower in PHI patients at the time of diagnosis of acute infection and after control of virus replication following one year of successful antiretroviral therapy. High-avidity HIV-specific CD8 T cells expressed lower levels of CD27 and CD28 and were enriched in cells with an exhausted phenotype, i.e. co-expressing PD-1/2B4/CD160. Of note, a significant increase in the functional avidity of HIV-specific CD8 T cells occurred in early-treated PHI patients experiencing a virus rebound after spontaneous treatment interruption. This increase in functional avidity was associated with the accumulation of PD-1/2B4/CD160 positive cells, loss of polyfunctionality and increased TCR renewal. The increased TCR renewal may provide the mechanistic basis for the generation of high-avidity HIV-specific CD8 T cells. These results provide insights on the relationships between functional avidity, viremia, T-cell exhaustion and TCR renewal of antiviral CD8 T cell responses. PMID:23853580

A novel bipolar phosphorescent host for highly efficient deep-red OLEDs at a wide luminance range of 1000-10 000 cd m(-2).

PubMed

Feng, Yansong; Li, Ping; Zhuang, Xuming; Ye, Kaiqi; Peng, Tai; Liu, Yu; Wang, Yue

2015-08-14

A novel phosphorescent host FPYPCA possessing the bipolar charge transporting ability realizes the most efficient deep-red PhOLED, which maintains very high-level EQEs of >23% at rather a high and wide luminance range of 1000-10 000 cd m(-2).

The CD4+ T cell regulatory network mediates inflammatory responses during acute hyperinsulinemia: a simulation study.

PubMed

Martinez-Sanchez, Mariana E; Hiriart, Marcia; Alvarez-Buylla, Elena R

2017-06-26

Obesity is frequently linked to insulin resistance, high insulin levels, chronic inflammation, and alterations in the behaviour of CD4+ T cells. Despite the biomedical importance of this condition, the system-level mechanisms that alter CD4+ T cell differentiation and plasticity are not well understood. We model how hyperinsulinemia alters the dynamics of the CD4+ T regulatory network, and this, in turn, modulates cell differentiation and plasticity. Different polarizing microenvironments are simulated under basal and high levels of insulin to assess impacts on cell-fate attainment and robustness in response to transient perturbations. In the presence of high levels of insulin Th1 and Th17 become more stable to transient perturbations, and their basin sizes are augmented, Tr1 cells become less stable or disappear, while TGFβ producing cells remain unaltered. Hence, the model provides a dynamic system-level framework and explanation to further understand the documented and apparently paradoxical role of TGFβ in both inflammation and regulation of immune responses, as well as the emergence of the adipose Treg phenotype. Furthermore, our simulations provide new predictions on the impact of the microenvironment in the coexistence of the different cell types, suggesting that in pro-Th1, pro-Th2 and pro-Th17 environments effector and regulatory cells can coexist, but that high levels of insulin severely diminish regulatory cells, especially in a pro-Th17 environment. This work provides a first step towards a system-level formal and dynamic framework to integrate further experimental data in the study of complex inflammatory diseases.

High sugar and butter (HSB) diet induces obesity and metabolic syndrome with decrease in regulatory T cells in adipose tissue of mice.

PubMed

Maioli, Tatiani Uceli; Gonçalves, Juliana Lauar; Miranda, Mariana Camila Gonçalves; Martins, Vinícius Dantas; Horta, Laila Sampaio; Moreira, Thais Garcias; Godard, Ana Lucia Brunialti; Santiago, Andrezza Fernanda; Faria, Ana Maria Caetano

2016-02-01

The purpose of the study was to develop a novel diet based on standard AIN93G diet that would be able to induce experimental obesity and impair immune regulation with high concentrations of both carbohydrate and lipids. To compare the effects of this high sugar and butter (HSB) diet with other modified diets, male C57BL/6 mice were fed either mouse chow, or AIN93G diet, or high sugar (HS) diet, or high-fat (HF) diet, or high sugar and butter (HSB) diet for 11 weeks ad libitum. HSB diet induced higher weight gain. Therefore, control AIN93G and HSB groups were chosen for additional analysis. Regulatory T cells were studied by flow cytometry, and cytokine levels were measured by ELISA. Although HF and HSB diets were able to induce a higher weight gain compatible with obesity in treated mice, HSB-fed mice presented the higher levels of serum glucose after fasting and the lowest frequency of regulatory T cells in adipose tissue. In addition, mice that were fed HSB diet presented higher levels of cholesterol and triglycerides, hyperleptinemia, increased resistin and leptin levels as well as reduced adiponectin serum levels. Importantly, we found increased frequency of CD4(+)CD44(+) effector T cells, reduction of CD4(+)CD25(+)Foxp3(+) and Th3 regulatory T cells as well as decreased levels of IL-10 and TGF-β in adipose tissue of HSB-fed mice. Therefore, HSB represents a novel model of obesity-inducing diet that was efficient in triggering alterations compatible with metabolic syndrome as well as impairment in immune regulatory parameters.

Dose-dependent effects of Lactobacillus rhamnosus on serum interleukin-17 production and intestinal T-cell responses in pigs challenged with Escherichia coli.

PubMed

Zhu, Yao-Hong; Li, Xiao-Qiong; Zhang, Wei; Zhou, Dong; Liu, Hao-Yu; Wang, Jiu-Feng

2014-03-01

The mechanism underlying the dose effect of probiotics on ameliorating diarrhea has not been fully elucidated. Here, low (1 × 10(9) CFU/ml) or high (1 × 10(11) CFU/ml) doses of Lactobacillus rhamnosus ATCC 7469 were administered orally to piglets for 1 week before F4 (K88)-positive enterotoxigenic Escherichia coli (F4(+) ETEC) challenge. Administration of a low, but not a high, dose of L. rhamnosus decreased the percentage of CD3(+) CD4(+) CD8(-) T cells in the peripheral blood. Notably, transiently increased serum concentrations of interleukin-17A (IL-17A) were observed after F4(+) ETEC challenge in pigs pretreated with a high dose of L. rhamnosus. Administration of L. rhamnosus increased the percentage of the small intestinal lamina propria CD3(+) CD4(+) CD8(-) cells and Peyer's patch CD3(+) CD4(-) CD8(-) and CD3(-) CD4(-) CD8(+) cells. The percentage of ileal intraepithelial CD3(+) CD4(-) CD8(+) cells increased only in the high-dose piglets. Administration of L. rhamnosus downregulated expression of ileal IL-17A after F4(+) ETEC challenge but had no effect on expression of gamma interferon (IFN-γ), IL-12, IL-4, and FOXP3 mRNA in the small intestine. Expression of jejunal IL-2, ileal transforming growth factor β1 (TGF-β1), and ileal IL-10 was upregulated in the low-dose piglets after F4(+) ETEC challenge. Our findings suggest that amelioration of infectious diarrhea in piglets by L. rhamnosus is associated with the generation of lamina propria CD3(+) CD4(+) CD8(-) T cells, the expansion of Peyer's patch CD3(+) CD4(-) CD8(-) and CD3(-) CD4(-) CD8(+) cells, and the attenuation of F4(+) ETEC-induced increase in CD3(+) CD4(+) CD8(+) T cells in the small intestine. However, consumption of high doses of L. rhamnosus may increase levels of serum IL-17A after F4(+) ETEC challenge, thus eliciting a strong proinflammatory response.

Dose-Dependent Effects of Lactobacillus rhamnosus on Serum Interleukin-17 Production and Intestinal T-Cell Responses in Pigs Challenged with Escherichia coli

PubMed Central

Zhu, Yao-Hong; Li, Xiao-Qiong; Zhang, Wei; Zhou, Dong; Liu, Hao-Yu

2014-01-01

The mechanism underlying the dose effect of probiotics on ameliorating diarrhea has not been fully elucidated. Here, low (1 × 109 CFU/ml) or high (1 × 1011 CFU/ml) doses of Lactobacillus rhamnosus ATCC 7469 were administered orally to piglets for 1 week before F4 (K88)-positive enterotoxigenic Escherichia coli (F4+ ETEC) challenge. Administration of a low, but not a high, dose of L. rhamnosus decreased the percentage of CD3+ CD4+ CD8− T cells in the peripheral blood. Notably, transiently increased serum concentrations of interleukin-17A (IL-17A) were observed after F4+ ETEC challenge in pigs pretreated with a high dose of L. rhamnosus. Administration of L. rhamnosus increased the percentage of the small intestinal lamina propria CD3+ CD4+ CD8− cells and Peyer's patch CD3+ CD4− CD8− and CD3− CD4− CD8+ cells. The percentage of ileal intraepithelial CD3+ CD4− CD8+ cells increased only in the high-dose piglets. Administration of L. rhamnosus downregulated expression of ileal IL-17A after F4+ ETEC challenge but had no effect on expression of gamma interferon (IFN-γ), IL-12, IL-4, and FOXP3 mRNA in the small intestine. Expression of jejunal IL-2, ileal transforming growth factor β1 (TGF-β1), and ileal IL-10 was upregulated in the low-dose piglets after F4+ ETEC challenge. Our findings suggest that amelioration of infectious diarrhea in piglets by L. rhamnosus is associated with the generation of lamina propria CD3+ CD4+ CD8− T cells, the expansion of Peyer's patch CD3+ CD4− CD8− and CD3− CD4− CD8+ cells, and the attenuation of F4+ ETEC-induced increase in CD3+ CD4+ CD8+ T cells in the small intestine. However, consumption of high doses of L. rhamnosus may increase levels of serum IL-17A after F4+ ETEC challenge, thus eliciting a strong proinflammatory response. PMID:24389928

Expansions of CD8+CD28- and CD8+TcRVbeta5.2+ T cells in peripheral blood of heavy alcohol drinkers.

PubMed

Arosa, F A; Porto, G; Cabeda, J M; Lacerda, R; Resende, D; Cruz, E; Cardoso, C; Fonseca, M; Simões, C; Rodrigues, P; Bravo, F; Oliveira, J C; Alves, H; Fraga, J; Justiça, B; de Sousa, M

2000-04-01

Despite heavy alcohol consumption, only a low percentage of heavy drinkers develop liver disease. Imbalances in T-cell subsets and iron metabolism parameters are common findings in heavy drinkers, yet the possible role played by discrete T-lymphocyte subsets under heavy alcohol consumption remains unclear. To gain new insights into the possible role played by T lymphocytes during alcohol consumption, characterization of CD28 expression and TcR repertoire in peripheral blood CD4+ and CD8+ T cells by two and three-color flow cytometry was performed. A group of heavy alcohol drinkers (AHD, n = 71) and a group of age-matched controls (n = 81), both HLA-phenotyped and HFE-genotyped, constituted the groups under study. Marked expansions of CD28- T cells within the CD8+ but not the CD4+ T-cell pool were observed in AHD compared with controls. These CD8+CD28- expansions were paralleled by expansions of CD8+ T cells bearing specific TcR Valpha/beta chains, namely VP5.2. Moreover, AHD, but not controls, carrying the H63D mutation in the HFE gene showed significantly higher percentages of CD28- T cells within the CD8+ T-cell pool than AHD carrying the normal HFE gene. Finally, high numbers of CD8+CD28- T cells in AHD were associated with lower levels of the liver-related enzymes ALT and GGT. This study showed that under active ethanol consumption, expansions of discrete CD8+ T-cell subsets occur within the CD8+ T-cell pool, that molecules of the MHC-class I locus seem to influence the extent of the expansions, and that high numbers of CD8+CD28- T cells are associated with low levels of liver enzymes in AHD.

Toxicological responses of Laeonereis acuta (Polychaeta, Nereididae) after acute, subchronic and chronic exposure to cadmium.

PubMed

Dolagaratz Carricavur, Arantxa; Chiodi Boudet, Leila; Romero, María Belén; Polizzi, Paula; Marcovecchio, Jorge Eduardo; Gerpe, Marcela

2018-03-01

The objective of this study was to analyze the toxicological responses of the estuarine polychaete Laeonereis acuta after acute (96h), subchronic (7 days) and chronic (14 days) exposure to cadmium (Cd). Concentrations of metallothioneins (MT), lipid peroxidation (LPO), total Cd and metal-rich granules (MRG) were evaluated. Seasonal variations of MT and LPO levels in the wild were also measured. Polychaetes were obtained in the Quequén estuary located southeast of Buenos Aires Province, Argentina. For the acute toxicity assay, individuals were exposed to 10; 30, 65; 310; 600; 1300; 2000; 4300; 8100; 16300µgCdL -1 , which included levels of environmental relevance and median lethal concentrations (LC 50 ) for related species of polychaete. Based on 96h LC 50 values, polychaetes were exposed to sublethal doses of Cd. The concentrations for both subchronic and chronic assays were: 10; 30; 65; 310; 600; 1300; 2000; 4300µgCdL -1 . The 96h LC 50 value was 8234.9µgL -1 , which was within the values reported for other species of polychaete, indicating a high tolerance to Cd. MT induction was not observed for any time exposure. In additoin, LPO levels showed no differences with respect to control levels, which indicated an absence of oxidative damage caused by Cd. However, the total Cd and MRG-Cd concentrations in L. acuta in all tested treatments showed significant differences with respect to control levels. L. acuta were able to accumulate Cd in their tissues in the form of granules which are the main mechanism of Cd detoxification. Copyright © 2017 Elsevier Inc. All rights reserved.

Oxidative stability of high-oleic sunflower oil in a porous starch carrier.

PubMed

Belingheri, Claudia; Giussani, Barbara; Rodriguez-Estrada, Maria Teresa; Ferrillo, Antonio; Vittadini, Elena

2015-01-01

This study evaluates the oxidation level of high-oleic sunflower oil (HOSO) plated onto porous starch as an alternative to spray drying. Encapsulated oils were subjected to accelerated oxidation by heat and light exposure, and peroxide value (PV) and conjugated dienes (CD) were measured. Bulk oil was the control. PV increased in all samples with increased light exposure, with similar values being reached by oil carried on porous starch and spray dried oil. The encapsulation processes determined a reduced effect of light on the increase of CD in the oil, as compared to bulk oil. Spray dried oil presented the highest CD in the experimental domain considered. Since similar levels of PV and lower levels of CD were shown in the HOSO carried on porous starch compared to the spray dried HOSO, plating flavour oils on porous starch could be a suitable technological alternative to spray drying, for flavour encapsulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

High soluble CD30 levels and associated anti-HLA antibodies in patients with failed renal allografts.

PubMed

Karahan, Gonca E; Caliskan, Yasar; Ozdilli, Kursat; Kekik, Cigdem; Bakkaloglu, Huseyin; Caliskan, Bahar; Turkmen, Aydin; Sever, Mehmet S; Oguz, Fatma S

2017-01-13

Serum soluble CD30 (sCD30), a 120-kD glycoprotein that belongs to the tumor necrosis factor receptor family, has been suggested as a marker of rejection in kidney transplant patients. The aim of this study was to evaluate the relationship between sCD30 levels and anti-HLA antibodies, and to compare sCD30 levels in patients undergoing hemodialysis (HD) with and without failed renal allografts and transplant recipients with functioning grafts. 100 patients undergoing HD with failed grafts (group 1), 100 patients undergoing HD who had never undergone transplantation (group 2), and 100 kidney transplant recipients (group 3) were included in this study. Associations of serum sCD30 levels and anti-HLA antibody status were analyzed in these groups. The sCD30 levels of group 1 and group 2 (154 ± 71 U/mL and 103 ± 55 U/mL, respectively) were significantly higher than those of the transplant recipients (group 3) (39 ± 21 U/mL) (p<0.001 and p<0.001). The serum sCD30 levels in group 1 (154 ± 71 U/mL) were also significantly higher than group 2 (103 ± 55 U/mL) (p<0.001). Anti-HLA antibodies were detected in 81 (81%) and 5 (5%) of patients in groups 1 and 2, respectively (p<0.001). When multiple regression analysis was performed to predict sCD30 levels, the independent variables in group 1 were the presence of class I anti-HLA antibodies (β = 0.295; p = 0.003) and age (β = -0.272; p = 0.005), and serum creatinine (β = 0.218; p = 0.027) and presence of class II anti-HLA antibodies (standardized β = 0.194; p = 0.046) in group 3. Higher sCD30 levels and anti-HLA antibodies in patients undergoing HD with failed renal allografts may be related to higher inflammatory status in these patients.

A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study.

PubMed

Rawstron, A C; Fazi, C; Agathangelidis, A; Villamor, N; Letestu, R; Nomdedeu, J; Palacio, C; Stehlikova, O; Kreuzer, K-A; Liptrot, S; O'Brien, D; de Tute, R M; Marinov, I; Hauwel, M; Spacek, M; Dobber, J; Kater, A P; Gambell, P; Soosapilla, A; Lozanski, G; Brachtl, G; Lin, K; Boysen, J; Hanson, C; Jorgensen, J L; Stetler-Stevenson, M; Yuan, C; Broome, H E; Rassenti, L; Craig, F; Delgado, J; Moreno, C; Bosch, F; Egle, A; Doubek, M; Pospisilova, S; Mulligan, S; Westerman, D; Sanders, C M; Emerson, R; Robins, H S; Kirsch, I; Shanafelt, T; Pettitt, A; Kipps, T J; Wierda, W G; Cymbalista, F; Hallek, M; Hillmen, P; Montserrat, E; Ghia, P

2016-04-01

In chronic lymphocytic leukemia (CLL) the level of minimal residual disease (MRD) after therapy is an independent predictor of outcome. Given the increasing number of new agents being explored for CLL therapy, using MRD as a surrogate could greatly reduce the time necessary to assess their efficacy. In this European Research Initiative on CLL (ERIC) project we have identified and validated a flow-cytometric approach to reliably quantitate CLL cells to the level of 0.0010% (10(-5)). The assay comprises a core panel of six markers (i.e. CD19, CD20, CD5, CD43, CD79b and CD81) with a component specification independent of instrument and reagents, which can be locally re-validated using normal peripheral blood. This method is directly comparable to previous ERIC-designed assays and also provides a backbone for investigation of new markers. A parallel analysis of high-throughput sequencing using the ClonoSEQ assay showed good concordance with flow cytometry results at the 0.010% (10(-4)) level, the MRD threshold defined in the 2008 International Workshop on CLL guidelines, but it also provides good linearity to a detection limit of 1 in a million (10(-6)). The combination of both technologies would permit a highly sensitive approach to MRD detection while providing a reproducible and broadly accessible method to quantify residual disease and optimize treatment in CLL.

Altered CD19/CD22 balance in Egyptian children and adolescents with systemic lupus erythematosus.

PubMed

El-Sayed, Zeinab A; Ragab, Seham M; Khalifa, Khaled A; El Ashmawy, Ramy A

2009-01-01

B cells from systemic lupus erythematosus (SLE) patients display signalling defects that may underlie disease pathogenesis activity.CD19 and CD22 play a major role as regulators of B-cell response. The aim of this study was to clarify the relationship between B cell surface markers namely CD19, CD20 and CD22 expression and clinical and laboratory indices of SLE activity. The study included 33 SLE patients and 20 healthy children and adolescents as controls. Flowcytometric assay of dual markers, CD19/CD20, and CD20/CD22 was done. SLE disease activity was assessed by SLEDAI score. CD22% was significantly higher while CD20% was significantly lower in the study compared to the control group. No significant difference was observed in both groups with respect to CD19% or CD19/CD22% ratio. The level of CD22 expression was significantly lower in high and very high active cases than in mild and moderate cases and negatively correlated with SLDEAI score and ESR. Results obtained showed that, B cell surface receptors CD20 and CD22 are significantly affected in patients with SLE, pointing to their possible involvement in the aetiopathogenesis of the disease and in the regulatory mechanisms in response to the immune disturbance.

Evaluation of serum sCD30 in renal transplantation patients with and without acute rejection.

PubMed

Cervelli, C; Fontecchio, G; Scimitarra, M; Azzarone, R; Famulari, A; Pisani, F; Battistoni, C; Di Iulio, B; Fracassi, D; Scarnecchia, M A; Papola, F

2009-05-01

Despite new immunosuppressive approaches, acute rejection episodes (ARE) are still a major cause of early kidney dysfunction with a negative impact on long-term allograft survival. Noninvasive markers able to identify renal ARE earlier than creatinine measurement include sCD30. We sought to establish whether circulating levels of sCD30 in pretransplantation and posttransplantation periods were of clinical relevance to avoid graft damage. Quantitative detection of serum sCD30 was performed using an enzyme-linked immunosorbent assay. Our results demonstrated that the mean concentrations of sCD30 were significantly higher in the sera of renal transplant recipients with ARE (30.04 U/mL) and in uremic patients on the waiting list (37.7 U/mL) compared with healthy controls (HC; 9.44 U/mL), but not nonrejecting patients (12.01 U/mL). Statistical analysis revealed a strong association between high sCD30 levels in posttransplantation sera and ARE risk. This study suggested that sCD30 levels were a reliable predictor of ARE among deceased-donor kidney recipients.

RANK Expression and Osteoclastogenesis in Human Monocytes in Peripheral Blood from Rheumatoid Arthritis Patients

PubMed Central

Kobashigawa, Tsuyoshi

2016-01-01

Rheumatoid arthritis (RA) appears as inflammation of synovial tissue and joint destruction. Receptor activator of NF-κB (RANK) is a member of the TNF receptor superfamily and a receptor for the RANK ligand (RANKL). In this study, we examined the expression of RANKhigh and CCR6 on CD14+ monocytes from patients with RA and healthy volunteers. Peripheral blood samples were obtained from both the RA patients and the healthy volunteers. Osteoclastogenesis from monocytes was induced by RANKL and M-CSF in vitro. To study the expression of RANKhigh and CCR6 on CD14+ monocytes, two-color flow cytometry was performed. Levels of expression of RANK on monocytes were significantly correlated with the level of osteoclastogenesis in the healthy volunteers. The expression of RANKhigh on CD14+ monocyte in RA patients without treatment was elevated and that in those receiving treatment was decreased. In addition, the high-level expression of RANK on CD14+ monocytes was correlated with the high-level expression of CCR6 in healthy volunteers. Monocytes expressing both RANK and CCR6 differentiate into osteoclasts. The expression of CD14+RANKhigh in untreated RA patients was elevated. RANK and CCR6 expressed on monocytes may be novel targets for the regulation of bone resorption in RA and osteoporosis. PMID:27822475

Cancer vaccine enhanced, non-tumor-reactive CD8(+) T cells exhibit a distinct molecular program associated with "division arrest anergy".

PubMed

Beyer, Marc; Karbach, Julia; Mallmann, Michael R; Zander, Thomas; Eggle, Daniela; Classen, Sabine; Debey-Pascher, Svenja; Famulok, Michael; Jäger, Elke; Schultze, Joachim L

2009-05-15

Immune-mediated tumor rejection relies on fully functional T-cell responses and neutralization of an adverse tumor microenvironment. In clinical trials, we detected peptide-specific but non-tumor-reactive and therefore not fully functional CD8(+) T cells post-vaccination against tumor antigens. Understanding the molecular mechanisms behind nontumor reactivity will be a prerequisite to overcome this CD8(+) T-cell deviation. We report that these non-tumor-reactive CD8(+) T cells are characterized by a molecular program associated with hallmarks of "division arrest anergy." Non-tumor-reactive CD8(+) T cells are characterized by coexpression of CD7, CD25, and CD69 as well as elevated levels of lck(p505) and p27(kip1). In vivo quantification revealed high prevalence of non-tumor-reactive CD8(+) T cells with increased levels during cancer vaccination. Furthermore, their presence was associated with a trend toward shorter survival. Dynamics and frequencies of non-target-reactive CD8(+) T cells need to be further addressed in context of therapeutic vaccine development in cancer, chronic infections, and autoimmune diseases.

Decreased serum levels of sCD40L and IL-31 correlate in treated patients with Relapsing-Remitting Multiple Sclerosis.

PubMed

de J Guerrero-García, José; Rojas-Mayorquín, Argelia E; Valle, Yeminia; Padilla-Gutiérrez, Jorge R; Castañeda-Moreno, Víctor A; Mireles-Ramírez, Mario A; Muñoz-Valle, José F; Ortuño-Sahagún, Daniel

2018-01-01

The CD40/CD40L system is a binding key for co-stimulation of immune cells. Soluble form of CD40L has been widely studied as marker of inflammatory and autoimmune diseases. Here we analyze serum concentrations of sCD40L, as well as 14 cytokines, in patients with Multiple Sclerosis (MS) treated with Glatiramer acetate or Interferon beta. In the healthy control group, we found in serum a highly positive correlation between sCD40L and Interleukin (IL)-31, an anti-inflammatory Th2 cytokine. Additionally, an important reduction in IL-31 and sCD40L serum levels, as well as a significant reduction in CD40 mRNA expression and complete depletion of CD40L mRNA, detected from peripheral blood cells, was found in treated patients with MS. Therefore, sCD40L and IL-31 must be taken into account as possible prognostic markers when analyzing the disease progress of MS in order to provide more personalized treatment. Copyright © 2017 Elsevier GmbH. All rights reserved.

FOXP3-expressing CD4(+) T-cell numbers increase in areas of duodenal gastric metaplasia and are associated to CD4(+) T-cell aggregates in the duodenum of Helicobacter pylori-infected duodenal ulcer patients.

PubMed

Kindlund, Bert; Sjöling, Asa; Hansson, Malin; Edebo, Anders; Hansson, Lars-Erik; Sjövall, Henrik; Svennerholm, Ann-Mari; Lundin, B Samuel

2009-06-01

We have previously demonstrated that Helicobacter pylori infection is associated with an increased number of CD4(+)CD25(high) regulatory T cells in the gastric and duodenal mucosa. In this study, we determined the number and localization of CD4(+) cells expressing the regulatory T-cell-specific transcription factor FOXP3 in the antrum and duodenum of duodenal ulcer patients, asymptomatic carriers, and uninfected individuals. We also determined gene expression levels of FOXP3 as well as anti- and proinflammatory cytokines before and after H. pylori eradication. Cellular FOXP3 expression was studied by immunofluorescence and flow cytometry, and transcription levels of FOXP3, interleukin (IL)-10, transforming growth factor-beta, CD4, and interferon-gamma were analyzed by real-time reverse transcription-polymerase chain reaction. We found an increased (6-fold) frequency of CD4(+)FOXP3(+) T cells in H. pylori-infected gastric mucosa; interestingly 26% of these cells did not co-express CD25. The increase of FOXP3-expressing T cells in the antrum of infected individuals was dependent on the presence of H. pylori, since eradication therapy resulted in 4-fold lower levels of FOXP3 and IL-10 mRNA in the antrum. Furthermore, higher numbers of CD4(+)FOXP3(+) T cells were found in areas of duodenal gastric metaplasia in the duodenum of duodenal ulcer patients compared to duodenal gastric metaplasia of asymptomatic individuals and healthy mucosa in both patient groups. In duodenal ulcer patients, the CD4(+)FOXP3(+) T cells were more highly associated to aggregates in the duodenal mucosa. The numbers of CD4(+)FOXP3(+) T cells are increased and localized in CD4(+) T-cell aggregates in areas of duodenal gastric metaplasia in duodenal ulcer patients.

Expression levels of transcription factors c-Fos and c-Jun and transmembrane protein HAb18G/CD147 in urothelial carcinoma of the bladder.

PubMed

Huhe, Muren; Liu, Shuangshuang; Zhang, Yang; Zhang, Zheng; Chen, Zhinan

2017-05-01

The aim of the present study was to investigate the prognostic significance of the expression of transcription factors, c-Fos, c-Jun and transmembrane protein CD147, in urothelial carcinoma of the bladder (UCB). The current study investigated the clinical significance of these factors in the development, progression and survival analysis of UCB. Immunohistochemistry was employed to analyze c‑Fos, c‑Jun and CD147 expression in 41 UCB cases and 34 non‑cancerous human bladder tissues. These results were scored in a semi‑quantitative manner based on the intensity and percentage of tumor cells that presented immunoreactivity. Protein levels of CD147, c‑Fos and c‑Jun expression were upregulated in 22 (53.7%), 10 (24.4%) and 9 (22.0%) UCB cases, respectively. High levels of c‑Jun correlated with the AJCC cancer staging manual (7th edition; P=0.038). Univariate analysis revealed that upregulated CD147 (P=0.038) or c‑Jun (P=0.008) was associated with poor overall survival (OS), respectively. Further analysis revealed that either CD147‑c‑Fos‑c‑Jun co‑expression (P=0.004), or CD147‑c‑Jun co‑expression (P=0.037) and c‑Fos‑c‑Jun co‑expression (P<0.001) were associated with poor OS. Multivariate analysis suggested that either upregulation of CD147, c‑Jun or c‑Fos were independent risk indicators for death in UCB patients. Increased expression of c‑Jun or CD147, as well as co‑expression of CD147‑c‑Jun, c‑Jun‑c‑Fos or CD147‑c‑Jun‑c‑Fos has prognostic significance for UCB patients. Therefore, high CD147 and c‑Jun expression may serve roles in tumor progression and may be diagnostic and therapeutic targets in UCB whether alone or in combination.

Combination of two anti-CD5 monoclonal antibodies synergistically induces complement-dependent cytotoxicity of chronic lymphocytic leukaemia cells.

PubMed

Klitgaard, Josephine L; Koefoed, Klaus; Geisler, Christian; Gadeberg, Ole V; Frank, David A; Petersen, Jørgen; Jurlander, Jesper; Pedersen, Mikkel W

2013-10-01

The treatment of chronic lymphocytic leukaemia (CLL) has been improved by introduction of monoclonal antibodies (mAbs) that exert their effect through secondary effector mechanisms. CLL cells are characterized by expression of CD5 and CD23 along with CD19 and CD20, hence anti-CD5 Abs that engage secondary effector functions represent an attractive opportunity for CLL treatment. Here, a repertoire of mAbs against human CD5 was generated and tested for ability to induce complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) both as single mAbs and combinations of two mAbs against non-overlapping epitopes on human CD5. The results demonstrated that combinations of two mAbs significantly increased the level of CDC compared to the single mAbs, while no enhancement of ADCC was seen with anti-CD5 mAb combinations. High levels of CDC and ADCC correlated with low levels of Ab-induced CD5 internalization and degradation. Importantly, an anti-CD5 mAb combination enhanced CDC of CLL cells when combined with the anti-CD20 mAbs rituximab and ofatumumab as well as with the anti-CD52 mAb alemtuzumab. These results suggest that an anti-CD5 mAb combination inducing CDC and ADCC may be effective alone, in combination with mAbs against other targets or combined with chemotherapy for CLL and other CD5-expressing haematological or lymphoid malignancies. © 2013 John Wiley & Sons Ltd.

A junction-level optoelectronic characterization of etching-induced damage for third-generation HgCdTe infrared focal-plane array photodetectors

NASA Astrophysics Data System (ADS)

Wang, Peng; Wang, Yueming; Wu, Mingzai; Ye, Zhenhua

2018-06-01

Third-generation HgCdTe-based infrared focal plane arrays require high aspect ratio trenches with admissible etch induced damage at the surface and sidewalls for effectively isolating the pixels. In this paper, the high-density inductively coupled plasma enhanced reaction ion etching technique has been used for micro-mesa delineation of HgCdTe for third-generation infrared focal-plane array detectors. A nondestructive junction-level optoelectronic characterization method called laser beam induced current (LBIC) is used to evaluate the lateral junction extent of HgCdTe etch-induced damage scanning electron microscopy. It is found that the LBIC profiles exhibit evident double peaks and valleys phenomena. The lateral extent of etch induced mesa damage of ∼2.4 μm is obtained by comparing the LBIC profile and the scanning electron microscopy image of etched sample. This finding will guide us to nondestructively identify the distributions of the etching damages in large scale HgCdTe micro-mesa.

CD4 T cell subsets in the Mucosa are CD28+Ki-67−HLA-DR−CD69+ but show differential infection based on α4β7 receptor expression during acute SIV infection

PubMed Central

Kader, Muhamuda; Bixler, Sandra; Roederer, Mario; Veazey, Ronald; Mattapallil, Joseph J.

2009-01-01

Background CD4 T cell depletion in the mucosa has been well documented during acute HIV and SIV infections. The demonstration the HIV/SIV can use the α4β7 receptor for viral entry suggests that these viruses selectively target CD4 T cells in the mucosa that express high levels of α4β7 receptor. Methods Mucosal samples obtained from SIV infected rhesus macaques during the early phase of infection were used for immunophenotypic analysis. CD4 T cell subsets were sorted based on the expression of β7 and CD95 to quantify the level of SIV infection in different subsets of CD4 T cells. Changes in IL-17, IL-21, IL-23 and TGFβ mRNA expression was determined using Taqman PCR. Results CD4 T cells in the mucosa were found to harbor two major population of cells; ~25% of CD4 T cells expressed the α4+β7hi phenotype, whereas the rest of the 75% expressed an α4+β7int phenotype. Both the subsets were predominantly CD28+Ki-67− HLA-DR− but CD69+, and expressed detectable levels of CCR5 on their surface. Interestingly, however, α4+β7hiCD4 T cells were found to harbor more SIV than the α4+β7int subsets at day 10 pi. Early infection was associated with a dramatic increase in the expression of IL-17, and IL-17 promoting cytokines IL-21, IL-23, and TGFβ that stayed high even after the loss of mucosal CD4 T cells. Conclusions Our results suggest that the differential expression of the α4β7 receptor contributes to the differences in the extent of infection in CD4 T cell subsets in the mucosa. Early infection associated dysregulation of the IL-17 network in mucosal tissues involves other non-Th-17 cells that likely contributes to the pro-inflammatory environment in the mucosa during acute stages of SIV infection. PMID:19863675

Survival Strategies of the Plant-Associated Bacterium Enterobacter sp. Strain EG16 under Cadmium Stress.

PubMed

Chen, Yanmei; Chao, Yuanqing; Li, Yaying; Lin, Qingqi; Bai, Jun; Tang, Lu; Wang, Shizhong; Ying, Rongrong; Qiu, Rongliang

2016-01-04

Plant-associated bacteria are of great interest because of their potential use in phytoremediation. However, their ability to survive and promote plant growth in metal-polluted soils remains unclear. In this study, a soilborne Cd-resistant bacterium was isolated and identified as Enterobacter sp. strain EG16. It tolerates high external Cd concentrations (Cd(2+) MIC, >250 mg liter(-1)) and is able to produce siderophores and the plant hormone indole-3-acetic acid (IAA), both of which contribute to plant growth promotion. Surface biosorption in this strain accounted for 31% of the total Cd accumulated. The potential presence of cadmium sulfide, shown by energy-dispersive X-ray (EDX) analysis, suggested intracellular Cd binding as a Cd response mechanism of the isolate. Cd exposure resulted in global regulation at the transcriptomic level, with the bacterium switching to an energy-conserving mode by inhibiting energy-consuming processes while increasing the production of stress-related proteins. The stress response system included increased import of sulfur and iron, which become deficient under Cd stress, and the redirection of sulfur metabolism to the maintenance of intracellular glutathione levels in response to Cd toxicity. Increased production of siderophores, responding to Cd-induced Fe deficiency, not only is involved in the Cd stress response systems of EG16 but may also play an important role in promoting plant growth as well as alleviating the Cd-induced inhibition of IAA production. The newly isolated strain EG16 may be a suitable candidate for microbially assisted phytoremediation due to its high resistance to Cd and its Cd-induced siderophore production, which is likely to contribute to plant growth promotion. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Survival Strategies of the Plant-Associated Bacterium Enterobacter sp. Strain EG16 under Cadmium Stress

PubMed Central

Chen, Yanmei; Li, Yaying; Lin, Qingqi; Bai, Jun; Tang, Lu; Wang, Shizhong; Ying, Rongrong

2016-01-01

Plant-associated bacteria are of great interest because of their potential use in phytoremediation. However, their ability to survive and promote plant growth in metal-polluted soils remains unclear. In this study, a soilborne Cd-resistant bacterium was isolated and identified as Enterobacter sp. strain EG16. It tolerates high external Cd concentrations (Cd2+ MIC, >250 mg liter−1) and is able to produce siderophores and the plant hormone indole-3-acetic acid (IAA), both of which contribute to plant growth promotion. Surface biosorption in this strain accounted for 31% of the total Cd accumulated. The potential presence of cadmium sulfide, shown by energy-dispersive X-ray (EDX) analysis, suggested intracellular Cd binding as a Cd response mechanism of the isolate. Cd exposure resulted in global regulation at the transcriptomic level, with the bacterium switching to an energy-conserving mode by inhibiting energy-consuming processes while increasing the production of stress-related proteins. The stress response system included increased import of sulfur and iron, which become deficient under Cd stress, and the redirection of sulfur metabolism to the maintenance of intracellular glutathione levels in response to Cd toxicity. Increased production of siderophores, responding to Cd-induced Fe deficiency, not only is involved in the Cd stress response systems of EG16 but may also play an important role in promoting plant growth as well as alleviating the Cd-induced inhibition of IAA production. The newly isolated strain EG16 may be a suitable candidate for microbially assisted phytoremediation due to its high resistance to Cd and its Cd-induced siderophore production, which is likely to contribute to plant growth promotion. PMID:26729719

Protein profile of basal prostate epithelial progenitor cells--stage-specific embryonal antigen 4 expressing cells have enhanced regenerative potential in vivo.

PubMed

Höfner, Thomas; Klein, Corinna; Eisen, Christian; Rigo-Watermeier, Teresa; Haferkamp, Axel; Sprick, Martin R

2016-04-01

The long-term propagation of basal prostate progenitor cells ex vivo has been very difficult in the past. The development of novel methods to expand prostate progenitor cells in vitro allows determining their cell surface phenotype in greater detail. Mouse (Lin(-)Sca-1(+) CD49f(+) Trop2(high)-phenotype) and human (Lin(-) CD49f(+) TROP2(high)) basal prostate progenitor cells were expanded in vitro. Human and mouse cells were screened using 242 anti-human or 176 antimouse monoclonal antibodies recognizing the cell surface protein profile. Quantitative expression was evaluated at the single-cell level using flow cytometry. Differentially expressed cell surface proteins were evaluated in conjunction with the known CD49f(+)/TROP2(high) phenotype of basal prostate progenitor cells and characterized by in vivo sandwich-transplantation experiments using nude mice. The phenotype of basal prostate progenitor cells was determined as CD9(+)/CD24(+)/CD29(+)/CD44(+)/CD47(+)/CD49f(+)/CD104(+)/CD147(+)/CD326(+)/Trop2(high) of mouse as well as human origin. Our analysis revealed several proteins, such as CD13, Syndecan-1 and stage-specific embryonal antigens (SSEAs), as being differentially expressed on murine and human CD49f(+) TROP2(+) basal prostate progenitor cells. Transplantation experiments suggest that CD49f(+) TROP2(high) SSEA-4(high) human prostate basal progenitor cells to be more potent to regenerate prostate tubules in vivo as compared with CD49f(+) TROP2(high) or CD49f(+) TROP2(high) SSEA-4(low) cells. Determination of the cell surface protein profile of functionally defined murine and human basal prostate progenitor cells reveals differentially expressed proteins that may change the potency and regenerative function of epithelial progenitor cells within the prostate. SSEA-4 is a candidate cell surface marker that putatively enables a more accurate identification of the basal PESC lineage. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

AhIRT1 and AhNRAMP1 metal transporter expression correlates with Cd uptake in peanuts under iron deficiency

PubMed Central

Xia, Shenglan; Deng, Rubo; Liu, Caifeng; Shi, Gangrong

2017-01-01

Fe deficiency may increase Cd accumulation in peanuts. However, the mechanisms are not yet fully understood. In the present study, two contrasting peanut cultivars, Luhua 8 (low seed-Cd cultivar) and Zhenghong 3 (high seed-Cd cultivar) were used to investigate the effect of Fe deficiency on the uptake and accumulation of cadmium (Cd) by hydroponic experiments. Under Fe-sufficient conditions, compared with Luhua 8, Zhenghong 3 had higher specific root length (SRL) and proportion of fine roots with a lower Km for Cd and showed slightly higher expression of AhIRT1 and AhNRAMP1 in the roots. These traits may be responsible for high capacity for Cd accumulation in Zhenghong 3. Under Fe deficiency, the increase of Cd accumulation was much larger in Zhenghong 3 than in Luhua 8. Kinetics studies revealed that the Vmax for Cd influx was 1.56-fold higher in Fe-deficient plants than in Fe-sufficient plants for Zhenghong 3, versus 0.48-fold higher for Luhua 8. Moreover, the increased expression levels of AhIRT1 and AhNRAMP1 induced by Fe deficiency was higher in Zhenghong 3 than in Luhua 8. Yeast complementation assays suggested that the AhIRT1 and AhNRAMP1 may function as transporters involved in Cd uptake. In conclusion, the different Cd accumulation between the two cultivars under Fe deficiency may be correlated with Vmax value for Cd uptake and the expression levels of AhIRT1 and AhNRAMP1 in the roots. PMID:28981520

Cadmium spiked soil modulates root organic acids exudation and ionic contents of two differentially Cd tolerant maize (Zea mays L.) cultivars.

PubMed

Javed, M Tariq; Akram, M Sohail; Tanwir, Kashif; Javed Chaudhary, Hassan; Ali, Qasim; Stoltz, Eva; Lindberg, Sylvia

2017-07-01

Our earlier work described that the roots of two maize cultivars, grown hydroponically, differentially responded to cadmium (Cd) stress by initiating changes in medium pH depending on their Cd tolerance. The current study investigated the root exudation, elemental contents and antioxidant behavior of the same maize cultivars [cv. 3062 (Cd-tolerant) and cv. 31P41 (Cd-sensitive)] under Cd stress. Plants were maintained in a rhizobox-like system carrying soil spiked with Cd concentrations of 0, 10, 20, 30, 40 and 50 μmol/kg soil. The root and shoot Cd contents increased, while Mg, Ca and Fe contents mainly decreased at higher Cd levels, and preferentially in the sensitive cultivar. Interestingly, the K contents increased in roots of cv. 3062 at low Cd treatments. The Cd stress caused acidosis of the maize root exudates predominantly in cv. 3062. The concentration of various organic acids was significantly increased in the root exudates of cv. 3062 with applied Cd levels. This effect was diminished in cv. 31P41 at higher Cd levels. Cd exposure increased the relative membrane permeability, anthocyanin (only in cv. 3062), proline contents and the activities of peroxidases (POD) and superoxide dismutase (SOD). The only exception was the catalase activity, which was diminished in both cultivars. Root Cd contents were positively correlated with the secretion of acetic acid, oxalic acid, glutamic acid, citric acid, and succinic acid. The antioxidants like POD and SOD exhibited a positive correlation with the organic acids under Cd stress. It is likly that a high exudation of dicarboxylic organic acids improves nutrient uptake and activities of antioxidants, which enables the tolerant cultivar to acclimatize in Cd polluted environment. Copyright © 2017 Elsevier Inc. All rights reserved.

High frequency of CD34+CD38-/low immature leukemia cells is correlated with unfavorable prognosis in acute myeloid leukemia.

PubMed

Plesa, Adriana; Dumontet, Charles; Mattei, Eve; Tagoug, Ines; Hayette, Sandrine; Sujobert, Pierre; Tigaud, Isabelle; Pages, Marie Pierre; Chelghoum, Youcef; Baracco, Fiorenza; Labussierre, Helene; Ducastelle, Sophie; Paubelle, Etienne; Nicolini, Franck Emmanuel; Elhamri, Mohamed; Campos, Lydia; Plesa, Claudiu; Morisset, Stéphane; Salles, Gilles; Bertrand, Yves; Michallet, Mauricette; Thomas, Xavier

2017-12-26

To evaluate the importance of the CD34+CD38- cell population when compared to the CD34+CD38+/low and CD34+CD38+/high leukemic cell sub-populations and to determine its correlations with leukemia characteristics and known prognostic factors, as well as with response to therapy and survival. Two hundred bone marrow samples were obtained at diagnosis from 200 consecutive patients with newly diagnosed acute myeloid leukemia (AML) were studied between September 2008 and December 2010 at our Institution (Hematology Department, Lyon, France). The CD34/CD38 cell profile was analyzed by multiparameter flowcytometry approach using 8C panels and FACS CANTO and Diva software (BD Bioscience). We analyzed CD34 and CD38 expression in bone marrow samples of 200 AML patients at diagnosis, and investigated the prognostic value of the most immature CD34+CD38- population. Using a cut-off value of 1% of CD34+CD38- from total "bulk leukemic cells" we found that a high (> 1%) level of CD34+CD38- blasts at diagnosis was correlated with advanced age, adverse cytogenetics as well as with a lower rate of complete response after induction and shorter disease-free survival. In a multivariate analysis considering age, leukocytosis, the % of CD34+ blasts cells and the standardized cytogenetic and molecular risk subgroups, a percentage of CD34+CD38- leukemic cells > 1% was an independent predictor of DFS [HR = 2.8 (1.02-7.73), P = 0.04] and OS [HR = 2.65 (1.09-6.43), P = 0.03]. Taken together, these results show that a CD34/CD38 "backbone" for leukemic cell analysis by multicolour flowcytometry at diagnosis provides useful prognostic information.

The CD14+CD16+ Inflammatory Monocyte Subset Displays Increased Mitochondrial Activity and Effector Function During Acute Plasmodium vivax Malaria

PubMed Central

Antonelli, Lis R. V.; Leoratti, Fabiana M. S.; Costa, Pedro A. C.; Rocha, Bruno C.; Diniz, Suelen Q.; Tada, Mauro S.; Pereira, Dhelio B.; Teixeira-Carvalho, Andrea; Golenbock, Douglas T.; Gonçalves, Ricardo; Gazzinelli, Ricardo T.

2014-01-01

Infection with Plasmodium vivax results in strong activation of monocytes, which are important components of both the systemic inflammatory response and parasite control. The overall goal of this study was to define the role of monocytes during P. vivax malaria. Here, we demonstrate that P. vivax–infected patients display significant increase in circulating monocytes, which were defined as CD14+CD16− (classical), CD14+CD16+ (inflammatory), and CD14loCD16+ (patrolling) cells. While the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytokines, the CD16+ cells, in particular the CD14+CD16+ monocytes, expressed the highest levels of activation markers, which included chemokine receptors and adhesion molecules. Morphologically, CD14+ were distinguished from CD14lo monocytes by displaying larger and more active mitochondria. CD14+CD16+ monocytes were more efficient in phagocytizing P. vivax-infected reticulocytes, which induced them to produce high levels of intracellular TNF-α and reactive oxygen species. Importantly, antibodies specific for ICAM-1, PECAM-1 or LFA-1 efficiently blocked the phagocytosis of infected reticulocytes by monocytes. Hence, our results provide key information on the mechanism by which CD14+CD16+ cells control parasite burden, supporting the hypothesis that they play a role in resistance to P. vivax infection. PMID:25233271

CD147, CD44, and the epidermal growth factor receptor (EGFR) signaling pathway cooperate to regulate breast epithelial cell invasiveness.

PubMed

Grass, G Daniel; Tolliver, Lauren B; Bratoeva, Momka; Toole, Bryan P

2013-09-06

The immunoglobulin superfamily glycoprotein CD147 (emmprin; basigin) is associated with an invasive phenotype in various types of cancers, including malignant breast cancer. We showed recently that up-regulation of CD147 in non-transformed, non-invasive breast epithelial cells is sufficient to induce an invasive phenotype characterized by membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invadopodia activity (Grass, G. D., Bratoeva, M., and Toole, B. P. (2012) Regulation of invadopodia formation and activity by CD147. J. Cell Sci. 125, 777-788). Here we found that CD147 induces breast epithelial cell invasiveness by promoting epidermal growth factor receptor (EGFR)-Ras-ERK signaling in a manner dependent on hyaluronan-CD44 interaction. Furthermore, CD147 promotes assembly of signaling complexes containing CD147, CD44, and EGFR in lipid raftlike domains. We also found that oncogenic Ras regulates CD147 expression, hyaluronan synthesis, and formation of CD147-CD44-EGFR complexes, thus forming a positive feedback loop that may amplify invasiveness. Last, we showed that malignant breast cancer cells are heterogeneous in their expression of surface-associated CD147 and that high levels of membrane CD147 correlate with cell surface EGFR and CD44 levels, activated EGFR and ERK1, and activated invadopodia. Future studies should evaluate CD147 as a potential therapeutic target and disease stratification marker in breast cancer.

Physiological responses to cadmium stress in strawberry treated with pomegranate peel-activated carbon.

PubMed

Naderi, Somayeh; Gholami, Mahdiyeh; Baninasab, Bahram; Afyuni, Majid

2018-05-12

Many reports have already been published regarding the removal of heavy metals from aqueous solutions onto activated carbon. However, the biosorbents' effect on the plant response still needs further investigation. In this study, activated carbon derived from the pomegranate peel [pomegranate activated carbons (PAC)] was used to see the effects of the addition of PAC on growing strawberry in Cd-contaminated sand. Cd accumulation and toxicity to strawberry was investigated by measuring the concentration of Cd in plant tissues and various biochemical activities of plant. Our results suggested that PAC had a high sorption capacity for Cd. Strawberry plant tried to deal with the Cd-induced oxidative stress by strengthening its antioxidant competences and decreasing Cd absorption. In comparison with the control, PAC applied to the sand decreased the level of lipid peroxidation and enhanced the carotenoid content. The greater tolerance of strawberry toward the level of Cd due to the application of PAC was associated with improving the physical conditions of the soil, increasing the amounts of some essential elements and decreasing the level of Cd absorption. Gaviota strawberry cultivar exposed to 5 or 10 mg kg -1 Cd was able to adopt a new metabolic equilibrium, allowing the plant to cope with this metal.

Cadmium accumulation and tolerance of Macleaya cordata: a newly potential plant for sustainable phytoremediation in Cd-contaminated soil.

PubMed

Nie, Jian; Liu, Yunguo; Zeng, Guangming; Zheng, Bohong; Tan, Xiaofei; Liu, Huan; Xie, Jieli; Gan, Chao; Liu, Wei

2016-05-01

Heavy metal pollution is a major concern of the public due to their threats to the safety of food chains. A 60-day pot experiment was conducted using Macleaya cordata as plant material to investigate the phytoremediation potential and anti-oxidative responses of M. cordata under different Cd stress. Significant growth inhibition phenomenon and toxic symptoms were not detected in the experiment. The high biomass of the plant provided high accumulation capacity for Cd with an average dry weight of 3.6 g. The maximum extraction amount of Cd was 393 μg·plant(-1), suggesting that this species had potential for phytoremediation of Cd-contaminated soil. A slight increase of chlorophyll (CHL) content was observed in Cd10 treatment. The plant was confirmed to have relatively high tolerance to the Cd stress on the basis of tolerance indexes (TI), relative water content, and CHLa/CHLb ratio. M. cordata could maintain high level of superoxide dismutase (SOD) activity under Cd stress, indicating strong tolerance capacity for reactive oxygen species (ROS) in plant cells. Catalase (CAT) activity show a certain range of decline in the experiment compare to the control. And peroxidase (POD) activity in leaves changed irregularly when compared to the control. The malondialdehyde (MDA) content increased as Cd concentration elevated compared to the control. In addition, as an inedible crop with relatively high economic value, M. cordata have shown the advantage of high biomass and high tolerance under Cd stress, which can provide a new plant resource for sustainable phytoremediation.

CD146 Expression Influences Periapical Cyst Mesenchymal Stem Cell Properties.

PubMed

Paduano, Francesco; Marrelli, Massimo; Palmieri, Francesca; Tatullo, Marco

2016-10-01

Recent studies have identified a new human dental derived progenitor cell population with multi-lineage differentiation potential referred to as human periapical cyst mesenchymal stem cells (hPCy-MSCs). In the present study, we compared two subpopulations of hPCy-MSCs characterised by the low or high expression of CD146 to establish whether this expression can regulate their stem cell properties. Using flow cytometry, we evaluated the stem cell marker profile of hPCy-MSCs during passaging. Furthermore, CD146 Low and CD146 High cells were sorted by magnetic beads and subsequently both cell populations were evaluated for differences in their proliferation, self-renewal, stem cell surface markers, stemness genes expression and osteogenic differentiation potential.We found that hPCy-MSCs possessed a stable expression of several mesenchymal stem cell surface markers, whereas CD146 expression declined during passaging.In addition, sorted CD146 Low cells proliferated significantly faster, displayed higher colony-forming unit-fibroblast capacity and showed higher expression of Klf4 when compared to the CD146 High subset. Significantly, the osteogenic potential of hPCy-MSCs was greater in the CD146 Low than in CD146 High population. These results demonstrate that CD146 is spontaneously downregulated with passaging at both mRNA and protein levels and that the high expression of CD146 reduces the proliferative, self-renewal and osteogenic differentiation potential of hPCy-MSCs. In conclusion, our study demonstrates that changes in the expression of CD146 can influence the stem cell properties of hPCy-MSCs.

Expression of CD10 predicts tumor progression and unfavorable prognosis in malignant melanoma.

PubMed

Oba, Junna; Nakahara, Takeshi; Hayashida, Sayaka; Kido, Makiko; Xie, Lining; Takahara, Masakazu; Uchi, Hiroshi; Miyazaki, Shogo; Abe, Takeru; Hagihara, Akihito; Moroi, Yoichi; Furue, Masutaka

2011-12-01

CD10 expression in malignant melanoma (MM) has been reported to increase according to tumor progression and metastasis; however, its association with patient outcome has not been clarified. We examined the immunohistochemical expression of CD10 in MM to determine whether or not it could serve as a marker for tumor progression and prognosis. A total of 64 formalin-fixed, paraffin-embedded samples of primary MM were immunostained for CD10. Similarly, 40 samples of melanocytic nevus and 20 of metastatic MM were analyzed for comparison. The following clinicopathologic variables were evaluated: age, gender, histologic type, tumor site, Breslow thickness, Clark level, the presence or absence of ulceration and tumor-infiltrating lymphocytes, and survival. Statistical analyses were performed to assess for associations. Several parameters were analyzed for survival using the Kaplan-Meier method and Cox proportional hazards model. Immunohistochemical analysis revealed that 34 of 64 cases (53%) of primary MM expressed CD10, compared with 15 of 20 cases (75%) of metastatic MM and only 4 of 40 cases (10%) of nevus. There was a significant positive relationship between CD10 expression and Breslow thickness, Clark level, and ulceration. Univariate analysis revealed 4 significant factors for shorter survival periods: CD10 expression, high Breslow thickness, high Clark level, and the presence of ulceration (P < .01 each). In multivariate analysis, CD10 expression was revealed to be a statistically significant and independent prognostic factor. The major limitation was the small sample size. CD10 expression may serve as a progression marker and can predict unfavorable prognosis in patients with MM. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project

PubMed Central

Kim, Youn H.; Tavallaee, Mahkam; Sundram, Uma; Salva, Katrin A.; Wood, Gary S.; Li, Shufeng; Rozati, Sima; Nagpal, Seema; Krathen, Michael; Reddy, Sunil; Hoppe, Richard T.; Nguyen-Lin, Annie; Weng, Wen-Kai; Armstrong, Randall; Pulitzer, Melissa; Advani, Ranjana H.; Horwitz, Steven M.

2015-01-01

Purpose In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored. Patients and Methods In this phase II study, patients with MF or SS with negligible to 100% CD30 expression levels were treated with brentuximab vedotin (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The primary end point was overall global response rate. Secondary end points included correlation of tissue CD30 expression level with clinical response, time to response, duration of response, progression-free and event-free survivals, and safety. Results Of the 32 patients enrolled and treated, 30 patients had available efficacy evaluations. Objective global response was observed in 21 (70%) of 30 patients (90% CI, 53% to 83%). CD30 expression assessed by immunohistochemistry was highly variable, with a median CD30max of 13% (range, 0% to 100%). Those with <5% CD30 expression had a lower likelihood of global response than did those with 5% or greater CD30 expression (P < .005). CD163 positive tumor-associated macrophages, many of which coexpress CD30, were abundant in tissue. Peripheral neuropathy was the most common adverse event. Conclusion Brentuximab vedotin demonstrated significant clinical activity in treatment-refractory or advanced MF or SS with a wide range of CD30 expression levels. Additional biomarker studies may help optimize rational design of combination therapies with brentuximab vedotin. PMID:26195720

Systemic Sclerosis Patients Present Alterations in the Expression of Molecules Involved in B-Cell Regulation

PubMed Central

Soto, Lilian; Ferrier, Ashley; Aravena, Octavio; Fonseca, Elianet; Berendsen, Jorge; Biere, Andrea; Bueno, Daniel; Ramos, Verónica; Aguillón, Juan Carlos; Catalán, Diego

2015-01-01

The activation threshold of B cells is tightly regulated by an array of inhibitory and activator receptors in such a way that disturbances in their expression can lead to the appearance of autoimmunity. The aim of this study was to evaluate the expression of activating and inhibitory molecules involved in the modulation of B cell functions in transitional, naive, and memory B-cell subpopulations from systemic sclerosis patients. To achieve this, blood samples were drawn from 31 systemic sclerosis patients and 53 healthy individuals. Surface expression of CD86, MHC II, CD19, CD21, CD40, CD22, Siglec 10, CD35, and FcγRIIB was determined by flow cytometry. IL-10 production was evaluated by intracellular flow cytometry from isolated B cells. Soluble IL-6 and IL-10 levels were measured by ELISA from supernatants of stimulated B cells. Systemic sclerosis patients exhibit an increased frequency of transitional and naive B cells related to memory B cells compared with healthy controls. Transitional and naive B cells from patients express higher levels of CD86 and FcγRIIB than healthy donors. Also, B cells from patients show high expression of CD19 and CD40, whereas memory cells from systemic sclerosis patients show reduced expression of CD35. CD19 and CD35 expression levels associate with different autoantibody profiles. IL-10+ B cells and secreted levels of IL-10 were markedly reduced in patients. In conclusion, systemic sclerosis patients show alterations in the expression of molecules involved in B-cell regulation. These abnormalities may be determinant in the B-cell hyperactivation observed in systemic sclerosis. PMID:26483788

DNA methylation is differentially associated with environmental cadmium exposure based on sex and smoking status

PubMed Central

Virani, Shama; Rentschler, Katie M.; Nishijo, Muneko; Ruangyuttikarn, Werawan; Swaddiwudhipong, Witaya; Basu, Niladri; Rozek, Laura S.

2016-01-01

The adverse health effects of cadmium (Cd) are well known in human populations; however, much of what is known about biological mechanisms of Cd comes from in vitro and animal studies. The adverse health outcomes due to high levels of Cd exposure in the population of Mae Sot, Thailand have been extensively characterized. Here, for the first time, this population is being studied in an epigenetic context. The objective of this study was to characterize the association between DNA methylation markers and Cd exposure, taking into account sex and smoking differences, in an adult population at an increased risk of experiencing adverse health outcomes from high body burden of Cd. One hundred and sixty-nine residents from known exposure areas of Mae Sot, Thailand and one hundred residents from non-exposed areas nearby were surveyed in 2012. Urine and blood samples were collected for measurement of urinary Cd (UCd) and DNA methylation of Cd-related markers (DNMT3B, MGMT, LINE-1, MT2A). UCd levels were 7 times higher in the exposed compared to the unexposed populations (exposed median: 7.4 μg/L, unexposed median: 1.0 μg/L, p <0.001). MGMT hypomethylation was associated with increasing levels of UCd in the total population. Sex-specific associations included MT2A and DNMT3B hypomethylation in women and LINE-1 hypermethylation in men with increasing UCd. Upon subanalysis, these associations separated by smoking status. In summary, environmental Cd exposure is associated with gene-specific DNA methylation in a sex and smoking dependent manner. PMID:26688266

Enforced IL-10 Expression Confers Type 1 Regulatory T Cell (Tr1) Phenotype and Function to Human CD4+ T Cells

PubMed Central

Andolfi, Grazia; Fousteri, Georgia; Rossetti, Maura; Magnani, Chiara F; Jofra, Tatiana; Locafaro, Grazia; Bondanza, Attilio; Gregori, Silvia; Roncarolo, Maria-Grazia

2012-01-01

Type 1 regulatory T (Tr1) cells are an inducible subset of CD4+ Tr cells characterized by high levels of interleukin (IL)-10 production and regulatory properties. Several protocols to generate human Tr1 cells have been developed in vitro. However, the resulting population includes a significant fraction of contaminating non-Tr1 cells, representing a major bottleneck for clinical application of Tr1 cell therapy. We generated an homogeneous IL-10–producing Tr1 cell population by transducing human CD4+ T cells with a bidirectional lentiviral vector (LV) encoding for human IL-10 and the marker gene, green fluorescent protein (GFP), which are independently coexpressed. The resulting GFP+ LV-IL-10–transduced human CD4+ T (CD4LV-IL-10) cells expressed, upon T-cell receptor (TCR) activation, high levels of IL-10 and concomitant low levels of IL-4, and markers associated with IL-10. Moreover, CD4LV-IL-10 T cells displayed typical Tr1 features: the anergic phenotype, the IL-10, and transforming growth factor (TGF)-β dependent suppression of allogeneic T-cell responses, and the ability to suppress in a cell-to-cell contact independent manner in vitro. CD4LV-IL-10 T cells were able to control xeno graft-versus-host disease (GvHD), demonstrating their suppressive function in vivo. These results show that constitutive over-expression of IL-10 in human CD4+ T cells leads to a stable cell population that recapitulates the phenotype and function of Tr1 cells. PMID:22692497

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients.

PubMed

Saison, J; Ferry, T; Demaret, J; Maucort Boulch, D; Venet, F; Perpoint, T; Ader, F; Icard, V; Chidiac, C; Monneret, G

2014-06-01

The mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (T(regs)) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4(+) T cell count (> or < 500/mm(3)). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4(+) lymphocytes, including T(reg) subsets, and CD8(+) T cells was performed. Percentages of activated CD4(+) T cells, T(regs), effector T(regs) and terminal effector T(regs) were found to be significantly elevated in iIR. Neither the percentage of activated CD8(+) T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4(+) T cell count and percentage of T(regs) were the only two parameters associated independently with iIR [odds ratio (OR) = 2·339, P = 0·001, and OR = 0·803, P = 0·041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4(+) and CD8(+) T cells, T(reg) percentages and very low-level viraemia. Causative interactions between T(regs) and CD4(+) T cells should now be explored prospectively in a large patients cohort. © 2014 British Society for Immunology.

Human Peripheral Blood Mononuclear Cells Exhibit Heterogeneous CD52 Expression Levels and Show Differential Sensitivity to Alemtuzumab Mediated Cytolysis

PubMed Central

Rao, Sambasiva P.; Sancho, Jose; Campos-Rivera, Juanita; Boutin, Paula M.; Severy, Peter B.; Weeden, Timothy; Shankara, Srinivas; Roberts, Bruce L.; Kaplan, Johanne M.

2012-01-01

Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs) from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs) display the highest number while natural killer (NK) cells, plasmacytoid dendritic cells (pDCs) and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC) studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs) on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact. PMID:22761788

The Co-Induced Effects of Molybdenum and Cadmium on the Trace Elements and the mRNA Expression Levels of CP and MT in Duck Testicles.

PubMed

Xia, Bing; Chen, Hua; Hu, Guoliang; Wang, Liqi; Cao, Huabin; Zhang, Caiying

2016-02-01

To investigate the chronic toxicity of molybdenum (Mo) and cadmium (Cd) on the trace elements and the mRNA expression levels of ceruloplasmin (CP) and metallothionein (MT) in duck testicles, 120 healthy 11-day-old male ducks were randomly divided into six groups with 20 ducks in each group. Ducks were treated with the diet containing different dosages of Mo or Cd. The source of Mo and Cd was hexaammonium molybdate ([(NH4)6Mo7O24·4H2O]) and cadmium sulfate (3CdSO4·8H2O), respectively, in this study. After being treated for 60 and 120 days, ten male birds in each group were randomly selected and euthanized and then testicles were aseptically collected for determining the mRNA expression levels of MT and CP, antioxidant indexes, and contents of trace elements in the testicle. In addition, testicle tissues at 120 days were subjected to histopathological analysis with the optical microscope. The results showed that co-exposure to Mo and Cd resulted in an increase in malondialdehyde (MDA) level while decrease in xanthine oxidase (XOD) and catalase (CAT) activities. The mRNA expression level of MT gene was upregulated while CP was decreased in combination groups. Contents of Mo, copper (Cu), iron (Fe), and zinc (Zn) decreased in combined groups while Cd increased in Cd and combined groups at 120 days. Furthermore, severe congestion, low sperm count, and malformation were observed in low dietary of Mo combined with Cd group and high dietary of Mo combined with Cd group. Our results suggested that Mo and Cd might aggravate testicular degeneration synergistically through altering the mRNA expression levels of MT and CP, increasing lipid peroxidation through inhibiting related enzyme activities and disturbing homeostasis of trace elements in testicles. Interaction of Mo and Cd may have a synergistic effect on the testicular toxicity.

Antibodies attenuate the capacity of dendritic cells to stimulate HIV-specific cytotoxic T lymphocytes

PubMed Central

Posch, Wilfried; Cardinaud, Sylvain; Hamimi, Chiraz; Fletcher, Adam; Mühlbacher, Annelies; Loacker, Klaus; Eichberger, Paul; Dierich, Manfred P.; Pancino, Gianfranco; Lass-Flörl, Cornelia; Moris, Arnaud; Saez-Cirion, Asier; Wilflingseder, Doris

2014-01-01

Background Control of HIV is suggested to depend on potent effector functions of the virus-specific CD8+ T-cell response. Antigen opsonization can modulate the capture of antigen, its presentation, and the priming of specific CD8+ T-cell responses. Objective We have previously shown that opsonization of retroviruses acts as an endogenous adjuvant for dendritic cell (DC)–mediated induction of specific cytotoxic T lymphocytes (CTLs). However, in some HIV-positive subjects, high levels of antibodies and low levels of complement fragments coat the HIV surface. Methods Therefore we analyzed the effect of IgG opsonization on the antigen-presenting capacity of DCs by using CD8+ T-cell proliferation assays after repeated prime boosting, by measuring the antiviral activity against HIV-infected autologous CD4+ T cells, and by determining IFN-γ secretion from HIV-specific CTL clones. Results We find that DCs exposed to IgG-opsonized HIV significantly decreased the HIV-specific CD8+ T-cell response compared with the earlier described efficient CD8+ T-cell activation induced by DCs loaded with complement-opsonized HIV. DCs exposed to HIV bearing high surface IgG levels after incubation in plasma from HIV-infected subjects acted as weak stimulators for HIV-specific CTL clones. In contrast, HIV opsonized with plasma from patients exhibiting high complement and low IgG deposition on the viral surface favored significantly higher activation of HIV-specific CD8+ T-cell clones. Conclusion Our ex vivo and in vitro observations provide the first evidence that IgG opsonization of HIV is associated with a decreased CTL-stimulatory capacity of DCs. PMID:23063584

Zn/Cd ratios and cadmium isotope evidence for the classification of lead-zinc deposits

PubMed Central

Wen, Hanjie; Zhu, Chuanwei; Zhang, Yuxu; Cloquet, Christophe; Fan, Haifeng; Fu, Shaohong

2016-01-01

Lead-zinc deposits are often difficult to classify because clear criteria are lacking. In recent years, new tools, such as Cd and Zn isotopes, have been used to better understand the ore-formation processes and to classify Pb-Zn deposits. Herein, we investigate Cd concentrations, Cd isotope systematics and Zn/Cd ratios in sphalerite from nine Pb-Zn deposits divided into high-temperature systems (e.g., porphyry), low-temperature systems (e.g., Mississippi Valley type [MVT]) and exhalative systems (e.g., sedimentary exhalative [SEDEX]). Our results showed little evidence of fractionation in the high-temperature systems. In the low-temperature systems, Cd concentrations were the highest, but were also highly variable, a result consistent with the higher fractionation of Cd at low temperatures. The δ114/110Cd values in low-temperature systems were enriched in heavier isotopes (mean of 0.32 ± 0.31‰). Exhalative systems had the lowest Cd concentrations, with a mean δ114/110Cd value of 0.12 ± 0.50‰. We thus conclude that different ore-formation systems result in different characteristic Cd concentrations and fraction levels and that low-temperature processes lead to the most significant fractionation of Cd. Therefore, Cd distribution and isotopic studies can support better understanding of the geochemistry of ore-formation processes and the classification of Pb-Zn deposits. PMID:27121538

Inflammation-induced CD69+ Kupffer cell feedback inhibits T cell proliferation via membrane-bound TGF-β1.

PubMed

Zhang, Xiang; Jiang, Zhengping; Gu, Yan; Liu, Yanfang; Cao, Xuetao; Han, Yanmei

2016-12-01

Kupffer cells, tissue-resident macrophage lineage cell, are enriched in vertebrate liver. The mouse F4/80 + Kupffer cells have been subclassified into two subpopulations according to their phenotype and function: CD68 + subpopulation with potent reactive oxygen species (ROS) production and phagocytic capacities, and CD11b + subpopulation with a potent capacity to produce T helper 1 cytokines. In addition, CD11b + Kupffer cells/macrophages may be migrated from the bone marrow or spleen, especially in inflammatory conditions of the liver. For analyzing diverse Kupffer cell subsets, we infected mice with Listeria monocytogenes and analyzed the phenotype variations of hepatic Kupffer cells. During L. monocytogenes infection, hepatic CD69 + Kupffer cells were significantly induced and expanded, and CD69 + Kupffer cells expressed higher level of CD11b, and particularly high level of membrane-bound TGF-β1 (mTGF-β1) but lower level of F4/80. We also found that clodronate liposome administration did not eliminate hepatic CD69 + Kupffer cell subset. We consider the hepatic CD69 + Kupffer cell population corresponds to CD11b + Kupffer cells, the bone marrow-derived population. Hepatic CD69 + Kupffer cells suppressed Ag-nonspecific and OVA-specific CD4 T cell proliferation through mTGF-β1 both in vitro and in vivo, meanwhile, they did not interfere with activation of CD4 T cells. Thus, we have identified a new subset of inflammation-induced CD69 + Kupffer cells which can feedback inhibit CD4 T cell response via cell surface TGF-β1 at the late stage of immune response against infection. CD69 + Kupffer cells may contribute to protect host from pathological injure by preventing overactivation of immune response.

High serum level of the soluble form of CD30 molecule in the early phase of HIV-1 infection as an independent predictor of progression to AIDS.

PubMed

Pizzolo, G; Vinante, F; Morosato, L; Nadali, G; Chilosi, M; Gandini, G; Sinicco, A; Raiteri, R; Semenzato, G; Stein, H

1994-06-01

To determine the serum levels of the soluble form of the CD30 (sCD30) activation molecule in the early phase of HIV-1 infection, and to investigate the possible correlation with evolution to AIDS. sCD30 values were determined by an enzyme-linked immunosorbent assay (ELISA) on serum samples collected at the time of the first evidence of HIV-1 infection in 110 individuals with a median follow-up of 56 months (range, 12-88 months), at the A1 (74 cases) or A2 (36 cases) stages of the 1993 revised Centers for Disease Control and Prevention classification. The data were evaluated using established clinical and immunological parameters, including circulating CD4+ T-cell count. The controls were 110 blood donors and 51 HIV-1-negative subjects belonging to groups at risk for HIV-1 infection. Elevated sCD30 levels (> 20 U/ml) were found in 83.6% of HIV-1-infected cases and in 47% of at-risk seronegatives. Data analysis revealed that HIV-1-infected patients with higher sCD30 levels (> 35 U/ml) experienced faster disease progression (P = 0.0002). This was also the case in patients at the earliest stage (A1) of HIV infection (P = 0.0027). In these latter cases the predictive value of sCD30 was independent of the initial absolute number of circulating CD4+ lymphocytes. Serum levels of sCD30 are increased in the large majority of patients in the early phase of HIV-1 infection and represent an indicator of progression to AIDS independent of other prognostic parameters.

Possible role of CD22, CD79b and CD20 expression in distinguishing small lymphocytic lymphoma from chronic lymphocytic leukemia.

PubMed

Jovanovic, Danijela; Djurdjevic, Predrag; Andjelkovic, Nebojsa; Zivic, Ljubica

2014-01-01

Flow cytometry has an important role in diagnosis and classification of B-cell lymphoproliferative disorders (BCLPDs). However, in distinguishing chronic lymphocytic leukemia (CLL) from small lymphocytic lymphoma (SLL) only clinical criteria are available so far. Aim of the study was to determine differences in the expression of common B cell markers (CD22, CD79b and CD20) on the malignant lymphocytes in the peripheral blood samples of CLL and SLL patients. Peripheral blood samples of 56 CLL and 11 SLL patients were analyzed by 5-color flow cytometry on the CD45/CD19/CD5 gate for CD22, CD79b and CD20. In the samples collected from the CLL patients, CD22 expression was detected in only 20% of patients in the low pattern, while in SLL patients the expression was medium and present in 90.9% of patients (p < 0.0001). For CD79b expression, statistical significance is reached both in the expression pattern, which was low/medium for CLL and high for SLL, and expression level (p = 0.006). The expression of CD20 was counted as the CD20/CD19 ratio. The average ratio was 0.512 in the CLL patients vs. 0.931 in the SLL patients (p = 0.0001). The pattern of expression and expression level of CD22, CD79b and CD20 in peripheral blood could be used for distinguishing SLL from CLL patients.

Development of radiopure cadmium tungstate crystal scintillators from enriched {sup 106}Cd and {sup 116}Cd to search for double beta decay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Danevich, F. A.; Boiko, R. S.; Chernyak, D. M.

2013-08-08

Cadmium tungstate crystal scintillators enriched in {sup 106}Cd up to 66% ({sup 106}CdWO{sub 4}) and in {sup 116}Cd up to 82% ({sup 116}CdWO{sub 4}) have been developed. The low radioactive contamination of the crystals measured on the level of ≤ 1.5 mBq/kg ({sup 40}K), ≤ 0.005 - 0.012 mBq/kg ({sup 226}Ra), 0.04 - 0.07 mBq/kg ({sup 228}Th) allows to carry out high sensitivity experiments to search for double beta processes in {sup 106}Cd and {sup 116}Cd.

CD4 cell responses to combination antiretroviral therapy in patients starting therapy at high CD4 cell counts.

PubMed

Wright, Stephen T; Carr, Andrew; Woolley, Ian; Giles, Michelle; Hoy, Jennifer; Cooper, David A; Law, Matthew G

2011-09-01

To examine CD4 cell responses to combination antiretroviral therapy (cART) in patients enrolled in the Australian HIV Observational Database who commenced cART at CD4 cell counts >350 cells per microliter. CD4 cell counts were modelled using random effects, repeated measurement models in 432 HIV-infected adults from Australian HIV Observational Database who commenced their first cART regimen and had a baseline CD4 count >350 cells per microliter. Using published AIDS and/or death incidence rates combined with the data summarized by time and predicted CD4 cell count, we calculated the expected reduction in risk of an event for different starting baseline CD4 strata. Mean CD4 counts increased above 500 cells per microliter in all baseline CD4 strata by 12 months (means of 596, 717, and 881 cells/μL in baseline CD4 strata 351-500, 501-650, and >650 cells/μL, respectively) and after 72 months since initiating cART, mean CD4 cell counts (by increasing baseline CD4 strata) were 689, 746, 742 cells per microliter. The expected reduction in risk of mortality for baseline CD4 counts >650 cells per microliter relative to 351-500 cells per microliter was approximately 8%, an absolute risk reduction 0.33 per 1000 treated patient-years. Patients starting cART at high CD4 cell counts (>650 cells/μL) tend to maintain this immunological level over 6 years of follow-up. Patients starting from 351 to 500 CD4 cells per microliter achieve levels of >650 cells per microliter after approximately 3 years of cART. Initiating cART with a baseline CD4 count 501-650 or >650 cells per microliter relative to 351-500 cells per microliter indicated a minimal reduction in risk of AIDS incidence and/or death.

Correlates of preserved CD4(+) T cell homeostasis during natural, nonpathogenic simian immunodeficiency virus infection of sooty mangabeys: implications for AIDS pathogenesis.

PubMed

Sumpter, Beth; Dunham, Richard; Gordon, Shari; Engram, Jessica; Hennessy, Margaret; Kinter, Audrey; Paiardini, Mirko; Cervasi, Barbara; Klatt, Nichole; McClure, Harold; Milush, Jeffrey M; Staprans, Silvija; Sodora, Donald L; Silvestri, Guido

2007-02-01

In contrast to HIV-infected humans, naturally SIV-infected sooty mangabeys (SMs) very rarely progress to AIDS. Although the mechanisms underlying this disease resistance are unknown, a consistent feature of natural SIV infection is the absence of the generalized immune activation associated with HIV infection. To define the correlates of preserved CD4(+) T cell counts in SMs, we conducted a cross-sectional immunological study of 110 naturally SIV-infected SMs. The nonpathogenic nature of the infection was confirmed by an average CD4(+) T cell count of 1,076 +/- 589/mm(3) despite chronic infection with a highly replicating virus. No correlation was found between CD4(+) T cell counts and either age (used as a surrogate marker for length of infection) or viremia. The strongest correlates of preserved CD4(+) T cell counts were a low percentage of circulating effector T cells (CD28(-)CD95(+) and/or IL-7R/CD127(-)) and a high percentage of CD4(+)CD25(+) T cells. These findings support the hypothesis that the level of immune activation is a key determinant of CD4(+) T cell counts in SIV-infected SMs. Interestingly, we identified 14 animals with CD4(+) T cell counts of <500/mm(3), of which two show severe and persistent CD4(+) T cell depletion (<50/mm(3)). Thus, significant CD4(+) T cell depletion does occasionally follow SIV infection of SMs even in the context of generally low levels of immune activation, lending support to the hypothesis of multifactorial control of CD4(+) T cell homeostasis in this model of infection. The absence of AIDS in these "CD4(low)" naturally SIV-infected SMs defines a protective role of the reduced immune activation even in the context of a significant CD4(+) T cell depletion.

Clinical Significance of PD-L1+ Exosomes in Plasma of Head and Neck Cancer Patients.

PubMed

Theodoraki, Marie-Nicole; Yerneni, Saigopalakrishna S; Hoffmann, Thomas K; Gooding, William E; Whiteside, Theresa L

2018-02-15

Purpose: The microenvironment of head and neck squamous cell carcinomas (HNSCC) is highly immunosuppressive. HNSCCs expressing elevated levels of PD-L1 have especially poor outcome. Exosomes that carry PD-L1 and suppress T-cell functions have been isolated from plasma of patients with HNSCC. The potential contributions of PD-L1 + exosomes to immune suppression and disease activity are evaluated. Experimental Design: Exosomes isolated from plasma of 40 HNSCC patients by size exclusion chromatography were captured on beads using anti-CD63 Abs, stained for PD-1 and PD-L1 and analyzed by flow cytometry. The percentages and mean fluorescence intensities (MFI) of PD-L1 + and PD-1 + exosome/bead complexes were correlated with the patients' clinicopathologic data. PD-L1 high or PD-L1 low exosomes were incubated with activated CD69 + human CD8 + T cells ± PD-1 inhibitor. Changes in CD69 expression levels on T cells were measured. Patients' plasma was tested for soluble PD-L1 (sPD-L1) by ELISA. Results: Levels of PD-L1 carried by exosomes correlated with patients' disease activity, the UICC stage and the lymph node status ( P = 0.0008-0.013). In contrast, plasma levels of sPD-L1 or exosome PD-1 levels did not correlate with any clinicopathologic parameters. CD69 expression levels were inhibited ( P < 0.03) by coincubation with PD-L1 high but not by PD-L1 low exosomes. Blocking of PD-L1 + exosome signaling to PD-1 + T cells attenuated immune suppression. Conclusions: PD-L1 levels on exosomes, but not levels of sPD-L1, associated with disease progression in HNSCC patients. Circulating PD-L1 + exosomes emerge as useful metrics of disease and immune activity in HNSCC patients. Circulating PD-L1 high exosomes in HNC patients' plasma but not soluble PD-L1 levels associate with disease progression. Clin Cancer Res; 24(4); 896-905. ©2017 AACR . ©2017 American Association for Cancer Research.

Biomarkers of oxidative stress and inflammation after wood smoke exposure in a reconstructed Viking Age house.

PubMed

Jensen, Annie; Karottki, Dorina Gabriela; Christensen, Jannie Marie; Bønløkke, Jakob Hjort; Sigsgaard, Torben; Glasius, Marianne; Loft, Steffen; Møller, Peter

2014-10-01

Exposure to particles from combustion of wood is associated with respiratory symptoms, whereas there is limited knowledge about systemic effects. We investigated effects on systemic inflammation, oxidative stress and DNA damage in humans who lived in a reconstructed Viking Age house, with indoor combustion of wood for heating and cooking. The subjects were exposed to high indoor concentrations of PM2.5 (700-3,600 µg/m(3)), CO (10.7-15.3 ppm) and NO2 (140-154 µg/m(3)) during a 1-week stay. Nevertheless, there were unaltered levels of genotoxicity, determined as DNA strand breaks and formamidopyrimidine DNA glycosylase and oxoguanine DNA glycosylase 1 sensitive sites in peripheral blood mononuclear cells. There were also unaltered expression levels of OGG1, HMOX1, CCL2, IL8, and TNF levels in leukocytes. In serum, there were unaltered levels of C-reactive protein, IL6, IL8, TNF, lactate dehydrogenase, cholesterol, triglycerides, and high-density lipoproteins. The wood smoke exposure was associated with decreased serum levels of sICAM-1, and a tendency to decreased sVCAM-1 levels. There was a minor increase in the levels of circulating monocytes expressing CD31, whereas there were unaltered expression levels of CD11b, CD49d, and CD62L on monocytes after the stay in the house. In conclusion, even a high inhalation exposure to wood smoke was associated with limited systemic effects on markers of oxidative stress, DNA damage, inflammation, and monocyte activation. © 2014 Wiley Periodicals, Inc.

Application of a rotation system to oilseed rape and rice fields in Cd-contaminated agricultural land to ensure food safety.

PubMed

Yu, Lingling; Zhu, Junyan; Huang, Qingqing; Su, Dechun; Jiang, Rongfeng; Li, Huafen

2014-10-01

This field experiment analyzed the phytoremediation effects of oilseed rape in moderately cadmium (Cd)-contaminated farmland and the food safety of successive rice in an oilseed rape-rice rotation system. Two oilseed rape cultivars accumulated Cd at different rates. The rapeseed cultivar Zhucang Huazi exhibited high Cd accumulation rates, higher than the legal limit for human consumption (0.2mgkg(-1)); Cd concentrations in the cultivar Chuanyou II-93 were all below the maximum allowed level. Planting oilseed rape increased the uptake of Cd by the successive rice crop compared with a previous fallow treatment. Most Cd concentrations of brown rice were below the maximum allowed level. The phytoextraction efficiency was lower in the moderately Cd-contaminated soil in field experiments. The results suggest screening rice cultivars with lower Cd accumulation can assure the food safety; the mobilization of heavy metals by roots of different plant species should be considered during crop rotation to assure food safety. Copyright © 2014 Elsevier Inc. All rights reserved.

Characterization of novel biomarkers in selecting for subtype specific medulloblastoma phenotypes.

PubMed

Liang, Lisa; Aiken, Christopher; McClelland, Robyn; Morrison, Ludivine Coudière; Tatari, Nazanin; Remke, Marc; Ramaswamy, Vijay; Issaivanan, Magimairajan; Ryken, Timothy; Del Bigio, Marc R; Taylor, Michael D; Werbowetski-Ogilvie, Tamra E

2015-11-17

Major research efforts have focused on defining cell surface marker profiles for characterization and selection of brain tumor stem/progenitor cells. Medulloblastoma is the most common primary malignant pediatric brain cancer and consists of 4 molecular subgroups: WNT, SHH, Group 3 and Group 4. Given the heterogeneity within and between medulloblastoma variants, surface marker profiles may be subtype-specific. Here, we employed a high throughput flow cytometry screen to identify differentially expressed cell surface markers in self-renewing vs. non-self-renewing SHH medulloblastoma cells. The top 25 markers were reduced to 4, CD271/p75NTR/NGFR, CD106/VCAM1, EGFR and CD171/NCAM-L1, by evaluating transcript levels in SHH tumors relative to samples representing the other variants. However, only CD271/p75NTR/NGFR and CD171/NCAM-L1 maintain differential expression between variants at the protein level. Functional characterization of CD271, a low affinity neurotrophin receptor, in cell lines and primary cultures suggested that CD271 selects for lower self-renewing progenitors or stem cells. Moreover, CD271 levels were negatively correlated with expression of SHH pathway genes. Our study reveals a novel role for CD271 in SHH medulloblastoma and suggests that targeting CD271 pathways could lead to the design of more selective therapies that lessen the broad impact of current treatments on developing nervous systems.

Involvement and prognosis value of CD8(+) T cells in giant cell arteritis.

PubMed

Samson, Maxime; Ly, Kim Heang; Tournier, Benjamin; Janikashvili, Nona; Trad, Malika; Ciudad, Marion; Gautheron, Alexandrine; Devilliers, Hervé; Quipourt, Valérie; Maurier, François; Meaux-Ruault, Nadine; Magy-Bertrand, Nadine; Manckoundia, Patrick; Ornetti, Paul; Maillefert, Jean-Francis; Besancenot, Jean-François; Ferrand, Christophe; Mesturoux, Laura; Labrousse, François; Fauchais, Anne-Laure; Saas, Philippe; Martin, Laurent; Audia, Sylvain; Bonnotte, Bernard

2016-08-01

CD8(+) T cells participate in the pathogenesis of some vasculitides. However, little is known about their role in Giant Cell Arteritis (GCA). This study was conducted to investigate CD8(+) T cell involvement in the pathogenesis of GCA. Analyses were performed at diagnosis and after 3 months of glucocorticoid treatment in 34 GCA patients and 26 age-matched healthy volunteers. Percentages of CD8(+) T-cell subsets, spectratype analysis of the TCR Vβ families of CD8(+) T cells, levels of cytokines and chemokines and immunohistochemistry of temporal artery biopsies (TAB) were assessed. Among total CD8(+) T cells, percentages of circulating cytotoxic CD8 T lymphocytes (CTL, CD3(+)CD8(+)perforin(+)granzymeB(+)), Tc17 (CD3(+)CD8(+)IL-17(+)), CD63(+)CD8(+) T cells and levels of soluble granzymes A and B were higher in patients than in controls, whereas the percentage of Tc1 cells (CD3(+)CD8(+)IFN-γ(+)) was similar. Moreover, CD8(+) T cells displayed a restricted TCR repertoire in GCA patients. Percentages of circulating CTL, Tc17 and soluble levels of granzymes A and B decreased after treatment. CXCR3 expression on CD8(+) T cells and its serum ligands (CXCL9, -10, -11) were higher in patients. Analyses of TAB revealed high expression of CXCL9 and -10 associated with infiltration by CXCR3(+)CD8(+) T cells expressing granzyme B and TiA1. The intensity of the CD8 T-cell infiltrate in TAB was predictive of the severity of the disease. This study demonstrates the implication and the prognostic value of CD8(+) T-cells in GCA and suggests that CD8(+) T-cells are recruited within the vascular wall through an interaction between CXCR3 and its ligands. Copyright © 2016 Elsevier Ltd. All rights reserved.

Elevated circulating endothelial cell-derived microparticle levels in patients with liver cirrhosis: a preliminary report

PubMed Central

Simon, Krzysztof Adam; Pazgan-Simon, Monika

2015-01-01

Aim of the study To determine plausible associations between liver cirrhosis and circulating endothelial cell-derived microparticles (EMPs), vascular endothelial growth factor (VEGF) levels and plasma nitric oxide (NO) metabolites. Material and methods Sixty patients with cirrhosis and 20 healthy control subjects were enrolled in the study. Circulating EMPs from platelet-poor plasma samples were examined by flow cytometry. These microparticles were categorized into endothelial cell-derived activated MPs (EMP-ac) (CD31+ CD42b– AN-V–) and endothelial cell-derived apoptotic MPs (EMP-ap) (CD31+ CD42b– AN-V+). Plasma VEGF levels were measured by enzyme-linked immunosorbent assay. Plasma NO metabolites (NOx–) levels were determined using a Greiss reaction method. Results Compared with the healthy control subjects, the patients with cirrhosis showed a significant increase in plasma levels of both phenotypes of EMPs. When the presence of ascites was considered, the plasma levels of EMP-ap were higher (p < 0.01), as well as NOx– (p < 0.05). EMP-ap positively correlated with VEGF level in all cirrhotic patients and this correlation was stronger in decompensated cirrhotic patients. In multivariate logistic regression analysis, the independent factors associated with the presence of ascites were high EMP-ap levels and elevated VEGF levels. Conclusions Elevated plasma levels of EMP-ap in addition to high levels of VEGF might be considered as valuable parameters for predicting the occurrence of ascites in cirrhotic patients. PMID:28856256

Endophytic bacterium Sphingomonas SaMR12 promotes cadmium accumulation by increasing glutathione biosynthesis in Sedum alfredii Hance.

PubMed

Pan, Fengshan; Meng, Qian; Wang, Qiong; Luo, Sha; Chen, Bao; Khan, Kiran Yasmin; Yang, Xiaoe; Feng, Ying

2016-07-01

A hydroponic experiment was conducted to verify the effects of inoculation with endophytic bacteria Sphingomonas SaMR12 on root growth, cadmium (Cd) uptake, reactive oxygen species (ROS), antioxidases, glutathione (GSH) and the related gene expression of Sedum alfredii Hance under different levels of Cd such as 0, 10, 25, 100 and 400 μM. The results showed that inoculation of SaMR12 improved Cd accumulation and upregulated glutathione synthase (GS) expression, but slightly reduced malondialdehyde (MDA) concentration and alleviated Cd-induced damage in roots. However it didn't alter the activities of antioxidant enzymes. When Cd concentration exceeded 25 μM, SaMR12 increased the concentration of GSH and the expression level of GSH1. At high Cd treatment levels (100 and 400 μM), SaMR12 significantly reduced H2O2 concentration and enhanced expression level of 1-Cys peroxiredoxin PER1 and ATPS genes. These results indicate that although SaMR12 has no significant effects on antioxidases activities, it reduces H2O2 concentration by enhancing GSH concentration and relevant genes expression, and subsequently improves Cd tolerance and accumulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

CD14+CD33+ myeloid cell-CCL11-eosinophil signature in ulcerative colitis.

PubMed

Lampinen, Maria; Waddell, Amanda; Ahrens, Richard; Carlson, Marie; Hogan, Simon P

2013-11-01

This study tested the hypothesis that eotaxins (CCL11, CCL24, and CCL26) and IL-5 contribute to eosinophil recruitment to the intestine in UC and that intestinal macrophages are important producers of CCL11 in this disease. Peripheral blood and rectal biopsy samples were obtained from patients with active (n=18) and quiescent UC (n=9), and control patients (n=7). Eosinophil and macrophage levels and activation were analyzed by flow cytometry. Rectal mRNA levels of CCL11, CCL24, CCL26, and IL-5 were determined by qRT-PCR. The cellular source of CCL11 was visualized by immunofluorescence analyses. Eosinophil numbers were elevated in the blood and rectum of active and quiescent UC patients compared with controls. Levels of activated eosinophils (CD66b(high)) correlated with disease severity. Rectal CCL11, CCL24, and CCL26 mRNA levels were increased in active UC, whereas only CCL11 was elevated in quiescent UC. Levels of CCL11, but not CCL24 and CCL26, positively correlated with eosinophil numbers. Numbers of CD14(+)CD33(+) cells correlated with CCL11 and eosinophil levels. Immunofluorescence analyses revealed the presence of CD14(+)CCL11(+) mononuclear cells in colonic biopsies in UC. These results support the hypothesis that CCL11 contributes to eosinophil recruitment in UC and that intestinal myeloid cells are a source of CCL11. Interestingly, rectal levels of CCL24, CCL26, and IL-5 only increase during active UC, coinciding with further elevation of eosinophil numbers and with the activation of rectal eosinophils. In conclusion, there is a link among CD14(+)CD33(+) myeloid cells, CCL11, and eosinophils in adult UC.

Investigations of Spectroscopic Factors and Sum Rules from the Single Neutron Transfer Reaction 111Cd(overrightarrow {{d}} ,p)112Cd

NASA Astrophysics Data System (ADS)

Jamieson, D. S.; Garrett, P. E.; Ball, G. C.; Demand, G. A.; Faestermann, T.; Finlay, P.; Green, K. L.; Hertenberger, R.; Krücken, R.; Leach, K. G.; Phillips, A. A.; Sumithrarachchi, C. S.; Triambak, S.; Wirth, H.-F.

2014-03-01

Cadmium isotopes have been presented for decades as excellent examples of vibrational nuclei, with low-lying levels interpreted as multi-phonon quadrupole, octupole, and mixed-symmetry states. A large amount of spectroscopic data has been obtained through various experimental studies of cadmiumisotopes. In the present work, the 111Cd(overrightarrow {{d}} ,p)112Cd reaction was used to investigate the single-particle structure of the 112Cd nucleus. A 22 MeV beam of polarized deuterons was obtained at the Maier-Leibnitz laboratory in Garching, Germany. The reaction ejectiles were momentum analyzed using a Q3D spectrograph, and 130 levels have been identified up to 4.2 MeV of excitation energy. Using DWBA analysis with optical model calculations, spin-parity assignments have been made for observed levels, and spectroscopic factors have been extracted from the experimental angular distributions of differential cross section and analyzing power. In this high energy resolution investigation, many additional levels have been observed compared with the previous (d,p) study using 8 MeV deuterons [1]. There were a total of 44 new levels observed, and the parity assignments of 34 levels were improved.

Increase of endothelial progenitor cells in acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia.

PubMed

Medinger, Michael; Heim, Dominik; Gerull, Sabine; Halter, Jörg; Krenger, Werner; Buser, Andreas; Lengerke, Claudia; Bucher, Christoph; Passweg, Jakob

2016-08-01

Circulating endothelial progenitor cells (EPCs; CD31+ CD34(bright)CD133+ CD45(dim) cells) are novel markers of endothelial dysfunction and related to inflammatory processes such as acute graft-versus-host disease (aGvHD). 47 patients with acute myeloid leukaemia (AML) who were in complete remission as they underwent allogeneic hematopoietic stem cell transplantation with myeloablative conditioning with PBSC as stem cell source were enrolled in the study. Blood samples for the quantitative analysis of circulating EPC levels were drawn at different time points in patients with and without aGvHD. CD34+ VEGFR2/KDR+ CD133+ triple-positive cells identified among CD34+ cells by FACS. EPC were quantified and data are presented as cells/ml whole blood. Circulating EPC levels were not significantly different in patients with and without aGvHD prior to conditioning (baseline) and at the time of engraftment. However, at diagnosis of aGvHD≥grade 2, EPC levels increased whereas in patients without aGvHD the EPC levels remained significantly lower (3021±278 versus 2322±195 cells/ml; p<0.001). Patients with steroid-refractory aGvHD had high levels of EPC throughout. EPC levels fell in responding patients. Our results demonstrate that the number of circulating EPCs is increased in patients with aGvHD compared to patients without aGvHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of EpCAMhighCD44+ cancer stem cells with EpCAMhighCD44- tumor cells in colon cancer by single-cell sequencing.

PubMed

Liu, Mingshan; Di, Jiabo; Liu, Yang; Su, Zhe; Jiang, Beihai; Wang, Zaozao; Su, Xiangqian

2018-03-26

Cancer stem cells (CSCs) are considered to be responsible for tumorigenesis and cancer relapse. EpCAM high CD44 + tumor cells are putative colorectal CSCs that express high levels of stem cell genes, while the EpCAM high CD44 - population mostly contains differentiated tumor cells (DTCs). This study aims to determine whether single CSC (EpCAM high CD44 + ) and DTC (EpCAM high CD44 - ) can be distinguished in terms of somatic copy number alterations (SCNAs). We applied fluorescence-activated cell sorting to isolate the CD45 - EpCAM high CD44 + and CD45 - EpCAM high CD44 - populations from two primary colon tumors, on which low-coverage single-cell whole-genome sequencing (WGS) was then performed ∼0.1x depth. We compared the SCNAs of the CSCs and DTCs at single-cell resolution. In total, 47 qualified single cells of the two populations underwent WGS. The single-cell SCNA profiles showed that there were obvious SCNAs in both the CSCs and DTCs of each patient, and each patient had a specific copy number alteration pattern. Hierarchical clustering and correlation analysis both showed that the SCNA profiles of CSCs and DTCs from the same patient had similar SCNA pattern, while there were regional differences in the CSCs and DTCs in certain patient. SCNAs of CSCs in the same patient were highly reproducible. Our data suggest that major SCNAs occurred at an early stage and were inherited steadily. The similarity of ubiquitous SCNAs between the CSCs and DTCs might have arisen from lineage differentiation. CSCs from the same patient had reproducible SCNA profiles, indicating that gain or loss in certain chromosome is required for colon cancer development.

High plasma levels of soluble intercellular adhesion molecule (ICAM)-1 are associated with cerebral malaria.

PubMed

Adukpo, Selorme; Kusi, Kwadwo A; Ofori, Michael F; Tetteh, John K A; Amoako-Sakyi, Daniel; Goka, Bamenla Q; Adjei, George O; Edoh, Dominic A; Akanmori, Bartholomew D; Gyan, Ben A; Dodoo, Daniel

2013-01-01

Cerebral malaria (CM) is responsible for most of the malaria-related deaths in children in sub-Saharan Africa. Although, not well understood, the pathogenesis of CM involves parasite and host factors which contribute to parasite sequestration through cytoadherence to the vascular endothelium. Cytoadherence to brain microvasculature is believed to involve host endothelial receptor, CD54 or intercellular adhesion molecule (ICAM)-1, while other receptors such as CD36 are generally involved in cytoadherence of parasites in other organs. We therefore investigated the contributions of host ICAM-1 expression and levels of antibodies against ICAM-1 binding variant surface antigen (VSA) on parasites to the development of CM. Paediatric malaria patients, 0.5 to 13 years were recruited and grouped into CM and uncomplicated malaria (UM) patients, based on well defined criteria. Standardized ELISA protocol was used to measure soluble ICAM-1 (sICAM-1) levels from acute plasma samples. Levels of IgG to CD36- or ICAM-1-binding VSA were measured by flow cytometry during acute and convalescent states. Wilcoxon sign rank-test analysis to compare groups revealed association between sICAM-1 levels and CM (p<0.0037). Median levels of antibodies to CD36-binding VSA were comparable in the two groups at the time of admission and 7 days after treatment was initiated (p>0.05). Median levels of antibodies to CD36-binding VSAs were also comparable between acute and convalescent samples within any patient group. Median levels of antibodies to ICAM-1-binding VSAs were however significantly lower at admission time than during recovery in both groups. High levels of sICAM-1 were associated with CM, and the sICAM-1 levels may reflect expression levels of the membrane bound form. Anti-VSA antibody levels to ICAM-binding parasites was more strongly associated with both UM and CM than antibodies to CD36 binding parasites. Thus, increasing host sICAM-1 levels were associated with CM whilst antibodies to parasite expressing non-ICAM-1-binding VSAs were not.

Circulating Endothelial Microparticles and Correlation of Serum 1,25-Dihydroxyvitamin D with Adiponectin, Nonesterified Fatty Acids, and Glycerol from Middle-Aged Men in China.

PubMed

Wan, Zhongxiao; Yu, Lugang; Cheng, Jinbo; Zhang, Zengli; Xu, Baohui; Pang, Xing; Zhou, Hui; Lei, Ting

2016-01-01

The aim of the present study is (1) to determine the correlation between circulating 1,25-dihydroxyvitamin D [25(OH)D] and adiponectin, nonesterified fatty acids (NEFAs), and glycerol and (2) to determine the alterations in circulating endothelial microparticles (EMPs) in Chinese male subjects with increased body mass index (BMI). A total of 45 male adults were enrolled with varied BMI [i.e., lean, overweight (OW), and obese (OB), N = 15 per group]. Blood samples were collected under overnight fasting condition, and plasma was isolated for the measurement of endothelial microparticles (EMPs), total and high-molecular weight (HMW) adiponectin, 25(OH)D, nonesterified fatty acids (NEFAs), and glycerol. Circulating 25(OH)D levels were inversely associated with total adiponectin, NEFA, and glycerol levels. There is no difference for CD62E+ or CD31+/CD42b- EMPs among 3 groups. In Chinese male adults with varied BMI, an inverse correlation existed between 25(OH)D levels and total adiponectin, NEFA, and glycerol levels; and there is no significant difference for CD62E+ or CD31+/CD42b- EMPs among lean, overweight, and obese subjects.

Circulating Endothelial Microparticles and Correlation of Serum 1,25-Dihydroxyvitamin D with Adiponectin, Nonesterified Fatty Acids, and Glycerol from Middle-Aged Men in China

PubMed Central

Wan, Zhongxiao; Yu, Lugang; Cheng, Jinbo; Zhang, Zengli; Xu, Baohui; Pang, Xing; Zhou, Hui; Lei, Ting

2016-01-01

The aim of the present study is (1) to determine the correlation between circulating 1,25-dihydroxyvitamin D [25(OH)D] and adiponectin, nonesterified fatty acids (NEFAs), and glycerol and (2) to determine the alterations in circulating endothelial microparticles (EMPs) in Chinese male subjects with increased body mass index (BMI). A total of 45 male adults were enrolled with varied BMI [i.e., lean, overweight (OW), and obese (OB), N = 15 per group]. Blood samples were collected under overnight fasting condition, and plasma was isolated for the measurement of endothelial microparticles (EMPs), total and high-molecular weight (HMW) adiponectin, 25(OH)D, nonesterified fatty acids (NEFAs), and glycerol. Circulating 25(OH)D levels were inversely associated with total adiponectin, NEFA, and glycerol levels. There is no difference for CD62E+ or CD31+/CD42b− EMPs among 3 groups. In Chinese male adults with varied BMI, an inverse correlation existed between 25(OH)D levels and total adiponectin, NEFA, and glycerol levels; and there is no significant difference for CD62E+ or CD31+/CD42b− EMPs among lean, overweight, and obese subjects. PMID:27314039

Health risk assessment of cadmium pollution emergency for urban populations in Foshan City, China.

PubMed

Dou, Ming; Zhao, Peipei; Wang, Yanyan; Li, Guiqiu

2017-03-01

With rapid socioeconomic development, water pollution emergency has become increasingly common and could potentially harm the environment and human health, especially heavy metal pollution. In this paper, we investigate the Cd pollution emergency that occurred in the Pearl River network, China, in 2005, and we build a migration and transformation model for heavy metals to simulate the spatiotemporal distribution of Cd concentrations under various scenarios of Cd pollution emergency in Foshan City. Moreover, human health hazard and carcinogenic risk for local residents of Foshan City were evaluated. The primary conclusions were as follows: (1) the number of carcinogen-affected people per year under scenario 1 reached 254.41 when the frequency was 0.1 year/time; specifically, the number of people with cancer per year in the area of the Datang, Lubao, and Nanbian waterworks was 189.36 accounting for 74% of the total number per year; (2) at the frequency of 5 years/time, the Lubao waterwork is the only one in extremely high- or high-risk grade, while besides it, the risk grade in the Datang, Nanbian, Xinan, Shitang, and Jianlibao waterworks is in the extremely high or high grade when the frequency is 0.1 year/time; (3) when Cd pollution accidents with the same level occurs again, Cd concentration decreases to a low level in the water only if the migration distance of Cd is at least 40-50 km. Based on the health risk assessment of Cd pollution, this study gives the recommendation that the distance should keep above 50 km in tidal river network of the Pearl River Delta between those factories existing the possibility of heavy metal pollution and the drinking water source. Only then can the public protect themselves from hazardous effects of higher levels of heavy metal.

Diet and habitat use influence Hg and Cd transfer to fish and consequent biomagnification in a highly contaminated area: Augusta Bay (Mediterranean Sea).

PubMed

Signa, Geraldina; Mazzola, Antonio; Tramati, Cecilia Doriana; Vizzini, Salvatrice

2017-11-01

Total mercury (T-Hg) and cadmium (Cd) were measured in twenty species of fish to study their bioaccumulation patterns and trophodynamics in the Augusta Bay food web. Adult and juvenile fish were caught in 2012 in Priolo Bay, south of the Augusta harbour (Central Mediterranean Sea), which is known for the high trace element and polycyclic aromatic hydrocarbon contamination level. T-Hg concentration was found to significantly increase along δ 15 N and from pelagic to benthic sedentary fish, revealing a marked influence of trophic position and habitat use (sensu Harmelin 1987) on T-Hg accumulation within ichthyofauna. Cd showed the opposite pattern, in line with the higher trace element (TE) excretion rates of high trophic level fish and the lower level of Cd environmental contamination. Trophic pathways were first characterised in the Priolo Bay food web using carbon and nitrogen stable isotopes (δ 13 C, δ 15 N) and a single main trophic pathway characterised the Priolo Bay food web. Biomagnification was then assessed, including basal sources (surface sediment, macroalgae), zooplankton, benthic invertebrates and fish. T-Hg and Cd were found to biomagnify and biodilute respectively based on the significant linear regressions between log[T-Hg] and log[Cd] vs. δ 15 N of sources and consumers and the trophic magnification factors (TMFs) of 1.22 and 0.83 respectively. Interestingly, different Cd behaviour was found considering only the benthic pathway which leads to the predatory gastropod Hexaplex trunculus. The positive slope and the higher TMF indicated active biomagnification in this benthic food web due to the high bioaccumulation efficiency of this benthic predator. Our findings provide new evidences about the role of Priolo sediments as a sources of pollutants for the food web, representing a threat to fish and, by domino effect, to humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Central memory CD4 T cells are associated with incomplete restoration of the CD4 T cell pool after treatment-induced long-term undetectable HIV viraemia.

PubMed

Rallón, Norma; Sempere-Ortells, José M; Soriano, Vincent; Benito, José M

2013-11-01

It is unclear to what extent T cell reconstitution may be possible in HIV-1-infected individuals on continuous successful highly active antiretroviral therapy (HAART). Herein, we analysed distinct phenotypic markers of immune recovery in patients with undetectable viraemia for 8 years, taking as reference untreated patients and healthy controls. Seventy-two subjects were examined: 28 HIV-1+ patients on successful long-term HAART, 24 HIV-1+ untreated viraemic patients and 20 age-matched healthy controls. Analysis of naive and memory CD4 and CD8 T cells was combined with measurements of activation status (expression of CD38) and with thymic function (expression of CD31). Statistical significance was determined by non-parametric tests. After long-term HAART, the majority of parameters were normalized compared with age-matched control values, including T cell activation and thymic function. However, absolute counts of naive and central memory CD4 T cells remained below normal levels. The only parameters significantly associated with CD4 counts at the end of follow-up were the pre-HAART CD4 count ( β ± SD = 0.54 ± 0.16, P = 0.003) and the level of CD4 central memory cells at the end of follow-up (β ± SD = 1.18 ± 0.23, P < 0.0001). Only patients starting HAART with CD4 counts >350 cells/mm(3) reached a complete normalization of CD4 counts. Even after long-term successful HAART, complete CD4 restoration may be attainable only in patients starting therapy with moderately high CD4 counts, prompting early initiation of antiretroviral therapy. Incomplete CD4 restoration may be associated with a defective restoration of central memory CD4 T cells, a cell subset with a pivotal role in T cell homeostasis.

Emotion Regulation in Adolescent Males with Attention-Deficit Hyperactivity Disorder: Testing the Effects of Comorbid Conduct Disorder.

PubMed

Northover, Clare; Thapar, Anita; Langley, Kate; van Goozen, Stephanie

2015-09-07

Although attention-deficit hyperactivity disorder (ADHD) has been linked to emotion dysregulation, few studies have experimentally investigated this whilst controlling for the effects of comorbid conduct disorder (CD). Economic decision-making games that assess how individuals respond to offers varying in fairness have been used to study emotion regulation. The present study compared adolescent boys with ADHD (n = 90), ADHD + CD (n = 94) and typical controls (n = 47) on the Ultimatum Game and examined the contribution of ADHD and CD symptom scores and callous and unemotional traits to acceptance levels of unfair offers. There were no significant differences in acceptance rates of fair and highly unfair offers between groups, and only boys with ADHD did not significantly differ from the controls. However, the subgroup of boys with ADHD and additional high levels of aggressive CD symptoms rejected significantly more ambiguous (i.e., moderately unfair) offers than any other subgroup, suggesting impaired emotion regulation in those with ADHD and aggressive CD. Correlations within the CD group showed that the rejection rate to moderately unfair offers was predicted by aggressive CD symptom severity, but not callous and unemotional traits. These findings highlight the fact that ADHD is a heterogeneous condition from an emotion regulation point of view.

A DNA prime-oral Listeria boost vaccine in rhesus macaques induces a SIV-specific CD8 T cell mucosal response characterized by high levels of α4β7 integrin and an effector memory phenotype

PubMed Central

Neeson, Paul; Boyer, Jean; Kumar, Sanjeev; Lewis, Mark G.; Veazey, Lennox MattiasRon; Weiner, David; Paterson, Yvonne

2006-01-01

In this study in Rhesus macaques, we tested whether IL-12 or IL-15 in a DNA prime-oral Listeria boost amplifies the SIV-Gag specific CD8 mucosal response. SIV-specific CD8 T cells were demonstrated in the peripheral blood (PB) in all test vaccine groups, but not the control group. SIV Gag-specific CD8 T cells in the PB expressed α4β7 integrin, the gut-homing receptor; a minor subset co-express αEβ7 integrin. SIV Gag-specific CD8 T cells were also detected in the gut tissue, intraepithelial (IEL) and lamina propria lymphocytes (LPL) of the duodenum and ileum. These cells were characterized by high levels of β7 integrin expression and a predominance of the effector memory phenotype. Neither Il-12 nor IL-15 amplified the frequency of SIV-specific CD8 T cells in the gut. Thus, the DNA prime oral Listeria boost strategy induced a mucosal SIV-Gag specific CD8 T cell response characterized by expression of the α4β7 integrin gut-homing receptor. PMID:16904153

Tissue-specific expression of human CD4 in transgenic mice.

PubMed Central

Gillespie, F P; Doros, L; Vitale, J; Blackwell, C; Gosselin, J; Snyder, B W; Wadsworth, S C

1993-01-01

The gene for the human CD4 glycoprotein, which serves as the receptor for human immunodeficiency virus type 1, along with approximately 23 kb of sequence upstream of the translational start site, was cloned. The ability of 5' flanking sequences to direct tissue-specific expression was tested in cell culture and in transgenic mice. A 5' flanking region of 6 kb was able to direct transcription of the CD4 gene in NIH 3T3 cells but did not result in detectable expression in the murine T-cell line EL4 or in four lines of transgenic mice. A larger 5' flanking region of approximately 23 kb directed high-level CD4 transcription in the murine T-cell line EL4 and in three independent lines of transgenic mice. Human CD4 expression in all tissues analyzed was tightly correlated with murine CD4 expression; the highest levels of human CD4 RNA expression were found in the thymus and spleen, with relatively low levels detected in other tissues. Expression of human CD4 protein in peripheral blood mononuclear cells was examined by flow cytometry in these transgenic animals and found to be restricted to the murine CD4+ subset of lymphocytes. Human CD4 protein, detected with an anti-human CD4 monoclonal antibody, was present on the surface of 45 to 50% of the peripheral blood mononuclear cells from all transgenic lines. Images PMID:8474453

Electrical Characterization of Molecular Beam Epitaxy Grown Mercury-Cadmium Alloy Under Low Magnetic Field Strength

NASA Astrophysics Data System (ADS)

Wijewarnasuriya, P. S.

HgCdTe alloy is currently the most important semiconductor material for IR detection technology. Different growth techniques are used to produce HgCdTe, but achieving a high-quality material is still a major objective in the field. Among the growth techniques for HgCdTe, molecular beam epitaxy (MBE) is one of the most promising, mainly because of its versatility. Furthermore, the growth by MBE is carried out at a low temperature which limits interdiffusion processes. The focus of this research is the understanding of the electrical properties of HgCdTe layers grown by MBE technique. Using a model based on a single discrete acceptor level near the valence band and a corresponding fully ionized donor level, a good fit to the observed Hall data on p-type epilayers was obtained. In some samples, another acceptor level was needed. Also, analysis of R _{h} data and low temperature mobilities indicated that the p-type MBE growth layers were highly compensated. This was also confirmed by mercury saturated annealing experiments. Annealing of (111)B epilayers with Hg pressure leads us to believe that Hg vacancies are responsible for the p-type character. The findings reveal that the electrical properties differ drastically between different growth orientations, with (111)B having the highest residual doping levels for a particular Cd composition. It is concluded that MBE growth for HgCdTe is essentially a Te rich growth and our understanding is that this extra Te is responsible for the n-type character in the epilayers. A comparison between HgCdTe twinned layers and twin-free layers has shown that electrically active acceptors and high hole mobilities are associated with the presence of twins. Incorporation of several foreign elements also tried and all were found to substitute the metal sites during growth. With magnetic field studies on R_ {h}, resistivity and conductivity tensor analysis, the band structure of the HgCdTe alloy is also investigated. Junction depth and the doping profile on low energy Ar ion sputtered epilayers are investigated and they are found to behave similar to the ion implanted layers.

Impact of benznidazole treatment on the functional response of Trypanosoma cruzi antigen-specific CD4+CD8+ T cells in chronic Chagas disease patients.

PubMed

Pérez-Antón, Elena; Egui, Adriana; Thomas, M Carmen; Puerta, Concepción J; González, John Mario; Cuéllar, Adriana; Segovia, Manuel; López, Manuel Carlos

2018-05-11

Chagas disease is caused by Trypanosoma cruzi. The persistence of the parasite is associated with the disease chronicity and the impairment of the cellular immune response. It has been reported that the CD4+CD8+ T cell population expands in chronic Chagas disease patients. Few studies have focused on this subset of cells, and very little is known about the impact of antiparasitic treatment on this population. Thirty-eight chronic Chagas disease patients (20 asymptomatic and 18 symptomatic) and twelve healthy controls were enrolled in this study. Peripheral blood mononuclear cells were stimulated with soluble T. cruzi antigens to analyze the production of cytokines and cytotoxic molecules by CD4+CD8+ T cells before and after benznidazole treatment. Additionally, expression and co-expression of five inhibitory receptors in these patients after treatment were studied using a multiparameter flow cytometry technique. The frequency of CD4+CD8+ T cells was higher in chronic Chagas disease patients compared with healthy donors. Furthermore, a higher ratio of CD4+CD8low/CD4+CD8high subpopulations was observed in chronic Chagas disease patients than in healthy donors. Additionally, CD4+CD8+ T cells from these patients expressed and co-expressed higher levels of inhibitory receptors in direct proportion to the severity of the pathology. Benznidazole treatment reduced the frequency of CD4+CD8+ T cells and decreased the ratio of CD4+CD8low/CD4+CD8high subpopulations. The co-expression level of the inhibitory receptor was reduced after treatment simultaneously with the enhancement of the multifunctional capacity of CD4+CD8+ T cells. After treatment, an increase in the frequency of T. cruzi antigen-specific CD4+CD8+ T cells expressing IL-2 and TNF-α was also observed. CD4+CD8+ T cells could play an important role in the control of T. cruzi infection since they were able to produce effector molecules for parasite control. Benznidazole treatment partially reversed the exhaustion process caused by T. cruzi infection in these cells with an improvement in the functional response of the T. cruzi antigen-specific CD4+CD8+ T cells.

Impact of benznidazole treatment on the functional response of Trypanosoma cruzi antigen-specific CD4+CD8+ T cells in chronic Chagas disease patients

PubMed Central

Pérez-Antón, Elena; Egui, Adriana; Thomas, M. Carmen; Puerta, Concepción J.; González, John Mario; Cuéllar, Adriana; Segovia, Manuel

2018-01-01

Background Chagas disease is caused by Trypanosoma cruzi. The persistence of the parasite is associated with the disease chronicity and the impairment of the cellular immune response. It has been reported that the CD4+CD8+ T cell population expands in chronic Chagas disease patients. Few studies have focused on this subset of cells, and very little is known about the impact of antiparasitic treatment on this population. Methodology Thirty-eight chronic Chagas disease patients (20 asymptomatic and 18 symptomatic) and twelve healthy controls were enrolled in this study. Peripheral blood mononuclear cells were stimulated with soluble T. cruzi antigens to analyze the production of cytokines and cytotoxic molecules by CD4+CD8+ T cells before and after benznidazole treatment. Additionally, expression and co-expression of five inhibitory receptors in these patients after treatment were studied using a multiparameter flow cytometry technique. Principal findings The frequency of CD4+CD8+ T cells was higher in chronic Chagas disease patients compared with healthy donors. Furthermore, a higher ratio of CD4+CD8low/CD4+CD8high subpopulations was observed in chronic Chagas disease patients than in healthy donors. Additionally, CD4+CD8+ T cells from these patients expressed and co-expressed higher levels of inhibitory receptors in direct proportion to the severity of the pathology. Benznidazole treatment reduced the frequency of CD4+CD8+ T cells and decreased the ratio of CD4+CD8low/CD4+CD8high subpopulations. The co-expression level of the inhibitory receptor was reduced after treatment simultaneously with the enhancement of the multifunctional capacity of CD4+CD8+ T cells. After treatment, an increase in the frequency of T. cruzi antigen-specific CD4+CD8+ T cells expressing IL-2 and TNF-α was also observed. Conclusions CD4+CD8+ T cells could play an important role in the control of T. cruzi infection since they were able to produce effector molecules for parasite control. Benznidazole treatment partially reversed the exhaustion process caused by T. cruzi infection in these cells with an improvement in the functional response of the T. cruzi antigen-specific CD4+CD8+ T cells. PMID:29750791

2B4 expression on natural killer cells increases in HIV-1 infected patients followed prospectively during highly active antiretroviral therapy

PubMed Central

Ostrowski, S R; Ullum, H; Pedersen, B K; Gerstoft, J; Katzenstein, T L

2005-01-01

Human immunodeficiency virus (HIV)-1 infection influences natural killer (NK) cell expression of inhibitory NK receptors and activating natural cytotoxicity receptors. It is unknown whether expression of the co-stimulatory NK cell receptor 2B4 (CD244) on NK cells and CD3+ CD8+ cells are affected by highly active antiretroviral therapy (HAART), low-level viraemia, proviral-DNA or immune activation in HIV-1 infected patients. A total of 101 HAART-treated HIV-1 infected patients with ≤ 200 HIV-RNA copies/ml were followed prospectively for 24 months. HIV-RNA was investigated 3-monthly and 2B4 expression on CD3− CD16+ NK cells and CD3+ CD8+ cells, proviral-DNA and plasma soluble tumour necrosis factor receptor (sTNFr)-II were investigated 6-monthly. For comparison, 2B4 expression was investigated in 20 healthy individuals. The concentration of 2B4+ NK cells was initially reduced in HIV-1 infected patients (P < 0·001) but increased to a normal level during the 24 months’ follow-up. The concentration of CD3+ CD8+ 2B4+ cells in HIV-1 infected patients was normal and did not change during follow-up. The relative fluorescence intensity (RFI) of 2B4 increased on both NK cells and CD3+ CD8+ cells during follow-up (both P < 0·001). Higher levels of proviral-DNA carrying cells and plasma sTNFrII were associated with reductions in the concentration of 2B4+ NK cells (all P < 0·05). HIV-RNA had no effect on 2B4 expression on NK cells or CD3+ CD8+ cells. These findings demonstrate that the concentration of 2B4+ NK cells normalizes during long-term HAART in HIV-1 infected patients. The finding that proviral-DNA and sTNFrII were associated negatively with the concentration of 2B4+ NK cells suggests that immune activation in HIV-1 infected patients receiving HAART influences the target cell recognition by NK cells. PMID:16045743

2B4 expression on natural killer cells increases in HIV-1 infected patients followed prospectively during highly active antiretroviral therapy.

PubMed

Ostrowski, S R; Ullum, H; Pedersen, B K; Gerstoft, J; Katzenstein, T L

2005-09-01

Human immunodeficiency virus (HIV)-1 infection influences natural killer (NK) cell expression of inhibitory NK receptors and activating natural cytotoxicity receptors. It is unknown whether expression of the co-stimulatory NK cell receptor 2B4 (CD244) on NK cells and CD3+ CD8+ cells are affected by highly active antiretroviral therapy (HAART), low-level viraemia, proviral-DNA or immune activation in HIV-1 infected patients. A total of 101 HAART-treated HIV-1 infected patients with < or = 200 HIV-RNA copies/ml were followed prospectively for 24 months. HIV-RNA was investigated 3-monthly and 2B4 expression on CD3- CD16+ NK cells and CD3+ CD8+ cells, proviral-DNA and plasma soluble tumour necrosis factor receptor (sTNFr)-II were investigated 6-monthly. For comparison, 2B4 expression was investigated in 20 healthy individuals. The concentration of 2B4+ NK cells was initially reduced in HIV-1 infected patients (P < 0.001) but increased to a normal level during the 24 months' follow-up. The concentration of CD3+ CD8+ 2B4+ cells in HIV-1 infected patients was normal and did not change during follow-up. The relative fluorescence intensity (RFI) of 2B4 increased on both NK cells and CD3+ CD8+ cells during follow-up (both P < 0.001). Higher levels of proviral-DNA carrying cells and plasma sTNFrII were associated with reductions in the concentration of 2B4+ NK cells (all P < 0.05). HIV-RNA had no effect on 2B4 expression on NK cells or CD3+ CD8+ cells. These findings demonstrate that the concentration of 2B4+ NK cells normalizes during long-term HAART in HIV-1 infected patients. The finding that proviral-DNA and sTNFrII were associated negatively with the concentration of 2B4+ NK cells suggests that immune activation in HIV-1 infected patients receiving HAART influences the target cell recognition by NK cells.

Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity

PubMed Central

Almeida, Jorge R.; Sauce, Delphine; Price, David A.; Papagno, Laura; Shin, So Youn; Moris, Arnaud; Larsen, Martin; Pancino, Gianfranco; Douek, Daniel C.; Autran, Brigitte; Sáez-Cirión, Asier

2009-01-01

CD8+ T cells are major players in the immune response against HIV. However, recent failures in the development of T cell–based vaccines against HIV-1 have emphasized the need to reassess our basic knowledge of T cell–mediated efficacy. CD8+ T cells from HIV-1–infected patients with slow disease progression exhibit potent polyfunctionality and HIV-suppressive activity, yet the factors that unify these properties are incompletely understood. We performed a detailed study of the interplay between T-cell functional attributes using a bank of HIV-specific CD8+ T-cell clones isolated in vitro; this approach enabled us to overcome inherent difficulties related to the in vivo heterogeneity of T-cell populations and address the underlying determinants that synthesize the qualities required for antiviral efficacy. Conclusions were supported by ex vivo analysis of HIV-specific CD8+ T cells from infected donors. We report that attributes of CD8+ T-cell efficacy against HIV are linked at the level of antigen sensitivity. Highly sensitive CD8+ T cells display polyfunctional profiles and potent HIV-suppressive activity. These data provide new insights into the mechanisms underlying CD8+ T-cell efficacy against HIV, and indicate that vaccine strategies should focus on the induction of HIV-specific T cells with high levels of antigen sensitivity to elicit potent antiviral efficacy. PMID:19389882

Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity.

PubMed

Almeida, Jorge R; Sauce, Delphine; Price, David A; Papagno, Laura; Shin, So Youn; Moris, Arnaud; Larsen, Martin; Pancino, Gianfranco; Douek, Daniel C; Autran, Brigitte; Sáez-Cirión, Asier; Appay, Victor

2009-06-18

CD8(+) T cells are major players in the immune response against HIV. However, recent failures in the development of T cell-based vaccines against HIV-1 have emphasized the need to reassess our basic knowledge of T cell-mediated efficacy. CD8(+) T cells from HIV-1-infected patients with slow disease progression exhibit potent polyfunctionality and HIV-suppressive activity, yet the factors that unify these properties are incompletely understood. We performed a detailed study of the interplay between T-cell functional attributes using a bank of HIV-specific CD8(+) T-cell clones isolated in vitro; this approach enabled us to overcome inherent difficulties related to the in vivo heterogeneity of T-cell populations and address the underlying determinants that synthesize the qualities required for antiviral efficacy. Conclusions were supported by ex vivo analysis of HIV-specific CD8(+) T cells from infected donors. We report that attributes of CD8(+) T-cell efficacy against HIV are linked at the level of antigen sensitivity. Highly sensitive CD8(+) T cells display polyfunctional profiles and potent HIV-suppressive activity. These data provide new insights into the mechanisms underlying CD8(+) T-cell efficacy against HIV, and indicate that vaccine strategies should focus on the induction of HIV-specific T cells with high levels of antigen sensitivity to elicit potent antiviral efficacy.

Immunophenotypic analysis of mast cells in mastocytosis: When and how to do it. Proposals of the Spanish Network on Mastocytosis (REMA).

PubMed

Escribano, Luis; Diaz-Agustin, Beatriz; López, Antonio; Núñez López, Rosa; García-Montero, Andrés; Almeida, Julia; Prados, Aranzazu; Angulo, Miguel; Herrero, Sonia; Orfao, Alberto

2004-03-01

Mastocytosis is a term used for a heterogeneous group of disorders characterized by an abnormal proliferation and accumulation of mast cells (MCs) in one or multiple tissues including skin, bone marrow, liver, spleen, and lymph nodes, among others. In recent years, multiparameter flow cytometric studies have shown that pathologic MCs from patients with mastocytosis display unique aberrant immunophenotypic characteristics as compared with normal MCs. Among other features, pathologic MCs show aberrant expression of CD25 and CD2 antigens and abnormally high levels of the CD11c and CD35 complement receptors, the CD59 complement regulatory molecule, the CD63 lysosomal membrane antigen, and the CD69 early-activation antigen. In addition, MCs from mastocytosis express abnormally low levels of CD117 and unexpectedly high light scatter and autofluorescence characteristics. These aberrant immunophenotypic features are of great relevance for the assessment of tissue involvement in mastocytosis with consequences in the diagnosis, classification, and follow-up of the disease and in its differential diagnosis with other entities. In this paper we provide the reader with information for the objective and reproducible identification of pathologic MCs by using quantitative multiparametric flow cytometry, information for their phenotypic characterization, and the criteria currently used for a correct interpretation of the immunophenotypic results obtained. Copyright 2004 Wiley-Liss, Inc.

Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo

PubMed Central

Iqbal, Asif J.; McNeill, Eileen; Kapellos, Theodore S.; Regan-Komito, Daniel; Norman, Sophie; Burd, Sarah; Smart, Nicola; Machemer, Daniel E. W.; Stylianou, Elena; McShane, Helen; Channon, Keith M.; Chawla, Ajay

2014-01-01

The recruitment of monocytes and their differentiation into macrophages at sites of inflammation are key events in determining the outcome of the inflammatory response and initiating the return to tissue homeostasis. To study monocyte trafficking and macrophage differentiation in vivo, we have generated a novel transgenic reporter mouse expressing a green fluorescent protein (GFP) under the control of the human CD68 promoter. CD68-GFP mice express high levels of GFP in both monocyte and embryo-derived tissue resident macrophages in adult animals. The human CD68 promoter drives GFP expression in all CD115+ monocytes of adult blood, spleen, and bone marrow; we took advantage of this to directly compare the trafficking of bone marrow–derived CD68-GFP monocytes to that of CX3CR1GFP monocytes in vivo using a sterile zymosan peritonitis model. Unlike CX3CR1GFP monocytes, which downregulate GFP expression on differentiation into macrophages in this model, CD68-GFP monocytes retain high-level GFP expression for 72 hours after differentiation into macrophages, allowing continued cell tracking during resolution of inflammation. In summary, this novel CD68-GFP transgenic reporter mouse line represents a powerful resource for analyzing monocyte mobilization and monocyte trafficking as well as studying the fate of recruited monocytes in models of acute and chronic inflammation. PMID:25030063

Effects of high CD4 cell counts on death and attrition among HIV patients receiving antiretroviral treatment: an observational cohort study.

PubMed

Tang, Zhenzhu; Pan, Stephen W; Ruan, Yuhua; Liu, Xuanhua; Su, Jinming; Zhu, Qiuying; Shen, Zhiyong; Zhang, Heng; Chen, Yi; Lan, Guanghua; Xing, Hui; Liao, Lingjie; Feng, Yi; Shao, Yiming

2017-06-09

Current WHO guidelines recommend initiating ART regardless of CD4+ cell count. In response, we conducted an observational cohort study to assess the effects of pre-ART CD4+ cell count levels on death, attrition, and death or attrition in HIV treated patients. This large HIV treatment cohort study (n = 49,155) from 2010 to 2015 was conducted in Guangxi, China. We used a Cox regression model to analyze associations between pre-ART CD4+ cell counts and death, attrition, and death or attrition. The average mortality and ART attrition rates among all treated patients were 2.63 deaths and 5.32 attritions per 100 person-years, respectively. Compared to HIV patients with <350 CD4+ cells/mm 3 at ART initiation, HIV patients with >500 CD4+ cells/mm 3 at ART initiation had a significantly lower mortality rate (Adjusted hazard ratio: 0.56, 95% CI: 0.40-0.79), but significantly higher ART attrition rate (AHR: 1.17, 95% CI: 1.03-1.33). Results from this study suggest that HIV patients with high CD4+ cell counts at the time of ART initiation may be at greater risk of treatment attrition. To further reduce ART attrition, it is imperative that patient education and healthcare provider training on ART adherence be enhanced and account for CD4 levels at ART initiation.

Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo.

PubMed

Iqbal, Asif J; McNeill, Eileen; Kapellos, Theodore S; Regan-Komito, Daniel; Norman, Sophie; Burd, Sarah; Smart, Nicola; Machemer, Daniel E W; Stylianou, Elena; McShane, Helen; Channon, Keith M; Chawla, Ajay; Greaves, David R

2014-10-09

The recruitment of monocytes and their differentiation into macrophages at sites of inflammation are key events in determining the outcome of the inflammatory response and initiating the return to tissue homeostasis. To study monocyte trafficking and macrophage differentiation in vivo, we have generated a novel transgenic reporter mouse expressing a green fluorescent protein (GFP) under the control of the human CD68 promoter. CD68-GFP mice express high levels of GFP in both monocyte and embryo-derived tissue resident macrophages in adult animals. The human CD68 promoter drives GFP expression in all CD115(+) monocytes of adult blood, spleen, and bone marrow; we took advantage of this to directly compare the trafficking of bone marrow-derived CD68-GFP monocytes to that of CX3CR1(GFP) monocytes in vivo using a sterile zymosan peritonitis model. Unlike CX3CR1(GFP) monocytes, which downregulate GFP expression on differentiation into macrophages in this model, CD68-GFP monocytes retain high-level GFP expression for 72 hours after differentiation into macrophages, allowing continued cell tracking during resolution of inflammation. In summary, this novel CD68-GFP transgenic reporter mouse line represents a powerful resource for analyzing monocyte mobilization and monocyte trafficking as well as studying the fate of recruited monocytes in models of acute and chronic inflammation. © 2014 by The American Society of Hematology.

Bone marrow–based homeostatic proliferation of mature T cells in nonhuman primates: implications for AIDS pathogenesis

PubMed Central

Paiardini, Mirko; Cervasi, Barbara; Engram, Jessica C.; Gordon, Shari N.; Klatt, Nichole R.; Muthukumar, Alagarraju; Else, James; Mittler, Robert S.; Staprans, Silvija I.; Sodora, Donald L.

2009-01-01

Bone marrow (BM) is the key hematopoietic organ in mammals and is involved in the homeostatic proliferation of memory CD8+ T cells. Here we expanded on our previous observation that BM is a preferential site for T-cell proliferation in simian immunodeficiency virus (SIV)–infected sooty mangabeys (SMs) that do not progress to AIDS despite high viremia. We found high levels of mature T-cell proliferation, involving both naive and memory cells, in healthy SMs and rhesus macaques (RMs). In addition, we observed in both species that lineage-specific, BM-based T-cell proliferation follows antibody-mediated in vivo CD4+ or CD8+ T-cell depletion, thus indicating a role for the BM in maintaining T-cell homeostasis under depleting circumstances. We also observed that, in SIV-infected SMs, but not RMs, the level of proliferation of BM-based CD4+ T cells is higher than that of circulating CD4+ T cells. Interestingly, limited BM-based CD4+ T-cell proliferation was found in SIV-infected SMs with low CD4+ T-cell counts, suggesting a regenerative failure in these animals. Collectively, these results indicate that BM is involved in maintaining T-cell homeostasis in primates and suggest a role for BM-based CD4+ T-cell proliferation in determining the benign nature of natural SIV infection of SMs. PMID:18832134

Bone marrow-based homeostatic proliferation of mature T cells in nonhuman primates: implications for AIDS pathogenesis.

PubMed

Paiardini, Mirko; Cervasi, Barbara; Engram, Jessica C; Gordon, Shari N; Klatt, Nichole R; Muthukumar, Alagarraju; Else, James; Mittler, Robert S; Staprans, Silvija I; Sodora, Donald L; Silvestri, Guido

2009-01-15

Bone marrow (BM) is the key hematopoietic organ in mammals and is involved in the homeostatic proliferation of memory CD8(+) T cells. Here we expanded on our previous observation that BM is a preferential site for T-cell proliferation in simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) that do not progress to AIDS despite high viremia. We found high levels of mature T-cell proliferation, involving both naive and memory cells, in healthy SMs and rhesus macaques (RMs). In addition, we observed in both species that lineage-specific, BM-based T-cell proliferation follows antibody-mediated in vivo CD4(+) or CD8(+) T-cell depletion, thus indicating a role for the BM in maintaining T-cell homeostasis under depleting circumstances. We also observed that, in SIV-infected SMs, but not RMs, the level of proliferation of BM-based CD4(+) T cells is higher than that of circulating CD4(+) T cells. Interestingly, limited BM-based CD4(+) T-cell proliferation was found in SIV-infected SMs with low CD4(+) T-cell counts, suggesting a regenerative failure in these animals. Collectively, these results indicate that BM is involved in maintaining T-cell homeostasis in primates and suggest a role for BM-based CD4(+) T-cell proliferation in determining the benign nature of natural SIV infection of SMs.

IL-7Rαlow memory CD8+ T cells are significantly elevated in patients with systemic lupus erythematosus.

PubMed

Kim, Jung-Sik; Cho, Bon-A; Sim, Ji Hyun; Shah, Kamini; Woo, Connie M; Lee, Eun Bong; Lee, Dong-Sup; Kang, Jae Seung; Lee, Wang Jae; Park, Chung-Gyu; Craft, Joe; Kang, Insoo; Kim, Hang-Rae

2012-09-01

Human effector memory (EM) CD8(+) T cells include IL-7Rα(high) and IL-7Rα(low) cells with distinct cellular characteristics, including the expression of cytotoxic molecules. Both NK cells and the NK cell-associated molecule 2B4 that is expressed on CD8(+) T cells promote cytotoxicity. Here we analysed the expression of 2B4 on IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells and its contribution to cytotoxicity. We also analysed the frequency of IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells in patients with SLE or lupus and in healthy individuals given the potential role of cytotoxic CD8(+) T cells in the pathogenesis of lupus. We used flow cytometry to measure the expression of 2B4 on IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells as well as the frequency of these cell populations in the peripheral blood of healthy individuals and patients with SLE. Also, 2B4-mediated cytotoxicity was quantitated in IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells using target cells with CD48 antigen. We found that IL-7Rα(high) EM CD8(+) T cells had higher levels of 2B4 expression compared with IL-7Rα(low) EM CD8(+) T cells. Triggering 2B4 enhanced the cytotoxic function of IL-7Rα(low) EM CD8(+) T cells against target cells. We also noticed that patients with SLE had an increased frequency of IL-7Rα(low) EM CD8(+) T cells that correlated with disease manifestation. Our findings show that SLE patients have increased IL-7Rα(low) EM CD8(+) T cells, possibly contributing to tissue damage through 2B4-mediated cytotoxicity.

CD28 in thymocyte development and peripheral T cell activation in mice exposed to suspended particulate matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drela, Nadzieja; Zesko, Izabela; Jakubowska, Martyna

2006-09-01

The CD28:B7 signaling pathway is very important for the activity of mature peripheral T lymphocytes and thymocyte development. The proper development of thymocytes into mature single positive CD4{sup +}and CD8{sup +} T cells is crucial for almost all immune functions. In naturally occurring conditions, T cells maturation in the thymus is influenced by environmental agents. The expression of CD28 and the distribution of CD28{sup low/high} thymocytes have been examined at various stages of thymocyte development in BALB/c mice exposed to air-suspended particulate matter (ASM). Acute exposure to ASM resulted in the decrease of CD28 expression in the total thymocyte population.more » The increase of the percentage of CD28{sup low} and the decrease of CD28{sup high} thymocytes were observed, which may account for the acceleration of thymocyte development under the conditions of elevated risk resulting from the exposure of animals to environmental xenobiotics. ASM exposure resulted in the increase of the level of proliferation of lymph node T cells induced by anti-CD3 and anti-CD28 monoclonal antibodies activation despite normal expression of CD28 molecule. In contrast, the level of proliferation of spleen T cells was lowered or normal dependently of the concentration of stimuli used for activation. Results of these studies demonstrate that acute exposure of mice to ASM can result in the progression of two contrasting processes in the immune system: upregulation of thymocyte development, which contributes to the maintenance of peripheral T cell pool, and over-activation of lymph node lymphocytes, which may lead to uncontrolled immunostimulation.« less

CD8 down-regulation and functional impairment of SIV-specific cytotoxic T lymphocytes in lymphoid and mucosal tissues during SIV infection.

PubMed

Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A; Veazey, Ronald S

2013-06-01

Functional impairment of virus-specific T cells is a hallmark of HIV/SIV infection, but the underlying mechanisms of this dysfunction are not well understood. To address this, we simultaneously analyzed the expression and intensity of CD8 and inhibitory PD-1 on CTL in blood and lymphoid tissues in SIV-infected rhesus macaques. The intensity (mean channel fluorescence) of CD8 expression was transiently down-regulated in early SIV infection (10-14 dpi), despite an increase in CD8(+) T cell proliferation. In chronic infection, CD8 expression was maintained at low levels on CD8(+) T cells in all tissues. Interestingly, Gag-specific CTLs were clearly divided into CD8high- and CD8low-expressing populations in SIV-infected macaques, and CD8low Gag-specific cells increased with disease progression, especially in lymphoid tissues when compared with peripheral blood or in Gag-vaccinated controls. Moreover, the CD8low CTL population secreted lower levels of cytokines upon SIV antigen stimulation and exhibited lower proliferative capacity during infection compared with the CD8high CTL population. Meanwhile, intensity of PD-1 expression on Gag-specific CTL in chronic infection was significantly higher than in acute SIV infection, although the frequencies of PD-1+ Gag-specific cells were similar in acute and chronic stages. In summary, down-regulation of CD8 expression and higher expression of PD-1 on SIV-specific CTLs could coordinately attenuate SIV-specific CTL responses and their ability to recognize virus-infected target cells, especially in lymphoid tissues, resulting in failure to contain viremia, and continued persistence and replication of HIV in lymphoid tissue reservoirs.

The effect of extracorporeal photopheresis alone or in combination therapy on circulating CD4+Foxp3+CD25- T-cells in patients with leukemic cutaneous T-cell lymphoma

PubMed Central

Shiue, Lisa H.; Couturier, Jacob; Lewis, Dorothy E.; Wei, Caimiao; Ni, Xiao; Duvic, Madeleine

2015-01-01

Purpose Extracorporeal photopheresis (ECP) alone or in combination therapy is effective for treatment of leukemic cutaneous T-cell lymphoma (L-CTCL), but its mechanism(s) of action remain unclear. This study was designed to investigate the effect of ECP on regulatory T-cell and CD8+ T-cells in L-CTCL patients. Experimental Design Peripheral blood from 18 L-CTCL patients at baseline, Day 2, 1-month, 3-month, and 6-month post-ECP therapy were analyzed by flow cytometry for CD4+CD25+/high, CD4+Foxp3+CD25+/-, CD3+CD8+, CD3+CD8+CD69+, and CD3+CD8+IFN-γ+ T-cells. Clinical responses were assessed and correlated with changes in these T-cell subsets. Results Twelve of 18 patients achieved clinical responses. The average baseline number of CD4+CD25+/high T-cells of PBMCs in L-CTCL patients was normal (2.2%), but increased at 6-month post-therapy (4.3%, p<0.01). The average baseline number of CD4+Foxp3+ T-cells out of CD4+ T-cells in 9 evaluable patients was high (66.8±13.7%), mostly CD25 negative. The levels of CD4+Foxp3+ T cells in responders were higher (n=6, 93.1±5.7%) than non-responders (n=3, 14.2±16.0%, p<0.01), and they declined in parallel with malignant T-cells. The numbers of CD3+CD8+CD69+ and CD3+CD8+ IFN-γ+ T-cells increased at 3-month post-therapy in 5 of 6 patients studied. Conclusions ECP alone or in combination therapy might be effective in L-CTCL patients whose malignant T-cells have a CD4+Foxp3+CD25- phenotype. PMID:25772268

FAT/CD36 expression alone is insufficient to enhance cellular uptake of oleate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eyre, Nicholas S.; Cleland, Leslie G.; Mayrhofer, Graham

2008-06-06

Fatty acid translocase (FAT/CD36) is one of several proteins implicated in receptor-mediated uptake of long-chain fatty acids (LCFAs). We have tested whether levels of FAT/CD36 correlate with cellular oleic acid import, using a Tet-Off inducible transfected CHO cell line. Consistent with our previous findings, FAT/CD36 was enriched in lipid raft-derived detergent-resistant membranes (DRMs) that also contained caveolin-1, the marker protein of caveolae. Furthermore in transfected cells, plasma membrane FAT/CD36 co-localized extensively with the lipid raft-enriched ganglioside GM1, and partially with a caveolin-1-EGFP fusion protein. Nevertheless, even at high levels of expression, FAT/CD36 did not affect uptake of oleic acid. Wemore » propose that the ability of FAT/CD36 to mediate enhanced uptake of LCFAs is dependent on co-expression of other proteins or factors that are lacking in CHO cells.« less

The therapeutic effect of mesenchymal stem cells on pulmonary myeloid cells following neonatal hyperoxic lung injury in mice.

PubMed

Al-Rubaie, Ali; Wise, Andrea F; Sozo, Foula; De Matteo, Robert; Samuel, Chrishan S; Harding, Richard; Ricardo, Sharon D

2018-06-08

Exposure to high levels of oxygen (hyperoxia) after birth leads to lung injury. Our aims were to investigate the modulation of myeloid cell sub-populations and the reduction of fibrosis in the lungs following administration of human mesenchymal stem cells (hMSC) to neonatal mice exposed to hyperoxia. Newborn mice were exposed to 90% O 2 (hyperoxia) or 21% O 2 (normoxia) from postnatal days 0-4. A sub-group of hyperoxia mice were injected intratracheally with 2.5X10 5 hMSCs. Using flow cytometry we assessed pulmonary immune cells at postnatal days 0, 4, 7 and 14. The following markers were chosen to identify these cells: CD45 + (leukocytes), Ly6C + Ly6G + (granulocytes), CD11b + CD11c + (macrophages); macrophage polarisation was assessed by F4/80 and CD206 expression. hMSCs expressing enhanced green fluorescent protein (eGFP) and firefly luciferase (fluc) were administered via the trachea at day 4. Lung macrophages in all groups were profiled using next generation sequencing (NGS) to assess alterations in macrophage phenotype. Pulmonary collagen deposition and morphometry were assessed at days 14 and 56 respectively. At day 4, hyperoxia increased the number of pulmonary Ly6C + Ly6G + granulocytes and F4/80 low CD206 low macrophages but decreased F4/80 high CD206 high macrophages. At days 7 and 14, hyperoxia increased numbers of CD45 + leukocytes, CD11b + CD11c + alveolar macrophages and F4/80 low CD206 low macrophages but decreased F4/80 high CD206 high macrophages. hMSCs administration ameliorated these effects of hyperoxia, notably reducing numbers of CD11b + CD11c + and F4/80 low CD206 low macrophages; in contrast, F4/80 high CD206 high macrophages were increased. Genes characteristic of anti-inflammatory 'M2' macrophages (Arg1, Stat6, Retnla, Mrc1, Il27ra, Chil3, and Il12b) were up-regulated, and pro-inflammatory 'M1' macrophages (Cd86, Stat1, Socs3, Slamf1, Tnf, Fcgr1, Il12b, Il6, Il1b, and Il27ra) were downregulated in isolated lung macrophages from hyperoxia-exposed mice administered hMSCs, compared to mice without hMSCs. Hydroxyproline assay at day 14 showed that the 2-fold increase in lung collagen following hyperoxia was reduced to control levels in mice administered hMSCs. By day 56 (early adulthood), hMSC administration had attenuated structural changes in hyperoxia-exposed lungs. Our findings suggest that hMSCs reduce neonatal lung injury caused by hyperoxia by modulation of macrophage phenotype. Not only did our cell-based therapy using hMSC induce structural repair, it limited the progression of pulmonary fibrosis.

Circulating brain derived neurotrophic factor (BDNF) and frequency of BDNF positive T cells in peripheral blood in human ischemic stroke: Effect on outcome.

PubMed

Chan, Adeline; Yan, Jun; Csurhes, Peter; Greer, Judith; McCombe, Pamela

2015-09-15

The aim of this study was to measure the levels of circulating BDNF and the frequency of BDNF-producing T cells after acute ischaemic stroke. Serum BDNF levels were measured by ELISA. Flow cytometry was used to enumerate peripheral blood leukocytes that were labelled with antibodies against markers of T cells, T regulatory cells (Tregs), and intracellular BDNF. There was a slight increase in serum BDNF levels after stroke. There was no overall difference between stroke patients and controls in the frequency of CD4(+) and CD8(+) BDNF(+) cells, although a subgroup of stroke patients showed high frequencies of these cells. However, there was an increase in the percentage of BDNF(+) Treg cells in the CD4(+) population in stroke patients compared to controls. Patients with high percentages of CD4(+) BDNF(+) Treg cells had a better outcome at 6months than those with lower levels. These groups did not differ in age, gender or initial stroke severity. Enhancement of BDNF production after stroke could be a useful means of improving neuroprotection and recovery after stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

Fanconi anemia genes are highly expressed in primitive CD34+ hematopoietic cells

PubMed Central

Aubé, Michel; Lafrance, Matthieu; Brodeur, Isabelle; Delisle, Marie-Chantal; Carreau, Madeleine

2003-01-01

Background Fanconi anemia (FA) is a complex recessive genetic disease characterized by progressive bone marrow failure (BM) and a predisposition to cancer. We have previously shown using the Fancc mouse model that the progressive BM failure results from a hematopoietic stem cell defect suggesting that function of the FA genes may reside in primitive hematopoietic stem cells. Methods Since genes involved in stem cell differentiation and/or maintenance are usually regulated at the transcription level, we used a semiquantitative RT-PCR method to evaluate FA gene transcript levels in purified hematopoietic stem cells. Results We show that most FA genes are highly expressed in primitive CD34-positive and negative cells compared to lower levels in more differentiated cells. However, in CD34- stem cells the Fancc gene was found to be expressed at low levels while Fancg was undetectable in this population. Furthermore, Fancg expression is significantly decreased in Fancc -/- stem cells as compared to wild-type cells while the cancer susceptibility genes Brca1 and Fancd1/Brac2 are upregulated in Fancc-/- hematopoietic cells. Conclusions These results suggest that FA genes are regulated at the mRNA level, that increased Fancc expression in LTS-CD34+ cells correlates with a role at the CD34+ differentiation stage and that lack of Fancc affects the expression of other FA gene, more specifically Fancg and Fancd1/Brca2, through an unknown mechanism. PMID:12809565

Circulating cathelicidin levels correlate with mucosal disease activity in ulcerative colitis, risk of intestinal stricture in Crohn's disease, and clinical prognosis in inflammatory bowel disease.

PubMed

Tran, Diana Hoang-Ngoc; Wang, Jiani; Ha, Christina; Ho, Wendy; Mattai, S Anjani; Oikonomopoulos, Angelos; Weiss, Guy; Lacey, Precious; Cheng, Michelle; Shieh, Christine; Mussatto, Caroline C; Ho, Samantha; Hommes, Daniel; Koon, Hon Wai

2017-05-12

Cathelicidin (LL-37) is an antimicrobial peptide known to be associated with various autoimmune diseases. We attempt to determine if cathelicidin can accurately reflect IBD disease activity. We hypothesize that serum cathelicidin correlates with mucosal disease activity, stricture, and clinical prognosis of IBD patients. Serum samples were collected from two separate cohorts of patients at the University of California, Los Angeles. Cohort 1 consisted of 50 control, 23 UC, and 28 CD patients. Cohort 2 consisted of 20 control, 57 UC, and 67 CD patients. LL-37 levels were determined by ELISA. Data from both cohorts were combined for calculation of accuracies in indicating mucosal disease activity, relative risks of stricture, and odds ratios of predicting disease development. Serum cathelicidin levels were inversely correlated with Partial Mayo Scores of UC patients and Harvey-Bradshaw Indices of CD patients. Among IBD patients with moderate or severe initial disease activity, the patients with high initial LL-37 levels had significantly better recovery than the patients with low initial LL-37 levels after 6-18 months, suggesting that high LL-37 levels correlate with good prognosis. Co-evaluation of LL-37 and CRP levels was more accurate than CRP alone or LL-37 alone in the correlation with Mayo Endoscopic Score of UC patients. Low LL-37 levels indicated a significantly elevated risk of intestinal stricture in CD patients. Co-evaluation of LL-37 and CRP can indicate mucosal disease activity in UC patients. LL-37 can predict future clinical activity in IBD patients and indicate risk of intestinal stricture in CD patients.

Plasma Level of Interleukin-35 as an Independent Prognostic Indicator in Hepatocellular Carcinoma.

PubMed

Qiu, Xiangting; Wang, Xinhua; Song, Yucui; Chen, Lingling

2016-12-01

Hepatocellular carcinoma is a major type of liver cancer with poor prognosis. The aim of the study was to determine the prognostic significance of plasma interleukin-35 level in hepatocellular carcinoma. A total of 153 hepatocellular carcinoma patients and 153 healthy controls were enrolled. Blood samples were obtained at admission. Plasma interleukin-35 level was analyzed by enzyme-linked immunosorbent assay. Distribution of T cell subset and expression of Fas/FasL protein were detected by flow cytometry. The patients were followed up for 2 years. Poor prognosis was defined as death of hepatocellular carcinoma. The plasma levels of interleukin-35 were significantly higher in the patients than the controls (25.1 ± 13.1, 9.3 ± 6.3 pg/mL, P < 0.001). After adjusted for multiple confounding factors, the multivariate logistic regression analyses reported that high level of interleukin-35 (≥25.0 pg/mL) was associated with the poor prognosis in the patients (OR 6.63, 95 % CI 3.27-13.47). Compared with the patients with low level of interleukin-35 (<25.0 pg/mL), the patients with high level of interleukin-35 showed higher frequencies of CD4+CD25+FoxP3+ and CD3+Foxp3+ regulatory T cells (P < 0.001 and P < 0.001) and also showed higher apoptosis levels of CD8+ T cells (P < 0.001). Circulating interleukin-35 concentration might be an independent prognostic indicator in hepatocellular carcinoma. Such prognostic significance could be partly involved in the activation of regulatory T cell and the apoptosis of CD8+ T cell.

Bioremediation of cadmium- and zinc-contaminated soil using Rhodobacter sphaeroides.

PubMed

Peng, Weihua; Li, Xiaomin; Song, Jingxiang; Jiang, Wei; Liu, Yingying; Fan, Wenhong

2018-04-01

Bioremediation using microorganisms is a promising technique to remediate soil contaminated with heavy metals. In this study, Rhodobacter sphaeroides was used to bioremediate soils contaminated with cadmium (Cd) and zinc (Zn). The study found that the treatment reduced the overall bioavailable fractions (e.g., exchangeable and carbonate bound phases) of Cd and Zn. More stable fractions (e.g., Fe-Mn oxide, organic bound, and residual phases (only for Zn)) increased after bioremediation. A wheat seedling experiment revealed that the phytoavailability of Cd was reduced after bioremediation using R. sphaeroides. After bioremediation, the exchangeable phases of Cd and Zn in soil were reduced by as much as 30.7% and 100.0%, respectively; the Cd levels in wheat leaf and root were reduced by as much as 62.3% and 47.2%, respectively. However, when the soils were contaminated with very high levels of Cd and Zn (Cd 54.97-65.33 mg kg -1 ; Zn 813.4-964.8 mg kg -1 ), bioremediation effects were not clear. The study also found that R. sphaeroides bioremediation in soil can enhance the Zn/Cd ratio in the harvested wheat leaf and root overall. This indicates potentially favorable application in agronomic practice and biofortification. Although remediation efficiency in highly contaminated soil was not significant, R. sphaeroides may be potentially and practically applied to the bioremediation of soils co-contaminated by Cd and Zn. Copyright © 2018 Elsevier Ltd. All rights reserved.

EMMPRIN/CD147 is an independent prognostic biomarker in cutaneous melanoma.

PubMed

Caudron, Anne; Battistella, Maxime; Feugeas, Jean-Paul; Pages, Cécile; Basset-Seguin, Nicole; Mazouz Dorval, Sarra; Funck Brentano, Elisa; Sadoux, Aurélie; Podgorniak, Marie-Pierre; Menashi, Suzanne; Janin, Anne; Lebbé, Céleste; Mourah, Samia

2016-08-01

CD147 has been implicated in melanoma invasion and metastasis mainly through increasing metalloproteinase synthesis and regulating VEGF/VEGFR signalling. In this study, the prognostic value of CD147 expression was investigated in a cohort of 196 cutaneous melanomas including 136 consecutive primary malignant melanomas, 30 lymph nodes, 16 in-transit and 14 visceral metastases. A series of 10 normal skin, 10 blue nevi and 10 dermal nevi was used as control. CD147 expression was assessed by immunohistochemistry, and the association of its expression with the clinicopathological characteristics of patients and survival was evaluated using univariate and multivariate statistical analyses. Univariate analysis showed that high CD147 expression was significantly associated with metastatic potential and with a reduced overall survival (P < 0.05 for both) in primary melanoma patients. CD147 expression level was correlated with histological factors which were associated with prognosis: Clark level, ulceration status and more particularly with Breslow index (r = 0.7, P < 10(-8) ). Multivariate analysis retained CD147 expression level and ulceration status as predicting factors for metastasis and overall survival (P < 0.05 for both). CD147 emerges as an important factor in the aggressive behaviour of melanoma and deserves further evaluation as an independent prognostic biomarker. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

CD147, CD44, and the Epidermal Growth Factor Receptor (EGFR) Signaling Pathway Cooperate to Regulate Breast Epithelial Cell Invasiveness*

PubMed Central

Grass, G. Daniel; Tolliver, Lauren B.; Bratoeva, Momka; Toole, Bryan P.

2013-01-01

The immunoglobulin superfamily glycoprotein CD147 (emmprin; basigin) is associated with an invasive phenotype in various types of cancers, including malignant breast cancer. We showed recently that up-regulation of CD147 in non-transformed, non-invasive breast epithelial cells is sufficient to induce an invasive phenotype characterized by membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invadopodia activity (Grass, G. D., Bratoeva, M., and Toole, B. P. (2012) Regulation of invadopodia formation and activity by CD147. J. Cell Sci. 125, 777–788). Here we found that CD147 induces breast epithelial cell invasiveness by promoting epidermal growth factor receptor (EGFR)-Ras-ERK signaling in a manner dependent on hyaluronan-CD44 interaction. Furthermore, CD147 promotes assembly of signaling complexes containing CD147, CD44, and EGFR in lipid raftlike domains. We also found that oncogenic Ras regulates CD147 expression, hyaluronan synthesis, and formation of CD147-CD44-EGFR complexes, thus forming a positive feedback loop that may amplify invasiveness. Last, we showed that malignant breast cancer cells are heterogeneous in their expression of surface-associated CD147 and that high levels of membrane CD147 correlate with cell surface EGFR and CD44 levels, activated EGFR and ERK1, and activated invadopodia. Future studies should evaluate CD147 as a potential therapeutic target and disease stratification marker in breast cancer. PMID:23888049

Significant differences in B-cell subpopulations characterize patients with chronic graft-versus-host disease-associated dysgammaglobulinemia.

PubMed

Kuzmina, Zoya; Greinix, Hildegard T; Weigl, Roman; Körmöczi, Ulrike; Rottal, Arno; Frantal, Sophie; Eder, Sandra; Pickl, Winfried F

2011-02-17

Manifestations of chronic graft-versus-host disease (cGVHD) can resemble those seen in immunodeficiency states and autoimmune disorders. Reports by us and others suggest an involvement of B cells in the pathogenesis of cGVHD. We investigated B-lymphocyte subpopulations in cGVHD cohorts defined by serum immunoglobulin G (IgG) levels to characterize novel biomarkers for impairment of humoral immunity after allogeneic hematopoietic stem cell transplantation. Seventy-six patients were enrolled a median of 46 months after hematopoietic stem cell transplantation. The hypogammaglobulinemia group had significantly diminished CD19(+) B cells (165 vs 454 vs 417 × 10⁶L) with elevated CD19(+)CD21(low) immature (16.5%, 7.7%, and 9.1%) and CD19(+)CD21(int-high)CD38(high)IgM(high) transitional (10.5% vs 4.2% vs 6.3%) B-cell proportions compared with the normogammaglobulinemia and hypergammaglobulinemia groups. CD19(+)CD10(-)CD27(-)CD21(high) naive B cells were highly elevated in all patients with cGVHD. CD19(+)CD27(+)IgD(+) non-class-switched (4 vs 12 vs 11 × 10⁶/L) and class-switched (7 vs 35 vs 42 × 10⁶/L) memory B cells were significantly lower in the hypogammaglobulinemia group compared with the others. Besides significantly higher B-cell activation factor/B-cell ratios, significantly more cGVHD patients with hypergammaglobulinemia had autoantibodies compared with the hypogammaglobulinemia subgroup (68% vs 24%, P = .024). In conclusion, B-cell subpopulations can serve as novel cellular biomarkers for immunodeficiency and autoimmunity indicating different pathogenetic mechanisms of cGVHD and encouraging future prospective longitudinal studies.

Root-to-shoot Cd translocation via the xylem is the major process determining shoot and grain cadmium accumulation in rice

PubMed Central

Uraguchi, Shimpei; Mori, Shinsuke; Kuramata, Masato; Kawasaki, Akira; Arao, Tomohito; Ishikawa, Satoru

2009-01-01

Physiological properties involved in divergent cadmium (Cd) accumulation among rice genotypes were characterized using the indica cultivar ‘Habataki’ (high Cd in grains) and the japonica cultivar ‘Sasanishiki’ (low Cd in grains). Time-dependence and concentration-dependence of symplastic Cd absorption in roots were revealed not to be responsible for the different Cd accumulation between the two cultivars because root Cd uptake was not greater in the Cd-accumulating cultivar ‘Habataki’ compared with ‘Sasanishiki’. On the other hand, rapid and greater root-to-shoot Cd translocation was observed in ‘Habataki’, which could be mediated by higher abilities in xylem loading of Cd and transpiration rate as a driving force. To verify whether different abilities in xylem-mediated shoot-to-root translocation generally account for the genotypic variation in shoot Cd accumulation in rice, the world rice core collection, consisting of 69 accessions which covers the genetic diversity of almost 32 000 accessions of cultivated rice, was used. The results showed strong correlation between Cd levels in xylem sap and shoots and grains among the 69 rice accessions. Overall, the results presented in this study revealed that the root-to-shoot Cd translocation via the xylem is the major and common physiological process determining the Cd accumulation level in shoots and grains of rice plants. PMID:19401409

Increasing CACNA1C expression in placenta containing high Cd level: an implication of Cd toxicity.

PubMed

Phuapittayalert, Laorrat; Saenganantakarn, Phisid; Supanpaiboon, Wisa; Cheunchoojit, Supaporn; Hipkaeo, Wiphawi; Sakulsak, Natthiya

2016-12-01

Cadmium (Cd) has known to produce many adverse effects on organs including placenta. Many essential transporters are involved in Cd transport pathways such as DMT-1, ZIP as well as L-VDCC. Fourteen pregnant women participated and were divided into two groups: high and low Cd-exposed (H-Cd, L-Cd) groups on the basis of their residential areas, Cd concentrations in the blood (B-Cd), urine (U-Cd), and placenta (P-Cd). The results showed that the B-Cd and U-Cd were significantly increased in H-Cd group (p < 0.05). Interestingly, the P-Cd in H-Cd group was elevated (p < 0.05) and positively related to their B-Cd and U-Cd values (p < 0.05). However, the mean cord blood Cd (C-Cd) concentration in H-Cd group was not significantly increased about 2.5-fold when comparing to L-Cd group. To determine the Cd accumulation in placental tissues, metallothionein-1A (MT-1A) and metallothionein-2A (MT-2A) expressions were used as biomarkers. The results revealed that mean MT-1A and MT-2A mRNAs and MT-1/2 proteins were up-regulated in H-Cd group (p < 0.05). In addition, the Ca channel alpha 1C (CACNA1C) mRNA and protein expressions were noticeably elevated in H-Cd group (p < 0.05). From these findings, we suggested that CACNA1C might be implicated in Cd transport in human placenta.

Tracing Cd, Zn and Pb pollution sources in bivalves using isotopes

NASA Astrophysics Data System (ADS)

Shiel, A. E.; Weis, D. A.; Orians, K. J.

2010-12-01

In a multi-tracer study, Cd, Zn and Pb isotopes (MC-ICP-MS) and elemental concentrations (HR-ICP-MS) are evaluated as tools to distinguish between natural and anthropogenic sources of these metals in bivalves from western Canada (British Columbia), the eastern USA, Hawaii and France. High Cd concentrations found in BC oysters have elicited economic and health concerns. The source of these high Cd levels is unknown but thought to be largely natural. High Cd levels in BC oysters are largely attributed to the natural upwelling of Cd-rich intermediate waters in the North Pacific as the δ114/110Cd (-0.69 to -0.09‰) and δ66/64Zn (0.28 to 0.36‰) values of BC oysters fall within the range reported for North Pacific seawater. Different contributions from anthropogenic sources account for the variability of Cd isotopic compositions of BC oysters; the lightest of these oysters are from the BC mainland. These oysters also have Pb isotopic compositions that reflect primarily anthropogenic sources (e.g., leaded and unleaded automotive gasoline and smelting of Pb ores, potentially historical). On the contrary, USA East Coast bivalves exhibit relatively light Cd isotopic compositions (δ114/110Cd = -1.20 to -0.54‰; lighter than reported for North Atlantic seawater) due to the high prevalence of industry on this coast. The Pb isotopic compositions of these bivalves indicate contributions from the combustion of coal. The large variability of environmental health among coastal areas in France is reflected in the broad range of Cd isotopic compositions exhibited by French bivalves (δ114/110Cd = -1.08 to -0.20‰). Oysters and mussels from the Marennes-Oléron basin and Gironde estuary have the lightest Cd isotopic compositions of the French oysters consistent with significant historical Cd emissions from the now-closed proximal Zn smelter. In these bivalves, significant declines in the Cd levels between 1984/7 and 2004/5 are not accompanied by a significant shift in the Cd isotopic composition toward natural values. The Mediterranean samples have isotopic compositions within error of the lighter end of the range reported for Mediterranean seawater. The Zn isotopic compositions of French oysters and mussels (δ66/64Zn = 0.39 to 0.46‰) are identical to those reported for North Atlantic seawater, with the exception of the much heavier compositions of oysters (δ66/64Zn = 1.03 to 1.15‰) from the polluted Gironde estuary. In agreement with Cd and Zn isotopic compositions, the Pb isotopic compositions of the French bivalves indicate primarily industrial (as opposed to automotive) sources; this is consistent with the collection of most of the French bivalve samples in 2004, after the complete phase-out of leaded gasoline in France. This study demonstrates the effective use of Cd and Zn isotopes to trace anthropogenic sources in the environment and the benefit of combining these tools with Pb isotope “fingerprinting” techniques to identify processes contributing metals. Use of these new geochemical tools requires site-specific knowledge of potential metal sources and their isotopic compositions.

Retinol as a micronutrients related to cervical local immunity: The expression of tumor necrosis factor-alpha specifically stimulated with E6 epitope of human papillomavirus type-16 and ratio of CD4+/CD8+ T cell in natural history of cervical cancer

NASA Astrophysics Data System (ADS)

Utami, T. W.; Aziz, M. F.; Ibrahim, F.; Andrijono

2017-08-01

Retinol is one of the antioxidant micronutrients that plays essential roles in the immune system, by preventing the persistence of modulating CD4+ and CD8+ T cells and cytokines production. Tumor Necrosis Factor-Alpha (TNF-α) is an acute pro-inflammatory cytokine which has many crucial roles in controlling HPV. In contrast, when persistent infection occurs, TNF-α induces carcinogenesis. The ratio of CD4+ cells to CD8+ T cells and adequate TNF-α production in acute HPV infection are key points for clearance. The aim of this research is to analyze the sufficiency level of retinol deposit, the expression of TNF-α, and the ratio of CD4+: CD8+ T cells in a normal cervix, clearance and persistent HPV subclinical infection, and cervical cancer group. The sufficiency level of retinol deposit was analyzed from peripheral blood using the ELISA method. The cervico-vaginal secretions, which were incubated for 24 hours, were stimulated specifically by E6 epitope HPV type-16, measuring TNF-α expression semi-quantitatively by the ELISpot method and CD4+/CD8+ T cells quantitatively by flowcytometry method. The sufficient level of retinol deposit in a normal cervix, clearance HPV subclinical infection, persistent, and cervical cancer group was 85%, 75% (OR 1.89), 33.3% (OR 11.33), and 75% (OR 1.89), respectively. The expression of TNF-α in normal cervix group was 10%, while for cervical cancer it was 75% (OR 27.00; p < 0.001). There was no expression in clearance and persistent HPV subclinical infection groups. A high ratio of CD4+: CD8+ T cells in the normal cervix and cervical cancer group was 10% and 25% (OR 0.33). There was no high ratio of CD4+: CD8+ T cells in clearance (OR 1.22) and persistent (OR 0.95) HPV subclinical infection groups. This study was able to prove that the normal cervix group has the highest retinol deposit sufficiency level and the cervical cancer group has the highest TNF-α expression (OR 27; p < 0.001). The lowest of retinol deposit sufficiency level was not in cervical cancer, but in the persistent HPV subclinical infection group (OR 11.33). There was significant correlation in TNF-α expression between cervical cancer and normal cervix (p < 0.001), cervical cancer and clearance subclinical HPV infection (p = 0.024), and between clearance and persistent group (p = 0.007).

CD10 and osteopontin expression in dentigerous cyst and ameloblastoma.

PubMed

Masloub, Shaimaa M; Abdel-Azim, Adel M; Elhamid, Ehab S Abd

2011-05-24

To investigate the expression of CD10 and osteopontin in dentigerous cyst and ameloblastoma and to correlate their expression with neoplastic potentiality of dentigerous cyst and local invasion and risk of local recurrence in ameloblastoma. CD10 and osteopontin expression was studied by means of immunohistochemistry in 9 cases of dentigerous cysts (DC) and 17 cases of ameloblastoma. There were 7 unicystic ameloblastoma (UCA) and 10 multicystic ameloblastoma (MCA). Positive cases were included in the statistical analysis, carried on the tabulated data using the Open Office Spreadsheet 3.2.1 under Linux operating system. Analysis of variance and correlation studies were performed using "R" under Linux operating system (R Development Core Team (2010). Tukey post-hoc test was also performed as a pair-wise test. The significant level was set at 0.05. High CD10 and osteopontin expression was observed in UCA and MCA, and low CD10 and osteopontin expression was observed in DC. Significant correlation was seen between CD10 and osteopontin expression and neoplastic potentiality of DC and local invasion and risk of recurrences in ameloblastoma. In DC, high CD10 and osteopontin expression may indicate the neoplastic potentiality of certain areas. In UCA & MCA, high CD10 and osteopontin expression may identify areas with locally invasive behavior and high risk of recurrence.

Awareness of chronic disease diagnosis amongst family members is associated with healthy dietary knowledge but not behaviour amongst Inuit in Arctic Canada.

PubMed

Pakseresht, M; Mead, E; Gittelsohn, J; Roache, C; Sharma, S

2010-10-01

The extent to which awareness of chronic disease (CD) diagnosis affects one's healthy food knowledge, self-efficacy and intentions or healthy dietary and physical activity (PA) behaviours remains unexplored among Inuit in Canada. A food frequency questionnaire and an adult impact questionnaire were used in a cross-sectional study to collect self-reported data on daily energy and nutrient intake, PA and the diagnosis of hypertension, diabetes, heart disease and cancer amongst adult Inuit and their family members. Associations between awareness of personal and family CD status and healthy food knowledge, self-efficacy and intentions, percentage of energy consumed from non-nutrient-dense foods and PA were assessed via ordinal logistic regression. Of the 266 participants, those who self-reported CD for both themselves and their relative(s) were more likely to have high healthy food knowledge [odds ratio (OR)=2.45] than those who did not. Reporting hypertension and heart disease amongst only relatives increased the likelihood of high knowledge (OR=5.20) and intentions (OR=5.10) for healthy eating. Heart disease in both participants and their relatives was associated with high levels of PA (OR=12.24). However, there were no associations when only participants (but not their relatives) reported having CD. A joint effect between a high level of education and awareness of CD was positively related to high food knowledge (OR=38.93). An inverse association between awareness of CD and unhealthy eating was not observed. Awareness of a relative having a CD was a more important factor in increasing knowledge and, to a lesser degree, self-efficacy or intentions to eat healthy than participants' awareness of personal CD. However, awareness was not associated with lower non-nutrient-dense food intake. © 2010 The Authors. Journal compilation © 2010 The British Dietetic Association Ltd.

Photochemical internalization (PCI) of immunotoxins targeting CD133 is specific and highly potent at femtomolar levels in cells with cancer stem cell properties.

PubMed

Bostad, Monica; Berg, Kristian; Høgset, Anders; Skarpen, Ellen; Stenmark, Harald; Selbo, Pål K

2013-06-28

CD133 is a putative cancer stem cell (CSC) marker for a number of different cancers and is suggested to be a therapeutic target. Since also normal stem cells express CD133 it is of paramount importance that targeting strategies provide a specific and efficient delivery of cytotoxic drugs in only CD133-positive CSCs. In this study, we have employed photochemical internalization (PCI), a minimally invasive method for light-controlled, specific delivery of membrane-impermeable macromolecules from endocytic vesicles to the cytosol, to specifically target CD133-positive cancer cells. We demonstrate that PCI increases the cytotoxic effect of an immunotoxin (IT) targeting CD133-expressing cancer cells of colon (WiDr and HCT116) and pancreas (BxPC-3) origin. The IT consisted of the mAb CD133/1 (AC133) bound to the ribosome inactivating plant toxin saporin (anti-CD133/1-sap). We show that TPCS2a-PCI of anti-CD133/1-sap is specific, and highly cytotoxic at femto-molar concentrations. Specific binding and uptake of CD133/1, was shown by fluorescence microscopy and co-localization with TPCS2a in endosomes/lysosomes was determined by confocal microscopy. CD133(high) WiDr cells, isolated by fluorescence activated cell sorting, had a 7-fold higher capacity to initiate spheroids than CD133(low) cells (P<0.001) and were resistant to photodynamic therapy (PDT). However, PDT-resistance was bypassed by the PCI strategy. Tumor initiation and aggressive growth in athymic nude mice was obtained with only 10 CD133(high) cells in contrast to CD133(low) cells where substantially higher cell numbers were needed. The excellent high efficacy and selectivity of eliminating CD133-expressing cells by PCI warrant further pre-clinical evaluations of this novel therapeutic approach. Copyright © 2013 Elsevier B.V. All rights reserved.

CD52 is expressed on human mast cells and is a potential therapeutic target in Waldenstrom's Macroglobulinemia and mast cell disorders.

PubMed

Santos, Daniel Ditzel; Hatjiharissi, Evdoxia; Tournilhac, Olivier; Chemaly, Mariana Z A; Leleu, Xavier; Xu, Lian; Patterson, Christopher; Branagan, Andrew R; Manning, Robert J; Ho, Allen W; Hunter, Zachary R; Dimmock, Elizabeth A; Kutok, Jeffery L; Churchill, Winthrop H; Castells, Mariana C; Tai, Yu-Tzu; Anderson, Kenneth C; Treon, Steven P

2006-05-01

Alemtuzumab is a monoclonal antibody used in the treatment of CD52-expressing B-cell malignancies, including Waldenstrom's macroglobulinemia (WM). Recent studies demonstrate high levels of alemtuzumab activity in relapsed/refractory disease. One potential target of alemtuzumab is bone marrow mast cells (BMMCs), which provide growth and survival signaling for WM lymphoplasmacytic cells. We therefore examined BMMCs (FceRI+, CD117+) from WM and other mast cell (MC) disorders for expression of CD52. We identified cell surface antigen expression by multicolor flow cytometric analysis and found CD52 expressed on human mast-derived cell line-1 (HMC-1) and LAD2 MC lines, on BMMC from 13 of 15 patients with WM, and on BMMCs from 4 of 4 patients with systemic mastocytosis (SM). None of 4 healthy donors expressed CD52. Reverse-transcriptase polymerase chain reaction analysis confirmed CD52 expression in the HMC-1 and LAD2 MC lines, in BMMCs from 14 of 15 patients with WM, and 3 of 3 patients with SM. CD52 transcripts were also detected in BMMCs from 6 of 6 healthy donors, despite the absence of CD52 cell surface expression. Importantly, we observed high levels of alemtuzumab-mediated, antibody-dependent, cell-mediated cytotoxicity against LAD2 MCs and BMMCs from patients with WM and SM. These studies demonstrate that CD52 is widely expressed on human MCs and WM bone marrow lymphoplasmacytic cells and provide the preclinical rationale for the use of alemtuzumab in the treatment of WM and possibly other MC-related disorders.

CD206-positive myeloid cells bind galectin-9 and promote a tumor-supportive microenvironment.

PubMed

Enninga, Elizabeth Ann L; Chatzopoulos, Kyriakos; Butterfield, John T; Sutor, Shari L; Leontovich, Alexey A; Nevala, Wendy K; Flotte, Thomas J; Markovic, Svetomir N

2018-05-07

In patients with metastatic melanoma, high blood levels of galectin-9 are correlated with worse overall survival and a bias towards a Th2 inflammatory state supportive of tumor growth. Although galectin-9 signaling through TIM3 on T cells has been described, less is known about the interaction of galectin-9 with macrophages. We aimed to determine whether galectin-9 is a binding partner of CD206 on macrophages and whether the result of this interaction is tumor-supportive. It was determined that incubation of CD68+ macrophages with galectin-9 or anti-CD206 blocked target binding and that both CD206 and galectin-9 were detected by immunoprecipitation of cell lysates. CD206 and galectin-9 had a binding affinity of 2.8 × 10 -7 M. Galectin-9 causes CD206+ macrophages to make significantly more FGF2 and monocyte chemoattractant protein (MCP-1), but less macrophage-derived chemokine (MDC). Galectin-9 had no effect on classical monocyte subsets, but caused expansion of the non-classical populations. Lastly, there was a positive correlation between increasing numbers of CD206 macrophages and galectin-9 expression in tumors, and high levels of CD206 macrophages correlated negatively with melanoma survival. These results indicate that galectin-9 binds CD206 on M2 macrophages, which appear to drive angiogenesis and the production of chemokines that support tumor growth and poor patient prognoses. Targeting this interaction systemically through circulating monocytes may therefore be a novel way to improve local anti-tumor effects by macrophages. This article is protected by copyright. All rights reserved.

CD63 tetraspanin is a negative driver of epithelial-to-mesenchymal transition in human melanoma cells.

PubMed

Lupia, Antonella; Peppicelli, Silvia; Witort, Ewa; Bianchini, Francesca; Carloni, Vinicio; Pimpinelli, Nicola; Urso, Carmelo; Borgognoni, Lorenzo; Capaccioli, Sergio; Calorini, Lido; Lulli, Matteo

2014-12-01

The CD63 tetraspanin is highly expressed in the early stages of melanoma and decreases in advanced lesions, suggesting it as a possible suppressor of tumor progression. We employed loss- and gain-of-gene-function approaches to investigate the role of CD63 in melanoma progression and acquisition of the epithelial-to-mesenchymal transition (EMT) program. We used two human melanoma cell lines derived from primary tumors and one primary human melanoma cell line isolated from a cutaneous metastasis, differing by levels of CD63 expression. CD63-silenced melanoma cells showed enhanced motility and invasiveness with downregulation of E-cadherin and upregulation of N-cadherin and Snail. In parallel experiments, transient and stable ectopic expression of CD63 resulted in a robust reduction of cell motility, invasiveness, and protease activities, which was proportional to the increase in CD63 protein level. Transfected cells overexpressing the highest level of CD63 when transplanted into immunodeficient mice showed a reduced incidence and rate of tumor growth. Moreover, these cells showed a reduction of N-cadherin, Vimentin, Zeb1, and a-SMA, and a significant resistance to undergo an EMT program both in basal condition and in the following stimulation with TGFβ. Thus, our results establish a previously unreported mechanistic link between the tetraspanin CD63 and EMT abrogation in melanoma.

CD127 and CD25 expression defines CD4+ T cell subsets that are differentially depleted during HIV infection.

PubMed

Dunham, Richard M; Cervasi, Barbara; Brenchley, Jason M; Albrecht, Helmut; Weintrob, Amy; Sumpter, Beth; Engram, Jessica; Gordon, Shari; Klatt, Nichole R; Frank, Ian; Sodora, Donald L; Douek, Daniel C; Paiardini, Mirko; Silvestri, Guido

2008-04-15

Decreased CD4(+) T cell counts are the best marker of disease progression during HIV infection. However, CD4(+) T cells are heterogeneous in phenotype and function, and it is unknown how preferential depletion of specific CD4(+) T cell subsets influences disease severity. CD4(+) T cells can be classified into three subsets by the expression of receptors for two T cell-tropic cytokines, IL-2 (CD25) and IL-7 (CD127). The CD127(+)CD25(low/-) subset includes IL-2-producing naive and central memory T cells; the CD127(-)CD25(-) subset includes mainly effector T cells expressing perforin and IFN-gamma; and the CD127(low)CD25(high) subset includes FoxP3-expressing regulatory T cells. Herein we investigated how the proportions of these T cell subsets are changed during HIV infection. When compared with healthy controls, HIV-infected patients show a relative increase in CD4(+)CD127(-)CD25(-) T cells that is related to an absolute decline of CD4(+)CD127(+)CD25(low/-) T cells. Interestingly, this expansion of CD4(+)CD127(-) T cells was not observed in naturally SIV-infected sooty mangabeys. The relative expansion of CD4(+)CD127(-)CD25(-) T cells correlated directly with the levels of total CD4(+) T cell depletion and immune activation. CD4(+)CD127(-)CD25(-) T cells were not selectively resistant to HIV infection as levels of cell-associated virus were similar in all non-naive CD4(+) T cell subsets. These data indicate that, during HIV infection, specific changes in the fraction of CD4(+) T cells expressing CD25 and/or CD127 are associated with disease progression. Further studies will determine whether monitoring the three subsets of CD4(+) T cells defined based on the expression of CD25 and CD127 should be used in the clinical management of HIV-infected individuals.

Upregulation of CD19⁺CD24(hi)CD38(hi) regulatory B cells is associated with a reduced risk of acute lung injury in elderly pneumonia patients.

PubMed

Song, Haihan; Xi, Jianjun; Li, Guang-Gang; Xu, Shumin; Wang, Chunmei; Cheng, Tingting; Li, Hongqiang; Zhang, Ying; Liu, Xiandong; Bai, Jianwen

2016-04-01

Acute lung injury (ALI) is a common complication in elderly pneumonia patients who have a rapid progression, and is accompanied by a high mortality rate. Because the treatment options of ALI are limited to supportive care, identifying pneumonia patients who are at higher risk of ALI development is the emphasis of many studies. Here, we approach this problem from an immunological perspective by examining CD19(+)CD24(hi)CD38(hi) B cells, an important participant in acute and chronic inflammation. We find that elderly pneumonia patients have elevated CD19(+)CD24(hi)CD38(hi) B cell frequency compared to healthy individuals. This B cell population may express a higher level of IL-10, which has been was shown to suppress CD4(+) T cell-mediated proinflammatory cytokine interferon gamma (IFNg) and tumor necrosis factor alpha (TNFa) production, through an IL-10-dependent mechanism. We also observe that the frequency of CD19(+)CD24(hi)CD38(hi) B cell is positively correlated with the frequency of CD4(+)CD25(+)Foxp3(+)Tregs in peripheral blood. Moreover, consistent with CD19(+)CD24(hi)CD38(hi) B cell's anti-inflammatory role, we find that pneumonia patients who later developed ALI have reduced level of CD19(+)CD24(hi)CD38(hi) B cells. Together, our results demonstrated that CD19(+)CD24(hi)CD38(hi) B cells in pneumonia patients possess regulatory function in vivo, and are associated with a reduced ALI risk.

Effects of continuous fertilization on bioavailability and fractionation of cadmium in soil and its uptake by rice (Oryza sativa L.).

PubMed

Huang, Qingqing; Yu, Yao; Wan, Yanan; Wang, Qi; Luo, Zhang; Qiao, Yuhui; Su, Dechun; Li, Huafen

2018-06-01

A four-year field trial was conducted in a rice paddy in southern China to determine the effects of continuous phosphate fertilizer, pig manure, chicken manure, and sewage sludge application on soil Cd accumulation in soil and Cd uptake by rice. The results showed that continuous application of fertilizers with higher Cd levels caused Cd to accumulate and redistribute in various soil fractions. In turn, these effects influenced Cd bioavailability in rice plants. After four years of phosphate fertilizer, pig manure, chicken manure, and sewage sludge application, the annual soil Cd accumulation rates were 0.007-0.032 mg kg -1 , 0.005-0.022 mg kg -1 , 0.002-0.013 mg kg -1 , and 0.032-0.087 mg kg -1 , respectively. Relative to the control, the pig- and chicken manure treatments significantly increased soil pH and reduced DTPA-extractable Cd (DTPA-Cd) and the exchangeable Cd fraction (Exc-Cd). In contrast, sewage sludge application significantly increased DTPA-Cd and Cd in all soil fractions. Phosphate fertilization had no significant effect on soil pH, DTPA-Cd, or Exc-Cd. Pearson's correlation coefficients showed that the rice grain Cd levels varied directly with DTPA-Cd, and Exc-Cd but inversely with soil pH. Pig- or chicken manure decreased rice grain Cd content, but sewage sludge increased both soil Cd availability and rice grain Cd uptake. Application of phosphate fertilizer had no significant effect on rice grain Cd content. The continuous use of organic- or phosphate fertilizer with elevated Cd content at high application rates may induce soil Cd accumulation and influence rice grain Cd accumulation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Revealing the structural nature of the Cd isotopes

NASA Astrophysics Data System (ADS)

Garrett, P. E.; Diaz Varela, A.; Green, K. L.; Jamieson, D. S.; Jigmeddorj, B.; Wood, J. L.; Yates, S. W.

2015-10-01

The even-even Cd isotopes have provided fertile ground for the investigation of collectivity in nuclei. Soon after the development of the Bohr model, the stable Cd isotopes were identified as nearly harmonic vibrators based on their excitation energy patterns. The measurements of enhanced B (E 2) values appeared to support this interpretation. Shape co-existing rotational-like intruder bands were discovered, and mixing between the configurations was invoked to explain the deviation of the decay pattern of multiphonon vibrational states. Very recently, a detailed analysis of the low-lying levels of 110Cd combining results of the (n ,n' γ) reaction and high-statistics β decay, provided strong evidence that the mixing between configurations is weak, except for the ground-state band and ``Kπ =0+ '' intruder band. The analysis of the levels in 110Cd has now been extended to 3 MeV, and combined with data for 112Cd and previous Coulomb excitation data for 114Cd, enables a detailed map of the E 2 collectivity in these nuclei, demanding a complete re-interpretation of the structure of the stable Cd isotopes.

Heavy metal concentrations in diploid and triploid oysters (Crassostrea gigas) from three farms on the north-central coast of Sinaloa, Mexico.

PubMed

Muñoz Sevilla, Norma Patricia; Villanueva-Fonseca, Brenda Paulina; Góngora-Gómez, Andrés Martin; García-Ulloa, Manuel; Domínguez-Orozco, Ana Laura; Ortega-Izaguirre, Rogelio; Campos Villegas, Lorena Elizabeth

2017-10-03

The concentrations of Cu, Cd, Pb, Zn, and Hg in diploid and triploid oysters from three farms (Guasave, Ahome, and Navolato) on the north-central coast of Sinaloa, Mexico, were assessed based on samples recovered during a single culture cycle 2013-2014. Metal burdens were more strongly correlated (p < 0.05) with the location of the farm than with either the ploidy or the interaction of both variables. The metal concentration ranking for oysters of both ploidies from the three farms was Zn > Cu > Cd > Pb > Hg. For all three farms, the mean concentrations of Cd and Pb in Crassostrea gigas were high, ranging from 2.52 to 7.98 μg/g wet weight for Cd and from 0.91 to 2.83 μg/g wet weight for Pb. Diploid and triploid oysters from the Guasave farm contained high levels of Cu (76.41 and 68.97 μg/g wet weight, respectively). Cu, Cd, and Zn were highly correlated (p < 0.05), and their concentrations may be influenced by agrochemical inputs. The mean levels of Cu for the Guasave farm and of Cd and Pb for all three farms exceeded permissible limits and represented a threat to human health during the sampling period (July 2014 to July 2014).

The planetary data system educational CD-ROM

NASA Technical Reports Server (NTRS)

Guinness, E. A.; Arvidson, R. E.; Martin, M.; Dueck, S.

1993-01-01

The Planetary Data System (PDS) is producing a special educational CD-ROM that contains samples of PDS datasets and is expected to be released in 1993. The CD-ROM will provide university-level instructors with PDS-compatible materials and information that can be used to construct student problem sets using real datasets. The main purposes of the CD-ROM are to facilitate wide use of planetary data and to introduce a large community to the PDS. To meet these objectives the Educational CD-ROM will also contain software to manipulate the data, background discussions about scientific questions that can be addressed with the data, and a suite of exercises that illustrate analysis techniques. Students will also be introduced to the SPICE concept, which is a new way of maintaining geometry and instrument information. The exercises will be presented at the freshman through graduate student levels. With simplification, some of the material should also be of use at the high school level.

MRI phenotypes with high neurodegeneration are associated with peripheral blood B-cell changes.

PubMed

Comabella, Manuel; Cantó, Ester; Nurtdinov, Ramil; Río, Jordi; Villar, Luisa M; Picón, Carmen; Castilló, Joaquín; Fissolo, Nicolás; Aymerich, Xavier; Auger, Cristina; Rovira, Alex; Montalban, Xavier

2016-01-15

Little is known about the mechanisms leading to neurodegeneration in multiple sclerosis (MS) and the role of peripheral blood cells in this neurodegenerative component. We aimed to correlate brain radiological phenotypes defined by high and low neurodegeneration with gene expression profiling of peripheral blood mononuclear cells (PBMC) from MS patients. Magnetic resonance imaging (MRI) scans from 64 patients with relapsing-remitting MS (RRMS) were classified into radiological phenotypes characterized by low (N = 27) and high (N = 37) neurodegeneration according to the number of contrast-enhancing lesions, the relative volume of non-enhancing black holes on T1-weighted images, and the brain parenchymal fraction. Gene expression profiling was determined in PBMC using microarrays, and validation of selected genes was performed by polymerase chain reaction (PCR). B-cell immunophenotyping was conducted by flow cytometry. Microarray analysis revealed the B-cell specific genes FCRL1, FCRL2, FCRL5 (Fc receptor-like 1, 2 and 5 respectively), and CD22 as the top differentially expressed genes between patients with high and low neurodegeneration. Levels for these genes were significantly down-regulated in PBMC from patients with MRI phenotypes characterized by high neurodegeneration and microarray findings were validated by PCR. In patients with high neurodegeneration, immunophenotyping showed a significant increase in the expression of the B-cell activation markers CD80 in naïve B cells (CD45+/CD19+/CD27-/IgD+), unswitched memory B cells (CD45+/CD19+/CD27+/IgD+), and switched memory B cells (CD45+/CD19+/CD27+/IgD-), and CD86 in naïve and switched memory B cells. These results suggest that RRMS patients with radiological phenotypes showing high neurodegeneration have changes in B cells characterized by down-regulation of B-cell-specific genes and increased activation status. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Expansion of PD-1-positive effector CD4 T cells in an experimental model of SLE: contribution to the self-organized criticality theory.

PubMed

Miyazaki, Yumi; Tsumiyama, Ken; Yamane, Takashi; Ito, Mitsuhiro; Shiozawa, Shunichi

2013-04-18

We have developed a systems biology concept to explain the origin of systemic autoimmunity. From our studies of systemic lupus erythematosus (SLE) we have concluded that this disease is the inevitable consequence of over-stimulating the host's immune system by repeated exposure to antigen to levels that surpass a critical threshold, which we term the system's "self-organized criticality". We observed that overstimulation of CD4 T cells in mice led to the development of autoantibody-inducing CD4 T cells (aiCD4 T) capable of generating various autoantibodies and pathological lesions identical to those observed in SLE. We show here that this is accompanied by the significant expansion of a novel population of effector T cells characterized by expression of programmed death-1 (PD-1)-positive, CD27(low), CD127(low), CCR7(low) and CD44(high)CD62L(low) markers, as well as increased production of IL-2 and IL-6. In addition, repeated immunization caused the expansion of CD8 T cells into fully-matured cytotoxic T lymphocytes (CTL) that express Ly6C(high)CD122(high) effector and memory markers. Thus, overstimulation with antigen leads to the expansion of a novel effector CD4 T cell population that expresses an unusual memory marker, PD-1, and that may contribute to the pathogenesis of SLE.

Genetic Ablation of CD38 Protects against Western Diet-Induced Exercise Intolerance and Metabolic Inflexibility.

PubMed

Chiang, Shian-Huey; Harrington, W Wallace; Luo, Guizhen; Milliken, Naphtali O; Ulrich, John C; Chen, Jing; Rajpal, Deepak K; Qian, Ying; Carpenter, Tiffany; Murray, Rusty; Geske, Robert S; Stimpson, Stephen A; Kramer, Henning F; Haffner, Curt D; Becherer, J David; Preugschat, Frank; Billin, Andrew N

2015-01-01

Nicotinamide adenine dinucleotide (NAD+) is a key cofactor required for essential metabolic oxidation-reduction reactions. It also regulates various cellular activities, including gene expression, signaling, DNA repair and calcium homeostasis. Intracellular NAD+ levels are tightly regulated and often respond rapidly to nutritional and environmental changes. Numerous studies indicate that elevating NAD+ may be therapeutically beneficial in the context of numerous diseases. However, the role of NAD+ on skeletal muscle exercise performance is poorly understood. CD38, a multi-functional membrane receptor and enzyme, consumes NAD+ to generate products such as cyclic-ADP-ribose. CD38 knockout mice show elevated tissue and blood NAD+ level. Chronic feeding of high-fat, high-sucrose diet to wild type mice leads to exercise intolerance and reduced metabolic flexibility. Loss of CD38 by genetic mutation protects mice from diet-induced metabolic deficit. These animal model results suggest that elevation of tissue NAD+ through genetic ablation of CD38 can profoundly alter energy homeostasis in animals that are maintained on a calorically-excessive Western diet.

CYP2E1-dependent and leptin-mediated hepatic CD57 expression on CD8 + T cells aid progression of environment-linked nonalcoholic steatohepatitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seth, Ratanesh Kumar; Das, Suvarthi; Kumar, Ashutosh

2014-01-01

Environmental toxins induce a novel CYP2E1/leptin signaling axis in liver. This in turn activates a poorly characterized innate immune response that contributes to nonalcoholic steatohepatitis (NASH) progression. To identify the relevant subsets of T-lymphocytes in CYP2E1-dependent, environment-linked NASH, we utilized a model of diet induced obese (DIO) mice that are chronically exposed to bromodichloromethane. Mice deficient in CYP2E1, leptin (ob/ob mice), or both T and B cells (Pfp/Rag2 double knockout (KO) mice) were used to delineate the role of each of these factors in metabolic oxidative stress-induced T cell activation. Results revealed that elevated levels of lipid peroxidation, tyrosyl radicalmore » formation, mitochondrial tyrosine nitration and hepatic leptin as a consequence of metabolic oxidative stress caused increased levels of hepatic CD57, a marker of peripheral blood lymphocytes including NKT cells. CD8 + CD57 + cytotoxic T cells but not CD4 + CD57 + cells were significantly decreased in mice lacking CYP2E1 and leptin. There was a significant increase in the levels of T cell cytokines IL-2, IL-1β, and IFN-γ in bromodichloromethane exposed DIO mice but not in mice that lacked CYP2E1, leptin or T and B cells. Apoptosis as evidenced by TUNEL assay and levels of cleaved caspase-3 was significantly lower in leptin and Pfp/Rag2 KO mice and highly correlated with protection from NASH. The results described above suggest that higher levels of oxidative stress-induced leptin mediated CD8 + CD57 + T cells play an important role in the development of NASH. It also provides a novel insight of immune dysregulation and may be a key biomarker in NASH. - Highlights: • Metabolic oxidative stress caused increased levels of hepatic CD57 expression. • CD8+ CD57+ cytotoxic T cells were decreased in mice lacking CYP2E1 and leptin. • There was a significant increase in T cell cytokines in toxin-treated mice. • Apoptosis was significantly lower in leptin and Pfp/Rag2 KO mice. • Leptin mediated CD8+CD57+ T cells play an important role in NASH.« less

Soluble CD30 in patients with antibody-mediated rejection of the kidney allograft.

PubMed

Slavcev, Antonij; Honsova, Eva; Lodererova, Alena; Pavlova, Yelena; Sajdlova, Helena; Vitko, Stefan; Skibova, Jelena; Striz, Ilja; Viklicky, Ondrej

2007-07-01

The aim of our retrospective study was to evaluate the clinical significance of measurement of the soluble CD30 (sCD30) molecule for the prediction of antibody-mediated (humoral) rejection (HR). Sixty-two kidney transplant recipients (thirty-one C4d-positive and thirty-one C4d-negative patients) were included into the study. Soluble CD30 levels were evaluated before transplantation and during periods of graft function deterioration. The median concentrations of the sCD30 molecule were identical in C4d-positive and C4d-negative patients before and after transplantation (65.5 vs. 65.0 and 28.2 vs. 36.0 U/ml, respectively). C4d+ patients who developed DSA de novo had a tendency to have higher sCD30 levels before transplantation (80.7+/-53.6 U/ml, n=8) compared with C4d-negative patients (65.0+/-33.4 U/ml, n=15). Soluble CD30 levels were evaluated as positive and negative (>or=100 U/ml and <100 U/ml respectively) and the sensitivity, specificity and accuracy of sCD30 estimation with regard to finding C4d deposits in peritubular capillaries were determined. The sensitivity of sCD30+ testing was generally below 40%, while the specificity of the test, i.e. the likelihood that if sCD30 testing is negative, C4d deposits would be absent, was 82%. C4d+ patients who developed DSA de novo were evaluated separately; the specificity of sCD30 testing for the incidence of HR in this cohort was 86%. We could not confirm in our study that high sCD30 levels (>or=100 U/ml) might be predictive for the incidence of HR. Negative sCD30 values might be however helpful for identifying patients with a low risk for development of DSA and antibody-mediated rejection.

Prognostic value of circulating VEGFR2+ bone marrow-derived progenitor cells in patients with advanced cancer.

PubMed

Massard, Christophe; Borget, Isabelle; Le Deley, Marie Cécile; Taylor, Melissa; Gomez-Roca, Carlos; Soria, Jean Charles; Farace, Françoise

2012-06-01

We hypothesised that host-related markers, possibly reflecting tumour aggressiveness, such as circulating endothelial cells (CEC) and circulating VEGFR2(+) bone marrow-derived (BMD) progenitor cells, could have prognostic value in patients with advanced cancer enrolled in early anticancer drug development trials. Baseline CECs (CD45(-)CD31(+)CD146(+)7AAD(-) cells) and circulating VEGFR2(+)-BMD progenitor cells (defined as CD45(dim)CD34(+)VEGFR2(+)7AAD(-) cells) were measured by flow-cytometry in 71 and 58 patients included in phase 1 trials testing novel anti-vascular or anti-angiogenic agents. Correlations between levels of CECs, circulating VEGFR2(+)-BMD progenitor cells, clinical and biological prognostic factors (i.e. the Royal Marsden Hospital (RMH) score), and overall survival (OS) were studied. The median value of CECs was 12 CEC/ml (range 0-154/ml). The median level of VEGFR2(+)-BMD progenitor cells was 1.3% (range 0-32.5%) of circulating BMD-CD34(+) progenitors. While OS was not correlated with CEC levels, it was significantly worse in patients with high VEGFR2(+)-BMD progenitor levels (>1%) (median OS 9.0 versus 17.0 months), and with a RMH prognostic score >0 (median OS 9.0 versus 24.2 months). The prognostic value of VEGFR2(+)-BMD progenitor levels remained significant (hazard ratio (HR) = 2.3, 95% confidence interval (CI), 1.1-4.6, p = 0.02) after multivariate analysis. A composite VEGFR2(+)-BMD progenitor level/RHM score ≥ 2 was significantly associated with an increased risk of death compared to scores of 0 or 1 (median OS 9.0 versus 18.4 months, HR = 2.6 (95%CI, 1.2-5.8, p = 0.02)). High circulating VEGFR2(+)-BMD progenitor levels are associated with poor prognostics and when combined to classical clinical and biological parameters could provide a new tool for patient selection in early anticancer drug trials. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Bone metabolism, biochemical markers of bone resorption and formation processes and interleukine 6 cytokin level during coeliac disease].

PubMed

Fekih, Monia; Sahli, Hela; Ben Mustapha, Nadia; Mestiri, Imen; Fekih, Moncef; Boubaker, Jalel; Kaabachi, Naziha; Sellami, Mohamed; Kallel, Lamia; Filali, Azza

2013-01-01

Celiac disease (CD) is characterized by a malabsorption syndrom. The bone anomalies are one of the principal complications of this disease. The osteoporosis frequency is high: 3.4% among patients having with CD versus 0.2% in the general population. To study the bone mineral density during the CD, to compare it to a control group and to determine the anomalies of biochemical markers of bone turn over and level of interleukin 6 cytokin (IL6) in these patients. All patients with CD have a measurement of bone mineral density by dual-energy x-ray absorptiometry (DXA), a biological exam with dosing calcemia, vitamin D, parathormone (PTH), the osteoblastic bone formation markers (serum osteocalcin, ALP phosphates alkaline), bone osteoclastic activity (C Télopeptide: CTX) and of the IL6. 42 patients were included, with a median age of 33.6 years. 52. 8% of the patients had a low level of D vitamine associated to a high level of PTH. An osteoporosis was noted in 21.5% of patients. No case of osteoporosis was detected in the control group. The mean level of the CTX, ostéocalcine and the IL6 was higher among patients having an osteoporosis or ostéopenia compared to patients with normal bone (p = 0,017). The factors associated with an bone loss (osteopenia or osteoporosis) were: an age > 30 years, a weight <50 kg, a level of ALP phosphates alkaline > 90 UI/ml, an hypo albuminemia < 40 g/l and a level of CTX higher than 1.2. Our study confirms the impact of the CD on the bone mineral statute. The relative risk to have an osteopenia or an osteoporosis was 5 in our series. The measurement of the osseous mineral density would be indicated among patients having a CD.

Prognostic Value of Dynamic Monitoring of Cellular Immunity and HMGB1 in Severe Sepsis: Delayed Chronic Inflammation may be the Leading Cause of Death in Late Severe Sepsis.

PubMed

Yu, Han; Qi, Zhijiang; Zhao, Lianxing; Shao, Rui; Fang, Yingying; Li, Chunsheng

2016-12-01

Sepsis is a life-threatening response to infection with a high mortality rate. In order to explore the prognostic value of dynamic monitoring of cellular immunity during late severe sepsis, we assessed levels of Tlymphocyte subsets, the human leukocyte antigen D-related (HLA-DR), and the high mobility group box-1 (HMGB1) protein. Study participants included 247 consecutive severe sepsis patients who were admitted to Beijing ChaoYang Hospital's Emergency Intensive Care Unit. Patients were divided into survivors and non-survivors based on 90-day survival rates, and clinical data were collected. T-lymphocyte subsets on days 1 and 7, HLA-DR on days 1 and 12, and HMGB1 on days 1, 3, 5, 7, and 12 were analyzed. Counts of CD3+, CD3+CD4+, and CD3+CD8+ T cells on day 1 in non-survivors were lower than those in survivors. By day 7, counts of all three types of T cells had increased in both survivors and non-survivors, but CD3+ and CD3+CD8+ T cells remained lower in non-survivors than in survivors. There was no significant difference in HLA-DR levels between survivors and non-survivors on day 1, but HLA-DR levels increased in survivors and decreased in non-survivors by day 12. In contrast, over days 1 - 12, HMGB1 levels increased in non-survivors and decreased in survivors. Patients with severe sepsis present with cellular immune dysfunction and persistent chronic inflammation, both of which may lead to death in the late phase of severe sepsis. Dynamic monitoring of indicators of cellular immunity and HMGB1 is useful for evaluating the immune status, chronic inflammation processes, and prognoses of patients with severe sepsis.

Efficient red organic electroluminescent devices by doping platinum(II) Schiff base emitter into two host materials with stepwise energy levels.

PubMed

Zhou, Liang; Kwok, Chi-Chung; Cheng, Gang; Zhang, Hongjie; Che, Chi-Ming

2013-07-15

In this work, organic electroluminescent (EL) devices with double light-emitting layers (EMLs) having stepwise energy levels were designed to improve the EL performance of a red-light-emitting platinum(II) Schiff base complex. A series of devices with single or double EML(s) were fabricated and characterized. Compared with single-EML devices, double-EML devices showed improved EL efficiency and brightness, attributed to better balance in carriers. In addition, the stepwise distribution in energy levels of host materials is instrumental in broadening the recombination zone, thus delaying the roll-off of EL efficiency. The highest EL current efficiency and power efficiency of 17.36 cd/A and 14.73 lm/W, respectively, were achieved with the optimized double-EML devices. At high brightness of 1000 cd/m², EL efficiency as high as 8.89 cd/A was retained.

Enhancing the Oncolytic Activity of CD133-Targeted Measles Virus: Receptor Extension or Chimerism with Vesicular Stomatitis Virus Are Most Effective

PubMed Central

Kleinlützum, Dina; Hanauer, Julia D. S.; Muik, Alexander; Hanschmann, Kay-Martin; Kays, Sarah-Katharina; Ayala-Breton, Camilo; Peng, Kah-Whye; Mühlebach, Michael D.; Abel, Tobias; Buchholz, Christian J.

2017-01-01

Therapy resistance and tumor recurrence are often linked to a small refractory and highly tumorigenic subpopulation of neoplastic cells, known as cancer stem cells (CSCs). A putative marker of CSCs is CD133 (prominin-1). We have previously described a CD133-targeted oncolytic measles virus (MV-CD133) as a promising approach to specifically eliminate CD133-positive tumor cells. Selectivity was introduced at the level of cell entry by an engineered MV hemagglutinin (H). The H protein was blinded for its native receptors and displayed a CD133-specific single-chain antibody fragment (scFv) as targeting domain. Interestingly, MV-CD133 was more active in killing CD133-positive tumors than the unmodified MV-NSe despite being highly selective for its target cells. To further enhance the antitumoral activity of MV-CD133, we here pursued arming technologies, receptor extension, and chimeras between MV-CD133 and vesicular stomatitis virus (VSV). All newly generated viruses including VSV-CD133 were highly selective in eliminating CD133-positive cells. MV-CD46/CD133 killed in addition CD133-negative cells being positive for the MV receptors. In an orthotopic glioma model, MV-CD46/CD133 and MVSCD-CD133, which encodes the super cytosine deaminase, were most effective. Notably, VSV-CD133 caused fatal neurotoxicity in this tumor model. Use of CD133 as receptor could be excluded as being causative. In a subcutaneous tumor model of hepatocellular cancer, VSV-CD133 revealed the most potent oncolytic activity and also significantly prolonged survival of the mice when injected intravenously. Compared to MV-CD133, VSV-CD133 infected a more than 104-fold larger area of the tumor within the same time period. Our data not only suggest new concepts and approaches toward enhancing the oncolytic activity of CD133-targeted oncolytic viruses but also raise awareness about careful toxicity testing of novel virus types. PMID:28695108

Molecular Cloning, Characterization, and Expression of a Catalase Gene in the Japanese Scallop Mizuhopecten yessoensis Induced in the Presence of Cadmium

NASA Astrophysics Data System (ADS)

Gao, Jialong; Ishizaki, Shoichiro; Nagashima, Yuji

2016-03-01

Cadmium (Cd) is known to influence the oxidative status of marine organisms and can induce the formation of reactive oxygen species (ROS). Catalase (CAT) is one of the important enzymes involved in scavenging high levels of ROS. In present study, we cloned CAT cDNA and investigated the response of this enzyme at the transcriptional level in the Japanese scallop Mizuhopecten yessoensis exposed to Cd. The full-length CAT cDNA (MyCAT) of 1,870 nucleotides including a 57 bp 5'-UTR, a coding sequence of 1,500 bp and a 313 bp 3'-UTR were identified from the scallop. The deduced amino acid sequence of MyCAT corresponds to 499 amino acids with predicted molecular weight of 56.48 kDa and contains highly conserved motifs of the proximal heme-binding site RLFSYSTH, proximal active signature FNRERIPERVVHAKGGG and three catalytic amino acid residues His72, Asn145, and Tyr355. Its significant homology to CATs from multiple alignments revealed that MyCAT had a high identity with CATs from other mollusks. CAT mRNA expression analysis revealed that expression level was highest in the digestive gland ( p < 0.01) but weak in muscle. Following exposure to 200 and 400 µg/l of Cd, a high amount of Cd was found to have accumulated in the digestive gland and CAT mRNA expression had significantly increased in this organ among 7-day exposed scallops ( p < 0.001). The result demonstrated that antioxidant enzymes such as CAT play important roles in counteracting Cd stress in M. yessoensis.

HTLV-1 Tax Specific CD8+ T Cells Express Low Levels of Tim-3 in HTLV-1 Infection: Implications for Progression to Neurological Complications

PubMed Central

Hasenkrug, Aaron M.; Jha, Aashish R.; Carvalho, Karina I.; Eccles-James, Ijeoma G.; Bruno, Fernanda R.; Vieira, Raphaella G. S.; York, Vanessa A.; Chew, Glen M.; Jones, R. Brad; Tanaka, Yuetsu; Neto, Walter K.; Sanabani, Sabri S.; Ostrowski, Mario A.; Segurado, Aluisio C.; Nixon, Douglas F.; Kallas, Esper G.

2011-01-01

The T cell immunoglobulin mucin 3 (Tim-3) receptor is highly expressed on HIV-1-specific T cells, rendering them partially “exhausted” and unable to contribute to the effective immune mediated control of viral replication. To elucidate novel mechanisms contributing to the HTLV-1 neurological complex and its classic neurological presentation called HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis), we investigated the expression of the Tim-3 receptor on CD8+ T cells from a cohort of HTLV-1 seropositive asymptomatic and symptomatic patients. Patients diagnosed with HAM/TSP down-regulated Tim-3 expression on both CD8+ and CD4+ T cells compared to asymptomatic patients and HTLV-1 seronegative controls. HTLV-1 Tax-specific, HLA-A*02 restricted CD8+ T cells among HAM/TSP individuals expressed markedly lower levels of Tim-3. We observed Tax expressing cells in both Tim-3+ and Tim-3− fractions. Taken together, these data indicate that there is a systematic downregulation of Tim-3 levels on T cells in HTLV-1 infection, sustaining a profoundly highly active population of potentially pathogenic T cells that may allow for the development of HTLV-1 complications. PMID:21541358

Distinctive CD8+ T cell and MHC class I signatures in polycythemia vera patients.

PubMed

Cardoso, Elsa M; Esgalhado, André J; Patrão, Luís; Santos, Mónica; Neves, Vasco Pinto; Martinez, Jorge; Patto, Maria Assunção Vaz; Silva, Helena; Arosa, Fernando A

2018-05-22

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by overproduction of red blood cells. We have performed a comprehensive characterization of blood immune cells for expression of naïve and memory receptors as well as β 2 m-associated and β 2 m-free MHC class I heavy chains, also known as closed and open conformers, respectively, in PV patients and age-matched controls (CTR). We show that the peripheral CD3 + CD8 + T cell pool in PV patients is clearly divided into two discrete populations, a more granular CD3 + CD8 high T cell population enriched in effector-memory CD45RA + T cells (CD8 + TEMRA) when compared to CTR (P < 0.001), and a less granular CD3 + CD8 int T cell population that is completely absent in the CTR group (78 vs. 0%, P < 0.001) and is a mixture of naïve (CD8 + T N ) and CD8 + TEMRA cells expressing intermediate levels of CD28, i.e., CD3 + CD8 int CD28 int . While the percentage of CD3 + CD8 int TN cells correlated positively with the number of erythrocytes, the percentage of CD3 + CD8 int TEMRA correlated negatively with the number of platelets. Finally, we report that PV patients' lymphocytes and monocytes display lower levels of closed (W6/32 + ) MHC-I conformers at the cell surface while exhibiting increased amounts of open (HC-10 + ) MHC-I conformers. The implications of this distinctive immune signature are discussed.

The antagonistic effect of selenium on cadmium-induced apoptosis via PPAR-γ/PI3K/Akt pathway in chicken pancreas.

PubMed

Jin, Xi; Jia, Tiantian; Liu, Ruohan; Xu, Shiwen

2018-06-01

The animal experiment was preformed to investigate the roles of PPAR-γ/PI3K/Akt pathway in apoptosis triggered by cadmium (Cd) and in the antagonistic effects of selenium (Se) on Cd in the pancreas of chicken. The current study showed that Cd treatment obviously increased the accumulation of Cd and directly led to lower activities of amylase, trypsin and lipase in chicken pancreas. The expression of PPAR-γ, PI3K, and Akt was declined, whereas the level of Bax, Cyt C and caspase-3 were increased in Cd group. In the result of TUNEL assay and the histological examination, typical apoptosis characteristics in the pancreas of Cd group were confirmed. Cd group also showed high levels of inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) content in pancreas. However, those Cd-induced changes were obviously alleviated in Cd + Se group. Our study revealed that Cd could impact the pancreas function and induce the activation of Bax and the overproduction of NO via PPAR-γ/PI3K/Akt pathway to promote apoptosis in chicken pancreas. However, Se could reduce Cd accumulation and antagonize Cd-triggered apoptosis in chicken pancreas. Copyright © 2018 Elsevier B.V. All rights reserved.

CD40 Ligand Promotes Mac-1 Expression, Leukocyte Recruitment, and Neointima Formation after Vascular Injury

PubMed Central

Li, Guohong; Sanders, John M.; Bevard, Melissa H.; Sun, ZhiQi; Chumley, James W.; Galkina, Elena V.; Ley, Klaus; Sarembock, Ian J.

2008-01-01

High levels of circulating soluble CD40 ligand (sCD40L) are frequently found in patients with hypercholesterolemia, diabetes, ischemic stroke, or acute coronary syndromes, predicting an increased rate of atherosclerotic plaque rupture and restenosis after coronary/carotid interventions. Clinical restenosis is characterized in part by exaggerated neointima formation, but the underlying mechanism remains incompletely understood. This study investigated the role of elevated sCD40L in neointima formation in response to vascular injury in an atherogenic animal model and explored the molecular mechanisms involved. apoE−/− mice fed a Western diet developed severe hypercholesterolemia, significant hyperglycemia, and high levels of plasma sCD40L. Neointima formation after carotid denudation injury was exaggerated in the apoE−/− mice. In vivo, blocking CD40L with anti-CD40L monoclonal antibody attenuated the early accumulation of Ly-6G+ neutrophils and Gr-1+ monocytes (at 3 days) and the late accumulation of Mac-2+ macrophages (at 28 days) in the denudated arteries; it also reduced the exaggerated neointima formation at 28 days. In vitro, recombinant CD40L stimulated platelet P-selectin and neutrophil Mac-1 expression and platelet-neutrophil co-aggregation and adhesive interaction. These effects were abrogated by anti-CD40L or anti-Mac-1 monoclonal antibody. Moreover, recombinant CD40L stimulated neutrophil oxidative burst and release of matrix metalloproteinase-9 in vitro. We conclude that elevated sCD40L promotes platelet-leukocyte activation and recruitment and neointima formation after arterial injury, potentially through enhancement of platelet P-selectin and leukocyte Mac-1 expression and oxidative activity. PMID:18349125

High serum soluble CD30 does not predict acute rejection in liver transplant patients.

PubMed

Matinlauri, I; Höckerstedt, K; Isoniemi, H

2006-12-01

Increased pre- and posttransplantation values of soluble CD30 (sCD30) have been shown to be associated with acute kidney transplant rejection. We sought to study whether high sCD30 could predict rejection early after liver transplantation. The study population included 54 consecutive liver transplant patients, whose samples were collected before liver transplantation and at discharge, which was at a mean time of 3 weeks after transplantation. During the first 6 months posttransplantation, 22 patients experienced an acute rejection episode. Serum sCD30 concentrations were measured by an enzyme-linked immunoassay; changes in serum sCD30 levels posttransplantation were also expressed as relative values compared with pretransplantation results. Liver patients before transplantation displayed higher serum sCD30 values compared with healthy controls: mean values +/- SD were 93 +/- 58 IU/mL vs 17 +/- 8 IU/mL, respectively. At 3 weeks after transplantation the mean sCD30 concentration in liver transplant patients decreased to 59 +/- 42 IU/mL (P = .005). The mean pretransplantation serum sCD30 value was slightly lower among rejecting vs nonrejecting patients: 78 +/- 43 IU/mL vs 104 +/- 65 IU/mL (P = NS). Posttransplantation values in both groups decreased significantly: 47 +/- 34 IU/mL in patients with rejection (P = .014) vs 69 +/- 45 IU/mL in patients without rejection (P = .012). The relative value at 3 weeks posttransplantation decreased slightly more among patients with vs without rejection (70% vs 88%; NS). No correlation was found between serum sCD30 and anti-HLA class I antibodies or crossmatch positivity. In conclusion, neither pre- nor posttransplantation sCD30 levels were associated with acute rejection in liver transplant patients.

Association of maternal serum cadmium level during pregnancy with risk of preterm birth in a Chinese population.

PubMed

Wang, Hua; Liu, Lu; Hu, Yong-Fang; Hao, Jia-Hu; Chen, Yuan-Hua; Su, Pu-Yu; Yu, Zhen; Fu, Lin; Tao, Fang-Biao; Xu, De-Xiang

2016-09-01

Cadmium (Cd) was a developmental toxicant that induces fetal malformation and growth restriction in mice. However, epidemiological studies about the association of maternal serum Cd level with risk of preterm birth were limited. This study was to investigate whether maternal serum Cd level during pregnancy is associated with risk of preterm birth in a Chinese population. Total 3254 eligible mother-and-singleton-offspring pairs were recruited. Maternal serum Cd level was measured by GFAAS. Based on tertiles, maternal serum Cd concentration was classified as low (LCd, <0.65 μg/L), medium (MCd, 0.65-0.94 μg/L) and high (HCd, ≥0.95 μg/L). Odds ratio (OR) for preterm birth was estimated using multiple logistic regression models. Results showed the rate of preterm birth among LCd, M-Cd and HCd was 3.5%, 3.8%, and 9.4%, respectively. Subjects with HCd had a significantly higher risk for preterm birth (OR: 2.86; 95%CI: 1.95, 4.19; P < 0.001) than did those with LCd. Adjusted OR for preterm birth was 3.02 (95%CI: 2.02, 4.50; P < 0.001) among subjects with HCd compared to subjects with LCd. Taken together, the above results suggest that maternal serum Cd level during pregnancy is positively associated with risk of preterm birth. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preparation of High Purity CdTe for Nuclear Detector: Electrical and Nuclear Characterization

NASA Astrophysics Data System (ADS)

Zaiour, A.; Ayoub, M.; Hamié, A.; Fawaz, A.; Hage-ali, M.

High purity crystal with controllable electrical properties, however, control of the electrical properties of CdTe has not yet been fully achieved. Using the refined Cd and Te as starting materials, extremely high-purity CdTe single crystals were prepared by the traditional vertical THM. The nature of the defects involved in the transitions was studied by analyzing the position of the energy levels by TSC method. The resolution of 4.2 keV (FWHM) confirms the high quality and stability of the detectors: TSC spectrum was in coherence with detectors spectrum with a horizontal plate between 0.2 and 0.6 eV. The enhancement in resolution of detectors with a full width at half- maximum (less than 0.31 meV), lead to confirm that the combination of vacuum distillation and zone refining was very effective to obtain more purified CdTe single crystals for photovoltaic or nuclear detectors with better physical properties.

The Regional Geochemistry of Soils and Willow in a Metamorphic Bedrock Terrain, Seward Peninsula, Alaska, 2005, and Its Possible Relation to Moose

USGS Publications Warehouse

Gough, L.P.; Lamothe, P.J.; Sanzolone, R.F.; Drew, L.J.; Maier, J.A.K.

2009-01-01

In 2005 willow leaves (all variants of Salix pulchra) and A-, B-, and C-horizon soils were sampled at 10 sites along a transect near the Quarry prospect and 11 sites along a transect near the Big Hurrah mine for the purpose of defining the spatial variability of elements and the regional geochemistry of willow and soil over Paleozoic metamorphic rocks potentially high in cadmium (Cd). Willow, a favorite browse of moose (Alces alces), has been shown by various investigators to bioaccumulate Cd. Moose in this region show clinical signs of tooth wear and breakage and are declining in population for unknown reasons. A trace element imbalance in their diet has been proposed as a possible cause for these observations. Cadmium, in high enough concentrations, is one dietary trace element that potentially could produce such symptoms. We report both the summary statistics for elements in willow and soils and the results of an unbalanced, one-way, hierarchical analysis of variance (ANOVA) (general linear model, GLM), which was constructed to measure the geochemical variability in willow (and soil) at various distance scales across the Paleozoic geologic unit high in bioavailable Cd. All of the geochemical data are presented in the Appendices. The two locations are separated by approximately 80 kilometers (km); sites within a location are approximately 0.5 kilometers apart. Duplicate soil samples collected within a site were separated by 0.05 km or slightly less. Results of the GLM are element specific and range from having very little regional variability to having most of their variance at the top (greater than 80 km) level. For willow, a significant proportion of the total variance occurred at the 'between locations' level for ash yield, barium (Ba), Cd, calcium (Ca), cobalt (Co), nickel (Ni), and zinc (Zn). For soils, concentrations of elements in all three soil horizons were similar in that most of the variability in the geochemical data occurred at the 'between locations' and the 'among sites at a location' GLM levels. Most of the variation in concentrations of Cd in soils occurred among sites (separated by 0.5 km) at both locations across all soil horizons and not between the two locations. Cd distribution across the landscape may be due to variation in soil mineralogy, especially the amount of graphite in soil, which has been associated with Cd. Although samples were collected on the same geologic unit, the geochemistry of soils was demonstrated to be uniform with depth but highly variable between locations separated by 80 km. This exploratory study establishes the presence of elevated levels of Cd in willow growing over Paleozoic bedrock in the Seward Peninsula. Further work is needed to definitively link these high Cd levels in willow browse to the health of moose.

Increased IL-15 Production and Accumulation of Highly Differentiated CD8+ Effector/Memory T Cells in the Bone Marrow of Persons with Cytomegalovirus

PubMed Central

Pangrazzi, Luca; Naismith, Erin; Meryk, Andreas; Keller, Michael; Jenewein, Brigitte; Trieb, Klemens; Grubeck-Loebenstein, Beatrix

2017-01-01

Cytomegalovirus (CMV) has been described as a contributor to immunosenescence, thus exacerbating age-related diseases. In persons with latent CMV infection, the CD8+ T cell compartment is irreversibly changed, leading to the accumulation of highly differentiated virus-specific CD8+ T cells in the peripheral blood. The bone marrow (BM) has been shown to play a major role in the long-term survival of antigen-experienced T cells. Effector CD8+ T cells are preferentially maintained by the cytokine IL-15, the expression of which increases in old age. However, the impact of CMV on the phenotype of effector CD8+ T cells and on the production of T cell survival molecules in the BM is not yet known. We now show, using BM samples obtained from persons who underwent hip replacement surgery because of osteoarthrosis, that senescent CD8+ TEMRA cells with a bright expression of CD45RA and a high responsiveness to IL-15 accumulate in the BM of CMV-infected persons. A negative correlation was found between CMV antibody (Ab) titers in the serum and the expression of CD28 and IL-7Rα in CD8+ TEMRAbright cells. Increased IL-15 mRNA levels were observed in the BM of CMV+ compared to CMV− persons, being particularly high in old seropositive individuals. In summary, our results indicate that a BM environment rich in IL-15 may play an important role in the maintenance of highly differentiated CD8+ T cells generated after CMV infection. PMID:28674537

TNF-α enhancement of CD62E mediates adhesion of non-small cell lung cancer cells to brain endothelium via CD15 in lung-brain metastasis.

PubMed

Jassam, Samah A; Maherally, Zaynah; Smith, James R; Ashkan, Keyoumars; Roncaroli, Federico; Fillmore, Helen L; Pilkington, Geoffrey J

2016-05-01

CD15, which is overexpressed on various cancers, has been reported as a cell adhesion molecule that plays a key role in non-CNS metastasis. However, the role of CD15 in brain metastasis is largely unexplored. This study provides a better understanding of CD15/CD62E interaction, enhanced by tumor necrosis factor-α (TNF-α), and its correlation with brain metastasis in non-small cell lung cancer (NSCLC). CD15 and E-selectin (CD62E) expression was demonstrated in both human primary and metastatic NSCLC cells using flow cytometry, immunofluorescence, and Western blotting. The role of CD15 was investigated using an adhesion assay under static and physiological flow live-cell conditions. Human tissue sections were examined using immunohistochemistry. CD15, which was weakly expressed on hCMEC/D3 human brain endothelial cells, was expressed at high levels on metastatic NSCLC cells (NCI-H1299, SEBTA-001, and SEBTA-005) and at lower levels on primary NSCLC (COR-L105 and A549) cells (P < .001). The highest expression of CD62E was observed on hCMEC/D3 cells activated with TNF-α, with lower levels on metastatic NSCLC cells followed by primary NSCLC cells. Metastatic NSCLC cells adhered most strongly to hCMEC/D3 compared with primary NSCLC cells. CD15 immunoblocking decreased cancer cell adhesion to brain endothelium under static and shear stress conditions (P < .0001), confirming a correlation between CD15 and cerebral metastasis. Both CD15 and CD62E expression were detected in lung metastatic brain biopsies. This study enhances the understanding of cancer cell-brain endothelial adhesion and confirms that CD15 plays a crucial role in adhesion in concert with TNF-α activation of its binding partner, CD62E. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

TNF-α enhancement of CD62E mediates adhesion of non–small cell lung cancer cells to brain endothelium via CD15 in lung-brain metastasis

PubMed Central

Jassam, Samah A.; Maherally, Zaynah; Smith, James R.; Ashkan, Keyoumars; Roncaroli, Federico; Fillmore, Helen L.; Pilkington, Geoffrey J.

2016-01-01

Background CD15, which is overexpressed on various cancers, has been reported as a cell adhesion molecule that plays a key role in non-CNS metastasis. However, the role of CD15 in brain metastasis is largely unexplored. This study provides a better understanding of CD15/CD62E interaction, enhanced by tumor necrosis factor-α (TNF-α), and its correlation with brain metastasis in non–small cell lung cancer (NSCLC). Methods CD15 and E-selectin (CD62E) expression was demonstrated in both human primary and metastatic NSCLC cells using flow cytometry, immunofluorescence, and Western blotting. The role of CD15 was investigated using an adhesion assay under static and physiological flow live-cell conditions. Human tissue sections were examined using immunohistochemistry. Results CD15, which was weakly expressed on hCMEC/D3 human brain endothelial cells, was expressed at high levels on metastatic NSCLC cells (NCI-H1299, SEBTA-001, and SEBTA-005) and at lower levels on primary NSCLC (COR-L105 and A549) cells (P < .001). The highest expression of CD62E was observed on hCMEC/D3 cells activated with TNF-α, with lower levels on metastatic NSCLC cells followed by primary NSCLC cells. Metastatic NSCLC cells adhered most strongly to hCMEC/D3 compared with primary NSCLC cells. CD15 immunoblocking decreased cancer cell adhesion to brain endothelium under static and shear stress conditions (P < .0001), confirming a correlation between CD15 and cerebral metastasis. Both CD15 and CD62E expression were detected in lung metastatic brain biopsies. Conclusion This study enhances the understanding of cancer cell-brain endothelial adhesion and confirms that CD15 plays a crucial role in adhesion in concert with TNF-α activation of its binding partner, CD62E. PMID:26472821

Extracellular Vesicle (EV) Array: microarray capturing of exosomes and other extracellular vesicles for multiplexed phenotyping.

PubMed

Jørgensen, Malene; Bæk, Rikke; Pedersen, Shona; Søndergaard, Evo K L; Kristensen, Søren R; Varming, Kim

2013-01-01

Exosomes are one of the several types of cell-derived vesicles with a diameter of 30-100 nm. These extracellular vesicles are recognized as potential markers of human diseases such as cancer. However, their use in diagnostic tests requires an objective and high-throughput method to define their phenotype and determine their concentration in biological fluids. To identify circulating as well as cell culture-derived vesicles, the current standard is immunoblotting or a flow cytometrical analysis for specific proteins, both of which requires large amounts of purified vesicles. Based on the technology of protein microarray, we hereby present a highly sensitive Extracellular Vesicle (EV) Array capable of detecting and phenotyping exosomes and other extracellular vesicles from unpurified starting material in a high-throughput manner. To only detect the exosomes captured on the EV Array, a cocktail of antibodies against the tetraspanins CD9, CD63 and CD81 was used. These antibodies were selected to ensure that all exosomes captured are detected, and concomitantly excluding the detection of other types of microvesicles. The limit of detection (LOD) was determined on exosomes derived from the colon cancer cell line LS180. It clarified that supernatant from only approximately 10(4) cells was needed to obtain signals or that only 2.5×10(4) exosomes were required for each microarray spot (~1 nL). Phenotyping was performed on plasma (1-10 µL) from 7 healthy donors, which were applied to the EV Array with a panel of antibodies against 21 different cellular surface antigens and cancer antigens. For each donor, there was considerable heterogeneity in the expression levels of individual markers. The protein profiles of the exosomes (defined as positive for CD9, CD63 and CD81) revealed that only the expression level of CD9 and CD81 was approximately equal in the 7 donors. This implies questioning the use of CD63 as a standard exosomal marker since the expression level of this tetraspanin was considerably lower.

Soluble immune receptor serum levels are associated with age, but not with clinical phenotype or disease severity in childhood atopic dermatitis.

PubMed

Ott, H; Wilke, J; Baron, J M; Höger, P H; Fölster-Holst, R

2010-04-01

Soluble immune receptors (SIRs) have been proposed as biomarkers in patients with atopic dermatitis (AD). However, their clinical applicability in affected children has rarely been studied. To assess the diagnostic usefulness of serum SIRs in childhood AD by correlating the obtained receptor profiles with serological parameters and clinical features such as age, AD phenotype and disease severity. We investigated 100 children with AD. The sCD14, sCD23, sCD25, sCD30, total IgE (tIgE) and eosinophilic cationic protein (ECP) were determined using sera of all children. The clinical phenotype was classified as extrinsic AD (ADe) or intrinsic AD (ADi) by the presence of allergen-specific IgE antibodies. A total of 55 male and 45 female children were recruited. The sCD23, sCD25 and sCD30 serum levels revealed significant age-dependency. At a mean SCORAD of 40 (range 8-98), none of the evaluated SIRs was correlated to disease severity. In all, 73% of patients suffered from ADe while 27% showed the ADi phenotype. None of the analysed SIRs differed significantly between ADe and ADi patients, while tIgE and ECP levels were elevated in the ADe subgroup. The current study provides evidence that sCD23, sCD25 and sCD30 serum levels are highly age-dependent. Serum concentrations of all investigated SIRs did not significantly correlate with disease severity in children with AD and were not differentially expressed in patients of different AD phenotypes. Therefore, we believe that the studied SIRs cannot be regarded as clinically useful biomarkers for the assessment of childhood AD.

All-trans Retinoic Acid Upregulates Reduced CD38 Transcription in Lymphoblastoid Cell Lines from Autism Spectrum Disorder

PubMed Central

Riebold, Mathias; Mankuta, David; Lerer, Elad; Israel, Salomon; Zhong, Songfa; Nemanov, Luba; Monakhov, Mikhail V; Levi, Shlomit; Yirmiya, Nurit; Yaari, Maya; Malavasi, Fabio; Ebstein, Richard P

2011-01-01

Deficits in social behavior in mice lacking the CD38 gene have been attributed to impaired secretion of oxytocin. In humans, similar deficits in social behavior are associated with autistic spectrum disorder (ASD), for which genetic variants of CD38 have been pinpointed as provisional risk factors. We sought to explore, in an in vitro model, the feasibility of the theory that restoring the level of CD38 in ASD patients could be of potential clinical benefit. CD38 transcription is highly sensitive to several cytokines and vitamins. One of these, all-trans retinoic acid (ATRA), a known inducer of CD38, was added during cell culture and tested on a large sample of N = 120 lymphoblastoid cell (LBC) lines from ASD patients and their parents. Analysis of CD38 mRNA levels shows that ATRA has an upmodulatory potential on LBC derived from ASD patients as well as from their parents. The next crucial issue addressed in our study was the relationship between levels of CD38 expression and psychological parameters. The results obtained indicate a positive correlation between CD38 expression levels and patient scores on the Vineland Adaptive Behavior Scale. In addition, analysis of the role of genetic polymorphisms in the dynamics of the molecule revealed that the genotype of a single-nucleotide polymorphism (rs6449182; C>G variation) in the CpG island of intron 1, harboring the retinoic-acid response element, exerts differential roles in CD38 expression in ASD and in parental LBC. In conclusion, our results provide an empirical basis for the development of a pharmacological ASD treatment strategy based on retinoids. PMID:21528155

The early expansion of anergic NKG2Apos/CD56dim/CD16neg natural killer cells represents a therapeutic target in haploidentical haematopoietic stem cell transplantation.

PubMed

Roberto, Alessandra; Di Vito, Clara; Zaghi, Elisa; Mazza, Emilia Maria Cristina; Capucetti, Arianna; Calvi, Michela; Tentorio, Paolo; Zanon, Veronica; Sarina, Barbara; Mariotti, Jacopo; Bramanti, Stefania; Tenedini, Elena; Tagliafico, Enrico; Bicciato, Silvio; Santoro, Armando; Roederer, Mario; Marcenaro, Emanuela; Castagna, Luca; Lugli, Enrico; Mavilio, Domenico

2018-04-26

Natural Killer cells are the first lymphocyte population to reconstitute early after non myelo-ablative and T cell-replete haploidentical hematopoietic stem cell transplantation with post-transplant infusion of cyclophosphamide. The present study characterizes the transient and predominant expansion starting from the 2nd week after haploidentical hematopoietic stem cell transplantation of a donor-derived unconventional subset of NKp46neg-low/CD56dim/CD16neg natural killer cells expressing remarkable high levels of CD94/NKG2A. Both transcription and phenotypic profiles indicated that unconventional NKp46neg-low/CD56dim/CD16neg natural killer cells are a distinct natural killer cell subpopulation with features of late stage differentiation, yet retaining proliferative capability and functional plasticity to generate conventional NKp46pos/CD56bright/CD16pos natural killer cells in response to interleukin-15 plus interleukin-18. While present at low frequency in healthy donors, unconventional NKp46neg-low/CD56dim/CD16neg natural killer cells are greatly expanded in the following 7 weeks after haploidentical hematopoietic stem cell transplantation and express high levels of the activating receptors NKGD and NKp30 as well as of the lytic granules Granzyme-B and Perforin. Nonetheless, NKp46neg-low/CD56dim/CD16neg natural killer cells displayed a markedly defective cytotoxicity that could be reversed by blocking the inhibitory receptor CD94/NKG2A. These data open new important perspectives to better understand the ontogenesis/homeostasis of human natural killer cells and to develop a novel immune-therapeutic approach that targets the inhibitory NKG2A check point, thus unleashing natural killer cell alloreactivity early after haploidentical hematopoietic stem cell transplantation. Copyright © 2018, Ferrata Storti Foundation.

The effects of music listening after a stressful task on immune functions, neuroendocrine responses, and emotional states in college students.

PubMed

Hirokawa, Eri; Ohira, Hideki

2003-01-01

The purpose of this study was to examine the effects of listening to high-uplifting or low-uplifting music after a stressful task on (a) immune functions, (b) neuroendocrine responses, and (c) emotional states in college students. Musical selections that were evaluated as high-uplifting or low-uplifting by Japanese college students were used as musical stimuli. Eighteen Japanese subjects performed stressful tasks before they experienced each of these experimental conditions: (a) high-uplifting music, (b) low-uplifting music, and (c) silence. Subjects' emotional states, the Secretory IgA (S-IgA) level, active natural killer (NK) cell level, the numbers of T lymphocyte CD4+, CD8+, CD16+, dopamine, norepinephrine, and epinephrine levels were measured before and after each experimental condition. Results indicated low-uplifting music had a trend of increasing a sense of well-being. High-uplifting music showed trends of increasing the norepinephrine level, liveliness, and decreasing depression. Active NK cells were decreased after 20 min of silence. Results of the study were inconclusive, but high-uplifting and low-uplifting music had different effects on immune, neuroendocrine, and psychological responses. Classification of music is important to research that examines the effects of music on these responses. Recommendations for future research are discussed.

Calcineurin B in CD4+ T Cells Prevents Autoimmune Colitis by Negatively Regulating the JAK/STAT Pathway.

PubMed

Mencarelli, Andrea; Vacca, Maurizio; Khameneh, Hanif Javanmard; Acerbi, Enzo; Tay, Alicia; Zolezzi, Francesca; Poidinger, Michael; Mortellaro, Alessandra

2018-01-01

Calcineurin (Cn) is a protein phosphatase that regulates the activation of the nuclear factor of activated T-cells (NFAT) family of transcription factors, which are key regulators of T-cell development and function. Here, we generated a conditional Cnb1 mouse model in which Cnb1 was specifically deleted in CD4 + T cells (Cnb1 CD4 mice) to delineate the role of the Cn-NFAT pathway in immune homeostasis of the intestine. The Cnb1 CD4 mice developed severe, spontaneous colitis characterized at the molecular level by an increased T helper-1-cell response but an unaltered regulatory T-cell compartment. Antibiotic treatment ameliorated the intestinal inflammation observed in Cnb1 CD4 mice, suggesting that the microbiota contributes to the onset of colitis. CD4 + T cells isolated from Cnb1 CD4 mice produced high levels of IFNγ due to increased activation of the JAK2/STAT4 pathway induced by IL-12. Our data highlight that Cn signaling in CD4 + T cells is critical for intestinal immune homeostasis in part by inhibiting IL-12 responsiveness of CD4 + T cells.

Trace metal levels, sources, and ecological risk assessment in a densely agricultural area from Saudi Arabia.

PubMed

Al-Wabel, Mohammad I; Sallam, Abd El-Azeem S; Usman, Adel R A; Ahmad, Mahtab; El-Naggar, Ahmed Hamdy; El-Saeid, Mohammed Hamza; Al-Faraj, Abdulelah; El-Enazi, Khaled; Al-Romian, Fahad A

2017-06-01

The present study was conducted in one of the most densely cultivated area of Al-Qassim region in Kingdom of Saudi Arabia to (i) monitor trace metal (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and Zn) contents in surface and subsurface soils, (ii) assess the pollution and potential ecological risk levels of trace metals, and (iii) identify trace metal sources using enrichment factor (EF), correlation matrix, and principal component analysis (PCA). The pollution levels of the analyzed trace metals calculated by the geoaccumulation index (I geo ) and contamination factor (C f ) suggested that the soils were highly contaminated with Cd and moderately contaminated with Pb. Based on the average values of EF, soil samples were found to present extremely high enrichment for Cd, significant enrichment for Pb, moderate enrichment for Zn, and deficient to minimal enrichment for other trace metals. Among the analyzed trace metals, a very high ecological risk was observed only in the case of Cd at some sampling sites. Meanwhile, other investigated trace metals had a low ecological risk. The results of PCA combined with correlation matrix suggested that Fe, Mn, Zn, Cu, Cr Ni, Cu, and Co represent natural abundance in soil, but Cd, Pb, and Cu are of anthropogenic inputs, mainly due to agrochemical and fertilizer applications. It could be generally concluded that the obtained results can be useful for assessing and conducting a future program for trace metal monitoring in agricultural areas of Saudi Arabia.

Immunity in the spleen and blood of mice immunized with irradiated Toxoplasma gondii tachyzoites.

PubMed

Zorgi, Nahiara Esteves; Galisteo, Andrés Jimenez; Sato, Maria Notomi; do Nascimento, Nanci; de Andrade, Heitor Franco

2016-08-01

Toxoplasma gondii infection induces a strong and long-lasting immune response that is able to prevent most reinfections but allows tissue cysts. Irradiated, sterilized T. gondii tachyzoites are an interesting vaccine, and they induce immunity that is similar to infection, but without cysts. In this study, we evaluated the cellular immune response in the blood and spleen of mice immunized with this preparation by mouth (v.o.) or intraperitoneally (i.p.) and analyzed the protection after challenge with viable parasites. BALB/c mice were immunized with three i.p. or v.o. doses of irradiated T. gondii tachyzoites. Oral challenge with ten cysts of the ME-49 or VEG strain at 90 days after the last dose resulted in high levels of protection with low parasite burden in the immunized animals. There were higher levels of specific IgG, IgA and IgM antibodies in the serum, and the i.p. immunized mice had higher levels of the high-affinity IgG and IgM antibodies than the orally immunized mice, which had more high-affinity IgA antibodies. B cells (CD19(+)), plasma cells (CD138(+)) and the CD4(+) and CD8(+) T cell populations were increased in both the blood and spleen. Cells from the spleen of the i.p. immunized mice also showed antigen-induced production of interleukin-10 (IL-10), interferon gamma (IFN-γ) and interleukin 4 (IL-4). The CD4(+) T cells, B cells and likely CD8(+) T cells from the spleens of the i.p. immunized mice proliferated with a specific antigen. The protection was correlated with the spleen and blood CD8(+) T cell, high-affinity IgG and IgM and antigen-induced IL-10 and IL-4 production. Immunization with irradiated T. gondii tachyzoites induces an immune response that is mediated by B cells and CD4(+) and CD8(+) T cells, with increased humoral and cellular immune responses that are necessary for host protection after infection. The vaccine is similar to natural infection, but free of tissue cysts; this immunity restrains infection at challenge and can be an attractive and efficient model for vaccine development in toxoplasmosis.

Transcriptional and functional studies of a Cd(II)/Pb(II)-responsive transcriptional regulator(CmtR) from Acidithiobacillus ferrooxidans ATCC 23270.

PubMed

Zheng, Chunli; Li, Yanjun; Nie, Li; Qian, Lin; Cai, Lu; Liu, Jianshe

2012-08-01

The acidophilic Acidithiobacillus ferrooxidans can resist exceptionally high cadmium (Cd) concentrations. This property is important for its use in biomining processes, where Cd and other metal levels range usually between 15 and 100 mM. To learn about the mechanisms that allow A. ferrooxidans cells to survive in this environment, a bioinformatic search of its genome showed the presence of that a Cd(II)/Pb(II)-responsive transcriptional regulator (CmtR) was possibly related to Cd homeostasis. The expression of the CmtR was studied by real-time reverse transcriptase PCR using A. ferrooxidans cells adapted for growth in the presence of high concentrations of Cd. The putative A. ferrooxidans Cd resistance determinant was found to be upregulated when this bacterium was exposed to Cd in the range of 15-30 mM. The CmtR from A. ferrooxidans was cloned and expressed in Escherichia coli, the soluble protein was purified by one-step affinity chromatography to apparent homogeneity. UV-Vis spectroscopic measurements showed that the reconstruction CmtR was able to bind Cd(II) forming Cd(II)-CmtR complex in vitro. The sequence alignment and molecular modeling showed that the crucial residues for CmtR binding were likely to be Cys77, Cys112, and Cys121. The results reported here strongly suggest that the high resistance of the extremophilic A. ferrooxidans to Cd including the Cd(II)/Pb(II)-responsive transcriptional regulator.

Ectopic expression of anti-HIV-1 shRNAs protects CD8{sup +} T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamata, Masakazu, E-mail: masa3k@ucla.edu; Kim, Patrick Y.; Ng, Hwee L.

Chimeric antigen receptors (CARs) are artificially engineered receptors that confer a desired specificity to immune effector T cells. As an HIV-1-specific CAR, CD4ζ CAR has been extensively tested in vitro as well as in clinical trials. T cells modified with this CAR mediated highly potent anti-HIV-1 activities in vitro and were well-tolerated in vivo, but exerted limited effects on viral load and reservoir size due to poor survival and/or functionality of the transduced cells in patients. We hypothesize that ectopic expression of CD4ζ on CD8{sup +} T cells renders them susceptible to HIV-1 infection, resulting in poor survival of those cells. To testmore » this possibility, highly purified CD8{sup +} T cells were genetically modified with a CD4ζ-encoding lentiviral vector and infected with HIV-1. CD8{sup +} T cells were vulnerable to HIV-1 infection upon expression of CD4ζ as evidenced by elevated levels of p24{sup Gag} in cells and culture supernatants. Concurrently, the number of CD4ζ-modified CD8{sup +} T cells was reduced relative to control cells upon HIV-1 infection. To protect these cells from HIV-1 infection, we co-expressed two anti-HIV-1 shRNAs previously developed by our group together with CD4ζ. This combination vector was able to suppress HIV-1 infection without impairing HIV-1-dependent effector activities of CD4ζ. In addition, the number of CD4ζ-modified CD8{sup +} T cells maintained similar levels to that of the control even under HIV-1 infection. These results suggest that protecting CD4ζ-modified CD8{sup +} T cells from HIV-1 infection is required for prolonged HIV-1-specific immune surveillance. - Highlights: • Ectopic expression of CD4ζ CAR in CD8{sup +} T cells renders them susceptible to HIV-1 infection. • Co-expression of two anti-HIV-1 shRNAs protects CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection. • Protecting CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection suppresses its cytopathic effect.« less

Urinary Cadmium Threshold to Prevent Kidney Disease Development.

PubMed

Satarug, Soisungwan; Ruangyuttikarn, Werawan; Nishijo, Muneko; Ruiz, Patricia

2018-05-01

The frequently observed association between kidney toxicity and long-term cadmium (Cd) exposure has long been dismissed and deemed not to be of clinical relevance. However, Cd exposure has now been associated with increased risk of developing chronic kidney disease (CKD). We investigated the link that may exist between kidney Cd toxicity markers and clinical kidney function measure such as estimated glomerular filtration rates (eGFR). We analyzed data from 193 men to 202 women, aged 16−87 years [mean age 48.8 years], who lived in a low- and high-Cd exposure areas in Thailand. The mean (range) urinary Cd level was 5.93 (0.05⁻57) μg/g creatinine. The mean (range) for estimated GFR was 86.9 (19.6−137.8) mL/min/1.73 m². Kidney pathology reflected by urinary β2-microglobulin (β2-MG) levels ≥ 300 μg/g creatinine showed an association with 5.32-fold increase in prevalence odds of CKD ( p = 0.001), while urinary Cd levels showed an association with a 2.98-fold greater odds of CKD prevalence ( p = 0.037). In non-smoking women, Cd in the highest urinary Cd quartile was associated with 18.3 mL/min/1.73 m² lower eGFR value, compared to the lowest quartile ( p < 0.001). Evidence for Cd-induced kidney pathology could thus be linked to GFR reduction, and CKD development in Cd-exposed people. These findings may help prioritize efforts to reassess Cd exposure and its impact on population health, given the rising prevalence of CKD globally.

Source of atmospheric heavy metals in winter in Foshan, China.

PubMed

Tan, Ji-Hua; Duan, Jing-Chun; Ma, Yong-Liang; Yang, Fu-Mo; Cheng, Yuan; He, Ke-Bin; Yu, Yong-Chang; Wang, Jie-Wen

2014-09-15

Foshan is a ceramics manufacturing center in the world and the most polluted city in the Pearl River Delta (PRD) in southern China measured by the levels of atmospheric heavy metals. PM2.5 samples were collected in Foshan in winter 2008. Among the 22 elements and ions analyzed, 7 heavy metals (Zn, V, Mn, Cu, As, Cd and Pb) were studied in depth for their levels, spatiotemporal variations and sources. The ambient concentrations of the heavy metals were much higher than the reported average concentrations in China. The levels of Pb (675.7 ± 378.5 ng/m(3)), As (76.6 ± 49.1 ng/m(3)) and Cd (42.6 ± 45.2 ng/m(3)) exceeded the reference values of NAAQS (GB3095-2012) and the health guidelines of the World Health Organization. Generally, the levels of atmospheric heavy metals showed spatial distribution as: downtown site (CC, Chancheng District)>urban sites (NH and SD, Nanhai and Shunde Districts)>rural site (SS, Shanshui District). Two sources of heavy metals, the ceramic and aluminum industries, were identified during the sampling period. The large number of ceramic manufactures was responsible for the high levels of atmospheric Zn, Pb and As in Chancheng District. Transport from an aluminum industry park under light north-west winds contributed high levels of Cd to the SS site (Shanshui District). The average concentration of Cd under north-west wind was 220 ng/m(3), 20.5 times higher than those under other wind directions. The high daily maximum enrichment factors (EFs) of Cd, Pb, Zn, As and Cu at all four sites indicated extremely high contamination by local emissions. Back trajectory analysis showed that the heavy metals were also closely associated with the pathway of air mass. A positive matrix factorization (PMF) method was applied to determine the source apportionment of these heavy metals. Five factors (industry including the ceramic industry and coal combustion, vehicle emissions, dust, transportation and sea salt) were identified and industry was the most important source of atmospheric heavy metals. The present paper suggests a control policy on the four heavy metals Cd, Pb, Zn, and Cu, and suggests the inclusion of As in the ceramic industry emission standard in the future. Copyright © 2014 Elsevier B.V. All rights reserved.

Seasonal variations in the concentrations of metals in Crassostrea corteziensis from Sonora, México.

PubMed

García-Rico, L; Tejeda-Valenzuela, L; Burgos-Hernández, A

2010-08-01

This study examines seasonal variations in the concentrations of Cd, Cu, Pb, and Hg in experimentally cultured Crassostrea corteziensis, an oyster species known to have high resistance to physical and chemical stressors. The highest levels of Cd (4.92 mg/kg), Cu (3.45 mg/kg), and Pb (0.67 mg/kg) were detected in oyster samples collected during the summer, while Hg concentrations were similar (0.03 to 0.04 mg/kg) throughout all seasons. Results indicate that except for Cd, Crassostrea corteziensis accumulates metals to levels below those recommended by the US. FDA and the Mexican government. For Cd, its concentration correlates more strongly with the temperature of the oyster's environment rather than to the oyster growth cycle.

Autophagy maturation associated with CD38-mediated regulation of lysosome function in mouse glomerular podocytes

PubMed Central

Xiong, Jing; Xia, Min; Xu, Ming; Zhang, Yang; Abais, Justine M; Li, Guangbi; Riebling, Christopher R; Ritter, Joseph K; Boini, Krishna M; Li, Pin-Lan

2013-01-01

Podocytes are highly differentiated glomerular epithelial cells that contribute to the glomerular barrier function of kidney. A role for autophagy has been proposed in maintenance of their cellular integrity, but the mechanisms controlling autophagy in podocytes are not clear. The present study tested whether CD38-mediated regulation of lysosome function contributes to autophagic flux or autophagy maturation in podocytes. Podocytes were found to exhibit a high constitutive level of LC3-II, a robust marker of autophagosomes (APs), suggesting a high basal level of autophagic activity. Treatment with the mTOR inhibitor, rapamycin, increased LC3-II and the content of both APs detected by Cyto-ID Green staining and autophagolysosomes (APLs) measured by acridine orange staining and colocalization of LC3 and Lamp1. Lysosome function inhibitor bafilomycin A1 increased APs, but decreased APLs content under both basal and rapamycin-induced conditions. Inhibition of CD38 activity by nicotinamide or silencing of CD38 gene produced the similar effects to that bafilomycin A1 did in podocytes. To explore the possibility that CD38 may control podocyte autophagy through its regulation of lysosome function, the fusion of APs with lysosomes in living podocytes was observed by co-transfection of GFP-LC3B and RFP-Lamp1 expression vectors. A colocalization of GFP-LC3B and RFP-Lamp1 upon stimulation of rapamycin became obvious in transfected podocytes, which could be substantially blocked by nicotinamide, CD38 shRNA, and bafilomycin. Moreover, blockade of the CD38-mediated regulation by PPADS completely abolished rapamycin-induced fusion of APs with lysosomes. These results indicate that CD38 importantly control lysosomal function and influence autophagy at the maturation step in podocytes. PMID:24238063

Residential Proximity to Major Roadways Is Associated With Increased Levels of AC133+ Circulating Angiogenic Cells.

PubMed

DeJarnett, Natasha; Yeager, Ray; Conklin, Daniel J; Lee, Jongmin; O'Toole, Timothy E; McCracken, James; Abplanalp, Wes; Srivastava, Sanjay; Riggs, Daniel W; Hamzeh, Ihab; Wagner, Stephen; Chugh, Atul; DeFilippis, Andrew; Ciszewski, Tiffany; Wyatt, Brad; Becher, Carrie; Higdon, Deirdre; Ramos, Kenneth S; Tollerud, David J; Myers, John A; Rai, Shesh N; Shah, Jasmit; Zafar, Nagma; Krishnasamy, Sathya S; Prabhu, Sumanth D; Bhatnagar, Aruni

2015-11-01

Previous studies have shown that residential proximity to a roadway is associated with increased cardiovascular disease risk. Yet, the nature of this association remains unclear, and its effect on individual cardiovascular disease risk factors has not been assessed. The objective of this study was to determine whether residential proximity to roadways influences systemic inflammation and the levels of circulating angiogenic cells. In a cross-sectional study, cardiovascular disease risk factors, blood levels of C-reactive protein, and 15 antigenically defined circulating angiogenic cell populations were measured in participants (n=316) with moderate-to-high cardiovascular disease risk. Attributes of roadways surrounding residential locations were assessed using geographic information systems. Associations between road proximity and cardiovascular indices were analyzed using generalized linear models. Close proximity (<50 m) to a major roadway was associated with lower income and higher rates of smoking but not C-reactive protein levels. After adjustment for potential confounders, the levels of circulating angiogenic cells in peripheral blood were significantly elevated in people living in close proximity to a major roadway (CD31(+)/AC133(+), AC133(+), CD34(+)/AC133(+), and CD34(+)/45(dim)/AC133(+) cells) and positively associated with road segment distance (CD31(+)/AC133(+), AC133(+), and CD34(+)/AC133(+) cells), traffic intensity (CD31(+)/AC133(+) and AC133(+) cells), and distance-weighted traffic intensity (CD31(+)/34(+)/45(+)/AC133(+) cells). Living close to a major roadway is associated with elevated levels of circulating cells positive for the early stem marker AC133(+). This may reflect an increased need for vascular repair. Levels of these cells in peripheral blood may be a sensitive index of cardiovascular injury because of residential proximity to roadways. © 2015 American Heart Association, Inc.

CD82 suppresses CD44 alternative splicing-dependent melanoma metastasis by mediating U2AF2 ubiquitination and degradation

PubMed Central

Fu, Ailing; Zhu, Huifeng; Ren, Qiao; Wang, Bochu; Xu, Xingran; Bai, Huiyuan; Dong, Cheng

2016-01-01

Melanoma is one of the most lethal forms of skin cancer due to its early metastatic spread. The variant form of CD44 (CD44v), a cell surface glycoprotein, is highly expressed on metastatic melanoma. The mechanisms of regulation of CD44 alternative splicing in melanoma and its pathogenic contributions are so far poorly understood. Here, we investigated the expression level of CD44 in a large set of melanocytic lesions at different stages. We found that the expression of CD44v8-10 and a splicing factor, U2AF2, is significantly increased during melanoma progression, while CD82/KAI1, a tetraspanin family of tumor suppressor, is reduced in metastatic melanoma. CD44v8-10 and U2AF2 expressions which are negatively correlated with CD82 levels are dramatically elevated in primary melanoma compared with dysplastic nevi and further increased in metastatic melanoma. We also showed that patients with higher CD44v8-10 and U2AF2 expression levels tended to have shorter survival. By using both in vivo and in vitro assays, we demonstrated that CD82 inhibits the production of CD44v8-10 on melanoma. Mechanistically, U2AF2 is a downstream target of CD82 and in malignant melanoma facilitates CD44v8-10 alternative splicing. U2AF2-mediated CD44 isoform switch is required for melanoma migration in vitro and lung and liver metastasis in vivo. Notably, overexpression of CD82 suppresses U2AF2 activity by inducing U2AF2 ubiquitination. In addition, our data suggested that enhancement of melanoma migration by U2AF2-dependent CD44v8-10 splicing is mediated by Src/FAK/RhoA activation and formation of stress fibers as well as CD44-E-selectin binding reinforcement. These findings uncovered a hitherto unappreciated function of CD82 in severing the linkage between U2AF2-mediated CD44 alternative splicing and cancer aggressiveness, with potential prognostic and therapeutic implications in melanoma. PMID:27041584

High Dietary Fat Intake during Lactation Promotes the Development of Social Stress-Induced Obesity in the Offspring of Mice.

PubMed

Tsuduki, Tsuyoshi; Yamamoto, Kazushi; E, Shuang; Hatakeyama, Yu; Sakamoto, Yu

2015-07-17

This study examined how a maternal high-fat diet (HD) during lactation and exposure of offspring to isolation stress influence the susceptibility of offspring to the development of obesity. C57BL/6J mice were fed a commercial diet (CD) during pregnancy and a CD or HD during lactation. Male offspring were weaned at three weeks of age, fed a CD until seven weeks of age, and fed a CD or HD until 11 weeks of age. Offspring were housed alone (isolation stress) or at six per cage (ordinary circumstances). Thus, offspring were assigned to one of eight groups: dams fed a CD or HD during lactation and offspring fed a CD or HD and housed under ordinary circumstances or isolation stress. Serum corticosterone level was significantly elevated by isolation stress. High-fat feeding of offspring reduced their serum corticosterone level, which was significantly elevated by a maternal HD. A maternal HD and isolation stress had combined effects in elevating the serum corticosterone level. These findings suggest that a maternal HD during lactation enhances the stress sensitivity of offspring. White adipose tissue weights were significantly increased by a maternal HD and isolation stress and by their combination. In addition, significant adipocyte hypertrophy was induced by a maternal HD and isolation stress and exacerbated by their combination. Thus, a maternal HD and isolation stress promote visceral fat accumulation and adipocyte hypertrophy, accelerating the progression of obesity through their combined effects. The mechanism may involve enhanced fatty acid synthesis and lipid influx from blood into adipose tissue. These findings demonstrate that a maternal HD during lactation may increase the susceptibility of offspring to the development of stress-induced obesity.

β-Adrenergic receptor antagonism prevents anxiety-like behavior and microglial reactivity induced by repeated social defeat.

PubMed

Wohleb, Eric S; Hanke, Mark L; Corona, Angela W; Powell, Nicole D; Stiner, La'Tonia M; Bailey, Michael T; Nelson, Randy J; Godbout, Jonathan P; Sheridan, John F

2011-04-27

Psychosocial stress is associated with altered immune function and development of psychological disorders including anxiety and depression. Here we show that repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior in a β-adrenergic receptor-dependent manner. Repeated social defeat also significantly increased the number of CD11b(+)/CD45(high)/Ly6C(high) macrophages that trafficked to the brain. In addition, several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86) after social defeat. Repeated social defeat also increased the presence of deramified microglia in the medial amygdala, prefrontal cortex, and hippocampus. Moreover, mRNA analysis of microglia indicated that repeated social defeat increased levels of interleukin (IL)-1β and reduced levels of glucocorticoid responsive genes [glucocorticoid-induced leucine zipper (GILZ) and FK506 binding protein-51 (FKBP51)]. The stress-dependent changes in microglia and macrophages were prevented by propranolol, a β-adrenergic receptor antagonist. Microglia isolated from socially defeated mice and cultured ex vivo produced markedly higher levels of IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 after stimulation with lipopolysaccharide compared with microglia from control mice. Last, repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior or microglia activation in the absence of functional IL-1 receptor type-1. These findings indicate that repeated social defeat-induced anxiety-like behavior and enhanced reactivity of microglia was dependent on activation of β-adrenergic and IL-1 receptors.

α4+β7hiCD4+ Memory T cells Harbor Most Th-17 cells and are Preferentially Infected During Acute SIV Infection

PubMed Central

Kader, Muhamuda; Wang, Xiaolei; Piatak, Michael; Lifson, Jeffrey; Roederer, Mario; Veazey, Ronald; Mattapallil, Joseph J.

2009-01-01

HIV/SIV are thought to infect minimally activated CD4+ T cells after viral entry. Not much is known about why SIV selectively targets these cells. Here we show that CD4+ T cells that express high levels of the α4β7 heterodimer are preferentially infected very early during the course of SIV infection. At day 2–4 post infection, α4+β7hiCD4+ T cells had ∼ 5x more SIV-gag DNA than β7−CD4+ T cells. α4+β7hiCD4+ T cells displayed a predominantly central memory (CD45RA−CD28+CCR7+) and resting (CD25−CD69−HLA-DR−Ki-67−) phenotype. Though the expression of detectable CCR5 was variable on α4+β7hi and β7−CD4+ T cells, both CCR5+ and CCR5− subsets of α4+β7hi and β7−CD4+ T cells were found to express sufficient levels of CCR5 mRNA suggesting that both these subsets could be efficiently infected by SIV. In line with this, we found similar levels of SIV infection in β7−CD4+CCR5+ and β7−CD4+CCR5− T cells. α4β7hiCD4+ T cells were found to harbor most Th-17 cells that were significantly depleted during acute SIV infection. Taken together, our results show that resting memory α4+β7hiCD4+ T cells in blood are preferentially depleted during acute SIV infection, and the loss of these cells alters the balance between Th-17 and Th-1 responses thereby contributing to disease pathogenesis. PMID:19571800

Can We Repurpose FDA-Approved Alefacept to Diminish the HIV Reservoir?

PubMed Central

Zaidi, Asifa; Meng, Qinglai; Popkin, Daniel

2016-01-01

Current anti-retroviral treatment (ART) for HIV is effective in maintaining HIV at undetectable levels. However, cessation of ART results in immediate and brisk rebound of viremia to high levels. This rebound is driven by an HIV reservoir mainly enriched in memory CD4+ T cells. In order to provide any form of functional HIV Cure, elimination of this viral reservoir has become the focus of current HIV cure strategies. Alefacept was initially developed for the treatment of chronic plaque psoriasis. Alefacept is a chimeric fusion protein consisting of the CD2-binding portion of human leukocyte function antigen-3 (LFA3) linked to the Fc region of human IgG1 (LFA3-Fc). Alefacept was designed to inhibit memory T cell activation that contributes to the chronic autoimmune disease psoriasis by blocking the CD2 coreceptor. However, it was found to deplete memory T cells that express high levels of CD2 via NK cell-mediated antibody dependent cell cytotoxicity (ADCC) in vivo. Phase II and phase III clinical trials of alefacept with psoriasis patients demonstrated promising results and an excellent safety profile. Subsequently, alefacept has been successfully repurposed for other memory T cell-mediated autoimmune diseases including skin diseases other than psoriasis, organ transplantation and type I diabetes (T1D). Herein, we review our specific strategy to repurpose the FDA approved biologic alefacept to decrease and hopefully someday eliminate the HIV reservoir, for which CD2hi memory CD4+ T cells are a significant contributor. PMID:27110598

IL-10 production by B cells expressing CD5 with the alternative exon 1B.

PubMed

Garaud, Soizic; Le Dantec, Christelle; de Mendoza, Agnès Revol; Mageed, Rizgar A; Youinou, Pierre; Renaudineau, Yves

2009-09-01

B lymphocytes are divided into two subpopulations, B1 and B2 cells based on expression of the T cell-associated protein CD5. Natural B1 cells are further divided into B1a cells that express CD5 on their membrane and B1b cells that do not but share most other biological characteristics of B1a cells. Recent studies from our laboratory have revealed, in humans, the existence of two alternative isoforms of the CD5 protein. A cell surface CD5 isoform which uses exon 1A (E1A) of the gene in B1a cells, and an intracellular isoform which uses exon 1B (E1B) mainly in human B1b cells. Indeed, the protein isoform encoded by transcripts containing E1B lack the leader peptide and is, thus, retained in the cytoplasm of B cells. The restriction of interleukin (IL)-10 to B1 lymphocytes in the mouse raises the possibility that the human CD5-E1B-expressing B cells produce IL-10. This prediction was confirmed in the CD5 negative Jok-1 B cells transfected with cDNA for either isoforms resulted in high level IL-10 production. Our data indicate that E1B-CD5-expressing B cells have the capacity to interfere with the immune response through their ability to produce high levels of IL-10.

Pretransplant soluble CD30 serum concentration does not affect kidney graft outcomes 3 years after transplantation.

PubMed

Kovač, J; Arnol, M; Vidan Jeras, B; Bren, A F; Kandus, A

2010-12-01

An elevated serum concentration of soluble the form of CD30 (sCD30), an activation marker of mainly T(H)2-type cytokines producing T lymphocytes, has been reported as a predictive factor for acute cellular rejection episodes and poor graft outcomes in kidney transplantation. This historic cohort study investigated the association of a pretransplant sCD30 serum concentrations with kidney graft function and graft survival 3 years posttransplantation in adult recipients of deceased donor kidney grafts, treated with monoclonal anti-CD25 antibodies as an induction treatment combined with a cyclosporine (CsA)-based maintenance triple therapy. The pretransplant sera of 296 recipients were tested for sCD30 content using a microsphere flow-cytometry assay. The estimated glomerular filtration rate (eGFR) was determined by the 4-variable Modification of Diet in Renal Disease equation. The incidences of graft loss were calculated with the use of Kaplan-Meier survival analysis and compared using the log-rank test. According to the distribution of the pretransplant sCD30 levels concentration ≥2700 pg/mL was defined as high (n = 146) and concentration <2700 pg/mL as low (n = 150). Three years posttransplantation, the eGFR was not significantly different in the recipients in high and low sCD30 groups (65 ± 24 vs 67 ± 21 mL/min/1.73 m(2); P = .43); there was no association between the eGFR 3 years after transplantation and the pretransplant sCD30 levels (r(2) = 0.002; P = .49). Graft survival 3 years after transplantation was also not different in the recipients in high and low sCD30 groups (P = .52). In our adult deceased-donor kidney graft recipients, the pretransplant sCD30 serum concentration was not a predictive factor of immunologic risk associated with the kidney graft function 3 years posttransplantation; neither did it affect graft survival 3 years after transplantation. The immunosuppression with anti-CD25 antibodies as an induction treatment combined with the CsA-based maintenance triple therapy could possibly be decisive for our findings. Copyright © 2010 Elsevier Inc. All rights reserved.

Serum sCD163 Levels Are Associated with Type 2 Diabetes Mellitus and Are Influenced by Coffee and Wine Consumption: Results of the Di@bet.es Study

PubMed Central

Rojo-Martínez, Gemma; Maymó-Masip, Elsa; Rodríguez, M. Mar; Solano, Esther; Goday, Albert; Soriguer, Federico; Valdés, Sergio; Chaves, Felipe Javier; Delgado, Elías; Colomo, Natalia; Hernández, Pilar

2014-01-01

Objective Serum levels of soluble TNF-like weak inducer of apoptosis (sTWEAK) and its scavenger receptor CD163 (sCD163) have been linked to insulin resistance. We analysed the usefulness of these cytokines as biomarkers of type 2 diabetes in a Spanish cohort, together with their relationship to food consumption in the setting of the Di@bet.es study. Research Design and Methods This is a cross-sectional, matched case-control study of 514 type 2 diabetes subjects and 517 controls with a Normal Oral Glucose Tolerance Test (NOGTT), using data from the Di@bet.es study. Study variables included clinical and demographic structured survey, food frequency questionnaire and physical examination. Serum concentrations of sTWEAK and sCD163 were measured by ELISA. Linear regression analysis determined which variables were related to sTWEAK and sCD163 levels. Logistic regression analysis was used to estimate odd ratios of presenting type 2 diabetes. Results sCD163 concentrations and sCD163/sTWEAK ratio were 11.0% and 15.0% higher, respectively, (P<0.001) in type 2 diabetes than in controls. Following adjustment for various confounders, the OR for presenting type 2 diabetes in subjects in the highest vs the lowest tertile of sCD163 was [(OR), 2,01 (95%CI, 1,46–2,97); P for trend <0.001]. Coffee and red wine consumption was negatively associated with serum levels of sCD163 (P = 0.0001 and; P = 0.002 for coffee and red wine intake, respectively). Conclusions High circulating levels of sCD163 are associated with type 2 diabetes in the Spanish population. The association between coffee and red wine intake and these biomarkers deserves further study to confirm its potential role in type 2 diabetes. PMID:24978196

Serum sCD163 levels are associated with type 2 diabetes mellitus and are influenced by coffee and wine consumption: results of the Di@bet.es study.

PubMed

Rojo-Martínez, Gemma; Maymó-Masip, Elsa; Rodríguez, M Mar; Solano, Esther; Goday, Albert; Soriguer, Federico; Valdés, Sergio; Chaves, Felipe Javier; Delgado, Elías; Colomo, Natalia; Hernández, Pilar; Vendrell, Joan; Chacón, Matilde R

2014-01-01

Serum levels of soluble TNF-like weak inducer of apoptosis (sTWEAK) and its scavenger receptor CD163 (sCD163) have been linked to insulin resistance. We analysed the usefulness of these cytokines as biomarkers of type 2 diabetes in a Spanish cohort, together with their relationship to food consumption in the setting of the Di@bet.es study. This is a cross-sectional, matched case-control study of 514 type 2 diabetes subjects and 517 controls with a Normal Oral Glucose Tolerance Test (NOGTT), using data from the Di@bet.es study. Study variables included clinical and demographic structured survey, food frequency questionnaire and physical examination. Serum concentrations of sTWEAK and sCD163 were measured by ELISA. Linear regression analysis determined which variables were related to sTWEAK and sCD163 levels. Logistic regression analysis was used to estimate odd ratios of presenting type 2 diabetes. sCD163 concentrations and sCD163/sTWEAK ratio were 11.0% and 15.0% higher, respectively, (P<0.001) in type 2 diabetes than in controls. Following adjustment for various confounders, the OR for presenting type 2 diabetes in subjects in the highest vs the lowest tertile of sCD163 was [(OR), 2,01 (95%CI, 1,46-2,97); P for trend <0.001]. Coffee and red wine consumption was negatively associated with serum levels of sCD163 (P = 0.0001 and; P = 0.002 for coffee and red wine intake, respectively). High circulating levels of sCD163 are associated with type 2 diabetes in the Spanish population. The association between coffee and red wine intake and these biomarkers deserves further study to confirm its potential role in type 2 diabetes.

Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score.

PubMed

Jary, Marine; Lecomte, Thierry; Bouché, Olivier; Kim, Stefano; Dobi, Erion; Queiroz, Lise; Ghiringhelli, Francois; Etienne, Hélène; Léger, Julie; Godet, Yann; Balland, Jérémy; Lakkis, Zaher; Adotevi, Olivier; Bonnetain, Franck; Borg, Christophe; Vernerey, Dewi

2016-11-15

In first-line metastatic colorectal cancer (mCRC), baseline prognostic factors allowing death risk and treatment strategy stratification are lacking. Syndecan-1 (CD138) soluble form was never described as a prognostic biomarker in mCRC. We investigated its additional prognostic value for overall survival (OS). mCRC patients with unresectable disease at diagnosis were treated with bevacizumab-based chemotherapy in two independent prospective clinical trials (development set: n = 126, validation set: n = 51, study NCT00489697 and study NCT00544011, respectively). Serums were collected at baseline for CD138 measurement. OS determinants were assessed and, based on the final multivariate model, a prognostic score was proposed. Two independent OS prognostic factors were identified: Lactate Dehydrogenase (LDH) high level (p = 0.0066) and log-CD138 high level (p = 0.0190). The determination of CD138 binary information (cutoff: 75 ng/mL) allowed the assessment of a biological prognostic score with CD138 and LDH values, identifying three risk groups for death (median OS= 38.9, 30.1 and 19.8 months for the low, intermediate and high risk groups, respectively; p < 0.0001). This score had a good discrimination ability (C-index = 0.63). These results were externally confirmed in the validation set. Our study provides robust evidence in favor of the additional baseline soluble CD138 prognostic value for OS, in mCRC patients. A simple biological scoring system is proposed including LDH and CD138 binary status values. © 2016 UICC.

Relationship of ethnicity and CD4 Count with glucose metabolism among HIV patients on Highly-Active Antiretroviral Therapy (HAART)

PubMed Central

2013-01-01

Background HIV patients on HAART are prone to metabolic abnormalities, including insulin resistance, lipodystrophy and diabetes. This study purports to investigate the relationship of ethnicity and CD4+ T cell count attained after stable highly-active antiretroviral treatment (HAART) with glucose metabolism in hyperrtriglyceridemic HIV patients without a history of diabetes. Methods Demographic, anthropometric, clinical, endocrinologic, energy expenditure and metabolic measures were obtained in 199 multiethnic, healthy but hypertriglyceridemic HIV-infected patients [46% Hispanic, 17% African-American, 37% Non-Hispanic White (NHW)] on stable HAART without a history of diabetes. The relationship of glucose and insulin responses to ethnicity, CD4 strata (low (<300/cc) or moderate-to-high (≥ 300/cc)), and their interaction was determined. Results African-Americans had significantly greater impairment of glucose tolerance (P < 0.05) and HbA1c levels (P < .001) than either Hispanics or NHWs. In multivariate models, after adjusting for confounders (age, sex, HIV/HAART duration, smoking, obesity, glucose, insulin and lipids), African-Americans and Hispanics had significantly higher HbA1c and 2-hour glucose levels than NHW’s. Demonstrating a significant interaction between ethnicity and CD4 count (P = 0.023), African Americans with CD4 <300/cc and Hispanics with CD4 ≥300/cc had the most impaired glucose response following oral glucose challenge. Conclusions Among hypertriglyceridemic HIV patients on HAART, African-Americans and Hispanics are at increased risk of developing diabetes. Ethnicity also interacts with CD4+ T cell count attained on stable HAART to affect post-challenge glycemic response. PMID:23607267

Analysis of the interaction between respiratory syncytial virus and lipid-rafts in Hep2 cells during infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Gaie; Jeffree, Chris E.; McDonald, Terence

2004-10-01

The assembly of respiratory syncytial virus (RSV) in lipid-rafts was examined in Hep2 cells. Confocal and electron microscopy showed that during RSV assembly, the cellular distribution of the complement regulatory proteins, decay accelerating factor (CD55) and CD59, changes and high levels of these cellular proteins are incorporated into mature virus filaments. The detergent-solubility properties of CD55, CD59, and the RSV fusion (F) protein were found to be consistent with each protein being located predominantly within lipid-raft structures. The levels of these proteins in cell-released virus were examined by immunoelectronmicroscopy and found to account for between 5% and 15% of themore » virus attachment (G) glycoprotein levels. Collectively, our findings suggest that an intimate association exists between RSV and lipid-raft membranes and that significant levels of these host-derived raft proteins, such as those regulating complement activation, are subsequently incorporated into the envelope of mature virus particles.« less

Effects of Interaction between Cadmium (Cd) and Selenium (Se) on Grain Yield and Cd and Se Accumulation in a Hybrid Rice (Oryza sativa) System.

PubMed

Huang, Baifei; Xin, Junliang; Dai, Hongwen; Zhou, Wenjing

2017-11-01

A pot experiment was conducted to investigate the interactive effects of cadmium (Cd) and selenium (Se) on their accumulation in three rice cultivars, which remains unclear. The results showed that Se reduced Cd-induced growth inhibition, and increased and decreased Se and Cd concentrations in brown rice, respectively. Cadmium concentrations in all tissues of the hybrid were similar to those in its male parent yet significantly lower than those in its female parent. Selenium reduced Cd accumulation in rice when Cd concentration exceeded 2.0 mg kg -1 ; however Se accumulation depended on the levels of Cd exposure. Finally, Cd had minimal effect on Se translocation within the three cultivars. We concluded that Cd concentration in brown rice is a heritable trait, making crossbreeding a feasible method for cultivating high-yield, low-Cd rice cultivars. Selenium effectively decreased the toxicity and accumulation of Cd, and Cd affected Se uptake but not translocation.

Downregulation of CD4+CD25+ regulatory T cells may underlie enhanced Th1 immunity caused by immunization with activated autologous T cells.

PubMed

Cao, Qi; Wang, Li; Du, Fang; Sheng, Huiming; Zhang, Yan; Wu, Juanjuan; Shen, Baihua; Shen, Tianwei; Zhang, Jingwu; Li, Dangsheng; Li, Ningli

2007-07-01

Regulatory T cells (Treg) play important roles in immune system homeostasis, and may also be involved in tumor immunotolerance by suppressing Th1 immune response which is involved in anti-tumor immunity. We have previously reported that immunization with attenuated activated autologous T cells leads to enhanced anti-tumor immunity and upregulated Th1 responses in vivo. However, the underlying molecular mechanisms are not well understood. Here we show that Treg function was significantly downregulated in mice that received immunization of attenuated activated autologous T cells. We found that Foxp3 expression decreased in CD4+CD25+ T cells from the immunized mice. Moreover, CD4+CD25+Foxp3+ Treg obtained from immunized mice exhibited diminished immunosuppression ability compared to those from naïve mice. Further analysis showed that the serum of immunized mice contains a high level of anti-CD25 antibody (about 30 ng/ml, p<0.01 vs controls). Consistent with a role of anti-CD25 response in the downregulation of Treg, adoptive transfer of serum from immunized mice to naïve mice led to a significant decrease in Treg population and function in recipient mice. The triggering of anti-CD25 response in immunized mice can be explained by the fact that CD25 was induced to a high level in the ConA activated autologous T cells used for immunization. Our results demonstrate for the first time that immunization with attenuated activated autologous T cells evokes anti-CD25 antibody production, which leads to impeded CD4+CD25+Foxp3+ Treg expansion and function in vivo. We suggest that dampened Treg function likely contributes to enhanced Th1 response in immunized mice and is at least part of the mechanism underlying the boosted anti-tumor immunity.

Enhanced radiosensitivity and radiation-induced apoptosis in glioma CD133-positive cells by knockdown of SirT1 expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, C.-J.; Hsu, C.-C.; Department of Surgery, Chi-Mei Medical Center, Taipei, Taiwan

2009-03-06

CD133-expressing glioma cells play a critical role in tumor recovery after treatment and are resistant to radiotherapy. Herein, we demonstrated that glioblastoma-derived CD133-positive cells (GBM-CD133{sup +}) are capable of self-renewal and express high levels of embryonic stem cell genes and SirT1 compared to GBM-CD133{sup -} cells. To evaluate the role of SirT1 in GBM-CD133{sup +}, we used a lentiviral vector expressing shRNA to knock-down SirT1 expression (sh-SirT1) in GBM-CD133{sup +}. Silencing of SirT1 significantly enhanced the sensitivity of GBM-CD133{sup +} to radiation and increased the level of radiation-mediated apoptosis. Importantly, knock-down of SirT1 increased the effectiveness of radiotherapy in themore » inhibition of tumor growth in nude mice transplanted with GBM-CD133{sup +}. Kaplan-Meier survival analysis indicated that the mean survival rate of GBM-CD133{sup +} mice treated with radiotherapy was significantly improved by Sh-SirT1 as well. In sum, these results suggest that SirT1 is a potential target for increasing the sensitivity of GBM and glioblastoma-associated cancer stem cells to radiotherapy.« less

PPARβ/δ ameliorates fructose-induced insulin resistance in adipocytes by preventing Nrf2 activation.

PubMed

Barroso, Emma; Rodríguez-Rodríguez, Rosalía; Chacón, Matilde R; Maymó-Masip, Elsa; Ferrer, Laura; Salvadó, Laia; Salmerón, Emilio; Wabistch, Martin; Palomer, Xavier; Vendrell, Joan; Wahli, Walter; Vázquez-Carrera, Manuel

2015-05-01

We studied whether PPARβ/δ deficiency modifies the effects of high fructose intake (30% fructose in drinking water) on glucose tolerance and adipose tissue dysfunction, focusing on the CD36-dependent pathway that enhances adipose tissue inflammation and impairs insulin signaling. Fructose intake for 8 weeks significantly increased body and liver weight, and hepatic triglyceride accumulation in PPARβ/δ-deficient mice but not in wild-type mice. Feeding PPARβ/δ-deficient mice with fructose exacerbated glucose intolerance and led to macrophage infiltration, inflammation, enhanced mRNA and protein levels of CD36, and activation of the JNK pathway in white adipose tissue compared to those of water-fed PPARβ/δ-deficient mice. Cultured adipocytes exposed to fructose also exhibited increased CD36 protein levels and this increase was prevented by the PPARβ/δ activator GW501516. Interestingly, the levels of the nuclear factor E2-related factor 2 (Nrf2), a transcription factor reported to up-regulate Cd36 expression and to impair insulin signaling, were increased in fructose-exposed adipocytes whereas co-incubation with GW501516 abolished this increase. In agreement with Nrf2 playing a role in the fructose-induced CD36 protein level increases, the Nrf2 inhibitor trigonelline prevented the increase and the reduction in insulin-stimulated AKT phosphorylation caused by fructose in adipocytes. Protein levels of the well-known Nrf2 target gene quinone oxidoreductase 1 (Nqo1) were increased in water-fed PPARβ/δ-null mice, suggesting that PPARβ/δ deficiency increases Nrf2 activity; and this increase was exacerbated in fructose-fed PPARβ/δ-deficient mice. These findings indicate that the combination of high fructose intake and PPARβ/δ deficiency increases CD36 protein levels via Nrf2, a process that promotes chronic inflammation and insulin resistance in adipose tissue. Copyright © 2015 Elsevier B.V. All rights reserved.

Expansion of CD11b+Ly6Ghigh and CD11b+CD49d+ myeloid cells with suppressive potential in mice with chronic inflammation and light-at-night-induced circadian disruption.

PubMed

Perfilyeva, Yuliya V; Abdolla, Nurshat; Ostapchuk, Yekaterina O; Tleulieva, Raikhan; Krasnoshtanov, Vladimir C; Belyaev, Nikolai N

2017-08-01

Myeloid-derived suppressor cells (MDSCs) are important negative regulators of immune processes in cancer and other pathological conditions. We suggested that MDSCs play a key role in pathogenesis of chronic inflammation, which precedes and, to a certain extent, induces carcinogenesis. The present study aimed at investigation of MDSCs arising during chronic inflammation and light-at-night (LN)-induced stress, which is shown to accelerate chronic diseases. 67 CD-1 mice and in vitro MDSC cultures. Adjuvant arthritis was induced by a subdermal injection of complete Freund's adjuvant. LN was induced by illumination of 750 lx at night. Flow cytometry for evaluation of cell phenotypes and MTT standard test for cell proliferation were used. Increased levels of splenic CD11b + Ly6G high and CD11b + CD49d + myeloid cells possessing suppressive potential in mice with adjuvant arthritis are shown. LN amplifies the process of CD11b + Ly6G high expansion in mice with adjuvant arthritis. Expression of CD62L and CD195 is elevated on the myeloid cells during exposure to LN. Our study raises the possibility that CD11b + Ly6G high and CD11b + CD49d + MDSCs play an important role in the induction of immunosuppressive environment typical for chronic inflammation. Also, LN can affect immune responses during chronic inflammation through recruitment of MDSCs from the bone marrow.

Soluble CD30 in renal transplant recipients: is it a good biomarker to predict rejection?

PubMed

Azarpira, Negar; Aghdaie, Mahdokht Hosein; Malekpour, Zahra

2010-01-01

It has been suggested that the serum soluble CD30 (sCD30) level may be a poten-tial marker for the prediction of acute allograft rejection in kidney transplant recipients. Therefore, its serum concentrations might offer a promising non-invasive tool to recognize patients with an increased risk for developing an acute graft rejection. We retrospectively correlate pre and post transplant level on post transplant graft survival, incidence of acute rejection and graft function using stored serum samples. Ninety-nine patients were divided in two separate groups: Group A in whom sample collection was done one day before transplantation and Group B where sample collection was done five days after transplantation. Younger recipients (aged less than 20 years) had higher sCD30 levels (P= 0.02). There was neither significant difference in the incidence of acute rejection nor incomplete response rate after anti rejection therapy in relation to pre transplant or post transplant sCD30. We could not find a significantly inferior graft survival rate in the high sCD30 group. In conclusion, younger patients had higher sCD30 concentrations however no correlation existed between the serum concentrations and occurrence of rejection episodes or graft survival.

Speciation, sources, and risk assessment of heavy metals in suburban vegetable garden soil in Xianyang City, Northwest China

NASA Astrophysics Data System (ADS)

Wang, Lijun; Tao, Wendong; Smardon, Richard C.; Xu, Xue; Lu, Xinwei

2017-07-01

Intensive anthropogenic activities can lead to soil heavy metal contamination resulting in potential risks to the environment and to human health. To reveal the concentrations, speciation, sources, pollution level, and ecological risk of heavy metals in vegetable garden soil, a total of 136 soil samples were collected from three vegetable production fields in the suburbs of Xianyang City, Northwest China. These samples were analyzed by inductively coupled plasma- atomic emission spectrometry and atomic fluorescence spectrometry. The results showed that the mean concentrations of Cd, Co, Cu, Mn, Pb, Zn, and Hg in vegetable garden soil were higher than the corresponding soil element background values of Shaanxi Province. The heavy metals studied in vegetable garden soil were primarily found in the residual fraction, averaging from 31.26% (Pb) to 90.23% (Cr). Considering the non-residual fractions, the mobility or potential risk was in the order of Pb (68.74%)>Co (60.54%)>Mn (59.28%) >Cd (53.54%) ≫Ni (23.36%) >Zn (22.73%)>Cu (14.93%)>V (11.81%)>Cr (9.78%). Cr, Mn, Ni, V, and As in the studied soil were related to soilforming parent materials, while Cu, Hg, Zn, Cd, Co, and Pb were associated with the application of plastic films, fertilizers, and pesticides, as well as traffic emissions and industrial fumes. Cr, Ni, V, and As presented low contamination levels, whereas Co, Cu, Mn, Pb, and Zn levels were moderate, and Cd and Hg were high. Ecological risk was low for Co, Cr, Cu, Mn, Pb, Zn, and As, with high risk observed for Cd and Hg. The overall pollution level and ecological risk of these heavy metals were high.

Speciation, sources, and risk assessment of heavy metals in suburban vegetable garden soil in Xianyang City, Northwest China

NASA Astrophysics Data System (ADS)

Wang, Lijun; Tao, Wendong; Smardon, Richard C.; Xu, Xue; Lu, Xinwei

2018-06-01

Intensive anthropogenic activities can lead to soil heavy metal contamination resulting in potential risks to the environment and to human health. To reveal the concentrations, speciation, sources, pollution level, and ecological risk of heavy metals in vegetable garden soil, a total of 136 soil samples were collected from three vegetable production fields in the suburbs of Xianyang City, Northwest China. These samples were analyzed by inductively coupled plasma- atomic emission spectrometry and atomic fluorescence spectrometry. The results showed that the mean concentrations of Cd, Co, Cu, Mn, Pb, Zn, and Hg in vegetable garden soil were higher than the corresponding soil element background values of Shaanxi Province. The heavy metals studied in vegetable garden soil were primarily found in the residual fraction, averaging from 31.26% (Pb) to 90.23% (Cr). Considering the non-residual fractions, the mobility or potential risk was in the order of Pb (68.74%)>Co (60.54%)>Mn (59.28%) >Cd (53.54%) ≫Ni (23.36%) >Zn (22.73%)>Cu (14.93%)>V (11.81%)>Cr (9.78%). Cr, Mn, Ni, V, and As in the studied soil were related to soilforming parent materials, while Cu, Hg, Zn, Cd, Co, and Pb were associated with the application of plastic films, fertilizers, and pesticides, as well as traffic emissions and industrial fumes. Cr, Ni, V, and As presented low contamination levels, whereas Co, Cu, Mn, Pb, and Zn levels were moderate, and Cd and Hg were high. Ecological risk was low for Co, Cr, Cu, Mn, Pb, Zn, and As, with high risk observed for Cd and Hg. The overall pollution level and ecological risk of these heavy metals were high.

Anti-CMV-IgG Positivity of Donors Is Beneficial for alloHSCT Recipients with Respect to the Better Short-Term Immunological Recovery and High Level of CD4+CD25high Lymphocytes

PubMed Central

Jaskula, Emilia; Dlubek, Dorota; Tarnowska, Agnieszka; Lange, Janusz; Mordak-Domagala, Monika; Suchnicki, Krzysztof; Sedzimirska, Mariola; Borowik, Agata; Mizia, Sylwia; Lange, Andrzej

2015-01-01

Hematopoietic stem cell transplantation from anti-cytomegalovirus immunoglobulin G (anti-CMV-IgG) positive donors facilitated immunological recovery post-transplant, which may indicate that chronic CMV infection has an effect on the immune system. This can be seen in the recipients after reconstitution with donor lymphocytes. We evaluated the composition of lymphocytes at hematologic recovery in 99 patients with hematologic malignancies post hematopoietic stem cell transplantation (HSCT). Anti-CMV-IgG seropositivity of the donor was associated with higher proportions of CD4+ (227.963 ± 304.858 × 106 vs. 102.050 ± 17.247 × 106 cells/L, p = 0.009) and CD4+CD25high (3.456 ± 0.436 × 106 vs. 1.589 ± 0.218 × 106 cells/L, p = 0.003) lymphocytes in the blood at hematologic recovery. The latter parameter exerted a diverse influence on the risk of acute graft-versus-host disease (GvHD) if low (1.483 ± 0.360 × 106 vs. 3.778 ± 0.484 × 106 cells/L, p < 0.001) and de novo chronic GvHD (cGvHD) if high (3.778 ± 0.780 × 106 vs. 2.042 ± 0.261 × 106 cells/L, p = 0.041). Higher values of CD4+ lymphocytes in patients who received transplants from anti-CMV-IgG-positive donors translated into a reduced demand for IgG support (23/63 vs. 19/33, p = 0.048), and these patients also exhibited reduced susceptibility to cytomegalovirus (CMV), Epstein–Barr virus (EBV) and/or human herpes 6 virus (HHV6) infection/reactivation (12/50 vs. 21/47, p = 0.032). Finally, high levels (≥0.4%) of CD4+CD25high lymphocytes were significantly associated with better post-transplant survival (56% vs. 38%, four-year survival, p = 0.040). Donors who experience CMV infection/reactivation provide the recipients with lymphocytes, which readily reinforce the recovery of the transplanted patients’ immune system. PMID:25807050

Carrier providers or killers: The case of Cu defects in CdTe

DOE PAGES

Yang, Ji -Hui; Metzger, Wyatt K.; Wei, Su -Huai

2017-07-24

Defects play important roles in semiconductors for optoelectronic applications. Common intuition is that defects with shallow levels act as carrier providers and defects with deep levels are carrier killers. Here, taking the Cu defects in CdTe as an example, we show that relatively shallow defects can play both roles. Using first-principles calculation methods combined with thermodynamic simulations, we study the dialectic effects of Cu-related defects on hole density and lifetime in bulk CdTe. Because CuCd can form a relatively shallow acceptor, we find that increased Cu incorporation into CdTe indeed can help achieve high hole density; however, too much Cumore » can cause significant non-radiative recombination. We discuss strategies to balance the contradictory effects of Cu defects based on the calculated impact of Cd chemical potential, copper defect concentrations, and annealing temperature on lifetime and hole density. Lastly, these findings advance the understanding of the potential complex defect behaviors of relatively shallow defect states in semiconductors.« less

Carrier providers or killers: The case of Cu defects in CdTe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Ji -Hui; Metzger, Wyatt K.; Wei, Su -Huai

Defects play important roles in semiconductors for optoelectronic applications. Common intuition is that defects with shallow levels act as carrier providers and defects with deep levels are carrier killers. Here, taking the Cu defects in CdTe as an example, we show that relatively shallow defects can play both roles. Using first-principles calculation methods combined with thermodynamic simulations, we study the dialectic effects of Cu-related defects on hole density and lifetime in bulk CdTe. Because CuCd can form a relatively shallow acceptor, we find that increased Cu incorporation into CdTe indeed can help achieve high hole density; however, too much Cumore » can cause significant non-radiative recombination. We discuss strategies to balance the contradictory effects of Cu defects based on the calculated impact of Cd chemical potential, copper defect concentrations, and annealing temperature on lifetime and hole density. Lastly, these findings advance the understanding of the potential complex defect behaviors of relatively shallow defect states in semiconductors.« less

Cadmium tolerance and accumulation in cultivars of a high-biomass tropical tree (Averrhoa carambola) and its potential for phytoextraction.

PubMed

Li, J T; Liao, B; Lan, C Y; Ye, Z H; Baker, A J M; Shu, W S

2010-01-01

Averrhoa carambola is a high-biomass tropical tree that has been identified as a Cd accumulator. In the present study, field survey, pot, and hydroponic experiments were conducted to investigate the variation of Cd tolerance and accumulation in cultivars of A. carambola as well as its potential for phytoextraction. In the field survey, it was found that concentrations of Cd in aerial tissues of A. carambola varied greatly among sites and cultivars. The Cd bioconcentration factors (BCFs) and Cd removals by the field-grown A. carambola differed significantly among sites but not among cultivars. Nonetheless, all four carambola cultivars investigated were able to accumulate considerably high concentrations of Cd in their shoots, which indicated that the 4-yr-old carambola stands could remove 0.3 to 51.8% of the total Cd content in the top 20-cm soil layer. When cultured in Cd-spiked soils, the carambola cultivar Hua-Di always showed higher Cd tolerance than the other cultivars; however, this tendency was not confirmed by hydroponic experiment. The Cd BCFs of cultivar Thailand grown in soils with 6 and 12 mg Cd kg(-1) were highest among cultivars, whereas this trend was reversed at 120 mg Cd kg(-1) treatment. Nevertheless, the pot- and hydroponics-grown carambola cultivars generally showed higher capacities to tolerate and accumulate Cd, compared with the control species. The present results indicate that a strong ability to tolerate and accumulate Cd seems to be a trait at the species level in A. carambola, although some degree of variances in both Cd tolerance and accumulation exists among cultivars.

NREL Collaboration Breaks 1-Volt Barrier in CdTe Solar Technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

2016-05-01

NREL scientists have worked with Washington State University and the University of Tennessee to improve the maximum voltage available from CdTe solar cells. Changes in dopants, stoichiometry, interface design, and defect chemistry improved the CdTe conductivity and carrier lifetime by orders of magnitude, thus enabling CdTe solar cells with open-circuit voltages exceeding 1 volt for the first time. Values of current density and fill factor for CdTe solar cells are already at high levels, but sub-par voltages has been a barrier to improved efficiencies. With voltages pushed beyond 1 volt, CdTe cells have a path to produce electricity at costsmore » less than fossil fuels.« less

Cytomegalovirus persistence and T-cell immunosenescence in people aged fifty and older: A systematic review.

PubMed

Weltevrede, Marlies; Eilers, Renske; de Melker, Hester E; van Baarle, Debbie

2016-05-01

Immunosenescence is the age-related deterioration of immunocompetence which is reflected in a poorer response to new antigens. This process is characterized by decreases in naïve T cells and increases in memory T cells. The highly prevalent β-herpesvirus cytomegalovirus (CMV) is thought to enhance T-cell immunosenescence. The aim of this study was to perform a systematic review on the current evidence regarding the relation between CMV-infection and immunosenescence in Western people aged fifty years and older. Studies that investigated the relation between CMV infection and immune parameters in Western people aged 50 years and older were eligible for inclusion. No restrictions were placed on study type. This article focuses on the relation between CMV infections as measured by serology and T cell subsets. A narrative approach to data synthesis was applied. In the majority of included studies higher levels of Effector Memory (EM) and TEMRA (Effector Memory T cells re-expressing CD45RA) cells were found in the CD4+ and the CD8+ T cell pools in CMV-seropositive elderly compared to CMV-seronegative elderly. No clear evidence was found for lower levels of naïve T cells in CMV-seropositive elderly compared to CMV-seronegative elderly. The total CD8+ T cell pool appeared to be larger in CMV-seropositive elderly in three out of four studies, while the total CD4+ T cell pool appeared to be smaller in CMV-seropositive elderly in two out of four studies. CMV seems to enhance immunosenescence based on the high levels of the highly differentiated EM and TEMRA cells in the CD8+ and CD4+ T cell pools. The relation of the shifts within the T cell compartments in CMV-seropositive elderly in relation to susceptibility to infectious diseases remains to be investigated. Copyright © 2016 Elsevier Inc. All rights reserved.

Zinc, lead, and cadmium levels in serum and milk of lactating women in Ibadan, Nigeria.

PubMed

Edem, Victory Fabian; Akintunde, Kikelomo; Adelaja, Yewande Adeola; Nwozo, Sarah O; Charles-Davies, Mabel

2017-01-01

Zinc (Zn) is known to interact with lead (Pb) and cadmium (Cd) reversing their toxicity and reducing their concentrations. However, lactating women are at high risk of developing Zn deficiency, which may result in Pb and Cd intoxication or increased exposure of breast-fed infants to Pb and Cd from breast milk. The aim of this study was to determine Zn, Pb, and Cd concentrations and examine their relationship in serum and breast milk of lactating women in Ibadan, Nigeria. Ninety-two lactating women were recruited into this study. Anthropometric measurements were assessed by standard methods while serum and breast milk concentrations of Zn, Pb, and Cd were assessed by atomic absorption spectrophotometry. Data analyzed statistically by Student's t test, Pearson's correlation coefficient, and a multiple regression model were significant at p < 0.05. Zn deficiency was observed in 12 (17.1%) of lactating women. Breast milk levels of Zn, Pb, and Cd were significantly higher than their levels in serum, whereas the ratios Zn:Pb and Zn:Cd in milk were significantly less than serum ratios. Significant negative correlation was observed between milk Pb and serum Zn:Pb while milk Cd correlated positively with milk Zn. Significant positive correlations were observed between serum Zn and serum Zn:Pb, serum Zn and serum Zn:Cd, as well as serum Zn:Cd and serum Zn:Pb. Serum Cd and serum Zn were significantly negatively related. Significant negative correlations between serum Pb and serum Zn:Pb as well as milk Zn:Pb. Serum Cd and serum Zn:Pb as well as serum Zn:Cd correlated negatively. Milk Cd and Zn/Cd positively related with milk Pb while milk Zn was a negatively related with milk Pb in a multiple regression model ( R 2 = 0.333; p = 0.023). Breast milk may be contaminated by toxic metals. However, Zn supplementation in deficient mothers may protect maternal and infant health.

Chinese medicine Ginseng and Astragalus granules ameliorate autoimmune diabetes by upregulating both CD4+FoxP3+ and CD8+CD122+PD1+ regulatory T cells.

PubMed

Wang, Yeshu; Xie, Qingfeng; Liang, Chun-Ling; Zeng, Qiaohuang; Dai, Zhenhua

2017-09-01

Type 1 diabetes mellitus (T1DM) is an autoimmune disease mainly mediated by effector T cells that are activated by autoantigen, thereby resulting in the destruction of pancreatic islets and deficiency of insulin. Cyclosporine is widely used as an immunosuppressant that suppresses autoimmunity in clinic. However, continuous treatments with conventional immunosuppressive drugs may cause severe side effects. Therefore it is important to seek alternative medicine. Chinese medicine Ginseng and Astragalus granule (GAG) was used to successfully treat type 2 diabetes mellitus in clinic in China. Here we found that GAG ameliorated T1DM in autoimmune NOD mice by increasing the level of insulin and reducing the level of blood glucose. Treatments with both GAG and CsA further decreased the blood glucose level. Moreover, GAG increased both CD4+FoxP3+ and CD8+CD122+PD-1+ Treg numbers in both spleens and lymph nodes of NOD mice. In particular, GAG could reverse a decline in CD4+FoxP3+ Tregs resulted from CsA treatments. The percentage of effector/memory CD8+ T cells (CD44 high CD62L low ) was significantly reduced by GAG, especially in the presence of low-doses of CsA. Histopathology also showed that GAG attenuated cellular infiltration and lowered CD3+ T cell numbers around and in islets. Thus, we demonstrated that GAG ameliorated autoimmune T1DM by upregulating both CD4+FoxP3+ and CD8+CD122+PD-1+ Tregs while GAG synergized with CsA to further suppress autoimmunity and T1DM by reversing the decline in CD4+FoxP3+ Tregs resulted from CsA treatments. This study may have important clinical implications for the treatment of T1DM using traditional Chinese medicine.

Relationships among DNA hypomethylation, Cd, and Pb exposure and risk of cigarette smoking-related urothelial carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Chi-Jung

Cigarette smoking and environmental exposure to heavy metals are important global health issues, especially for urothelial carcinoma (UC). However, the effects of cadmium and lead exposure, as well as the levels of DNA hypomethylation, on UC risk are limited. We evaluated the possible exposure sources of Cd and Pb and the relationship among DNA hypomethylation, urinary Cd and Pb levels, and UC risk. We recruited 209 patients with UC and 417 control patients for a hospital-based case–control study between June 2011 and August 2014. We collected environmental exposure-related information with questionnaires. Blood and urine samples were analyzed to measure themore » Cd and Pb exposure and 5-methyl-2′-deoxycytidine levels as a proxy for DNA methylation. Multivariate logistic regression and 95% confidence intervals were applied to estimate the risk for UC. Study participants with high Cd and Pb exposure in blood or urine had significantly increased risk of UC, especially among the smokers. After adjusting for age and gender, the possible connections of individual cumulative cigarette smoking or herb medicine exposure with the increased levels of Cd and Pb were observed in the controls. Participants with 8.66%–12.39% of DNA hypomethylation had significantly increased risk of UC compared with those with ≥ 12.39% of DNA hypomethylation. Environmental factors including cigarette smoking and herb medicine may contribute to the internal dose of heavy metals levels. Repeat measurements of heavy metals with different study design, detailed dietary information, and types of herb medicine should be recommended for exploring UC carcinogenesis in future studies. - Highlights: • Smoking and herb medicine ingestion is associated with increased urinary Cd and Pb levels. • Urinary levels of Cd and Pb are associated with increased risk of UC. • UC carcinogenesis might have partially resulted from DNA hypomethylation.« less

High intracytoplasmatic levels of Il-4 and Il-5 in a patient with Gleichs syndrome: case report.

PubMed

Novembre, E; Mori, F; Arcangeli, F; Cianferoni, A; Bernardini, R; Pucci, N; Annunziato, F; Parronchi, P; De Martino, M; Vierucci, A

2006-01-01

Gleichs syndrome is characterized by recurrent localized angioedema, hypereosinophilia, elevated levels of IgM, rapid weight gain, itchy urticaria and fever. Little is known about the pathogenesis of this disease. Increased serum levels for IL5, IL6 and C5a have been reported before and during clinical exacerbations. In order to better understand the role of the T cells in Gleichs syndrome we analyzed the intracellular cytokine expression in CD3+ cells of a patient affected by the disease. As hypereosinophilia was documented, we asked whether IL-4 and IL-5 levels were increased, and the intracytoplasmatic expression of these Th2-cytokines was determined. The percentage of T lymphocytes (CD3-gated cells) of both CD8- and CD8+ phenotype expressing different cytokines showed an unusually high percentage of Th2-related cytokine (IL-4, IL-5 and IL-13) expressing T lymphocytes. The two new variants (myeloproliferative and lymphoproliferative) seem to account for hypereosinophilia in patients with hypereosinophilic syndrome (HES). In the lymphroliferative variant, the presence of a clonal CD3-CD4+ Th2 like lymphocyte secreting IL-4 and IL-5 in peripheral blood, may explain the hypereosinophilia and the hyper-IgE. In our study we show that the patient had a lymphoproliferative variant and her T cell had a Th2 type phenotype. Moreover, we suggest that Th2 lymphocytes may play a role in the pathogenesis of Gleichs syndrome. Further studies are needed to evaluate the possibility that a polyclonal aspecific activation of Th2 type cells can lead to hypereosinophilia, IgE production and the other manifestations typical of Gleichs syndrome.

Development and validation of a fluorescent microsphere immunoassay for soluble CD30 testing.

PubMed

Pavlov, Igor; Martins, Thomas B; Delgado, Julio C

2009-09-01

Testing for soluble CD30 (sCD30), an indicator of Th2 immune response, is a useful prognostic marker in solid organ transplantation, lymphoproliferative disorders, autoimmunity, and various parasitic diseases. In this study we report the development and validation of a fluorescent microsphere immunoassay for the detection of sCD30 in serum, plasma, and culture supernatants. The dynamic range of this assay is 1 to 400 ng/ml, and the rate of recovery of various concentrations of recombinant sCD30 ranges from 97 to 116% (average recovery, 105%). The test showed a high degree of precision in both intra-assay and interassay studies (coefficients of variation, as high as 7% and 8%, respectively), with a sensitivity of 1 ng/ml. The normal reference range calculated for a cohort of 151 healthy individuals was 1 to 29 ng/ml. The clinical usefulness of the sCD30 fluorescent microsphere immunoassay was demonstrated by showing that levels of sCD30 have a positive correlation with specimens containing high titers of anti-double-stranded DNA antibodies and high titers of immunoglobulin G against Leishmania species. Given the multiplexing potential of the sCD30 fluorescent microsphere immunoassay reported in this study, it is expected that testing of sCD30 concentrations along with those of other cytokines will become an important diagnostic tool for selected immunological and inflammatory diseases where Th2-type cytokine responses have been reported.

Development and Validation of a Fluorescent Microsphere Immunoassay for Soluble CD30 Testing▿

PubMed Central

Pavlov, Igor; Martins, Thomas B.; Delgado, Julio C.

2009-01-01

Testing for soluble CD30 (sCD30), an indicator of Th2 immune response, is a useful prognostic marker in solid organ transplantation, lymphoproliferative disorders, autoimmunity, and various parasitic diseases. In this study we report the development and validation of a fluorescent microsphere immunoassay for the detection of sCD30 in serum, plasma, and culture supernatants. The dynamic range of this assay is 1 to 400 ng/ml, and the rate of recovery of various concentrations of recombinant sCD30 ranges from 97 to 116% (average recovery, 105%). The test showed a high degree of precision in both intra-assay and interassay studies (coefficients of variation, as high as 7% and 8%, respectively), with a sensitivity of 1 ng/ml. The normal reference range calculated for a cohort of 151 healthy individuals was 1 to 29 ng/ml. The clinical usefulness of the sCD30 fluorescent microsphere immunoassay was demonstrated by showing that levels of sCD30 have a positive correlation with specimens containing high titers of anti-double-stranded DNA antibodies and high titers of immunoglobulin G against Leishmania species. Given the multiplexing potential of the sCD30 fluorescent microsphere immunoassay reported in this study, it is expected that testing of sCD30 concentrations along with those of other cytokines will become an important diagnostic tool for selected immunological and inflammatory diseases where Th2-type cytokine responses have been reported. PMID:19605595

Fuzhengpaidu granule regulates immune activation molecules CD38 and human leukocyte antigen-D related on CD4+ and CD8+ T cells in patients with acquired immunodeficiency syndrome/human immunodeficiency virus.

PubMed

Jiang, Feng; Zhang, Rongxin; Gu, Zhenfang; Zhang, Huailing; Guo, Huijun; Deng, Xin; Liang, Jian

2013-08-01

To evaluate the effect of Fuzhengpaidu granule (FZPDG) on immune activation molecules CD38 and human leukocyte antigen-D related (HLA-DR) on CD4+ and CD8+ cells in HIV/AIDS patients, and to explore the underlying mechanism of this therapy. Plasma changes in CD3+, CD4+, CD8+, CD3 + CD4 + CD38 +, CD3 + CD4 + HLA-DR+, CD3 + CD8+CD38+, and CD3+CD8+HLA-DR+ levels in HIV/ AIDS patients treated with FZPDG for six months were examined by flow cytometry and compared with levels in healthy controls. The clinical trial included 34 outpatients with HIV/AIDS. Before treatment, plasma levels of CD38+ and HLA-DR+ on CD4/CD8 cells were higher than those in 28 health controls (P < 0.05). There were no significant changes in serum levels of CD3+, CD4+, and CD8+ T cells between pretreatment baseline versus after treatment, which were 82.85% +/- 5.41%, 14.57% +/- 10.31% and 54.55% +/- 11.43% before treatment and 79.15% +/- 8.21%, 19.96% +/- 9.58% and 56.36% +/- 11.67% after treatment, respectively (P > 0.05). Plasma levels of CD3+ CD4+CD38+ and CD3+CD4+HLA-DR+ were 2.3% +/-2.2% and 7.8% +/- 5.5% before treatment and 1.2% +/-0.8% and 2.6% +/- 1.0% after treatment, respectively. Plasma levels of CD3+CD8+CD38+ and CD3+CD8+ HLA-DR+ were 41.4% +/- 13.4% and 17.8% +/- 11.3% before treatment, which changed to 27.1% +/- 10.2% and 3.8% +/- 2.4% after treatment, respectively (P < 0.05). HIV/AIDS patients exhibited an immune activation profile following FZPDG treatment. A potential mechanism of action for FZPDG appears to lie in its ability to up-regulate CD38 and HLA-DR levels on CD4+ T cells, and down-regulate them on CD8+ cells, thereby modulating immune activation of CD4+and CD8+T cells.

Cadmium accumulation in the rootless macrophyte Wolffia globosa and its potential for phytoremediation.

PubMed

Xie, Wan-Ying; Huang, Qing; Li, Gang; Rensing, Christopher; Zhu, Yong-Guan

2013-01-01

Cadmium (Cd) pollution around the world is a serious issue demanding acceptable solutions, one of which is phytoremediation that is both cost-effective and eco-friendly. Removal of Cd from contaminated water using plants with high growth rates and sufficient Cd accumulation abilities could be an appropriate choice. Here, we investigated a potential Cd accumulator, Wolffia, a rootless duckweed with high growth rate. Cd uptake, accumulation, tolerance, and phytofiltration ability by Wolffia globosa were examined. Furthermore, the effects of arsenic (As) on Cd uptake and phytofiltration by W. globosa were also studied. Cd uptake kinetics showed a linear pattern and a hyperbolic pattern without a plateau in lower (0-2 microM) and higher (0-200 microM) Cd concentration ranges, respectively, suggesting rapid Cd uptake by W. globosa Cd accumulation ability by W. globosa was higher at Cd concentrations < 10 microM than at >10 microM. All the five species of Wolffia exposed to I microM Cd for 5 days accumulated > 500 mg Cd kg(-1) DW. Ten gram fresh W. globosa could diminish almost all the Cd (2 microM) in a 200 mL solution. This enormous accumulation ability was mostly due to passive adsorption of Cd by the apoplast. Arsenic had no significant effect on Cd uptake and phytofiltration. The fresh fronds also showed a great As extracting ability. The results indicated that Wolffia is a strong Cd accumulator and has great Cd phytoremediation potential. Therefore, this plant can be used in fresh aquatic environments co-contaminated by low-levels of Cd and As.

Revisiting liver disease progression in HIV/HCV-coinfected patients: the influence of vitamin D, insulin resistance, immune status, IL28B and PNPLA3.

PubMed

Mandorfer, Mattias; Payer, Berit A; Schwabl, Philipp; Steiner, Sebastian; Ferlitsch, Arnulf; Aichelburg, Maximilian C; Stättermayer, Albert F; Ferenci, Peter; Obermayer-Pietsch, Barbara; Grabmeier-Pfistershammer, Katharina; Trauner, Michael; Peck-Radosavljevic, Markus; Reiberger, Thomas

2015-03-01

To perform a comprehensive study on independent modulators of liver fibrosis progression and determinants of portal pressure considering immune status, insulin resistance (IR), serum 25-hydroxyvitamin D (25(OH)D) levels, genetic variants of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and interleukin 28B (IL28B) in a thoroughly documented cohort of HIV/hepatitis C-coinfected (HIV/HCV) patients. 25(OH)D deficiency (25(OH)DDEF), IR and low CD4(+) T-lymphocyte nadir (lowCD4NAD) were defined as 25(OH)D <20 ng × ml(-1) , HOMA-IR >2 and CD4nadir <200 cells × μl(-1) respectively. Liver fibrosis progression rate (FPR) was calculated as METAVIR F units divided by the number of years since HCV infection. Patients with a FPR > median FPR were assigned to the highFPR group. Among 86 HIV/HCV, the median FPR was 0.167 units × years(-1) . While the prevalence of prior alcohol abuse, lowCD4NAD and 25(OH)DDEF was higher among highFPR patients, the prevalence of IR was comparable. The association between 25(OH)DDEF and FPR was confirmed in a subgroup of patients with METAVIR stage F0/F1/F2 in which 25(OH)D levels are not affected by the severity of liver disease. The distribution of IL28B C/C and PNPLA3 non-C/C was similar, while PNPLA3 G/G was exclusively observed in highFPR patients. LowCD4NAD (OR: 2.95; 95% CI: 1.05-8.24; P = 0.039) and 25(OH)DDEF (OR: 5.62; 95% CI: 2.05-15.38; P = 0.001) were independently associated with highFPR and showed an additive effect. Portal pressure correlated with prior alcohol abuse, HCV-genotype 3, CD4(+) nadir and 25(OH)D levels. Two potentially modifiable factors, CD4(+) nadir and 25(OH)D levels, were both independent modulators of liver fibrosis progression and determinants of portal pressure. Further studies are warranted to assess the relevance of PNPLA3 for FPR in HIV/HCV. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of cadmium on the physiological parameters and the subcellular cadmium localization in the potato (Solanum tuberosum L.).

PubMed

Xu, Dongyu; Chen, Zhifan; Sun, Ke; Yan, Dong; Kang, Mingjie; Zhao, Ye

2013-11-01

The pollution of agricultural soils with cadmium (Cd) has become a serious problem worldwide. The potato (Solanum tuberosum L.) was used to investigate how different concentrations of Cd (1, 5, and 25mgkg(-1)) affected the physiological parameters and the subcellular distribution of Cd in the potato. The analyses were conducted using scanning electron microscopy coupled with energy dispersive X-ray (SEM-EDX). The results suggest that the leaf is the organ with the highest accumulation of Cd. The malondialdehyde (MDA) content increased and the chlorophyll content decreased in response to high level of Cd. The SEM-EDX microanalysis revealed that Cd was primarily deposited in the spongy and palisade tissues of the leaf. Furthermore, Cd was also detected in the cortex and the adjacent phloem and was observed inside the intercellular space, the interior surface of the plasma membrane, and on the surface of the elliptical starch granules in the tubers of the potato. Although low concentrations of Cd migrated from the root to the tuber, the accumulation of Cd in the tuber exceeded the standard for food security. Therefore, the planting of potato plants in farmland containing Cd should be seriously evaluated because Cd-containing potatoes might present high health risk to humans. Copyright © 2013 Elsevier Inc. All rights reserved.

Accumulation of M1-like macrophages in type 2 diabetic islets is followed by a systemic shift in macrophage polarization.

PubMed

Cucak, Helena; Grunnet, Lars Groth; Rosendahl, Alexander

2014-01-01

Human T2D is characterized by a low-grade systemic inflammation, loss of β-cells, and diminished insulin production. Local islet immunity is still poorly understood, and hence, we evaluated macrophage subpopulations in pancreatic islets in the well-established murine model of T2D, the db/db mouse. Already at 8 weeks of disease, on average, 12 macrophages were observed in the diabetic islets, whereas only two were recorded in the nondiabetic littermates. On a detailed level, the islet resident macrophages increased fourfold compared with nondiabetic littermates, whereas a pronounced recruitment (eightfold) of a novel subset of macrophages (CD68+F4/80-) was observed. The majority of the CD68+F4/80+ but only 40% of the CD68+F4/80- islet macrophages expressed CD11b. Both islet-derived macrophage subsets expressed moderate MHC-II, high galectin-3, and low CD80/CD86 levels, suggesting the cells to be macrophages rather than DCs. On a functional level, the vast majority of the macrophages in the diabetic islets was of the proinflammatory, M1-like phenotype. The systemic immunity in diabetic animals was characterized by a low-grade inflammation with elevated cytokine levels and increase of splenic cytokine, producing CD68+F4/80- macrophages. In late-stage diabetes, the cytokine signature changed toward a TGF-β-dominated profile, coinciding with a significant increase of galectin-3-positive macrophages in the spleen. In summary, our results show that proinflammatory M1-like galectin-3+ CD80/CD86(low) macrophages invade diabetic islets. Moreover, the innate immunity matures in a diabetes-dependent manner from an initial proinflammatory toward a profibrotic phenotype, supporting the concept that T2D is an inflammatory disease.

Human Beta Defensin 2 Selectively Inhibits HIV-1 in Highly Permissive CCR6⁺CD4⁺ T Cells.

PubMed

Lafferty, Mark K; Sun, Lingling; Christensen-Quick, Aaron; Lu, Wuyuan; Garzino-Demo, Alfredo

2017-05-16

Chemokine receptor type 6 (CCR6)⁺CD4⁺ T cells are preferentially infected and depleted during HIV disease progression, but are preserved in non-progressors. CCR6 is expressed on a heterogeneous population of memory CD4⁺ T cells that are critical to mucosal immunity. Preferential infection of these cells is associated, in part, with high surface expression of CCR5, CXCR4, and α4β7. In addition, CCR6⁺CD4⁺ T cells harbor elevated levels of integrated viral DNA and high levels of proliferation markers. We have previously shown that the CCR6 ligands MIP-3α and human beta defensins inhibit HIV replication. The inhibition required CCR6 and the induction of APOBEC3G. Here, we further characterize the induction of apolipoprotein B mRNA editing enzyme (APOBEC3G) by human beta defensin 2. Human beta defensin 2 rapidly induces transcriptional induction of APOBEC3G that involves extracellular signal-regulated kinases 1/2 (ERK1/2) activation and the transcription factors NFATc2, NFATc1, and IRF4. We demonstrate that human beta defensin 2 selectively protects primary CCR6⁺CD4⁺ T cells infected with HIV-1. The selective protection of CCR6⁺CD4⁺ T cell subsets may be critical in maintaining mucosal immune function and preventing disease progression.

Salicylic Acid Alleviates the Cadmium Toxicity in Barley Seedlings1

PubMed Central

Metwally, Ashraf; Finkemeier, Iris; Georgi, Manfred; Dietz, Karl-Josef

2003-01-01

Salicylic acid (SA) plays a key role in plant disease resistance and hypersensitive cell death but is also implicated in hardening responses to abiotic stressors. Cadmium (Cd) exposure increased the free SA contents of barley (Hordeum vulgare) roots by a factor of about 2. Cultivation of dry barley caryopses presoaked in SA-containing solution for only 6 h or single transient addition of SA at a 0.5 mm concentration to the hydroponics solution partially protected the seedlings from Cd toxicity during the following growth period. Both SA treatments had little effect on growth in the absence of Cd, but increased root and shoot length and fresh and dry weight and inhibited lipid peroxidation in roots, as indicated by malondialdehyde contents, in the presence of Cd. To test whether this protection was due to up-regulation of antioxidant enzymes, activities and transcript levels of the H2O2-metabolizing enzymes such as catalase and ascorbate peroxidase were measured in control and SA-treated seedlings in the presence or absence of 25 μm Cd. Cd stress increased the activity of these enzymes by variable extent. SA treatments strongly or completely suppressed the Cd-induced up-regulation of the antioxidant enzyme activities. Slices from leaves treated with SA for 24 h also showed an increased level of tolerance toward high Cd concentrations as indicated by chlorophyll a fluorescence parameters. The results support the conclusion that SA alleviates Cd toxicity not at the level of antioxidant defense but by affecting other mechanisms of Cd detoxification. PMID:12746532

CD127 and CD25 Expression Defines CD4+ T Cell Subsets That Are Differentially Depleted during HIV Infection1

PubMed Central

Dunham, Richard M.; Cervasi, Barbara; Brenchley, Jason M.; Albrecht, Helmut; Weintrob, Amy; Sumpter, Beth; Engram, Jessica; Gordon, Shari; Klatt, Nichole R.; Frank, Ian; Sodora, Donald L.; Douek, Daniel C.; Paiardini, Mirko; Silvestri, Guido

2009-01-01

Decreased CD4+ T cell counts are the best marker of disease progression during HIV infection. However, CD4+ T cells are heterogeneous in phenotype and function, and it is unknown how preferential depletion of specific CD4+ T cell subsets influences disease severity. CD4+ T cells can be classified into three subsets by the expression of receptors for two T cell-tropic cytokines, IL-2 (CD25) and IL-7 (CD127). The CD127+CD25low/− subset includes IL-2-producing naive and central memory T cells; the CD127−CD25− subset includes mainly effector T cells expressing perforin and IFN-γ; and the CD127lowCD25high subset includes FoxP3-expressing regulatory T cells. Herein we investigated how the proportions of these T cell subsets are changed during HIV infection. When compared with healthy controls, HIV-infected patients show a relative increase in CD4+CD127−CD25− T cells that is related to an absolute decline of CD4+CD127+CD25low/− T cells. Interestingly, this expansion of CD4+CD127− T cells was not observed in naturally SIV-infected sooty mangabeys. The relative expansion of CD4+CD127−CD25− T cells correlated directly with the levels of total CD4+ T cell depletion and immune activation. CD4+CD127−CD25− T cells were not selectively resistant to HIV infection as levels of cell-associated virus were similar in all non-naive CD4+ T cell subsets. These data indicate that, during HIV infection, specific changes in the fraction of CD4+ T cells expressing CD25 and/or CD127 are associated with disease progression. Further studies will determine whether monitoring the three subsets of CD4+ T cells defined based on the expression of CD25 and CD127 should be used in the clinical management of HIV-infected individuals. PMID:18390743

Microarray-based analysis of cadmium-responsive microRNAs in rice (Oryza sativa)

PubMed Central

Ding, Yanfei; Chen, Zhen; Zhu, Cheng

2011-01-01

MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate specific target mRNAs at the post-transcriptional level. Plant miRNAs have been implicated in developmental processes and adaptations to environmental stresses. Cadmium (Cd) is a non-essential heavy metal that is highly toxic to plants. To investigate the responsive functions of miRNAs under Cd stress, miRNA expression in Cd-stressed rice (Oryza sativa) was profiled using a microarray assay. A total of 19 Cd-responsive miRNAs were identified, of which six were further validated experimentally. Target genes were also predicted for these Cd-responsive miRNAs, which encoded transcription factors, and proteins associated with metabolic processes or stress responses. In addition, the mRNA levels of several targets were negatively correlated with the corresponding miRNAs under Cd stress. Promoter analysis showed that metal stress-responsive cis-elements tended to occur more frequently in the promoter regions of Cd-responsive miRNAs. These findings suggested that miRNAs played an important role in Cd tolerance in rice, and highlighted a novel molecular mechanism of heavy metal tolerance in plants. PMID:21362738

IL-15 induces CD8+ T cells to acquire functional NK receptors capable of modulating cytotoxicity and cytokine secretion.

PubMed

Correia, Margareta P; Costa, Alexandra V; Uhrberg, Markus; Cardoso, Elsa M; Arosa, Fernando A

2011-05-01

During the last years several authors have described a small population of CD8+ T cells expressing NK receptors (NKRs). Although their origin remains largely unknown, we have recently demonstrated that IL-15 is capable of inducing NKR expression in purified human CD8+CD56- T cells. In this study we show that IL-15-driven NKR induction in CD8+ T cells was linked with CD56 de novo acquisition, consistent with an effector-memory phenotype, increased anti-apoptotic levels, high granzyme B/perforin expression and with the ability of displaying in vitro NK-like cytotoxicity. Interestingly, dissection of NKR functional outcome in IL-15-cultured CD8+ T cells revealed: (i) that NKG2D cross-linking was able per se to upregulate degranulation levels and (ii) that KIR and NKG2A cross-linking upregulated secretion of cytokines such as IFN-γ, TNF-α, IL-1β and IL-10. These results suggest that IL-15 is capable of differentiating CD8+ T cells into NK-like T cells displaying a regulatory phenotype. Copyright © 2010 Elsevier GmbH. All rights reserved.

Association of Glioblastoma Multiforme Stem Cell Characteristics, Differentiation, and Microglia Marker Genes with Patient Survival

PubMed Central

Balz, Ellen; Herzog, Susann; Plantera, Laura; Vogelgesang, Silke; Seifert, Carolin; Bialke, Angela; Venugopal, Chitra; Singh, Sheila K.; Hoffmann, Wolfgang; Schroeder, Henry W. S.

2018-01-01

Patients with glioblastoma multiforme (GBM) are at high risk to develop a relapse despite multimodal therapy. Assumedly, glioma stem cells (GSCs) are responsible for treatment resistance of GBM. Identification of specific GSC markers may help to develop targeted therapies. Here, we performed expression analyses of stem cell (ABCG2, CD44, CD95, CD133, ELF4, Nanog, and Nestin) as well as differentiation and microglia markers (GFAP, Iba1, and Sparc) in GBM compared to nonmalignant brain. Furthermore, the role of these proteins for patient survival and their expression in LN18 stem-like neurospheres was analyzed. At mRNA level, ABCG2 and CD95 were reduced, GFAP was unchanged; all other investigated markers were increased in GBM. At protein level, CD44, ELF4, Nanog, Nestin, and Sparc were elevated in GBM, but only CD133 and Nestin were strongly associated with survival time. In addition, ABCG2 and GFAP expression was decreased in LN18 neurospheres whereas CD44, CD95, CD133, ELF4, Nanog, Nestin, and Sparc were upregulated. Altogether only CD133 and Nestin were associated with survival rates. This raises concerns regarding the suitability of the other target structures as prognostic markers, but makes both CD133 and Nestin candidates for GBM therapy. Nevertheless, a search for more specific marker proteins is urgently needed. PMID:29535786

Ligation of CD8α on human natural killer cells prevents activation-induced apoptosis and enhances cytolytic activity

PubMed Central

Addison, Elena G; North, Janet; Bakhsh, Ismail; Marden, Chloe; Haq, Sumaira; Al-Sarraj, Samia; Malayeri, Reza; Wickremasinghe, R Gitendra; Davies, Jeffrey K; Lowdell, Mark W

2005-01-01

It has been previously shown that the subset of human natural killer (NK) cells which express CD8 in a homodimeric α/α form are more cytotoxic than their CD8– counterparts but the mechanisms behind this differential cytolytic activity remained unknown. Target cell lysis by CD8– NK cells is associated with high levels of effector cell apoptosis, which is in contrast to the significantly lower levels found in the CD8α+ cells after lysis of the same targets. We report that cross-linking of the CD8α chains on NK cells induces rapid rises in intracellular Ca2+ and increased expression of CD69 at the cell surface by initiating the influx of extracellular Ca2+ ions. We demonstrate that secretion of cytolytic enzymes initiates NK-cell apoptosis from which CD8α+ NK cells are protected by an influx of exogenous calcium following ligation of CD8 on the NK-cell surface. This ligation is through interaction with fellow NK cells in the cell conjugate and can occur when the target cells lack major histocompatibility complex (MHC) Class I expression. Protection from apoptosis is blocked by preincubation of the NK cells with anti-MHC Class I antibody. Thus, in contrast to the CD8– subset, CD8α+ NK cells are capable of sequential lysis of multiple target cells. PMID:16236125

Resistance to age-dependent thymic atrophy in long-lived mice that are deficient in pregnancy-associated plasma protein A

PubMed Central

Vallejo, Abbe N.; Michel, Joshua J.; Bale, Laurie K.; Lemster, Bonnie H.; Borghesi, Lisa; Conover, Cheryl A.

2009-01-01

Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase that controls the tissue availability of insulin-like growth factor (IGF). Homozygous deletion of PAPPA in mice leads to lifespan extension. Since immune function is an important determinant of individual fitness, we examined the natural immune ecology of PAPPA−/− mice and their wild-type littermates reared under specific pathogen-free condition with aging. Whereas wild-type mice exhibit classic age-dependent thymic atrophy, 18-month-old PAPPA−/− mice maintain discrete thymic cortex and medulla densely populated by CD4+CD8+ thymocytes that are capable of differentiating into single-positive CD4 and CD8 T cells. Old PAPPA−/− mice have high levels of T cell receptor excision circles, and have bone marrows enriched for subsets of thymus-seeding progenitors. PAPPA−/− mice have an overall larger pool of naive T cells, and also exhibit an age-dependent accumulation of CD44+CD43+ memory T cells similar to wild-type mice. However, CD43+ T cell subsets of old PAPPA−/− mice have significantly lower prevalence of 1B11 and S7, glycosylation isoforms known to inhibit T cell activation with normal aging. In bioassays of cell activation, splenic T cells of old PAPPA−/− mice have high levels of activation antigens and cytokine production, and also elicit Ig production by autologous B cells at levels equivalent to young wild-type mice. These data suggest an IGF-immune axis of healthy longevity. Controlling the availability of IGF in the thymus by targeted manipulation of PAPPA could be a way to maintain immune homeostasis during postnatal development and aging. PMID:19549878

Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia

PubMed Central

Porter, David L.; Levine, Bruce L.; Kalos, Michael; Bagg, Adam; June, Carl H.

2012-01-01

SUMMARY We designed a lentiviral vector expressing a chimeric antigen receptor with specificity for the B-cell antigen CD19, coupled with CD137 (a costimulatory receptor in T cells [4-1BB]) and CD3-zeta (a signal-transduction component of the T-cell antigen receptor) signaling domains. A low dose (approximately 1.5×105 cells per kilogram of body weight) of autologous chimeric antigen receptor–modified T cells reinfused into a patient with refractory chronic lymphocytic leukemia (CLL) expanded to a level that was more than 1000 times as high as the initial engraftment level in vivo, with delayed development of the tumor lysis syndrome and with complete remission. Apart from the tumor lysis syndrome, the only other grade 3/4 toxic effect related to chimeric antigen receptor T cells was lymphopenia. Engineered cells persisted at high levels for 6 months in the blood and bone marrow and continued to express the chimeric antigen receptor. A specific immune response was detected in the bone marrow, accompanied by loss of normal B cells and leukemia cells that express CD19. Remission was ongoing 10 months after treatment. Hypogammaglobulinemia was an expected chronic toxic effect. PMID:21830940

Prognostic Value of Cd95, Active Caspase-3, and Bcl-2 Expression in Adult Patients With De Novo Acute Lymphoblastic Leukemia.

PubMed

Montiel-Cervantes, Laura Arcelia; Reyes-Maldonado, Elba; Garcia-Chavez, Jaime; Hernandez-Caballero, Alvaro; Molina-Aguilar, Rubiraida; Garcia-Ruiz Esparza, Miriam America; Vela-Ojeda, Jorge

2018-04-18

Acute lymphoblastic leukemia is an aggressive malignant disease with high mortality rates in adults. The expression levels of CD95, active caspase-3, and Bcl-2 were determined in 111 patients with de novo acute lymphoblastic leukemia (ALL) and correlated with overall survival (OS) and disease-free survival (DFS). The immunophenotyped ok leukemia and the expression of CD95, active caspase-3, and Bcl-2, were determined by flow cytometry. Apoptotic variables were correlated by Spearman test, and survival by Kaplan-Meier method. Log-rank test was used to compare survival curves. From a total of 111 patients, 56 cases were B-ALL, 16 T-ALL, 16 B-ALL/CD33 + , and 23 ambiguous lineage-AL (AmbLin-AL). The median expression of CD95 (61.5%) and active-caspase-3 (19.4%) was higher in T-ALL (p < 0.05), whereas Bcl-2 was lower in T-ALL (p < 0.038). There was a highly significant correlation in B-ALL, B-ALL/CD33 + and AmbLin-AL between CD95 and Bcl-2, CD95-Active caspase-3, and Bcl-2-Active caspase-3; while in T-ALL, there was only a correlation between CD95-Active caspase-3, and Bcl-2-Active caspase-3. OS and DFS were better for T-ALL than the other groups, especially in patients having higher values of CD95 and active caspase 3, and lower values of Bcl-2. The worse survival rates were observed in patients with B-ALL/CD33 + , and AmbLin-AL. The prognosis of ALL in adults is influenced by the expression levels of Bcl-2, active-caspase-3, and CD95. Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.

Simultaneous evaluation of lymphocyte subpopulations in the liver and in peripheral blood mononuclear cells of HCV-infected patients: relationship with histological lesions

PubMed Central

PERNOLLET, M; JOUVIN-MARCHE, E; LEROY, V; VIGAN, I; ZARSKI, J -P; MARCHE, P N

2002-01-01

Intrahepatic lymphocytes are believed to be involved in the immunopathogenesis of hepatitis C virus (HCV) infection and the evolution of HCV-induced hepatitis. In the present study, we examined the three main intrahepatic lymphocyte subsets, namely CD3+CD56− conventional T lymphocytes, CD3+CD56+ natural T (NT) lymphocytes and CD3−CD56+ natural killer (NK) lymphocytes in HCV-infected patients. The proportion of each lymphocyte subset was evaluated both in liver biopsies and in samples of peripheral blood lymphocytes (PBL) by flow cytometry in 21 patients with histologically proven chronic hepatitis C. Simultaneously, alanine aminotransferase (ALT) levels, viral load and histological lesions were assessed. Neither NT nor NK populations correlated with any biochemical, viral or histological parameters. Furthermore, Vα24+ NT lymphocytes showed no preferential enrichment in the liver of HCV-infected patients. Regarding conventional T lymphocytes, a highly significant linear correlation was found between intrahepatic CD3+CD56− T lymphocytes and the Knodell score, a numerical score for assessing histological activity and fibrosis (r = 0·715, P < 0·0001) and more specifically with the periportal necrosis parameter, which is the main lesion of chronic hepatitis C. In addition, analysis of the peripheral compartment revealed a high correlation between values of CD3+CD56− lymphocytes and both Knodell score (r = 0·624, P = 0·003) and serum ALT levels and again with periportal necrosis. The strong correlation between the proportion of peripheral CD3+CD56− conventional T lymphocytes and the severity of hepatic lesions leads us to propose that evaluation of this accessible peripheral population could be used as an indicator test for the severity of histological lesions in chronic hepatitis C. Abbreviations: PMID:12452844

Spatial luminescence imaging of dopant incorporation in CdTe Films

DOE PAGES

Guthrey, Harvey; Moseley, John; Colegrove, Eric; ...

2017-01-25

State-of-the-art cathodoluminescence (CL) spectrum imaging with spectrum-per-pixel CL emission mapping is applied to spatially profile how dopant elements are incorporated into Cadmium telluride (CdTe). Emission spectra and intensity monitor the spatial distribution of additional charge carriers through characteristic variations in the CL emission based on computational modeling. Our results show that grain boundaries play a role in incorporating dopants in CdTe exposed to copper, phosphorus, and intrinsic point defects in CdTe. Furthermore, the image analysis provides critical, unique feedback to understand dopant incorporation and activation in the inhomogeneous CdTe material, which has struggled to reach high levels of hole density.

Early endothelial damage detected by circulating particles in baboons fed a diet high in simple carbohydrates in conjunction with saturated or unsaturated fat.

PubMed

Shi, Qiang; Hodara, Vida; Meng, Qinghe; Voruganti, V Saroja; Rice, Karen; Michalek, Joel E; Comuzzie, Anthony G; VandeBerg, John L

2014-01-01

Studies have shown that high-fat diets cause blood vessel damage, however, assessing pathological effects accurately and efficiently is difficult. In this study, we measured particle levels of static endothelium (CD31+ and CD105+) and activated endothelium (CD62E+, CD54+ and CD106+) in plasma. We determined individual responses to two dietary regimens in two groups of baboons. One group (n = 10), was fed a diet high in simple carbohydrates and saturated fats (the HSF diet) and the other (n = 8) received a diet high in simple carbohydrates and unsaturated fats (the HUF diet). Plasma samples were collected at 0, 3, and 7 weeks. The percentages of CD31+ and CD62E+ particles were elevated at 3 weeks in animals fed either diet, but these elevations were statistically significant only in animals fed the HUF diet. Surprisingly, both percentages and counts of CD31+ particles were significantly lower at week 7 compared to week 0 and 3 in the HSF group. The median absolute counts of CD105+ particles were progressively elevated over time in the HSF group with a significant increase from week 0 to 7; the pattern was somewhat different for the HUF group with significant increase from week 3 to 7. The counts of CD54+ particles exhibited wide variation in both groups during the dietary challenge, while the median counts of CD106+ particles were significantly lower at week 3 than at week 0 and week 7. Endothelial particles exhibited time-dependent changes, suggesting they were behaving as quantifiable surrogates for the early detection of vascular damage caused by dietary factors.

High CMV IgG antibody levels are associated to a lower CD4+ RESPONSE to antiretroviral therapy in HIV-infected women.

PubMed

Giuliano, Marina; Pirillo, Maria Franca; Liotta, Giuseppe; Andreotti, Mauro; Jere, Haswell; Sagno, Jean-Baptiste; Ciccacci, Fausto; Amici, Roberta; Marazzi, Maria Cristina; Vella, Stefano; Palombi, Leonardo; Mancinelli, Sandro

2017-11-01

Virtually all HIV-infected women in sub-Saharan Africa have evidence of Cytomegalovirus (CMV) infection and levels of specific anti-CMV IgG have been suggested to represent more intense reactivation of subclinical infection. Studies have also shown direct influence of CMV on lymphocytes. The aim of this study was to determine if levels of anti-CMV specific antibodies could impact on the immunological response to antiretroviral treatment (ART) in HIV-infected pregnant women. CMV-specific IgG were measured in HIV-infected pregnant women at 26 weeks of gestation (before ART initiation). Women received ART until 6 months postpartum or indefinitely according to local guidelines at the time of the study. Immunological and virological responses were assessed 6 months and 24 months after delivery. A total of 81 women were studied. At baseline high levels (above the median) of specific IgG were associated to a low CD4+ cell count (P<0.001), a high viral load (P=0.003), and to an older age (P=0.051). In a multivariate model adjusting for baseline CD4+ count, baseline viral load and age, the presence of low levels of CMV IgG was the only independent predictor of a a CD4+ count above 500/mm 3 24 months after delivery among women on continuous therapy. In this cohort, levels of CVM IgG had a significant influence on the immunological response to ART, adding information to the known impact of CMV infection in the HIV-positive population, and underlining the need of new strategies to contain the infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Cd pollution and ecological risk assessment for mining activity zone in Karst Area

NASA Astrophysics Data System (ADS)

Yang, B.; He, J. L.; Wen, X. M.; Tan, H.

2017-08-01

The monitored soil samples were collected from farmland in the area with mining activity in Karst area in Liupanshui. In this article, moss bag technology and TSP were used simultaneously for Cd transportation and deposition in the study area. Geostatistics and GIS were then used for the spatial distribution of Cd in the soil. Afterwards, Cd pollution to the soil environment and human health was studied by using the geo-accumulation index and potential ecological risk index methods. The results indicated that atmospheric deposition is the major route of Cd pollution. A moderate to strong pollution of Cd in the area and the degree of potential ecological risk was in a high level in the study area. Furthermore, Cd pollution in Liupanshui may originate from mining activity and atmospheric deposition.

Evaluation of Microvascularity by CD34 Expression in Esophagus and Oral Squamous Cell Carcinoma.

PubMed

Shahsavari, Fatemeh; Farhadi, Sareh; Sadri, Donia; Sedehi, Marzieh

2015-06-01

The present study was scheduled to evaluate microvascularity by CD34 expression in esophagus and oral squamous cell carcinoma. This study was scheduled using 40 paraffin blocked samples including 20 of oral SCC and 20 of esophagus ones and Immunohistochemical staining was conducted using CD34 monoclonal antibody. Exact fisher test was used to evaluate frequency of expression between two studied groups. There was significant correlation between age and tumor size with CD34 expression in oral SCC samples (p < 0.05) and no significant correlation between sex and tumor differentiation level (grading) (p > 0.05). Also, there was no significant correlation between age, sex, tumor size and tumor differentiation level (grading) with CD34 expression in esophagus SCC samples (p > 0.05). There was no significant difference of CD34 expression frequency in oral and esophagus SCC (p = 0/583). Finally, CD34 expression was reported 'high' for major cases of esophagus and oral SCCs. It seems, other angiogenetic or nonangiogenetic factors except CD34 may play more important role and explain the different clinical behavior of SCC at recent different locations. Other factors would be considered along with CD34 expression to interpret different clinical behavior of SCC at recent different locations.

Infrared LED Enhanced Spectroscopic CdZnTe Detector Working under High Fluxes of X-rays

PubMed Central

Pekárek, Jakub; Dědič, Václav; Franc, Jan; Belas, Eduard; Rejhon, Martin; Moravec, Pavel; Touš, Jan; Voltr, Josef

2016-01-01

This paper describes an application of infrared light-induced de-polarization applied on a polarized CdZnTe detector working under high radiation fluxes. We newly demonstrate the influence of a high flux of X-rays and simultaneous 1200-nm LED illumination on the spectroscopic properties of a CdZnTe detector. CdZnTe detectors operating under high radiation fluxes usually suffer from the polarization effect, which occurs due to a screening of the internal electric field by a positive space charge caused by photogenerated holes trapped at a deep level. Polarization results in the degradation of detector charge collection efficiency. We studied the spectroscopic behavior of CdZnTe under various X-ray fluxes ranging between 5×105 and 8×106 photons per mm2 per second. It was observed that polarization occurs at an X-ray flux higher than 3×106 mm−2·s−1. Using simultaneous illumination of the detector by a de-polarizing LED at 1200 nm, it was possible to recover X-ray spectra originally deformed by the polarization effect. PMID:27690024

Evaluation of CD30 as a marker for th2 lymphocytes in bronchoalveolar lavage in interstitial lung diseases.

PubMed

Petkova, D; Xaubet, A; Picado, C; Filella, X; Agusti, C; Luburich, P; Rodriguez-Roisin, R

2000-04-01

Several studies have been carried out to clarify the relationship between CD30 expression and Th2 lymphocytes, although the results have been controversial. To investigate whether CD30 is a useful marker for Th2 lymphocytes in bronchoalveolar lavage (BAL) in interstitial lung diseases (ILD), we studied six control subjects and 31 patients with ILD (12 with idiopathic pulmonary fibrosis, seven with hypersensitivity pneumonitis, three with chronic eosinophilic pneumonia and nine with sarcoidosis). The levels of interleukin-5 (IL-5) (secreted by Th2 cells), interferon-gamma (IFNgamma) (secreted by Th1 cells) and the expression of CD30 on lymphocytes were determined in BAL fluid. There were no differences in the percentage of CD30+ lymphocytes between controls and patients with ILD (0.8+0.4% vs. 2+/-0.4%). In order to determine the relationship between Th2 cells and CD30 expression, we divided the patients into two groups according to BAL IL-5 levels. Group I consisted of eight patients (three chronic eosinophilic pneumonia, three hypersensitivity pneumonitis, two idiopathic pulmonary fibrosis) with high IL-5 levels (298+/-138 pg ml(-1)). Group II consisted of the remaining 23 ILD patients with normal IL-5 levels (0.9+/-0.6 pg ml(-1)). The percentage of eosinophils in BAL fluid was significantly higher in group I compared with group 11 (34+/-16% vs. 3+/-1%, P < 0.05). A correlation between CD30+ lymphocytes and IL-5 in group 1 was not shown. There were no differences in the number of CD30+ I we found a significant correlation between IL-5 levels and the percentage of eosinophils (r = 0.95, P < 0.0001). Our results suggest that CD30 does not appear to be a useful marker for Th2 lymphocytes in BAL from patients with ILD.

Complement Factor H as a potential atherogenic marker in chronic Chagas disease.

PubMed

Lidani, Kárita Cláudia Freitas; Sandri, Thaisa Lucas; Andrade, Fabiana Antunes; Bavia, Lorena; Nisihara, Renato; Reason, Iara J Messias

2018-05-19

We aimed to investigate the association between plasma levels of complement Factor H (FH) with cardiac involvement, inflammatory and cardiometabolic parameters in patients with chronic Chagas disease (CD). FH plasmatic levels were determined in 80 chronic CD patients. Glycemic index, lipidogram (high-density lipoprotein cholesterol HDL-C, low-density lipoprotein cholesterol LDL-C, triglycerides and total cholesterol), and Ultrasensitive C-Reactive Protein (uCRP) values were obtained from medical records. Height, weight, body mass index (BMI) blood pressure and left ventricular ejection fraction (LVEF) were obtained from echocardiography exams. Comparisons between chronic CD clinical forms were performed using Mann-Whitney test and correlation Spearman test. FH levels were correlated positively with triglycerides (p=0.001, r=0.39), LDL-C (p=0.009, r=0.3), cholesterol (p=0.02, r=0.28), uCRP (p=0.029, r=0.31) and BMI (p=0.008, r=0.34); and negatively with HDL-C (p=0.03, r=-0.25) levels. Dyslipidemic patients showed higher FH levels compared to normolipidemic, although no difference for FH levels were observed between chronic CD clinical forms. Alternative pathway of complement may be a link between immune response and metabolic disorders, with important immunoregulatory role in chronic CD. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Codoping in SnTe: Enhancement of Thermoelectric Performance through Synergy of Resonance Levels and Band Convergence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Gangjian; Shi, Fengyuan; Hao, Shiqiang

2015-04-22

We report a significant enhancement of the thermoelectric performance of p-type SnTe over a broad temperature plateau with a peak ZT value of similar to 1.4 at 923 K through In/Cd codoping and a CdS nanostructuring approach. Indium and cadmium play different but complementary roles in modifying the valence band structure of SnTe. Specifically, In-doping introduces resonant levels inside the valence bands, leading to a considerably improved Seebeck coefficient at low temperature. Cd-doping, however, increases the Seebeck coefficient of SnTe remarkably in the mid- to high-temperature region via a convergence of the light and heavy hole bands and an enlargementmore » of the band gap. Combining the two dopants in SnTe yields enhanced Seebeck coefficient and power factor over a wide temperature range due to the synergy of resonance levels and valence band convergence, as demonstrated by the Pisarenko plot and supported by first-principles band structure calculations. Moreover, these codoped samples can be hierarchically structured on all scales (atomic point defects by doping, nanoscale precipitations by CdS nanostructuring, and mesoscale grains by SPS treatment) to achieve highly effective phonon scattering leading to strongly reduced thermal conductivities. In addition to the high maximum ZT the resultant large average ZT of similar to 0.8 between 300 and 923 K makes SnTe an attractive p-type material for high-temperature thermoelectric power generation.« less

Effects of elevated CO2 levels on root morphological traits and Cd uptakes of two Lolium species under Cd stress*

PubMed Central

Jia, Yan; Tang, Shi-rong; Ju, Xue-hai; Shu, Li-na; Tu, Shu-xing; Feng, Ren-wei; Giusti, Lorenzino

2011-01-01

This study was conducted to investigate the combined effects of elevated CO2 levels and cadmium (Cd) on the root morphological traits and Cd accumulation in Lolium multiflorum Lam. and Lolium perenne L. exposed to two CO2 levels (360 and 1000 μl/L) and three Cd levels (0, 4, and 16 mg/L) under hydroponic conditions. The results show that elevated levels of CO2 increased shoot biomass more, compared to root biomass, but decreased Cd concentrations in all plant tissues. Cd exposure caused toxicity to both Lolium species, as shown by the restrictions of the root morphological parameters including root length, surface area, volume, and tip numbers. These parameters were significantly higher under elevated levels of CO2 than under ambient CO2, especially for the number of fine roots. The increases in magnitudes of those parameters triggered by elevated levels of CO2 under Cd stress were more than those under non-Cd stress, suggesting an ameliorated Cd stress under elevated levels of CO2. The total Cd uptake per pot, calculated on the basis of biomass, was significantly greater under elevated levels of CO2 than under ambient CO2. Ameliorated Cd toxicity, decreased Cd concentration, and altered root morphological traits in both Lolium species under elevated levels of CO2 may have implications in food safety and phytoremediation. PMID:21462388

CD10 is a marker for cycling cells with propensity to apoptosis in childhood ALL

PubMed Central

Cutrona, G; Tasso, P; Dono, M; Roncella, S; Ulivi, M; Carpaneto, E M; Fontana, V; Comis, M; Morabito, F; Spinelli, M; Frascella, E; Boffa, L C; Basso, G; Pistoia, V; Ferrarini, M

2002-01-01

CD10 constitutes a favourable prognostic marker for childhood acute lymphoblastic leukaemia. Since correlations between CD10, cell cycle and apoptotic abilities were demonstrated in various cell types, we investigated whether differences existed in the cycling/apoptotic abilities of CD10-positive and CD10-negative B acute lymphoblastic leukaemia cells. Twenty-eight cases of childhood acute lymphoblastic leukaemia (mean age of 6.8 years) were subdivided into two groups according to high (17 cases, 93.2±4.5%, MRFI 211±82 CD10-positive cells) or low (11 cases, 11.5±6.2%, MRFI 10±7 CD10-negative cells) expression of CD10. CD10-positive acute lymphoblastic leukaemia cells were cycling cells with elevated c-myc levels and propensity to apoptosis, whereas CD10-negative acute lymphoblastic leukaemia cells had lower cycling capacities and c-myc levels, and were resistant to apoptosis in vitro. A close correlation between all these properties was demonstrated by the observations that the few CD10-positive cells found in the CD10-negative acute lymphoblastic leukaemia group displayed elevated c-myc and cycling capacities and were apoptosis prone. Moreover, exposure of CD10-positive acute lymphoblastic leukaemia B cells to a peptide nucleic acid anti-gene specific for the second exon of c-myc caused inhibition of c-myc expression and reduced cell cycling and apoptotic abilities as well as decreased CD10 expression. British Journal of Cancer (2002) 86, 1776–1785. doi:10.1038/sj.bjc.6600329 www.bjcancer.com © 2002 Cancer Research UK PMID:12087466

Effect of sodium chloride and cadmium on the growth, oxidative stress and antioxidant enzyme activities of Zygosaccharomyces rouxii

NASA Astrophysics Data System (ADS)

Li, Chunsheng; Xu, Ying; Jiang, Wei; Lv, Xin; Dong, Xiaoyan

2014-06-01

Zygosaccharomyces rouxii is a salt-tolerant yeast species capable of removing cadmium (Cd) pollutant from aqueous solution. Presently, the physiological characteristics of Z. rouxii under the stress of sodium chloride (NaCl) and Cd are poorly understood. This study investigated the effects of NaCl and Cd on the growth, oxidative stress and antioxidant enzyme activities of Z. rouxii after stress treatment for 24 h. Results showed that NaCl or Cd alone negatively affected the growth of Z. rouxii, but the growth-inhibiting effect of Cd on Z. rouxii was reduced in the presence of NaCl. Flow cytometry assay showed that under Cd stress, NaCl significantly reduced the production of reactive oxygen species (ROS) and cell death of Z. rouxii compared with those in the absence of NaCl. The activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) of Z. rouxii were significantly enhanced by 2%-6% NaCl, which likely contributed to the high salt tolerance of Z. rouxii. The POD activity was inhibited by 20 mg L-1 Cd while the SOD and CAT activities were enhanced by 8 mg L-1 Cd and inhibited by 20 mg L-1 or 50 mg L-1 Cd. The inhibitory effect of high-level Cd on the antioxidant enzyme activities of Z. rouxii was counteracted by the combined use of NaCl, especially at 6%. This probably accounted for the decrease in Cd-induced ROS production and cell death of Z. rouxii after incubation with NaCl and Cd. Our work provided physiological clues as to the use of Z. rouxii as a biosorbent for Cd removal from seawater and liquid highly salty food.

Landau level splitting in Cd3As2 under high magnetic fields

NASA Astrophysics Data System (ADS)

Zhang, Cheng; Cao, Junzhi; Liang, Sihang; Xia, Zhengcai; Li, Liang; Xiu, Faxian

2015-03-01

Three-dimensional (3D) topological Dirac semimetals (TDSs) are a new kind of Dirac materials that adopt nontrivial topology in band structure and possess degenerated massless Dirac fermions in the bulk. It has been proposed that TDSs can be driven to other exotic phases like Weyl semimetals, topological insulators and topological superconductors by breaking certain symmetries. Here we report the first transport evidence of Landau level splitting in TDS Cd3As2 single crystals under high magnetic fields, suggesting the removal of spin degeneracy by breaking time reversal symmetry (TRS). The observed Landau level splitting is originated from the joint contributions of orbit and Zeeman splitting in Cd3As2. In addition, the detected Berry phase is found to vary from nontrivial to trivial at different field directions, revealing a fierce competition between the orbit-coupled field strength and the field-generated mass term. Our results demonstrate a feasible path to generate a Weyl semimetal phase based on the TDSs by breaking TRS.

Age at gluten introduction and risk of celiac disease.

PubMed

Aronsson, Carin Andrén; Lee, Hye-Seung; Liu, Edwin; Uusitalo, Ulla; Hummel, Sandra; Yang, Jimin; Hummel, Michael; Rewers, Marian; She, Jin-Xiong; Simell, Olli; Toppari, Jorma; Ziegler, Anette-G; Krischer, Jeffrey; Virtanen, Suvi M; Norris, Jill M; Agardh, Daniel

2015-02-01

The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children. TEDDY (The Environmental Determinants of Diabetes in the Young) is a prospective birth cohort study. Newborn infants (N = 6436) screened for high-risk HLA-genotypes for CD were followed up in Finland, Germany, Sweden, and the United States. Information about infant feeding was collected at clinical visits every third month. The first outcome was persistent positive for tissue transglutaminase autoantibodies (tTGA), the marker for CD. The second outcome was CD, defined as either a diagnosis based on intestinal biopsy results or on persistently high levels of tTGA. Swedish children were introduced to gluten earlier (median: 21.7 weeks) compared with children from Finland (median: 26.1 weeks), Germany, and the United States (both median: 30.4 weeks) (P < .0001). During a median follow-up of 5.0 years (range: 1.7-8.8 years), 773 (12%) children developed tTGA and 307 (5%) developed CD. Swedish children were at increased risk for tTGA (hazard ratio: 1.74 [95% CI: 1.47-2.06]) and CD (hazard ratio: 1.76 [95% CI: 1.34-2.24]) compared with US children, respectively (P < .0001).Gluten introduction before 17 weeks or later than 26 weeks was not associated with increased risk for tTGA or CD, adjusted for country, HLA, gender, and family history of CD, neither in the overall analysis nor on a country-level comparison. In TEDDY, the time to first introduction to gluten introduction was not an independent risk factor for developing CD. Copyright © 2015 by the American Academy of Pediatrics.

Characterization of colonic dendritic cells in normal and colitic mice.

PubMed

Cruickshank, Sheena M; English, Nicholas R; Felsburg, Peter J; Carding, Simon R

2005-10-28

Recent studies demonstrating the direct involvement of dendritic cells (DC) in the activation of pathogenic T cells in animal models of inflammatory bowel disease identify DC as important antigen presenting cells in the colon. However, very little is known about the properties of colonic DC. Using immunohistochemistry, electron microscopy and flow cytometry we have characterized and compared colonic DC in the colon of healthy animals and interleukin-2-deficient (IL2(-/-)) mice that develop colitis. In the healthy colon, DC resided within the lamina propria and in close association with the basement membrane of colonic villi. Type 1 myeloid (CD11c(+), CD11b(+), B220(-), CD8alpha(-)) DC made up the largest (40-45%) population and all DC expressed low levels of CD80, CD86, and CD40, and had high endocytic activity consistent with an immature phenotype. In colitic IL2(-/-) mice, colonic DC numbers increased four- to five-fold and were localized within the epithelial layer and within aggregates of T and B cells. They were also many more DC in mesenteric lymph nodes (MLN). The majority (>85%) of DC in the colon and MLN of IL2(-/-) mice were type 1 myeloid, and expressed high levels of MHC class II, CD80, CD86, CD40, DEC 205, and CCR5 molecules and were of low endocytic activity consistent with mature DC. These findings demonstrate striking changes in the number, distribution and phenotype of DC in the inflamed colon. Their intimate association with lymphocytes in the colon and draining lymph nodes suggest that they may contribute directly to the ongoing inflammation in the colon.

Characterization of colonic dendritic cells in normal and colitic mice

PubMed Central

Cruickshank, Sheena M; English, Nicholas R; Felsburg, Peter J; Carding, Simon R

2005-01-01

AIM: Recent studies demonstrating the direct involvement of dendritic cells (DC) in the activation of pathogenic T cells in animal models of inflammatory bowel disease identify DC as important antigen presenting cells in the colon. However, very little is known about the properties of colonic DC. METHODS: Using immunohistochemistry, electron microscopy and flow cytometry we have characterized and compared colonic DC in the colon of healthy animals and interleukin-2-deficient (IL2-/-) mice that develop colitis. RESULTS: In the healthy colon, DC resided within the lamina propria and in close association with the basement membrane of colonic villi. Type 1 myeloid (CD11c+, CD11b+, B220-, CD8α-) DC made up the largest (40-45%) population and all DC expressed low levels of CD80, CD86, and CD40, and had high endocytic activity consistent with an immature phenotype. In colitic IL2-/- mice, colonic DC numbers increased four- to five-fold and were localized within the epithelial layer and within aggregates of T and B cells. They were also many more DC in mesenteric lymph nodes (MLN). The majority (>85%) of DC in the colon and MLN of IL2-/- mice were type 1 myeloid, and expressed high levels of MHC class II, CD80, CD86, CD40, DEC 205, and CCR5 molecules and were of low endocytic activity consistent with mature DC. CONCLUSION: These findings demonstrate striking changes in the number, distribution and phenotype of DC in the inflamed colon. Their intimate association with lymphocytes in the colon and draining lymph nodes suggest that they may contribute directly to the ongoing inflammation in the colon. PMID:16419163

High efficient expression of a functional humanized single-chain variable fragment (scFv) antibody against CD22 in Pichia pastoris.

PubMed

Zarei, Najmeh; Vaziri, Behrouz; Shokrgozar, Mohammad Ali; Mahdian, Reza; Fazel, Ramin; Khalaj, Vahid

2014-12-01

Single-chain variable fragments (scFvs) have recently emerged as attractive candidates in targeted immunotherapy of various malignancies. The anti-CD22 scFv is able to target CD22, on B cell surface and is being considered as a promising molecule in targeted immunotherapy of B cell malignancies. The recombinant anti-CD22 scFv has been successfully expressed in Escherichia coli; however, the insufficient production yield has been a major bottleneck for its therapeutic application. The methylotrophic yeast Pichia pastoris has become a highly popular expression host for the production of a wide variety of recombinant proteins such as antibody fragments. In this study, we used the Pichia expression system to express a humanized scFv antibody against CD22. The full-length humanized scFv gene was codon optimized, cloned into the pPICZαA and expressed in GS115 strain. The maximum production level of the scFv (25 mg/L) were achieved at methanol concentration, 1 %; pH 6.0; inoculum density, OD600 = 3 and the induction time of 72 h. The correlation between scFv gene dosage and expression level was also investigated by real-time PCR, and the results confirmed the presence of such correlation up to five gene copies. Immunofluorescence and flow cytometry studies and Biacore analysis demonstrated binding to CD22 on the surface of human lymphoid cell line Raji and recombinant soluble CD22, respectively. Taken together, the presented data suggest that the Pichia pastoris can be considered as an efficient host for the large-scale production of anti-CD22 scFv as a promising carrier for targeted drug delivery in treatment of CD22(+) B cell malignancies.

In Vivo Selection of CD4+ T Cells Transduced with a Gamma-Retroviral Vector Expressing a Single-Chain Intrabody Targeting HIV-1 Tat

PubMed Central

Braun, Stephen E.; Taube, Ran; Zhu, Quan; Wong, Fay Eng; Murakami, Akikazu; Kamau, Erick; Dwyer, Markryan; Qiu, Gang; Daigle, Janet; Carville, Angela; Johnson, R. Paul

2012-01-01

Abstract We evaluated the potential of an anti–human immunodeficiency virus (HIV) Tat intrabody (intracellular antibody) to promote the survival of CD4+ cells after chimeric simian immunodeficiency virus (SIV)/HIV (SHIV) infection in rhesus macaques. Following optimization of stimulation and transduction conditions, purified CD4+ T cells were transduced with GaLV-pseudotyped retroviral vectors expressing either an anti-HIV-1 Tat or a control single-chain intrabody. Ex vivo intrabody-gene marking was highly efficient, averaging four copies per CD4+ cell. Upon reinfusion of engineered autologous CD4+ cells into two macaques, high levels of gene marking (peak of 0.6% and 6.8% of peripheral blood mononuclear cells (PBMCs) and 0.3% or 2.2% of the lymph node cells) were detected in vivo. One week post cell infusion, animals were challenged with SHIV 89.6p and the ability of the anti-HIV Tat intrabody to promote cell survival was evaluated. The frequency of genetically modified CD4+ T cells progressively decreased, concurrent with loss of CD4+ cells and elevated viral loads in both animals. However, CD4+ T cells expressing the therapeutic anti-Tat intrabody exhibited a relative survival advantage over an 8- and 21-week period compared with CD4+ cells expressing a control intrabody. In one animal, this survival benefit of anti-Tat transduced cells was associated with a reduction in viral load. Overall, these results indicate that a retrovirus-mediated anti-Tat intrabody provided significant levels of gene marking in PBMCs and peripheral tissues and increased relative survival of transduced cells in vivo. PMID:22734618

High-risk oncogenic HPV genotype infection associates with increased immune activation and T cell exhaustion in ART-suppressed HIV-1-infected women

PubMed Central

Papasavvas, Emmanouil; Surrey, Lea F.; Glencross, Deborah K.; Azzoni, Livio; Joseph, Jocelin; Omar, Tanvier; Feldman, Michael D.; Williamson, Anna-Lise; Siminya, Maureen; Swarts, Avril; Yin, Xiangfan; Liu, Qin; Firnhaber, Cynthia; Montaner, Luis J.

2016-01-01

ABSTRACT Persistence of human papillomavirus (HPV) and cervical disease in the context of HIV co-infection can be influenced by introduction of antiretroviral therapy (ART) and sustained immune activation despite ART. We conducted a cross-sectional study in order to evaluate immune activation/exhaustion in ART-suppressed HIV+ women with or without high-risk (HR) HPV-related cervical intraepithelial neoplasia (CIN). 55 South African women were recruited in three groups: HR (-) (n = 16) and HR (+) (n = 15) HPV with negative cervical histopathology, and HR (+) HPV with CIN grade 1/2/3 (n = 24). Sampling included endocervical brushing (HPV DNA genotyping), Pap smear (cytology), colposcopic punch biopsy (histopathology, histochemical evaluation of immune cells), and peripheral blood (clinical assessment, flow cytometry-based immune subset characterization). Statistics were done using R2.5.1. Irrespective of the presence of CIN, HR (+) HPV women had higher circulating levels of T cells expressing markers of activation/exhaustion (CD38, PD1, CTLA-4, BTLA, CD160), Tregs, and myeloid subsets expressing corresponding ligands (PDL1, PDL2, CD86, CD40, HVEM) than HR (-) HPV women. A decrease in circulating NK cells was associated with CIN grade. CD4+ T cell count associated negatively with T cell exhaustion and expression of negative regulators on myeloid cells. Women with CIN when compared to HR (-) HPV women, had higher cervical cell density in stroma and epithelium for CD4+, CD68+, and CD11c+ cells, and only in stroma for CD8+ cells. We conclude that in ART-suppressed HIV-infected women with HPV co-infection the levels of T and myeloid cell activation/exhaustion are associated with the presence of HR HPV genotypes. PMID:27467943

[Pollution Evaluation and Risk Assessment of Heavy Metals from Atmospheric Deposition in the Parks of Nanjing].

PubMed

Wang, Cheng; Qian, Xin; Li, Hui-ming; Sun, Yi-xuan; Wang, Jin-hua

2016-05-15

Contents of heavy metals involving As, Cd, Cr, Cu, Ni, Pb and Zn from atmospheric deposition in 10 parks of Nanjing were analyzed. The pollution level, ecological risk and health risk were evaluated using Geoaccumulation Index, Potential Ecological Risk Index and the US EPA Health Risk Assessment Model, respectively. The results showed that the pollution levels of heavy metals in Swallow Rock Park, Swallow Rock Park and Mochou Lake Park were higher than the others. Compared to other cities such as Changchun, Wuhan and Beijing, the contents of heavy metals in atmospheric deposition of parks in Nanjing were higher. The evaluation results of Geoaccumulation Index showed that Pb was at moderate pollution level, Zn and Cu were between moderate and serious levels, while Cd was between serious and extreme levels. The ecological risk level of Cd was high. The assessment results of Health Risk Assessment Model indicated that there was no non-carcinogenic risk for all the seven heavy metals. For carcinogenic risk, the risks of Cd, Cr and Ni were all negligible (Risk < 1 x 10⁻⁶), whereas As had carcinogenic risk possibility but was considered to be acceptable (10⁻⁶ < Risk < 10⁻⁴).

Bilateral breast keloids in an elderly woman associated with bilateral breast cancers and high concentration of serum tumor growth factor-β.

PubMed

Sakaguchi, Masanobu; Fukumoto, Takeshi; Fujishima, Fumiyoshi; Fukuda, Kaori; Kozaru, Takeshi; Ban, Masao; Oka, Masahiro

2017-11-01

We report a case of bilateral annular breast keloids in a 72-year-old woman who had been suffering from bilateral breast cancers. Histopathologically, the keloids showed unique distribution of α-SMA+, CD34- myofibroblasts and α-SMA-, CD34+ fibroblasts depending on the region. High serum levels of tumor growth factor-β were detected at 6 months after the development of the breast keloids, but not at 10 months. CD163-positive cells were abundantly detected in the skin of the elevated portion of the keloids. In contrast, these cells were considerably less numerous in the skin of the central healing portion compared with the skin of the elevated expanding portion. One interesting idea based on these results is that high levels of tumor growth factor-β released from CD163-positive cells played a crucial role in the formation of breast keloids through active induction of fibroblast differentiation into myofibroblasts. The present case strongly supports the previously proposed idea that keloids can form as a paraneoplastic phenomenon in breast cancer patients with keloid constitution. © 2017 Japanese Dermatological Association.

Martensitic transformations, structure, and strengthness of processed high-nitrogen and high-carbon ferrous alloys

NASA Astrophysics Data System (ADS)

Kaputkina, L. M.; Prokoshkina, V. G.

2003-10-01

Structures and properties of metastable austenitic alloys Fe-18Cr-16Ni-I2Mn-(0.17 to 0. 50)N, Fe-18Cr-12Mn-(0.48 to 1.12)N, Fe-18Cr-(0.1 to 1.18)N, and Fe-(12 to 20)Ni-(0.6 to 1.3)C, Fe-(6 to 8)Mn-(0.6 to 1.0)C, Fe-(5 to 6)Cr-(4 to 5)Mn-(0.6 to 0.8)C, Fe-6Cr-(1.0 to 1.3)C resulting from martensitic transformations under cooling and cold deformation (CD), as well as following tempering processes, were studied by magnetometry, X-ray and electron microscopy analyses, hardness measurements and mechanical properties tests. Martensite with a b.c.t. lattice was formed in all alloys with M_s{>}-196^circC during cooling. Under CD transformations of γ{to}α, γ{to}\\varepsilon{to}α, or γ{to}\\varepsilon types were realized depending on the alloy composition. Carbon increased but nitrogen decreased stacking fault energy. Thus carbon assists α-martensite formation but nitrogen promotese. As CD level and/or concentration of carbon and nitrogen increase residual stresses resulting from the CD also increase. The martensitic transformation during CD can decrease the residual stresses. Kinetic of tempering of b.c.t. thermal martensite differs from those of CD-induced martensite. In the second case, deformation aging, texture, and residual stresses are more visible. The maximal strengthening under CD takes place in (Mn+N)-steels. (Cr+N) and (Cr+Mn+N)-steels are high-strength, non-magnetic and corrosion resistant and are easily hardened by a low level of plastic deformation.

Cell Homogeneity Indispensable for Regenerative Medicine by Cultured Human Corneal Endothelial Cells.

PubMed

Hamuro, Junji; Toda, Munetoyo; Asada, Kazuko; Hiraga, Asako; Schlötzer-Schrehardt, Ursula; Montoya, Monty; Sotozono, Chie; Ueno, Morio; Kinoshita, Shigeru

2016-09-01

To identify the subpopulation (SP) among heterogeneous cultured human corneal endothelial cells (cHCECs) devoid of cell-state transition applicable for cell-based therapy. Subpopulation presence in cHCECs was confirmed via surface CD-marker expression level by flow cytometry. CD markers effective for distinguishing distinct SPs were selected by analyzing those on established cHCECs with a small cell area and high cell density. Contrasting features among three typical cHCEC SPs was confirmed by PCR array for extracellular matrix (ECM). Combined analysis of CD markers was performed to identify the SP (effector cells) applicable for therapy. ZO-1 and Na+/K+ ATPase, CD200, and HLA expression were compared among heterogeneous SPs. Flow cytometry analysis identified the effector cell expressing CD166+CD105-CD44-∼+/-CD26-CD24-, but CD200-, and the presence of other SPs with CD166+ CD105-CD44+++ (CD26 and CD24, either + or -) was confirmed. PCR array revealed three distinct ECM expression profiles. Some SPs expressed ZO-1 and Na+/K+ ATPase at comparable levels with effector cells, while only one SP expressed CD200, but not on effector cells. Human leukocyte antigen expression was most reduced in the effector SP. The proportion of effector cells (E-ratio) inversely paralleled donor age and decreased during prolonged culture passages. The presence of Rho-associated protein kinase (ROCK) inhibitor increased the E-ratio in cHCECs. The average area of effector cells was approximately 200∼220 μm2, and the density of cHCECs exceeded 2500 cells/mm2. A specified cultured effector cell population sharing the surface phenotypes with mature HCECs in corneal tissues may serve as an alternative to donor corneas for the treatment of corneal endothelial dysfunction.

Effect of Inoculation with Glomus versiforme on Cadmium Accumulation, Antioxidant Activities and Phytochelatins of Solanum photeinocarpum

PubMed Central

Tan, Shi-Yun; Jiang, Qiu-Yun; Zhuo, Feng; Liu, Hui; Wang, Yu-Tao; Li, Shao-Shan; Ye, Zhi-Hong; Jing, Yuan-Xiao

2015-01-01

The plant growth, phosphate acquisition, Cd translocation, phytochelatins (PCs) production and antioxidant parameters [superoxide dismutase (SOD), catalase (CAT), guaiacol peroxidase (POD), ascorbate peroxidase (APX), glutathione reductase (GR), glutathione (GSH), ascorbate (ASA) and malonaldehyde (MDA)] were investigated in Cd-hyperaccumulator Solanum photeinocarpum inoculated with Glomus versiforme BGC GD01C (Gv) in Cd-added soils (0, 5, 10, 20, 40 mg Cd kg-1 soil). Mycorrhizal colonization rates were generally high (from 77% to 94%), and hardly affected by Cd. Gv colonization significantly enhanced P acquisition, growth and total Cd uptakes in both shoots and roots of S. photeinocarpum at all Cd levels. Meanwhile, Gv symbiosis significantly increased Cd concentration in the roots, and decreased Cd concentration in the shoots at all Cd levels, which indicates that Gv could promote phytostabilization by enhancing Cd accumulation in the roots to inhibit its translocation to shoots and the “dilution effects” linked to an increase in plant dry matter yield and a reduced Cd partitioning to shoots. Moreover, the improvement of CAT, POD and APX activities in the leaves of mycorrhizal plants infers that Gv symbiosis helped S. photeinocarpum to relieve oxidative damage to biomolecules in Cd-contaminated soil. The evident decline of MDA content in the leaves of mycorrhizal plants indicates that Gv symbiosis evidently improved antioxidant activities, and the enhancement of PCs production in the leaves of mycorrhizal plants suggests that Gv-inoculated plant may be more efficient to relieve Cd phytotoxicity. Therefore, the possible mechanisms of Cd phytotoxicity alleviation by Gv can be concluded as the decline of Cd concentration in the shoots and the improvement of P acquisition, PCs production and activities of CAT, POD, APX in mycorrhizal plants. PMID:26176959

Antigen expression level threshold tunes the fate of CD8 T cells during primary hepatic immune responses.

PubMed

Tay, Szun Szun; Wong, Yik Chun; McDonald, David M; Wood, Nicole A W; Roediger, Ben; Sierro, Frederic; Mcguffog, Claire; Alexander, Ian E; Bishop, G Alex; Gamble, Jennifer R; Weninger, Wolfgang; McCaughan, Geoffrey W; Bertolino, Patrick; Bowen, David G

2014-06-24

CD8 T-cell responses to liver-expressed antigens range from deletional tolerance to full effector differentiation resulting in overt hepatotoxicity. The reasons for these heterogeneous outcomes are not well understood. To identify factors that govern the fate of CD8 T cells activated by hepatocyte-expressed antigen, we exploited recombinant adenoassociated viral vectors that enabled us to vary potential parameters determining these outcomes in vivo. Our findings reveal a threshold of antigen expression within the liver as the dominant factor determining T-cell fate, irrespective of T-cell receptor affinity or antigen cross-presentation. Thus, when a low percentage of hepatocytes expressed cognate antigen, high-affinity T cells developed and maintained effector function, whereas, at a high percentage, they became functionally exhausted and silenced. Exhaustion was not irreversibly determined by initial activation, but was maintained by high intrahepatic antigen load during the early phase of the response; cytolytic function was restored when T cells primed under high antigen load conditions were transferred into an environment of low-level antigen expression. Our study reveals a hierarchy of factors dictating the fate of CD8 T cells during hepatic immune responses, and provides an explanation for the different immune outcomes observed in a variety of immune-mediated liver pathologic conditions.

Serum Analysis of Tryptophan Catabolism Pathway: Correlation with Crohn’s Disease Activity

PubMed Central

Gupta, Nitin K; Thaker, Ameet I; Kanuri, Navya; Riehl, Terrence E; Rowley, Christopher W; Stenson, William F; Ciorba, Matthew A

2011-01-01

BACKGROUND Indoleamine 2,3 dioxygenase 1 (IDO1) is a tryptophan catabolizing enzyme with immunotolerance promoting functions. We sought to determine if increased gut expression of IDO1 in Crohn’s disease (CD) would result in detectable changes in serum levels of tryptophan and the initial IDO1 pathway catabolite, kynurenine. METHODS Individuals were prospectively enrolled through the Washington University Digestive Diseases Research Center. Montreal classification was used for disease phenotyping. Disease severity was categorized by physician’s global assessment. Serum tryptophan and kynurenine were measured by high pressure liquid chromatography. IDO1 immunohistochemical staining was performed on formalin-fixed tissue blocks. RESULTS 25 CD patients and 11 controls were enrolled. 8 CD patients had serum collected at two different time points and levels of disease activity. Strong IDO1 expression exists in both the lamina propria and epithelium during active CD compared to controls. Suppressed serum tryptophan levels and an elevated kynurenine/tryptophan (K/T) ratio were found in individuals with active CD as compared to those in remission or the control population. K/T ratios correlated positively with disease activity as well as with C-reactive protein and erythrocyte sedimentation rate. In the subgroup of CD patients with two serum measurements, tryptophan levels elevated while kynurenine levels and the K/T ratio lowered as the disease activity lessened. CONCLUSIONS IDO1 expression in Crohn’s disease is associated with lower serum tryptophan and an elevated K/T ratio. These levels may serve a reasonable objective marker of gut mucosal immune activation and surrogate for Crohn’s Disease activity. PMID:21823214

Accumulation of heavy metals in soil and their transfer to leafy vegetables in the region of Dhaka Aricha Highway, Savar, Bangladesh.

PubMed

Aktaruzzaman, M; Fakhruddin, A N M; Chowdhury, M A Z; Fardous, Z; Alam, M K

2013-04-01

Accumulation of heavy metals in environmental matrices is a potential risk to living system due to their uptake by plants and subsequent introduction into the food chain. A study was conducted to investigate the heavy metals concentration in soils and leafy vegetables samples along the Dhaka Aricha Road to assess their potential ecological risk. Heavy metals concentration was analyzed by Atomic Absorption Spectroscopy. Concentrations ofallthetestedheavy metals except Cd in soil samples were below the permissible level. The mean concentration of Cd was found 3.99 +/- 1.85 mg kg(-1). Concentrations of all the tested heavy metals except Cd and Cr in vegetables samples were lower than recommended level. Mean concentration of Cd and Cr were found 1.00 +/- 0.68 mg kg(-1) and 2.32 +/- 0.84 mg kg(-1), respectively. Based on the Potential Ecological Risk Index, Cd posed very high risk to the local ecosystem due to its higher Risk Factor, > 320 and based on Transfer Factor of Pb and Cd were found higher accumulator among the tested metals. The results of present study revealed that the bioconcentration of heavy metals along the Dhaka Aricha Road posed high risk to the ecosystem. Considering the Transfer Factor of Cd and Pb it can be suggested that plants and leafy vegetables grow in the soil near Dhaka Aricha Road should not be used as food or feed.

Tissue partition and risk assessments of trace elements in Indo-Pacific Finless Porpoises (Neophocaena phocaenoides) from the Pearl River Estuary coast, China.

PubMed

Zhang, Xiyang; Lin, Wenzhi; Yu, Ri-Qing; Sun, Xian; Ding, Yulong; Chen, Hailiang; Chen, Xi; Wu, Yuping

2017-10-01

Throughout the last few decades, an increased number of stranded marine mammals, particularly the Indo-Pacific Finless Porpoises (Neophocaena phocaenoides), were observed in the Pearl River Estuary (PRE). As long-lived, apex predators vulnerable to bioaccumulation of contaminants, the tissue residue levels and health risk of trace elements (TEs) in N. phocaenoides from the PRE have been little studied. Eleven typical TEs distributed in skin, liver and kidney tissues were investigated from 25 specimens stranded along the PRE from 2007 to 2015 in the present study. It revealed that most TEs were highly accumulated in internal organs (liver and kidney), except for Zn with high residue levels in external skin. Compared with the TEs in prey items, the residue levels of Hg, Se, Zn, Cu, Cd and Cr in N. phocaenoides increased 4-618 times, indicating a potentially significant biomagnification. Sex-related differences of TE accumulation were not obvious, except for renal Mn, in which the females showed lower mean concentrations than males. Significantly positive correlations between body length and TE levels were found for Hg, Se and Cd. Results of the calculated risk quotients (RQ) suggested that the risks to N. phocaenoides from consumption of prey items were generally low, but further attentions should be paid to Cd, Cr, Cu, Hg and As due to the elevated RQ values. The concentrations of Hg, Cd and Se in the epidermis were positively correlated with the levels found in internal organs. Our investigation provides evidence to support the use of skin as one biomonitoring approach on Hg, Cd and Se contamination of internal tissues in this species. Copyright © 2017 Elsevier Ltd. All rights reserved.

Predictive Value of Tertiary Lymphoid Structures Assessed by High Endothelial Venule Counts in the Neoadjuvant Setting of Triple-Negative Breast Cancer

PubMed Central

Song, In Hye; Heo, Sun-Hee; Bang, Won Seon; Park, Hye Seon; Park, In Ah; Kim, Young-Ae; Park, Suk Young; Roh, Jin; Gong, Gyungyub; Lee, Hee Jin

2017-01-01

Purpose The tertiary lymphoid structure (TLS) is an important source of tumor-infiltrating lymphocytes (TILs), which have a strong prognostic and predictive value in triple-negative breast cancer (TNBC). A previous study reported that the levels of CXCL13 mRNA expression were associated with TLSs, but measuring the gene expression is challenging in routine practice. Therefore, this study evaluated the MECA79-positive high endothelial venule (HEV) densities and their association with the histopathologically assessed TLSs in biopsy samples. In addition, the relationship of TLSs with the CXCL13 transcript levels and clinical outcomes were examined. Materials and Methods A total of 108 TNBC patients treated with neoadjuvant chemotherapy (NAC) were studied. The amounts of TILs and TLSs were measured histopathologically using hematoxylin and eosin–stained slides. The HEV densities and TIL subpopulations were measured by immunohistochemistry for MECA79, CD3, CD8, and CD20. CXCL13mRNA expression levels using a NanoString assay (NanoString Technologies). Results The mean number of HEVs in pre-NAC biopsies was 12 (range, 0 to 72). The amounts of TILs and TLSs, HEV density, and CXCL13 expression showed robust correlations with each other. A lower pre-NAC clinical T stage, higher TIL and TLS levels, a higher HEV density, CD20-positive cell density, and CXCL13 expression were significant predictors of a pathologic complete response (pCR). Higher CD8-positive cell density and levels of CXCL13 expression were significantly associated with a better disease-free survival rate. Conclusion MECA79-positive HEV density in pre-NAC biopsies is an objective and quantitative surrogate marker of TLS and might be a valuable tool for predicting pCR of TNBC in routine pathology practice. PMID:27488875

Sustained CD4+ T cell-driven lymphopenia without a compensatory IL-7/IL-15 response among high-grade glioma patients treated with radiation and temozolomide

PubMed Central

Ellsworth, Susannah; Balmanoukian, Ani; Kos, Ferdynand; Nirschl, Christopher J; Nirschl, Thomas R; Grossman, Stuart A; Luznik, Leo; Drake, Charles G

2014-01-01

Prolonged lymphopenia correlating with decreased survival commonly occurs among glioma patients undergoing radiation therapy (RT) and temozolomide (TMZ) treatment. To better understand the pathophysiology of this phenomenon, we prospectively monitored serum cytokine levels and lymphocyte subsets in 15 high-grade glioma patients undergoing combined radiation and TMZ (referred to as RT/TMZ) treatment. Sufficient data for analysis were acquired from 11 of the patients initially enrolled. Lymphocyte phenotyping data were obtained using cytofluorometric analysis and serum cytokine levels were measured using the a multiplex bead-based assays. Total lymphocyte counts (TLCs) were > 1000 cells per μL peripheral blood in 10/11 patients at baseline, but dropped significantly after treatment. Specifically, after RT/TMZ therapy, the TLCs were found to be < 500 cells/μL in 2/11 patients, 500–1000 cells/μL in 7/11 patients, and > 1000 cells/μL in the remaining 2 patients. Among residual mononuclear blood cells, we observed a proportional drop in B and CD4+ T cells but not in CD8+ T lymphocytes. Natural killer cells remained to near-to-baseline levels and there was a transient and slight (insignificant) increase in regulatory T cells (Tregs). The circulating levels of IL-7 and IL-15 remained low despite marked drops in both the total and CD4+ T lymphocyte counts. Thus, patients with malignant glioma undergoing RT/TMZ treatment exhibit a marked decline in TLCs, affecting both CD4+ T cells and B lymphocytes, in the absence of a compensatory increase in interleukin-7 levels. The failure to mount an appropriate homeostatic cytokine response may be responsible for the prolonged lymphopenia frequently observed in these patients. PMID:24790790

Genomic Profile and Pathologic Features of Diffuse Large B-Cell Lymphoma Subtype of Methotrexate-associated Lymphoproliferative Disorder in Rheumatoid Arthritis Patients.

PubMed

Carreras, Joaquim; Yukie Kikuti, Yara; Miyaoka, Masashi; Hiraiwa, Shinichiro; Tomita, Sakura; Ikoma, Haruka; Kondo, Yusuke; Shiraiwa, Sawako; Ando, Kiyoshi; Sato, Shinji; Suzuki, Yasuo; Miura, Ikuo; Roncador, Giovanna; Nakamura, Naoya

2018-05-05

Rheumatoid arthritis patients often develop the diffuse large B-cell lymphoma subtype of methotrexate-associated lymphoproliferative disorder (DLBCL). We characterized the genomic profile and pathologic characteristics of 20 biopsies using an integrative approach. DLBCL was associated with extranodal involvement, a high/high-intermediate international prognostic index in 53% of cases, and responded to MTX withdrawal. The phenotype was nongerminal center B-cell in 85% of samples and Epstein-Barr encoding region positive (EBER) in 65%, with a high proliferation index and intermediate MYC expression levels. The immune microenvironment showed high numbers of CD8 cytotoxic T lymphocytes and CD163 M2 macrophages with an (CD163/CD68) M2 ratio of 3.6. Its genomic profile was characterized by 3p12.1-q25.31, 6p25.3, 8q23.1-q24.3, and 12p13.33-q24.33 gains, 6q22.31-q24.1 and 13q21.33-q34 losses, and 1p36.11-p35.3 copy neutral loss-of-heterozygosity. This profile was closer to nongerminal center B-cell DLBCL not-otherwise-specified, but with characteristic 3q, 12q, and 20p gains and lower 9p losses (P<0.05). We successfully verified array results using fluorescent DNA in situ hybridization on PLOD2, MYC, WNT1, and BCL2. Protein immunohistochemistry revealed that DLBCL expressed high IRF4 (6p25.3) and SELPLG (12q24.11) levels, intermediate TNFRSF14 (1p36.32; the exons 1 to 3 were unmutated), BTLA (3q13.2), PLOD2 (3q24), KLHL6 (3q27.1), and MYC (8q24.21) levels, and low AICDA (12p13.31) and EFNB2 (13q33.3) levels. The correlation between the DNA copy number and protein immunohistochemistry was confirmed for BTLA, PLOD2, and EFNB2. The characteristics of EBER versus EBER cases were similar, with the exception of specific changes: EBER cases had higher numbers of CD163 M2 macrophages and FOXP3 regulatory T lymphocytes, high programmed cell death 1 ligand 1 expression levels, slightly fewer genomic changes, and 3q and 4p focal gains. In conclusion, DLBCL has a characteristic genomic profile with 3q and 12 gains, 13q loss, different expression levels of relevant pathogenic biomarkers, and a microenvironment with high numbers of cytotoxic T lymphocytes and M2 macrophages.

Do neurocognitive deficits in decision making differentiate conduct disorder subtypes?

PubMed

Fanti, Kostas A; Kimonis, Eva R; Hadjicharalambous, Maria-Zoe; Steinberg, Laurence

2016-09-01

The present study aimed to test whether neurocognitive deficits involved in decision making underlie subtypes of conduct-disorder (CD) differentiated on the basis of callous-unemotional (CU) traits. Eighty-five participants (M age = 10.94 years) were selected from a sample of 1200 children based on repeated assessment of CD and CU traits. Participants completed a multi-method battery of well-validated measures of risky decision making and associated constructs of selective attention and future orientation (Stroop, Stoplight, and Delay-Discounting Tasks). Findings indicated that impaired decision making, selective attention, and future orientation contribute to the antisocial presentations displayed by children with CD, irrespective of level of CU traits. Youth high on CU traits without CD showed less risky decision making, as indicated by their performance on the Stoplight laboratory task, than those high on both CD and CU traits, suggesting a potential protective factor against the development of antisocial behavior.

T cell receptor αβ diversity inversely correlates with pathogen-specific antibody levels in human cytomegalovirus infection.

PubMed

Wang, George C; Dash, Pradyot; McCullers, Jonathan A; Doherty, Peter C; Thomas, Paul G

2012-04-04

A diverse T cell receptor (TCR) repertoire capable of recognizing a broad range of antigenic peptides is thought to be central to effective pathogen-specific immunity by counteracting escape mutations, selecting high-avidity T cells, and providing T cell specificities with comprehensive functional characteristics. However, evidence that TCR diversity is important for the successful control of human infections is limited. A single-cell strategy for the clonotypic analysis of human CD8⁺ TCRαβ repertoires was used to probe the diversity and magnitude of individual human cytomegalovirus (CMV)-specific CD8⁺ T cells recovered directly ex vivo. We found that CD8⁺ TCRαβ repertoire diversity, but not the size of the CD8⁺ T cell response, was inversely related to circulating CMV-specific antibody levels, a measure that has been correlated epidemiologically with differential mortality risks and found here to be higher in persons with detectable (versus undetectable) CMV viral loads. Overall, our findings indicate that CD8⁺ T cell diversity may be more important than T cell abundance in limiting the negative consequences of CMV persistence, demonstrate high prevalence of both TCRα and TCRβ public motif usage, and suggest that a highly diverse TCRαβ repertoire may be an important benchmark and target in the success of immunotherapeutic strategies.

Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab.

PubMed

Malka, D; Boige, V; Jacques, N; Vimond, N; Adenis, A; Boucher, E; Pierga, J Y; Conroy, T; Chauffert, B; François, E; Guichard, P; Galais, M P; Cvitkovic, F; Ducreux, M; Farace, F

2012-04-01

We investigated whether circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC) patients. In a substudy of the randomized phase II FNCLCC ACCORD 13/0503 trial, CECs (CD45- CD31+ CD146+ 7-amino-actinomycin- cells) were enumerated in 99 patients by four-color flow cytometry at baseline and after one cycle of treatment. We correlated CEC levels with objective response rate (ORR), 6-month progression-free survival (PFS) rate (primary end point of the trial), PFS, and overall survival (OS). Multivariate analyses of potential prognostic factors, including CEC counts and Köhne score, were carried out. By multivariate analysis, high baseline CEC levels were the only independent prognostic factor for 6-month PFS rate (P < 0.01) and were independently associated with worse PFS (P = 0.02). High CEC levels after one cycle were the only independent prognostic factor for ORR (P = 0.03). High CEC levels at both time points independently predicted worse ORR (P = 0.025), 6-month PFS rate (P = 0.007), and PFS (P = 0.02). Köhne score was the only variable associated with OS. CEC levels at baseline and after one treatment cycle may independently predict ORR and PFS in mCRC patients starting first-line bevacizumab and chemotherapy.

On the certification of cadmium at trace and ultratrace levels in standard reference materials using ID ICP-MS.

PubMed

Murphy, K E; Long, S E; Vocke, R D

2007-04-01

Analytical methods used for the isotope dilution inductively coupled plasma mass spectrometric (ID-ICP-MS) measurement of Cd at microg kg(-1) and sub-microg kg(-1) levels are described and applied to the certification of new dietary supplement, blood, and serum Standard Reference Materials (SRMs). The materials are: SRM 3240 Ephedra sinica Stapf Aerial Parts, SRM 3241 Ephedra sinica Stapf Native Extract, SRM 3243 Ephedra-Containing Solid Oral Dosage Form, SRM 3244 Ephedra-Containing Protein Powder, SRM 966 Toxic Metals in Bovine Blood, Level 1 (L1) and Level 2 (L2), and SRM 1598a Animal Serum. The concentration of Cd in the materials ranges from 120 microg kg(-1) down to 0.03 microg kg(-1). At these levels, the factors that most influence the accuracy of the ICP-MS data are the procedure blank and spectral and nonspectral interferences. Nonspectral interference, caused by the high concentration of dissolved solids in the matrices investigated, resulted in signal suppression. Matrix separation was used to enhance signal intensity and to reduce spectral interference for the accurate determination of Cd in SRM 1598a and SRM 3244. Chromatographic separation procedures using Chelex for SRM 1598a and anion exchange for SRM 3244 were optimized to achieve the desired separation characteristics without substantially increasing the procedure blank. Sensitivity for the determination of Cd in serum was additionally enhanced through the use of desolvation nebulization. We determined that separations were not required for the accurate ICP-MS determination of Cd in SRM 3240, SRM 3241, SRM 3243, and SRM 966 L2 under optimized analysis conditions. These samples were diluted to a minimum volume and introduced to the ICP-MS via low flow (40-100 microL/min) microconcentric nebulizers. SRM 966 L1 was also analyzed directly, but results were highly variable. The ID-ICP-MS sample preparation and ratio measurement protocols described here resulted in total expanded uncertainties of less than 1% for the determination of 90.85 microg kg(-1) Cd in SRM 3240, and less than 10% total expanded uncertainty for the determination of 0.0468 microg kg(-1) Cd in SRM 1598a.

Evidence for a link between sphingolipid metabolism and expression of CD1d and MHC-class II: monocytes from Gaucher disease patients as a model.

PubMed

Balreira, Andrea; Lacerda, Lúcia; Miranda, Clara Sá; Arosa, Fernando A

2005-06-01

Gaucher disease (GD) is an autosomal recessive inherited defect of the lysosomal enzyme glucocerebrosidase (GluCerase) that leads to glucosylceramide (GluCer) accumulation. We previously demonstrated the existence of imbalances in certain lymphocyte populations in GD patients. We now show that GluCerase-deficient monocytes from GD patients or monocytes from healthy subjects treated with conduritol-B-epoxide (CBE), an irreversible inhibitor of GluCerase activity, display high levels of surface expression of the lipid-binding molecule CD1d. GluCerase-deficient monocytes from GD patients also showed increased surface expression of major histocompatibility complex (MHC)-class II, but not of other lysosomal trafficking molecules, such as CD63 and MHC-class I. However, CD1d and MHC-class II mRNA levels were not increased. GluCerase-deficient monocytes from GD patients undergoing enzyme replacement therapy also exhibited increased levels of CD1d and MHC-class II and imbalances in the percentage of CD4+, CD8+, and Valpha24+ T cells. Interestingly, follow-up studies revealed that enzyme replacement therapy induced a decrease in MHC-class II expression and partial correction of the CD4+ T cell imbalances. These results reveal a new link between sphingolipid accumulation in monocytes and the expression of certain MHC molecules that may result in imbalances of regulatory T cell subsets. These immunological anomalies may contribute to the clinical heterogeneity in GD patients.

[Effect of Nano Zeolite on Chemical Fractions of Cd in Soil and Its Uptake by Cabbage].

PubMed

Xiong, Shi-juan; Xu, Wei-hong; Xie, Wen-wen; Chen, Rong; Chen, Yong-qin; Chi, Sun-lin; Chen, Xu- gen; Zhang, Jin-zhong; Xiong, Zhi-ting; Wang, Zheng-yin; Xie, De-ti

2015-12-01

Incubation experiments were carried out to investigate the influence of different nano zeolite (NZ) and ordinary zeolite (OZ) levels(0, 5, 10 and 20 g · kg⁻¹) on the change trends in fraction distribution coefficient (FDC) of Cd when exposed to different Cadmium (Cd) levels (1, 5, 10 and 15 mg · kg⁻¹), and pot experiments were carried out to investigate their influence on soil Cd fraction and Cd uptake by cabbage. The results in incubation experiments showed that the application of nano zeolite as well as ordinary zeolite effectively decreased the FDC of exchangeable Cd and increased the FDC of Fe-Mn oxide fraction. The FDC of soil Cd from 0 d to 28 d was deceased at first, then increased and tended to be stable, and finally increased. At the end of incubation, the FDC of soil exchangeable Cd decreased from 72.0%-88.0% to 30.0%-66.4%. Exchangeable fraction Cd was the most dominant Cd fraction in soil during the whole incubation. The results in pot experiment indicated that the application of nano zeolite and ordinary zeolite decreased the concentration and FDC of soil exchangeable Cd, and concurrently the concentration and FDC of Cd in carbonate, Fe-Mn oxide, organic matter and residual fraction were increased. The lowest EX-Cd was observed in the treatment with high dose of nano zeolite (20 g · kg⁻¹). The FDC of exchangeable Cd showed significant negative relationship with the soil pH (P < 0.05), and was concurrently extremely positively correlated with Cd concentration in shoot and root of cabbage (P < 0.01). Soil pH increased by 1.8%-45.5% and 6.1%-54.3% in the presence of zeolite when exposed to 5 mg · kg⁻¹ 1 and Cd, respectively; FDC of exchangeable Cd decreased by 16.3%-47.7% and 16.2%-46.7%; Cd concentration in each tissues of cabbage decreased by 1.0%-75.0% and 3.8%-53.2%, respectively. Moreover, the reduction effect of nano zeolite on soil and plant Cd was better than that of ordinary zeolite. The growth of cabbage was stimulated by low and medium zeolite doses (≤ 10 g · kg⁻¹), while inhibited by high zeolite doses (20 g · kg⁻¹). Compared to ordinary zeolite, the biomass of Chinese cabbage was significantly increased by Nano zeolite, while the exchangeable Cd in soil as well as Cd concentration and Cd accumulation of cabbage were significantly reduced.

Low Antigen Dose in Adjuvant-Based Vaccination Selectively Induces CD4 T Cells with Enhanced Functional Avidity and Protective Efficacy

PubMed Central

Wang, Yichuan; Solaymani-Mohammadi, Shahram; Frey, Blake; Kulkarni, Shweta; Andersen, Peter; Agger, Else Marie; Sui, Yongjun

2017-01-01

T cells with high functional avidity can sense and respond to low levels of cognate Ag, a characteristic that is associated with more potent responses against tumors and many infections, including HIV. Although an important determinant of T cell efficacy, it has proven difficult to selectively induce T cells of high functional avidity through vaccination. Attempts to induce high-avidity T cells by low-dose in vivo vaccination failed because this strategy simply gave no response. Instead, selective induction of high-avidity T cells has required in vitro culturing of specific T cells with low Ag concentrations. In this study, we combined low vaccine Ag doses with a novel potent cationic liposomal adjuvant, cationic adjuvant formulation 09, consisting of dimethyldioctadecylammonium liposomes incorporating two immunomodulators (monomycolyl glycerol analog and polyinosinic-polycytidylic acid) that efficiently induces CD4 Th cells, as well as cross-primes CD8 CTL responses. We show that vaccination with low Ag dose selectively primes CD4 T cells of higher functional avidity, whereas CD8 T cell functional avidity was unrelated to vaccine dose in mice. Importantly, CD4 T cells of higher functional avidity induced by low-dose vaccinations showed higher cytokine release per cell and lower inhibitory receptor expression (PD-1, CTLA-4, and the apoptosis-inducing Fas death receptor) compared with their lower-avidity CD4 counterparts. Notably, increased functional CD4 T cell avidity improved antiviral efficacy of CD8 T cells. These data suggest that potent adjuvants, such as cationic adjuvant formulation 09, render low-dose vaccination a feasible and promising approach for generating high-avidity T cells through vaccination. PMID:28348274

Experimental study on neuroendocrinological and immunological characteristics of the military-trained artillerymen.

PubMed

Li, Xin; Huang, Wen-xu; Lu, Ju-ming; Yang, Guang; Ma, Fang-ling; Lan, Ya-ting; Meng, Jun-hua; Dou, Jing-tao

2012-04-01

Over one million soldiers were treated for battle- or training-fatigue during World War II. Of all ground combat troops, 37% were discharged for psychiatric reasons due to fatigue. The neuroendocrinological and immunological systems played important roles in the work-related fatigue of military personnel. The aim of this study was to investigate the characteristics of fatigue associated with military operations, and we observed changes in the regulatory functions of the neuroendocrinological and immunological systems that may provide theoretical support for improving the combat effectiveness of armies. A total of 240 soldiers from the Field Artillery regiment were selected as subjects. Researchers and subjects received training before participating in the study. Data of the subjects' medical histories, physical examinations, scores on a fatigue assessment scale, and assessments of pituitary-adrenal hormones (adrenal cortical hormone (ACTH), cortical hormone (F), and 24-hour urine-free cortisol (UFC)), pituitary-gonadal hormones (luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol (E2), and prolactin (PRL)), pituitary-thyroid hormones (thyroid-stimulating hormone (TSH), thyroxine (TT4), triiodothyronine (TT3), free thyroxine (FT4), and free triiodothyronine (FT3)), and cellular immune parameters (CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), B, and NK cells) were investigated before and after large-scale and high-intensity field exercises. Data were statistically analyzed with Student's t test using SPSS software (version 13.0), and P values < 0.05 were deemed to be significant. After the high-intensity military training, the scores on the fatigue scale reflected significant increases of feeling of unpleasantness among soldiers. Additionally, the symptom checklist showed notable increases in somatization scores and significant decreases in psychoticism scores. After intensive military work, levels of plasma ACTH, F, and UFC of soldiers were decreased (P < 0.01). The level of testosterone decreased significantly after the maneuver ((23.51 ± 6.49) versus (18.89 ± 5.89) nmol/L; P < 0.001), whereas the thyroid function (TT3, FT4, and FT3) was markedly increased after the maneuver (P < 0.01). The number of CD3(+), CD4(+), CD4(+)/CD8(+) cells, and B lymphocytes were decreased (P < 0.05), and NK cells were increased (P < 0.001) after the maneuver. Following high-intensity military operations, the psychological tolerance of soldiers was depressed. And the hypoadrenocorticism (the functional decreases of hypothalamic-pituitary-gonadal and abnormal pituitary-thyroid axis) contributed to the increased levels of fatigue. Hypoimmunity may increase the susceptibility to diseases after high-intensity military operations.

A Five-Year Longitudinal Analysis of Sooty Mangabeys Naturally Infected with Simian Immunodeficiency Virus Reveals a Slow but Progressive Decline in CD4+ T-Cell Count Whose Magnitude Is Not Predicted by Viral Load or Immune Activation▿

PubMed Central

Taaffe, Jessica; Chahroudi, Ann; Engram, Jessica; Sumpter, Beth; Meeker, Tracy; Ratcliffe, Sarah; Paiardini, Mirko; Else, James; Silvestri, Guido

2010-01-01

Natural simian immunodeficiency virus (SIV) infection in sooty mangabeys (SMs) typically does not result in AIDS, despite high-level viremia and significant depletion of mucosal CD4+ T cells. Here, we report the results of the first longitudinal study of a large cohort of SMs naturally infected with SIV (n = 78) housed at the Yerkes National Primate Research Center from which samples were obtained three times over a 5-year period. In this study, we observed (i) no signs of simian AIDS, (ii) stable SIV loads, (iii) a slow but progressive decline in CD4+ T-cell counts (from a mean of 1,067.0 cells/mm3 at time point 1 to 764.8 cells/mm3 at time point 3) and increases in the numbers of animals with CD4+ T-cell levels below 500 and 200 cells/mm3 (from 8 to 28 of 78 and from 1 to 4 of 78, respectively), (iv) progressive declines in percentages of naïve CD4+ and CD8+ T cells (from 37.7 to 24.8% and from 21.0 to 13.0%, respectively), and (v) stably low levels of activated/proliferating T cells as well as CD4+ CCR5+ T cells. Since the level of total CD4+ T cells and the fraction of naïve T cells in SIV-uninfected SMs also declined, it is possible that some of these observations are related to aging, as the SIV-infected animals were significantly older than the uninfected animals. In contrast to the decline in CD4+ T cell counts in individuals infected with human immunodeficiency virus (HIV), the decline in CD4+ T cell counts in SMs naturally infected with SIV over a 5-year period was not predicted by either plasma viremia or levels of T-cell activation. Taken together, these results confirm that natural SIV infection is nonprogressive from a clinical, virological, and immunological point of view and that stable levels of viremia associated with persistently low-level immune activation represent key differences from the natural course of HIV infection in humans. PMID:20335252

A five-year longitudinal analysis of sooty mangabeys naturally infected with simian immunodeficiency virus reveals a slow but progressive decline in CD4+ T-cell count whose magnitude is not predicted by viral load or immune activation.

PubMed

Taaffe, Jessica; Chahroudi, Ann; Engram, Jessica; Sumpter, Beth; Meeker, Tracy; Ratcliffe, Sarah; Paiardini, Mirko; Else, James; Silvestri, Guido

2010-06-01

Natural simian immunodeficiency virus (SIV) infection in sooty mangabeys (SMs) typically does not result in AIDS, despite high-level viremia and significant depletion of mucosal CD4(+) T cells. Here, we report the results of the first longitudinal study of a large cohort of SMs naturally infected with SIV (n = 78) housed at the Yerkes National Primate Research Center from which samples were obtained three times over a 5-year period. In this study, we observed (i) no signs of simian AIDS, (ii) stable SIV loads, (iii) a slow but progressive decline in CD4(+) T-cell counts (from a mean of 1,067.0 cells/mm(3) at time point 1 to 764.8 cells/mm(3) at time point 3) and increases in the numbers of animals with CD4(+) T-cell levels below 500 and 200 cells/mm(3) (from 8 to 28 of 78 and from 1 to 4 of 78, respectively), (iv) progressive declines in percentages of naïve CD4(+) and CD8(+) T cells (from 37.7 to 24.8% and from 21.0 to 13.0%, respectively), and (v) stably low levels of activated/proliferating T cells as well as CD4(+) CCR5(+) T cells. Since the level of total CD4(+) T cells and the fraction of naïve T cells in SIV-uninfected SMs also declined, it is possible that some of these observations are related to aging, as the SIV-infected animals were significantly older than the uninfected animals. In contrast to the decline in CD4(+) T cell counts in individuals infected with human immunodeficiency virus (HIV), the decline in CD4(+) T cell counts in SMs naturally infected with SIV over a 5-year period was not predicted by either plasma viremia or levels of T-cell activation. Taken together, these results confirm that natural SIV infection is nonprogressive from a clinical, virological, and immunological point of view and that stable levels of viremia associated with persistently low-level immune activation represent key differences from the natural course of HIV infection in humans.

Modeling the instability behavior of thin film devices: Fermi Level Pinning

NASA Astrophysics Data System (ADS)

Moeini, Iman; Ahmadpour, Mohammad; Gorji, Nima E.

2018-05-01

We investigate the underlying physics of degradation/recovery of a metal/n-CdTe Schottcky junction under reverse or forward bias stressing conditions. We used Sah-Noyce-Shockley (SNS) theory to investigate if the swept of Fermi level pinning at different levels (under forward/reverse bias) is the origin of change in current-voltage characteristics of the device. This theory is based on Shockley-Read-Hall recombination within the depletion width and takes into account the interface defect levels. Fermi Level Pinning theory was primarily introduced by Ponpon and developed to thin film solar cells by Dharmadasa's group in Sheffield University-UK. The theory suggests that Fermi level pinning at multiple levels occurs due to high concentration of electron-traps or acceptor-like defects at the interface of a Schottky or pn junction and this re-arranges the recombination rate and charage collection. Shift of these levels under stress conditions determines the change in current-voltage characteristics of the cell. This theory was suggested for several device such as metal/n-CdTe, CdS/CdTe, CIGS/CdS or even GaAs solar cells without a modeling approach to clearly explain it's physics. We have applied the strong SNS modeling approach to shed light on Fermi Level Pinning theory. The modeling confirms that change in position of Fermi Level and it's pining in a lower level close to Valence band increases the recombination and reduces the open-circuit voltage. In contrast, Fermi Level pinning close to conduction band strengthens the electric field at the junction which amplifies the carrier collection and boosts the open-circuit voltage. This theory can well explain the stress effect on device characteristics of various solar cells or Schottky junctions by simply finding the right Fermi level pinning position at every specific stress condition.

Analysis of iron, zinc, selenium and cadmium in paraffin-embedded prostate tissue specimens using inductively coupled plasma mass-spectrometry

USGS Publications Warehouse

Sarafanov, A.G.; Todorov, T.I.; Kajdacsy-Balla, A.; Gray, Michael A.; MacIas, V.; Centeno, J.A.

2008-01-01

Formalin-fixed paraffin-embedded (FFPE) tissue specimens represent a valuable and abundant resource of pathologic material for various biomedical studies. In the present study, we report the application of high-resolution inductively coupled mass-spectrometry (ICP-MS) for quantification of Fe, Zn, Se and Cd in FFPE prostate tissue. These elements have a possible role in the development of prostate diseases: while Zn and Se are needed for a healthy prostate, Cd shows multiple toxic and carcinogenic effects. Excessive accumulation of Fe induces the production of highly reactive hydroxyl radical species, which may play a role in cancer etiopathogenesis. To assess whether the levels of these metals in the FFPE prostate tissue represent their original content, we compared their levels with those in the fresh tissue (on dry weight basis) in samples obtained from 15 patients. We found that in FFPE tissue, the recoveries of Se, Fe, Cd and Zn were progressively decreased, 97??11% (r=0.88), 82??22% (r=0.86), 59??23% (r=0.69) and 24??11% (r=0.38), respectively. Thus, the use of correction factors, determined as k=0.16 for Se, k=0.20 for Fe, k=0.27 for Cd and k=0.67 for Zn, is required to estimate the retrospective levels of these elements in the parental non-processed fresh (wet) prostate tissue. The technique used in this study enables the analysis of archival FFPE prostate tissue for the concentrations of Fe, Zn, Se and Cd to study association between the levels of these metals and prostate disease. ?? 2008.

Lethal and sublethal effects of cadmium in the white shrimp Palaemonetes argentinus: a comparison between populations from contaminated and reference sites.

PubMed

Chiodi Boudet, Leila; Polizzi, Paula; Romero, María Belén; Robles, Alicia; Gerpe, Marcela

2013-03-01

In the present study, the acute toxicity of cadmium (Cd) in white shrimp (Palaemonetes argentinus) from a metal polluted lagoon (Los Padres, LP) and from unpolluted lagoon (Nahuel Ruca, NR) was evaluated. Both population, were exposed to 3.06, 12.26, 30.66, 61.32, 306 and 613.2 μg Cd · L(-1) for 96-h. The sublethal effects of Cd were examined by two cellular biomarkers: metallothionein (MT) and lipid peroxidation (LPO). The seasonal variations of biomarkers in both lagoons were also evaluated. P. argentinus demonstrated a high sensitivity to Cd, with values of 96-h LC50 lower and close to those of highly sensitive species; therefore, can be proposed as a good indicator species. The LC(50) values of shrimp from LP (24-h: 269.8, 48-h: 67.45, 72-h: 30.66, 96-h: 24.50 μg Cd · L(-1)) were higher than those from NR (24-h: 153.3, 48-h: 32.65, 72-h: 18.40, 96-h: 12.26 μg Cd · L(-1)), indicating a higher tolerance to Cd, and it was related to their origin. Differential responses in terms of MT induction and LPO between populations were also detected. In NR shrimps, the MT synthesis was induced very fast (24-h) and even at the minimum concentration tested (3.06 μg Cd · L(-1)), while no increases were observed in LPO levels. In contrast, the MT and LPO levels in LP shrimps were not increased relative to control, although they were more tolerant to Cd than those of NR; suggesting the presence of another mechanism involved in the detoxification of Cd. The differences in both sensitivity and biochemical responses to Cd may be related with their environmental histories. Copyright © 2012 Elsevier Inc. All rights reserved.

Integration and task shifting for TB/HIV care and treatment in highly resource-scarce settings: one size may not fit all.

PubMed

Van Rie, Annelies; Patel, Monita R; Nana, Mbonze; Vanden Driessche, Koen; Tabala, Martine; Yotebieng, Marcel; Behets, Frieda

2014-03-01

A crucial question in managing HIV-infected patients with tuberculosis (TB) concerns when and how to initiate antiretroviral therapy (ART). The effectiveness of CD4-stratified ART initiation in a nurse-centered, integrated TB/HIV program at primary care in Kinshasa, Democratic Republic of Congo, was assessed. Prospective cohort study was conducted to assess the effect of CD4-stratified ART initiation by primary care nurses (513 TB patients, August 2007 to November 2009). ART was to be initiated at 1 month of TB treatment if CD4 count is <100 cells per cubic millimeter, at 2 months if CD4 count is 100-350 cells per cubic millimeter, and at the end of TB treatment after CD4 count reassessment if CD4 count is >350 cells per cubic millimeter. ART uptake and mortality were compared with a historical prospective cohort of 373 HIV-infected TB patients referred for ART to a centralized facility and 3577 HIV-negative TB patients (January 2006 to May 2007). ART uptake increased (17%-69%, P < 0.0001) and mortality during TB treatment decreased (20.1% vs 9.8%, P < 0.0003) after decentralized, nurse-initiated, CD4-stratified ART. Mortality among TB patients with CD4 count >100 cells per cubic millimeter was similar to that of HIV-negative TB patients (5.6% vs 6.3%, P = 0.65), but mortality among those with CD4 count <100 cells per cubic millimeter remained high (18.8%). Nurse-centered, CD4-stratified ART initiation at primary care level was effective in increasing timely ART uptake and reducing mortality among TB patients but may not be adequate to prevent mortality among those presenting with severe immunosuppression. Further research is needed to determine the optimal management at primary care level of TB patients with CD4 counts <100 cells per cubic millimeter.

Does pretransplant soluble CD30 serum concentration affect deceased-donor kidney graft function 3 years after transplantation?

PubMed

Kovac, J; Arnol, M; Vidan-Jeras, B; Bren, A F; Kandus, A

2008-06-01

Elevated serum concentrations of soluble CD30 molecule (sCD30) have been related to acute cellular rejection and poor graft outcomes in kidney transplantation. This historical cohort study investigated the association of pretransplant sCD30 serum concentrations with kidney graft function expressed as estimated glomerular filtration rate (GFR) at 3 years after transplantation. Pretransplant sera from 176 adult deceased-donor kidney graft recipients were tested for sCD30 content using a commercially available automated enzyme-linked immunosorbent assay. The immunosuppression consisted of induction therapy with monoclonal anti-CD25 antibodies and a maintenance regimen of cyclosporine (CsA)-based therapy. GFR was estimated (eGFR) by the four-variable Modification of Diet in Renal Disease (MDRD) Study equation. According to the distribution of pretransplant sCD30 levels (median 66.7 U/mL; interquartile range, 46.6 to 98.6 U/mL), a concentration of 66 U/mL or higher was defined as high (n = 89) and below 66 U/mL as low (n = 87). Three years after transplantation, eGFR was not significantly different among recipients in high versus low sCD30 groups (69 +/- 23 mL/min/1.73m2 vs 66 +/- 21 mL/min/1.73m2; P = .327) and there was no correlation between eGFR and pretransplant sCD30 levels (r2 = 0.001; P = .73). Upon multivariate regression analysis, donor age, recipient body mass index at transplantation, and acute rejection episodes were independent variables affecting eGFR at 3 years after transplantation. This study showed that pretransplant sCD30 serum concentrations were not associated with deceased-donor kidney graft function at 3 years after transplantation. The immunosuppression with anti-CD25 antibodies and a triple CsA-based maintenance regimen could possibly be decisive for our findings.

High Cellular Monocyte Activation in People Living With Human Immunodeficiency Virus on Combination Antiretroviral Therapy and Lifestyle-Matched Controls Is Associated With Greater Inflammation in Cerebrospinal Fluid

PubMed Central

Booiman, Thijs; Wit, Ferdinand W.; Maurer, Irma; De Francesco, Davide; Sabin, Caroline A.; Harskamp, Agnes M.; Prins, Maria; Garagnani, Paolo; Pirazzini, Chiara; Franceschi, Claudio; Fuchs, Dietmar; Gisslén, Magnus; Winston, Alan; Reiss, Peter; Reiss, P.; Wit, F. W. N. M.; Schouten, J.; Kooij, K. W.; van Zoest, R. A.; Elsenga, B. C.; Janssen, F. R.; Heidenrijk, M.; Zikkenheiner, W.; van der Valk, M.; Kootstra, N. A.; Booiman, T.; Harskamp-Holwerda, A. M.; Boeser-Nunnink, B.; Maurer, I.; Mangas Ruiz, M. M.; Girigorie, A. F.; Villaudy, J.; Frankin, E.; Pasternak, A.; Berkhout, B.; van der Kuyl, T.; Portegies, P.; Schmand, B. A.; Geurtsen, G. J.; ter Stege, J. A.; Klein Twennaar, M.; Majoie, C. B. L. M.; Caan, M. W. A.; Su, T.; Weijer, K.; Bisschop, P. H. L. T.; Kalsbeek, A.; Wezel, M.; Visser, I.; Ruhé, H. G.; Franceschi, C.; Garagnani, P.; Pirazzini, C.; Capri, M.; Dall’Olio, F.; Chiricolo, M.; Salvioli, S.; Hoeijmakers, J.; Pothof, J.; Prins, M.; Martens, M.; Moll, S.; Berkel, J.; Totté, M.; Kovalev, S.; Gisslén, M.; Fuchs, D.; Zetterberg, H.; Winston, A.; Underwood, J.; McDonald, L.; Stott, M.; Legg, K.; Lovell, A.; Erlwein, O.; Doyle, N.; Kingsley, C.; Sharp, D. J.; Leech, R.; Cole, J. H.; Zaheri, S.; Hillebregt, M. M. J.; Ruijs, Y. M. C.; Benschop, D. P.; Burger, D.; de Graaff-Teulen, M.; Guaraldi, G.; Bürkle, A.; Sindlinger, T.; Moreno-Villanueva, M.; Keller, A.; Sabin, C.; de Francesco, D.; Libert, C.; Dewaele, S.

2017-01-01

Abstract Background. Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). Methods. A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation, intestinal damage, and inflammation in plasma and cerebrospinal fluid (CSF) of PLHIV with suppressed plasma viremia on combination antiretroviral therapy and age and demographically comparable HIV-negative individuals participating in the Comorbidity in Relation to AIDS (COBRA) cohort and, where appropriate, age-matched blood bank donors (BBD). Results. People living with HIV, HIV-negative individuals, and BBD had comparable percentages of classical, intermediate, and nonclassical monocytes. Expression of CD163, CD32, CD64, HLA-DR, CD38, CD40, CD86, CD91, CD11c, and CX3CR1 on monocytes did not differ between PLHIV and HIV-negative individuals, but it differed significantly from BBD. Principal component analysis revealed that 57.5% of PLHIV and 62.5% of HIV-negative individuals had a high monocyte activation profile compared with 2.9% of BBD. Cellular monocyte activation in the COBRA cohort was strongly associated with soluble markers of monocyte activation and inflammation in the CSF. Conclusions. People living with HIV and HIV-negative COBRA participants had high levels of cellular monocyte activation compared with age-matched BBD. High monocyte activation was predictive for inflammation in the CSF. PMID:28680905

Soluble CD30 is more relevant to disease activity of atopic dermatitis than soluble CD26

PubMed Central

Katoh, N; Hirano, S; Suehiro, M; Ikenaga, K; Yamashita, T; Sugawara, N; Yasuno, H

2000-01-01

It is suggested that CD30 and CD26 are surface molecules expressed on activated Th2 and Th1 cells, respectively. We examined plasma levels of soluble CD26 (sCD26) and sCD30 in patients with atopic dermatitis (AD) when their eruptions were aggravated and in non-atopic healthy controls, and then analysed the possible correlation between these values and the levels of several clinical markers. The plasma levels of both sCD30 and sCD26 were significantly higher in AD patients than in controls, both in exacerbation status and after conventional treatment. Multiple regression analyses showed that plasma sCD30 was a much better predictor of the levels of serum IgE, serum LDH and plasma sCD25, and the area and the score of AD eruption than sCD26, although elevated levels of both sCD30 and sCD26 are associated with these clinical predictors of AD. Importantly, sCD30 plasma levels decreased significantly in AD patients after conventional treatment, while no significant transition was noted in the concentration of sCD26. Moreover, a significant reduction of sCD30 levels was observed in the group of patients whose eruption score was reduced > 50%, whereas it was not in those < 50%. These findings provide evidence that the successful treatment of AD is associated with down-activation of Th2. PMID:10931130

Concentration of cadmium in cacao beans and its relationship with soil cadmium in southern Ecuador.

PubMed

Chavez, E; He, Z L; Stoffella, P J; Mylavarapu, R S; Li, Y C; Moyano, B; Baligar, V C

2015-11-15

Cadmium (Cd) content in cacao beans above a critical level (0.6 mg kg(-1)) has raised concerns in the consumption of cacao-based chocolate. Little is available regarding Cd concentration in soil and cacao in Ecuador. The aim of this study was to determine the status of Cd in both, soils and cacao plants, in southern Ecuador. Soil samples were collected from 19 farms at 0-5, 5-15, 15-30, and 30-50 cm depths, whereas plant samples were taken from four nearby trees. Total recoverable and extractable Cd were measured at the different soil depths. Total recoverable Cd ranged from 0.88 to 2.45 and 0.06 to 2.59, averaged 1.54 and 0.85 mg kg(-1), respectively in the surface and subsurface soils whereas the corresponding values for M3-extractable Cd were 0.08 to 1.27 and 0.02 to 0.33 with mean values of 0.40 and 0.10 mg kg(-1). Surface soil in all sampling sites had total recoverable Cd above the USEPA critical level for agricultural soils (0.43 mg kg(-1)), indicating that Cd pollution occurs. Since both total recoverable and M3-extractable Cd significantly decreased depth wise, anthropogenic activities are more likely the source of contamination. Cadmium in cacao tissues decreased in the order of beans>shell>leaves. Cadmium content in cacao beans ranged from 0.02 to 3.00, averaged 0.94 mg kg(-1), and 12 out of 19 sites had bean Cd content above the critical level. Bean Cd concentration was highly correlated with M3- or HCl-extractable Cd at both the 0-5 and 5-15 cm depths (r=0.80 and 0.82 for M3, and r=0.78 and 0.82 for HCl; P<0.01). These results indicate that accumulation of Cd in surface layers results in excessive Cd in cacao beans and M3- or HCl-extractable Cd are suitable methods for predicting available Cd in the studied soils. Copyright © 2015 Elsevier B.V. All rights reserved.

Metal contamination of soils and crops affected by the Chenzhou lead/zinc mine spill (Hunan, China).

PubMed

Liu, Hongyu; Probst, Anne; Liao, Bohan

2005-03-01

In 1985, the collapse of the tailing dam in Chenzhou lead/zinc mine (Hunan, southern China) led to the spread of mining waste spills on the farmland along the Dong River. After the accident, an urgent soil cleaning up was carried out in some places. Seventeen years later, cereal (rice, maize, and sorghum), pulses (soybean, Adzuki bean, mung bean and peanut), vegetables (ipomoea, capsicum, taro and string bean) and the rooted soils were sampled at four sites: (1) the mining area (SZY), (2) the area still covered with the mining tailing spills (GYB), (3) the cleaned area from mining tailing spills (JTC), and (4) a background site (REF). Metal concentrations in the crops and soils were analyzed to evaluate the long-term effects of the spilled waste on the soil and the potential human exposure through food chains. The results showed that the physical-chemical properties of the soils obviously changed due to the different farming styles used by each individual farmer. Leaching effects and plant extraction of metals from some soils were quite weak. Certain soils were still heavily polluted with As, Cd, Zn, Pb and Cu. The contamination levels were in the order of GYB>SZY>JTC showing that the clean-up treatment was effective. The maximum allowable concentration (MAC) levels for Chinese agricultural soils were still highly exceeded, particularly for As and Cd (followed by Zn, Pb and Cu), with mean concentrations of 709 and 7.6 mg kg(-1), respectively. These concentrations exceed the MAC levels by 24 times for As and 13 times for Cd at GYB. Generally, the edible leaves or stems of crops were more heavily contaminated than seeds or fruits. Ipomoea was the most severely contaminated crop. The concentrations of Cd and Pb were 3.30 and 76.9 mg kg(-1) in ipomoea leaves at GYB, which exceeded the maximum permit levels (0.5 mg kg(-1) for Cd and 9 mg kg(-1) for Pb) by 6.6 and 8.5 times, respectively. Taro (+skin) could accumulate high concentrations of Zn and Cd in the edible stem, and rice and capsicum had high Cd concentration in the edible parts. However, the toxic element concentrations in maize, sorghum, Adzuki bean, soybean and mung bean remained lower than the threshold levels. The bio-accumulation factors (BAFs) of crops were in the order: Cd>Zn>Cu>Pb>As. BAF was typically lower in the edible seeds or fruits than in stems and leaves. The accumulation effect strongly depends on the crop's physiological properties, the mobility, of the metals, and the availability of metals in soils but not entirely on the total element concentrations in the soils. Even so, the estimated daily intake amount of Cu, Zn, Cd, and Pb from the crops grown in the affected three sites and arsenic at SZY and GYB exceeded the RDA (Recommended dietary allowance) levels. Subsequently, the crops grown in Chenzhou Pb/Zn mine waste affected area might have a hazardous effect on the consumer's health. This area still needs effective measures to cure the As, Cd, Pb, Zn and Cu contamination.

Soluble CD30 and HLA antibodies as potential risk factors for kidney transplant rejection.

PubMed

Slavcev, Antonij; Lácha, Jiri; Honsová, Eva; Sajdlová, Helena; Lodererová, Alena; Vitko, Stefan; Skibová, Jelena; Striz, Ilja

2005-06-01

Recent literary data suggest that high pre- and post-transplant serum levels of the soluble CD30 (sCD30) molecule may be a risk factor for acute rejection and worse prognosis of the transplanted kidney. The aim of our study was to correlate the concentrations of sCD30 and the presence of HLA antibodies as defined by flow cytometry and ELISA with the clinical course and graft prognosis after transplantation. One hundred and seventeen kidney transplant patients were included into the study. The incidence of rejection episodes, graft function and graft survival for up to 1 year post-transplant were evaluated. Soluble CD30 levels before transplantation were virtually the same in patients who experienced rejection and in non-rejecting patients. In both patient groups, a significant decrease of sCD30 was detected 2 weeks after transplantation (104.4 U/ml before vs. 37.0 U/ml post-transplant, P < 0.001). However, there was a substantial difference in the level of decrease of sCD30 between rejecting and non-rejecting patients. Patients without rejection had lower sCD30 values (31.2 U/ml post-transplant) compared to patients who experienced rejection episodes (62.9 U/ml), P < 0.04. Multifactorial analysis showed that antibodies to HLA class II antigens and elevated concentrations of sCD30 shortly after transplantation were associated with increased risk for acute rejection in the first post-transplant year. Measurement of soluble CD30 after transplantation, taken into consideration with the presence of HLA class II antibodies, might be helpful for evaluating the potential risk for acute rejection.

Levels of human platelet-derived soluble CD40 ligand depend on haplotypes of CD40LG-CD40-ITGA2

PubMed Central

Aloui, Chaker; Prigent, Antoine; Tariket, Sofiane; Sut, Caroline; Fagan, Jocelyne; Cognasse, Fabrice; Chakroun, Tahar; Garraud, Olivier; Laradi, Sandrine

2016-01-01

Increased circulating soluble CD40 ligand (sCD40L) is commonly associated with inflammatory disorders. We aimed to investigate whether gene polymorphisms in CD40LG, CD40 and ITGA2 are associated with a propensity to secrete sCD40L; thus, we examined this issue at the level of human platelets, the principal source of sCD40L. We performed single polymorphism and haplotype analyses to test for the effect of twelve polymorphisms across the CD40LG, CD40 and ITGA2 genes in blood donors. ITGA2 presented a positive association with rs1126643, with a significant modification in sCD40L secretion (carriers of C allele, P = 0.02), unlike the investigated CD40LG and CD40 polymorphisms. One CD40LG haplotype (TGGC) showing rs975379 (C/T), rs3092952 (A/G), rs3092933 (A/G) and rs3092929 (A/C) was associated with increased sCD40L levels (1.906 μg/L (95% CI: 1.060 to 2.751); P = 0.000009). The sCD40L level was associated with the inter-chromosomal CD40LG/CD40/ITGA2 haplotype (ATC), displaying rs3092952 (A/G), rs1883832 (C/T) and rs1126643 (C/T), with increased sCD40L levels (P = 0.0135). Our results help to decipher the genetic role of CD40LG, CD40 and ITGA2 with regard to sCD40L levels found in platelet components. Given the crucial role of sCD40L, this haplotype study in a transfusion model may be helpful to further determine the role of haplotypes in inflammatory clinical settings. PMID:27094978

Molecular beam epitaxial growth, transmittance and photoluminescence spectra of zinc-blende CdTe thin films with high-quality on perovskite SrTiO3 (1 1 1) substrates

NASA Astrophysics Data System (ADS)

Song, Kun; Zhu, Xuanting; Tang, Kai; Bai, W.; Zhu, Liangqing; Yang, Jing; Zhang, Yuanyuan; Tang, Xiaodong; Chu, Junhao

2018-03-01

High-crystalline quality CdTe thin films are grown on the largely lattice-mismatched SrTiO3 (STO) (1 1 1) substrates by molecular beam epitaxy. A transformation from a three dimensional regime to a two dimensional one is observed by the reflection high energy electron diffraction (RHEED) and atomic force microscopy (AFM). The formation of an elastic deformation CdTe layer on STO (1 1 1), namely a pseudomorphic growth mode with a critical thickness of ∼40 nm, is supported by the RHEED, AFM and X-ray diffraction. Crystal structures and epitaxial relationships of CdTe epitaxial films on STO (1 1 1) are characterized by 2θ-ω scans and reciprocal space mapping. Two strong absorption peaks at the energies of ∼1.621 eV and ∼1.597 eV at 5 K are clearly observed for a ∼120 nm thick CdTe epitaxial film, which are proposed to be ascribed to the strained and unstrained epitaxial CdTe layers, respectively. Moreover, the presence of the exciton band while the absence of deep level defect states for the ∼120 nm thick CdTe film characterized by the temperature dependent photoluminescence spectra further supports the high-crystalline quality.

CD4+CD73+ T cells are associated with lower T-cell activation and C reactive protein levels and are depleted in HIV-1 infection regardless of viral suppression

PubMed Central

Schuler, Patrick J.; Macatangay, Bernard J.C.; Saze, Zenichiro; Jackson, Edwin K.; Riddler, Sharon A.; Buchanan, William G.; Hilldorfer, Benedict B.; Mellors, John W.; Whiteside, Theresa L.; Rinaldo, Charles R.

2013-01-01

Background The role of the adenosine (ADO) suppression pathway, specifically CD39-expressing and CD73-expressing CD4+ T cells in HIV-1 infection is unclear. Methods We evaluated the frequency and numbers of CD4+CD39+ and CD4+CD73+ T cells, activated T cells, and plasma C reactive protein (CRP) levels in 36 HIV-1-positive individuals and 10 normal controls (NC). Low-level plasma viremia was evaluated using single copy assay. Mass spectrometry was used to measure hydrolysis of ATP by ectoenzyme-expressing CD4+ T cells, whereas cyclic adenosine monophosphate (cAMP) levels were measured using enzyme immunoassay. Suppression of T-cell function by exogenous ADO and CD4+CD73+ T cells was tested by flow cytometry. Results CD39 and CD73 are expressed in different CD4+ T-cell subsets. CD4+CD73+ T cells do not express CD25 and FOXP3, and their frequency and numbers were lower in HIV-1-positive individuals regardless of virologic suppression (P = 0.005 and P < 0.001, respectively). CD4+CD73+ numbers inversely correlated with CD4+CD38+DR+ (P = 0.002), CD8+CD38+DR+ T-cell frequency (P = 0.05), and plasma CRP levels (P = 0.01). Both subsets are required for hydrolysis of exogenous ATP to ADO and can increase CD4+ T-cell cAMP levels when incubated with exogenous ATP. Low-level viremia did not correlate with activated T-cell frequency. In vitro, ADO suppressed T-cell activation and cytokine expression. CD4+CD73+ T cells suppressed T-cell proliferation only in the presence of exogenous 5′-AMP. Conclusion The ADO-producing CD4+CD73+ subset of T cells is depleted in HIV-1-positive individuals regardless of viral suppression and may play a key role in controlling HIV-1-associated immune activation. PMID:24005375

Variability in emotional/behavioral problems in boys with oppositional defiant disorder or conduct disorder: the role of arousal.

PubMed

Schoorl, Jantiene; Van Rijn, Sophie; De Wied, Minet; Van Goozen, Stephanie H M; Swaab, Hanna

2016-08-01

It is often reported that children with oppositional defiant disorder (ODD) or conduct disorder (CD) are under-aroused. However, the evidence is mixed, with some children with ODD/CD displaying high arousal. This has led to the hypothesis that different profiles of arousal dysfunction may exist within children with ODD/CD. This knowledge could explain variability within children with ODD/CD, both in terms of specific types of aggression as well as comorbid symptoms (e.g., other emotional/behavioral problems). We measured heart rate variability (HRV), heart rate (HR) and skin conductance level (SCL) during rest and stress, and obtained parent and teacher reports of aggression, anxiety, attention problems and autism traits in a sample of 66 ODD/CD and 36 non-clinical boys (aged 8-12 years). The ODD/CD group scored significantly higher on aggression, anxiety, attention problems and autism traits than the controls; boys with ODD/CD also had higher resting HRs than controls, but HR stress, HRV and SCL did not differ. Hierarchical regressions showed different physiological profiles in subgroups of boys with ODD/CD based on their type of aggression; a pattern of high baseline HR and SCL, but low stress HRV was related to reactive aggression, whereas the opposite physiological pattern (low HR, low stress SCL, high stress HRV) was related to proactive aggression. Furthermore, high stress SCL was related to anxiety symptoms, whereas low stress SCL was related to attention problems. These findings are important because they indicate heterogeneity within boys with ODD/CD and highlight the importance of using physiology to differentiate boys with different ODD/CD subtypes.

Endothelial Progenitor Cell Levels Predict Future Physical Function: An Exploratory Analysis From the VA Enhanced Fitness Study.

PubMed

Povsic, Thomas J; Sloane, Richard; Pieper, Carl F; Pearson, Megan P; Peterson, Eric D; Cohen, Harvey J; Morey, Miriam C

2016-03-01

Levels of circulating progenitor cells (CPCs) are depleted with aging and chronic injury and are associated with level of physical functioning; however, little is known about the correlation of CPCs with longer-term measures of physical capabilities. We sought to determine the association of CPCs with future levels of physical function and with changes in physical function over time. CPCs were measured in 117 participants with impaired glucose tolerance in the Enhanced Fitness clinical trial based on the cell surface markers CD34 and CD133 and aldehyde dehydrogenase (ALDH) activity at baseline, 3 months, and 12 months. Physical function was assessed using usual and rapid gait speed, 6-minute walk distance, chair stand time, and SF-36 physical functioning score and reassessed at 3 and 12 months after clinical intervention. Higher baseline levels of CD133(+), CD34(+), CD133(+)CD34(+), and ALDH(br) were each highly predictive of faster gait speed and longer distance walked in 6 minutes at both 3 and 12 months. These associations remained robust after adjustment for age, body mass index, baseline covariates, and inflammation and were independent of interventions to improve physical fitness. Further, higher CPC levels predicted greater improvements in usual and rapid gait speed over 1 year. Baseline CPC levels are associated not only with baseline mobility but also with future physical function, including changes in gait speed. These findings suggest that CPC measurement may be useful as a marker of both current and future physiologic aging and functional decline. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

IL-1R and MyD88 signalling in CD4+ T cells promote Th17 immunity and atherosclerosis.

PubMed

Engelbertsen, Daniel; Rattik, Sara; Wigren, Maria; Vallejo, Jenifer; Marinkovic, Goran; Schiopu, Alexandru; Björkbacka, Harry; Nilsson, Jan; Bengtsson, Eva

2018-01-01

The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper sub-sets. In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4+ T cells in atherosclerosis. We transferred apoe-/-myd88+/+ or apoe-/-myd88-/- CD4+ T cells to T- and B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared with mice given apoe-/-myd88+/+ CD4+ T cells. CD4+ T cells from apoe-/-myd88-/- produced less IL-17 but similar levels of IFN-γ. Treatment of human CD4+ T cells with a MyD88 inhibitor inhibited IL-17 secretion in vitro. Transfer of il1r1-/- CD4+ T cells recapitulated the phenotype seen by transfer of myd88-/- CD4+ T cells with reduced lesion development and a reduction in Th17 and IL-17 production compared with wild type CD4+ T cell recipients. Relative collagen content of lesions was reduced in mice receiving il1r1-/- CD4+ T cells. We demonstrate that both IL1R and MyD88 signalling in CD4+ T cells promote Th17 immunity, plaque growth and may regulate plaque collagen levels. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

Human Immune Disorder Arising from Mutation of the α Chain of the Interleukin-2 Receptor

NASA Astrophysics Data System (ADS)

Sharfe, Nigel; Dadi, Harjit K.; Shahar, Michal; Roifman, Chaim M.

1997-04-01

Profound cellular immunodeficiency occurs as the result of mutations in proteins involved in both the differentiation and function of mature lymphoid cells. We describe here a novel human immune aberration arising from a truncation mutation of the interleukin-2 receptor α chain (CD25), a subunit of the tripartite high-affinity receptor for interleukin 2. This immunodeficiency is characterized by decreased numbers of peripheral T cells displaying abnormal proliferation but normal B cell development. Extensive lymphocytic infiltration of tissues, including lung, liver, gut, and bone, is observed, accompanied by tissue atrophy and inflammation. Although mature T cells are present, the absence of CD25 does affect the differentiation of thymocytes. While displaying normal development of CD2, CD3, CD4, and CD8 expression, CD25-deficient cortical thymocytes do not express CD1, and furthermore they fail to normally down-regulate levels of the anti-apoptotic protein bcl-2.

CD83 is a new potential biomarker and therapeutic target for Hodgkin lymphoma.

PubMed

Li, Ziduo; Ju, Xinsheng; Lee, Kenneth; Clarke, Candice; Hsu, Jennifer L; Abadir, Edward; Bryant, Christian E; Pears, Suzanne; Sunderland, Neroli; Heffernan, Scott; Hennessy, Annemarie; Lo, Tsun-Ho; Pietersz, Geoffrey A; Kupresanin, Fiona; Fromm, Phillip D; Silveira, Pablo A; Tsonis, Con; Cooper, Wendy A; Cunningham, Ilona; Brown, Christina; Clark, Georgina J; Hart, Derek N J

2018-04-01

Chemotherapy and hematopoietic stem cell transplantation are effective treatments for most Hodgkin lymphoma patients, however there remains a need for better tumor-specific target therapy in Hodgkin lymphoma patients with refractory or relapsed disease. Herein, we demonstrate that membrane CD83 is a diagnostic and therapeutic target, highly expressed in Hodgkin lymphoma cell lines and Hodgkin and Reed-Sternberg cells in 29/35 (82.9%) Hodgkin lymphoma patient lymph node biopsies. CD83 from Hodgkin lymphoma tumor cells was able to trogocytose to surrounding T cells and, interestingly, the trogocytosing CD83 + T cells expressed significantly more programmed death-1 compared to CD83 - T cells. Hodgkin lymphoma tumor cells secreted soluble CD83 that inhibited T-cell proliferation, and anti-CD83 antibody partially reversed the inhibitory effect. High levels of soluble CD83 were detected in Hodgkin lymphoma patient sera, which returned to normal in patients who had good clinical responses to chemotherapy confirmed by positron emission tomography scans. We generated a human anti-human CD83 antibody, 3C12C, and its toxin monomethyl auristatin E conjugate, that killed CD83 positive Hodgkin lymphoma cells but not CD83 negative cells. The 3C12C antibody was tested in dose escalation studies in non-human primates. No toxicity was observed, but there was evidence of CD83 positive target cell depletion. These data establish CD83 as a potential biomarker and therapeutic target in Hodgkin lymphoma. Copyright© 2018 Ferrata Storti Foundation.

Growth, cadmium uptake and accumulation of maize (Zea mays L.) under the effects of arbuscular mycorrhizal fungi.

PubMed

Liu, Lingzhi; Gong, Zongqiang; Zhang, Yulong; Li, Peijun

2014-12-01

The effects of three arbuscular mycorrhizal fungi isolates on Cd uptake and accumulation by maize (Zea mays L.) were investigated in a planted pot experiment. Plants were inoculated with Glomus intraradices, Glomus constrictum and Glomus mosseae at three different Cd concentrations. The results showed that root colonization increased with Cd addition during a 6-week growth period, however, the fungal density on roots decreased after 9-week growth in the treatments with G. constrictum and G. mosseae isolates. The percentage of mycorrhizal colonization by the three arbuscular mycorrhizal fungi isolates ranged from 22.7 to 72.3%. Arbuscular mycorrhizal fungi inoculations decreased maize biomass especially during the first 6-week growth before Cd addition, and this inhibitory effect was less significant with Cd addition and growth time. Cd concentrations and uptake in maize plants increased with arbuscular mycorrhizal fungi colonization at low Cd concentration (0.02 mM): nonetheless, it decreased at high Cd concentration (0.20 mM) after 6-week growth period. Inoculation with G. constrictum isolates enhanced the root Cd concentrations and uptake, but G. mosseae isolates showed the opposite results at high Cd concentration level after 9 week growth period, as compared to non-mycorrhizal plants. In conclusion, maize plants inoculated with arbuscular mycorrhizal fungi were less sensitive to Cd stress than uninoculated plants. G. constrictum isolates enhanced Cd phytostabilization and G. mosseae isolates reduced Cd uptake in maize (Z. mays L.).

The Majority of HIV Type 1 DNA in Circulating CD4+ T Lymphocytes Is Present in Non-Gut-Homing Resting Memory CD4+ T Cells

PubMed Central

Xu, Yin; Bailey, Michelle; Seddiki, Nabila; Suzuki, Kazuo; Murray, John M.; Gao, Yuan; Yan, Celine; Cooper, David A.; Kelleher, Anthony D.; Koelsch, Kersten K.; Zaunders, John

2013-01-01

Abstract Memory CD4+ T lymphocytes in peripheral blood that express integrins α4ß7 preferentially recirculate through gut-associated lymphoid tissue (GALT), a proposed site of significant HIV-1 replication. Tregs and activated CD4+ T cells in GALT could also be particularly susceptible to infection. We therefore hypothesized that infection of these subsets of memory CD4+ T cells may contribute disproportionately to the HIV-1 reservoir. A cross-sectional study of CD4+ T cell subsets of memory CD45RO+ cells in peripheral blood mononuclear cells (PBMCs) was conducted using leukapheresis from eight subjects with untreated chronic HIV-1 infection. Real-time polymerase chain reaction (PCR) was used to quantify total and integrated HIV-1 DNA levels from memory CD4+ T cells sorted into integrin β7+ vs. β7−, CD25+CD127low Treg vs. CD127high, and activated CD38+ vs. CD38−. More than 80% of total HIV-1 DNA was found to reside in the integrin β7-negative non-gut-homing subset of CD45RO+ memory CD4+ T cells. Less than 10% was found in highly purified Tregs or CD38+ activated memory cells. Similarly, integrated HIV-1 DNA copies were found to be more abundant in resting non-gut-homing memory CD4+ T cells (76%) than in their activated counterparts (23%). Our investigations showed that the majority of both total and integrated HIV-1 DNA was found within non-gut-homing resting CD4+ T cells. PMID:23971972

Slit2 Modulates the Inflammatory Phenotype of Orbit-Infiltrating Fibrocytes in Graves' Disease.

PubMed

Fernando, Roshini; Grisolia, Ana Beatriz Diniz; Lu, Yan; Atkins, Stephen; Smith, Terry J

2018-06-15

Human CD34 + fibrocytes, circulating monocyte lineage progenitor cells, have recently been implicated in thyroid-associated ophthalmopathy (TAO), the ocular manifestation of Graves' disease (GD). Fibrocytes express constitutive MHC class II (MHC-2) and, surprisingly, thyroglobulin (Tg) and functional thyrotropin (TSH) receptor (TSHR). Underlying expression of these thyroid proteins is the autoimmune regulator protein (AIRE). Fibrocytes respond robustly to TSH and thyroid-stimulating Igs by generating extremely high levels of inflammatory cytokines, such as IL-6. In TAO, they appear to infiltrate the orbit, where they transition to CD34 + orbital fibroblasts (OF). There, they coexist with CD34 - OF as a mixed fibroblast population (GD-OF). In contrast to fibrocytes, GD-OF express vanishingly low levels of MHC-2, Tg, TSHR, and AIRE. Further, the amplitude of IL-6 induction by TSH in GD-OF is substantially lower. The molecular basis for this divergence between fibrocytes and CD34 + OF remains uncertain. In this article, we report that Slit2, an axon guidance glycoprotein, is constitutively expressed by the CD34 - OF subset of GD-OF. Culture conditioned medium (CM) generated by incubating with GD-OF and CD34 - OF substantially reduces levels of MHC-2, Tg, TSHR, and AIRE in fibrocytes. Expression can be restored by specifically depleting CM of Slit2. The effects of CD34 - OF CM are mimicked by recombinant human Slit2. TSH induces Slit2 levels in GD-OF by enhancing both Slit2 gene transcription and mRNA stability. These findings suggest that Slit2 represents a TSH-inducible factor within the TAO orbit that can modulate the inflammatory phenotype of CD34 + OF and therefore may determine the activity and severity of the disease. Copyright © 2018 by The American Association of Immunologists, Inc.

Effect of exogenous nitric oxide on antioxidative system and S-nitrosylation in leaves of Boehmeria nivea (L.) Gaud under cadmium stress.

PubMed

Wang, Dafei; Liu, Yunguo; Tan, Xiaofei; Liu, Hongyu; Zeng, Guangming; Hu, Xinjiang; Jian, Hao; Gu, Yanling

2015-03-01

Cadmium (Cd)-induced growth inhibition is one of the primary factors limiting phytoremediation effect of Boehmeria nivea (L.) Gaud in contaminated soil. Sodium nitroprusside (SNP), a donor of nitric oxide (NO), has been evidenced to alleviate Cd toxicity in many plants. However, as an important mechanism of NO in orchestrating cellular functions, S-nitrosylation is still poorly understood in its relation with Cd tolerance of plants. In this study, higher exogenous NO levels were found to coincide with higher S-nitrosylation level expressed as content of S-nitrosothiols (SNO). The addition of low concentration (100 μM) SNP increased the SNO content, and it simultaneously induced an alleviating effect against Cd toxicity by enhancing the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR) and reduced the accumulation of H2O2 as compared with Cd alone. Application of S-nitrosoglutathione reductase (GSNOR) inhibitors dodecanoic acid (DA) in 100 μM SNP group brought in an extra elevation in S-nitrosylation level and further reinforced the effect of SNP. While the additions of 400 μM SNP and 400 μM SNP + 50 μM DA further elevated the S-nitrosylation level, it markedly weakened the alleviating effect against Cd toxicity as compared with the addition of 100 μM SNP. This phenomenon could be owing to excess consumption of glutathione (GSH) to form SNO under high S-nitrosylation level. Therefore, the present study indicates that S-nitrosylation is involved in the ameliorating effect of SNP against Cd toxicity. This involvement exhibited a concentration-dependent property.

CD10/neutral endopeptidase 24.11 in developing human fetal lung. Patterns of expression and modulation of peptide-mediated proliferation.

PubMed

Sunday, M E; Hua, J; Torday, J S; Reyes, B; Shipp, M A

1992-12-01

The cell membrane-associated enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) functions in multiple organ systems to downregulate responses to peptide hormones. Recently, CD10/NEP was found to hydrolyze bombesin-like peptides (BLP), which are mitogens for normal bronchial epithelial cells and small cell lung carcinomas. Growth of BLP-responsive small cell lung carcinomas was potentiated by CD10/NEP inhibition, implicating CD10/NEP in regulation of BLP-mediated tumor growth. BLP are also likely to participate in normal lung development because high BLP levels are found in fetal lung, and bombesin induces proliferation and maturation of human fetal lung in organ cultures and murine fetal lung in utero. To explore potential roles for CD10/NEP in regulating peptide-mediated human fetal lung development, we have characterized temporal and cellular patterns of CD10/NEP expression and effects of CD10/NEP inhibition in organ cultures. Peak CD10/NEP transcript levels are identified at 11-13 wk gestation by Northern blots and localized to epithelial cells and mesenchyme of developing airways by in situ hybridization. CD10/NEP immunostaining is most intense in undifferentiated airway epithelium. In human fetal lung organ cultures, inhibition of CD10/NEP with either phosphoramidon or SCH32615 increases thymidine incorporation by 166-182% (P < 0.025). The specific BLP receptor antagonist, [Leu13-psi(CH2NH)Leu14]bombesin abolishes these effects on fetal lung growth, suggesting that CD10/NEP modulates BLP-mediated proliferation. CD10/NEP expression in the growing front of airway epithelium and the effects of CD10/NEP inhibitors in lung explants implicate the enzyme in the regulation of peptide-mediated fetal lung growth.

Bean Metal-Responsive Element-Binding Transcription Factor Confers Cadmium Resistance in Tobacco1

PubMed Central

Sun, Na; Liu, Meng; Zhang, Wentao; Yang, Wanning; Bei, Xiujuan; Ma, Hui; Qiao, Fan; Qi, Xiaoting

2015-01-01

Cadmium (Cd) is highly toxic to plants. Modulation of Cd-responsive transcription is an important way for Cd detoxification in plants. Metal-responsive element (MRE) is originally described in animal metallothionein genes. Although functional MREs also exist in Cd-regulated plant genes, specific transcription factors that bind MRE to regulate Cd tolerance have not been identified. Previously, we showed that Cd-inducible bean (Phaseolus vulgaris) stress-related gene2 (PvSR2) produces a short (S) PvSR2 transcript (S-PvSR2) driven by an intronic promoter. Here, we demonstrate that S-PvSR2 encodes a bean MRE-binding transcription factor1 (PvMTF-1) that confers Cd tolerance in tobacco (Nicotiana tabacum). PvMTF-1 expression was up-regulated by Cd at the levels of RNA and protein. Importantly, expression of PvMTF-1 in tobacco enhanced Cd tolerance, indicating its role in regulating Cd resistance in planta. This was achieved through direct regulation of a feedback-insensitive Anthranilate Synthase α-2 chain gene (ASA2), which catalyzes the first step for tryptophan biosynthesis. In vitro and in vivo DNA-protein interaction studies further revealed that PvMTF-1 directly binds to the MRE in the ASA2 promoter, and this binding depends on the zinc finger-like motif of PvMTF-1. Through modulating ASA2 up-regulation by Cd, PvMTF-1 increased free tryptophan level and subsequently reduced Cd accumulation, thereby enhancing Cd tolerance of transgenic tobacco plants. Consistent with this observation, tobacco transiently overexpressing ASA2 also exhibited increased tolerance to Cd. We conclude that PvMTF-1 is a zinc finger-like transcription factor that links MRE to Cd resistance in transgenic tobacco through activation of tryptophan biosynthesis. PMID:25624396

Bioavailability of Cadmium in Inexpensive Jewelry

PubMed Central

Miller, Jennifer; Guinn, Daphne; Pearson, Janna

2011-01-01

Objectives: We evaluated the bioavailability of Cd in 86 components of 57 jewelry items found to contain high levels of Cd (> 10,000 ppm) by X-ray fluorescence (XRF), using extractions that simulate mouthing or swallowing of jewelry items. Methods: We screened jewelry for Cd content by XRF. Bioavailability was measured in two ways. Items were placed in saline solution at 37°C for 6 hr to simulate exposures from mouthing of jewelry items. Items were placed in dilute hydrochloric acid (HCl) at 37°C for 6–96 hr, simulating the worst-case scenario of a child swallowing a jewelry item. Damaged pieces of selected samples were also extracted by both methods to determine the effect of breaching the outer plating on bioavailability. Total Cd content of all items was determined by atomic absorption. Results: The 6-hr saline extraction yielded as much as 2,200 µg Cd, and 24-hr dilute HCl extraction yielded a maximum of > 20,000 µg Cd. Leaching of Cd in dilute HCl increased linearly over 6–96 hr, indicating potential for increasing harm the longer an item remains in the stomach. Damage to jewelry by breaching the outer plating generally, but not always, increased Cd release. Bioavailability did not correlate directly with Cd content. Conclusions: These results indicate the potential for dangerous Cd exposures to children who wear, mouth, or accidentally swallow high-Cd jewelry items. PMID:21377949

[Evolution of paroxysmal nocturnal hemoglobinuria clone during an hemolytic crisis in a patient with aplastic anemia. Flow cytometry study].

PubMed

Canalejo, K; Galassi, N; Riera, N; Bengió, R; Aixalá, M

2001-01-01

The expansion of paroxysmal nocturnal hemoglobinuria (PHN) clone was evaluated in a patient with aplastic anemia (AA) of 18 years of evolution during an hemolytic crisis. On day 0, Ham and Sucrosa tests were positive and hematological parameters were altered. Low hemoglobin (Hb) levels and erythrocyte and leukocyte counts were found and continued decreasing on days 7 and 24 (last day of study). High LDH levels, indirect bilirubin and reticulocyte counts were detected throughout. We evaluated CD55 and CD59 on erythrocytes by flow cytometry. Our results showed low CD55 expression with respect to the normal pattern. Since day 0, CD59 staining detected two red cell populations: PNH I (48%), cells with positive fluorescence similar to normal and PNH III (52%), negative cells (PNH clone). These negative cells increased, reaching 70% on day 24. Other membrane anchored leukocyte proteins were also absent (CD14) or decreased (CD16). We found a good correlation between clinical observations, evolution of the laboratory values and expansion of the PNH clone.