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Sample records for internal cd levels

  1. Vitamin D, d-dimer, Interferon γ, and sCD14 Levels are Independently Associated with Immune Reconstitution Inflammatory Syndrome: A Prospective, International Study☆

    PubMed Central

    Musselwhite, Laura W.; Andrade, Bruno B.; Ellenberg, Susan S.; Tierney, Ann; Belaunzaran-Zamudio, Pablo F.; Rupert, Adam; Lederman, Michael M.; Sanne, Ian; Sierra Madero, Juan G.; Sereti, Irini

    2016-01-01

    To determine the immunological profile most important for IRIS prediction, we evaluated 20 baseline plasma biomarkers in Acquired Immunodeficiency Syndrome (AIDS) patients initiating antiretroviral therapy (ART). Patients were enrolled in a randomized, placebo-controlled ART initiation trial in South Africa and Mexico to test whether maraviroc could prevent IRIS. Participants were classified prospectively as having IRIS within 6 months of ART initiation. Twenty plasma biomarkers were measured at study enrollment for 267 participants. Biomarkers were tested for predicting IRIS with adjustment for covariates chosen through forward stepwise selection. Sixty-two participants developed IRIS and of these 19 were tuberculosis (TB)-IRIS. Baseline levels of vitamin D and higher d-dimer, interferon gamma (IFNγ), and sCD14 were independently associated with risk of IRIS in multivariate analyses. TB-IRIS cases exhibited a distinct biosignature from IRIS related to other pathogens, with increased levels of C-reactive protein (CRP), sCD14, IFNγ, and lower levels of Hb that could be captured by a composite risk score. Elevated markers of Type 1 T helper (Th1) response, monocyte activation, coagulation and low vitamin D were independently associated with IRIS risk. Interventions that decrease immune activation and increase vitamin D levels warrant further study. PMID:26981576

  2. Vitamin D, d-dimer, Interferon γ, and sCD14 Levels are Independently Associated with Immune Reconstitution Inflammatory Syndrome: A Prospective, International Study.

    PubMed

    Musselwhite, Laura W; Andrade, Bruno B; Ellenberg, Susan S; Tierney, Ann; Belaunzaran-Zamudio, Pablo F; Rupert, Adam; Lederman, Michael M; Sanne, Ian; Sierra Madero, Juan G; Sereti, Irini

    2016-02-01

    To determine the immunological profile most important for IRIS prediction, we evaluated 20 baseline plasma biomarkers in Acquired Immunodeficiency Syndrome (AIDS) patients initiating antiretroviral therapy (ART). Patients were enrolled in a randomized, placebo-controlled ART initiation trial in South Africa and Mexico to test whether maraviroc could prevent IRIS. Participants were classified prospectively as having IRIS within 6 months of ART initiation. Twenty plasma biomarkers were measured at study enrollment for 267 participants. Biomarkers were tested for predicting IRIS with adjustment for covariates chosen through forward stepwise selection. Sixty-two participants developed IRIS and of these 19 were tuberculosis (TB)-IRIS. Baseline levels of vitamin D and higher d-dimer, interferon gamma (IFNγ), and sCD14 were independently associated with risk of IRIS in multivariate analyses. TB-IRIS cases exhibited a distinct biosignature from IRIS related to other pathogens, with increased levels of C-reactive protein (CRP), sCD14, IFNγ, and lower levels of Hb that could be captured by a composite risk score. Elevated markers of Type 1 T helper (Th1) response, monocyte activation, coagulation and low vitamin D were independently associated with IRIS risk. Interventions that decrease immune activation and increase vitamin D levels warrant further study. PMID:26981576

  3. Internalization and molecular interactions of human CD21 receptor.

    PubMed

    Tessier, Jacques; Cuvillier, Armelle; Glaudet, Florence; Khamlichi, Ahmed Amine

    2007-03-01

    The human CD21 is a receptor for cleavage fragments of the third complement component and for Epstein-Barr virus. Previous mutational studies showed that the cytoplasmic domain of CD21 is absolutely required for internalization of either ligand. With the exception of CD19, CD81, Leu-13 and CD35 that can form a complex with CD21 at the cell surface, no other partner that interacts with the hCD21 transmembrane or the cytoplasmic domain was identified. We investigated the internalization capacity of hCD21 tail mutants in the absence of B cell receptor cross-linking by using stable murine B cell transfectants. We provide evidence that at least two internalization motifs are activated when hCD21 binds a monoclonal antibody. In order to identify the cellular proteins that interact with the hCD21 transmembrane and cytoplasmic domains, we combined a mutational mapping with a two-hybrid system approach both in yeast and in mammalian cells. We identified four novel partners that are involved in intracellular trafficking, sorting or cytoskeleton remodeling and we mapped the hCD21 transmembrane and tail subdomains they interact with. We discuss the potential physiological significance of these findings in the context of hCD21 internalization and intracellular trafficking. PMID:17118449

  4. Looking at soluble CD23 levels to predict lymphoma.

    PubMed

    2001-10-01

    As we noted in our first article on lymphoma, there isn't any quick and simple test to diagnose or predict which PHAs will develop this cancer. Nor are there any symptoms that specifically occur from having lymphoma. To try to remedy the situation, researchers in Italy have been monitoring levels of the a protein called soluble CD23 (sCD23) in the blood and fluid surrounding the brain--cerebrospinal fluid (CSF). They have found higher-than-normal levels of sCD23 in the CSF of PHAs who have brain lymphoma. PMID:11768872

  5. Defect energy levels in Cd-based compounds

    SciTech Connect

    Castaldini, A.; Cavallini, A.; Fraboni, B.; Polenta, L.

    1996-12-01

    The influence of deep levels on the electrical and optical properties of semiconductors is widely acknowledged. We have utilized several complementary spectroscopic techniques to investigate the deep traps in undoped CdTe, CdTe:Cl and Cd{sub 0.8}Zn{sub 0.2}Te. The electrical activity of the defects has been studied by DLTS, PICTS and P-DLTS while their optical properties have been characterized by cathodoluminescence, CL. Various deep levels have been found and by critically comparing the results obtained with the different techniques in different samples, we were able to achieve a better understanding of the nature of the defects.

  6. Levels of expression of CD19 and CD20 in chronic B cell leukaemias.

    PubMed Central

    Ginaldi, L; De Martinis, M; Matutes, E; Farahat, N; Morilla, R; Catovsky, D

    1998-01-01

    AIMS: To investigate whether the antigen levels of the B cell lineage markers CD19 and CD20 can distinguish between normal and neoplastic B cells or characterise distinct expression patterns among the chronic B cell leukaemias. METHODS: Peripheral blood cells from 70 patients with B cell disorders and 17 healthy donors were analysed by quantitative flow cytometry. Direct immunofluorescence staining was performed with phycoerythrin conjugated CD19 and CD20 monoclonal antibodies. Standard microbeads with different capacities to bind mouse immunoglobulins were used to convert the mean fluorescence intensity (MFI) values into number of antigen molecules/cell, expressed as antibody binding capacity (ABC). RESULTS: CD19 and CD20 ABC values in leukaemic B cells differed from those of normal blood B lymphocytes. The results identified distinct profiles of CD19 and CD20 expression in the various types of B cell leukaemias. In all leukaemias studied except hairy cell leukaemia (HCL), CD19 expression was significantly lower than the mean (SD) value in normal B cells (22 (7) x 10(3) molecules/cell), as follows: chronic lymphocytic leukaemia (CLL), 13 (7) x 10(3); B prolymphocytic leukaemia (B-PLL), 16 (9) x 10(3); splenic lymphoma with villous lymphocytes (SLVL), 15 (11) x 10(3); mantle cell lymphoma (MCL), 10 (7) x 10(3). In HCL there was strong CD19 expression (38 (16) x 10(3)). In contrast, the level of expression of membrane CD20 was higher than the mean (SD) value in normal B cells (94 (16) x 10(3) molecules/cell) in MCL (123 (51) x 10(3)); B-PLL (129 (47) x 10(3)); SLVL (167 (72) x 10(3)); and HCL (312 (110) x 10(3)); while it was significantly lower (65 (11) x 10(3)) in CLL compared with normal B cells and the other B cell leukaemias. CONCLUSIONS: Quantitative determination of CD19 and CD20 may provide useful diagnostic information for the study of B lymphoproliferative disorders. PMID:9708202

  7. History in the Making: A Report from Microsoft's First International Conference on CD ROM.

    ERIC Educational Resources Information Center

    Rosen, David

    1986-01-01

    Reviews important developments of Microsoft's first international conference on CD ROM, focusing on the announcement of a new medium called Compact Disc-Interactive (CD-I). Discussion covers CD-I's design, applications, kinds of programming made possible compatibility with current CD ROM products, impact on consumer market, and impact on overall…

  8. 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

  9. Cladribine and Fludarabine Nucleoside Change the Levels of CD Antigens on B-Lymphoproliferative Disorders

    PubMed Central

    Cassano, Carlos; Mactier, Swetlana; Mulligan, Stephen P.; Belov, Larissa; Huang, Pauline; Christopherson, Richard I.

    2010-01-01

    The purine analogs, fludarabine nucleoside (FdA), and cladribine (CdA) (1 μM, 24 hours), significantly changed the levels of some surface antigens on the human B-cell lines MEC2 and Raji. Changes in the surface proteins were identified using a Cluster of Differentiation (CD) antibody microarray that captures live cells and confirmed by flow cytometry. For Raji cells, CdA up-regulated CD10, CD54, CD80, and CD86, with repression of CD22, while FdA up-regulated CD20, CD54, CD80, CD86 and CD95. For MEC2 cells, CdA up-regulated CD11a, CD20, CD43, CD45, CD52, CD54, CD62L, CD80, CD86, and CD95, but FdA had no effect. Up-regulation of particular CD antigens induced on a B-cell lymphoproliferative disorder by a purine analog could provide targets for therapeutic antibodies with synergistic cell killing. PMID:22084681

  10. 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

  11. Circulating levels of the innate and humoral immune regulators CD14 and CD23 are associated with adult glioma

    PubMed Central

    Zhou, Mi; Wiemels, Joseph L.; Bracci, Paige; Wrensch, Margaret R.; Mccoy, Lucie; Rice, Terri; Sison, Jennette; Patoka, Joseph; Wiencke, John K.

    2012-01-01

    Allergy history has been consistently inversely associated with glioma risk. Two serologic markers, soluble CD23 (sCD23) and soluble CD14 (sCD14), are part of the innate and adaptive humoral immune systems and modulate allergic responses in opposite directions, with sCD23 enhancing and sCD14 blunting inflammatory responses. We measured sCD23 and sCD14 in serum from blood that was drawn at a single time point from 1079 glioma patients post diagnosis and 736 healthy controls. Glioma was strongly associated with high sCD14 (highest vs. lowest quartile OR = 3.94 (95% CI: 2.98-5.21) and low sCD23 (lowest vs. highest quartile OR=2.5 (95% CI: 1.89-3.23)). Results were consistent across glioma histologic types and grades, but were strongest for glioblastoma. While temozolomide treatment was not associated with either sCD14 or sCD23 levels among cases, those taking dexamethasone had somewhat lower sCD23 levels than those not taking dexamethasone. However, sCD23 was associated with case status regardless of dexamethasone treatment. These results augment the long observed association between allergies and glioma and support a role for the innate and adaptive humoral functions of the immune system, and in particular immunoregulatory proteins, in gliomagenesis. PMID:20719886

  12. Circulating levels of the innate and humoral immune regulators CD14 and CD23 are associated with adult glioma.

    PubMed

    Zhou, Mi; Wiemels, Joseph L; Bracci, Paige M; Wrensch, Margaret R; McCoy, Lucie S; Rice, Terri; Sison, Jennette D; Patoka, Joseph S; Wiencke, John K

    2010-10-01

    Allergy history has been consistently inversely associated with glioma risk. Two serologic markers, soluble CD23 (sCD23) and soluble CD14 (sCD14), are part of the innate and adaptive humoral immune systems and modulate allergic responses in opposite directions, with sCD23 enhancing and sCD14 blunting inflammatory responses. We measured sCD23 and sCD14 in serum from blood that was drawn at a single time point from 1,079 glioma patients postdiagnosis and 736 healthy controls. Glioma was strongly associated with high sCD14 [highest versus lowest quartile odds ratio (OR), 3.94; 95% confidence interval (95% CI), 2.98-5.21] and low sCD23 (lowest versus highest quartile OR, 2.5; 95% CI, 1.89-3.23). Results were consistent across glioma histologic types and grades, but were strongest for glioblastoma. Whereas temozolomide treatment was not associated with either sCD14 or sCD23 levels among cases, those taking dexamethasone had somewhat lower sCD23 levels than those not taking dexamethasone. However, sCD23 was associated with case status regardless of dexamethasone treatment. These results augment the long-observed association between allergies and glioma and support a role for the innate and adaptive humoral functions of the immune system, in particular immunoregulatory proteins, in gliomagenesis. PMID:20719886

  13. CD26 Expression on T Helper Populations and sCD26 Serum Levels in Patients with Rheumatoid Arthritis

    PubMed Central

    Cordero, Oscar J.; Varela-Calviño, Rubén; López-González, Tania; Calviño-Sampedro, Cristina; Viñuela, Juan E.; Mouriño, Coral; Hernández-Rodríguez, Íñigo; Rodríguez-López, Marina; Aspe de la Iglesia, Bruno; Pego, José María

    2015-01-01

    We studied dipeptidyl peptidase IV (DPP-IV, CD26) expression in different T helper cells and serum soluble DPP-IV/sCD26 levels in rheumatoid arthritis (RA) patients, correlated these with disease activity score (DAS), and examined how they were affected by different therapies, conventional or biological (anti-TNF, anti-CD20 and anti-IL6R or Ig-CTLA4). The percentage of CD4+CD45R0+CD26- cells was greatly reduced in patients (up to 50%) when compared with healthy subjects. Three other subsets of CD4 cells, including a CD26high Th1-associated population, changed variably with therapies. Data from these subsets (frequency and staining density) significantly correlated with DAS28 or DAS28 components but different in each group of patients undergoing the different therapies. Th17 and Th22 subsets were implicated in RA as independent CCR4+ and CCR4- populations each, with distinct CD26 expression, and were targeted with varying efficiency by each therapy. Serum DPP-IV activity rather than sCD26 levels was lower in RA patients compared to healthy donors. DPP-IV and sCD26 serum levels were found related to specific T cell subsets but not to disease activity. We conclude that, according to their CD26 expression, different cell subsets could serve to monitor RA course, and an uncharacterized T helper CD26- subset, not targeted by therapies, should be monitored for early diagnosis. PMID:26177310

  14. Multimolecular signaling complexes enable Syk-mediated signaling of CD36 internalization.

    PubMed

    Heit, Bryan; Kim, Hani; Cosío, Gabriela; Castaño, Diana; Collins, Richard; Lowell, Clifford A; Kain, Kevin C; Trimble, William S; Grinstein, Sergio

    2013-02-25

    CD36 is a versatile receptor known to play a central role in the development of atherosclerosis, the pathogenesis of malaria, and the removal of apoptotic cells. Remarkably, the short cytosolically exposed regions of CD36 lack identifiable motifs, which has hampered elucidation of its mode of signaling. Using a combination of phosphoprotein isolation, mass spectrometry, superresolution imaging, and gene silencing, we have determined that the receptor induces ligand internalization through a heteromeric complex consisting of CD36, β1 and/or β2 integrins, and the tetraspanins CD9 and/or CD81. This receptor complex serves to link CD36 to the adaptor FcRγ, which bears an immunoreceptor tyrosine activation motif. By coupling to FcRγ, CD36 is able to engage Src-family kinases and Syk, which in turn drives the internalization of CD36 and its bound ligands. PMID:23395392

  15. CdSe quantum dot internalization by Bacillus subtilis and Escherichia coli

    NASA Technical Reports Server (NTRS)

    Kloepfer, Jeremiah A.; Mielke, Randall E.; Nadeau, Jay L.

    2004-01-01

    Biological labeling has been demonstrated with CdSe quantum dots in a variety of animal cells, but bacteria are harder to label because of their cell walls. We discuss the challenges of using minimally coated, bare CdSe quantum dots as luminescent internal labels for bacteria.

  16. Laser Disks at the Library Door: The Microsoft First International Conference on CD-ROM.

    ERIC Educational Resources Information Center

    Miller, David C.

    1986-01-01

    Description of First International CD-ROM Conference held by Microsoft, Inc., in March, 1986, covers types of participants, hardware and support services, and technical standards and intellectual property rights as market barriers. The importance of librarians planning for CD-ROM is stressed, and a detailed directory of references and contacts is…

  17. Contribution of NADPH Oxidase to Membrane CD38 Internalization and Activation in Coronary Arterial Myocytes

    PubMed Central

    Xu, Ming; Li, Xiao-Xue; Ritter, Joseph K.; Abais, Justine M.; Zhang, Yang; Li, Pin-Lan

    2013-01-01

    The CD38-ADP-ribosylcyclase-mediated Ca2+ signaling pathway importantly contributes to the vasomotor response in different arteries. Although there is evidence indicating that the activation of CD38-ADP-ribosylcyclase is associated with CD38 internalization, the molecular mechanism mediating CD38 internalization and consequent activation in response to a variety of physiological and pathological stimuli remains poorly understood. Recent studies have shown that CD38 may sense redox signals and is thereby activated to produce cellular response and that the NADPH oxidase isoform, NOX1, is a major resource to produce superoxide (O2·−) in coronary arterial myocytes (CAMs) in response to muscarinic receptor agonist, which uses CD38-ADP-ribosylcyclase signaling pathway to exert its action in these CAMs. These findings led us hypothesize that NOX1-derived O2·− serves in an autocrine fashion to enhance CD38 internalization, leading to redox activation of CD38-ADP-ribosylcyclase activity in mouse CAMs. To test this hypothesis, confocal microscopy, flow cytometry and a membrane protein biotinylation assay were used in the present study. We first demonstrated that CD38 internalization induced by endothelin-1 (ET-1) was inhibited by silencing of NOX1 gene, but not NOX4 gene. Correspondingly, NOX1 gene silencing abolished ET-1-induced O2·− production and increased CD38-ADP-ribosylcyclase activity in CAMs, while activation of NOX1 by overexpression of Rac1 or Vav2 or administration of exogenous O2·− significantly increased CD38 internalization in CAMs. Lastly, ET-1 was found to markedly increase membrane raft clustering as shown by increased colocalization of cholera toxin-B with CD38 and NOX1. Taken together, these results provide direct evidence that Rac1-NOX1-dependent O2·− production mediates CD38 internalization in CAMs, which may represent an important mechanism linking receptor activation with CD38 activity in these cells. PMID:23940720

  18. Bismuth-induced deep levels and carrier compensation in CdTe

    SciTech Connect

    Du, Mao-Hua

    2008-01-01

    First-principles calculations show that Bi on Cd site in CdTe can be either a donor, Bi_Cd+, or an acceptor, Bi_Cd- , depending on the Fermi level. The can bind a substitutional O (O_Te) with large binding energy of 1.40 eV. The calculated (0/-) transition level for B_Cd- - O_Te complex is in good agreement with the observed deep hole trapping level. Bi can also substitute Te to form an acceptor. The amphoteric nature of Bi in CdTe results in the pinning of the Fermi level and the high resistivity. We also discuss the origin of p-type CdTe at high Bi doping level.

  19. Multi-level 3D implementation of thermo-pneumatic pumping on centrifugal microfluidic CD platforms.

    PubMed

    Thio, Tzer Hwai Gilbert; Ibrahim, Fatimah; Al-Faqheri, Wisam; Soin, Norhayati; Abdul Kahar, Maria Kahar Bador; Madou, Marc

    2013-01-01

    Thermo-pneumatic (TP) pumping is a method employing the principle of expanding heated air to transfer fluids back towards the CD center on the centrifugal microfluidic CD platform. While the TP features are easy to fabricate as no moving parts are involved, it consumes extra real estate on the CD, and because heating is involved, it introduces unnecessary heating to the fluids on the CD. To overcome these limitations, we introduce a multi-level 3D approach and implement forced convection heating. In a multi-level 3D CD, the TP features are relocated to a separate top level, while the microfluidic process remains on a lower bottom level. This allows for heat shielding of the fluids in the microfluidic process level, and also improve usage of space on the CD. To aid in future implementations of TP pumping on a multi-level 3D CD, studies on the effect of heat source setting, and the effect of positioning the TP feature (it distance from the CD center) on CD surface heating are also presented. In this work, we successfully demonstrate a multi-level 3D approach to implement TP pumping on the microfluidic CD platform. PMID:24110985

  20. Comparative evaluation of salivary soluble CD44 levels in periodontal health and disease

    PubMed Central

    Kaur, Sumeet; Narayanswamy, Savitha; Ramesh, Alampalli Viswanathamurthy

    2014-01-01

    Context: Inflammation, immunoactivation, and malignant diseases are associated with increased plasma levels of soluble CD44 (sCD44). Serum sCD44 has been recognized as a diagnostic marker in smoking-induced diseases. Aim: (1) To assess the levels of salivary sCD44 in periodontal health and disease. (2) To compare the levels of salivary sCD44 in smokers and nonsmokers. (3) To assess if salivary sCD44 levels could be used as a diagnostic marker for periodontitis. Setting and Design: A total of 60 patients were divided into three groups viz. Group A - healthy, Group B - aggressive periodontitis and Group C - chronic periodontitis (Subdivided into C1 - chronic periodontitis smokers and C2 - chronic periodontitis nonsmokers). Materials and Methods: The plaque index, gingival index (GI), probing depth and clinical attachment level; along with the radiographs were recorded. The saliva sample collected at baseline was stored at −80°C. The sCD44 levels were analyzed using ELISA. Statistical Analysis Used: ANOVA test and Mann–Whitney's test was used to compare readings between all the groups and Pearson correlation was calculated for CD44 and all the clinical parameters in each group. Results: Highest mean sCD44 was recorded in Group C2 followed by Group C1. The GI was positively correlated with CD44 levels in chronic periodontitis group. Contrary to previous reports nonsmokers subjects had higher CD44 levels as compared to smoker. Conclusion: Soluble CD44 levels were positively correlated with periodontal disease. Thus, salivary sCD44 could be considered as a one of the biomarker for periodontitis that is, aggressive and chronic periodontitis. PMID:25624630

  1. Serum levels of soluble CD44 variant isoforms are elevated in rheumatoid arthritis.

    PubMed

    Kittl, E M; Haberhauer, G; Ruckser, R; Selleny, S; Rech-Weichselbraun, I; Hinterberger, W; Bauer, K

    1997-01-01

    Serum levels of soluble CD44 variant proteins including sequences encoded by exon v5 and exon v6 (sCD44v5, sCD44v6) were determined in patients with inflammatory rheumatic diseases: 56 with rheumatoid arthritis (RA+) and 31 with miscellaneous inflammatory rheumatic diseases (MIRD). There were very significantly higher serum levels of sCD44v5 and sCD44v6 in patients with RA+ than in those with MIRD (RA+ to MIRD: sCD44v5: 81 +/- 54 ng/ml to 33 +/- 13 ng/ml; sCD44v6: 237 +/- 124 ng/ml to 166 +/- 53 ng/ml; both P < 0.001). In RA+ elevated serum levels of sCD44v5 were correlated with the inflammatory activity of disease. In 17 patients with RA+ three or four follow-up measurements of sCD44v5 were performed within 6 months. The development of sCD44v5 serum levels reflected the clinical course of disease in the patients investigated. PMID:9032816

  2. In vitro soluble CD30 levels in patients with chronic stable coronary artery disease.

    PubMed

    Mahmoudi, Mohammad Jafar; Hedayat, Mona; Rezaei, Nima; Saboor-Yaraghi, Ali-Akbar; Mahmoudi, Maryam

    2011-12-01

    The CD30 antigen seems to play a costimulatory role in maintaining the physiological balance between T-helper (Th)1/Th2 immune responses. In this study, plasma and in vitro soluble CD30 (sCD30) secretion was investigated in patients with coronary artery disease (CAD) as a plausible marker of dysregulated immune response.Twenty one patients with angiographically confirmed CAD and 31 healthy controls took part in this study. The levels of the activation marker sCD30 were determined in plasma and phytohaemagglutinin (PHA)-stimulated and unstimulated peripheral blood mononuclear cell cultures by ELISA. Plasma sCD30 levels did not differ significantly between the patients and controls. However, spontaneous sCD30 secretion was significantly lower in patients with CAD compared to controls (p < 0.001). The soluble CD30 levels were significantly increased in the supernatant of PHA-stimulated PBMCs compared to unstimulated cultures in both groups of patients and controls (p < 0.001). PHA-stimulated sCD30 secretion was found to be lower in patients compared to controls; however, the difference was not statistically significant. Plasma sCD30 levels were not statistically different in patients with chronic stable CAD, a well-known Th1-mediated disease, compared to controls; whereas decreased spontaneous and PHA-stimulated sCD30 secretion in patients with CAD might indicate the progressive shift towards a Th1 immune response. PMID:22184265

  3. Improving wafer level CD uniformity for logic applications utilizing mask level metrology and process

    NASA Astrophysics Data System (ADS)

    Cohen, Avi; Trautzsch, Thomas; Buttgereit, Ute; Graitzer, Erez; Hanuka, Ori

    2013-09-01

    Critical Dimension Uniformity (CDU) is one of the key parameters necessary to assure good performance and reliable functionality of any integrated circuit (IC). The extension of 193nm based lithography usage combined with design rule shrinkage makes process control, in particular the wafer level CDU control, an extremely important and challenging task in IC manufacturing. In this study the WLCD-CDC closed loop solution offered by Carl Zeiss SMS was examined. This solution aims to improve the wafer level intra-field CDU without the need to run wafer prints and extensive wafer CD metrology. It combines two stand-alone tools: The WLCD tool which measures CD based on aerial imaging technology while applying the exact scanner-used illumination conditions to the photomask and the CDC tool which utilizes an ultra-short femto-second laser to write intra-volume shading elements (Shade-In Elements™) inside the photomask bulk material. The CDC process changes the dose going through the photomask down to the wafer, hence the wafer level intra-field CDU improves. The objective of this study was to evaluate how CDC process is affecting the CD for different type of features and pattern density which are typical for logic and system on chip (SOC) devices. The main findings show that the linearity and proximity behavior is maintained by the CDC process and CDU and CDC Ratio (CDCR) show a linear behavior for the different feature types. Finally, it was demonstrated that the CDU errors of the targeted (critical) feature have been effectively eliminated. In addition, the CDU of all other features have been significantly improved as well.

  4. Anti-CD20 antibody promotes cancer escape via enrichment of tumor-evoked regulatory B cells expressing low levels of CD20 and CD137L.

    PubMed

    Bodogai, Monica; Lee Chang, Catalina; Wejksza, Katarzyna; Lai, Jinping; Merino, Maria; Wersto, Robert P; Gress, Ronald E; Chan, Andrew C; Hesdorffer, Charles; Biragyn, Arya

    2013-04-01

    The possible therapeutic benefits of B-cell depletion in combating tumoral immune escape have been debated. In support of this concept, metastasis of highly aggressive 4T1 breast cancer cells in mice can be abrogated by inactivation of tumor-evoked regulatory B cells (tBreg). Here, we report the unexpected finding that B-cell depletion by CD20 antibody will greatly enhance cancer progression and metastasis. Both murine and human tBregs express low levels of CD20 and, as such, anti-CD20 mostly enriches for these cells. In the 4T1 model of murine breast cancer, this effect of enriching for tBregs suggests that B-cell depletion by anti-CD20 may not be beneficial at all in some cancers. In contrast, we show that in vivo-targeted stimulation of B cells with CXCL13-coupled CpG oligonucleotides (CpG-ODN) can block cancer metastasis by inhibiting CD20(Low) tBregs. Mechanistic investigations suggested that CpG-ODN upregulates low surface levels of 4-1BBL on tBregs to elicit granzyme B-expressing cytolytic CD8(+) T cells, offering some explanative power for the effect. These findings underscore the immunotherapeutic importance of tBreg inactivation as a strategy to enhance cancer therapy by targeting both the regulatory and activating arms of the immune system in vivo. PMID:23365136

  5. Properties of {sup 112}Cd from the (n,n'{gamma}) reaction: Levels and level densities

    SciTech Connect

    Garrett, P. E.; Lehmann, H.; Jolie, J.; McGrath, C. A.; Yeh, Minfang; Younes, W.; Yates, S. W.

    2001-08-01

    Levels in {sup 112}Cd have been studied through the (n,n'{gamma}) reaction with monoenergetic neutrons. An extended set of experiments that included excitation functions, {gamma}-ray angular distributions, and {gamma}{gamma} coincidence measurements was performed. A total of 375 {gamma} rays were placed in a level scheme comprising 200 levels (of which 238 {gamma}-ray assignments and 58 levels are newly established) up to 4 MeV in excitation. No evidence to support the existence of 47 levels as suggested in previous studies was found, and these have been removed from the level scheme. From the results, a comparison of the level density is made with the constant temperature and back-shifted Fermi gas models. The back-shifted Fermi gas model with the Gilbert-Cameron spin cutoff parameter provided the best overall fit. Without using the neutron resonance information and only fitting the cumulative number of low-lying levels, the level density parameters extracted are a sensitive function of the maximum energy used in the fit.

  6. CdTe and ZnTe metal interface formation and Fermi-level pinning

    NASA Technical Reports Server (NTRS)

    Wahi, A. K.; Carey, G. P.; Chiang, T. T.; Lindau, I.; Spicer, W. E.

    1989-01-01

    Interfacial morphology and Fermi-level pinning behavior at the interfaces of Al, Ag, and Pt with UHV-cleaved CdTe and ZnTe are studied using X-ray photoelectron and ultraviolet photoemission spectroscopies. Results are compared to metal/HgCdTe interface formation. For Al/CdTe, a case is found where significantly greater intermixing occurs in CdTe than seen on HgCdTe. The Al/ZnTe interface is also more abrupt than Al/CdTe. Band bending results for interfaces of all three metals with p-CdTe and p-ZnTe are presented and implications for metal/HgZnTe interface formation are considered.

  7. CD-ROM Proceedings International Symposium on Erosion and Landscape Evolution (ISELE)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This CD-ROM contains the abstracts and full papers for the proceedings from the ASABE specialty conference, the International Symposium on Erosion and Landscape Evolution (ISELE), held September 18-21, 2011 at the Hilton Anchorage Hotel in Anchorage, Alaska. Three extended abstracts from the meeting...

  8. Accumulation and localization of cadmium in potato (Solanum tuberosum) under different soil Cd levels.

    PubMed

    Chen, Zhifan; Zhao, Ye; Gu, Lei; Wang, Shuifeng; Li, Yongliang; Dong, Fangli

    2014-06-01

    Phytoavailability and uptake mechanism of Cd in edible plant tissues grown on metal polluted agricultural soils has become a growing concern worldwide. Uptake, transport, accumulation and localization of cadmium in potato organs under different soil Cd levels were investigated using inductively-coupled plasma mass spectrometry and energy dispersive X-ray microanalysis. Results indicated that Cd contents in potato organs increased with increasing soil Cd concentrations, and the order of Cd contents in different organs was leaves > stems/roots > tubers. Root-to-stem Cd translocation coefficients ranged from 0.89 to 1.81. Cd localization in potato tissues suggested that leaves and stems should be the main compartment of Cd storage and uptake. Although low concentrations of Cd migrated from the root to tuber, Cd accumulation in the tuber exceeded the standard for food security. Therefore, the planting of potato plants in farmland containing Cd should be closely evaluated due to its potential to present health risks. PMID:24682567

  9. Increased internalization of complement inhibitor CD59 may contribute to endothelial inflammation in obstructive sleep apnea.

    PubMed

    Emin, Memet; Wang, Gang; Castagna, Francesco; Rodriguez-Lopez, Josanna; Wahab, Romina; Wang, Jing; Adams, Tessa; Wei, Ying; Jelic, Sanja

    2016-01-01

    Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH) during transient cessation of breathing, triples the risk for cardiovascular diseases. We used a phage display peptide library as an unbiased approach to investigate whether IH, which is specific to OSA, activates endothelial cells (ECs) in a distinctive manner. The target of a differentially bound peptide on ECs collected from OSA patients was identified as CD59, a major complement inhibitor that protects ECs from the membrane attack complex (MAC). A decreased proportion of CD59 is located on the EC surface in OSA patients compared with controls, suggesting reduced protection against complement attack. In vitro, IH promoted endothelial inflammation predominantly via augmented internalization of CD59 and consequent MAC deposition. Increased internalization of endothelial CD59 in IH appeared to be cholesterol-dependent and was reversed by statins in a CD59-dependent manner. These studies suggest that reduced complement inhibition may mediate endothelial inflammation and increase vascular risk in OSA patients. PMID:26738794

  10. 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

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

    1995-12-01

    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

  11. Cell surface Glut1 levels distinguish human CD4 and CD8 T lymphocyte subsets with distinct effector functions

    PubMed Central

    Cretenet, Gaspard; Clerc, Isabelle; Matias, Maria; Loisel, Severine; Craveiro, Marco; Oburoglu, Leal; Kinet, Sandrina; Mongellaz, Cédric; Dardalhon, Valérie; Taylor, Naomi

    2016-01-01

    CD4 and CD8 T lymphocyte activation requires the generation of sufficient energy to support new biosynthetic demands. Following T cell receptor (TCR) engagement, these requirements are met by an increased glycolysis, due, at least in part, to induction of the Glut1 glucose transporter. As Glut1 is upregulated on tumor cells in response to hypoxia, we assessed whether surface Glut1 levels regulate the antigen responsiveness of human T lymphocytes in both hypoxic and atmospheric oxygen conditions. Notably, Glut1 upregulation in response to TCR stimulation was significantly higher in T lymphocytes activated under hypoxic as compared to atmospheric oxygen conditions. Furthermore, TCR-stimulated human T lymphocytes sorted on the basis of Glut1-Lo and Glut1-Hi profiles maintained distinct characteristics, irrespective of the oxygen tension. While T cells activated in hypoxia divided less than those activated in atmospheric oxygen, Glut1-Hi lymphocytes exhibited increased effector phenotype acquisition, augmented proliferation, and an inverted CD4/CD8 ratio in both oxygen conditions. Moreover, Glut1-Hi T lymphocytes exhibited a significantly enhanced ability to produce IFN-γ and this secretion potential was completely dependent on continued glycolysis. Thus, Glut1 surface levels identify human T lymphocytes with distinct effector functions in both hypoxic and atmospheric oxygen tensions. PMID:27067254

  12. Serum Levels of Soluble CD26, A Novel Prognostic Marker for Hepatitis E Infection

    PubMed Central

    Rafiei, Alireza; Ajami, Abolghasem; Mohammad Mirabi, Araz; Saffar, Mohammad Jafar; Amjadi, Omolbanin; Haghshenas, Mohammad Reza; Abedian, Farshideh; Khaje-Enayati, Pouya

    2016-01-01

    Background: Even without treatment, most acute hepatitis E virus (HEV) infected patients resolve HEV but sometimes the disease leads to acute liver failure, chronic infection, or extrahepatic symptoms. The mechanisms of HEV pathogenesis appear to be substantially immune mediated. However, the immune responses to HEV are not precisely identified. Objectives: This study aimed to evaluate the Th1/Th2 ratio by investigating serum soluble markers from Th1 and Th2 cells in acute HEV infected patients. Patients and Methods: This case-control study included 35 acute HEV infected patients and 35 age and gender matched anti-HEV negative healthy controls. The serum levels of Interferon (IFN)-γ, IL-4, soluble CD26 (sCD26) and sCD30 were determined by the enzyme-linked immunosorbent assay. Results: The results showed a significant difference in IFN-γ and sCD26 (P < 0.0001 and P = 0.001) yet not IL-4 and sCD30 (P = 0.354 and P = 0.159) between acute HEV patients and controls, respectively. There was a positive direct correlation between serum levels of sCD26 and IFN-γ in acute HEV patients (r = 0.64, P = 0.001). In addition, the ratio of sCD26/sCD30 in the acute HEV group was more than two folds higher than in the HEV negative controls. Conclusions: Acute HEV infection shows a pattern of Th1-type immune response, and the direct significant positive correlation between the serum level of sCD26 and IFN-γ in acute HEV infected patients, suggests that the trend of sCD26 levels is a valuable marker for predicting hepatic inflammation in hepatitis E. PMID:27127593

  13. Elevated levels of soluble CD163 in sera and fluids from rheumatoid arthritis patients and inhibition of the shedding of CD163 by TIMP-3

    PubMed Central

    MATSUSHITA, N; KASHIWAGI, M; WAIT, R; NAGAYOSHI, R; NAKAMURA, M; MATSUDA, T; HOGGER, P; GUYRE, P M; NAGASE, H; MATSUYAMA, T

    2002-01-01

    The aim of the present study was to evaluate levels of soluble CD 163 in sera and fluids from rheumatoid arthritis (RA) patients and elucidate the mechanism that regulates the shedding of CD163. Levels of soluble CD163 in sera and fluids from RA patients were examined by a sandwich enzyme immunoassay and Western blotting. To determine the effects of tissue inhibitors of metalloproteinase (TIMPs) on the shedding of CD163 from monocytes/macrophages, levels of soluble CD163 in cultures of monocytes/macrophages and the expression of CD163 on monocytes/macrophages in the presence or absence of TIMPs were examined by a sandwich enzyme immunoassay and flow cytometry, respectively. The clinical marker that was most associated with serum levels of soluble CD163 was levels of CRP. TIMP-3, but not TIMP-1 or TIMP-2, inhibited the shedding of CD163 from monocytes/macrophages. It was shown that serum levels of soluble CD163 are a sensitive and reliable marker to monitor activated macrophages in synovitis from RA patients and the results imply that the responsible proteinase for the shedding of CD163 is not a member of the matrix metalloproteinases, but is likely to be a member of ADAMs. PMID:12296867

  14. [TLR9 expression is positively correlated with the levels of CD38, HLA-DR and CD95 on peripheral blood mononuclear cells in chronic HBV infected patients].

    PubMed

    Mao, Xuefeng; Peng, Lishan; Liu, Xian; Yang, Yang; Wang, Qihui; Wang, Dengrong; Xiao, Jian; Leng, Jing

    2016-05-01

    Objective To explore the relationship between the expression of TLR9 and the levels of CD38, HLA-DR and CD95 on peripheral blood mononuclear cells (PBMCs) of chronic hepatitis B virus (HBV) infected patients. Methods70 chronic HBV infected patients and 12 healthy donors were enrolled in this study, and density gradient centrifugation was used to isolate PBMCs from peripheral blood with EDTA for anticoagulation. Flow cytometry was used to detect the levels of TLR9, CD38, HLA-DR and CD95 on PBMCs. Results Compared to the healthy donors, chronic HBV infected patients with low viral load or high viral load had significantly higher levels of TLR9, HLA-DR and CD95 on PMBCs. Furthermore, the co-expression rates of TLR9 and CD38, HLA-DR, CD95 on PBMCs were obviously higher than those of the healthy donors. Correlation analysis showed that the expression of TLR9 was positively correlated with CD38 (r=0.345), HLA-DR (r=0.334), CD95 (r=0.227) on PBMCs in the patients with chronic HBV infection. Conclusion The expression of TLR9 increased and was positively associated with CD38, HLA-DR and CD95 on PBMCs during chronic HBV infection. PMID:27126946

  15. Orbital alignment at the internal interface of arylthiol functionalized CdSe molecular hybrids

    SciTech Connect

    Li, Zhi; Schlaf, Rudy; Mazzio, Katherine A.; Okamoto, Ken; Luscombe, Christine K.

    2015-04-21

    Organic-inorganic nanoparticle molecular hybrid materials are interesting candidates for improving exciton separation in organic solar cells. The orbital alignment at the internal interface of cadmium selenide (ArS-CdSe) hybrid materials functionalized with covalently attached arylthiolate moieties was investigated through X-ray photoemission spectroscopy (XPS) and ultraviolet photoemission spectroscopy (UPS). A physisorbed interface between arylthiol (ArSH) ligands and CdSe nanoparticles was also investigated for comparison. This interface was created via a multi-step thin film deposition procedure in-vacuo, where the surface was characterized after each experimental step. This enabled the direct comparison of ArSH/CdSe interfaces produced via physisorption and ArS-CdSe covalently attached hybrid materials, which rely on a chemical reaction for their synthesis. All material depositions were performed using an electrospray deposition, which enabled the direct injection of solution-originating molecular species into the vacuum system. This method allows XPS and UPS measurements to be performed immediately after deposition without exposure to the atmosphere. Transmission electron microscopy was used to determine the morphology and particle size of the deposited materials. Ultraviolet-visible spectroscopy was used to estimate the optical band gap of the CdSe nanoparticles and the HOMO-LUMO gap of the ArSH ligands. These experiments showed that hybridization via covalent bonds results in an orbital realignment at the ArSH/CdSe interface in comparison to the physisorbed interface. The orbital alignment within the hybrid caused a favorable electron injection barrier, which likely facilitates exciton-dissociation while preventing charge-recombination.

  16. Pachyman treatment improves CD4+CD25+ Treg counts and serum interleukin 4 and interferon γ levels in a mouse model of Kawasaki disease.

    PubMed

    Chu, Mao-Ping; Wang, Dan; Zhang, Ying-Ying; Li, Bao-Qing; Zhou, Ai-Hua; Chen, Xi-Wen; Qian, Yan

    2012-05-01

    The aim of this study was to explore the effect of pachyman, a mushroom extract, on CD4+CD25+ regulatory T cells (Tregs), serum interleukin 4 (IL-4) and interferon γ (IFN-γ) levels in a mouse model of Kawasaki disease. Lactobacillus casei cell wall extract was diluted to 1 mg/ml in PBS and administered to mice by intraperitoneal injection to establish a model of Kawasaki disease. Sixty female mice were used in this study, 40 of which were randomly assigned to a model (normal saline by gavage, n=20) or experimental group (200 mg/kg/day pachyman by gavage, n=20). The remaining 20 mice were disease and treatment-free, and were used as the control group. Compared to the control mice, mice in the model group exhibited a significantly lower percentage of CD4+CD25+ Tregs and significantly higher serum IL-4 and IFN-γ levels (P<0.05). However, CD4+CD25+ Tregs significantly increased and IL-4 and IFN-γ levels significantly decreased in experimental mice following pachyman treatment (P<0.05). Further analysis showed a negative correlation between CD4+CD25+ Tregs and IL-4/IFN-γ levels (P<0.05). In conclusion, pachyman improves immune function in a mouse model of Kawasaki disease by upregulating CD4+CD25+ Tregs, which may inhibit the cytokine secretion of Th1 and Th2 cells. PMID:22367425

  17. Dynamic Change of CD34 Level during the Survival Process of Narrow Pedicle Flap

    PubMed Central

    Wu, Lijun; Zhao, Tianlan; Yu, Daojiang; Chen, Qi; Han, Wenya; Yu, Wenyuan; Sun, Wei

    2015-01-01

    Objective To evaluate the dynamic change of CD34 level during the survival process of narrow pedicle flaps. Methods Twenty-five white pigs were randomly and equally divided into 5 experimental groups. Five different type of narrow pedicle with different length-to-width ratio were employed, and each type of narrow pedicle was covered with 5 different size random flaps and which was classified into A, B, C, D and E for 5 groups. Group A was control group. Each type narrow pedicle with 5 different skin flaps were implanted onto the back of the pigs along the midline of back with a reverse direction. A 0.3 cm×0.3 cm full thickness skin flap in the middle of distal segment was collected and on 3rd, 5th, 7th and 14th days of post-operation. The expression of CD34 was measured by immunohistochemistry and enzyme-linked immunosorbent (ELISA). Results Histological examination showed that with the increasing of length-to-width ratio of the narrow pedicle skin flaps, the expression of CD34 increased in the skin flaps. Increased level of CD34 was found on 3rd day post-operation, and the peak expression was found on 7th day. Persistent high level of CD34 was found until 14th day. Conclusion Increased CD34 level in the distal skin flap, there is the association between CD34 level and ischemia injury. Moreover, CD34 expression plays an important role during the repair processes of pedicle flaps. PMID:26561392

  18. Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors

    PubMed Central

    Castley, Alison; Williams, Leah; James, Ian; Guelfi, George; Berry, Cassandra; Nolan, David

    2016-01-01

    We investigate the associations of three established plasma biomarkers in the context of HIV and treatment-related variables including a comprehensive cardiovascular disease risk assessment, within a large ambulatory HIV cohort. Patients were recruited in 2010 to form the Royal Perth Hospital HIV/CVD risk cohort. Plasma sCD14, sCD163 and CXCL10 levels were measured in 475 consecutive patients with documented CVD risk (age, ethnicity, gender, smoking, blood pressure, BMI, fasting metabolic profile) and HIV treatment history including immunological/virological outcomes. The biomarkers assessed showed distinct associations with virological response: CXCL10 strongly correlated with HIV-1 RNA (p<0.001), sCD163 was significantly reduced among ‘aviraemic’ patients only (p = 0.02), while sCD14 was unaffected by virological status under 10,000 copies/mL (p>0.2). Associations between higher sCD163 and protease inhibitor therapy (p = 0.05) and lower sCD14 with integrase inhibitor therapy (p = 0.02) were observed. Levels of sCD163 were also associated with CVD risk factors (age, ethnicity, HDL, BMI), with a favourable influence of Framingham score <10% (p = 0.04). Soluble CD14 levels were higher among smokers (p = 0.002), with no effect of other CVD risk factors, except age (p = 0.045). Our findings confirm CXCL10, sCD163 and sCD14 have distinct associations with different aspects of HIV infection and treatment. Levels of CXCL10 correlated with routinely monitored variables, sCD163 levels reflect a deeper level of virological suppression and influence of CVD risk factors, while sCD14 levels were not associated with routinely monitored variables, with evidence of specific effects of smoking and integrase inhibitor therapy warranting further investigation. PMID:27355513

  19. CD44 regulates Wnt signaling at the level of LRP6

    PubMed Central

    Orian-Rousseau, Véronique; Schmitt, Mark

    2015-01-01

    CD44 was recently identified as a positive feedback regulator of Wnt/β-catenin signaling. This regulation occurs at the level of low-density lipoprotein receptor-related protein 6 phosphorylation and membrane targeting. These findings broaden our understanding of the Wnt pathway activation process and open new perspectives for anti-CD44 therapies in diseases associated with Wnt induction, including colorectal cancer. PMID:27308483

  20. Expression of fas protein on CD4+T cells irradiated by low level He-Ne

    NASA Astrophysics Data System (ADS)

    Nie, Fan; Zhu, Jing; Zhang, Hui-Guo

    2005-07-01

    Objective: To investigate the influence on the Expression of Fas protein on CD4+ T cells irradiated by low level He-Ne laser in the cases of psoriasis. Methods:the expression of CD4+ T Fas protein was determined in the casee of psoriasis(n=5) pre and post-low level laser irradiation(30 min、60min and 120min)by flow cytometry as compared withthe control(n=5). Results:In the cases of psoriasis,the expression of CD4+T FAS protein 21.4+/-3.1% was increased significantly than that of control group 16.8+/-2.1% pre-irradiation, p<0.05in the control,there is no difference between pre and post- irradiation,p>0.05in the cases , the expression of CD4+T Fas protein wae positively corelated to the irradiation times, when the energy density arrived to 22.92J/cm2(60 minutes)and 45.84J/cm2(120minutes), the expression of CD4+ T Fas protein was increased significantly as compared with pre-irradiation,p<0.05.Conclusion: The expression of CD4+T Fas protein may be increased by low level He-Ne laser irradiation ,the uncontrolled status of apoptosis could be corrected.

  1. High serum levels of soluble CD40-L in patients with undifferentiated nasopharyngeal carcinoma: pathogenic and clinical relevance

    PubMed Central

    Caggiari, Laura; Guidoboni, Massimo; Vaccher, Emanuela; Barzan, Luigi; Franchin, Giovanni; Gloghini, Annunziata; Martorelli, Debora; Zancai, Paola; Bortolin, Maria Teresa; Mazzucato, Mario; Serraino, Diego; Carbone, Antonino; De Paoli, Paolo; Dolcetti, Riccardo

    2007-01-01

    Background Engagement of CD40 promotes survival of undifferentiated nasopharyngeal carcinoma (UNPC) cells and similar effects are induced by the EBV oncoprotein LMP-1 that is expressed in a fraction of cases. Considering that CD40 may be activated also by the soluble isoform of CD40L (sCD40L), we investigated the serum levels of sCD40L in a series of 61 UNPC patients from Italy, a non-endemic area for this disease. Results At diagnosis, serum samples of UNPC patients contained significantly higher levels of sCD40L than age-matched healthy controls (p < 0.001). High levels of sCD40L (i.e., >18 ng/ml) were more frequently found in patients <40 years of age (p = 0.03) and with distant metastases at presentation (p = 0.03). Serum levels of sCD40L were inversely associated with the expression of the EBV oncoprotein LMP-1 (p = 0.03), which mimics a constitutively activated CD40. The amount of sCD40L decreased in a fraction of patients treated with local radiotherapy alone. Moreover, CD40L+ lymphoid cells admixed to neoplastic UNPC cells were detected in cases with high serum levels of sCD40L, suggesting that sCD40L is probably produced within the tumor mass. Conclusion sCD40L may contribute to CD40 activation in UNPC cells, particularly of LMP-1-negative cases, further supporting the crucial role of CD40 signalling in the pathogenesis of UNPC. sCD40L levels may be useful to identify UNPC patients with occult distant metastases at presentation. PMID:17331231

  2. Levels of circulating CD45dimCD34+VEGFR2+ progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors

    PubMed Central

    Farace, F; Gross-Goupil, M; Tournay, E; Taylor, M; Vimond, N; Jacques, N; Billiot, F; Mauguen, A; Hill, C; Escudier, B

    2011-01-01

    Background: Predicting the efficacy of antiangiogenic therapy would be of clinical value in patients (pts) with metastatic renal cell carcinoma (mRCC). We tested the hypothesis that circulating endothelial cell (CEC), bone marrow-derived CD45dimCD34+VEGFR2+ progenitor cell or plasma angiogenic factor levels are associated with clinical outcome in mRCC pts undergoing treatment with tyrosine kinase inhibitors (TKI). Methods: Fifty-five mRCC pts were prospectively monitored at baseline (day 1) and day 14 during treatment (46 pts received sunitinib and 9 pts received sorafenib). Circulating endothelial cells (CD45−CD31+CD146+7-amino-actinomycin (7AAD)− cells) were measured in 1 ml whole blood using four-color flow cytometry (FCM). Circulating CD45dimCD34+VEGFR2+7AAD− progenitor cells were measured in progenitor-enriched fractions by four-color FCM. Plasma VEGF, sVEGFR2, SDF-1α and sVCAM-1 levels were determined by ELISA. Correlations between baseline CEC, CD45dimCD34+VEGFR2+7AAD− progenitor cells, plasma factors, as well as day 1–day 14 changes in CEC, CD45dimCD34+VEGFR2+7AAD− progenitor, plasma factor levels, and response to TKI, progression-free survival (PFS) and overall survival (OS) were examined. Results: No significant correlation between markers and response to TKI was observed. No association between baseline CEC, plasma VEGF, sVEGFR-2, SDF-1α, sVCAM-1 levels with PFS and OS was observed. However, baseline CD45dimCD34+VEGFR2+7AAD− progenitor cell levels were associated with PFS (P=0.01) and OS (P=0.006). Changes in this population and in SDF-1α levels between day 1 and day 14 were associated with PFS (P=0.03, P=0.002). Changes in VEGF and SDF-1α levels were associated with OS (P=0.02, P=0.007). Conclusion: Monitoring CD45dimCD34+VEGFR2+ progenitor cells, plasma VEGF and SDF-1α levels could be of clinical interest in TKI-treated mRCC pts to predict outcome. PMID:21386843

  3. Push pull microfluidics on a multi-level 3D CD.

    PubMed

    Thio, Tzer Hwai Gilbert; Ibrahim, Fatimah; Al-Faqheri, Wisam; Moebius, Jacob; Khalid, Noor Sakinah; Soin, Norhayati; Kahar, Maria Kahar Bador Abdul; Madou, Marc

    2013-08-21

    A technique known as thermo-pneumatic (TP) pumping is used to pump fluids on a microfluidic compact disc (CD) back towards the CD center against the centrifugal force that pushes liquids from the center to the perimeter of the disc. Trapped air expands in a TP air chamber during heating, and this creates positive pressure on liquids located in chambers connected to that chamber. While the TP air chamber and connecting channels are easy to fabricate in a one-level CD manufacturing technique, this approach provides only one way pumping between two chambers, is real-estate hungry and leads to unnecessary heating of liquids in close proximity to the TP chamber. In this paper, we present a novel TP push and pull pumping method which allows for pumping of liquid in any direction between two connected liquid chambers. To ensure that implementation of TP push and pull pumping also addresses the issue of space and heating challenges, a multi-level 3D CD design is developed, and localized forced convection heating, rather than infra-red (IR) is applied. On a multi-level 3D CD, the TP features are placed on a top level separate from the rest of the microfluidic processes that are implemented on a lower separate level. This approach allows for heat shielding of the microfluidic process level, and efficient usage of space on the CD for centrifugal handling of liquids. The use of localized forced convection heating, rather than infra-red (IR) or laser heating in earlier implementations allows not only for TP pumping of liquids while the CD is spinning but also makes heat insulation for TP pumping and other fluidic functions easier. To aid in future implementations of TP push and pull pumping on a multi-level 3D CD, study on CD surface heating is also presented. In this contribution, we also demonstrate an advanced application of pull pumping through the implementation of valve-less switch pumping. PMID:23774994

  4. Interleukin-18 and CD30 serum levels in patients with moderate-severe depression.

    PubMed

    Merendino, Rosaria Alba; Di Rosa, Antonio Enrico; Di Pasquale, Giuseppe; Minciullo, Paola Lucia; Mangraviti, Carmela; Costantino, Antonella; Ruello, Antonella; Gangemi, Sebastiano

    2002-08-01

    Interleukin-18 (IL-18), a pro-inflammatory cytokine that plays an important role in the T-cell-helper type 1 response, is a new member of the family of cytokines produced in the brain. CD30 is a marker of T-cell-helper type 2 lymphocytes. We evaluated IL-18 and CD30 serum levels in 10 patients affected by moderate-severe depression (MSD). We demonstrated for the first time that serum IL-18 levels of MSD patients were significantly higher than those of healthy donors. On the contrary, no significant difference was found between serum CD30 levels of MSD patients compared with those of healthy donors. These data strengthen the hypothesis that MSD disease is associated with an inflammatory response, mainly T-cell-helper type 1, and suggest an important role for IL-18 in the pathophysiology of MSD. PMID:12396479

  5. Reduction of Fermi level pinning and recombination at polycrystalline CdTe surfaces by laser irradiation

    SciTech Connect

    Simonds, Brian J.; Kheraj, Vipul; Palekis, Vasilios; Ferekides, Christos; Scarpulla, Michael A.

    2015-06-14

    Laser processing of polycrystalline CdTe is a promising approach that could potentially increase module manufacturing throughput while reducing capital expenditure costs. For these benefits to be realized, the basic effects of laser irradiation on CdTe must be ascertained. In this study, we utilize surface photovoltage spectroscopy (SPS) to investigate the changes to the electronic properties of the surface of polycrystalline CdTe solar cell stacks induced by continuous-wave laser annealing. The experimental data explained within a model consisting of two space charge regions, one at the CdTe/air interface and one at the CdTe/CdS junction, are used to interpret our SPS results. The frequency dependence and phase spectra of the SPS signal are also discussed. To support the SPS findings, low-temperature spectrally-resolved photoluminescence and time-resolved photoluminescence were also measured. The data show that a modest laser treatment of 250 W/cm{sup 2} with a dwell time of 20 s is sufficient to reduce the effects of Fermi level pinning at the surface due to surface defects.

  6. The Interplay of Antigen Affinity, Internalization, and Pharmacokinetics on CD44-Positive Tumor Targeting of Monoclonal Antibodies.

    PubMed

    Glatt, Dylan M; Beckford Vera, Denis R; Parrott, Matthew C; Luft, J Christopher; Benhabbour, S Rahima; Mumper, Russell J

    2016-06-01

    Monoclonal antibodies (mAbs) offer promise as effective tumor targeting and drug delivery agents for cancer therapy. However, comparative biological and clinical characteristics of mAbs targeting the same tumor-associated antigen (TAA) often differ widely. This study examined the characteristics of mAbs that impact tumor targeting using a panel of mAb clones specific to the cancer-associated cell-surface receptor and cancer stem cell marker CD44. CD44 mAbs were screened for cell-surface binding, antigen affinity, internalization, and CD44-mediated tumor uptake by CD44-positive A549 cells. It was hypothesized that high-affinity, rapidly internalizing CD44 mAbs would result in high tumor uptake and prolonged tumor retention. Although high-affinity clones rapidly bound and were internalized by A549 cells in vitro, an intermediate-affinity clone demonstrated significantly greater tumor uptake and retention than high-affinity clones in vivo. Systemic exposure, rather than high antigen affinity or rapid internalization, best associated with tumor targeting of CD44 mAbs in A549 tumor-bearing mice. PMID:27079967

  7. Investigation of deep level defects in CdTe thin films

    SciTech Connect

    Shankar, H.; Castaldini, A.; Dauksta, E.; Medvid, A.; Cavallini, A.

    2014-02-21

    In the past few years, a large body of work has been dedicated to CdTe thin film semiconductors, as the electronic and optical properties of CdTe nanostructures make them desirable for photovoltaic applications. The performance of semiconductor devices is greatly influenced by the deep levels. Knowledge of parameters of deep levels present in as-grown materials and the identification of their origin is the key factor in the development of photovoltaic device performance. Photo Induced Current Transient Spectroscopy technique (PICTS) has proven to be a very powerful method for the study of deep levels enabling us to identify the type of traps, their activation energy and apparent capture cross section. In the present work, we report the effect of growth parameters and LASER irradiation intensity on the photo-electric and transport properties of CdTe thin films prepared by Close-Space Sublimation method using SiC electrical heating element. CdTe thin films were grown at three different source temperatures (630, 650 and 700 °C). The grown films were irradiated with Nd:YAG LASER and characterized by Photo-Induced Current Transient Spectroscopy, Photocurrent measurementand Current Voltage measurements. The defect levels are found to be significantly influenced by the growth temperature.

  8. Hepatitis C Virus Induces Epidermal Growth Factor Receptor Activation via CD81 Binding for Viral Internalization and Entry

    PubMed Central

    Diao, Jingyu; Pantua, Homer; Ngu, Hai; Komuves, Laszlo; Diehl, Lauri; Schaefer, Gabriele

    2012-01-01

    While epidermal growth factor receptor (EGFR) has been shown to be important in the entry process for multiple viruses, including hepatitis C virus (HCV), the molecular mechanisms by which EGFR facilitates HCV entry are not well understood. Using the infectious cell culture HCV model (HCVcc), we demonstrate that the binding of HCVcc particles to human hepatocyte cells induces EGFR activation that is dependent on interactions between HCV and CD81 but not claudin 1. EGFR activation can also be induced by antibody mediated cross-linking of CD81. In addition, EGFR ligands that enhance the kinetics of HCV entry induce EGFR internalization and colocalization with CD81. While EGFR kinase inhibitors inhibit HCV infection primarily by preventing EGFR endocytosis, antibodies that block EGFR ligand binding or inhibitors of EGFR downstream signaling have no effect on HCV entry. These data demonstrate that EGFR internalization is critical for HCV entry and identify a hitherto-unknown association between CD81 and EGFR. PMID:22855500

  9. Progesterone Levels Associate with a Novel Population of CCR5+CD38+ CD4 T Cells Resident in the Genital Mucosa with Lymphoid Trafficking Potential.

    PubMed

    Swaims-Kohlmeier, Alison; Haaland, Richard E; Haddad, Lisa B; Sheth, Anandi N; Evans-Strickfaden, Tammy; Lupo, L Davis; Cordes, Sarah; Aguirre, Alfredo J; Lupoli, Kathryn A; Chen, Cheng-Yen; Ofotukun, Igho; Hart, Clyde E; Kohlmeier, Jacob E

    2016-07-01

    The female genital tract (FGT) provides a means of entry to pathogens, including HIV, yet immune cell populations at this barrier between host and environment are not well defined. We initiated a study of healthy women to characterize resident T cell populations in the lower FGT from lavage and patient-matched peripheral blood to investigate potential mechanisms of HIV sexual transmission. Surprisingly, we observed FGT CD4 T cell populations were primarily CCR7(hi), consistent with a central memory or recirculating memory T cell phenotype. In addition, roughly half of these CCR7(hi) CD4 T cells expressed CD69, consistent with resident memory T cells, whereas the remaining CCR7(hi) CD4 T cells lacked CD69 expression, consistent with recirculating memory CD4 T cells that traffic between peripheral tissues and lymphoid sites. HIV susceptibility markers CCR5 and CD38 were increased on FGT CCR7(hi) CD4 T cells compared with blood, yet migration to the lymphoid homing chemokines CCL19 and CCL21 was maintained. Infection with GFP-HIV showed that FGT CCR7(hi) memory CD4 T cells are susceptible HIV targets, and productive infection of CCR7(hi) memory T cells did not alter chemotaxis to CCL19 and CCL21. Variations of resident CCR7(hi) FGT CD4 T cell populations were detected during the luteal phase of the menstrual cycle, and longitudinal analysis showed the frequency of this population positively correlated to progesterone levels. These data provide evidence women may acquire HIV through local infection of migratory CCR7(hi) CD4 T cells, and progesterone levels predict opportunities for HIV to access these novel target cells. PMID:27233960

  10. Influence of deep level defects on carrier lifetime in CdZnTe:In

    SciTech Connect

    Guo, Rongrong; Jie, Wanqi Wang, Ning; Zha, Gangqiang; Xu, Yadong; Wang, Tao; Fu, Xu

    2015-03-07

    The defect levels and carrier lifetime in CdZnTe:In crystal were characterized with photoluminescence, thermally stimulated current measurements, as well as contactless microwave photoconductivity decay (MWPCD) technique. An evaluation equation to extract the recombination lifetime and the reemission time from MWPCD signal is developed based on Hornbeck-Haynes trapping model. An excellent agreement between defect level distribution and carrier reemission time in MWPCD signal reveals the tail of the photoconductivity decay is controlled by the defect level reemission effect. Combining {sup 241}Am gamma ray radiation response measurement and laser beam induced transient current measurement, it predicted that defect level with the reemission time shorter than the collection time could lead to better charge collection efficiency of CdZnTe detector.

  11. Development of Novel Anti-Cd20 Monoclonal Antibodies and Modulation in Cd20 Levels on Cell Surface: Looking to Improve Immunotherapy Response

    PubMed Central

    Singh, Vijay; Gupta, Damodar; Almasan, Alexandru

    2016-01-01

    Rituximab has been revolutionized and validated CD20 targeting monoclonal antibody. Although, it is widely used for lymphoma therapy and many patients have been benefited. However significant numbers of patients are refractory or developed resistance to current therapies due to low level of CD20 expression and/or availability on cells surface. Thus development of novel anti-CD20 mAbs with great cell killing ability and enhance CD20 levels on cell surface can potentially exploit lymphoma therapy. In this scenario, we are summarizing the recently developed mAbs against CD20 and compounds that have ability to induce CD20 expression at significant level. We also are providing information regarding combination strategy for use of radiation and anti-CD20 mAbs in vitro. However, it will need to be determined by rigorous at pre-clinical and clinic testing. We hope this review will be beneficial for current research in the area of immunotherapy or radio-immunotherapy. PMID:27413424

  12. Internalization and recycling of ALCAM/CD166 detected by a fully human single-chain recombinant antibody.

    PubMed

    Piazza, Tiziana; Cha, Emanuela; Bongarzone, Italia; Canevari, Silvana; Bolognesi, Andrea; Polito, Letizia; Bargellesi, Antonio; Sassi, Francesca; Ferrini, Silvano; Fabbi, Marina

    2005-04-01

    Activated leukocyte cell adhesion molecule (ALCAM/CD166), a member of the immunoglobulin superfamily with five extracellular immunoglobulin-like domains, promotes heterophilic (ALCAM-CD6) and homophilic (ALCAM-ALCAM) cell-cell interactions. Here we describe a fully human single-chain antibody fragment (scFv) directed to ALCAM/CD166. We selected the I/F8 scFv from a phage display library of human V-gene segments by cell panning and phage internalization into IGROV-I human ovary carcinoma cells. The I/F8 specificity was identified as ALCAM/CD166 by matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) peptide mass fingerprinting of the I/F8-immunoprecipitated protein. The I/F8 scFv reacts with the human, monkey and murine ALCAM/CD166 molecule, indicating that the recognized epitope is highly conserved. The I/F8 scFv completely abolished binding of both ALCAM/Fc and CD6/Fc soluble ligands, whereas it did not compete with the anti-ALCAM/CD166 murine monoclonal antibodies J4-81 and 3A6 and therefore recognizes a different epitope. Engagement through I/F8 scFv, 3A6 monoclonal antibody or CD6/Fc ligand induced ALCAM/CD166 internalization, with a kinetics slower than that of transferrin in the same cells. Newly internalized I/F8-ALCAM complexes colocalized with clathrin but not with caveolin and we demonstrated, using surface biotinylation and recycling assays, that endocytosed ALCAM/CD166 recycles back to the cell surface. Such an endocytic pathway allows the efficient delivery of an I/F8 scFv-saporin immunotoxin into tumor cells, as the conjugates are able to selectively kill cell lines expressing ALCAM/CD166. Altogether these data provide evidence of the suitability of the I/F8 scFv for further functional analysis of ALCAM/CD166 and intracellular delivery of effector moieties. PMID:15769845

  13. Low CD36 and LOX-1 Levels and CD36 Gene Subexpression Are Associated with Metabolic Dysregulation in Older Individuals with Abdominal Obesity.

    PubMed

    Madrigal-Ruíz, Perla-Monserrat; Navarro-Hernández, Rosa-Elena; Ruíz-Quezada, Sandra-Luz; Corona-Meraz, Fernanda-Isadora; Vázquez-Del Mercado, Mónica; Gómez-Bañuelos, Eduardo; Castro-Albarran, Jorge; Sandoval-García, Flavio; Flores-Alvarado, Luis-Javier; Martín-Marquez, Beatriz-Teresita

    2016-01-01

    Background. Obesity study in the context of scavenger receptors has been linked to atherosclerosis. CD36 and LOX-1 are important, since they have been associated with atherogenic and metabolic disease but not fat redistribution. The aim of our study was to determinate the association between CD36 and LOX-1 in presence of age and abdominal obesity. Methods. This is a cross-sectional study that included 151 healthy individuals, clinically and anthropometrically classified into two groups by age (<30 and ≥30 years old) and abdominal obesity (according to World Health Organization guidelines). We excluded individuals with any chronic and metabolic illness, use of medication, or smoking. Fasting blood samples were taken to perform determination of CD36 mRNA expression by real-time PCR, lipid profile and metabolic and low grade inflammation markers by routine methods, and soluble scavenger receptors (CD36 and LOX-1) by ELISA. Results. Individuals ≥30 years old with abdominal obesity presented high atherogenic index, lower soluble scavenger receptor levels, and subexpression of CD36 mRNA (54% less). On the other hand, individuals <30 years old with abdominal adiposity presented higher levels in the same parameters, except LOX-1 soluble levels. Conclusion. In this study, individuals over 30 years of age presented low soluble scavenger receptors levels pattern and CD36 gene subexpression, which suggest the chronic metabolic dysregulation in abdominal obesity. PMID:27525284

  14. Low CD36 and LOX-1 Levels and CD36 Gene Subexpression Are Associated with Metabolic Dysregulation in Older Individuals with Abdominal Obesity

    PubMed Central

    Castro-Albarran, Jorge; Sandoval-García, Flavio; Flores-Alvarado, Luis-Javier

    2016-01-01

    Background. Obesity study in the context of scavenger receptors has been linked to atherosclerosis. CD36 and LOX-1 are important, since they have been associated with atherogenic and metabolic disease but not fat redistribution. The aim of our study was to determinate the association between CD36 and LOX-1 in presence of age and abdominal obesity. Methods. This is a cross-sectional study that included 151 healthy individuals, clinically and anthropometrically classified into two groups by age (<30 and ≥30 years old) and abdominal obesity (according to World Health Organization guidelines). We excluded individuals with any chronic and metabolic illness, use of medication, or smoking. Fasting blood samples were taken to perform determination of CD36 mRNA expression by real-time PCR, lipid profile and metabolic and low grade inflammation markers by routine methods, and soluble scavenger receptors (CD36 and LOX-1) by ELISA. Results. Individuals ≥30 years old with abdominal obesity presented high atherogenic index, lower soluble scavenger receptor levels, and subexpression of CD36 mRNA (54% less). On the other hand, individuals <30 years old with abdominal adiposity presented higher levels in the same parameters, except LOX-1 soluble levels. Conclusion. In this study, individuals over 30 years of age presented low soluble scavenger receptors levels pattern and CD36 gene subexpression, which suggest the chronic metabolic dysregulation in abdominal obesity. PMID:27525284

  15. Enhanced Soluble Serum CD40L and Serum P-Selectin Levels in Primary Aldosteronism.

    PubMed

    Petramala, L; Iacobellis, G; Carnevale, R; Marinelli, C; Zinnamosca, L; Concistrè, A; Galassi, M; Iannucci, G; Lucia, P; Pignatelli, P; Ciardi, A; Violi, F; De Toma, G; Letizia, C

    2016-07-01

    Primary aldosteronism (PA) is one of the most frequent forms of secondary hypertension, associated with atherosclerosis and higher risk of cardiovascular events. Platelets play a key role in the atherosclerotic process. The aim of the study was to evaluate the platelet activation by measuring serum levels of soluble CD40L (sCD40L) and P-selectin (sP-selectin) in consecutive PA patients [subgroup: aldosterone-secreting adrenal adenoma (APA) and bilateral adrenal hyperplasia (IHA)], matched with essential hypertensive (EH) patients. The subgroup of APA patients was revaluated 6-months after unilateral adrenalectomy. In all PA group, we measured higher serum levels of both sP-selectin (14.29±9.33 pg/ml) and sCD40L (9.53±4.2 ng/ml) compared to EH patients (9.39±5.3 pg/ml and 3.54±0.94 ng/ml, respectively; p<0.001). After removal of APA, PA patients showed significant reduction of blood pressure (BP) values, plasma aldosterone (PAC) levels and ARR-ratio, associated with a significant reduction of sP-selectin (16.74±8.9 pg/ml vs. 8.1±3.8 pg/ml; p<0.01) and sCD40L (8.6±1 ng/ml vs. 5.24±0.94 ng/ml; p<0.001). In PA patients, we found a significant correlation between sP-selectin and sCD40L with PAC (r=0.52, p<0.01; r=0.50, p<0.01, respectively); this correlation was stronger in APA patients (r=0.54; p<0.01 r=0.63; p<0.01, respectively). Our results showed that PA is related to platelet activation, expressed as higher plasma values of sCD40L and sP-selectin values. Surgical treatment and consequent normalization of aldosterone secretion was associated with significant reduction of sCD40L and sP-selectin values in APA patients. PMID:27101095

  16. Binding of HCV E2 to CD81 induces RANTES secretion and internalization of CC chemokine receptor 5.

    PubMed

    Nattermann, J; Nischalke, H D; Feldmann, G; Ahlenstiel, G; Sauerbruch, T; Spengler, U

    2004-11-01

    Hepatitis C virus (HCV) infection has been shown to be associated with reduced expression of the CC chemokine receptor (CCR) 5, and reduced responsiveness of lymphocytes to chemokines. However, the mechanism by which HCV alters CCR5 expression remains unclear. Here, we investigated whether altered CCR5 expression in hepatitis C results from interactions of CD81 with the HCV E2 protein. Peripheral blood mononuclear cells (PBMC) from HCV-negative individuals were prepared by Ficoll density gradient separation. PBMC subpopulations (CD4+, CD8+ lymphocytes, CD19+ B cells, natural killer (NK) cells and monocyte-derived dendritic cells) were isolated and stimulated with immobilized HCV E2, and changes in CCR5 expression and CC-chemokine secretion were determined. Migration assays were performed using a 5-microm nitrocellulose filter microchamber system according to the manufacturer's recommendations. Exposure of PBMC to HCV E2 induced a dose-dependent release of regulated on activation normal T-cell-expressed and secreted (RANTES), down-regulation of CCR5 expression and intracellular accumulation of CCR5. This effect was blocked by preincubation of PBMC with anti-CD81. RANTES release following exposure to HCV E2 was mainly attributable to CD8+ cells. After exposure to HCV E2 markedly fewer CD8-positive lymphocytes were attracted by RANTES when compared with CD8+ cells that were studied in the absence of HCV E2. Our results suggest that interaction of HCV E2 with CD81 leads to increased RANTES secretion by CD8+ lymphocytes which induces down-regulation of CCR5 surface via receptor internalization resulting in altered lymphocyte migration. PMID:15500552

  17. Investigation of trap levels in HgCdTe IR detectors through low frequency noise spectroscopy

    NASA Astrophysics Data System (ADS)

    Ciura, L.; Kolek, A.; Kębłowski, A.; Stanaszek, D.; Piotrowski, A.; Gawron, W.; Piotrowski, J.

    2016-03-01

    Low frequency noise spectroscopy is a valuable tool for studying narrow gap semiconductor materials and devices. In the paper, the method of traps investigation with low frequency noise spectroscopy was presented, together with quantitative analysis of the results obtained for high-operating-temperature, fast response, Hg1‑x Cd x Te mid-wavelength infrared detectors. The hole trap levels in these devices are Cd-content independent and take the value E T ≅ 140 meV or E T ≅ 40 meV. The level at E T ≅ 140 meV was found for almost all tested detectors. The level around E T = 40 meV was found in two samples. Apart from the hole traps, three electron traps were also found. Their energy levels follow the trend lines E T = 0.35E g(x) and E T = 0.75E g(x). All trap energies are consistent with the results reported in the literature for Hg1‑x Cd x Te devices.

  18. CD4+ T-helper-cell responses in mice with low-level Candida albicans infection.

    PubMed Central

    Mencacci, A; Spaccapelo, R; Del Sero, G; Enssle, K H; Cassone, A; Bistoni, F; Romani, L

    1996-01-01

    Resistance and susceptibility to Candida albicans infection have been shown to be dependent upon the activation of CD4+ T helper (Th) type 1 or Th2 cells, respectively. To study the type, kinetics, and cytokine dependency of CD4+ Th-cell responses in low-level C. albicans infection, susceptible mice were infected with sublethal doses of C. albicans and assessed for parameters of CD4+ Th-dependent immunity. Interleukin (IL)-12 and gamma interferon were always produced early in infection regardless of the pathogen load. In contrast, production of IL-4, and hence Th2-cell reactivity, was strictly dose dependent, being induced at the higher dose of the fungus. Production of IL-12 correlated with a successful control of infection in mice exposed to the lower doses of C. albicans but not with the development of acquired immunity. An antigenic stimulus appeared to be required for IL-12 to induce a protective anticandidal response. Cytokine depletion in vivo revealed that neutralization of IL-4 was protective early but not late in infection, suggesting a different role for IL-4 in the induction versus maintenance of an ongoing anticandidal Th response. Late in infection, an exacerbative effect was also observed upon IL-12 neutralization. These results indicate that the fungal burden and timing of cytokine appearance greatly influence CD4+ Th induction and effector functions in mice with candidiasis. PMID:8945525

  19. Composition dependence of the mercury vacancies energy levels in HgCdTe: Evolution of the ``negative-U'' property

    NASA Astrophysics Data System (ADS)

    Gemain, F.; Robin, I. C.; Feuillet, G.

    2013-12-01

    HgCdTe films grown by liquid phase epitaxy with different Cd compositions were post-annealed to control the Hg vacancy concentration. Then temperature-dependent Hall measurements and photoluminescence measurements allowed us to study the evolution of the Hg vacancy acceptor levels with the cadmium composition. For Cd compositions below 33% the Hg vacancies in HgCdTe present a negative-U property with the ionized state V- stabilized compared to the neutral state V0. For Cd compositions higher than 45%, the Hg vacancies in HgCdTe present a more standard level ordering with the ionized state V- at higher energy than the neutral state V0.

  20. Genetic Variants of CD40 Gene Are Associated with Coronary Artery Disease and Blood Lipid Levels

    PubMed Central

    Zhou, Liting; Xie, Lin; Zheng, Dongchun; Li, Na; Zhu, Jian; Wang, Shuyue; Li, Bo; Ye, Lin

    2016-01-01

    Objectives. The present study aimed to evaluate the effect of CD40 and CXCR4 genes polymorphisms on CAD susceptibility and the blood lipid levels and history of cardiovascular risk factors in a Chinese Han population. Materials and Methods. A total of 583 unrelated patients with CAD and 540 controls were recruited. Two tag SNPs (rs4239702 and rs1535045) at the CD40 locus and one tag SNP (rs2228014) at the CXCR4 locus were genotyped using the SEQUENOM Mass-ARRAY system. Results. After adjusting the risk factors, the frequency of rs1535045-T allele was also higher in patients than controls. Haplotype analysis showed that the rs4239702(C)-rs1535045(T) haplotype was associated with CAD. People with rs4239702-TT genotype had higher blood lipid levels in case group while it was not in the control group. History of cardiovascular risk factors showed no association for the three SNPs in case group and control group. Conclusions. rs1535045 in CD40 gene is likely to be associated with CAD in the Chinese Han population. rs4239702(C)-rs1535045(T) haplotype was associated with CAD. Only in CAD patients, the blood lipid level of patients with rs4239702-TT genotype was higher than other patients. CXCR4 gene may not relate to CAD. PMID:27200368

  1. Bi20 (fBTA05), a novel trifunctional bispecific antibody (anti-CD20 x anti-CD3), mediates efficient killing of B-cell lymphoma cells even with very low CD20 expression levels.

    PubMed

    Stanglmaier, Michael; Faltin, Margot; Ruf, Peter; Bodenhausen, Annette; Schröder, Petra; Lindhofer, Horst

    2008-09-01

    Trifunctional bispecific antibodies can efficiently mediate tumor cell killing by redirecting T cells and immune accessory cells to the tumor cell. Here, we describe the new trifunctional antibody, Bi20 (FBTA05, anti-CD20 x anti-CD3), that connects B cells and T cells via its variable regions and recruits FcgammaRI(+) accessory immune cells via its Fc region. Bi20 mediated efficient and specific lysis of B-cell lines and of B cells with low CD20 expression levels that were derived from CLL patients. Remarkably, T-cell activation and tumor cell killing occurred in an entirely autologous setting without additional effector cells in 5 of 8 samples. In comparison, rituximab, a chimeric monoclonal CD20 antibody, demonstrated a significantly lower B-cell eradication rate. Additionally, Bi20, but not rituximab, upregulated the activation markers CD25 and CD69 on both CD4(+) and CD8(+) T cells in the presence of accessory immune cells. CD14(+) accessory cells and the monocyte cell line THP-1 were activated via binding of the Fc region of Bi20, given that T cells were simultaneously engaged by the antibody. Bi20 induced a strong Th1 cytokine pattern characterized by high IFN-gamma and very low IL-4 secretion. In conclusion, Bi20 may offer new immunotherapeutic options for the treatment of B-cell lymphomas. PMID:18546289

  2. Effect of Co-planted Purslane (Portulaca Oleracea L.) on Cd Accumulation by Sunflower in Different Levels of Cd Contamination and Salinity: A Pot Study.

    PubMed

    Ashrafi, Ali; Zahedi, Morteza; Soleimani, Mohsen

    2015-01-01

    Heavy metal bioaccumulation can be affected by various crop-weed interactions that potentially exist in agroecosystems. A pot experiment was conducted to evaluate the role of rhizosphere interaction of sunflower and purslane (Portulaca oleracea L.) weed on cadmium (Cd) uptake and its allocation to sunflower grains. The experimental treatments consisted of two cropping systems (mono and mixed culture), two adjusted salinity levels (0 and 0.5% NaCl) and three artificial levels of Cd in soil (Control, 3 and 6 mg kg(-1)). The results showed that the growth of sunflower in the presence of purslane in comparison to mono culture of sunflower led to change of total Cd content and Cd allocated to grains only in saline conditions. Promoting effects of salinity on Cd concentration of grain were alleviated where sunflower was co-planted with purslane. Besides, supply of Zn in grains of co-planted sunflower was strongly affected by salinity. Results of this study revealed that although co-planted purslane could alter conditions in the shared rhizosphere, it had no effect on enhancing Cd uptake by neighboring sunflower directly. PMID:26091425

  3. The Accumulation of Intracellular ITEGE and DIPEN Neoepitopes in Bovine Articular Chondrocytes Is Mediated by CD44 Internalization of Hyaluronan

    PubMed Central

    Flory, Jennifer J. Embry; Fosang, Amanda J.; Knudson, Warren

    2011-01-01

    Objective A dramatic loss of aggrecan proteoglycan from cartilage is associated with osteoarthritis. The fate of residual G1 domains of aggrecan is unknown, but inefficient turnover of these domains may impede subsequent repair and retention of newly synthesized aggrecan. Thus, the objective of this study was to determine whether ITEGE- and DIPEN-containing G1 domains, generated in situ, are internalized by articular chondrocytes, and whether these events are dependent on hyaluronan (HA) and its receptor, CD44. Methods ITEGE and DIPEN neoepitopes were detected by immunofluorescence staining of bovine articular cartilage chondrocytes treated with or without interleukin-1α (IL-1α). Additionally, purified ITEGE- or DIPEN-containing G1 domains were aggregated with HA and then added to articular chondrocytes, articular chondrocytes transfected with CD44Δ67, or COS-7 cells transfected with or without full-length CD44. Internalized epitopes were distinguished by their resistance to extensive trypsinization of the cell surface. Results Both ITEGE and DIPEN were visualized within the extracellular cell-associated matrix of chondrocytes as well as within intracellular vesicles. Following trypsinization, the intracellular accumulation of both epitopes was clearly visible. IL-1 treatment increased extracellular as well as intracellular ITEGE epitope accumulation. Once internalized, the ITEGE neoepitope became localized within the nucleus and displayed little colocalization with HA, DIPEN, or other G1 domain epitopes. The internalization of both ITEGE and DIPEN G1 domains was dependent on the presence of HA and CD44. Conclusion One important mechanism for the elimination of residual G1 domains following extracellular degradation of aggrecan is CD44-mediated co-internalization with HA. PMID:16447219

  4. 124In levels populated in the β decay of 124Cd

    NASA Astrophysics Data System (ADS)

    Batchelder, J. C.; Brewer, N. T.; Gross, C. J.; Grzywacz, R.; Hamilton, J. H.; Karny, M.; Fijalkowska, A.; Liu, S. H.; Miernik, K.; Padgett, S. W.; Paulauskas, S. V.; Rykaczewski, K. P.; Ramayya, A. V.; Stracener, D. W.; Wolińska-Cichocka, M.

    2016-08-01

    The β decay of 124Cd into levels in 124In was reinvestigated at the Holifield Radioactive Ion Beam Facility. Fifty-MeV protons were bombarded on uranium targets and the induced fission products were mass separated and deposited on a moving tape in the center of an array of γ detectors. The resulting γ -γ coincidences revealed appreciable disagreement with previous work and has resulted in a revised ordering of the low-energy states in 124In. The resulting partial decay scheme has four energy levels, three of which are new.

  5. Investigation of the origin of deep levels in CdTe doped with Bi

    SciTech Connect

    Saucedo, E.; Franc, J.; Elhadidy, H.; Horodysky, P.; Ruiz, C. M.; Bermudez, V.; Sochinskii, N. V.

    2008-05-01

    Combining optical (low temperature photoluminescence), electrical (thermoelectric effect spectroscopy), and structural (synchrotron X-ray powder diffraction) methods, the defect structure of CdTe doped with Bi was studied in crystals with dopant concentration in the range of 10{sup 17}-10{sup 19} at./cm{sup 3}. The semi-insulating state observed in crystals with low Bi concentration is assigned to the formation of a shallow donor level and a deep donor recombination center. Studying the evolution of lattice parameter with temperature, we postulate that the deep center is formed by a Te-Te dimer and their formation is explained by a tetrahedral to octahedral distortion, due to the introduction of Bi in the CdTe lattice. We also shows that this model agrees with the electrical, optical, and transport charge properties of the samples.

  6. Deep electronic levels in high-pressure Bridgman Cd{sub 1-x}Zn{sub x}Te

    SciTech Connect

    Szeles, C.; Shan, Y.Y.; Lynn, K.G.; Eissler, E.E.

    1995-12-01

    The behavior of deep electronic levels was studied as a function of Zn concentration in CdZnTe crystals grown by the high-pressure Bridgman technique using thermoelectric effect spectroscopy. A significant increase of the thermal ionization energies of hole traps was observed with the increasing Zn content of the ternary compound. The effect explains the stronger hole trapping and the resulting much shorter hole lifetime usually observed in CdZnTe as compared to CdTe. The behavior also suggests increased carrier recombination and explains the strong deterioration of electron collection in detectors fabricated from CdZnTe of high Zn concentration.

  7. Response of the Internal Electric Field in CdZnTe to Illumination at Multiple Optical Powers

    NASA Astrophysics Data System (ADS)

    Washington, Aaron L.; Teague, Lucile C.; Duff, Martine C.; Burger, Arnold; Groza, Michael; Buliga, Vladimir

    2012-10-01

    Manipulation of CdZnTe (CZT) crystals using illumination is a useful tool for altering the internal electric field present under normal bias conditions. The interactions with carriers that are trapped at either terminal are visualized by the electric field distribution through polarization. In this report, we demonstrate an ability to selectively manipulate the internal electric field of CZT using multiple-wavelength light illumination at various optical powers. The internal electric field polarization can be controlled using changes in optical power. We also investigate the electric field distributions using multiple optical powers to examine the light response as a function of light penetration depth.

  8. CdSe Quantum-Dot-Sensitized Solar Cell with ~100% Internal Quantum Efficiency

    SciTech Connect

    Fuke, Nobuhiro; Hoch, Laura B.; Koposov, Alexey Y.; Manner, Virginia W.; Werder, Donald J.; Fukui, Atsushi; Koide, Naoki; Katayama, Hiroyuki; Sykora, Milan

    2010-10-20

    We have constructed and studied photoelectrochemical solar cells (PECs) consisting of a photoanode prepared by direct deposition of independently synthesized CdSe nanocrystal quantum dots (NQDs) onto a nanocrystalline TiO2 film (NQD/TiO2), aqueous Na2S or Li2S electrolyte, and a Pt counter electrode. We show that light harvesting efficiency (LHE) of the NQD/TiO2 photoanode is significantly enhanced when the NQD surface passivation is changed from tri-n-octylphosphine oxide (TOPO) to 4-butylamine (BA). In the PEC the use of NQDs with a shorter passivating ligand, BA, leads to a significant enhancement in both the electron injection efficiency at the NQD/TiO2 interface and charge collection efficiency at the NQD/electrolyte interface, with the latter attributed mostly to a more efficient diffusion of the electrolyte through the pores of the photoanode. We show that by utilizing BA-capped NQDs and aqueous Li2S as an electrolyte, it is possible to achieve ~100% internal quantum efficiency of photon-to-electron conversion, matching the performance of dye-sensitized solar cells.

  9. Elevated Serum Levels of Soluble CD30 in Ankylosing Spondylitis Patients and Its Association with Disease Severity-Related Parameters

    PubMed Central

    Gao, Rongfen; Sun, Wei; Chen, Yu; Su, Yuying; Wang, Chenqiong; Dong, Lingli

    2015-01-01

    Soluble CD30 (sCD30), a transmembrane glycoprotein that belongs to the tumor necrosis factor receptor (TNFR) superfamily, has been shown to be associated with various pathological conditions. This study was designed to measure the levels of serum sCD30 in patients with ankylosing spondylitis (AS) and to evaluate the relationships between serum sCD30 levels and other disease severity-related indexes, including bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAS), and bath ankylosing spondylitis functional index (BASFI). Our results demonstrated significantly elevated sCD30 levels in AS patients compared to healthy controls (HCs) with mean values of 32.0 ± 12.2 and 24.9 ± 8.0 ng/mL, respectively (P** = 0.007), suggesting a potential role of sCD30 in the pathogenesis of AS. However, no significant correlations of sCD30 with BASDAI, ASDAS, or BASFI were detected in our study (P > 0.05). Therefore, sCD30 cannot be used as a reliable marker for reflecting disease activity and functional ability of AS patients. PMID:26273636

  10. Comparative studies on Pb and Cd levels in parasites of terrestrial and aquatic animals

    SciTech Connect

    Sures, B.; Taraschewski, H.

    1995-12-31

    Several fish parasites (Acanthocephala, Cestoda, Nematoda) and organs of their respective intermediate and final hosts were analyzed for heavy metals by electrothermal atomic absorption spectrometry (ET-AAS). Pb and Cd were also quantified in the liver fluke Fasciola hepatica as well as in different organs of the large intestinal roundworm Ascaris suum. The levels of these heavy metals in the parasites were compared to those of muscle, liver, kidney and intestine of the respective definitive hosts cattle and swine obtained from a slaughter house. Most parasites accumulated significantly higher levels of metals than their final hosts. This was most conspicuous in acanthocephalans which contained up to 3 {times} 10{sup 3} fold more lead than the muscle of their fish hosts and up to 1.1 {times} 10{sup 4} more lead than the water surrounding the fish. In these helminths cadmium was enriched up to 400 fold compared to the muscle of the fish and up to 2.7 {times} 10{sup 4} compared to the water. In contrast to the accumulation capacity of adult acanthocephalans their larvae contained about 30 to 180 times less Pb and Cd. Thus, the predominant accumulation of both metals appears in the adult worms. The cestodes of fish and the liver flukes of cattle accumulated the metals up to 200 fold compared to the muscle of their hosts. The nematodes did not contain higher levels of the metals than their hosts. Thus, parasites, especially acanthocephalans, seem to be sensitive bioindicators of Pb and Cd in their environments.

  11. Identification of the double acceptor levels of the mercury vacancies in HgCdTe

    NASA Astrophysics Data System (ADS)

    Gemain, F.; Robin, I. C.; De Vita, M.; Brochen, S.; Lusson, A.

    2011-03-01

    Photoluminescence and temperature-dependent Hall measurements of nonintentionally doped HgCdTe epilayers were compared. These films were grown by liquid phase epitaxy and postannealed under different conditions as follows: a p-type annealing was used to control the mercury vacancy concentration and a n-type annealing under saturated Hg atmosphere was used to fill the mercury vacancies. The comparison of the photoluminescence measurements with Hall effect measurements allows us to identify the two acceptor energy levels of the mercury vacancy and to evidence its "negative-U" property corresponding to a stabilization of the ionized state V- of the mercury vacancy compared to its neutral state V0.

  12. Elevated plasma-soluble CD16 levels in porcine reproductive and respiratory syndrome virus-infected pigs: correlation with ADAM17-mediated shedding.

    PubMed

    Gu, Weihong; Guo, Longjun; Li, Ren; Niu, Junwei; Luo, Xiaolei; Zhang, Jian; Xu, Yunfei; Tian, Zhijun; Feng, Li; Wang, Yue

    2016-03-01

    Soluble CD16 (sCD16) is closely correlated with chronic diseases in humans. Here, plasma sCD16 levels in pigs were increased by infection with porcine reproductive and respiratory syndrome virus (PRRSV) but not with porcine epidemic diarrhea virus, porcine circovirus type 2 and pseudorabies virus. Of interest, PRRSV attached to blood neutrophils and reduced surface CD16 expression on neutrophils. In vitro data confirmed that PRRSV caused CD16 shedding in neutrophils. Further analyses revealed that ADAM17 was involved in porcine CD16 shedding. Thus, our findings suggest that increase in sCD16 levels may be an indicator of PRRSV infection. PMID:26653711

  13. CD4(+), CD25(+), FOXP3 (+) T Regulatory Cell Levels in Obese, Asthmatic, Asthmatic Obese, and Healthy Children.

    PubMed

    Donma, Metin; Karasu, Erkut; Ozdilek, Burcu; Turgut, Burhan; Topcu, Birol; Nalbantoglu, Burcin; Donma, Orkide

    2015-08-01

    The aim of this prospective case control study is to determine CD4(+), CD25(+), and FoxP3(+) T regulatory cells (Tregs) and T helper cells (Ths) in obese, asthmatic, asthmatic obese, and healthy children. Obese (n = 40), asthmatic (n = 40), asthmatic obese (n = 40), and healthy children (n = 40) were included in this study. Blood samples collected from children were marked with CD4, CD25, ve Foxp3 in order to detect Tregs and Ths by flow cytometric method. Statistical analyses were performed. p ≤ 0.05 was chosen as meaningful threshold. Tregs exhibiting anti-inflammatory nature were significantly lower in obese (0.16 %; p ≤ 0.001), asthmatic (0.25 %; p ≤ 0.01), and asthmatic obese (0.29 %; p ≤ 0.05) groups than control group (0.38 %). Ths were counted higher in asthma group than control (p ≤ 0.01) and obese (p ≤ 0.001) groups. T cell immunity plays important roles in chronic inflammatory diseases such as obesity and asthma pathogeneses. Decreased numbers of Tregs found in obese, asthmatic, and asthmatic obese children might represent a challenge of these cells. PMID:25655390

  14. Distribution of Cd and Zn levels in soils and Acacia xanthophloea Benth. from Lake Nakuru National Park Kenya.

    PubMed

    Dharani, N; Onyari, J M; Kinyamario, J I; Maina, D M; Mavuti, K M

    2010-09-01

    Cadmium and zinc from anthropogenic sources in Lake Nakuru were investigated. High metal levels (mg/kg) in soils (Cd < or = 16.3 and Zn < or = 280) and Acacia xanthophloea (Cd < or = 32 and Zn < or = 310) were observed at polluted sites. Significant variations in metal values were evaluated using ANOVA (F test) and student's t test at p < 0.05 and metal correlations studied. High levels of metals in soils and unhealthy/dying Acacia were obtained at polluted sites. Significant positive correlation was obtained between Cd and Zn in soils and plants. Acacia sp are effective biomonitor of environmental quality in areas subjected to pollution. PMID:20623266

  15. Macroautophagy Proteins Control MHC Class I Levels on Dendritic Cells and Shape Anti-viral CD8(+) T Cell Responses.

    PubMed

    Loi, Monica; Müller, Anne; Steinbach, Karin; Niven, Jennifer; Barreira da Silva, Rosa; Paul, Petra; Ligeon, Laure-Anne; Caruso, Assunta; Albrecht, Randy A; Becker, Andrea C; Annaheim, Nicolas; Nowag, Heike; Dengjel, Jörn; García-Sastre, Adolfo; Merkler, Doron; Münz, Christian; Gannagé, Monique

    2016-05-01

    The macroautophagy machinery has been implicated in MHC class II restricted antigen presentation. Here, we report that this machinery assists in the internalization of MHC class I molecules. In the absence of the autophagy factors Atg5 and Atg7, MHC class I surface levels are elevated due to decreased endocytosis and degradation. Internalization of MHC class I molecules occurs less efficiently if AAK1 cannot be recruited via Atg8/LC3B. In the absence of Atg-dependent MHC class I internalization, dendritic cells stimulate CD8(+) T cell responses more efficiently in vitro and in vivo. During viral infections, lack of Atg5 results in enhanced influenza- and LCMV-specific CD8(+) T cell responses in vivo. Elevated influenza-specific CD8(+) T cell responses are associated with better immune control of this infection. Thus, the macroautophagy machinery orchestrates T cell immunity by supporting MHC class II but compromises MHC class I restricted antigen presentation. PMID:27117419

  16. The Serum Levels of the Soluble Factors sCD40L and CXCL1 Are Not Indicative of Endometriosis

    PubMed Central

    Pateisky, Petra; Pils, Dietmar; Kuessel, Lorenz; Szabo, Ladislaus; Walch, Katharina; Obwegeser, Reinhard; Wenzl, René; Yotova, Iveta

    2016-01-01

    Endometriosis is a benign but troublesome gynecological condition, characterized by endometrial-like tissue outside the uterine cavity. Lately, the discovery and validation of noninvasive diagnostic biomarkers for endometriosis is one of the main priorities in the field. As the disease elicits a chronic inflammatory reaction, we focused our interest on two factors well known to be involved in inflammation and neoplastic processes, namely, soluble CD40 Ligand and CXCL1, and asked whether differences in the serum levels of sCD40L and CXCL1 in endometriosis patients versus controls can serve as noninvasive disease markers. A total of n = 60 women were included in the study, 31 endometriosis patients and 29 controls, and the serum levels of sCD40L and CXCL1 were measured by enzyme-linked immunosorbent assay. Overall, there were no statistically significant differences in the levels of expression of both sCD40L and CXCL1 between patients and controls. This study adds useful clinical data showing that the serum levels of the soluble factors sCD40L and CXCL1 are not associated with endometriosis and are not suitable as biomarkers for disease diagnosis. However, we found a trend toward lower levels of sCD40L in the deep infiltrating endometriosis subgroup making it a potentially interesting target worth further investigation. PMID:27190986

  17. The Toll-like receptor 2 (TLR2) ligand FSL-1 is internalized via the clathrin-dependent endocytic pathway triggered by CD14 and CD36 but not by TLR2

    PubMed Central

    Shamsul, Haque M; Hasebe, Akira; Iyori, Mitsuhiro; Ohtani, Makoto; Kiura, Kazuto; Zhang, Diya; Totsuka, Yasunori; Shibata, Ken- ichiro

    2010-01-01

    Little is known of how Toll-like receptor (TLR) ligands are processed after recognition by TLRs. This study was therefore designed to investigate how the TLR2 ligand FSL-1 is processed in macrophages after recognition by TLR2. FSL-1 was internalized into the murine macrophage cell line, RAW264.7. Both chlorpromazine and methyl-β-cyclodextrin, which inhibit clathrin-dependent endocytosis, reduced FSL-1 uptake by RAW264.7 cells in a dose-dependent manner but nystatin, which inhibits caveolae- and lipid raft-dependent endocytosis, did not. FSL-1 was co-localized with clathrin but not with TLR2 in the cytosol of RAW264.7 cells. These results suggest that internalization of FSL-1 is clathrin dependent. In addition, FSL-1 was internalized by peritoneal macrophages from TLR2-deficient mice. FSL-1 was internalized by human embryonic kidney 293 cells transfected with CD14 or CD36 but not by the non-transfected cells. Also, knockdown of CD14 or CD36 in the transfectants reduced FSL-1 uptake. In this study, we suggest that (i) FSL-1 is internalized into macrophages via a clathrin-dependent endocytic pathway, (ii) the FSL-1 uptake by macrophages occurs irrespective of the presence of TLR2, and (iii) CD14 and CD36 are responsible for the internalization of FSL-1. PMID:20113368

  18. High levels of functional endopeptidase 24.11 (CD10) activity on human thymocytes: preferential expression on immature subsets.

    PubMed Central

    Mari, B; Breittmayer, J P; Guerin, S; Belhacene, N; Peyron, J F; Deckert, M; Rossi, B; Auberger, P

    1994-01-01

    Although it is now well established that cells of the immune system express most of the exopeptidases described so far, little information is available concerning the identification and the characterization of the peptidases associated with the surface of human thymocytes. In the present study we have focused on CD10 expression on thymocytes using both FACS and enzymatic analysis. Unfractionated intact human thymocytes were shown to express significant levels of CD10-specific enzymatic activity, as assessed by the hydrolysis of the neutral endopeptidase (NEP) substrate Suc-Ala-Ala-Phe-pNA and of D-Ala2-Leu-enkephalin, a typical NEP substrate. CD10 activity was abolished by specific NEP inhibitors, including thiorphan, retrothiorphan and phosphoramidon. Moreover, high performance liquid chromatography (HPLC) analysis showed that intact thymocytes and purified NEP hydrolysed thymopentin, a thymic factor known to induce the maturation of prothymocytes into thymocytes. Finally, CD 10/NEP was preferentially associated with CD3- CD3low and immature CD4- CD8- thymocytes. The data demonstrate for the first time that human thymocytes express functional NEP and suggest a role for this enzyme in the maturation of human thymocytes. PMID:7959879

  19. Circulating promyelocytes and low levels of CD16 expression on polymorphonuclear leukocytes accompany early-onset periodontitis.

    PubMed Central

    Nemoto, E; Nakamura, M; Shoji, S; Horiuchi, H

    1997-01-01

    Early-onset periodontitis (EOP) is characterized by rapidly progressive alveolar bone loss, chemotactic defects of neutrophils, and significant familial aggregation. We found immature myeloid lineage cells, defined as promyelocytes, in the peripheral blood in patients with EOP. A hematological examination of peripheral blood cells showed normal reference values regarding cell proportions. Flow cytometry revealed significantly lower expression of CD16, a glycosylphosphatidylinositol (GPI)-anchored protein, on peripheral neutrophils in patients compared with those in age- and sex-matched healthy controls, whereas the levels of CD11a and CD11b expression were similar. The chemotactic response of neutrophils was lower toward not only formyl-methionyl-leucyl-phenylalanine but also complement fragment C5a than that of healthy controls. The expression of another GPI-anchored protein, CD14, was equally expressed by controls and patients. Therefore, the low level of CD16 expression was not due to the incomplete synthesis of the GPI anchor. GPI anchors of CD16 on neutrophils from controls and patients were both partially resistant to phosphatidylinositol-specific phospholipase C. The presence of promyelocytes in peripheral blood, low expression of CD16, and low chemotactic response of neutrophils suggest that patients with EOP have an abnormal maturation system in myeloid lineage cells in the bone marrow, which may be associated with the onset and course of EOP. PMID:9284170

  20. Increased synovial fluid levels of soluble CD23 are associated with an erosive status in rheumatoid arthritis (RA)

    PubMed Central

    Ribbens, C; Bonnet, V; Kaiser, M J; Andre, B; Kaye, O; Franchimont, N; De Groote, D; Beguin, Y; Malaise, M G

    2000-01-01

    Synovial fluid (SF) levels of soluble CD23 (sCD23) were determined in 96 patients presenting with an inflammatory knee effusion (73 with RA and 23 with reactive arthritis (ReA) serving as a control inflammatory non-erosive group) and were correlated with the degree of joint destruction, with local immune parameters (IL-1β, IL-3, IL-4, IL-6, IL-8, IL-10, IL-12 and sCD25) and with serum markers of inflammation, C-reactive protein and erythrocyte sedimentation rate. RA patients, classified as erosive or not according to Larsen’s grade, were separated as follows: (i) 13 patients with non-erosive RA; (ii) 16 RA patients with erosions in hands but not in knees, matched for disease duration with the first group; (iii) 44 RA patients with hand and knee erosions, matched with the second group for rheumatoid factor positivity but of longer disease duration. SF sCD23 levels were significantly increased in both erosive RA groups compared with non-erosive diseases, whether RA or ReA (P < 0·05), whose SF levels were not different. SF IL-10 showed a similar profile to that of SF sCD23 and was the only other parameter characteristic of erosive RA, but no direct correlation was found between the two. SF sCD23 was significantly correlated with IL-12 (r = 0·65, P = 0·0001) and sCD25 (r = 0·39, P = 0·0019) exclusively in the two erosive RA populations. In conclusion, these data showing that increased levels of sCD23 are not only found in the SF of erosive joints but also in knee SF of patients with erosive RA but without knee x-ray-diagnosed erosions suggest that this parameter might be of predictive value for joint destruction. Longitudinal studies are however needed to confirm its potential clinical interest. PMID:10759783

  1. Levels at Streamflow Gaging Stations--A CD-ROM Based Training Class

    USGS Publications Warehouse

    Nolan, K. Michael; Jacobson, Nathan; Erickson, Robert; Landon, Stanley

    2003-01-01

    Streamgages record the elevation of the water surface above some reference surface, or datum. This datum is assumed to remain unchanged throughout the life of the gage. However, the elevation of gages and their supporting structures often change over time as a result of earthmovement, floods, ice, and debris. The surveying practice of leveling is used to establish datum for new gage structures and to check for vertical movement of those structures over time. Vertical changes in gage structures can affect stage-discharge relations and, thus, could result in incorrect discharge determinations. Datum checks are used to correct stage-discharge relations and allow the USGS to document gage datum throughout the life of a gage. This training presentation describes methods currently used by the U.S. Geological Survey to run levels at gaging stations. The presentation is narrated, but you control the pace of the presentation. If the computer you are using can view 'MPEG' videos you will be able to take advantage of videos found within the presentation. A test, found at the end of the presentation, can be taken to assess how well you understood the training material. The class is registered as class SW1307 with the National Training Center of the U.S. Geologcial Survey. The presentation was developed using Macromedia Director 8.5(1) and is contained in the file 'WRI-4002.exe', which should auto-launch after the CD-ROM is inserted in the PC. The program only runs on a windows-based personal computer (PC). A sound card and speakers are necessary to take advantage of the narration that accompanies the presentation. Text of narrations is provided, if you are unable to listen to the narrations. Instructions for installing and running the presentation are included in the file ' Intro.html'. The file 'Intro.html' is on the CD-ROM containing the presentation and is available from the presentation's help menu.

  2. FIR Synchrotron Spectroscopy of High Torsional Levels of CD_3OH: the Tau of Methanol

    NASA Astrophysics Data System (ADS)

    Lees, Ronald M.; Xu, Li-Hong; Billinghurst, Brant E.

    2015-06-01

    Sub-bands involving high torsional levels of the CD_3OH isotopologue of methanol have been analyzed in Fourier transform spectra recorded at the Far-Infrared beamline of the Canadian Light Source synchrotron in Saskatoon. Energy term values for A and E torsional species of the third excited torsional state, v_t = 3, are now almost complete up to rotational levels K = 15, and thirteen substates have so far been identified for v_t = 4. The spectra show interesting close groupings of high-v_t sub-bands related by Dennison's torsional symmetry label τ, rather than A and E, that can be understood in terms of a simple and universal free-rotor "spectral predictor" chart. Transitions between states on the same free rotor curve have torsional overlap matrix elements close to unity, so give rise to strong sub-bands providing radiative routes for rapid population transfer through the high torsional manifold. Where the energy curves for the v_t = 3 and 4 ground-state torsional levels pass through the excited vibrational states, strong resonances can occur and a number of anharmonic and Coriolis interactions have been detected through perturbations to the spectra and appearance of forbidden transitions due to strong mixing and intensity borrowing.

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

    SciTech Connect

    Zha, Gangqiang; Yang, Jian; Xu, Lingyan; Feng, Tao; Wang, Ning; Jie, Wanqi

    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 can be explained using the deep trap model.

  4. Recent international developments in low-level waste disposal

    SciTech Connect

    Mitchell, S.J.; Lakey, L.T.; Harmon, K.M.

    1986-11-01

    Recent international developments in low-level waste (LLW) disposal have included a move away from ocean dumping and a trend towards engineered and deeper dispoosal. Siting efforts have accelerated as interim storage facilities and existing sites reach capacity. The suspension of ocean dumping by the London Dumping Conventions of 1983 and 1985 has affected the LLW disposal practices of several countries, including the United Kingdom, Belgium, the Netherlands, Switzerland, and Japan. Their plans now include disposal in trenches, shallow concrete pits, deep mines, sub-seabed caverns, horizontal mountain tunnels, and long-term storage facilities. Other recent developments include selection of the semi-desert Vaalputs site in South Africa, licensing activities for the Konrad mine site in the Federal Republic of Germany, design of at-reactor sites in Finland, and construction of a Baltic Sea site in Sweden. Also, the French have recently selected the Aube site for engineered disposal in monoliths and tumuli, now used at the La Manche site.

  5. Internal field switching in CdSe quantum dot films on Si.

    PubMed

    Sarkar, Shaibal K; Cohen, Hagai; Hodes, Gary

    2005-01-13

    If a thin film (tens of nm) of CdSe quantum dots (4 nm diameter) is deposited by chemical bath deposition onto various substrates, the films, although essentially intrinsic, behave as if they were n-type with respect to charge separation. However, films deposited under certain deposition conditions on Si (both n(+)- and p(+)-type) behave as if they were p-type. In this case, we show that it is possible to switch this p-type photoresponse by either light illumination intensity or injection of electrons from an external filament. Using both surface photovoltage spectroscopy and a novel adaptation of X-ray photoelectron spectroscopy, we show how this behavior results from a Cd(OH)(2) layer adsorbed at the Si surface at the beginning of the deposition. This response is explained by a competition between a high concentration of relatively shallow hole traps in the CdSe and a lower concentration of deeper electron traps in the Cd(OH)(2). The relative occupancies of these traps determine the fields in the film and their response to external parameters. PMID:16851002

  6. Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization - A minimally invasive cancer stem cell-targeting strategy.

    PubMed

    Bostad, Monica; Olsen, Cathrine Elisabeth; Peng, Qian; Berg, Kristian; Høgset, Anders; Selbo, Pål Kristian

    2015-05-28

    The cancer stem cell (CSC) marker CD133 is an attractive target to improve antitumor therapy. We have used photochemical internalization (PCI) for the endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin (PCIAC133-saporin). PCI employs an endocytic vesicle-localizing photosensitizer, which generates reactive oxygen species upon light-activation causing a rupture of the vesicle membranes and endosomal escape of entrapped drugs. Here we show that AC133-saporin co-localizes with the PCI-photosensitizer TPCS2a, which upon light exposure induces cytosolic release of AC133-saporin. PCI of picomolar levels of AC133-saporin in colorectal adenocarcinoma WiDr cells blocked cell proliferation and induced 100% inhibition of cell viability and colony forming ability at the highest light doses, whereas no cytotoxicity was obtained in the absence of light. Efficient PCI-based CD133-targeting was in addition demonstrated in the stem-cell-like, triple negative breast cancer cell line MDA-MB-231 and in the aggressive malignant melanoma cell line FEMX-1, whereas no enhanced targeting was obtained in the CD133-negative breast cancer cell line MCF-7. PCIAC133-saporin induced mainly necrosis and a minimal apoptotic response based on assessing cleavage of caspase-3 and PARP, and the TUNEL assay. PCIAC133-saporin resulted in S phase arrest and reduced LC3-II conversion compared to control treatments. Notably, co-treatment with Bafilomycin A1 and PCIAC133-saporin blocked LC3-II conversion, indicating a termination of the autophagic flux in WiDr cells. For the first time, we demonstrate laser-controlled targeting of CD133 in vivo. After only one systemic injection of AC133-saporin and TPCS2a, a strong anti-tumor response was observed after PCIAC133-saporin. The present PCI-based endosomal escape technology represents a minimally invasive strategy for spatio-temporal, light-controlled targeting of CD133+ cells in localized primary tumors or metastasis. PMID:25758331

  7. Cell Membrane CD44v6 Levels in Squamous Cell Carcinoma of the Lung: Association with High Cellular Proliferation and High Concentrations of EGFR and CD44v5

    PubMed Central

    Ruibal, Álvaro; Aguiar, Pablo; Del Río, María Carmen; Nuñez, Matilde Isabel; Pubul, Virginia; Herranz, Michel

    2015-01-01

    Membranous CD44v6 levels in tumors and surrounding samples obtained from 94 patients with squamous cell lung carcinomas were studied and compared to clinical stage, cellular proliferation, membranous CD44v5 levels, epidermal growth factor receptor EGFR and cytoplasmatic concentrations of CYFRA 21.1. CD44v6 positive values were observed in 33/38 non-tumor samples and in 76/94 tumor samples, but there were not statistically significant differences between both subgroups. In CD44v6 positive tumor samples, CD44v6 was not associated with clinical stage, histological grade, ploidy and lymph node involvement, but significant association was found with high cellular proliferation. Likewise, CD44v6 positive tumors had significantly higher levels of EGFR and CD44v5. In patients with squamous cell lung carcinomas and clinical stage I, positive CD44v6 cases were associated with the same parameters. Furthermore, positive CD44v5 squamous tumors were associated significantly with histological grade III and lower levels of CYFRA21.1. Our findings support the value of CD44v6 as a possible indicator of poor outcome in patients with squamous lung carcinomas. PMID:25809603

  8. Cell membrane CD44v6 levels in squamous cell carcinoma of the lung: association with high cellular proliferation and high concentrations of EGFR and CD44v5.

    PubMed

    Ruibal, Álvaro; Aguiar, Pablo; Del Río, María Carmen; Nuñez, Matilde Isabel; Pubul, Virginia; Herranz, Michel

    2015-01-01

    Membranous CD44v6 levels in tumors and surrounding samples obtained from 94 patients with squamous cell lung carcinomas were studied and compared to clinical stage, cellular proliferation, membranous CD44v5 levels, epidermal growth factor receptor EGFR and cytoplasmatic concentrations of CYFRA 21.1. CD44v6 positive values were observed in 33/38 non-tumor samples and in 76/94 tumor samples, but there were not statistically significant differences between both subgroups. In CD44v6 positive tumor samples, CD44v6 was not associated with clinical stage, histological grade, ploidy and lymph node involvement, but significant association was found with high cellular proliferation. Likewise, CD44v6 positive tumors had significantly higher levels of EGFR and CD44v5. In patients with squamous cell lung carcinomas and clinical stage I, positive CD44v6 cases were associated with the same parameters. Furthermore, positive CD44v5 squamous tumors were associated significantly with histological grade III and lower levels of CYFRA21.1. Our findings support the value of CD44v6 as a possible indicator of poor outcome in patients with squamous lung carcinomas. PMID:25809603

  9. Teaching about International Conflict and Peacemaking at the Grassroots Level

    ERIC Educational Resources Information Center

    Rossi, John Allen

    2003-01-01

    In this article, the author relates the changing nature of international conflict and peacemaking since the end of the cold war to the development of a school curriculum that focuses on pressing international issues that are shared by people around the world. He also analyzes the implications of the changing world for curriculum development and…

  10. NIPBL expression levels in CdLS probands as a predictor of mutation type and phenotypic severity.

    PubMed

    Kaur, Maninder; Mehta, Devanshi; Noon, Sarah E; Deardorff, Matthew A; Zhang, Zhe; Krantz, Ian D

    2016-06-01

    Cornelia de Lange syndrome (CdLS) is a rare, genetically heterogeneous multisystem developmental disorder with a high degree of variability in its clinical presentation. Approximately 65% of probands harbor mutations in genes that encode core components (SMC1A, SMC3, and RAD21) or regulators (NIPBL, HDAC8) of the cohesin complex, of which mutations in NIPBL are the most common. Cohesin plays a canonical role in sister chromatid cohesion during cell division and non-canonical roles in DNA repair, stem cell maintenance and differentiation, and regulation of gene expression. Disruption of the latter role seems to be the major contributor to the underlying molecular pathogenesis of CdLS. NIPBL is required for loading and unloading the cohesin complex onto chromosomes. The expression levels of NIPBL itself appear to be tightly regulated and highly evolutionarily conserved. Droplet digital PCR was used to quantify NIPBL mRNA expression levels with high precision from a cohort of 37 samples (NIPBL, SMC1A, SMC3, and HDAC8 mutation positive probands and negative control). Probands with severe forms of CdLS or severe mutation types were found to have lower levels of NIPBL in comparison to phenotypically milder patients and controls. Levels of NIPBL also correlated with the presence of mutations in different CdLS-causing genes. The data suggests that NIPBL levels are closely correlated with the severity of CdLS and with specific causative genes and types of mutations. ddPCR may provide a tool to assist in diagnostic approaches to CdLS, for genetic counseling and prognosis, and for monitoring potential therapeutic modalities in the future. © 2016 Wiley Periodicals, Inc. PMID:27125329

  11. [Serum soluble CD44 isoform variant 5 level in patients with seropositive rheumatoid arthritis treated with cyclosporin A].

    PubMed

    Feyertag, J; Haberhauer, G; Skoumal, M; Kittl, E M; Bauer, K; Dunky, A

    2000-01-01

    CD44 is a widely expressed cell surface glycoprotein which is involved in many cell-cell and cell-matrix interactions. Expression of soluble CD44 splice variants is strictly regulated and is linked to a high rate of cell division. Serum levels of soluble CD44 variant 5 (sCD44v5) were determined in 14 patients with erosive RA. Patients were divided into two groups. In group 1 cyclosporin A treatment (CYA) was initiated after the first visit. In group 2 preliminary CYA was continued. Controls were performed after 6 months. We found a significant decrease of swollen joint count (SJC) and sCD44v5 in group 1. No effect of CYA was found on c-reactive protein, erythrocyte sedimentation rate and IgM-rheumatoid factor (IgM-RF). In group 2 a significant decrease of CRP was found. Therefore we conclude that measurement of sCD44v5 might be useful in monitoring RA+ patients with CYA. PMID:11261266

  12. Identification of a millisecond isomeric state in 129Cd81via the detection of internal conversion and Compton electrons

    SciTech Connect

    Taprogge, J.; Jungclaus, A.; Grawe, H.; Nishimura, S.; Xu, Z. Y.; Doornenbal, P.; Lorusso, G.; Nacher, E.; Simpson, G. S.; Soderstrom, P. A.; Sumikama, T.; Kondev, F. G.

    2014-11-10

    The decay of an isomeric state in the neutron-rich nucleus 129Cd has been observed via the detection of internal conversion and Compton electrons providing first experimental information on excited states in this nucleus. The isomer was populated in the projectile fission of a 238U beam at the Radioactive Isotope Beam Factory at RIKEN. From the measured yields of γ-rays and internal conversion electrons, a multipolarity of E 3 was tentatively assigned to the isomeric transition. A half-life of T1/2=3.6(2) msT1/2=3.6(2) ms was determined for the new state which was assigned a spin of (21/2+)(21/2+), based on a comparison to shell model calculations performed using state-of-the-art realistic effective interactions.

  13. Graduate-level entry to nursing: international perspectives.

    PubMed

    Ingrams, Paula

    2016-05-26

    Paula Ingrams, Practice Education Coordinator, NHS Education for Scotland, provides an overview of her international scholarship into the views of academics, clinical staff and nursing students on graduate nurses and graduates within nursing. PMID:27231739

  14. International low level waste disposal practices and facilities

    SciTech Connect

    Nutt, W.M.

    2011-12-19

    The safe management of nuclear waste arising from nuclear activities is an issue of great importance for the protection of human health and the environment now and in the future. The primary goal of this report is to identify the current situation and practices being utilized across the globe to manage and store low and intermediate level radioactive waste. The countries included in this report were selected based on their nuclear power capabilities and involvement in the nuclear fuel cycle. This report highlights the nuclear waste management laws and regulations, current disposal practices, and future plans for facilities of the selected international nuclear countries. For each country presented, background information and the history of nuclear facilities are also summarized to frame the country's nuclear activities and set stage for the management practices employed. The production of nuclear energy, including all the steps in the nuclear fuel cycle, results in the generation of radioactive waste. However, radioactive waste may also be generated by other activities such as medical, laboratory, research institution, or industrial use of radioisotopes and sealed radiation sources, defense and weapons programs, and processing (mostly large scale) of mineral ores or other materials containing naturally occurring radionuclides. Radioactive waste also arises from intervention activities, which are necessary after accidents or to remediate areas affected by past practices. The radioactive waste generated arises in a wide range of physical, chemical, and radiological forms. It may be solid, liquid, or gaseous. Levels of activity concentration can vary from extremely high, such as levels associated with spent fuel and residues from fuel reprocessing, to very low, for instance those associated with radioisotope applications. Equally broad is the spectrum of half-lives of the radionuclides contained in the waste. These differences result in an equally wide variety of

  15. Landau level splitting in Cd3As2 under high magnetic fields

    PubMed Central

    Cao, Junzhi; Liang, Sihang; Zhang, Cheng; Liu, Yanwen; Huang, Junwei; Jin, Zhao; Chen, Zhi-Gang; Wang, Zhijun; Wang, Qisi; Zhao, Jun; Li, Shiyan; Dai, Xi; Zou, Jin; Xia, Zhengcai; Li, Liang; Xiu, Faxian

    2015-01-01

    Three-dimensional topological Dirac semimetals (TDSs) are a new kind of Dirac materials that exhibit linear energy dispersion in the bulk and can be viewed as three-dimensional graphene. 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 experiment on Landau level splitting in TDS Cd3As2 single crystals under high magnetic fields, suggesting the removal of spin degeneracy by breaking time reversal symmetry. The detected Berry phase develops an evident angular dependence and possesses a crossover from non-trivial to trivial state under high magnetic fields, a strong hint for a fierce competition between the orbit-coupled field strength and the field-generated mass term. Our results unveil the important role of symmetry breaking in TDSs and further demonstrate a feasible path to generate a Weyl semimetal phase by breaking time reversal symmetry. PMID:26165390

  16. Student Interactions with CD-ROM Storybooks: A Look at Potential Relationships between Multiple Intelligence Strengths and Levels of Interaction

    ERIC Educational Resources Information Center

    Huffman, Celia A.

    2012-01-01

    This study looked at the potential relationship that may exist between students' intelligence strengths, in particular their spatial and kinesthetic strengths, and their combined cognitive and metacognitive levels of interaction with a CD-ROM storybook. The multiple intelligence strengths of a sample of students, measured via the MIDAS/My…

  17. Levels of circulating myeloid subpopulations and of heme oxygenase-1 do not predict CD4+ T cell recovery after the initiation of antiretroviral therapy for HIV disease

    PubMed Central

    2014-01-01

    The level (or frequency) of circulating monocyte subpopulations such as classical (CD14hiCD16-) and non-classical (CD14dimCD16+) monocytes varies during the course of HIV disease progression and antiretroviral therapy (ART). We hypothesized that such variation and/or differences in the degree to which these cells expressed the immunoregulatory enzyme, heme oxygenase-1 (HO-1), would be associated with CD4+ T cell recovery after the initiation of ART. This hypothesis was tested in a cross-sectional study of four groups of HIV-infected subjects, including those who were seronegative, untreated virologic controllers [detectable viral load (VL) of <1000 copies/mL], untreated virologic non-controllers [VL > 10,000 copies/mL], and ART-mediated virologic controllers [VL < 75 copies/mL]. A longitudinal analysis of ART-treated subjects was also performed along with regression analysis to determine which biomarkers were associated with and/or predictive of CD4+ T cell recovery. Suppressive ART was associated with increased levels of classical monocyte subpopulations (CD14hiCD16-) and decreased levels of non-classical monocyte populations (CD14dimCD16+). Among peripheral blood mononuclear cells (PBMCs), HO-1 was found to be most highly up-regulated in CD14+ monocytes after ex vivo stimulation. Neither the levels of monocyte subpopulations nor of HO-1 expression in CD14+ monocytes were significantly associated with the degree of CD4+ T cell recovery. Monocyte subpopulations and HO-1 gene expression were, however, restored to normal levels by suppressive ART. These results suggest that the level of circulating monocyte subpopulations and their expression of HO-1 have no evident relationship to CD4+ T cell recovery after the initiation of ART. PMID:25180041

  18. Increased serum levels of soluble l-selectin (CD62L) in patients with active systemic lupus erythematosus (SLE)

    PubMed Central

    Font, J; Pizcueta, P; Ramos-Casals, M; Cervera, R; García-Carrasco, M; Navarro, M; Ingelmo, M; Engel, P

    2000-01-01

    The adhesion molecule l-selectin (CD62L) mediates lymphocyte recirculation and leucocyte rolling on vascular endothelium at sites of inflammation. Serum levels of soluble l-selectin (sl-selectin) were measured in patients with SLE in order to relate these levels to clinical activity and immunological parameters. An ELISA was used to detect the soluble form of human l-selectin (CD62L) in 42 patients with SLE and in 33 healthy individuals. The mean ± s.e.m. values of sl-selectin were 1285 ± 121 ng/ml for patients with SLE and 986 ± 180 ng/ml for healthy blood donors, but there was no significant difference. When patients with active SLE were analysed, higher levels of circulating sl-selectin were found when compared with patients without activity (1497 ± 167 ng/ml versus 941 ± 150 ng/ml; P = 0.028). We found a significant correlation between the levels of sl-selectin and of dsDNA antibodies (r = 0.36, P = 0.044) and between levels of sl-selectin and SLE Disease Activity Index (SLEDAI) score (r = 0.42, P = 0.003). Patients with active SLE studied cross-sectionally showed significant elevations of sl-selectin (CD62L) compared with controls. Thus, the levels of this soluble adhesion molecule correlated with active disease and levels of anti-dsDNA antibodies. PMID:10606979

  19. Pollution of mycological surfaces in hospital emergency departments correlates positively with blood NKT CD3+ 16+ 56+ and negatively with CD4+ cell levels of their staff

    PubMed Central

    Suska, Milena; Kiepura, Anna; Winnicka, Izabela; Leszczyński, Paweł; Bielawska-Drózd, Agata; Cieślik, Piotr; Kubiak, Leszek; Depczyńska, Daria; Brewczyńska, Aleksandra; Skopińska-Różewska, Ewa; Kocik, Janusz

    2016-01-01

    The aim of the present study was the assessment of the putative influence of yeast and filamentous fungi in healthcare and control (office) workplaces (10 of each kind) on immune system competence measured by NK (natural killer), CD4+, and NKT (natural killer T lymphocyte) cell levels in the blood of the personnel employed at these workplaces. Imprints from floors and walls were collected in winter. The blood was taken in spring the following year, from 40 men, 26 to 53 years old, healthcare workers of hospital emergency departments (HED), who had been working for at least five years in their current positions, and from 36 corresponding controls, working in control offices. Evaluation of blood leukocyte subpopulations was done by flow cytometry. The qualitative analysis of the surface samples revealed a prevalence of strains belonging to Aspergillus spp. and Penicillium spp. genus. There was no statistically significant difference between the level of NKT; however, the percentage of NK cells was lower in the blood of HED workers than in the blood of offices personnel. Spearman analysis revealed the existence of positive correlation (r = 0.4677, p = 0.002) between the total CFU/25 cm2 obtained by imprinting method from walls and floors of HED and the percentage of NKT (CD3+16+56+) lymphocytes collected from the blood of their personnel, and negative correlation (r = –0. 3688, p = 0.019) between this parameter of fungal pollution and the percentage of CD4+ lymphocytes in the blood of HED staff. No other correlations were found. PMID:27095925

  20. Pollution of mycological surfaces in hospital emergency departments correlates positively with blood NKT CD3(+) 16(+) 56(+) and negatively with CD4(+) cell levels of their staff.

    PubMed

    Suska, Milena; Lewicki, Sławomir; Kiepura, Anna; Winnicka, Izabela; Leszczyński, Paweł; Bielawska-Drózd, Agata; Cieślik, Piotr; Kubiak, Leszek; Depczyńska, Daria; Brewczyńska, Aleksandra; Skopińska-Różewska, Ewa; Kocik, Janusz

    2016-01-01

    The aim of the present study was the assessment of the putative influence of yeast and filamentous fungi in healthcare and control (office) workplaces (10 of each kind) on immune system competence measured by NK (natural killer), CD4(+), and NKT (natural killer T lymphocyte) cell levels in the blood of the personnel employed at these workplaces. Imprints from floors and walls were collected in winter. The blood was taken in spring the following year, from 40 men, 26 to 53 years old, healthcare workers of hospital emergency departments (HED), who had been working for at least five years in their current positions, and from 36 corresponding controls, working in control offices. Evaluation of blood leukocyte subpopulations was done by flow cytometry. The qualitative analysis of the surface samples revealed a prevalence of strains belonging to Aspergillus spp. and Penicillium spp. genus. There was no statistically significant difference between the level of NKT; however, the percentage of NK cells was lower in the blood of HED workers than in the blood of offices personnel. Spearman analysis revealed the existence of positive correlation (r = 0.4677, p = 0.002) between the total CFU/25 cm(2) obtained by imprinting method from walls and floors of HED and the percentage of NKT (CD3(+)16(+)56(+)) lymphocytes collected from the blood of their personnel, and negative correlation (r = -0. 3688, p = 0.019) between this parameter of fungal pollution and the percentage of CD4(+) lymphocytes in the blood of HED staff. No other correlations were found. PMID:27095925

  1. CD1A-positive cells and HSP60 (HSPD1) levels in keratoacanthoma and squamous cell carcinoma.

    PubMed

    Cabibi, Daniela; Conway de Macario, Everly; Ingrao, Sabrina; Porcasi, Rossana; Zucco, Francesco; Macario, Alberto J L; Cappello, Francesco; Rappa, Francesca

    2016-01-01

    CD1a is involved in presentation to the immune system of lipid antigen derived from tumor cells with subsequent T cell activation. Hsp60 is a molecular chaperone implicated in carcinogenesis by, for instance, modulating the immune reaction against the tumor. We have previously postulated a synergism between CD1a and Hsp60 as a key factor in the activation of an effective antitumor immune response in squamous epithelia. Keratoacantomas (KAs) are benign tumors that however can transform into squamous cell carcinomas (SCCs), but the reasons for this malignization are unknown. In a previous study, we found that CD1a-positive cells are significantly more numerous in KA than in SCC. In this study, we analyzed a series of KAs and SCCs by immunohistochemistry for CD1a and Hsp60. Our results show that the levels of both are significantly lower in KA than in SCC and support the hypothesis that KA may evolve towards SCC if there is a failure of the local modulation of the antitumor immune response. The data also show that immunohistochemistry for CD1a and Hsp60 can be of help in differential diagnosis between KAs and well-differentiated forms of SCC. PMID:26442925

  2. Resonant quantum kicked rotor with two internal levels

    NASA Astrophysics Data System (ADS)

    Hernández, Guzmán; Romanelli, Alejandro

    2013-04-01

    We study a system consisting of a quantum kicked rotor with an additional degree of freedom. We show analytically and numerically that this model is characterized by its quantum resonances with ballistic spreading and by the entanglement between the internal and momentum degrees of freedom. We conclude that the model shows certain interesting similarities with the standard quantum walk on the line.

  3. Effectiveness of UK and International A-Level Assessment in Predicting Performance in Engineering

    ERIC Educational Resources Information Center

    Birch, David M.; Rienties, Bart

    2014-01-01

    In many universities, admissions decisions are made based upon the advanced-level (A-Level) results. The purpose of this study was to assess the value of A-level and international equivalents as a predictor of early achievement in higher education. About 135 UK and 92 international undergraduate engineering students from 35 countries were assessed…

  4. Circulating CD36 and oxLDL levels are associated with cardiovascular risk factors in young subjects

    PubMed Central

    2014-01-01

    Background Cardiovascular disease (CVD) results from a combination of abnormalities in lipoprotein metabolism, oxidative stress, chronic inflammation, and susceptibility to thrombosis. Atherosclerosis is the major cause of CVD. CD36 has been shown to play a critical role in the development of atherosclerotic lesions by its capacity to bind and promote endocytosis of oxidized low-density lipoprotein (oxLDL) and is implicated in the formation of foam cells. The purpose of this research was to evaluate whether there is an association of sCD36 and oxLDL levels with cardiovascular risk factors in young subjects. Methods A total of 188 subjects, 18 to 25 years old, 133 normal-weight and 55 obese subjects from the state of Guerrero, Mexico were recruited in the study. The lipid profile and glucose levels were measured by enzymatic colorimetric assays. Enzyme-linked immunosorbant assays (ELISA) for oxLDL and sCD36 were performed. Statistical analyses of data were performed with Wilcoxon- Mann Whitney and chi-square tests as well as with multinomial regression. Results TC, LDL-C, TG, oxLDL and sCD36 levels were higher in obese subjects than in normal-weight controls, as well as, monocyte and platelet counts (P < 0.05). Obese subjects had 5.8 times higher risk of sCD36 in the third tertil (>97.8 ng/mL) than normal-weight controls (P = 0.014), and 7.4 times higher risk of oxLDL levels in third tertile (>48 U/L) than control group. The subjects with hypercholesterolemia, hypertriglyceridemia, fasting impaired LDL-C had a higher risk of oxLDL levels in the third tertile (>48 U/L) than the control group (P < 0.05). Conclusions Circulating CD36 and oxLDL levels are associated with cardiovascular risk factors in young subjects and may be potential early markers for cardiovascular disease (CVD). PMID:24766787

  5. Effect of Te Inclusions on Internal Electric Field of CdMnTe Gamma-Ray Detectors

    SciTech Connect

    Babalola, O.S.; Bolotnikov, A.; Egarievwe, S.; Hossain, A.; Burger, A.; James, R.

    2009-08-02

    We studied two separate as-grown CdMnTe crystals by Infrared (IR) microscopy and Pockels effect imaging, and then developed an algorithm to analyze and visualize the electric field within the crystals’ bulk. In one of the two crystals the size and distribution of inclusions within the bulk promised to be more favorable in terms of efficiency as a detector crystal. However, the Te inclusions were arranged in characteristic ‘planes’. Pockels imaging revealed an accumulation of charges in the region of these planes. We demonstrated that the planes induced stress within the bulk of the crystal that accumulated charges, thereby causing non-uniformity of the internal electric field and degrading the detector’s performance.

  6. Effect of Te inclusions on internal electric field of CdMnTe gamma-ray detector

    NASA Astrophysics Data System (ADS)

    Babalola, Oluseyi Stephen; Bolotnikov, Aleksey E.; Egarievwe, Stephen U.; Hossain, Anwar M.; Burger, Arnold; James, Ralph B.

    2009-08-01

    We studied two separate as-grown CdMnTe crystals by Infrared (IR) microscopy and Pockels effect imaging, and then developed an algorithm to analyze and visualize the electric field within the crystals' bulk. In one of the two crystals the size and distribution of inclusions within the bulk promised to be more favorable in terms of efficiency as a detector crystal. However, the Te inclusions were arranged in characteristic 'planes'. Pockels imaging revealed an accumulation of charges in the region of these planes. We demonstrated that the planes induced stress within the bulk of the crystal that accumulated charges, thereby causing non-uniformity of the internal electric field and degrading the detector's performance.

  7. [CD226 monoclonal antibody induces variation of intracytosolic free calcium level in human umbilical vein endothelial cells].

    PubMed

    Chen, Li-Hua; Liu, Xue-Song; Liu, Fei; Jin, Bo-Quan

    2003-06-25

    In order to study the possible mechanism of CD226 monoclonal antibody (mAb)-mediated intracellular message transduction in human umbilical vein endothelial cells (HUVECs), the influence of CD226 mAb and its cross-linking by secondary antibody (II Ab) on the concentration changes in [Ca(2+)](i) in the HUVECs under different conditions were determined by confocal laser scanning microscopy. The main results are as follows. (1) When the culture medium was balanced by Hanks Buffer, [Ca(2+)](i) in HUVECs increased slowly after stimulation by CD226 mAb, whereas [Ca(2+)](i) increase was accompanied by [Ca(2+)](o) decrease after the mAb was cross-linked by goat anti-mouse IgG. Then [Ca(2+)](i) and [Ca(2+)](o) all returned to the normal level. (2) When the culture medium was balanced by D-Hanks buffer, [Ca(2+)](i) in HUVECs showed little variation when the cells were stimulated by CD226 mAb, but [Ca(2+)](i) decreased markedly after cross-linking. (3) When HUVECs were pretreated with EGTA, there was no variation in [Ca(2+)](i) of HUVECs after CD226 mAb stimulation alone or cross-linking of the mAb. Our results suggest that stimulation by CD226 mAb and cross-linking by goat anti-mouse IgG induce the variation of [Ca(2+)](i) in HUVECs under different conditions and the variation of [Ca(2+)](i) in HUVECs may play an important role in many physiological and pathological processes. PMID:12817306

  8. CD163 and c-Met expression in the lymph node and the correlations between elevated levels of serum free light chain and the different clinicopathological parameters of advanced classical Hodgkin's lymphoma

    PubMed Central

    Bedewy, Magdy; El-Maghraby, Shereen

    2013-01-01

    Background Advances in the understanding of Hodgkin's lymphoma (HL) show various functions of infiltrating immune cells and cytokines in relation to clinical outcomes. The expression of CD163 and c-Met has been suggested to have a role in lymphoid malignancy. Thus, we evaluated the expressions of CD163, c-Met, and serum free light chain (sFLC) in relation to the clinicopathological features of patients with advanced classical HL (cHL). Methods We assessed the expression of CD163 and c-Met in 34 patients with cHL through immunohistochemistry on the lymph node biopsy sections and the levels of pretreatment sFLC were estimated using ELISA. Results High CD163 expression correlated with increased age, B symptoms, International Prognostic Score (IPS) ≥3, mixed cellularity subtype, and low response to treatment. Further, high c-Met expression correlated with increased age at diagnosis, leukocytosis, B symptoms, and lower chance to achieve complete remission. The sFLC levels correlated with increased age at diagnosis, lymphopenia, IPS ≥3, B symptoms, and lower complete remission rates. Conclusion In advanced cHL, increased expression of CD163 and c-Met showed a significant association with adverse prognostic parameters and poor response to treatment. Pretreatment high sFLC level also correlated with poor risk factors, suggesting its use as a candidate prognostic marker. A comprehensive approach for prognostic markers might represent a step towards developing a tailored therapeutic approach for HL. PMID:23826581

  9. CD68+ cell count, early evaluation with PET and plasma TARC levels predict response in Hodgkin lymphoma.

    PubMed

    Cuccaro, Annarosa; Annunziata, Salvatore; Cupelli, Elisa; Martini, Maurizio; Calcagni, Maria L; Rufini, Vittoria; Giachelia, Manuela; Bartolomei, Francesca; Galli, Eugenio; D'Alò, Francesco; Voso, Maria T; Leone, Giuseppe; Giordano, Alessandro; Larocca, Luigi M; Hohaus, Stefan

    2016-03-01

    Early response evaluation with [(18) F]fluordeoxyglucose (FDG) positron emission tomography after 2 cycles of chemotherapy (interim PET) has been indicated as the strongest predictor for outcome in classical Hodgkin lymphoma (HL). We studied the prognostic role of the number of tumor-infiltrating CD68+ cells and of the plasma levels of TARC (thymus and activation-regulated chemokine) in the context of interim PET in 102 patients with classical HL treated with Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD). After 2 ABVD cycles, interim PET according to Deauville criteria was negative (score 0-3) in 85 patients and positive (score 4-5) in 15 patients (2 patients technically not evaluable). TARC levels were elevated in 89% of patients at diagnosis, and decreased after 2 cycles in 82% of patients. Persistently elevated TARC levels in 18% of patients were significantly associated with a positive PET result (P = 0.007). Strong predictors for progression-free survival (PFS) were a negative interim PET (85% vs. 28%, P < 0.0001) and CD68+ cell counts <5% (89% vs. 67%, P = 0.006), while TARC levels at diagnosis and at interim evaluation had no prognostic role. In multivariate analysis, interim PET, CD68+ cell counts and presence of B-symptoms were independently associated with PFS. We conclude that although TARC levels are a biomarker for early response evaluation, they cannot substitute for interim PET as outcome predictor in HL. The evaluation of CD68 counts and B-symptoms at diagnosis may help to identify low-risk patients regardless positive interim PET. PMID:26758564

  10. Extracellular Processing of the Cartilage Proteoglycan Aggregate and Its Effect on CD44-mediated Internalization of Hyaluronan*

    PubMed Central

    Danielson, Ben T.; Knudson, Cheryl B.; Knudson, Warren

    2015-01-01

    In many cells hyaluronan receptor CD44 mediates the endocytosis of hyaluronan and its delivery to endosomes/lysosomes. The regulation of this process remains largely unknown. In most extracellular matrices hyaluronan is not present as a free polysaccharide but often is found in complex with other small proteins and macromolecules such as proteoglycans. This is especially true in cartilage, where hyaluronan assembles into an aggregate structure with the large proteoglycan termed aggrecan. In this study when purified aggrecan was added to FITC-conjugated hyaluronan, no internalization of hyaluronan was detected. This suggested that the overall size of the aggregate prevented hyaluronan endocytosis and furthermore that proteolysis of the aggrecan was a required prerequisite for local, cell-based turnover of hyaluronan. To test this hypothesis, limited C-terminal digestion of aggrecan was performed to determine whether a size range of aggrecan exists that permits hyaluronan endocytosis. Our data demonstrate that only limited degradation of the aggrecan monomer was required to allow for hyaluronan internalization. When hyaluronan was combined with partially degraded, dansyl chloride-labeled aggrecan, blue fluorescent aggrecan was also visualized within intracellular vesicles. It was also determined that sonicated hyaluronan of smaller molecular size was internalized more readily than high molecular mass hyaluronan. However, the addition of intact aggrecan to hyaluronan chains sonicated for 5 and 10 s reblocked their endocytosis, whereas aggregates containing 15-s sonicated hyaluronan were internalized. These data suggest that hyaluronan endocytosis is regulated in large part by the extracellular proteolytic processing of hyaluronan-bound proteoglycan. PMID:25733665

  11. Serum level of soluble interleukin-2 receptor correlates with CD25 expression in patients with T lymphoblastic lymphoma.

    PubMed

    Toji, Tomohiro; Takata, Katsuyoshi; Sato, Yasuharu; Miyata-Takata, Tomoko; Hayashi, Eiko; Habara, Toshiyuki; Maeda, Yoshinobu; Tanimoto, Mitsune; Yoshino, Tadashi

    2015-08-01

    Acute lymphoblastic leukaemia/lymphoma (ALL/LBL) is an aggressive form of non-Hodgkin's lymphoma (NHL) affecting B-cells or T-cells, respectively. The serum level of soluble interleukin-2 receptor (sIL-2R) is known to reflect the immune activity and tumour volume in aggressive NHL; however, the release of sIL-2R in LBL has not been extensively studied. Further, the relationship between sIL-2R release and the expression level of IL-2R α subunit (CD25) remains unknown. In the present study, we examined the serum level of sIL-2R in 23 patients with T lymphoblactic lymphoma (T-LBL) and compared these with the levels in 20 patient with T acute lymphoblastic leukaemia (T-ALL), 40 patients with diffuse large B-cell lymphoma (DLBCL) and 40 patients with peripheral T-cell lymphoma (PTCL), not otherwise specified. The release of sIL-2R into the serum in patients with T-LBL was significantly lower than that for T-ALL, DLBCL and PTCL (p<0.001). Immunohistochemistry revealed that CD25 expression was correlated with the serum level of sIL-2R in T-LBL (p=0.0069), whereas no correlation was found to exist between serum sIL-2R levels and CD25 expression in patients with DLBCL (p=0.348) and PTCL (p=0.266). Furthermore, double immunohistochemical analysis revealed that CD25-positive cells were also found to be Foxp3-positive non-neoplastic T-cells. In conclusion, CD25-positive non-neoplastic T-cells in T-LBL are presumed to be the primary source of sIL-2R, and the low number of cells present results in a lower level of sIL-2R released into the serum compared with the other aggressive and highly aggressive lymphomas. PMID:25935549

  12. The Severity of Visceral Leishmaniasis Correlates with Elevated Levels of Serum IL-6, IL-27 and sCD14

    PubMed Central

    dos Santos, Priscila L.; de Oliveira, Fabrícia A.; Santos, Micheli Luize B.; Cunha, Luana Celina S.; Lino, Michelle T. B.; de Oliveira, Michelle F. S.; Bomfim, Manuela O. M.; Silva, Angela Maria; de Moura, Tatiana R.; de Jesus, Amélia R.; Duthie, Malcolm S.; Reed, Steven G.; de Almeida, Roque P.

    2016-01-01

    Background Visceral leishmaniasis (VL) is a severe disease caused by infection with protozoa of the genus Leishmania. Classic VL is characterized by a systemic infection of phagocytic cells and an intense activation of the inflammatory response. It is unclear why 90% of infected individuals do not develop the disease while a minority develop the classical form. Furthermore, among those that develop disease, a small group progresses to more severe form that is unresponsive to treatment. The presence of inflammatory mediators in serum could theoretically help to control the infection. However, there is also a release of anti-inflammatory mediators that could interfere with the control of parasite multiplication. In this study, we took advantage of the spectrum of outcomes to test the hypothesis that the immune profile of individuals infected with Leishmania (L.) infantum is associated with the development and severity of disease. Methodology/Principal Findings Sera from patients with confirmed diagnosis of VL were evaluated for the presence of numerous molecules, and levels compared with healthy control and asymptomatic infected individuals. Conclusions/Principal Findings Although differences were not observed in LPS levels, higher levels of sCD14 were detected in VL patients. Our data suggest that L. infantum may activate the inflammatory response via CD14, stimulating a generalized inflammatory response with production of several cytokines and soluble molecules, including IFN-γ, IL-27, IL-10, IL-6 and sCD14. These molecules were strongly associated with hepatosplenomegaly, neutropenia and thrombocytopenia. We also observed that IL-6 levels greater than 200 pg/ml were strongly associated with death. Together our data reinforce the close relationship of IFN-γ, IL-10, IL-6, TNF-α and IL-27 in the immune dynamics of VL and suggest the direct participation of sCD14 in the activation of the immune response against L. infantum. PMID:26814478

  13. Microporous Cd(II) metal-organic framework as fluorescent sensor for nitroaromatic explosives at the sub-ppm level

    NASA Astrophysics Data System (ADS)

    Wang, Xing-Po; Han, Lu-Lu; Wang, Zhi; Guo, Ling-Yu; Sun, Di

    2016-03-01

    A novel Cd(II) metal-organic framework (MOF) based on a rigid biphenyltetracarboxylic acid, [Cd4(bptc)2(DMA)4(H2O)2·4DMA] (1) was successfully synthesized under the solvothermal condition and characterized by single-crystal X-ray diffraction and further consolidated by elemental analyses, powder X-ray diffraction (PXRD), infrared spectra (IR) and luminescent measurements. Single crystal X-ray diffraction analysis reveals that compound 1 is 4-connected PtS (Point symbol: {42·84}) network based on [Cd2(COO)4] secondary building units (SBUs). Its inherent porous and emissive characteristics make them to be a suitable fluorescent probe to sense small solvents and nitroaromatic explosives. Compound 1 shows obviously solvent-dependent emissive behaviors, especially for acetone with very high fluorescence quenching effect. Moreover, compound 1 displays excellent sensing of nitroaromatic explosives at sub-ppm level, giving a detection limit of 0.43 ppm and 0.37 ppm for nitrobenzene (NB) and p-nitrotoluene (PNT), respectively. This shows this Cd(II) MOF can be used as fluorescence probe for the detection of nitroaromatic explosives.

  14. Study on abnormal intra-field CD uniformity induced by Efese-tilt application upon complex leveling scheme

    NASA Astrophysics Data System (ADS)

    Deng, Guogui; Hao, Jingan; Cai, Boxiu; Xing, Bin; Yao, Xin; Zhang, Qiang; Li, Tianhui; Lin, Yi-Shih; Wu, Qiang; Shi, Xuelong

    2014-03-01

    Critical dimension uniformity (CDU) of hole layer is becoming more and more crucial and tightened alongside with the technology node being driven into 28 nm and beyond, since the critical dimension (CD) variation of 2-dimensional (2D) hole pattern is intrinsically harder to control than that of 1D pattern (line/space). As the process window becomes more marginal with the more advanced technology node, although at the cost of contrast loss, EFESE tilt (focus drilling method) is one handy trick for its DOF enhancement capability (1-3). We observed an abnormal up to 6 nm ADI CD trend-down in Y-direction (exposure scan direction) in the strictly repeated via-hole patterns within an about 8 mm x 6 mm chip in condition 1 wafer with pre-layer patterns (short as C1 wafer) where EFESE tilt is applied. No CD trend-down or trend up in X-direction. This C1 hole layer uses EFESE tilt to improve DOF. This CD trend-down phenomenon is thoroughly investigated and a model of "effective EFESE tilt" is proposed and verified. Based on the model, we made a further step into the assessment of another focus drilling method, i.e. EFESE High Range (HR) and evaluate its performance under the same complex leveling scheme. Through all this analysis, we give an insight of the safety zone for applying EFESE tilt for future reference.

  15. The effects of a CD-ROM textbook on student achievement and cognition-level attainment of undergraduate biology students

    NASA Astrophysics Data System (ADS)

    Ludrick, Brad Burton

    Purpose of the study. This study was designed to measure the effects of CD-ROM textbook integration on student achievement and student cognition-level-attainment for undergraduate general biology students. Four sections of general biology were selected as the study group. Two sections served as the experimental group receiving CD-ROM textbook integration. The remaining two sections served as the control group, and were taught biological content utilizing a traditional textbook. Procedure. This study employed a pre-experimental research design, static group comparison (Ary, Jacobs, & Razavieh, 1996: 331), to determine if a CD-ROM textbook had significant effects on student cognition-level-attainment and content achievement of undergraduate biology students. The study was conducted during the 2001 spring semester at Southeastern Oklahoma State University. The duration of the treatment was approximately sixteen weeks. Four sections of general biology (N = 101) were selected as the study group. Two of the four sections of general biology (n = 48) were randomly selected by the researcher via coin toss to serve as the experimental group, Group A, and were taught biological content utilizing a CD-ROM Textbook. The remaining two sections of general biology (n = 53) served as the control group, Group B, and were taught biological content utilizing a traditional textbook. Various statistical tests were used in analysis of the data. The ten null hypotheses were tested at the .05 level of significance. The Statistical Package for the Social Sciences program (SPSS), version 9.0 (SPSS, 1999), was used to process the data. Results. The results determined by this study were the overall effects of the CD-ROM textbook did not significantly differ from the effects of the traditional textbook on student content achievement and cognition-level-attainment. Conclusions. The utilization of CD-ROM textbook instruction is not superior at improving student achievement of biology content, as

  16. The sensitivity of chronic myeloid leukemia CD34 cells to Bcr-Abl tyrosine kinase inhibitors is modulated by ceramide levels.

    PubMed

    Wang, Jiaqiao; Hu, June; Jin, Zhiliang; Wan, Huihui

    2016-08-01

    Despite BCR-ABL tyrosine kinase inhibitors (TKIs) improved outcome of patients with chronic myeloid leukemia (CML), resistance still develops when progresses to blast phase (BP). The mechanisms underlying resistance to TKIs are not well understood. In this study, we analyzed ceramide levels in CD34 cells derived from BP-CML patients and healthy donor bone marrow (BM) using liquid chromatography mass spectrometry. We found that ceramide level was significantly lower in BP-CML CD34 compared with normal BM counterparts. BP-CML CD34 ceramide(low) were more resistant to BCR-ABL TKIs compared to BP-CML CD34 ceramide(normal). Both mRNA and proteins levels of sphingomyelin synthase 1 and 2 are lower in BP-CML CD34 ceramide(low) compared to normal BM CD34 cells, suggesting that these two ceramide synthesis enzymes maybe the mechanism of how ceramide level is suppressed. Importantly, up-regulation of cellular ceramide level induces apoptosis of multiple CML cell lines and BP-CML CD34 progenitors. Combination of BCR-ABL TKIs with ceramide analog is synergistic in targeting BP-CML 34 progenitors. Collectively, our work provides evidence that down-regulation of ceramide level is involved in the resistance of BP-CML CD34 progenitors to TKIs treatment. Targeting ceramide metabolism together with BCR-ABL inhibition makes it an attractive addition to the armamentarium in BP-CML treatment. PMID:27244255

  17. Factorial and Item-Level Invariance of an Emotional Intelligence Scale across Groups of International Students

    ERIC Educational Resources Information Center

    Wang, Chuang; Kim, Do-Hong; Ng, Kok-Mun

    2012-01-01

    This study examined the factorial and item-level invariance of Wong and Law's emotional intelligence scale (WLEIS) in a sample of 375 international students in U.S. universities. Confirmatory factor analysis (CFA) and differential item functioning (DIF) analysis were employed at the test and item level, respectively. International students from…

  18. Acculturation Level, Perceived English Fluency, Perceived Social Support Level, and Depression among Taiwanese International Students

    ERIC Educational Resources Information Center

    Dao, Tam K.; Lee, Donghyuck; Chang, Huang L.

    2007-01-01

    This study examined the relationship between acculturation, perceived English fluency, social support, and depression among 112 graduate Taiwanese international students. Ordinary Least Squares analyses were conducted on 112 graduate Taiwanese international students from a university in southeastern United States. Results indicated that those…

  19. Internal electric-field-lines distribution in CdZnTe detectors measured using X-ray mapping

    SciTech Connect

    Bolotnikov,A.E.; , .; Camarda, G.S.; Cui, Y.; Hossain, A.; Yang, G.; Yao, H.W.; James, R.B.

    2009-10-19

    The ideal operation of CdZnTe devices entails having a uniformly distributed internal electric field. Such uniformity especially is critical for thick long-drift-length detectors, such as large-volume CPG and 3-D multi-pixel devices. Using a high-spatial resolution X-ray mapping technique, we investigated the distribution of the electric field in real devices. Our measurements demonstrate that in thin detectors, <5 mm, the electric field-lines tend to bend away from the side surfaces (i.e., a focusing effect). In thick detectors, >1 cm, with a large aspect ratio (thickness-to-width ratio), we observed two effects: the electric field lines bending away from or towards the side surfaces, which we called, respectively, the focusing field-line distribution and the defocusing field-line distribution. In addition to these large-scale variations, the field-line distributions were locally perturbed by the presence of extended defects and residual strains existing inside the crystals. We present our data clearly demonstrating the non-uniformity of the internal electric field.

  20. Internal electric-field-lines distribution in CdZnTe detectors measured using X-ray mapping

    SciTech Connect

    Bolotnikov,A.E.; Camarda, G.S.; Cui, Y.; Hossain, A.; Yang, G.; Yao, H.W.; James, R.B.

    2008-06-01

    The ideal operation of CdZnTe devices entails having a uniformly distributed internal electric field. Such uniformity especially is critical for thick long-drift-length detectors, such as large-volume CPG and 3-D multi-pixel devices. Using a high-spatial resolution X-ray mapping technique, we investigated the distribution of the electric field in real devices. Our measurements demonstrate that in thin detectors, <5 mm, the electric field-lines tend to bend away from the side surfaces (i.e., a focusing effect). In thick detectors, 21 cm, with a large aspect ratio (thickness-to-width ratio), we observed two effects: the electric field lines bending away from or towards the side surfaces, which we called, respectively, the focusing field-line distribution and the defocusing field-line distribution. In addition to these large-scale variations, the field-line distributions were locally perturbed by the presence of extended defects and residual strains existing inside the crystals. We present our data clearly demonstrating the non-uniformity of the internal electric field.

  1. CD90 is upregulated in gastric cancer tissues and inhibits gastric cancer cell apoptosis by modulating the expression level of SPARC protein.

    PubMed

    Zhu, Guang Chao; Gao, Lu; He, Junyu; Long, Yuehua; Liao, Shan; Wang, Haiyun; Li, Xujuan; Yi, Wei; Pei, Zhen; Wu, Minghua; Xiang, Juanjuan; Peng, Shuping; Ma, Jian; Zhou, Ming; Zeng, Zhaoyang; Xiang, Bo; Xiong, Wei; Tang, Ke; Cao, Li; Li, Xiaoling; Li, Guiyuan; Zhou, Yanhong

    2015-11-01

    Cluster of differentiation 90 (CD90) (Thy-1) plays important roles in the oncogenesis in various types of malignancies. In the present study, we investigated the expression of CD90 in gastric cancer (GC) tissues by q-PCR, immunohistochemistry (IHC), and western blot technologies. The results showed that CD90 was overexpressed in gastric cancer tissues compared with the level in the adjacent non‑cancerous tissues. To explore the possible mechanism of CD90 in GC, we elucidated the effect of CD90 on the apoptosis of AGS gastric cancer cells, and found that a considerable decrease in apoptotic cells was observed for AGS cells with CD90 overexpression. Meanwhile, the rate of apoptotic cells was increased in the AGS cells with CD90 interference (siCD90) compared with that in the AGS cells. Cell apoptosis is closely related to a reduction in mitochondrial membrane potential (ΔΨm) and an increase in intracellular reactive oxygen species (ROS) and calcium ion (Ca2+) concentrations. Our results showed that overexpression of CD90 in the AGS gastric cancer cells led to an increase in ΔΨm and a decrease in intracellular ROS and Ca2+ concentrations. At the same time, siCD90 reduced ΔΨm and the increase in intracellular ROS and Ca2+ concentrations. Furthermore, we identified and confirmed that CD90 functions by modulating the expression level of secreted protein, acidic, cysteine‑rich (osteonectin) (SPARC) in vitro through LC‑MS/MS analyses and western blot technology. In summary, our results suggest that CD90 is upregulated in gastric cancer and inhibits gastric cancer cell apoptosis by modulating the expression level of SPARC protein. PMID:26329007

  2. Abalone visceral extract inhibit tumor growth and metastasis by modulating Cox-2 levels and CD8+ T cell activity

    PubMed Central

    2010-01-01

    Background Abalone has long been used as a valuable food source in East Asian countries. Although the nutritional importance of abalone has been reported through in vitro and in vivo studies, there is little evidence about the potential anti-tumor effects of abalone visceral extract. The aim of the present study is to examine anti-tumor efficacy of abalone visceral extract and to elucidate its working mechanism. Methods In the present study, we used breast cancer model using BALB/c mouse-derived 4T1 mammary carcinoma and investigated the effect of abalone visceral extract on tumor development. Inhibitory effect against tumor metastasis was assessed by histopathology of lungs. Cox-2 productions by primary and secondary tumor were measured by real-time RT-PCR and immunoblotting (IB). Proliferation assay based on [3H]-thymidine incorporation and measurement of cytokines and effector molecules by RT-PCR were used to confirm tumor suppression efficacy of abalone visceral extract by modulating cytolytic CD8+ T cells. The cytotoxicity of CD8+ T cell was compared by JAM test. Results Oral administration of abalone visceral extract reduced tumor growth (tumor volume and weight) and showed reduced metastasis as confirmed by decreased level of splenomegaly (spleen size and weight) and histological analysis of the lung metastasis (gross analysis and histological staining). Reduced expression of Cox-2 (mRNA and protein) from primary tumor and metastasized lung was also detected. In addition, treatment of abalone visceral extract increased anti-tumor activities of CD8+ T cells by increasing the proliferation capacity and their cytolytic activity. Conclusions Our results suggest that abalone visceral extract has anti-tumor effects by suppressing tumor growth and lung metastasis through decreasing Cox-2 expression level as well as promoting proliferation and cytolytic function of CD8+ T cells. PMID:20961430

  3. Evaluation of serum sTWEAK and sCD163 levels in patients with acute and chronic coronary artery disease

    PubMed Central

    Ilter, Abdulselam; Orem, Cihan; Balaban Yucesan, Fulya; Sahin, Mursel; Hosoglu, Yusuf; Kurumahmutoglu, Elif; Ozer Yaman, Serap; Orem, Asim

    2015-01-01

    Background: Recent studies have suggested soluble tumor necrotizing factor-like weak inducer of apoptosis (sTWEAK) and sCD163 may be a potential cardiovascular biomarker. We aimed to evaluate sTWEAK and sCD163 levels and predictive values in patients with chronic coronary artery disease (CAD) and acute coronary syndrome (ACS). Methods: Two hundred fourteen angiography-made patients were enrolled in the study and divided into 3 groups: 30 controls with normal angiograms, 99 patients with ACS, 85 patients with chronic CAD. sTWEAK, sCD163 and CRP levels were measured. Receivers operating characteristic (ROC) curve analysis were performed to determine the predictive values of sTWEAK and sCD163 levels and the sCD163/sTWEAK ratio. Gensini scores were used to assess severity of CAD. Results: sTWEAK levels in chronic CAD and ACS patients were lower compared to the control group (P<0.0001). sCD163 levels (P<0.0001) and the sCD163/sTWEAK ratio (P<0.0001) were higher in the ACS patients compared to the control and chronic CAD patients. ROC analysis revealed low sTWEAK level and high sCD163/sTWEAK ratio predicted chronic CAD, and low sTWEAK, high sCD163, CRP levels and sCD163/sTWEAK ratio predicted ACS. According to ROC analyses, significance of sTWEAK levels for chronic CAD was more marked compared to ACS (P<0.0001 vs P=0.001) and significance of sCD163/sTWEAK ratio was greater than sTWEAK for ACS (P<0.0001 vs P=0.001). These parameters didn’t correlate with severity of disease, obtained gensini scoring, in chronic CAD. Conclusions: It was concluded thatsTWEAK level may be a diagnostic marker of especially chronic CAD, sCD163 level of ACS, and the sCD163/sTWEAK ratio of both chronic CAD and ACS. PMID:26309601

  4. NOTCH1 mutations associate with low CD20 level in chronic lymphocytic leukemia: evidence for a NOTCH1 mutation-driven epigenetic dysregulation.

    PubMed

    Pozzo, F; Bittolo, T; Arruga, F; Bulian, P; Macor, P; Tissino, E; Gizdic, B; Rossi, F M; Bomben, R; Zucchetto, A; Benedetti, D; Degan, M; D'Arena, G; Chiarenza, A; Zaja, F; Pozzato, G; Rossi, D; Gaidano, G; Del Poeta, G; Deaglio, S; Gattei, V; Dal Bo, M

    2016-01-01

    In chronic lymphocytic leukemia (CLL), NOTCH1 mutations have been associated with clinical resistance to the anti-CD20 rituximab, although the mechanisms behind this peculiar behavior remain to be clarified. In a wide CLL series (n=692), we demonstrated that CLL cells from NOTCH1-mutated cases (87/692) were characterized by lower CD20 expression and lower relative lysis induced by anti-CD20 exposure in vitro. Consistently, CD20 expression by CLL cells was upregulated in vitro by γ-secretase inhibitors or NOTCH1-specific small interfering RNA and the stable transfection of a mutated (c.7541-7542delCT) NOTCH1 intracellular domain (NICD-mut) into CLL-like cells resulted in a strong downregulation of both CD20 protein and transcript. By using these NICD-mut transfectants, we investigated protein interactions of RBPJ, a transcription factor acting either as activator or repressor of NOTCH1 pathway when respectively bound to NICD or histone deacetylases (HDACs). Compared with controls, NICD-mut transfectants had RBPJ preferentially complexed to NICD and showed higher levels of HDACs interacting with the promoter of the CD20 gene. Finally, treatment with the HDAC inhibitor valproic acid upregulated CD20 in both NICD-mut transfectants and primary CLL cells. In conclusion, NOTCH1 mutations are associated with low CD20 levels in CLL and are responsible for a dysregulation of HDAC-mediated epigenetic repression of CD20 expression. PMID:26165233

  5. Decreased Circulating Interleukin-35 Levels Are Related to Interleukin-4-Producing CD8+ T Cells in Patients with Allergic Asthma.

    PubMed

    Wang, Wei; Li, Ping; Yang, Jiong

    2015-08-01

    Interleukin (IL)-35 is a newly discovered suppressive cytokine and has been shown to alleviate inflammatory and autoimmune diseases. The purpose of this study was to investigate immunomodulatory capacity of IL-35 in patients with allergic asthma. IL-35 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) were detected by quantitative real-time PCR (qPCR). The frequencies of cytotoxic T cells (Tc)1, Tc2 and Tc17 cells were measured by flow cytometry. Plasma levels of IL-35, interferon (IFN)-γ, IL-4, and IL-17 were examined by enzyme-linked immunosorbent assay (ELISA). The correlations between plasma IL-35 levels and Tc1, Tc2, and Tc17 cytokine production in allergic asthmatics (n = 25) and healthy controls (n = 12) were analyzed by Pearson's test. IL-35 protein and mRNA expression levels were down-regulated in allergic asthmatics compared with healthy controls. The frequencies of Tc2 and Tc17 cells were significantly increased in patients with asthma, and the frequency of Tc1 cells did not differ between asthmatic patients and healthy controls. Similarly, plasma levels of IL-4 and IL-17 were significantly increased in asthmatic patients, while there was no difference in IFN-γ levels between allergic asthma patients and healthy controls. More importantly, plasma IL-35 protein levels were negatively correlated with the frequency of IL-4-producing CD8+ T (Tc2) cells and with the IL-4 level in patients with allergic asthma. Our results suggest that decreased circulating IL-35 levels could contribute to the pathogenesis of allergic asthma by regulating CD8+ T cells. PMID:26547705

  6. Changes in PINCH and hpTau levels in the CSF of HIV patients correlate with CD4 count

    PubMed Central

    Adiga, Radhika; Ozdemir, Ahmet Y.; Carides, Alexandra; Wasilewski, Melissa; Yen, William; Chitturi, Pallavi; Ellis, Ronald; Langford, Dianne

    2014-01-01

    Several studies report associations between the PINCH (particularly interesting new cysteine histidine-rich) protein and HIV-associated CNS disease. PINCH is detected in the CSF of HIV patients and changes in levels during disease may be indicative of changes in disease status over time. PINCH binds hyperphosphorylated Tau (hpTau) in the brain and CSF, but little is known about the relevance of these interactions to HIV CNS disease. In this study, PINCH and hpTau levels were assessed in three separate CSF samples collected longitudinally from 20 HIV+ participants before and after initiating antiretroviral therapy, or before and after a change in the current regimen. The intervals were approximately 1 (T2), and 3-7 (T3) months from the initial visit (baseline, T1). Correlational analyses were conducted for CSF levels of PINCH and hpTau and other variables including blood CD4+ T-cell count, plasma and CSF viral burden, CSF neopterin, white blood cell (WBC) count, and antiretroviral CNS penetration-effectiveness (CPE). Values for PINCH and hpTau were determined for each patient by calculating the fold changes between the second (T2) and third measurements (T3) from the baseline measurement (T1). Statistical analyses showed that the fold-change in CSF PINCH protein from T1 to T2 were significantly higher in participants with CD4 counts >200 cells/mm3 at T2 compared to those with CD4 counts <200 cells/mm3 at T2. This trend persisted irrespective of plasma or CSF viral burden or anti-retroviral therapy CPE scores. The fold-changes in PINCH levels between T1 and T2, and T1 and T3 were highly correlated to the fold changes in hpTau at T2/T1 and T3/T1 (correlation co-efficient = 0.69, p-value < 0.001, correlation co-efficient = 0.83, p-value <0.0001, respectively). In conclusion, in these HIV participants, changes in CSF levels of PINCH appear to correlate with changes in blood CD4 count and with changes in CSF hpTau levels, but not with plasma or CSF viral burden

  7. Screening of Cd-safe genotypes of Chinese cabbage in field condition and Cd accumulation in relation to organic acids in two typical genotypes under long-term Cd stress.

    PubMed

    Wang, Xu; Shi, Yi; Chen, Xin; Huang, Bin

    2015-11-01

    A 65-day field experiment was conducted to select cadmium (Cd)-safe genotypes (CSGs) among 21 Chinese cabbage genotypes in a low Cd-contaminated soil (0.66 mg kg(-1)). Seven CSGs were identified based on their Cd tolerance, shoot Cd concentrations, Cd enrichment factors (EFs), and translocation factors (TFs). Then, Beijingxin3, a typical CSG, together with Qiuxiang, a typical non-CSG for comparison, was selected for a subsequent 80-day field micro-plot experiment under four levels of Cd stress to evaluate the reliability of CSG screening and the role of organic acids in Cd accumulation and tolerance. Beijingxin3 was confirmed to be safe to grow in soil with Cd level up to 3.39 mg kg(-1), with Cd accumulation in its shoots well below the permitted level, and Qiuxiang was still poor in tolerating low Cd stress (1.31 mg kg(-1)). With increasing the Cd stress, Cd accumulation and citrate concentrations increased in shoots and roots of both genotypes, and oxalate concentrations increased significantly in Beijingxin3 roots. Both oxalate and citrate concentrations were significantly positively related to Cd accumulation for Beijingxin3 roots. High accumulation in oxalate and citrate induced by Cd stress in Beijingxin3 roots could benefit its internal tolerance to long-term Cd stress with more Cd accumulation in its roots and less Cd accumulation in its shoots. PMID:26081776

  8. Plasma Levels of Neopterin and C-Reactive Protein (CRP) in Tuberculosis (TB) with and without HIV Coinfection in Relation to CD4 Cell Count

    PubMed Central

    Skogmar, Sten; Schön, Thomas; Balcha, Taye Tolera; Sturegård, Erik; Jansson, Marianne; Björkman, Per

    2015-01-01

    Background While the risk of TB is elevated in HIV-positive subjects with low CD4 cell counts, TB may in itself be associated with CD4 lymphocytopenia. We investigated markers of immune activation (neopterin) and inflammation (CRP) in TB patients with and without HIV coinfection and their association with CD4 cell levels, and determined their predictive capacity as alternative markers of advanced immunosuppression. Methods Participants selected from a cohort of adults with TB at Ethiopian health centers (195 HIV+/TB+, 170 HIV-/TB+) and 31 controls were tested for plasma levels of neopterin and CRP. Baseline levels of neopterin and CRP were correlated to CD4 cell count before and after anti-TB treatment (ATT). The performance to predict CD4 cell strata for both markers were investigated using receiver operating curves. Results Levels of both biomarkers were elevated in TB patients (neopterin: HIV+/TB+ 54 nmol/l, HIV-/TB+ 23 nmol/l, controls 3.8 nmol/l; CRP: HIV+/TB+ 36 μg/ml, HIV-/TB+ 33 μg/ml, controls 0.5 μg/ml). Neopterin levels were inversely correlated (-0.53, p<0.001) to CD4 cell count, whereas this correlation was weaker for CRP (-0.25, p<0.001). Neither of the markers had adequate predictive value for identification of subjects with CD4 cell count <100 cells/mm3 (area under the curve [AUC] 0.64 for neopterin, AUC 0.59 for CRP). Conclusion Neopterin levels were high in adults with TB, both with and without HIV coinfection, with inverse correlation to CD4 cell count. This suggests that immune activation may be involved in TB-related CD4 lymphocytopenia. However, neither neopterin nor CRP showed promise as alternative tests for immunosuppression in patients coinfected with HIV and TB. PMID:26630153

  9. β decay of semi-magic 130Cd: Revision and extension of the level scheme of 130In

    NASA Astrophysics Data System (ADS)

    Jungclaus, A.; Grawe, H.; Nishimura, S.; Doornenbal, P.; Lorusso, G.; Simpson, G. S.; Söderström, P.-A.; Sumikama, T.; Taprogge, J.; Xu, Z. Y.; Baba, H.; Browne, F.; Fukuda, N.; Gernhäuser, R.; Gey, G.; Inabe, N.; Isobe, T.; Jung, H. S.; Kameda, D.; Kim, G. D.; Kim, Y.-K.; Kojouharov, I.; Kubo, T.; Kurz, N.; Kwon, Y. K.; Li, Z.; Sakurai, H.; Schaffner, H.; Shimizu, Y.; Steiger, K.; Suzuki, H.; Takeda, H.; Vajta, Zs.; Watanabe, H.; Wu, J.; Yagi, A.; Yoshinaga, K.; Benzoni, G.; Bönig, S.; Chae, K. Y.; Coraggio, L.; Daugas, J.-M.; Drouet, F.; Gadea, A.; Gargano, A.; Ilieva, S.; Itaco, N.; Kondev, F. G.; Kröll, T.; Lane, G. J.; Montaner-Pizá, A.; Moschner, K.; Mücher, D.; Naqvi, F.; Niikura, M.; Nishibata, H.; Odahara, A.; Orlandi, R.; Patel, Z.; Podolyák, Zs.; Wendt, A.

    2016-08-01

    The β decay of the semi-magic nucleus 130Cd has been studied at the RIBF facility at the RIKEN Nishina Center. The high statistics of the present experiment allowed for a revision of the established level scheme of 130In and the observation of additional β feeding to high-lying core-excited states in 130In. The experimental results are compared to shell-model calculations employing a model space consisting of the full major N =50 - 82 neutron and Z =28 - 50 proton shells and the NA-14 interaction, and good agreement is found.

  10. Serine/threonine-protein phosphatase 1 α levels are paralleling olfactory memory formation in the CD1 mouse.

    PubMed

    Winding, Christiana; Sun, Yanwei; Höger, Harald; Bubna-Littitz, Hermann; Pollak, Arnold; Schmidt, Peter; Lubec, Gert

    2011-06-01

    Although olfactory discrimination has already been studied in several mouse strains, data on protein levels linked to olfactory memory are limited. Wild mouse strains Mus musculus musculus, Mus musculus domesticus and CD1 laboratory outbred mice were tested in a conditioned odor preference task and trained to discriminate between two odors, Rose and Lemon, by pairing one odor with a sugar reward. Six hours following the final test, mice were sacrificed and olfactory bulbs (OB) were taken for gel-based proteomics analyses and immunoblotting. OB proteins were extracted, separated by 2-DE and quantified using specific software (Proteomweaver). Odor-trained mice showed a preference for the previously rewarded odor suggesting that conditioned odor preference occurred. In CD1 mice levels, one out of 482 protein spots was significantly increased in odor-trained mice as compared with the control group; it was in-gel digested by trypsin and chymotrypsin and analyzed by tandem mass spectrometry (nano-ESI-LC-MS/MS). The spot was unambiguously identified as serine/threonine-protein phosphatase PP1-α catalytic subunit (PP-1A) and differential levels observed in gel-based proteomic studies were verified by immunoblotting. PP-1A is a key signalling element in synaptic plasticity and memory processes and is herein shown to be paralleling olfactory discrimination representing olfactory memory. PMID:21647921

  11. Increased serum levels of soluble CD44-isoform v5 in rheumatic diseases are restricted to seropositive rheumatoid arthritis.

    PubMed

    Haberhauer, G; Kittl, E M; Skoumal, M; Hübl, W; Wagner, E; Bayer, P M; Bauer, K; Dunky, A

    1997-01-01

    Serum levels of sCD44v5 were measured in 134 patients with definite inflammatory rheumatic diseases (IRD) using a sandwich type ELISA. 94 patients suffered from erosive IgM-rheumatoid factor positive rheumatoid arthritis (RA+), 20 with undifferentiated seronegative polyarthritis, 12 with osteoarthropathia psoriatica and psoriasis vulgaris, 3 with systemic lupus erythematosus, 3 with scleroderma and 2 with reactive arthritis. Elevated serum levels (> 58 ng/ml to 221 ng/ml; median: 93 ng/ml) were only detected in 54/94 (57%) patients with RA+, but not in other IRD. They correlated with advanced stages of disease (Steinbrocker stages III + IV; p < 0.05), elevated CRP-levels (p < 0.01) and higher measurements of IgM rheumatoid factor. PMID:9150806

  12. Toxic metal (Pb, Cd, As and Hg) and organochlorine residue levels in hake (Merluccius merluccius) from the Marmara Sea, Turkey.

    PubMed

    Aksu, Abdullah; Balkis, Nuray; Taşkin, Omer S; Erşan, Mahmut S

    2011-11-01

    Toxic metals (Pb, Cd, As and Hg) and organochlorine residue levels were measured in hake (Merluccius merluccius) from the Marmara Sea. Biota samples were collected by a trawling cruise of the R/V ARAR in August and December 2009. The concentrations of toxic metals varied between Pb, 3.23-14.4; Cd, <0.01-2.14; Hg, 0.01-0.18 and As, 0.01-0.21 [Formula: see text]g g(-1) dry wt. Pb levels in the Marmara Sea were found to be higher than the critical limits set by the both Turkish Ministry of Environment for Aquatic Products (1 μg g(-1) wet wt.) and European countries (2.0 μg g(-1), UNEP 1985). In contrast, As and Hg levels were found to be lower than the critical limits for two periods. Cd contents of fish from the Marmara Sea were also comparable to or slightly lower than contents of fish from the Southern Black Sea Shelf. The results of organochlorine residues ranged between total HCH, <0.05 and 99 ng g(-1); endrin, <0.001 and 381 ng g(-1); alpha-endosulphan, <0.05 and 90 ng g(-1); beta-endosulphan, <0.05 and 15.3 ng g(-1); o,p DDE, 3.5 and 52.4 ng g(-1); p,p DDE, 7.4 and 139 ng g(-1); o,p DDD, 1.5 and 90.2 ng g(-1) and p,p DDD, 2.7 and 86 ng g(-1) wet weight. The rivers for the distribution of organochlorine levels in the Marmara Sea ordered from highest to lowest as Dil R. > Susurluk R. > Biga R. > Gönen R. The high levels of o,p and p,p DDE, and o,p and p,p DDD compounds, which are metabolites of DDT, indicate its illegal use. Toxic metal and organochlorine residue levels of fish are significantly higher than levels from the Mediterranean Sea. PMID:21336486

  13. Immunohistochemistry as a valuable tool to assess CD30 expression in peripheral T-cell lymphomas: high correlation with mRNA levels.

    PubMed

    Bossard, Céline; Dobay, Maria Pamela; Parrens, Marie; Lamant, Laurence; Missiaglia, Edoardo; Haioun, Corinne; Martin, Antoine; Fabiani, Bettina; Delarue, Richard; Tournilhac, Olivier; Delorenzi, Mauro; Gaulard, Philippe; de Leval, Laurence

    2014-11-01

    The extended use of brentuximab-vedotin was reported for CD30(+) nonanaplastic peripheral T-cell lymphomas (PTCLs) with promising efficacy. CD30 status assessment is thus a critical factor for therapeutic decision, but the reliability of immunohistochemistry (IHC) in evaluating its expression remains to be defined. This prompted us to investigate the correlation between semiquantitative CD30 protein assessment by IHC and messenger RNA (mRNA) assessment by microarrays in a cohort of 376 noncutaneous PTCLs representative of the main entities. By IHC, CD30 expression was heterogeneous across and within entities and significantly associated with large tumor cell size. In addition to 100% anaplastic large-cell lymphomas, 57% of other PTCL entities were CD30-positive at a 5% threshold. CD30 protein expression was highly correlated to mRNA levels. mRNA levels were bimodal, separating high from low CD30-expressing PTCL cases. We conclude that IHC is a valuable tool in clinical practice to assess CD30 expression in PTCLs. PMID:25224410

  14. The Internal Validation of Level II and Level III Respiratory Therapy Examinations. Final Report.

    ERIC Educational Resources Information Center

    Jouett, Michael L.

    This project began with the delineation of the roles and functions of respiratory therapy personnel by the American Association for Respiratory Therapy. In Phase II, The Psychological Corporation used this delineation to develop six proficiency examinations, three at each of two levels. One exam at each level was designated for the purpose of the…

  15. CD4+ T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa

    PubMed Central

    Geng, Elvin H; Neilands, Torsten B; Thièbaut, Rodolphe; Bosco Bwana, Mwebesa; Nash, Denis; Moore, Richard D; Wood, Robin; Marcel Zannou, Djimon; Althoff, Keri N; Lian Lim, Poh; Nachega, Jean B; Easterbrook, Philippa J; Kambugu, Andrew; Little, Francesca; Nakigozi, Gertrude; Nakanjako, Damalie; Kiggundu, Valerian; Chung Ki Li, Patrick; Bangsberg, David R; Fox, Matthew P; Prozesky, Hans W; Hunt, Peter W; Davies, Mary-Ann; Reynolds, Steven J; Egger, Matthias; Yiannoutsos, Constantin T; Vittinghoff, Eric V; Deeks, Steven G; Martin, Jeffrey N

    2015-01-01

    Background: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. Methods: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitor-based regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/µl in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. Results: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/µl was 529/µl [95% confidence interval (CI): 517–541] in North America, 494/µl (95% CI: 429–559) in West Africa, 515/µl (95% CI: 508–522) in Southern Africa, 503/µl (95% CI: 478–528) in Asia and 437/µl (95% CI: 425–449) in East Africa. Conclusions: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level. PMID:25859596

  16. Validation of cytogenetic risk groups according to International Prognostic Scoring Systems by peripheral blood CD34+FISH: results from a German diagnostic study in comparison with an international control group

    PubMed Central

    Braulke, Friederike; Platzbecker, Uwe; Müller-Thomas, Catharina; Götze, Katharina; Germing, Ulrich; Brümmendorf, Tim H.; Nolte, Florian; Hofmann, Wolf-Karsten; Giagounidis, Aristoteles A. N.; Lübbert, Michael; Greenberg, Peter L.; Bennett, John M.; Solé, Francesc; Mallo, Mar; Slovak, Marilyn L.; Ohyashiki, Kazuma; Le Beau, Michelle M.; Tüchler, Heinz; Pfeilstöcker, Michael; Nösslinger, Thomas; Hildebrandt, Barbara; Shirneshan, Katayoon; Aul, Carlo; Stauder, Reinhard; Sperr, Wolfgang R.; Valent, Peter; Fonatsch, Christa; Trümper, Lorenz; Haase, Detlef; Schanz, Julie

    2015-01-01

    International Prognostic Scoring Systems are used to determine the individual risk profile of myelodysplastic syndrome patients. For the assessment of International Prognostic Scoring Systems, an adequate chromosome banding analysis of the bone marrow is essential. Cytogenetic information is not available for a substantial number of patients (5%–20%) with dry marrow or an insufficient number of metaphase cells. For these patients, a valid risk classification is impossible. In the study presented here, the International Prognostic Scoring Systems were validated based on fluorescence in situ hybridization analyses using extended probe panels applied to cluster of differentiation 34 positive (CD34+) peripheral blood cells of 328 MDS patients of our prospective multicenter German diagnostic study and compared to chromosome banding results of 2902 previously published patients with myelodysplastic syndromes. For cytogenetic risk classification by fluorescence in situ hybridization analyses of CD34+ peripheral blood cells, the groups differed significantly for overall and leukemia-free survival by uni- and multivariate analyses without discrepancies between treated and untreated patients. Including cytogenetic data of fluorescence in situ hybridization analyses of peripheral CD34+ blood cells (instead of bone marrow banding analysis) into the complete International Prognostic Scoring System assessment, the prognostic risk groups separated significantly for overall and leukemia-free survival. Our data show that a reliable stratification to the risk groups of the International Prognostic Scoring Systems is possible from peripheral blood in patients with missing chromosome banding analysis by using a comprehensive probe panel (clinicaltrials.gov identifier:01355913). PMID:25344522

  17. Correlation between viral load, plasma levels of CD4 - CD8 T lymphocytes and AIDS-related oral diseases: a multicentre study on 30 HIV+ children in the HAART era.

    PubMed

    Nesti, M; Carli, E; Giaquinto, C; Rampon, O; Nastasio, S; Giuca, M R

    2012-01-01

    This experimental retrospective multicenter study carried out on 30 seropositive children treated with Highly Active Antiretroviral Therapy (HAART), between the ages of 18 months and 14 years, in the clinical categories Centers for Disease Control (CDC) classification 1993 A (mildly symptomatic), B (moderately symptomatic) and C (severely symptomatic) aims to: 1) clinically and immunologically demonstrate the therapeutic benefits of HAART; 2) monitor the frequency of AIDS-related oral diseases in seropositive children with HAART therapy; 3) monitor the plasma levels of total CD4, CD4 percent, CD8 percent, CD4-CD8 lymphocytes and viral load from 1997 to 30 April, 2011. The statistic methods used are the analysis of covariance and the Bonferroni Test. More than 100 AIDS-related oral diseases were found in the study samples, the most frequent being: oral candidiasis, oropharyngeal candidiasis, HSV-1 herpetic esophagyitis, herpetic gingivolstomatitis (RHOG), recurrent aphthous stomatitis (RAS), parotid swelling, oral hairy leukoplakia (OHL), Herpes simplex 1 (HSV-1), linear gingival erythema (LGE), necrotizing gingivitis (NUG), facial lipodistrophy, facial-cervical lymphadenopathy (FCL), xerostomia, dysgeusia, hyposmia, oral mucosa hyperpigmentation (OMP). The Bonferroni test showed a significant difference between the mean plasma values (mpVTL) of total CD4, CD4 percentage, CD4-CD8 T lymphocytes and Viral Load (VL) of the various oral diseases found in the study samples. The therapeutic benefits of HAART are: immune reconstitution; reduction of the HIV/AIDS-related stomatology diseases; prevention and cure of the AIDS correlated neoplasias; reduction in maternal-fetal transmission of the HIV virus. The negative effects of HAART in relation to odontostomatolgy are: increase in oral lesions from HPV; xerostomia; dysgeusia/ageusia, hyposmia, perioral paresthesia; hyperpigmentation of oral mucosa; facial lipodystrophy, recurrent aphthous stomatitis (RAS). No case of

  18. Histone acetylation at the single-cell level: a marker of memory CD8+ T cell differentiation and functionality.

    PubMed

    Dispirito, Joanna R; Shen, Hao

    2010-05-01

    Following stimulation, memory T (T(M)) cells rapidly express many effector functions, a hallmark feature that allows them to provide protective immunity. Recent studies suggest that genes involved in this rapid recall response may maintain an open chromatin structure in resting T(M) cells via epigenetic modifications. However, these studies have mostly focused on a few loci, and the techniques used required a large number of cells. We have developed a flow cytometric assay measuring histone modifications in individual murine T cells in combination with lineage-specific markers. In this study, we show that the per-cell level of a marker of open chromatin, diacetylated histone H3 (diAcH3), increases as naive CD8(+) T cells develop into T(M) cells, demonstrating a novel correlation between the differentiation state of a CD8(+) T cell and its abundance of a specific histone modification. Furthermore, our results show that T(M) cells defective in rapid recall ability have less diAcH3 than their fully functional counterparts, indicating that the diAcH3 level of individual T(M) cells is a useful marker for assessing their functionality. PMID:20308634

  19. Diminished CD4+/CD25+ T cell and increased IFN-gamma levels occur in dogs vaccinated with Leishmune in an endemic area for visceral leishmaniasis.

    PubMed

    de Lima, Valéria Marçal Felix; Ikeda, Fabiana Augusta; Rossi, Cláudio N; Feitosa, Mary Marcondes; Vasconcelos, Rosemeride Oliveira; Nunes, Caris Maroni; Goto, Hiro

    2010-06-15

    The Leishmune vaccine has been used in endemic areas to prevent canine visceral leishmaniasis in Brazil, but cytokine production induced by vaccination has rarely been investigated in dogs. This study aimed to evaluate the immune response of dogs vaccinated with Leishmune FML vaccine (Fort Dodge) against total antigen of Leishmania (Leishmania) chagasi (TAg) and FML. Twenty healthy dogs from Araçatuba, São Paulo, Brazil, an endemic leishmaniasis area, received three consecutive subcutaneous injection of Leishmune vaccine at 21-day intervals. PBMC were isolated before and 10 days after completing vaccination and lymphoproliferative response and antibody production against FML or total promastigote antigen were tested. Cytokines IFN-gamma, IL-4 and TNF-alpha were measured in culture supernatant and CD4+/CD25+ and CD8+/CD25+ T cell presence was determined. Analysis of the data indicated that the vaccine conferred humoral responses (100%) against both antigens and cellular immunity to FML (85%) and total antigen (80%), the supernatant of cultured cells stimulated with TAg and FML showed an increase in IFN-gamma (P<0.05), and the vaccine reduced CD4+/CD25+ T cell presence compared to that observed before vaccination. These responses may constitute part of the immune mechanism induced by Leishmune. PMID:20132994

  20. Intracellular calcium levels are differentially regulated in T lymphocytes triggered by anti-CD2 and anti-CD3 monoclonal antibodies.

    PubMed

    Spinozzi, F; Agea, E; Bistoni, O; Belia, S; Travetti, A; Gerli, R; Muscat, C; Bertotto, A

    1995-03-01

    Antigen and/or mitogen-driven T-cell activation is mediated by a rise in intracellular free Ca2+, as second messenger. A regulatory key role for this process is represented by membrane-associated [Ca2+/Mg2+] ATP-ase that is mainly devoted to extrusion of intracellular ion excess. In the present study we have investigated the kinetics of CA2+ fluxes in both resting and already activated (Jurkat T-cell line) T lymphocytes after CD3 and CD2 (T11(2) and T11(3)) triggering and focused our attention on plasma membrane [Ca2+/Mg2+] ATP-ase activity. In both resting T cells and Jurkat cell line, the CD2 stimulation was able to determine a rise in intracellular free Ca2+ higher than that observed after CD3 triggering. In addition, this calcium signal was independent of negative feedback control exerted by [Ca2+/Mg2+] ATP-ase, as well as of IP3 generation. Thus the CD2 molecular system may, together with cell-adhesion properties, act as an amplifier of Ca2+ signals that, if delivered in the context of other molecular systems, such as CD3 or MHC class II antigens, are essentially devoted to the polyclonal co-stimulatory recruitment of a larger cellular repertoire. PMID:7662514

  1. Effects of Pb plus Cd mixtures on toxicity, and internal electrolyte and osmotic balance in the rainbow trout (Oncorhynchus mykiss).

    PubMed

    Clemow, Yvonne H; Wilkie, Michael P

    2015-04-01

    The physiological and toxicological effects of Cd and Pb have been thoroughly studied, but relatively little work has been done to determine how mixtures of these metals affect fishes in soft (<100 μmol L(-1)Ca(2+)) slightly acidic (pH ∼6) waters typical of many lakes in the Canadian Shield and other regions. Recently, it has been suggested that acute exposure to Cd plus Pb mixtures (3h) had greater than additive effects on both Ca(2+) and Na(+) influx, which could potentially exacerbate disturbances to ion balance and result in greater toxicity in rainbow trout (Oncorhynchus mykiss). The goal of the present study was to test this hypothesis by assessing the physiological and toxicological effects of Cd plus Pb mixtures over longer time periods (3-5 days), but at relatively low, more environmentally relevant concentrations of these metals. Accordingly, toxicity and measurements of blood acid-base regulation (PaO2, pHa), hematology (Ht, Hb, MCHC, and Protein), ionic composition (body ions and plasma Ca(2+), Na(+), Cl(-), osmolality), unidirectional Na(+) fluxes and branchial Na(+)/K(+)-ATPase activity were measured in rainbow trout exposed to Cd plus Pb mixtures. Experiments on rainbow trout, implanted with dorsal aortic catheters for repetitive blood sampling, demonstrated that exposure to Pb alone (26 nmol PbL(-1)) was less toxic than Cd alone (6 nmol CdL(-1)), which was much less toxic to the fish than a Cd plus Pb mixture (7 nmol CdL(-1) plus 45 nmol PbL(-1)), which led to greater than additive 80% mortality by 5d. Both Cd and Pb inhibited Na(+) influx over 3d exposure to the metals, which was partially offset by decreases in the diffusive efflux (outflux) of Na(+) across the gill. Despite an absence of detectable effects of Pb alone on plasma ion balance, Cd plus Pb mixtures exacerbated Cd-induced reductions in plasma Ca(2+) concentration, and resulted in pronounced reductions in plasma Na(+), Cl(-), and osmolality. No effects on Na(+)/K(+)-ATPase activity

  2. Cloning and high level expression of the biologically active extracellular domain of Macaca mulatta CD40 in Pichia pastoris.

    PubMed

    Zhu, Shengyun; Wan, Lin; Yang, Hao; Cheng, Jingqiu; Lu, Xiaofeng

    2016-03-01

    The CD40-mediated immune response contributes to a wide variety of chronic inflammatory diseases. CD40 antagonists have potential as novel therapies for immune disorders. However, the CD40 pathway has not been well characterized in the rhesus monkey Macaca mulatta, which is a valuable animal model for human immune disease. An 834 bp transcript was cloned from peripheral blood mononuclear cells (PBMCs) of rhesus monkey using specific primers designed according to the predicted sequence of M. mulatta CD40 (mmCD40) in GenBank. Sequence analysis demonstrated that mmCD40 is highly homologous to human CD40 (hCD40), with an amino acid sequence identity of 94%. Genes encoding the extracellular domain of mmCD40 and the Fc fragment of the hIgG1 were inserted into a pPIC9K plasmid to produce mmCD40Ig by Pichia pastoris. Approximately 15-20 mg of the mmCD40Ig protein with ∼90% purity could be recovered from 1 L of culture. The purified mmCD40Ig protein can form dimers and can specifically bind CD40L-positive cells. Additionally, the mmCD40Ig protein can bind hCD40L protein in phosphate buffered saline and form a stable combination in a size-exclusion chromatography assay using a Superdex 200 column. Moreover, mmCD40Ig is as efficient as M. mulatta CTLA4Ig (mmCTLA4Ig) to suppress Con A-stimulated lymphocyte proliferation. Additionally, mmCD40Ig only showed mild immunosuppressive activity in a one-way mixed lymphocyte reaction (MLR) system. These results suggest that mmCD40Ig secreted by P. pastoris was productive and functional, and it could be used as a tool for pathogenesis and therapies for chronic inflammatory diseases in a M. mulatta model. PMID:26586612

  3. Differences in CD44 Surface Expression Levels and Function Discriminates IL-17 and IFN-γ Producing Helper T Cells

    PubMed Central

    Schumann, Julia; Stanko, Katarina; Schliesser, Ulrike; Appelt, Christine; Sawitzki, Birgit

    2015-01-01

    CD44 is a prominent activation marker which distinguishes memory and effector T cells from their naïve counterparts. It also plays a role in early T cell signaling events as it is bound to the lymphocyte-specific protein kinase and thereby enhances T cell receptor signalling. Here, we investigated whether IFN-γ and IL-17 producing T helper cells differ in their CD44 expression and their dependence of CD44 for differentiation. Stimulation of CD4+ T cells with allogeneic dendritic cells resulted in the formation of three distinguishable populations: CD44+, CD44++ and CD44+++. In vitro and in vivo generated allo-reactive IL-17 producing T helper cells were mainly CD44+++ as compared to IFN-γ+ T helper cells, which were CD44++. This effect was enhanced under polarizing conditions. T helper 17 polarization led to a shift towards the CD44+++ population, whereas T helper 1 polarization diminished this population. Furthermore, blocking CD44 decreased IL-17 secretion, while IFN-γ was barely affected. Titration experiments revealed that low T cell receptor and CD28 stimulation supported T helper 17 rather than T helper 1 development. Under these conditions CD44 could act as a co-stimulatory molecule and replace CD28. Indeed, rested CD44+++CD4+ T cells contained already more total and especially phosphorylated zeta-chain-associated protein kinase 70 as compared to CD44++ cells. Our results support the notion, that CD44 enhances T cell receptor signaling strength by delivering lymphocyte-specific protein kinase, which is required for induction of IL-17 producing T helper cells. PMID:26172046

  4. Education for Sustainability: Developing a Postgraduate-Level Subject with an International Perspective

    ERIC Educational Resources Information Center

    Buchan, Graeme D.; Spellerberg, Ian F.; Blum, Winfried E. H.

    2007-01-01

    Purpose: To describe the development and structure of a new Master's-level subject entitled "Aspects of sustainability: an international perspective" as a potential model, adoptable by other tertiary-level educators. Design/methodology/approach: This paper describes the evolution and re-shaping of a subject designed for postgraduate students from…

  5. Mean Levels and Correlates of Perfectionism in International Baccalaureate and General Education Students

    ERIC Educational Resources Information Center

    Shaunessy, Elizabeth; Suldo, Shannon M.; Friedrich, Allison

    2011-01-01

    This exploratory study examined the mean levels of perfectionism among 178 general education students and 141 students enrolled in the International Baccalaureate (IB) program, a rigorous academic curriculum. The study also explored perfectionism in relation to grade level and student outcomes (psychological functioning, academic achievement).…

  6. Constitutive expression levels of CD95 and Bcl-2 as well as CD95 function and spontaneous apoptosis in vitro do not predict the response to induction chemotherapy and relapse rate in childhood acute lymphoblastic leukaemia.

    PubMed

    Wuchter, C; Karawajew, L; Ruppert, V; Schrappe, M; Harbott, J; Ratei, R; Dörken, B; Ludwig, W D

    2000-07-01

    CD95 (Fas/APO-1) expression and function and Bcl-2 expression, as well as spontaneous apoptosis in vitro, have been shown to be predictive markers for the in vivo response to chemotherapy in acute myeloid leukaemia (AML). To determine the clinical significance of apoptosis-regulating factors in acute lymphoblastic leukaemia (ALL), we investigated cell samples of children with ALL who had been included in the German ALL Berlin-Frankfurt-Münster (BFM) study using flow cytometry for constitutive expression levels of CD95 (n = 110) and Bcl-2 (n = 110). Furthermore, we determined the extent of spontaneous apoptosis in vitro (n = 102) and susceptibility to anti-CD95-induced apoptosis (CD95-sensitivity) (n = 97). We correlated these findings with the functional activity of the multidrug resistance (MDR)-associated P-glycoprotein (P-gp), as detected by the rhodamine123 efflux test, immunophenotype, cytogenetics and clinical data of the patients examined. Good responders to initial prednisone therapy ('prednisone response') revealed significantly higher Bcl-2 expression levels [5.4 +/- 3.4 relative fluorescence intensity (RFI), n = 68] than poor responders (3.7 +/- 2.6 RFI, n = 42; P = 0.002). There was no significant correlation between the other investigated parameters and prednisone response. Moreover, neither the CD95 and Bcl-2 expression levels nor the extent of spontaneous apoptosis in vitro, CD95 sensitivity or P-gp function were correlated with the response to induction chemotherapy or relapse rate, either for B-cell precursor ALL or T-cell ALL. No consistent pattern of change in CD95 (n = 10) and Bcl-2 expression (n = 9) was noted in cases studied at both initial diagnosis and relapse. In conclusion, our findings underline the different cell biological features of primary AML and ALL cells. PMID:10930993

  7. Plasma Prostaglandin E2 Levels Correlated with the Prevention of Intravenous Immunoglobulin Resistance and Coronary Artery Lesions Formation via CD40L in Kawasaki Disease

    PubMed Central

    Kuo, Ho-Chang; Wang, Chih-Lu; Yang, Kuender D.; Lo, Mao-Hung; Hsieh, Kai-Sheng; Li, Sung-Chou

    2016-01-01

    Background A form of systemic vasculitis, Kawasaki disease (KD) occurs most frequently in children under the age of five years old. Previous studies have found that Prostaglandin E2 (PGE2) correlates with KD, although the related mechanisms are still unknown. CD40L may also be a marker of vasculitis in KD, so this study focuses on PGE2 and CD40L expression in KD. Materials and Methods This study consisted of a total of 144 KD patients, whose intravenous immunoglobulin (IVIG)/coronary arterial lesion (CAL) formation resistance was evaluated. PGE2 levels were evaluated in vitro to study the effect of CD40L on CD4+ T lymphocytes. Results PGE2 levels significantly increased after IVIG treatment (p<0.05), especially in patients who responded to initial IVIG treatment (p = 0.004) and for patients without CAL formation (p = 0.016). Furthermore, an in vitro study revealed that IVIG acted as a trigger for PGE2 expression in the acute-stage mononuclear cells of KD patients. According to our findings, both IVIG and PGE2 can impede surface CD40L expressions on CD4+ T lymphocytes (p<0.05). Conclusions The results of this study are among the first to find that plasma PGE2 is correlated with the prevention of IVIG resistance and CAL formation through CD40L in KD. PMID:27525421

  8. Resonance energy transfer based on shallow and deep energy levels of biotin-polyethylene glycol/polyamine stabilized CdS quantum dots

    NASA Astrophysics Data System (ADS)

    Lü, W.; Tokuhiro, Y.; Umezu, I.; Sugimura, A.; Nagasaki, Y.

    2006-10-01

    Fluorescent resonance energy transfer between the poly(ethylene glycol)-b-poly(2-(N ,N-dimethylamino)ethyl methacrylate) stabilized CdS quantum dots (QDs) and texas-red streptavidin was observed. We propose a four-state model to explain photoluminescence (PL) process of CdS QDs and suggest that there are two emission processes originated from shallow and deep trap energy levels corresponding to fast and slow components of PL decay, respectively. Energy transfer mechanism was discussed based on Dexter theory [J. Chem. Phys. 21, 863 (1953)] and the proposed four-state model. It is found that the energy transfer efficiency of deep energy level is higher than that of shallow energy level. The calculated distance between QD and texas red with the parameters of shallow energy level is the same with that of deep level, which indicates that the proposed model is reasonable for explaining the PL dynamics of CdS QDs.

  9. Factors associated with higher levels of depressive symptoms among international university students in the Philippines.

    PubMed

    Lee, Romeo B; Maria, Madelene Sta; Estanislao, Susana; Rodriguez, Cristina

    2013-11-01

    Over the years, the number of international university students has been increasing in the Philippines. Depression tends to be common among this demographic sector, because of the varying challenges and expectations associated with studying abroad. Depression can be prevented if its symptoms, particularly those at higher levels, are identified and addressed early and effectively. This survey examined the social and demographic factors that are significantly associated with higher levels of depressive symptoms. One hundred twenty-six international university students were interviewed using the University Students Depression Inventory. Of the 13 factors analyzed, 3 were found with statistically significant associations with more intense levels of depressive symptoms. These factors were: level of satisfaction with one's financial condition, level of closeness with parents, and level of closeness with peers. In identifying international students with greater risk for depression, characteristics related to their financial condition and primary group relationships can be considered. There is a need to carry out more studies to confirm this initial evidence. The findings can help guide further discourse, research and program to benefit international students with higher levels of depressive symptoms. PMID:24450248

  10. In utero exposure to benzene increases embryonic c-Myb and Pim-1 protein levels in CD-1 mice

    SciTech Connect

    Wan, Joanne; Winn, Louise M.

    2008-05-01

    Benzene is a known human leukemogen, but its role as an in utero leukemogen remains controversial. Epidemiological studies have correlated parental exposure to benzene with an increased incidence of childhood leukemias. We hypothesize that in utero exposure to benzene may cause leukemogenesis by affecting the embryonic c-Myb/Pim-1 signaling pathway and that this is mediated by oxidative stress. To investigate this hypothesis, pregnant CD-1 mice were treated with either 800 mg/kg of benzene or corn oil (i.p.) on days 10 and 11 of gestation and in some cases pretreated with 25 kU/kg of PEG-catalase. Phosphorylated and total embryonic c-Myb and Pim-1 protein levels were assessed using Western blotting and maternal and embryonic oxidative stress were assessed by measuring reduced to oxidized glutathione ratios. Our results show increased oxidative stress at 4 and 24 h after exposure, increased phosphorylated Pim-1 protein levels 4 h after benzene exposure, and increased Pim-1 levels at 24 and 48 h after benzene exposure. Embryonic c-Myb levels were elevated at 24 h after exposure. PEG-catalase pretreatment prevented benzene-mediated increases in embryonic c-Myb and Pim-1 protein levels, and benzene-induced oxidative stress. These results support a role for ROS in c-Myb and Pim-1 alterations after in utero benzene exposure.

  11. Split Dirac cones in HgTe/CdTe quantum wells due to symmetry-enforced level anticrossing at interfaces

    NASA Astrophysics Data System (ADS)

    Tarasenko, S. A.; Durnev, M. V.; Nestoklon, M. O.; Ivchenko, E. L.; Luo, Jun-Wei; Zunger, Alex

    2015-02-01

    HgTe is a band-inverted compound which forms a two-dimensional topological insulator if sandwiched between CdTe barriers for a HgTe layer thickness above the critical value. We describe the fine structure of Dirac states in the HgTe/CdTe quantum wells of critical and close-to-critical thicknesses and show that the necessary creation of interfaces brings in another important physical effect: the opening of a significant anticrossing gap between the tips of the Dirac cones. The level repulsion driven by the natural interface inversion asymmetry of zinc-blende heterostructures considerably modifies the electron states and dispersion but preserves the topological transition at the critical thickness. By combining symmetry analysis, atomistic calculations, and extended k .p theory with interface terms, we obtain a quantitative description of the energy spectrum and extract the interface mixing coefficient. We discuss how the fingerprints of the predicted zero-magnetic-field splitting of the Dirac cones could be detected experimentally by studying magnetotransport phenomena, cyclotron resonance, Raman scattering, and THz radiation absorption.

  12. Numerical Modeling of HgCdTe Solidification: Effects of Phase Diagram, Double-Diffusion Convection and Microgravity Level

    NASA Technical Reports Server (NTRS)

    Bune, Andris V.; Gillies, Donald C.; Lehoczky, Sandor L.

    1997-01-01

    Melt convection, along with species diffusion and segregation on the solidification interface are the primary factors responsible for species redistribution during HgCdTe crystal growth from the melt. As no direct information about convection velocity is available, numerical modeling is a logical approach to estimate convection. Furthermore influence of microgravity level, double-diffusion and material properties should be taken into account. In the present study, HgCdTe is considered as a binary alloy with melting temperature available from a phase diagram. The numerical model of convection and solidification of binary alloy is based on the general equations of heat and mass transfer in two-dimensional region. Mathematical modeling of binary alloy solidification is still a challenging numericial problem. A Rigorous mathematical approach to this problem is available only when convection is not considered at all. The proposed numerical model was developed using the finite element code FIDAP. In the present study, the numerical model is used to consider thermal, solutal convection and a double diffusion source of mass transport.

  13. Exploring Resonance Levels and Nanostructuring in the PbTe-CdTe System and Enhancement of the Thermoelectric Figure of Merit

    SciTech Connect

    Ahn, Kyunghan; Han, Mi-Kyung; He, Jiaqing; Androulakis, John; Ballikaya, Sedat; Uher, Ctirad; Dravid, Vinayak; Kanatzidis, Mercouri G.

    2010-04-14

    We explored the effect of Cd substitution on the thermoelectric properties of PbTe in an effort to test a theoretical hypothesis that Cd atoms on Pb sites of the rock salt lattice can increase the Seebeck coefficient via the formation of a resonance level in the density of states near the Fermi energy. We find that the solubility of Cd is less than previously reported, and CdTe precipitation occurs to create nanostructuring, which strongly suppresses the lattice thermal conductivity. We present detailed characterization including structural and spectroscopic data, transmission electron microscopy, and thermoelectric transport properties of samples of PbTe-x% CdTe-0.055% PbI2 (x = 1, 3, 5, 7, 10), PbTe-1% CdTe-y% PbI2 (y = 0.03, 0.045, 0.055, 0.08, 0.1, 0.2), PbTe-5% CdTe-y% PbI2 (y = 0.01, 0.03, 0.055, 0.08), and PbTe-1% CdTe-z% Sb (z = 0.3, 0.5, 1, 1.5, 2, 3, 4, 5, 6). All samples follow the Pisarenko relationship, and no enhancement of the Seebeck coefficient was observed that could be attributed to a resonance level or a distortion in the density of states. A maximum ZT of 1.2 at 720 K was achieved for the PbTe-1% CdTe-0.055% PbI2 sample arising from a high power factor of 17 μW/(cm K2) and a very low lattice thermal conductivity of 0.5 W/(m K) at 720 K.

  14. Bevacizumab specifically decreases elevated levels of circulating KIT+CD11b+ cells and IL-10 in metastatic breast cancer patients

    PubMed Central

    Cattin, Sarah; Fellay, Benoît; Pradervand, Sylvain; Trojan, Andreas; Ruhstaller, Thomas

    2016-01-01

    Background Whether bevacizumab exerts its anti-tumor properties through systemic effects beyond local inhibition of angiogenesis and how these effects can be monitored in patients, remain largely elusive. To address these questions, we investigated bone marrow-derived cells and cytokines in the peripheral blood of metastatic breast cancer patients undergoing therapy with bevacizumab. Methods Circulating endothelial cells (CEC), circulating endothelial progenitor (CEP) and circulating CD11b+ cells in metastatic breast cancer patients before and during therapy with paclitaxel alone (n = 11) or in combination with bevacizumab (n = 10) were characterized using flow cytometry, real time PCR and RNASeq. Circulating factors were measured by ELISA. Aged-matched healthy donors were used as baseline controls (n = 12). Results Breast cancer patients had elevated frequencies of CEC, CEP, TIE2+CD11b+ and KIT+CD11b+ cell subsets. CEC decreased during therapy, irrespective of bevacizumab, while TIE2+CD11b+ remained unchanged. KIT+CD11b+ cells decreased in response to paclitaxel with bevacizumab, but not paclitaxel alone. Cancer patients expressed higher mRNA levels of the M2 polarization markers CD163, ARG1 and IL-10 in CD11b+ cells and increased levels of the M2 cytokines IL-10 and CCL20 in plasma. M1 activation markers and cytokines were low or equally expressed in cancer patients compared to healthy donors. Chemotherapy with paclitaxel and bevacizumab, but not with paclitaxel alone, significantly decreased IL-10 mRNA in CD11b+ cells and IL-10 protein in plasma. Conclusions This pilot study provides evidence of systemic immunomodulatory effects of bevacizumab and identified circulating KIT+CD11b+ cells and IL-10 as candidate biomarkers of bevacizumab activity in metastatic breast cancer patients. PMID:26840567

  15. Macrophage entry mediated by HIV Envs from brain and lymphoid tissues is determined by the capacity to use low CD4 levels and overall efficiency of fusion

    SciTech Connect

    Thomas, Elaine R.; Dunfee, Rebecca L.; Stanton, Jennifer; Bogdan, Derek; Taylor, Joann; Kunstman, Kevin; Bell, Jeanne E.; Wolinsky, Steven M.; Gabuzda, Dana . E-mail: dana_gabuzda@dfci.harvard.edu

    2007-03-30

    HIV infects macrophages and microglia in the central nervous system (CNS), which express lower levels of CD4 than CD4+ T cells in peripheral blood. To investigate mechanisms of HIV neurotropism, full-length env genes were cloned from autopsy brain and lymphoid tissues from 4 AIDS patients with HIV-associated dementia (HAD). Characterization of 55 functional Env clones demonstrated that Envs with reduced dependence on CD4 for fusion and viral entry are more frequent in brain compared to lymphoid tissue. Envs that mediated efficient entry into macrophages were frequent in brain but were also present in lymphoid tissue. For most Envs, entry into macrophages correlated with overall fusion activity at all levels of CD4 and CCR5. gp160 nucleotide sequences were compartmentalized in brain versus lymphoid tissue within each patient. Proline at position 308 in the V3 loop of gp120 was associated with brain compartmentalization in 3 patients, but mutagenesis studies suggested that P308 alone does not contribute to reduced CD4 dependence or macrophage-tropism. These results suggest that HIV adaptation to replicate in the CNS selects for Envs with reduced CD4 dependence and increased fusion activity. Macrophage-tropic Envs are frequent in brain but are also present in lymphoid tissues of AIDS patients with HAD, and entry into macrophages in the CNS and other tissues is dependent on the ability to use low receptor levels and overall efficiency of fusion.

  16. Greek Mythology: Literature Curriculum, Levels C-D [Grades Three and Four]; Teacher's Guide.

    ERIC Educational Resources Information Center

    Oregon Univ., Eugene. Oregon Elementary English Project.

    This curriculum guide is intended to introduce elementary school students to Greek mythology. The authors suggest that the selections be presented by the teacher as lively and imaginative stories; the more abstract aspects of the myths should be largely ignored until students reach the junior high school level. In addition to the myths themselves,…

  17. Optical and Electrical Studies of the Double Acceptor Levels of the Mercury Vacancies in HgCdTe

    NASA Astrophysics Data System (ADS)

    Gemain, F.; Robin, I. C.; Brochen, S.; De Vita, M.; Gravrand, O.; Lusson, A.

    2012-10-01

    Correlations between photoluminescence and temperature-dependent Hall measurements were carried out on unintentionally doped HgCdTe epilayers with cadmium composition of 32.7%. These films were grown by liquid-phase epitaxy and post-annealed under different conditions as follows: a p-type annealing was used to control the mercury vacancy concentration, and an n-type annealing under saturated mercury atmosphere was used to fill the mercury vacancies. Comparison of the results obtained by these two characterization techniques allowed us to identify the two acceptor energy levels of the mercury vacancy. Moreover, the "U-negativity" of the vacancy was evidenced: the ionized state V- is stabilized under the neutral state V0 by the dominance of the Jahn-Teller effect over Coulombic repulsion. Finally, three epilayers with different cadmium compositions were also characterized to complete this study.

  18. Reduced sTWEAK and Increased sCD163 Levels in HIV-Infected Patients: Modulation by Antiretroviral Treatment, HIV Replication and HCV Co-Infection

    PubMed Central

    Beltrán, Luis M.; García Morillo, José S.; Egido, Jesús; Noval, Manuel Leal; Ferrando-Martinez, Sara; Blanco-Colio, Luis M.; Genebat, Miguel; Villar, José R.; Moreno-Luna, Rafael; Moreno, Juan Antonio

    2014-01-01

    Background Patients infected with the human immunodeficiency virus (HIV) have an increased risk of cardiovascular disease due to increased inflammation and persistent immune activation. CD163 is a macrophage scavenger receptor that is involved in monocyte-macrophage activation in HIV-infected patients. CD163 interacts with TWEAK, a member of the TNF superfamily. Circulating levels of sTWEAK and sCD163 have been previously associated with cardiovascular disease, but no previous studies have fully analyzed their association with HIV. Objective The aim of this study was to analyze circulating levels of sTWEAK and sCD163 as well as other known markers of inflammation (hsCRP, IL-6 and sTNFRII) and endothelial dysfunction (sVCAM-1 and ADMA) in 26 patients with HIV before and after 48 weeks of antiretroviral treatment (ART) and 23 healthy subjects. Results Patients with HIV had reduced sTWEAK levels and increased sCD163, sVCAM-1, ADMA, hsCRP, IL-6 and sTNFRII plasma concentrations, as well as increased sCD163/sTWEAK ratio, compared with healthy subjects. Antiretroviral treatment significantly reduced the concentrations of sCD163, sVCAM-1, hsCRP and sTNFRII, although they remained elevated when compared with healthy subjects. Antiretroviral treatment had no effect on the concentrations of ADMA and sTWEAK, biomarkers associated with endothelial function. The use of protease inhibitors as part of antiretroviral therapy and the presence of HCV-HIV co-infection and/or active HIV replication attenuated the ART-mediated decrease in sCD163 plasma concentrations. Conclusion HIV-infected patients showed a proatherogenic profile characterized by increased inflammatory, immune-activation and endothelial-dysfunction biomarkers that partially improved after ART. HCV-HIV co-infection and/or active HIV replication enhanced immune activation despite ART. PMID:24594990

  19. Negative Factor from SIV Binds to the Catalytic Subunit of the V-ATPase to Internalize CD4 and to Increase Viral Infectivity

    PubMed Central

    Mandic, Robert; Fackler, Oliver T.; Geyer, Matthias; Linnemann, Thomas; Zheng, Yong-Hui; Peterlin, B. Matija

    2001-01-01

    The accessory protein negative factor (Nef) from human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) is required for optimal viral infectivity and the progression to acquired immunodeficiency syndrome (AIDS). Nef interacts with the endocytic machinery, resulting in the down-regulation of cluster of differentiation antigen 4 (CD4) and major histocompatibility complex class I (MHCI) molecules on the surface of infected cells. Mutations in the C-terminal flexible loop of Nef result in a lower rate of internalization by this viral protein. However, no loop-dependent binding of Nef to adaptor protein-2 (AP-2), which is the adaptor protein complex that is required for the internalization of proteins from the plasma membrane, could be demonstrated. In this study we investigated the relevance of different motifs in Nef from SIVmac239 for its internalization, CD4 down-regulation, binding to components of the trafficking machinery, and viral infectivity. Our data suggest that the binding of Nef to the catalytic subunit H of the vacuolar membrane ATPase (V-ATPase) facilitates its internalization. This binding depends on the integrity of the whole flexible loop. Subsequent studies on Nef mutant viruses revealed that the flexible loop is essential for optimal viral infectivity. Therefore, our data demonstrate how Nef contacts the endocytic machinery in the absence of its direct binding to AP-2 and suggest an important role for subunit H of the V-ATPase in viral infectivity. PMID:11179428

  20. A low level of dietary selenium has both beneficial and toxic effects and is protective against Cd-toxicity in the least killifish Heterandria formosa.

    PubMed

    Xie, Lingtian; Wu, Xing; Chen, Hongxing; Dong, Wu; Cazan, Alfy Morales; Klerks, Paul L

    2016-10-01

    As an essential element, selenium (Se) is beneficial at low levels yet toxic at high levels. The present study assessed the effects of dietary exposure to Se in the least killifish Heterandria formosa, and investigated how this exposure influences the effects of a subsequent exposure to cadmium (Cd). The fish were pre-exposed to an environmentally relevant concentration (2 μg g(-1) dry wt) of dietary selenite (Se(4+)) or seleno-l-methionine (Se-Met) for 10 d. The same fish were then exposed to 0.5 mg L(-1) of Cd for 5 d. Both Se(IV) and Se-Met rapidly accumulated in H. formosa. Results for the two Se species were generally similar in this study. Fish exposed to Se had lower levels of lipid peroxidation (measured as levels of thiobarbituric acid reactive substances or TBARS) and a higher catalase (CAT) activity. In contrast, their Na(+)/K(+)-ATPase activity was reduced. The Cd exposure resulted in an increase in lipid peroxidation and decreases in the activities of catalase and Na(+)/K(+)-ATPase. The Cd-exposed H. formosa that were pre-exposed to Se had lower Cd body burdens, less lipid peroxidation, and higher catalase activity, than did fish not pre-exposed to Se. The Se exposure did not have a protective effect on the Cd-induced reduction in Na(+)/K(+)-ATPase activity. These results clearly demonstrate that a Se-enriched diet reduces some (but not all) forms of Cd-toxicity and that Se can simultaneously have beneficial and detrimental effects, making it difficult to predict the net outcome of changes in dietary Se levels for fish. PMID:27448316

  1. Mapping Zn, Cu and Cd contents at the small catchment level after dispersion of contaminants by agricultural practices

    NASA Astrophysics Data System (ADS)

    Vidal Vázquez, E.; Mirás-Avalos, J. M.; Paz-Ferreiro, J.

    2009-04-01

    Dispersion of trace metals into the rural environment through the use of sewage sludge, fertilizers and manure has been worldwide reported. In El Abelar (Coruña province, Spain), pig slurry was discharged during years intensively into an agricultural field by means of a device which constituted a point source of contamination. The application point was located near the head of an elementary basin, so that slurry was dispersed by runoff into neighboring grassland and maize fields. In addition, diffuse pollution was also present in the study area as a consequence of cattle grazing. Water quality was monitored during and after slurry application at the outlet of a small catchment (about 10.7 ha in surface) draining the study fields. High levels of nutrients, including heavy metals, were found in drainage water. The main objectives of this paper are to determine the spatial variability of Cu, Zn and Cd as extracted by NO3H, EDTA and Ca2Cl and to evaluate the risk of accumulation of these heavy metals at the small catchment level. A set of 55 soil samples were taken from the top soil layer (0-20 cm) of the studied catchment, following a random sampling scheme. Fe, Mn, Cu, Zn and Cd contents were determined i) after digestion by nitric acid in a microwave (USEPA-SW-846 3051) ii) after extraction with EDTA and iii) after extraction with Cl2Ca. Element contents in the extracts were determined by ICP-MS. Summary statistics indicate that variability in Cu, Zn and Cd contents over the study area was very high. For example, after NO3H digestion Zn contents ranged from 29.66 to 141.77 3 mg kg-1 and Cu contents varied from 10.45 to 72.7 3 mg kg-1. High Cu and Zn contents result from accumulation as a consequence of slurry discharge. Also, some hot spots with high levels of Cd (> 3 mg kg-1 after NO3H) with respect to background values were recorded. Geostatistics provides all necessary tools to analyze the spatial variability of soil properties over a landscape. The spatial

  2. Correlation of combustor acoustic power levels inferred from internal fluctuating pressure measurements

    NASA Technical Reports Server (NTRS)

    Vonglahn, U. H.

    1978-01-01

    Combustion chamber acoustic power levels inferred from internal fluctuating pressure measurements are correlated with operating conditions and chamber geometries over a wide range. The variables include considerations of chamber design (can, annular, and reverse-flow annular) and size, number of fuel nozzles, burner staging and fuel split, airflow and heat release rates, and chamber inlet pressure and temperature levels. The correlated data include those obtained with combustion component development rigs as well as engines.

  3. Improving International-Level Chess Players' Performance with an Acceptance-Based Protocol: Preliminary Findings

    ERIC Educational Resources Information Center

    Ruiz, Francisco J.; Luciano, Carmen

    2012-01-01

    This study compared an individual, 4-hr intervention based on acceptance and commitment therapy (ACT) versus a no-contact control condition in improving the performance of international-level chess players. Five participants received the brief ACT protocol, with each matched to another chess player with similar characteristics in the control…

  4. Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism

    PubMed Central

    Ansari, Morad; Poke, Gemma; Ferry, Quentin; Williamson, Kathleen; Aldridge, Roland; Meynert, Alison M; Bengani, Hemant; Chan, Cheng Yee; Kayserili, Hülya; Avci, Şahin; Hennekam, Raoul C M; Lampe, Anne K; Redeker, Egbert; Homfray, Tessa; Ross, Alison; Falkenberg Smeland, Marie; Mansour, Sahar; Parker, Michael J; Cook, Jacqueline A; Splitt, Miranda; Fisher, Richard B; Fryer, Alan; Magee, Alex C; Wilkie, Andrew; Barnicoat, Angela; Brady, Angela F; Cooper, Nicola S; Mercer, Catherine; Deshpande, Charu; Bennett, Christopher P; Pilz, Daniela T; Ruddy, Deborah; Cilliers, Deirdre; Johnson, Diana S; Josifova, Dragana; Rosser, Elisabeth; Thompson, Elizabeth M; Wakeling, Emma; Kinning, Esther; Stewart, Fiona; Flinter, Frances; Girisha, Katta M; Cox, Helen; Firth, Helen V; Kingston, Helen; Wee, Jamie S; Hurst, Jane A; Clayton-Smith, Jill; Tolmie, John; Vogt, Julie; Tatton–Brown, Katrina; Chandler, Kate; Prescott, Katrina; Wilson, Louise; Behnam, Mahdiyeh; McEntagart, Meriel; Davidson, Rosemarie; Lynch, Sally-Ann; Sisodiya, Sanjay; Mehta, Sarju G; McKee, Shane A; Mohammed, Shehla; Holden, Simon; Park, Soo-Mi; Holder, Susan E; Harrison, Victoria; McConnell, Vivienne; Lam, Wayne K; Green, Andrew J; Donnai, Dian; Bitner-Glindzicz, Maria; Donnelly, Deirdre E; Nellåker, Christoffer; Taylor, Martin S; FitzPatrick, David R

    2014-01-01

    Background Cornelia de Lange syndrome (CdLS) is a multisystem disorder with distinctive facial appearance, intellectual disability and growth failure as prominent features. Most individuals with typical CdLS have de novo heterozygous loss-of-function mutations in NIPBL with mosaic individuals representing a significant proportion. Mutations in other cohesin components, SMC1A, SMC3, HDAC8 and RAD21 cause less typical CdLS. Methods We screened 163 affected individuals for coding region mutations in the known genes, 90 for genomic rearrangements, 19 for deep intronic variants in NIPBL and 5 had whole-exome sequencing. Results Pathogenic mutations [including mosaic changes] were identified in: NIPBL 46 [3] (28.2%); SMC1A 5 [1] (3.1%); SMC3 5 [1] (3.1%); HDAC8 6 [0] (3.6%) and RAD21 1 [0] (0.6%). One individual had a de novo 1.3 Mb deletion of 1p36.3. Another had a 520 kb duplication of 12q13.13 encompassing ESPL1, encoding separase, an enzyme that cleaves the cohesin ring. Three de novo mutations were identified in ANKRD11 demonstrating a phenotypic overlap with KBG syndrome. To estimate the number of undetected mosaic cases we used recursive partitioning to identify discriminating features in the NIPBL-positive subgroup. Filtering of the mutation-negative group on these features classified at least 18% as ‘NIPBL-like’. A computer composition of the average face of this NIPBL-like subgroup was also more typical in appearance than that of all others in the mutation-negative group supporting the existence of undetected mosaic cases. Conclusions Future diagnostic testing in ‘mutation-negative’ CdLS thus merits deeper sequencing of multiple DNA samples derived from different tissues. PMID:25125236

  5. CXCL8, IL-1β and sCD200 are pro-inflammatory cytokines and their levels increase in the circulation of breast carcinoma patients

    PubMed Central

    Celik, Betul; Yalcin, Arzu Didem; Genc, Gizem Esra; Bulut, Tangul; Kuloglu Genc, Sibel; Gumuslu, Saadet

    2016-01-01

    The influence of biomarkers on carcinogenesis has been investigated extensively. Whether they promote carcinogenesis or work against cancer development remains to be elucidated. To the best of our knowledge, the novel molecule cluster of differentiation 200 (CD200) has not been studied on human breast cancer subjects. The present study aimed to evaluate interleukin-1β (IL-1β), C-X-C motif chemokine ligand 8 (CXCL8), cancer antigen 15.3 (CA 15.3) and the soluble CD200 (sCD200) levels in the serum samples of breast carcinoma patients in order to predict their role in breast carcinoma. The subjects included individuals with early and advanced stage breast cancers, as well as healthy controls. Commercially available ELISA kits were used to measure the serum concentrations of sCD200, IL-1β, CXCL8, CA 15.3, C-reactive protein (CRP) and leukocyte count. A total of 130 subjects were recruited; 50 early stage cancer, 50 advanced stage and 30 control subjects. Serum sCD200, CXCL8, IL-1β and CRP levels were significantly higher in the early as well as the advanced stage breast cancer patients compared to the control group. The level of CA 15.3 was statistically different between early and advanced stage. There were significant positive correlations between IL-1β and CXCL8, and IL-1β and serum sCD200 levels in the control group. These correlations did not persist in the early or the advanced stage cancer groups except CRP and CA 15.3, but new correlations appeared between serum sCD200 level and leukocyte count for advanced stage breast cancer group. Multivariate regression correlation analysis revealed positive correlation between IL-1β and sCD200; and IL-1β and CXCL8. In conclusion, sCD200, CXCL8, CA 15.3 and IL-1β are proinflammatory molecules and their levels are influenced in breast cancer patients. PMID:27446554

  6. A genome-wide linkage scan reveals CD53 as an important regulator of innate TNF-α levels

    PubMed Central

    Bos, Steffan D; Lakenberg, Nico; van der Breggen, Ruud; Houwing-Duistermaat, Jeanine J; Kloppenburg, Margreet; de Craen, Anton JM; Beekman, Marian; Meulenbelt, Ingrid; Slagboom, P Eline

    2010-01-01

    Cytokines are major immune system regulators. Previously, innate cytokine profiles determined by lipopolysaccharide stimulation were shown to be highly heritable. To identify regulating genes in innate immunity, we analyzed data from a genome-wide linkage scan using microsatellites in osteoarthritis (OA) patients (The GARP study) and their innate cytokine data on interleukin (IL)-1β, IL-1Ra, IL-10 and tumor necrosis factor (TNF)α. A confirmation cohort consisted of the Leiden 85-Plus study. In this study, a linkage analysis was followed by manual selection of candidate genes in linkage regions showing LOD scores over 2.5. An single-nucleotide polymorphism (SNP) gene tagging method was applied to select SNPs on the basis of the highest level of gene tagging and possible functional effects. QTDT was used to identify the SNPs associated with innate cytokine production. Initial association signals were modeled by a linear mixed model. Through these analyses, we identified 10 putative genes involved in the regulation of TNFα. SNP rs6679497 in gene CD53 showed significant association with TNFα levels (P=0.001). No association of this SNP was observed with OA. A novel gene involved in the innate immune response of TNFα is identified. Genetic variation in this gene may have a role in diseases and disorders in which TNFα is closely involved. PMID:20407468

  7. Cyclosporin A inhibits CD11a/CD18 adhesion molecules due to inhibition of TNFα and IL-1β levels in the mouse model of pleurisy induced by carrageenan

    PubMed Central

    Dalmarco, Eduardo Monguilhott; Medeiros, Yara Santos

    2008-01-01

    The mouse model of pleurisy induced by carrageenan is characterized by a significant enhancement of cell migration due to neutrophils 4 h after pleurisy induction. Forty-eight hours after pleurisy induction, a significant increase in cell migration due to mononuclear cells occurs. Recently, studies in our laboratory have demonstrated that cyclosporine A (CsA) inhibits leukocyte migration in the pleural cavity and lungs in the mouse model of pleurisy induced by carrageenan. In the present work we evaluated whether CsA was able to downregulate CD11a/CD18 adhesion molecule in the lungs, as well as TNFα and IL-1β levels in the fluid leakage of the pleural cavity in this model. Our results showed that CsA significantly decreased CD11a/CD18 in the lungs, as well as TNFα and IL-1β levels in the fluid leakage of the pleural cavity 4 h and 48 h after pleurisy induction. It is our hypothesis that the inhibitory effect elicited by CsA upon these adhesion molecules may be also be attributed to the downregulation of TNFα and IL-1β cytokines. PMID:19262158

  8. International Mussel Watch: A global assessment of environmental levels of chemical contaminants

    SciTech Connect

    Not Available

    1992-01-01

    The primary goal of the International Mussel Watch is to ascertain and assess the levels of chlorinated hydrocarbon pesticide (CHP) and polychlorinated biphenyls (PCB) in bivalves collected from coastal marine waters throughout the world. Increased use of these persistent toxic biocides may result in contamination of living coastal resources from whole ecosystems to specific food resources with consequent implication for human health and the integrity of marine communities. Another goal for the International Mussel Watch Project will be to help develop a sustainable activity for observation and monitoring chemical contamination in especially susceptible regions of the world's oceans.

  9. Monocyte surface expression of Fcγ receptor RI (CD64), a biomarker reflecting type-I interferon levels in systemic lupus erythematosus

    PubMed Central

    2010-01-01

    Introduction More than half of systemic lupus erythematosus (SLE) patients show evidence of excess type I interferon (IFN-I) production, a phenotype associated with renal disease and certain autoantibodies. However, detection of IFN-I proteins in serum is unreliable, and the measurement of interferon-stimulated gene (ISG) expression is expensive and time consuming. The aim of this study was to identify a surrogate marker for IFN-I activity in clinical samples for monitoring disease activity and response to therapy. Methods Monocyte surface expression of Fcγ receptors (FcγRs), chemokine receptors, and activation markers were analyzed with flow cytometry in whole blood from patients with SLE and healthy controls. FcγR expression also was measured in peripheral blood mononuclear cells (PBMCs) from healthy controls cultured with Toll-like receptor (TLR) agonists, cytokines, or serum from SLE patients. Expression of ISGs was analyzed with real-time PCR. Results Circulating CD14+ monocytes from SLE patients showed increased surface expression of FcγRI (CD64). The mean fluorescent intensity of CD64 staining correlated highly with the ISG expression (MX1, IFI44, and Ly6E). In vitro, IFN-I as well as TLR7 and TLR9 agonists, induced CD64 expression on monocytes from healthy controls. Exposure of monocytes from healthy controls to SLE sera also upregulated the expression of CD64 in an IFN-I-dependent manner. Decreased CD64 expression was observed concomitant with the reduction of ISG expression after high-dose corticosteroid therapy. Conclusions Expression of CD64 on circulating monocytes is IFN-I inducible and highly correlated with ISG expression. Flow-cytometry analysis of CD64 expression on circulating monocytes is a convenient and rapid approach for estimating IFN-I levels in SLE patients. PMID:20478071

  10. Down-regulation of promoter methylation level of CD4 gene after MDV infection in MD-susceptible chicken line

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease virus (MDV) is an oncovirus that induces lymphoid tumors in susceptible chickens, and may affect the epigenetic stability of the CD4 gene. The purpose of this study was to find how the effect of MDV infection on DNA methylation status of the CD4 gene differed between MD-resistant (L6...

  11. 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

  12. CD14+CD16+ and CD14+CD163+ monocyte subpopulations in kidney allograft transplantation

    PubMed Central

    2014-01-01

    Background Monocytes represent a heterogeneous population of cells subdivided according to the expression level of membrane antigens. A pro-inflammatory (intermediate/nonclassical) subpopulation of monocytes is defined by expression of CD16. CD163 seems to be characteristically preferentially expressed by immunosuppressive monocytes. The aim of our study was to evaluate the distribution of monocyte subpopulations in 71 patients with kidney allograft transplantation. Results The phenotype was evaluated by flow cytometry in defined time points. The proportions of peripheral CD14+CD16+ monocytes were downregulated immediately after the kidney transplantation and basiliximab treatment partially attenuated this trend. The transient downregulation of the CD14+CD16+ subpopulation was adjusted to basal values in two months. The proportions of CD14+CD163+ monocytes were transiently upregulated early after the kidney transplantation and remained higher during the first month in most patients. In ATG treated patients, the expansion of CD14+CD163+ monocytes was delayed but their upregulation lasted longer. In vitro data showed the direct effect of ATG and methylprednisolone on expression of CD16 and CD163 molecules while basiliximab did not affect the phenotype of cultured monocytes. Conclusions We assume from our data that kidney allograft transplantation is associated with modulation of monocyte subpopulations (CD14+CD16+ and CD14+CD163+) partially affected by an immunosuppressive regime used. PMID:24499053

  13. Preexisting Levels of CD4 T Cells Expressing PD-1 Are Related to Overall Survival in Prostate Cancer Patients Treated with Ipilimumab.

    PubMed

    Kwek, Serena S; Lewis, Jera; Zhang, Li; Weinberg, Vivian; Greaney, Samantha K; Harzstark, Andrea L; Lin, Amy M; Ryan, Charles J; Small, Eric J; Fong, Lawrence

    2015-09-01

    Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) blockade can induce tumor regression and improved survival in cancer patients. This treatment can enhance adaptive immune responses without an exogenous vaccine, but the immunologic biomarkers associated with improved clinical outcome in cancer patients are not fully established. A phase Ib trial in patients with metastatic, castration-resistant prostate cancer was performed combining ipilimumab with sargramostim (GM-CSF). In addition to evaluating ipilimumab dose, patients were followed clinically for response and overall survival, and for immunomodulation of circulating T cells. PSA declines of ≥50% and radiographic responses were observed at doses of ≥3 mg/kg/dose. Timing of clinical responses could be either immediate or delayed. Durable responses were also observed off treatment. A subset of patients experienced long-term survival with or without objective clinical responses. The relationship between T-cell phenotype in peripheral blood and overall survival was examined retrospectively. We found that the treatment induced an increase in the levels of CD4(+) effector T (Teff) cells, regulatory T cells, PD-1(+) CD4 Teff cells, and PD-1(+) CD8 T cells. However, these increased levels were not associated with overall survival. Instead, low pretreatment baseline levels of PD-1(+) CD4 Teff cells were found to correlate with longer overall survival. Furthermore, baseline levels of PD-1(+) CD4 Teff cells from patients with shorter overall survival were higher than from cancer-free male control subjects. These results suggest that preexisting expression of immunologic checkpoint marker PD-1 on CD4 Teff cells may help identify patients that may benefit from ipilimumab treatment. PMID:25968455

  14. Heavy metal levels (Pb, Cd, Cr and Hg) in the adult general population near an urban solid waste incinerator.

    PubMed

    Zubero, Miren Begoña; Aurrekoetxea, Juan José; Ibarluzea, Jesús María; Arenaza, Maria Jesús; Rodríguez, Carlos; Sáenz, José Ramón

    2010-09-15

    In 2005 an urban solid waste incinerator (SWI) was commissioned in Bilbao (Basque Country, Spain). Serum and urine samples were collected from 95 and 107 volunteers in 2006 and 2008 respectively, of which 62 were repeats from the same individuals. Blood lead levels (BPb) were determined, as were the concentrations of cadmium (Cd), chromium (Cr) and mercury (Hg) in urine (UCd, UCr and UHg). The town of Alonsotegi and a borough of Bilbao (Altamira, Rekalde) were considered to be close, less than 2 km from the plant, and correspond to an urban environment with high traffic density. The areas of reference were a borough of Bilbao (Santutxu-Zurbaran), 5 km from the plant, also in an urban area with high traffic density, and a small town with little industrial activity and low traffic density (Balmaseda) 20 km from the plant; neither of these is downwind from the site with respect to prevailing winds. There was a significant correlation for BPb, r=0.63 (p<0.001), between the two surveys. However, there was no linear correlation for the other three metals (UCd, UCr and UHg), between the two sampling periods (p>0.05). Multiple linear regression models did not show increases over time of the levels of BPb, UCd, UCr and UHg in the areas close to the SWI compared to those of areas located further away, after adjusting for confounding variables. These results reinforce the hypothesis that populations near modern plants for solid waste incineration do not manifest increased levels of heavy metals. PMID:20659760

  15. Serum Levels of Soluble CD26/Dipeptidyl Peptidase-IV in Type 2 Diabetes Mellitus and Its Association with Metabolic Syndrome and Therapy with Antidiabetic Agents in Malaysian Subjects

    PubMed Central

    Ahmed, Radwan H.; Huri, Hasniza Zaman; Al-Hamodi, Zaid; Salem, Sameer D.; Muniandy, Sekaran

    2015-01-01

    Background A soluble form of CD26/dipeptidyl peptidase-IV (sCD26/DPP-IV) induces DPP-IV enzymatic activity that degrades incretin. We investigated fasting serum levels of sCD26/DPP-IV and active glucagon-like peptide-1 (GLP-1) in Malaysian patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MetS), as well as the associations between sCD26/DPP-IV levels, MetS, and antidiabetic therapy. Methods We assessed sCD26/DPP-IV levels, active GLP-1 levels, body mass index (BMI), glucose, insulin, A1c, glucose homeostasis indices, and lipid profiles in 549 Malaysian subjects (including 257 T2DM patients with MetS, 57 T2DM patients without MetS, 71 non-diabetics with MetS, and 164 control subjects without diabetes or metabolic syndrome). Results Fasting serum levels of sCD26/DPP-IV were significantly higher in T2DM patients with and without MetS than in normal subjects. Likewise, sCD26/DPP-IV levels were significantly higher in patients with T2DM and MetS than in non-diabetic patients with MetS. However, active GLP-1 levels were significantly lower in T2DM patients both with and without MetS than in normal subjects. In T2DM subjects, sCD26/DPP-IV levels were associated with significantly higher A1c levels, but were significantly lower in patients using monotherapy with metformin. In addition, no significant differences in sCD26/DPP-IV levels were found between diabetic subjects with and without MetS. Furthermore, sCD26/DPP-IV levels were negatively correlated with active GLP-1 levels in T2DM patients both with and without MetS. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-cholesterol (LDL-c) levels. Conclusion Serum sCD26/DPP-IV levels increased in T2DM subjects with and without MetS. Active GLP-1 levels decreased in T2DM patients both with and without MetS. In addition, sCD26/DPP-IV levels were associated with Alc levels and negatively correlated with active GLP-1 levels. Moreover, metformin

  16. Impact of CD4+ Lymphocytes and HIV Infection on Anti-Müllerian Hormone Levels in a Large Cohort of HIV-infected and -uninfected Women

    PubMed Central

    Scherzer, Rebecca; Bacchetti, Peter; Messerlian, Geralyn; Goderre, Johanna; Maki, Pauline M.; Seifer, David B.; Anastos, Kathryn; Karim, Roksana; Greenblatt, Ruth M.

    2014-01-01

    Problem Effects of HIV infection on ovarian function and aging are unclear. Method of Study Anti-Müllerian Hormone (AMH) levels were analyzed in 2621 HIV-infected and 941 uninfected participants using left-censored longitudinal models. Results Age-adjusted AMH levels were 16% lower in women with undetectable viremia and 26% lower in detectable viremia, relative to uninfected women. Current CD4 count associated with higher AMH in both HIV-infected and HIV-uninfected women. After controlling for current and nadir CD4, AMH was ~15% higher in HIV-infected relative to uninfected women, regardless of HIV viremia. Gravidity, amenorrhea, and nadir total lymphocyte counts associated with higher AMH; hormonal contraceptive use and past weight loss associated with lower AMH. Conclusions CD4+ lymphocyte counts were associated with AMH in both HIV-infected and uninfected women. After adjustment for CD4 counts and age, HIV infection was associated with higher AMH. CD4 T cells and cellular activation may influence ovarian granulosa cell function. PMID:25339186

  17. Human CD4+CD39+ regulatory T cells produce adenosine upon co-expression of surface CD73 or contact with CD73+ exosomes or CD73+ cells

    PubMed Central

    Schuler, P J; Saze, Z; Hong, C-S; Muller, L; Gillespie, D G; Cheng, D; Harasymczuk, M; Mandapathil, M; Lang, S; Jackson, E K; Whiteside, T L

    2014-01-01

    While murine CD4+CD39+ regulatory T cells (Treg) co-express CD73 and hydrolyze exogenous (e) adenosine triphosphate (ATP) to immunosuppressive adenosine (ADO), surface co-expression of CD73 on human circulating CD4+CD39+ Treg is rare. Therefore, the ability of human Treg to produce and utilize ADO for suppression remains unclear. Using mass spectrometry, we measured nucleoside production by subsets of human CD4+CD39+ and CD4+CD39(–)CD73+ T cells or CD19+ B cells isolated from blood of 30 volunteers and 14 cancer patients. CD39 and CD73 expression was evaluated by flow cytometry, Western blots, confocal microscopy or reverse transcription–polymerase chain reaction (RT–PCR). Circulating CD4+CD39+ Treg which hydrolyzed eATP to 5′-AMP contained few intracytoplasmic granules and had low CD73 mRNA levels. Only ∼1% of these Treg were CD39+CD73+. In contrast, CD4+CD39negCD73+ T cells contained numerous CD73+ granules in the cytoplasm and strongly expressed surface CD73. In vitro-generated Treg (Tr1) and most B cells were CD39+CD73+. All these CD73+ T cell subsets and B cells hydrolyzed 5′-AMP to ADO. Exosomes isolated from plasma of normal control (NC) or cancer patients carried enzymatically active CD39 and CD73+ and, when supplied with eATP, hydrolyzed it to ADO. Only CD4+CD39+ Treg co-incubated with CD4+CD73+ T cells, B cells or CD39+CD73+ exosomes produced ADO. Thus, contact with membrane-tethered CD73 was sufficient for ADO production by CD4+CD39+ Treg. In microenvironments containing CD4+CD73+ T cells, B cells or CD39+CD73+ exosomes, CD73 is readily available to CD4+CD39+CD73neg Treg for the production of immunosuppressive ADO. PMID:24749746

  18. Infusing Interactive, Multimedia CD-ROM Technology into the First-Year College-Level Geology Curriculum: Recent Examples from Radford University, United States.

    ERIC Educational Resources Information Center

    Sethi, Parvinder S.; Newbill, Phyllis Leary

    In recent years, several CD-ROM-based instructional technology applications have been developed for use in both high school and college level classrooms. As multimedia authoring techniques evolve as important tools for teaching, it is imperative that teachers and multimedia authors understand the importance of focusing on specifically how the…

  19. International project on individual monitoring and radiation exposure levels in interventional cardiology.

    PubMed

    Padovani, R; Le Heron, J; Cruz-Suarez, R; Duran, A; Lefaure, C; Miller, D L; Sim, H K; Vano, E; Rehani, M; Czarwinski, R

    2011-03-01

    Within the Information System on Occupational Exposure in Medicine, Industry and Research (ISEMIR), a new International Atomic Energy Agency initiative, a Working Group on interventional cardiology, aims to assess staff radiation protection (RP) levels and to propose an international database of occupational exposures. A survey of regulatory bodies (RBs) has provided information at the country level on RP practice in interventional cardiology (IC). Concerning requirements for wearing personal dosemeters, only 57 % of the RB specifies the number and position of dosemeters for staff monitoring. Less than 40 % of the RBs could provide occupational doses. Reported annual median effective dose values (often <0.5 mSv) were lower than expected considering validated data from facility-specific studies, indicating that compliance with continuous individual monitoring is often not achieved in IC. A true assessment of annual personnel doses in IC will never be realised unless a knowledge of monitoring compliance is incorporated into the analysis. PMID:21051431

  20. Fermi level stabilization and band edge energies in Cd{sub x}Zn{sub 1−x}O alloys

    SciTech Connect

    Detert, Douglas M.; Tom, Kyle B.; Dubon, Oscar D.; Battaglia, Corsin; Javey, Ali; Denlinger, Jonathan D.; Lim, Sunnie H. N.; Anders, André; Yu, Kin M.; Walukiewicz, Wladek

    2014-06-21

    We have measured the band edge energies of Cd{sub x}Zn{sub 1−x}O thin films as a function of composition by three independent techniques: we determine the Fermi level stabilization energy by pinning the Fermi level with ion irradiation, measure the binding energy of valence band states and core levels by X-ray photoelectron spectroscopy, and probe shifts in the conduction band and valence band density of states using soft X-ray absorption and emission spectroscopy, respectively. The three techniques find consensus in explaining the origin of compositional trends in the optical-bandgap narrowing upon Cd incorporation in wurtzite ZnO and widening upon Zn incorporation in rocksalt CdO. The conduction band minimum is found to be stationary for both wurtzite and rocksalt alloys, and a significant upward rise of the valence band maximum accounts for the majority of these observed bandgap changes. Given these band alignments, alloy disorder scattering is found to play a negligible role in decreasing the electron mobility for all alloys. These band alignment details, combined with the unique optical and electrical properties of the two phase regimes, make CdZnO alloys attractive candidates for photoelectrochemical water splitting applications.

  1. Simulation of the internal dynamics of solid-fuel rocket engines on the basis of the STAR-CD suite

    NASA Astrophysics Data System (ADS)

    Volkov, K. N.; Denisikhin, S. V.; Emel'Yanov, V. N.

    2006-07-01

    Flows in the channels of solid-fuel charges with cross sections having different views in plan and flows in the prenozzle volume and the nozzle unit of a solid-fuel rocket engine have been simulated on the basis of the STAR-CD suite for different types of charges and different designs of the input part of the engine nozzle. The influence of the compressibility, turbulence, geometric factors, and flow rate on the distributions of gasdynamic parameters in the working region of the engine has been investigated.

  2. Integrated Pharmacokinetic/Pharmacodynamic Analysis for Determining the Minimal Anticipated Biological Effect Level of a Novel Anti-CD28 Receptor Antagonist BMS-931699.

    PubMed

    Yang, Zheng; Wang, Haiqing; Salcedo, Theodora W; Suchard, Suzanne J; Xie, Jenny H; Schneeweis, Lumelle A; Fleener, Catherine A; Calore, James D; Shi, Rong; Zhang, Sean X Y; Rodrigues, A David; Car, Bruce D; Marathe, Punit H; Nadler, Steven G

    2015-12-01

    BMS-931699 (lulizumab pegol), a domain antibody (dAb) conjugated with 40-kDa branched polyethylene glycol, is a human anti-CD28 receptor antagonist under development for the treatment of inflammatory and autoimmune diseases. In the present work, the minimal anticipated biologic effect level (MABEL) was determined for BMS-931699 by integrating all the available preclinical data. The relevance of the in vitro mixed lymphocyte reaction (MLR) assay to a whole blood CD28 receptor occupancy (RO) assessment, as well as the relationship between the CD28 RO and the inhibition of T-cell-dependent antibody response to keyhole limpet hemocyanin in vivo, was demonstrated through an integrated pharmacokinetic/pharmacodynamic analysis using anti-hCD28 dAb-001 (differing from BMS-931699 by two additional amino acids at the N-terminus) and a mouse surrogate. Based on this analysis, the EC10 value (0.32 nM) from the human MLR assay and the human plasma volume (0.04 l/kg) were employed to calculate the MABEL (0.01 mg) of BMS-931699 in humans, with a CD28 RO predicted to be ≤10%. The estimated MABEL dose was threefold higher than the value derived from the binding constant and twofold less than the MABEL converted from animal efficacy studies based on the body surface area. Furthermore, it was 2900-fold lower than the human equivalent dose derived from the no observed adverse effect level in monkeys (15 mg/kg/week for 5 doses, intravenous dosing) with a 10-fold safety factor applied. Therefore, the MABEL dose represented a sound approach to mitigate any potential risk in targeting CD28 and was successfully used as the first-in-human starting dose for BMS-931699. PMID:26442523

  3. Interplay between T Cell Receptor Binding Kinetics and the Level of Cognate Peptide Presented by Major Histocompatibility Complexes Governs CD8+ T Cell Responsiveness*

    PubMed Central

    Irving, Melita; Zoete, Vincent; Hebeisen, Michael; Schmid, Daphné; Baumgartner, Petra; Guillaume, Philippe; Romero, Pedro; Speiser, Daniel; Luescher, Immanuel; Rufer, Nathalie; Michielin, Olivier

    2012-01-01

    Through a rational design approach, we generated a panel of HLA-A*0201/NY-ESO-1157–165-specific T cell receptors (TCR) with increasing affinities of up to 150-fold from the wild-type TCR. Using these TCR variants which extend just beyond the natural affinity range, along with an extreme supraphysiologic one having 1400-fold enhanced affinity, and a low-binding one, we sought to determine the effect of TCR binding properties along with cognate peptide concentration on CD8+ T cell responsiveness. Major histocompatibility complexes (MHC) expressed on the surface of various antigen presenting cells were peptide-pulsed and used to stimulate human CD8+ T cells expressing the different TCR via lentiviral transduction. At intermediate peptide concentration we measured maximum cytokine/chemokine secretion, cytotoxicity, and Ca2+ flux for CD8+ T cells expressing TCR within a dissociation constant (KD) range of ∼1–5 μm. Under these same conditions there was a gradual attenuation in activity for supraphysiologic affinity TCR with KD < ∼1 μm, irrespective of CD8 co-engagement and of half-life (t1/2 = ln 2/koff) values. With increased peptide concentration, however, the activity levels of CD8+ T cells expressing supraphysiologic affinity TCR were gradually restored. Together our data support the productive hit rate model of T cell activation arguing that it is not the absolute number of TCR/pMHC complexes formed at equilibrium, but rather their productive turnover, that controls levels of biological activity. Our findings have important implications for various immunotherapies under development such as adoptive cell transfer of TCR-engineered CD8+ T cells, as well as for peptide vaccination strategies. PMID:22549784

  4. Alirocumab, a Therapeutic Human Antibody to PCSK9, Does Not Affect CD81 Levels or Hepatitis C Virus Entry and Replication into Hepatocytes

    PubMed Central

    Ramanathan, Aarti; Gusarova, Viktoria; Stahl, Neil; Gurnett-Bander, Anne; Kyratsous, Christos A.

    2016-01-01

    Background Proprotein convertase subtilisin/kexin type 9 (PSCK9) is secreted mainly from the liver and binds to the low-density lipoprotein receptor (LDLR), reducing LDLR availability and thus resulting in an increase in LDL-cholesterol. While the LDLR has been implicated in the cell entry process of the hepatitis C virus (HCV), overexpression of an artificial non-secreted, cell membrane-bound form of PCSK9 has also been shown to reduce surface expression of CD81, a major component of the HCV entry complex, leading to concerns that pharmacological inhibition of PCSK9 may increase susceptibility to HCV infection by increasing either CD81 or LDLR availability. Here, we evaluated effects of PCSK9 and PCSK9 blockade on CD81 levels and HCV entry with a physiologically relevant model using native secreted PCSK9 and a monoclonal antibody to PCSK9, alirocumab. Methods and Results Flow cytometry and Western blotting of human hepatocyte Huh-7 cells showed that, although LDLR levels were reduced when cells were exposed to increasing PCSK9 concentrations, there was no correlation between total or surface CD81 levels and the presence and amount of soluble PCSK9. Moreover, inhibiting PCSK9 with the monoclonal antibody alirocumab did not affect expression levels of CD81. In an in vitro model of HCV entry, addition of soluble PCSK9 or treatment with alirocumab had no effect on the ability of either lentiviral particles bearing the HCV glycoproteins or JFH-1 based cell culture virus to enter hepatocytes. Consistent with these in vitro findings, no differences were observed in hepatic CD81 levels using in vivo mouse models, including Pcsk9-/- mice compared with wild-type controls and hyperlipidemic mice homozygous for human Pcsk9 and heterozygous for Ldlr deletion, treated with either alirocumab or isotype control antibody. Conclusion These results suggest that inhibition of PCSK9 with alirocumab has no effect on CD81 and does not result in increased susceptibility to HCV entry

  5. Neopterin and Soluble CD14 Levels as Indicators of Immune Activation in Cases with Indeterminate Pattern and True Positive HIV-1 Infection

    PubMed Central

    Uysal, Hayriye Kırkoyun; Sohrabi, Pari; Habip, Zafer; Saribas, Suat; Kocazeybek, Emre; Seyhan, Fatih; Calışkan, Reyhan; Bonabi, Esad; Yuksel, Pelin; Birinci, Ilhan; Uysal, Omer; Kocazeybek, Bekir

    2016-01-01

    Background We aimed to evaluate the roles of the plasma immune activation biomarkers neopterin and soluble CD14 (sCD14) in the indirect assessment of the immune activation status of patients with the indeterminate HIV-1 (IHIV-1) pattern and a true HIV-1-positive infection (PCG). Methods This cross-sectional and descriptive study included eighty-eight patients with the IHIV-1 pattern, 100 patients in the PCG, and 100 people in a healthy control group (HCG). Neopterin and sCD14 levels were determined by competitive and sandwich ELISA methods, respectively. Results Mean neopterin and sCD14 levels among those with the IHIV-1 pattern were significantly lower than among the PCG (p < 0.001 and p = 0.001, respectively), but they were similiar to those in the HCG (p = 0.57 and p = 0.66, respectively. Mean neopterin and sCD14 levels among the PCG were found to be significantly higher than among those with the IHIV-1 pattern (p < 0.001 and p = 0.001, respectively) and among those in the HCG (p = 0.001, p < 0.001, respectively). Neopterin did not have adequate predictive value for identifying those in the PCG (area under the curve [AUC] = 0.534; 95% CI, 0.463–0.605; p = 0.4256); sCD14 also had poor predictive value but high specificity (100%) for identifying those in the PCG (AUC = 0.627; 95% CI, 0.556–0.694; p = 0.0036). Conclusions While low levels of these two biomarkers were detected among those with the IHIV-1 pattern, they were found in high levels among those in the PCG. These two markers obviously cannot be used as a sceening test because they have low sensitivies. Taken together, we suggest that neopterin and sCD14 may be helpful because they both have high specificity (92%-100%) as indirect non-specific markers for predicting the immune activation status of individuals, whether or not they have true positive HIV-1. PMID:27031691

  6. Inhibition of G-Protein βγ Signaling Decreases Levels of Messenger RNAs Encoding Proinflammatory Cytokines in T Cell Receptor-Stimulated CD4+ T Helper Cells

    PubMed Central

    Hynes, Thomas R.; Yost, Evan A.; Hartle, Cassandra M.; Ott, Braden J.

    2015-01-01

    Background: Inhibition of G-protein βγ (Gβγ) signaling was found previously to enhance T cell receptor (TCR)-stimulated increases in interleukin 2 (IL-2) mRNA in CD4+ T helper cells, suggesting that Gβγ might be a useful drug target for treating autoimmune diseases, as low dose IL-2 therapy can suppress autoimmune responses. Because IL-2 may counteract autoimmunity in part by shifting CD4+ T helper cells away from the Type 1 T helper cell (TH1) and TH17 subtypes towards the TH2 subtype, the purpose of this study was to determine if blocking Gβγ signaling affected the balance of TH1, TH17, and TH2 cytokine mRNAs produced by CD4+ T helper cells. Methods: Gallein, a small molecule inhibitor of Gβγ, and siRNA-mediated silencing of the G-protein β1 subunit (Gβ1) were used to test the effect of blocking Gβγ on mRNA levels of cytokines in primary human TCR-stimulated CD4+ T helper cells. Results: Gallein and Gβ1 siRNA decreased interferon-γ (IFN-γ) and IL-17A mRNA levels in TCR-stimulated CD4+ T cells grown under TH1-promoting conditions. Inhibiting Gβγ also decreased mRNA levels of STAT4, which plays a positive role in TH1 differentiation and IL-17A production. Moreover, mRNA levels of the STAT4-regulated TH1-associated proteins, IL-18 receptor β chain (IL-18Rβ), mitogen-activated protein kinase kinase kinase 8 (MAP3K8), lymphocyte activation gene 3 (LAG-3), natural killer cell group 7 sequence (NKG7), and oncostatin M (OSM) were also decreased upon Gβγ inhibition. Gallein also increased IL-4, IL-5, IL-9, and IL-13 mRNA levels in TCR-stimulated memory CD4+ T cells grown in TH2-promoting conditions. Conclusions: Inhibiting Gβγ to produce these shifts in cytokine mRNA production might be beneficial for patients with autoimmune diseases such as rheumatoid arthritis (RA), Crohn’s disease (CD), psoriasis, multiple sclerosis (MS), and Hashimoto’s thyroiditis (HT), in which both IFN-γ and IL-17A are elevated. PMID:27095999

  7. Examining the Dynamic Structure of Daily Internalizing and Externalizing Behavior at Multiple Levels of Analysis.

    PubMed

    Wright, Aidan G C; Beltz, Adriene M; Gates, Kathleen M; Molenaar, Peter C M; Simms, Leonard J

    2015-01-01

    Psychiatric diagnostic covariation suggests that the underlying structure of psychopathology is not one of circumscribed disorders. Quantitative modeling of individual differences in diagnostic patterns has uncovered several broad domains of mental disorder liability, of which the Internalizing and Externalizing spectra have garnered the greatest support. These dimensions have generally been estimated from lifetime or past-year comorbidity patters, which are distal from the covariation of symptoms and maladaptive behavior that ebb and flow in daily life. In this study, structural models are applied to daily diary data (Median = 94 days) of maladaptive behaviors collected from a sample (N = 101) of individuals diagnosed with personality disorders (PDs). Using multilevel and unified structural equation modeling, between-person, within-person, and person-specific structures were estimated from 16 behaviors that are encompassed by the Internalizing and Externalizing spectra. At the between-person level (i.e., individual differences in average endorsement across days) we found support for a two-factor Internalizing-Externalizing model, which exhibits significant associations with corresponding diagnostic spectra. At the within-person level (i.e., dynamic covariation among daily behavior pooled across individuals) we found support for a more differentiated, four-factor, Negative Affect-Detachment-Hostility-Disinhibition structure. Finally, we demonstrate that the person-specific structures of associations between these four domains are highly idiosyncratic. PMID:26732546

  8. Systemic Cytokine Levels Do Not Predict CD4+ T-Cell Recovery After Suppressive Combination Antiretroviral Therapy in Chronic Human Immunodeficiency Virus Infection

    PubMed Central

    Norris, Philip J.; Zhang, Jinbing; Worlock, Andrew; Nair, Sangeetha V.; Anastos, Kathryn; Minkoff, Howard L.; Villacres, Maria C.; Young, Mary; Greenblatt, Ruth M.; Desai, Seema; Landay, Alan L.; Gange, Stephen J.; Nugent, C. Thomas; Golub, Elizabeth T.; Keating, Sheila M.

    2016-01-01

    Background. Subjects on suppressive combination antiretroviral therapy (cART) who do not achieve robust reconstitution of CD4+ T cells face higher risk of complications and death. We studied participants in the Women's Interagency HIV Study with good (immunological responder [IR]) or poor (immunological nonresponder [INR]) CD4+ T-cell recovery after suppressive cART (n = 50 per group) to determine whether cytokine levels or low-level viral load correlated with INR status. Methods. A baseline sample prior to viral control and 2 subsequent samples 1 and 2 years after viral control were tested. Serum levels of 30 cytokines were measured at each time point, and low-level human immunodeficiency virus (HIV) viral load and anti-HIV antibody levels were measured 2 years after viral suppression. Results. There were minimal differences in cytokine levels between IR and INR subjects. At baseline, macrophage inflammatory protein-3β levels were higher in IR subjects; after 1 year of suppressive cART, soluble vascular endothelial growth factor-R3 levels were higher in IR subjects; and after 2 years of suppressive cART, interferon gamma-induced protein 10 levels were higher in INR subjects. Very low-level HIV viral load and anti-HIV antibody levels did not differ between IR and INR subjects. Conclusions. These results imply that targeting residual viral replication might not be the optimum therapeutic approach for INR subjects. PMID:26966697

  9. Systemic Cytokine Levels Do Not Predict CD4(+) T-Cell Recovery After Suppressive Combination Antiretroviral Therapy in Chronic Human Immunodeficiency Virus Infection.

    PubMed

    Norris, Philip J; Zhang, Jinbing; Worlock, Andrew; Nair, Sangeetha V; Anastos, Kathryn; Minkoff, Howard L; Villacres, Maria C; Young, Mary; Greenblatt, Ruth M; Desai, Seema; Landay, Alan L; Gange, Stephen J; Nugent, C Thomas; Golub, Elizabeth T; Keating, Sheila M

    2016-01-01

    Background.  Subjects on suppressive combination antiretroviral therapy (cART) who do not achieve robust reconstitution of CD4(+) T cells face higher risk of complications and death. We studied participants in the Women's Interagency HIV Study with good (immunological responder [IR]) or poor (immunological nonresponder [INR]) CD4(+) T-cell recovery after suppressive cART (n = 50 per group) to determine whether cytokine levels or low-level viral load correlated with INR status. Methods.  A baseline sample prior to viral control and 2 subsequent samples 1 and 2 years after viral control were tested. Serum levels of 30 cytokines were measured at each time point, and low-level human immunodeficiency virus (HIV) viral load and anti-HIV antibody levels were measured 2 years after viral suppression. Results.  There were minimal differences in cytokine levels between IR and INR subjects. At baseline, macrophage inflammatory protein-3β levels were higher in IR subjects; after 1 year of suppressive cART, soluble vascular endothelial growth factor-R3 levels were higher in IR subjects; and after 2 years of suppressive cART, interferon gamma-induced protein 10 levels were higher in INR subjects. Very low-level HIV viral load and anti-HIV antibody levels did not differ between IR and INR subjects. Conclusions.  These results imply that targeting residual viral replication might not be the optimum therapeutic approach for INR subjects. PMID:26966697

  10. Safety and efficacy of intrathecal rituximab in children with B cell lymphoid CD20+ malignancies: An international retrospective study.

    PubMed

    Ceppi, Francesco; Weitzman, Sheila; Woessmann, Wilhelm; Davies, Kimberly; Lassaletta, Alvaro; Reismüller, Bettina; Mellgren, Karin; Uyttebroeck, Anne; Maia, Iris; Abdullah, Shaker; Miakova, Natasha; Glaser, Darryl; Cohn, Richard; Abla, Oussama; Attarbaschi, Andishe; Alexander, Sarah

    2016-05-01

    Central nervous system (CNS) involvement in patients with mature B non-Hodgkin lymphoma, post-transplantation proliferative disorder and acute lymphoblastic leukemia confers a significantly inferior prognosis as compared to patients without CNS disease. Intrathecal (IT) or intraventricular administration of rituximab is an option for this group of patients. We report 25 children with CNS involvement of CD20+ B lymphoid malignancies who received in total 163 IT/intraventricular rituximab doses. The median number of doses received by each patient was 6, with a median dose of 25 mg. The most common adverse events were Grades 1 and 2 peripheral neuropathies in five patients (20%), allergy in two patients, and headache in two patients. These events were self-limited, occurring in the 48 hours after treatment and resolving within 24 hr. Three patients presented with more severe though transient side effects, one with a Grade III neuropathy and two with seizure. Eighteen patients (72%) of those treated with IT/intraventricular rituximab, with or without other CNS directed treatment, achieved a CNS remission. This case series suggests that IT/intraventricular rituximab has therapeutic efficacy and relatively limited toxicity. Prospective trials of IT/intraventricular rituximab for patients with CNS involvement of CD20 + B lymphoid malignancies are warranted. Am. J. Hematol. 91:486-491, 2016. © 2016 Wiley Periodicals, Inc. PMID:26872652

  11. High conservation level of CD8(+) T cell immunogenic regions within an unusual H1N2 human influenza variant.

    PubMed

    Komadina, Naomi; Quiñones-Parra, Sergio M; Kedzierska, Katherine; McCaw, James M; Kelso, Anne; Leder, Karin; McVernon, Jodie

    2016-10-01

    Current seasonal influenza vaccines require regular updates due to antigenic drift causing loss of effectiveness and therefore providing little or no protection against novel influenza A subtypes. Next generation vaccines capable of eliciting CD8(+) T cell (CTL) mediated cross-protective immunity may offer a long-term alternative strategy. However, measuring pre- and existing levels of CTL cross-protection in humans is confounded by differences in infection histories across individuals. During 2000-2003, H1N2 viruses circulated persistently in the human population for the first time and we hypothesized that the viral nucleoprotein (NP) contained novel CTL epitopes that may have contributed to the survival of the viruses. This study describes the immunogenic NP peptides of H1N1, H2N2, and H3N2 influenza viruses isolated from humans over the past century, 1918-2003, by comparing this historical dataset to reference NP peptides from H1N2 that circulated in humans during 2000-2003. Observed peptides sequences ranged from highly conserved (15%) to highly variable (12%), with variation unrelated to reported immunodominance. No unique NP peptides which were exclusive to the H1N2 viruses were noted. However, the virus had inherited the NP from a recently emerged H3N2 variant containing novel peptides, which may have assisted its persistence. Any advantage due to this novelty was subsequently lost with emergence of a newer H3N2 variant in 2003. Our approach has potential to provide insight into the population context in which influenza viruses emerge, and may help to inform immunogenic peptide selection for CTL-inducing influenza vaccines. J. Med. Virol. 88:1725-1732, 2016. © 2016 Wiley Periodicals, Inc. PMID:26950895

  12. The entry-level occupational therapy clinical doctorate: advantages, challenges, and international issues to consider.

    PubMed

    Brown, Ted; Crabtree, Jeffrey L; Mu, Keli; Wells, Joe

    2015-04-01

    Internationally, occupational therapy education has gone through several paradigm shifts during the last few decades, moving from certificate to diploma to bachelors to masters and now in some instances to clinical doctorate as the entry-level professional credential to practice. In the United States there is a recommendation under consideration by the American Occupational Therapy Association (AOTA) that by 2025, all occupational therapy university programs will move to the clinical doctorate level. It should be noted, however, that the AOTA Board can only make recommendations and it is the Accreditation Council for Occupational Therapy Education (ACOTE) who has regulatory authority to approve such a change. What are the potential implications for the profession, our clients, and funders of occupational therapy services? What are the primary drivers for the move towards the clinical doctorate being the educational entry point? Is the next step in the evolution of occupational therapy education globally a shift to the entry-level clinical doctorate? This article reviews current literature and discusses issues about the occupational therapy entry-level clinical doctorate. The published evidence available about the occupational therapy entry-level clinical doctorate is summarized and the perceived or frequently cited pros and cons of moving to the clinical doctorate as the singular entry point to occupational therapy practice are considered. The potential impacts of the introduction of the clinical doctorate as the entry-to-practice qualification across the United States on the occupational therapy community internationally will be briefly discussed. If the United States moves toward the entry-level clinical doctorate as the only educational starting point for the profession, will other jurisdictions follow suit? Further discourse and investigation of this issue both inside and outside of the United States is needed so that informed decisions can be made. PMID

  13. Internal and external forcing of sea level variability in the Black Sea

    NASA Astrophysics Data System (ADS)

    Volkov, Denis L.; Landerer, Felix W.

    2015-11-01

    The variability of sea level in the Black Sea is forced by a combination of internal and external processes of atmospheric, oceanic, and terrestrial origin. We use a combination of satellite altimetry and gravity, tide gauge, river discharge, and atmospheric re-analysis data to provide a comprehensive up-to-date analysis of sea level variability in the Black Sea and to quantify the role of different environmental factors that force the variability. The Black Sea is part of a large-scale climatic system that includes the Mediterranean and the North Atlantic. The seasonal sea level budget shows similar contributions of fresh water fluxes (precipitation, evaporation, and river discharge) and the Black Sea outflow, while the impact of the net surface heat flux is smaller although not negligible. We find that the nonseasonal sea level time series in the Black and Aegean seas are significantly correlated, the latter leading by 1 month. This lag is attributed to the adjustment of sea level in the Black Sea to externally forced changes of sea level in the Aegean Sea and to the impact of river discharge. The nonseasonal sea level budget in the Black Sea is dominated by precipitation and evaporation over the sea itself, but external processes such as river discharge and changes in the outflow can also cause some large synoptic-scale sea level anomalies. Sea level is strongly coupled to terrestrial water storage over the Black Sea drainage basin, which is modulated by the North Atlantic Oscillation (NAO). We show that during the low/high NAO southwesterly/northeasterly winds near the Strait of Gibraltar and southerly/northerly winds over the Aegean Sea are able to dynamically increase/decrease sea level in the Mediterranean and Black seas, respectively.

  14. Development of an immune function assay by measuring intracellular adenosine triphosphate (iATP) levels in mitogen-stimulated CD4+ T lymphocytes.

    PubMed

    Naderi, Hadi; Najafi, Alireza; Khoshroo, Mohammad; Tajik, Nader

    2016-01-01

    We developed an immune function assay for monitoring CD4+ T cells activity based on changes in intracellular adenosine triphosphate (iATP) levels after phytohemagglutinin (PHA) stimulation. Blood samples were obtained from 40 healthy subjects and 30 RTRs and incubated with 5 µg/mL of PHA for 15-18 hr at 37°C and 5% CO2. Afterward, the CD4+ T cells were separated by antibody-coated magnetic beads and lysed. Then, iATP content in unstimulated and stimulated conditions was measured by luciferin-luciferase reaction using a log-log standard curve. The iATP levels showed significant increase in CD4+ T cells in both healthy persons (mean: 550 ± 142 ng/mL vs. 109 ± 54 ng/mL) and RTRs (mean: 394 ± 160 ng/mL vs. 52 ± 37 ng/mL) after PHA stimulation (P < 0.001). However, the iATP production in RTRs was significantly lower than that in healthy individuals; both prior to and after stimulation with PHA (P < 0.001). No gender-specific difference in iATP production was observed between women and men subjects. This rapid and low-cost assay reflects the degree of immune cell function through assessment of CD4+ T cells activation. Thus, it can be used for evaluation of immune system status in immunodeficient individuals as well as in immunosuppressed transplant recipients who needs drug adjustment. PMID:27089103

  15. Theoretical Analysis of Effects of Deep Level, Back Contact, and Absorber Thickness on Capacitance-Voltage Profiling of CdTe Thin-Film Solar Cells

    SciTech Connect

    Li, J. V.; Halverson, A. F.; Sulima, O. V.; Bansal, S.; Burst, J. M.; Barnes, T. M.; Gessert, T. A.; Levi, D. H.

    2012-05-01

    The apparent carrier density profile measured by the capacitance-voltage technique in CdTe thin-film solar cells frequently displays a distinctive U-shape. We show that, even assuming a uniform carrier density, such a U-shape may arise from deep levels, a non-ohmic back-contact, and a thin absorber, which are commonly present in practical CdTe thin-film solar cells. A thin CdTe absorber contributes to the right branch of the U-shape due to a punch-through effect at reverse or zero biases, when the CdTe absorber is nearly fully depleted. A rectifying back-contact contributes to both branches of the U-shape due to voltage sharing with the front junction under a forward bias and early punch-through under a reverse bias. Deep levels contribute to the right branch, but also raise the bottom of the U-shape, leading to an overestimate of carrier density.

  16. Toxic metal (Pb, Cd, Cr, and Hg) levels in Rapana venosa (Valenciennes, 1846), Eriphia verrucosa (Forskal, 1775), and sediment samples from the Black Sea littoral (Thrace, Turkey).

    PubMed

    Mülayim, A; Balkıs, H

    2015-06-15

    Rapana venosa (Valenciennes, 1846) and Eriphia verrucosa (Forskal, 1775) are the dominant benthic invertebrate species along the Thrace Coast of the western Black Sea. The aim of this study was to determine toxic metal (Hg, Cr, Cd, and Pb) accumulation levels in these species, as well as within littoral sediments from this area. Our results showed that all of the metals, except for Cd, were below that in average shale. The measured accumulation levels were mostly within the range of what is naturally found within the earth's crust. However, some study stations did have increased concentrations, indicating anthropogenic pollution in these areas. The Cd contents of E. verrucosa collected from all our study stations were well above the limits set by the Turkish Food Codex, especially in Kıyıköy, whereas Pb content was close to the limit at all stations and exceeded the limit in Kıyıköy, but Hg content was below the limit at all stations. Cd content of R. venosa exceeded the limit only in Kumköy. Pb content was below the limit, and Hg was at or slightly above the limit at all stations. PMID:25913797

  17. A Threshold Level of Intratumor CD8+ T-cell PD1 Expression Dictates Therapeutic Response to Anti-PD1.

    PubMed

    Ngiow, Shin Foong; Young, Arabella; Jacquelot, Nicolas; Yamazaki, Takahiro; Enot, David; Zitvogel, Laurence; Smyth, Mark J

    2015-09-15

    Despite successes, thus far, a significant proportion of the patients treated with anti-PD1 antibodies have failed to respond. We use mouse tumor models of anti-PD1 sensitivity and resistance and flow cytometry to assess tumor-infiltrating immune cells immediately after therapy. We demonstrate that the expression levels of T-cell PD1 (PD1(lo)), myeloid, and T-cell PDL1 (PDL1(hi)) in the tumor microenvironment inversely correlate and dictate the efficacy of anti-PD1 mAb and function of intratumor CD8(+) T cells. In sensitive tumors, we reveal a threshold for PD1 downregulation on tumor-infiltrating CD8(+) T cells below which the release of adaptive immune resistance is achieved. In contrast, PD1(hi) T cells in resistant tumors fail to be rescued by anti-PD1 therapy and remain dysfunctional unless intratumor PDL1(lo) immune cells are targeted. Intratumor Tregs are partly responsible for the development of anti-PD1-resistant tumors and PD1(hi) CD8(+) T cells. Our analyses provide a framework to interrogate intratumor CD8(+) T-cell PD1 and immune PDL1 levels and response in human cancer. PMID:26208901

  18. CD4(+)CD25 (+)CD127 (low/-) T cells: a more specific Treg population in human peripheral blood.

    PubMed

    Yu, Ning; Li, Xiaomei; Song, Weiya; Li, Dongmei; Yu, Daliang; Zeng, Xiaofeng; Li, Mengtao; Leng, Xiaomei; Li, Xiangpei

    2012-12-01

    The quantitative identification and enrichment of viable regulatory T cells (Treg) requires reliable surface markers that are selectively expressed on Treg. Foxp3 is the accepted marker of nTreg, but it cannot be used to isolate cells for functional studies. In this study, we compared four staining profiles of Treg, including CD4(+)CD25(high) T cells, CD4(+)CD39(+) T cells, CD4(+)CD73(+) T cells, and CD4(+)CD25(+)CD127(low/-) T cells. We found that CD4(+)CD25(+)CD127(low/-) T cells expressed the highest level of Foxp3 and had the strongest correlation with CD4(+)CD25(+)Foxp3(+) T cells, the accepted identifying characteristics for "real" nTreg cells. Moreover, functional data showed that CD4(+)CD25(+)CD127(low/-) T cells could effectively suppress the proliferation of CD4(+)CD25(-) T cells, suggesting that compared with the other three populations, CD4(+)CD25(+)CD127(low/-) T cells best fit the definition of naturally occurring regulatory T cells in human peripheral blood. Finally, we showed that CD4(+)CD25(+)CD127(low/-) can be used to quantitate Treg cells in individuals with systemic lupus erythematosus supporting the use of CD4(+)CD25(+)CD127(low/-) to identify human Treg cells. PMID:22752562

  19. Antibody Response to Achromobacter xylosoxidans during HIV Infection Is Associated with Lower CD4 Levels and Increased Lymphocyte Activation

    PubMed Central

    Purnajo, Intan; Richman, Douglas D.; Smith, Davey M.; Gianella, Sara

    2014-01-01

    Inflammation during HIV infection is associated with worse disease outcomes and progression. Many mechanisms have been indicted, including HIV itself, coinfections, and gut microbial translocation. Concerning microbial translocation, we hypothesized that adaptive immune responses to a specific bacterial species known to be present in gut-associated lymphoid tissue are higher among HIV-infected individuals than among HIV-uninfected controls and are associated with T cell activation and lower CD4 T cell counts. By characterizing the IgG response to Achromobacter xylosoxidans, we found that HIV-infected participants who were immunoresponsive (n = 48) had significantly lower CD4 percentages (P = 0.01), greater CD4 activation (percentages of RA− CD38+) (P = 0.03), and higher soluble CD14 (P = 0.01). HIV-positive individuals had higher anti-A. xylosoxidans IgG titers than HIV-uninfected individuals (P = 0.04). The results suggest an abnormal adaptive immune activation to gut microflora during HIV infection. PMID:24173027

  20. Schistosoma haematobium Infection and CD4+ T-Cell Levels: A Cross-Sectional Study of Young South African Women

    PubMed Central

    Galaphaththi-Arachchige, Hashini Nilushika; Holmen, Sigve D.; Lillebø, Kristine; Onsrud, Mathias; Gundersen, Svein Gunnar; Taylor, Myra; Ndhlovu, Patricia; Kjetland, Eyrun F.

    2015-01-01

    Schistosoma (S.) haematobium causes urogenital schistosomiasis and has been hypothesized to adversely impact HIV transmission and progression. On the other hand it has been hypothesized that HIV could influence the manifestations of schistosomiasis. In this cross-sectional study, we explored the association between urogenital S. haematobium infection and CD4 cell counts in 792 female high-school students from randomly selected schools in rural KwaZulu-Natal, South Africa. We also investigated the association between low CD4 cell counts in HIV positive women and the number of excreted schistosome eggs in urine. Sixteen percent were HIV positive and 31% had signs of urogenital schistosomiasis (as determined by genital sandy patches and / or abnormal blood vessels on ectocervix / vagina by colposcopy or presence of eggs in urine). After stratifying for HIV status, participants with and without urogenital schistosomiasis had similar CD4 cell counts. Furthermore, there was no significant difference in prevalence of urogenital schistosomiasis in HIV positive women with low and high CD4 cell counts. There was no significant difference in the number of eggs excreted in urine when comparing HIV positive and HIV negative women. Our findings indicate that urogenital schistosomiasis do not influence the number of circulating CD4 cells. PMID:25768005

  1. An evaluation of internal event level 1 PRA methods used in NUREG-1150

    SciTech Connect

    Camp, A.L.; Cramond, W.R.

    1989-01-01

    As part of the effort to support NUREG-1150, Sandia National Laboratories and its subcontractors have developed innovative techniques for efficiently performing internal event Level I probabilistic risk assessments. This methodology is one of the alternatives for industry to use in performing individual plant evaluations in the future. While this new methodology was very successful, there are some areas where improvements can be made. This paper evaluates the strengths and weaknesses of the methodology and makes some important recommendations for modifications in order to provide insights to future users. 10 refs.

  2. Internal self-ordering in In(Sb,As), (In,Ga)Sb, and (Cd,Zn,Mn)Se nano-agglomerates/quantum dots

    SciTech Connect

    Moeck, P.; Topuria, T.; Browning, N. D.; Booker, G. R.; Mason, N. J.; Nicholas, R. J.; Dobrowolska, M.; Lee, S.; Furdyna, J. K.

    2001-08-13

    Nano-agglomerates of In(Sb,As) in InAs, (In,Ga)Sb in GaSb, and (Cd,Zn,Mn)Se in (Zn,Mn)Se are classified by transmission electron microscopy. In scanning transmission electron microscopy, atomic resolution Z-contrast images reveal different modes of internal compositional modulation on the atomic length scale, resulting for all three material systems in nano-agglomerates of an appropriate size that may constitute a new type of quantum dot. For other nano-agglomerates of In(Sb,As) in InAs and (In,Ga)Sb in GaSb, we observed a second type of nanoscale ordering that results in nano-agglomerates with an internal compositional modulation on a length scale of a few nm. Both types of compositional modulation are discussed as having arisen from a rather long-term structural response to a combination of internal and external strains. {copyright} 2001 American Institute of Physics.

  3. The limits of levels: Understanding the International Adult Literacy Surveys (IALS)

    NASA Astrophysics Data System (ADS)

    St. Clair, Ralf

    2012-12-01

    The International Adult Literacy Survey (IALS), an initiative of the Organization for Economic Cooperation and Development (OECD), was carried out in the early to mid-1990s across more than 20 countries. It was followed in the early years of the 21st century by the Adult Literacy and Life Skills (ALL) survey and the Programme for the International Assessment of Adult Competencies (PIAAC, currently in data analysis). This article reviews the philosophical basis, theoretical underpinnings and data analysis of the original and subsequent IALS-based surveys. The purpose is to inform users of the survey data of what the surveys can, and cannot, provide. The author argues that the key use of these surveys is providing insights into population-level distribution of one form of literacy, namely a particular kind of text consumption in a developed society. He also points out the challenges regarding the use of the survey series for making international comparisons, for documenting change over time and for representing broad models of literacy. The tendency to use the survey findings for these uses is considered by the author as a misuse of the data, which leaves the potential of the IALS surveys to provide insights into the effectiveness and equity of different educational systems largely untapped.

  4. Downregulation effects of beta-elemene on the levels of plasma endotoxin, serum TNF-alpha, and hepatic CD14 expression in rats with liver fibrosis.

    PubMed

    Liu, Jianguo; Zhang, Zhe; Gao, Jiechang; Xie, Jiwen; Yang, Lin; Hu, Shenjun

    2011-03-01

    It has been demonstrated that β-elemene could protect against carbon tetrachloride (CCl(4))-induced liver fibrosis in our laboratory work, and the aim of this paper is to reveal the protective mechanisms of β-elemene. The hepatic fibrosis experimental model was induced by the hypodermical injection of CCl(4) in Wistar male rats. β-elemene was intraperitoneally administered into rats for 8 weeks (0.1 mL/100 g bodyweight per day), and plasma endotoxin content was assayed by biochemistry. The serum TNF-α level was detected using radioactive immunity. CD14 expression in rat livers was measured by immunohistochemistry and Western blot. The results showed that β-elemene can downregulate the levels of plasma endotoxins, serum TNF-α, and hepatic CD14 expression in rats with liver fibrosis. β-elemene plays an important role in downregulating the lipopolysaccharide signal transduction pathway, a significant pathway in hepatic fibrosis development. PMID:21681682

  5. A study to establish international diagnostic reference levels for paediatric computed tomography.

    PubMed

    Vassileva, J; Rehani, M; Kostova-Lefterova, D; Al-Naemi, H M; Al Suwaidi, J S; Arandjic, D; Bashier, E H O; Kodlulovich Renha, S; El-Nachef, L; Aguilar, J G; Gershan, V; Gershkevitsh, E; Gruppetta, E; Hustuc, A; Jauhari, A; Kharita, Mohammad Hassan; Khelassi-Toutaoui, N; Khosravi, H R; Khoury, H; Kralik, I; Mahere, S; Mazuoliene, J; Mora, P; Muhogora, W; Muthuvelu, P; Nikodemova, D; Novak, L; Pallewatte, A; Pekarovič, D; Shaaban, M; Shelly, E; Stepanyan, K; Thelsy, N; Visrutaratna, P; Zaman, A

    2015-07-01

    The article reports results from the largest international dose survey in paediatric computed tomography (CT) in 32 countries and proposes international diagnostic reference levels (DRLs) in terms of computed tomography dose index (CTDI vol) and dose length product (DLP). It also assesses whether mean or median values of individual facilities should be used. A total of 6115 individual patient data were recorded among four age groups: <1 y, >1-5 y, >5-10 y and >10-15 y. CTDIw, CTDI vol and DLP from the CT console were recorded in dedicated forms together with patient data and technical parameters. Statistical analysis was performed, and international DRLs were established at rounded 75th percentile values of distribution of median values from all CT facilities. The study presents evidence in favour of using median rather than mean of patient dose indices as the representative of typical local dose in a facility, and for establishing DRLs as third quartile of median values. International DRLs were established for paediatric CT examinations for routine head, chest and abdomen in the four age groups. DRLs for CTDI vol are similar to the reference values from other published reports, with some differences for chest and abdomen CT. Higher variations were observed between DLP values, based on a survey of whole multi-phase exams. It may be noted that other studies in literature were based on single phase only. DRLs reported in this article can be used in countries without sufficient medical physics support to identify non-optimised practice. Recommendations to improve the accuracy and importance of future surveys are provided. PMID:25836685

  6. Examining the Dynamic Structure of Daily Internalizing and Externalizing Behavior at Multiple Levels of Analysis

    PubMed Central

    Wright, Aidan G. C.; Beltz, Adriene M.; Gates, Kathleen M.; Molenaar, Peter C. M.; Simms, Leonard J.

    2015-01-01

    Psychiatric diagnostic covariation suggests that the underlying structure of psychopathology is not one of circumscribed disorders. Quantitative modeling of individual differences in diagnostic patterns has uncovered several broad domains of mental disorder liability, of which the Internalizing and Externalizing spectra have garnered the greatest support. These dimensions have generally been estimated from lifetime or past-year comorbidity patters, which are distal from the covariation of symptoms and maladaptive behavior that ebb and flow in daily life. In this study, structural models are applied to daily diary data (Median = 94 days) of maladaptive behaviors collected from a sample (N = 101) of individuals diagnosed with personality disorders (PDs). Using multilevel and unified structural equation modeling, between-person, within-person, and person-specific structures were estimated from 16 behaviors that are encompassed by the Internalizing and Externalizing spectra. At the between-person level (i.e., individual differences in average endorsement across days) we found support for a two-factor Internalizing–Externalizing model, which exhibits significant associations with corresponding diagnostic spectra. At the within-person level (i.e., dynamic covariation among daily behavior pooled across individuals) we found support for a more differentiated, four-factor, Negative Affect-Detachment-Hostility-Disinhibition structure. Finally, we demonstrate that the person-specific structures of associations between these four domains are highly idiosyncratic. PMID:26732546

  7. International Olympic Committee consensus statement on thermoregulatory and altitude challenges for high-level athletes.

    PubMed

    Bergeron, M F; Bahr, R; Bärtsch, P; Bourdon, L; Calbet, J A L; Carlsen, K H; Castagna, O; González-Alonso, J; Lundby, C; Maughan, R J; Millet, G; Mountjoy, M; Racinais, S; Rasmussen, P; Singh, D G; Subudhi, A W; Young, A J; Soligard, T; Engebretsen, L

    2012-09-01

    Challenging environmental conditions, including heat and humidity, cold, and altitude, pose particular risks to the health of Olympic and other high-level athletes. As a further commitment to athlete safety, the International Olympic Committee (IOC) Medical Commission convened a panel of experts to review the scientific evidence base, reach consensus, and underscore practical safety guidelines and new research priorities regarding the unique environmental challenges Olympic and other international-level athletes face. For non-aquatic events, external thermal load is dependent on ambient temperature, humidity, wind speed and solar radiation, while clothing and protective gear can measurably increase thermal strain and prompt premature fatigue. In swimmers, body heat loss is the direct result of convection at a rate that is proportional to the effective water velocity around the swimmer and the temperature difference between the skin and the water. Other cold exposure and conditions, such as during Alpine skiing, biathlon and other sliding sports, facilitate body heat transfer to the environment, potentially leading to hypothermia and/or frostbite; although metabolic heat production during these activities usually increases well above the rate of body heat loss, and protective clothing and limited exposure time in certain events reduces these clinical risks as well. Most athletic events are held at altitudes that pose little to no health risks; and training exposures are typically brief and well-tolerated. While these and other environment-related threats to performance and safety can be lessened or averted by implementing a variety of individual and event preventative measures, more research and evidence-based guidelines and recommendations are needed. In the mean time, the IOC Medical Commission and International Sport Federations have implemented new guidelines and taken additional steps to mitigate risk even further. PMID:22685119

  8. Strong mucosal immune responses in SIV infected macaques contribute to viral control and preserved CD4+ T-cell levels in blood and mucosal tissues

    PubMed Central

    2011-01-01

    Background Since there is still no protective HIV vaccine available, better insights into immune mechanism of persons effectively controlling HIV replication in the absence of any therapy should contribute to improve further vaccine designs. However, little is known about the mucosal immune response of this small unique group of patients. Using the SIV-macaque-model for AIDS, we had the rare opportunity to analyze 14 SIV-infected rhesus macaques durably controlling viral replication (controllers). We investigated the virological and immunological profile of blood and three different mucosal tissues and compared their data to those of uninfected and animals progressing to AIDS-like disease (progressors). Results Lymphocytes from blood, bronchoalveolar lavage (BAL), and duodenal and colonic biopsies were phenotypically characterized by polychromatic flow cytometry. In controllers, we observed higher levels of CD4+, CD4+CCR5+ and Gag-specific CD8+ T-cells as well as lower immune activation in blood and all mucosal sites compared to progressors. However, we could also demonstrate that immunological changes are distinct between these three mucosal sites. Intracellular cytokine staining demonstrated a significantly higher systemic and mucosal CD8+ Gag-specific cellular immune response in controllers than in progressors. Most remarkable was the polyfunctional cytokine profile of CD8+ lymphocytes in BAL of controllers, which significantly dominated over their blood response. The overall suppression of viral replication in the controllers was confirmed by almost no detectable viral RNA in blood and all mucosal tissues investigated. Conclusion A strong and complex virus-specific CD8+ T-cell response in blood and especially in mucosal tissue of SIV-infected macaques was associated with low immune activation and an efficient suppression of viral replication. This likely afforded a repopulation of CD4+ T-cells in different mucosal compartments to almost normal levels. We

  9. Metal uptake of tomato and alfalfa plants as affected by water source, salinity, and Cd and Zn levels under greenhouse conditions.

    PubMed

    Gharaibeh, Mamoun A; Marschner, Bernd; Heinze, Stefanie

    2015-12-01

    Irrigation with wastewater is a promising option to improve crop yields and to reduce pressure on freshwater sources. However, heavy metal concentrations in wastewater may cause health concerns. A greenhouse pot experiment was conducted in order to determine cadmium (Cd) and zinc (Zn) concentrations in sandy soil and plant tissues of tomato (Lycopersicon esculentum L.) and alfalfa (Medicago sativa L.). A 2 × 2 × 4 × 2 factorial treatment arrangement was utilized. Two water sources, fresh (FW) or treated wastewater (TWW), at two salinity levels (1 and 3 dS m(-1)) containing different levels of Cd and Zn were used. Samples were collected after a 90-day growth period. It was observed that the growth of both plants was depressed at the highest metal level (L3). Metal accumulation in plant parts increased with the increase of metal concentration and salinity in irrigation water. At low salinity, water source was the main factor which controlled metal accumulation, whereas, at high salinity, chloride appeared to be the principal factor controlling metal uptake regardless of water source. Metal translocation from roots to shoots increased in TWW-irrigated plants, even in the controls. Tomatoes accumulated Cd up to and above critical levels safe for human consumption, even though Cd concentration in irrigation water did not exceed the current recommended values. Therefore, food production in sandy soils may well pose a health hazard when irrigated with TWW containing heavy metals. Complexation with dissolved organic compounds (DOC) in TWW may be to be the principal factor responsible for increased metal uptake and transfer at low salinity, thereby increasing the risk of heavy metal contamination of food and forage crops. PMID:26206131

  10. Energy Band Gap, Intrinsic Carrier Concentration and Fermi Level of CdTe Bulk Crystal between 304 K and 1067 K

    NASA Technical Reports Server (NTRS)

    Su, Ching-Hua

    2007-01-01

    Optical transmission measurements were performed on CdTe bulk single crystal. It was found that when a sliced and polished CdTe wafer was used, a white film started to develop when the sample was heated above 530 K and the sample became opaque. Therefore, a bulk crystal of CdTe was first grown in the window area by physical vapor transport; the optical transmission was then measured and from which the energy band gap was derived between 304 and 1067 K. The band gaps of CdTe can be fit well as a function of temperature using the Varshini expression: Eg (e V) = 1.5860 - 5.9117xl0(exp -4) T(sup 2)/(T + 160). Using the band gap data, the high temperature electron-hole equilibrium was calculated numerically by assuming the Kane's conduction band structure and a heavy-hole parabolic valance band. The calculated intrinsic carrier concentrations agree well with the experimental data reported previously. The calculated intrinsic Fermi levels between 270 and 1200 K were also presented.

  11. Low dietary levels of Al, Pb and Cd may affect the non-enzymatic antioxidant capacity in caged honey bees (Apis mellifera).

    PubMed

    Gauthier, Maxime; Aras, Philippe; Jumarie, Catherine; Boily, Monique

    2016-02-01

    Several hypotheses have been proposed to explain the abnormally high mortality rate observed in bee populations in Europe and North America. While studies based on the effects of pesticides are paramount, the metals present in agroecosystems are often overlooked. Sources of metals are linked to the nature of soils and to agricultural practices, namely the use of natural or chemical nutrients as well as residual materials from waste-water treatment sludge. The aim of this study was to investigate the effects of metals on honey bees exposed for 10 days to environmentally realistic concentrations of Al, Pb and Cd (dissolved in syrup). The monitoring of syrup consumption combined with the quantification of metals in bees revealed the following order for metal bioconcentration ratios: Cd > Pb > Al. Alpha-tocopherol, metallothionein-like proteins (MTLPs) and lipid peroxidation were quantified. When bees were exposed to increasing amounts of Cd, a marked augmentation of MTLPs levels was found. Lead (Pb) and Cd caused an increase in α-tocopherol content, while alteration of lipid peroxidation was observed only with Al exposure. These findings raise concerns about the bioavailability and the additional threat posed by metals for pollinators in agricultural areas while providing new insights for potential use of the honey bee as a sentinel species for metal exposure. PMID:26421624

  12. Hydroquinone, a reactive metabolite of benzene, enhances interleukin-4 production in CD4+ T cells and increases immunoglobulin E levels in antigen-primed mice

    PubMed Central

    Lee, M H; Chung, S W; Kang, B Y; Kim, K-M; Kim, T S

    2002-01-01

    Exposure to cigarette smoke is known to increase the risk of the development of allergic disease. The mechanism is not well understood. In this study, we determined the effect of hydroquinone (HQ), a major metabolite of benzene present in large quantities in cigarette tar, on interleukin-4 (IL-4) production by CD4+ T cells. HQ significantly enhanced IL-4 production by keyhole limpet haemocyanin (KLH)-primed CD4+ T cells in a dose-dependent manner. The enhancing effect of HQ on IL-4 production was maximal at a concentration of 50 µm. It increased the level of IL-4 production approximately 10-fold. HQ enhanced IL-4 mRNA expression and also IL-4 gene promoter activity, suggesting that the enhancing effect of HQ on IL-4 production may occur at the transcriptional level. Furthermore, the injection of KLH-primed mice with HQ resulted in a significant increase in the levels of IL-4 and immunoglobulin E. These findings provide evidence that HQ, a major component of cigarette tar, may enhance allergic immune responses by inducing the production of IL-4 in CD4+ T cells. PMID:12153512

  13. Prediction of noise levels and annoyance from aircraft run-ups at Vancouver International Airport.

    PubMed

    Scherebnyj, Katrina; Hodgson, Murray

    2007-10-01

    Annoyance complaints resulting from engine run-ups have been increasing at Vancouver International Airport for several years. To assist the Airport in managing run-up noise levels, a prediction tool based on a Green's function parabolic equation (GFPE) model has been consolidated, evaluated, and applied. It was extended to include more realistic atmospheric and ground input parameters. Measurements were made of the noise-radiation characteristics of a CRJ200 jet aircraft. The GFPE model was validated by comparing predictions with results in the literature. A sensitivity analysis showed that predicted levels are relatively insensitive to small variations in geometry and ground impedance, but relatively sensitive to variations in wind speed, atmosphere type, and aircraft heading and power setting. Predicted noise levels were compared with levels measured at noise monitoring terminals. For the four cases for which all input information was available, agreement was within 10 dBA. For events for which some information had to be estimated, predictions were within 20 dBA. The predicted annoyance corresponding to the run-up events considered ranged from 1.8% to 9.5% of people awoken, suggesting that noise complaints can be expected. PMID:17902830

  14. CD3+CD8+CD161high Tc17 cells are depleted in HIV-infection.

    PubMed

    Gaardbo, Julie Christine; Hartling, Hans Jakob; Thorsteinsson, Kristina; Ullum, Henrik; Nielsen, Susanne Dam

    2013-02-20

    CD8 Tc17 cells with pro-inflammatory properties have only recently been acknowledged, and Tc17 cells in HIV-infection are not described. CD3CD8CD161 Tc17 cells and the production of interleukin (IL)-17 were examined in untreated and treated HIV-infected patients, HIV-hepatitis C virus co-infected patients, and healthy controls. Depletion of CD3CD8CD161 Tc17 cells and diminished production of IL-17 in HIV-infected patients were found. The level of Tc17 cells was associated with the CD4 cell count in treated patients. PMID:23135168

  15. Metal-induced stress in bivalves living along a gradient of Cd contamination: relating sub-cellular metal distribution to population-level responses.

    PubMed

    Perceval, Olivier; Couillard, Yves; Pinel-Alloul, Bernadette; Giguère, Anik; Campbell, Peter G C

    2004-09-20

    The use of biomarkers to assess the impacts of contaminants on aquatic ecosystems has noticeably increased over the past few years. Few of these studies, however, have contributed to the prediction of ecologically significant effects (i.e., at the population or community levels). The present field study was designed to evaluate the potential of metallothionein (MT) and sub-cellular metal partitioning measurements for predicting toxic effects at higher levels of the biological organization in freshwater bivalves (Pyganodon grandis) chronically exposed to Cd. For that purpose, we quantitatively sampled P. grandis populations in the littoral zone of nine lakes on the Precambrian Canadian Shield during two consecutive summers (1998 and 1999); lakes were characterized by contrasting Cd levels but similar trophic status. We tested relationships between the population status of P. grandis (i.e., growth parameters, density, biomass, secondary production, turnover ratio and cumulative fecundity) and (i) ambient Cd concentrations, (ii) sub-organismal responses (MT concentrations in the gill cytosol of individuals and Cd concentrations in three metal-ligand pools identified as M-HMW, the high molecular weight pool, M-MT, the metallothionein-like pool and M-LMW, the low molecular weight pool) and (iii) ecological confounding factors (food resources, presence of host fishes for the obligatory parasitic larval stage of P. grandis). Our results show that littoral density, live weight, dry viscera biomass, production and cumulative fecundity decreased with increasing concentrations of the free-cadmium ion in the environment (Pearson's r ranging from -0.63 to -0.78). On the other hand, theoretical maximum shell lengths (L( infinity )) in our populations were related to both the dissolved Ca concentration and food quality (sestonic C and N concentrations). Overall, Cd concentrations in the gill cytosolic HMW pool of the individual molluscs were the biomarker response that was most

  16. Identification and Characterization of CD44RC, a Novel Alternatively Spliced Soluble CD44 Isoform that can Potentiate the Hyaluronan Binding Activity of Cell Surface CD44

    PubMed Central

    Chiu, Roland K; Carpenito, Carmine; Dougherty, Shona T; Hayes, Gregory M; Dougherty, Graeme J

    1999-01-01

    Abstract Soluble CD44 proteins generated by proteolytic cleavage or aberrant intron retention have been shown to antagonize the ligand binding activity of the corresponding cell surface receptor, inducing apoptosis and inhibiting tumor growth. Interestingly, such findings appear to contradict recent studies demonstrating a correlation between the presence of high levels of soluble CD44 in the serum of cancer patients and poor prognosis. In the present study, we report the cloning of a novel, naturally occurring, differentially expressed, soluble CD44 isoform, designated CD44RC, which, in contrast to previously described soluble CD44 proteins, can dramatically enhance the hyaluronan binding activity of cell surface CD44. Sequence analysis suggests that CD44RC is generated by an alternative splicing event in which the 3′ end of CD44 exon 2 is spliced into an internal splice acceptor site present within exon 18, altering reading frame and giving rise to a soluble protein with a unique COOH terminus. Functional studies suggest that CD44RC enhances hyaluronan binding by adhering to chondroitin sulfate side-chains attached to cell surface CD44, generating a multivalent complex with increased avidity for hyaluronan. PMID:10933060

  17. Two-Year Follow-up Study of Mycobacterium tuberculosis Antigen-Driven IFN-γ Responses and Macrophage sCD14 Levels After Tuberculosis Contact.

    PubMed

    Druszczynska, Magdalena; Wlodarczyk, Marcin; Kielnierowski, Grzegorz; Kawka, Malwina; Rudnicka, Wieslawa

    2016-06-01

    Clinical data regarding the prediction of active tuberculosis (TB) development in close TB contacts are scarce. To address this problem, we performed a 2-year follow-up study of Mycobacterium tuberculosis (M.tb) antigen-driven IFN-gamma responses and serum levels of soluble macrophage CD14 receptor in individuals with recent or prolonged M.tb exposure. Between June 2011 and June 2013, we studied 60 healthy Polish adults with recent household or long-term work TB contact and individuals without known M.tb exposure. All of them underwent baseline and repeated testing with IGRA (IFN-gamma release assay) and serum sCD14 ELISA quantification. Frequencies of IGRA results differed at the baseline and follow-up testing. IGRA reversions were noticed in almost one-third of Work TB Contacts and no participants from the Household TB Contact group. IGRA conversions were found in 40 % of Household TB Contacts. No correlation between the IGRA result and the sCD14 level was observed. IFN-γ variability has important implications for clinical practice and requires caution in interpreting the results to distinguish new infections from nonspecific inter-individual variations in cytokine responses. The impairment of IFN-γ response in some individuals with prolonged M.tb exposure representing a resistant immune status does not allow considering IGRA results as reliable and credible. Monitoring the serum sCD14 level can reduce the likelihood of a false prediction of active TB development in close TB contacts showing an M.tb-specific increase in the IFN-gamma production in repeated IGRA testing. PMID:27570313

  18. A distinct population of nonphagocytic and low level CD4+ null lymphocytes produce IFN-alpha after stimulation by herpes simplex virus-infected cells

    SciTech Connect

    Sandberg, K.; Matsson, P.; Alm, G.V. )

    1990-08-01

    Human PBMC were stimulated for 6 h in vitro by HSV or Sendai virus (SV) and analyzed by flow cytometry. IFN-alpha producing cells (IPC) were identified through their content of IFN-alpha mRNA by in situ hybridization using a 35S-labeled IFN-alpha 2 cRNA probe. The IPC induced by HSV-infected WISH cells lacked capacity to adhere to and phagocytose latex particles. The induction of IFN-alpha by free infectious SV occurring in monocytes was abolished by phagocytosis of latex particles present in the cultures during the induction period. Such latex particles actually enhanced the IFN-alpha response induced by glutaraldehyde-fixed HSV- or SV-infected WISH cells or by free intact HSV. The HSV-induced IPC did not express the CD14 Ag expressed on monocytes. Cell sorting was performed on HSV-induced PBMC labeled with phycoerythrin-conjugated anti-CD3 and FITC-conjugated anti-CD4 mAb. A small population consisting of 1.4% of all PBMC, which was CD3- but expressed low but significant levels of CD4, contained the majority of the IPC with a 50-fold increase of their frequency. This cell population had a forward- and right-angle light scatter different from typical monocytes/macrophages. The results therefore further delineate IPC among PBMC into monocytes, being stimulated by viruses such as SV. Another distinct population of infrequent but highly efficient IPC, tentatively designated natural IFN-alpha producing cells, is activated by stimuli such as HSV.

  19. An Examination of Individual Level Factors in Stress and Coping Processes: Perspectives of Chinese International Students in the United States

    ERIC Educational Resources Information Center

    Yan, Kun; Berliner, David C.

    2011-01-01

    No empirical research has focused solely upon understanding the stress and coping processes of Chinese international students in the United States. This qualitative inquiry examines the individual-level variables that affect the stress-coping process of Chinese international students and how they conceptualize and adapt to their stress at an…

  20. Training Level, Acculturation, Role Ambiguity, and Multicultural Discussions in Training and Supervising International Counseling Students in the United States

    ERIC Educational Resources Information Center

    Ng, Kok-Mun; Smith, Shannon D.

    2012-01-01

    This research partially replicated Nilsson and Anderson's "Professional Psychology: Research and Practice" (2004) study on training and supervising international students. It investigated the relationships among international counseling students' training level, acculturation, supervisory working alliance (SWA), counseling self-efficacy (COSE),…

  1. Fractionated neem leaf extract is safe and increases CD4+ cell levels in HIV/AIDS patients.

    PubMed

    Mbah, A U; Udeinya, I J; Shu, E N; Chijioke, C P; Nubila, T; Udeinya, F; Muobuike, Angela; Mmuobieri, Ancila; Obioma, Maria S

    2007-01-01

    The safety and effect of an acetone-water neem leaf extract (IRAB) on CD4 cells was investigated in 60 HIV/AIDS patients as part of an ongoing study to determine the influence of neem on immunity and viral load in HIV/AIDS. Patients were confirmed as HIV I or II positive, as having CD4 cell count, less than 300 cells/microL, and as antiretrovirally naïve. They were given oral IRAB (1.0 g daily for 12 weeks). Clinical and laboratory tests were carried out at baseline and at 4 weekly intervals. Thus, the patients served as their own controls. Sixty patients completed treatment. Fifty (83.33%) were completely compliant with respect to laboratory tests. Increase in mean CD4 cells, 266 cells/microL (159%), for the 50 patients was significant (P < 0.001) between baseline and week 12. Erythrocyte sedimentation rate (64 mm/hr at baseline) was 16 mm/hr at week 12, whereas total number of incidences of HIV/AIDS-related pathologies decreased from 120 at baseline to 5. Mean bodyweight, hemoglobin concentration, and lymphocyte differential count increased significantly by 12% (P < 0.05), 24% (P < 0.0001), and 20% (P < 0.0001), respectively. There were no adverse effects and no abnormalities in kidney and liver function parameters. The results support the safety of IRAB in HIV/AIDS, and its significant influence on CD4 cells may be useful in the formulation of multidrug combination therapies for HIV/AIDS. However, its antiretroviral activity is being evaluated in our laboratory. PMID:17667213

  2. Early deprivation and home basal cortisol levels: a study of internationally adopted children.

    PubMed

    Kertes, Darlene A; Gunnar, Megan R; Madsen, Nicole J; Long, Jeffrey D

    2008-01-01

    Animal studies reveal that early deprivation impairs regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis, potentially increasing vulnerability to stressors throughout life. To examine early deprivation effects on basal HPA axis activity in humans, basal cortisol levels were examined in 164 internationally adopted children who had experienced varying degrees of preadoption deprivation. Duration of institutional care, age at adoption, and parent ratings of preadoption neglect indexed a latent factor of Deprived Care. Adoption measures of height and weight standardized to World Health Organisation norms indexed a latent factor of Growth Delay that was viewed as another reflection of deprivation. Cortisol samples were collected 3.3-11.6 years postadoption (Md = 7.3 years) at home on 3 days approximately 30 min after wakeup and before bedtime. Both early a.m. levels and the decrease in cortisol across the day were examined. A structural equation model revealed that preadoption Deprived Care predicted Growth Delay at adoption and Growth Delay predicted higher morning cortisol levels and a larger diurnal cortisol decrease. PMID:18423090

  3. Evaluation of internal contamination levels after a radiological dispersal device incident using portal monitors.

    PubMed

    Palmer, R C; Hertel, N E; Ansari, A; Manger, R P; Freibert, E J

    2012-08-01

    Following a radioactive dispersal device (RDD) incident, it may be necessary to evaluate the internal contamination levels of a large number of potentially affected individuals to determine if immediate medical follow-up is necessary. Since the current laboratory capacity to screen for internal contamination is limited, rapid field screening methods can be useful in prioritising individuals. This study evaluated the suitability of a radiation portal monitor for such screening. A model of the portal monitor was created for use with models of six anthropomorphic phantoms in Monte Carlo N-Particle Transport Code Version 5 (MCNP) X-5 Monte Carlo Team (MCNP-A General Monte Carlo N-Particle Transport Code Version 5. LA-CP-03-0245. Vol. 2. Los Alamos National Laboratory, 2004.). The count rates of the portal monitor were simulated for inhalation and ingestion of likely radionuclides from an RDD for each of the phantoms. The time-dependant organ concentrations of the radionuclides were determined using Dose and Risk Calculation Software Eckerman, Leggett, Cristy, Nelson, Ryman, Sjoreen and Ward (Dose and Risk Calculation Software Ver. 8.4. ORNL/TM-2001/190. Oak Ridge National Laboratory, 2006.). Portal monitor count rates corresponding to a committed effective dose E(50) of 10 mSv are reported. PMID:22332142

  4. Evaluation of internal contamination levels after a radiological dispersal device incident using portal monitors

    SciTech Connect

    Palmer, R.C.; Hertel, Nolan; Ansari, A.; Manger, Ryan P; Freibert, E.J.

    2012-01-01

    Following a radioactive dispersal device (RDD) incident, it may be necessary to evaluate the internal contamination levels of a large number of potentially affected individuals to determine if immediate medical follow-up is necessary. Since the current laboratory capacity to screen for internal contamination is limited, rapid field screening methods can be useful in prioritizing individuals. This study evaluated the suitability of a radiation portal monitor for such screening. A model of the portal monitor was created for use with models of six anthropomorphic phantoms in Monte Carlo N-Particle Transport Code Version 5 (MCNP) X-5 Monte Carlo Team (MCNP A General Monte Carlo N-Particle Transport Code Version 5. LA-CP-03-0245. Vol. 2. Los Alamos National Laboratory, 2004.). The count rates of the portal monitor were simulated for inhalation and ingestion of likely radionuclides from an RDD for each of the phantoms. The time-dependant organ concentrations of the radionuclides were determined using Dose and Risk Calculation Software Eckerman, Leggett, Cristy, Nelson, Ryman, Sjoreen and Ward (Dose and Risk Calculation Software Ver. 8.4. ORNL/TM-2001/190. Oak Ridge National Laboratory, 2006.). Portal monitor count rates corresponding to a committed effective dose E(50) of 10 mSv are reported.

  5. Overview of the International Space Station System Level Trace Contaminant Injection Test

    NASA Technical Reports Server (NTRS)

    Tatara, James D.; Perry, Jay L.; Franks, Gerald D.

    1997-01-01

    Trace contaminant control onboard the International Space Station will be accomplished not only by the Trace Contaminant Control Subassembly but also by other Environmental Control and Life Support System subassemblies. These additional removal routes include absorption by humidity condensate in the Temperature and Humidity Control Condensing Heat Exchanger and adsorption by the Carbon Dioxide Removal Assembly. The Trace Contaminant Injection Test, which was performed at NASA's Marshall Space Flight Center, investigated the system-level removal of trace contaminants by the International Space Station Atmosphere Revitalization, and Temperature/Humidity Control Subsystems, (November-December 1997). It is a follow-on to the Integrated Atmosphere Revitalization Test conducted in 1996. An estimate for the magnitude of the assisting role provided by the Carbon Dioxide Removal Assembly and the Temperature and Humidity Control unit was obtained. In addition, data on the purity of Carbon Dioxide Removal Assembly carbon dioxide product were obtained to support Environmental Control and Life Support System Air Revitalization Subsystem loop closure.

  6. Absolute frequency measurement at 10-16 level based on the international atomic time

    NASA Astrophysics Data System (ADS)

    Hachisu, H.; Fujieda, M.; Kumagai, M.; Ido, T.

    2016-06-01

    Referring to International Atomic Time (TAI), we measured the absolute frequency of the 87Sr lattice clock with its uncertainty of 1.1 x 10-15. Unless an optical clock is continuously operated for the five days of the TAI grid, it is required to evaluate dead time uncertainty in order to use the available five-day average of the local frequency reference. We homogeneously distributed intermittent measurements over the five-day grid of TAI, by which the dead time uncertainty was reduced to low 10-16 level. Three campaigns of the five (or four)-day consecutive measurements have resulted in the absolute frequency of the 87Sr clock transition of 429 228 004 229 872.85 (47) Hz, where the systematic uncertainty of the 87Sr optical frequency standard amounts to 8.6 x 10-17.

  7. Trypanosoma cruzi Epimastigotes Are Able to Manage Internal Cholesterol Levels under Nutritional Lipid Stress Conditions

    PubMed Central

    Pereira, Miria Gomes; Visbal, Gonzalo; Salgado, Leonardo T.; Vidal, Juliana Cunha; Godinho, Joseane L. P.; De Cicco, Nuccia N. T.; Atella, Geórgia C.; de Souza, Wanderley; Cunha-e-Silva, Narcisa

    2015-01-01

    Trypanosoma cruzi epimastigotes store high amounts of cholesterol and cholesteryl esters in reservosomes. These unique organelles are responsible for cellular digestion by providing substrates for homeostasis and parasite differentiation. Here we demonstrate that under nutritional lipid stress, epimastigotes preferentially mobilized reservosome lipid stocks, instead of lipid bodies, leading to the consumption of parasite cholesterol reservoirs and production of ergosterol. Starved epimastigotes acquired more LDL-NBD-cholesterol by endocytosis and distributed the exogenous cholesterol to their membranes faster than control parasites. Moreover, the parasites were able to manage internal cholesterol levels, alternating between consumption and accumulation. With normal lipid availability, parasites esterified cholesterol exhibiting an ACAT-like activity that was sensitive to Avasimibe in a dose-dependent manner. This result also implies that exogenous cholesterol has a role in lipid reservoirs in epimastigotes. PMID:26068009

  8. Trypanosoma cruzi Epimastigotes Are Able to Manage Internal Cholesterol Levels under Nutritional Lipid Stress Conditions.

    PubMed

    Pereira, Miria Gomes; Visbal, Gonzalo; Salgado, Leonardo T; Vidal, Juliana Cunha; Godinho, Joseane L P; De Cicco, Nuccia N T; Atella, Geórgia C; de Souza, Wanderley; Cunha-e-Silva, Narcisa

    2015-01-01

    Trypanosoma cruzi epimastigotes store high amounts of cholesterol and cholesteryl esters in reservosomes. These unique organelles are responsible for cellular digestion by providing substrates for homeostasis and parasite differentiation. Here we demonstrate that under nutritional lipid stress, epimastigotes preferentially mobilized reservosome lipid stocks, instead of lipid bodies, leading to the consumption of parasite cholesterol reservoirs and production of ergosterol. Starved epimastigotes acquired more LDL-NBD-cholesterol by endocytosis and distributed the exogenous cholesterol to their membranes faster than control parasites. Moreover, the parasites were able to manage internal cholesterol levels, alternating between consumption and accumulation. With normal lipid availability, parasites esterified cholesterol exhibiting an ACAT-like activity that was sensitive to Avasimibe in a dose-dependent manner. This result also implies that exogenous cholesterol has a role in lipid reservoirs in epimastigotes. PMID:26068009

  9. International program to study subseabed disposal of high-level radioactive wastes

    SciTech Connect

    Carlin, E.M.; Hinga, K.R.; Knauss, J.A.

    1984-01-01

    This report provides an overview of the international program to study seabed disposal of nuclear wastes. Its purpose is to inform legislators, other policy makers, and the general public as to the history of the program, technological requirements necessary for feasibility assessment, legal questions involved, international coordination of research, national policies, and research and development activities. Each of these major aspects of the program is presented in a separate section. The objective of seabed burial, similar to its continental counterparts, is to contain and to isolate the wastes. The subseabed option should not be confuesed with past practices of ocean dumping which have introduced wastes into ocean waters. Seabed disposal refers to the emplacement of solidified high-level radioactive waste (with or without reprocessing) in certain geologically stable sediments of the deep ocean floor. Specially designed surface ships would transport waste canisters from a port facility to the disposal site. Canisters would be buried from a few tens to a few hundreds of meters below the surface of ocean bottom sediments, and hence would not be in contact with the overlying ocean water. The concept is a multi-barrier approach for disposal. Barriers, including waste form, canister, ad deep ocean sediments, will separate wastes from the ocean environment. High-level wastes (HLW) would be stabilized by conversion into a leach-resistant solid form such as glass. This solid would be placed inside a metallic canister or other type of package which represents a second barrier. The deep ocean sediments, a third barrier, are discussed in the Feasibility Assessment section. The waste form and canister would provide a barrier for several hundred years, and the sediments would be relied upon as a barrier for thousands of years. 62 references, 3 figures, 2 tables.

  10. Translation of HLA-HIV associations to the cellular level: HIV adapts to inflate CD8 T cell responses against Nef and HLA-adapted variant epitopes.

    PubMed

    Almeida, Coral-Ann M; Bronke, Corine; Roberts, Steven G; McKinnon, Elizabeth; Keane, Niamh M; Chopra, Abha; Kadie, Carl; Carlson, Jonathan; Haas, David W; Riddler, Sharon A; Haubrich, Richard; Heckerman, David; Mallal, Simon; John, Mina

    2011-09-01

    Strong statistical associations between polymorphisms in HIV-1 population sequences and carriage of HLA class I alleles have been widely used to identify possible sites of CD8 T cell immune selection in vivo. However, there have been few attempts to prospectively and systematically test these genetic hypotheses arising from population-based studies at a cellular, functional level. We assayed CD8 T cell epitope-specific IFN-γ responses in 290 individuals from the same cohort, which gave rise to 874 HLA-HIV associations in genetic analyses, taking into account autologous viral sequences and individual HLA genotypes. We found immunological evidence for 58% of 374 associations tested as sites of primary immune selection and identified up to 50 novel HIV-1 epitopes using this reverse-genomics approach. Many HLA-adapted epitopes elicited equivalent or higher-magnitude IFN-γ responses than did the nonadapted epitopes, particularly in Nef. At a population level, inclusion of all of the immunoreactive variant CD8 T cell epitopes in Gag, Pol, Nef, and Env suggested that HIV adaptation leads to an inflation of Nef-directed immune responses relative to other proteins. We concluded that HLA-HIV associations mark viral epitopes subject to CD8 T cell selection. These results can be used to guide functional studies of specific epitopes and escape mutations, as well as to test, train, and evaluate analytical models of viral escape and fitness. The inflation of Nef and HLA-adapted variant responses may have negative effects on natural and vaccine immunity against HIV and, therefore, has implications for diversity coverage approaches in HIV vaccine design. PMID:21821798

  11. Structural requirements for C3d,g/Epstein-Barr virus receptor (CR2/CD21) ligand binding, internalization, and viral infection.

    PubMed

    Carel, J C; Myones, B L; Frazier, B; Holers, V M

    1990-07-25

    The structure of CR2, the human C3d,g/EBV receptor (CR2/CD21) consists of 15 or 16 60-70 amino acid repeats called short consensus repeats (SCRs) followed by a transmembrane and a 34-amino acid intracytoplasmic domain. Functions of CR2 include binding the human complement component C3d,g when it is covalently attached to targets or cross-linked in the fluid phase. In addition, CR2 binds the Epstein-Barr virus (EBV) and mediates internalization of EBV and subsequent infection of cells. In order to explore functional roles of the repetitive extracytoplasmic SCR structure and the intracytoplasmic domain of CR2, we have created truncated CR2 (rCR2) mutants bearing serial deletions of extracytoplasmic SCRs and also the intracytoplasmic tail. We then stably transfected these rCR2 mutants into two cell lines, murine fibroblast L cells and human erythroleukemic K562 cells. Phenotypic analysis of these expressed mutants revealed that 1) The C3d,g- and EBV-binding sites are found in the two amino-terminal SCRs of CR2, 2) expression of SCRs 3 and 4 is further required for high affinity binding to soluble cross-linked C3d,g, 3) the intracytoplasmic domain of CR2 is not required for binding C3d,g or EBV but is necessary for internalization of cross-linked C3d,g as well as for EBV infection of cells, 4) monoclonal anti-CR2 antibodies with similar activities react with single widely separated epitopes, and 5) no functional roles can yet be clearly assigned to SCRs 5-15, as rCR2 mutants not containing these SCRs show no major differences from wild-type rCR2 in binding or internalizing cross-linked C3d,g or mediating EBV binding and infection. PMID:1695627

  12. Decreased CD127 Expression on CD4+ T-Cells and Elevated Frequencies of CD4+CD25+CD127− T-Cells in Children with Long-Lasting Type 1 Diabetes

    PubMed Central

    Glowinska-Olszewska, Barbara; Rusak, Malgorzata; Jeznach, Marta; Grubczak, Kamil; Lipinska, Danuta; Milewska, Anna Justyna; Dabrowska, Milena; Jablonska, Ewa; Kretowski, Adam; Gorska, Maria; Bodzenta-Lukaszyk, Anna; Bossowski, Artur

    2013-01-01

    Pathobiology of type 1 diabetes (T1D) is predominantly associated with T-cell-related actions. Homeostasis of majority of T-cells is critically dependent on signals mediated by CD127 (interleukin-7 receptor, IL-7R). In contrast, regulatory T-cells express very little CD127 and thereby may be delineated by CD4+CD25+CD127− phenotype. Here we aimed to analyze CD127 expression on CD4+ and CD8+ T-cells and enumerate CD4+CD25+CD127− T-cells in long-lasting T1D. T-cells were analyzed by flow cytometry and immunologic data were correlated with vascular, metabolic, and inflammatory parameters. We demonstrated significantly decreased CD127 levels on CD4+, but not CD8+, T cells in T1D pediatric patients. Interestingly, frequencies of CD4+CD25+CD127− T-cells were significantly enhanced in T1D children and correlated well with frequencies of CD34+CD144+ endothelial progenitor cells and CD4+CD25− T-cells. Levels of CD127 on both CD4+ and CD8+ T-cells in T1D patients were not correlated to each other or HbA1C. Interestingly, however, CD127 levels on CD4+ T-cells were significantly correlated to frequencies of CD4+CD25+CD127− T-cells, whereas CD127 levels on CD8+ T-cells were significantly correlated to concentrations of VEGF and triglycerides. Our data indicate that CD127 expression is differentially modulated on CD4+ and CD8+ T-cells in the course of T1D. Moreover, we demonstrated that, in contrast to recent-onset T1D, long-lasting T1D is associated with enhancement of T-cells with regulatory phenotype. PMID:24348676

  13. The Market Place: An Internal View of the Future of CD-ROM--The Perspective of the H. W. Wilson Company.

    ERIC Educational Resources Information Center

    Miller, Frank W.; Loeding, Deborah Voigt

    1989-01-01

    Discussion of technological developments in library reference services focuses on contributions of the H. W. Wilson Company and highlights CD-ROM technology. Topics discussed include online access; menu-driven systems; CD-ROM hardware and software concerns; user response to CD-ROM; quality control of databases; pricing considerations; and future…

  14. Comparison of basic physical fitness, aerobic capacity, and isokinetic strength between national and international level high school freestyle swimmers

    PubMed Central

    Bae, Young-Hyeon; Yu, Jae-Ho; Lee, Suk Min

    2016-01-01

    [Purpose] This study aimed to compare basic physical fitness, aerobic capacity, and isokinetic strength between international and national level freestyle high school student swimmers. [Subjects and Methods] A total of 28 participants (14 international level swimmers and 14 national level freestyle high school student swimmers) with no known pathology were included. We used a cross-sectional study to examine three variables: basic physical fitness, aerobic capacity, and isokinetic strength. [Results] The mean values of these variables in the international level swimmers were higher than those in the national level swimmers. Swimmers are generally physically fit with a good competition record. [Conclusion] An appropriate training program, which considers specific individual characteristics is likely to have a positive impact on the improvement of total physical fitness, and subsequently, on the performance of the freestyle high school swimmer. PMID:27134379

  15. International safeguards relevant to geologic disposal of high-level wastes and spent fuels

    SciTech Connect

    Pillay, K.K.S.; Picard, R.R.

    1989-01-01

    Spent fuels from once-through fuel cycles placed in underground repositories have the potential to become attractive targets for diversion and/or theft because of their valuable material content and decreasing radioactivity. The first geologic repository in the US, as currently designed, will contain approximately 500 Mt of plutonium, 60,000 Mt of uranium and a host of other fissile and strategically important elements. This paper identifies some of the international safeguards issues relevant to the various proposed scenarios for disposing of the spent fuel. In the context of the US program for geologic disposal of spent fuels, this paper highlights several issues that should be addressed in the near term by US industries, the Department of Energy, and the Nuclear Regulatory Commission before the geologic repositories for spent fuels become a reality. Based on US spent fuel discharges, an example is presented to illustrate the enormity of the problem of verifying spent fuel inventories. The geologic disposal scenario for high-level wastes originating from defense facilities produced a practicably irrecoverable'' waste form. Therefore, safeguards issues for geologic disposal of high-level waste now in the US are less pressing. 56 refs. , 2 figs.

  16. Investigation of the relationship between motor vehicle operating cost and levels of service using internal methods

    SciTech Connect

    Croft, F.M. Jr.

    1984-01-01

    This study was undertaken to accomplish three specific objectives pertaining to the measurement of traffic flow quality, namely: 1) to demonstrate that the internal energy of the traffic stream as determined by the parameter, acceleration noise, can be used as a quantitative measure of the quality of traffic flow on an urban freeway; 2) to demonstrate that vehicle operating costs are related to the parameter acceleration noise; and 3) to determine the effect that level of service has on operating costs by using the parameter acceleration noise. Traffic flow data were collected from sections of Interstate 65 in Louisville, Kentucky, using a floating car equipped with a Greenshields Traffic Analyzer. The traffic analyzer data were later reduced using an interactive computer program to yield values of acceleration noise. The traffic analyzer data, traffic volumn counts, and highway geometric data were used as inputs into the computer program RUNCOST to calculate vehicle operating costs. The relationship between acceleration noise and the traffic flow parameters of speed, volume, and density were analyzed using scatter diagrams and plots of the mean values of each parameter for each level of service. The relationship between operating cost and the traffic flow parameters of speed, volume, and density were also analyzed. It was concluded that acceleration noise due to traffic interaction is a quantitative measure of traffic flow quality.

  17. Soluble CD44 interacts with intermediate filament protein vimentin on endothelial cell surface.

    PubMed

    Päll, Taavi; Pink, Anne; Kasak, Lagle; Turkina, Marina; Anderson, Wally; Valkna, Andres; Kogerman, Priit

    2011-01-01

    CD44 is a cell surface glycoprotein that functions as hyaluronan receptor. Mouse and human serum contain substantial amounts of soluble CD44, generated either by shedding or alternative splicing. During inflammation and in cancer patients serum levels of soluble CD44 are significantly increased. Experimentally, soluble CD44 overexpression blocks cancer cell adhesion to HA. We have previously found that recombinant CD44 hyaluronan binding domain (CD44HABD) and its non-HA-binding mutant inhibited tumor xenograft growth, angiogenesis, and endothelial cell proliferation. These data suggested an additional target other than HA for CD44HABD. By using non-HA-binding CD44HABD Arg41Ala, Arg78Ser, and Tyr79Ser-triple mutant (CD443MUT) we have identified intermediate filament protein vimentin as a novel interaction partner of CD44. We found that vimentin is expressed on the cell surface of human umbilical vein endothelial cells (HUVEC). Endogenous CD44 and vimentin coprecipitate from HUVECs, and when overexpressed in vimentin-negative MCF-7 cells. By using deletion mutants, we found that CD44HABD and CD443MUT bind vimentin N-terminal head domain. CD443MUT binds vimentin in solution with a Kd in range of 12-37 nM, and immobilised vimentin with Kd of 74 nM. CD443MUT binds to HUVEC and recombinant vimentin displaces CD443MUT from its binding sites. CD44HABD and CD443MUT were internalized by wild-type endothelial cells, but not by lung endothelial cells isolated from vimentin knock-out mice. Together, these data suggest that vimentin provides a specific binding site for soluble CD44 on endothelial cells. PMID:22216242

  18. Global energy and water cycle experiment (GEWEX) continental-scale international project (GCIP); reference data sets CD-ROM

    USGS Publications Warehouse

    Rea, Alan; Cederstrand, Joel R.

    1994-01-01

    The data sets on this compact disc are a compilation of several geographic reference data sets of interest to the global-change research community. The data sets were chosen with input from the Global Energy and Water Cycle Experiment (GEWEX) Continental-Scale International Project (GCIP) Data Committee and the GCIP Hydrometeorology and Atmospheric Subpanels. The data sets include: locations and periods of record for stream gages, reservoir gages, and meteorological stations; a 500-meter-resolution digital elevation model; grid-node locations for the Eta numerical weather-prediction model; and digital map data sets of geology, land use, streams, large reservoirs, average annual runoff, average annual precipitation, average annual temperature, average annual heating and cooling degree days, hydrologic units, and state and county boundaries. Also included are digital index maps for LANDSAT scenes, and for the U.S. Geological Survey 1:250,000, 1:100,000, and 1:24,000-scale map series. Most of the data sets cover the conterminous United States; the digital elevation model also includes part of southern Canada. The stream and reservoir gage and meteorological station files cover all states having area within the Mississippi River Basin plus that part of the Mississippi River Basin lying within Canada. Several data-base retrievals were processed by state, therefore many sites outside the Mississippi River Basin are included.

  19. Influence of a Diester Glucocorticoid Spray on the Cortisol Level and the CCR4(+) CD4(+) Lymphocytes in Dogs with Atopic Dermatitis: Open Study.

    PubMed

    Fujimura, Masato; Ishimaru, Hironobu

    2014-01-01

    This study investigated the influence of 0.00584% hydrocortisone aceponate spray (HCA; Cortavance Virbac SA, Carros, France) on blood serum cortisol levels and peripheral blood CCR4(+) CD4(+) T-lymphocyte levels in dogs with atopic dermatitis. Patients were randomly divided into group I (N = 8) and group II (N = 8). The dogs in group I were sprayed with HCA on the affected skin once a day for three weeks. The dogs in group II were treated once a day for 3 days followed by no treatment for 4 days for a total of three weeks. For the dogs in group I and group II the CADESI-03 scores before and after use of HCA showed significant reduction (P < 0.01). The postcortisol level after the use of HCA in group I showed 36.0% decrease and showed significant suppression (P < 0.01). By comparison, the use of HCA on group II did not show decrease in postcortisol levels. There was a tendency of suppression for hypothalamus-pituitary gland-adrenal gland system, but it was not serious influence. In addition, there was no influence on peripheral blood CCR4(+) CD4(+) lymphocytes percentage in dogs in group I after treatment with HCA. PMID:26464935

  20. Influence of a Diester Glucocorticoid Spray on the Cortisol Level and the CCR4+ CD4+ Lymphocytes in Dogs with Atopic Dermatitis: Open Study

    PubMed Central

    Fujimura, Masato; Ishimaru, Hironobu

    2014-01-01

    This study investigated the influence of 0.00584% hydrocortisone aceponate spray (HCA; Cortavance Virbac SA, Carros, France) on blood serum cortisol levels and peripheral blood CCR4+ CD4+ T-lymphocyte levels in dogs with atopic dermatitis. Patients were randomly divided into group I (N = 8) and group II (N = 8). The dogs in group I were sprayed with HCA on the affected skin once a day for three weeks. The dogs in group II were treated once a day for 3 days followed by no treatment for 4 days for a total of three weeks. For the dogs in group I and group II the CADESI-03 scores before and after use of HCA showed significant reduction (P < 0.01). The postcortisol level after the use of HCA in group I showed 36.0% decrease and showed significant suppression (P < 0.01). By comparison, the use of HCA on group II did not show decrease in postcortisol levels. There was a tendency of suppression for hypothalamus—pituitary gland—adrenal gland system, but it was not serious influence. In addition, there was no influence on peripheral blood CCR4+ CD4+ lymphocytes percentage in dogs in group I after treatment with HCA. PMID:26464935

  1. High level expression and purification of the enzymatically active cytoplasmic region of human CD45 phosphatase from yeast.

    PubMed

    Pacitti, A; Stevis, P; Evans, M; Trowbridge, I; Higgins, T J

    1994-06-30

    The cytoplasmic region of human CD45 corresponding to residues 584-1281 was inserted downstream of the alcohol dehydrogenase promoter and transfected into a haploid strain of yeast. Expression of recombinant CD45 in yeast reached as high as 5% of the soluble protein. Following removal of cellular debris by centrifugation and an ammonium sulfate precipitation step, the enzyme was purified using phenyl-Sepharose chromatography, preparative gel filtration, Mono Q anion exchange chromatography and a final analytical gel filtration step. Enzymatically active material with a purity of > or = 98% was obtained with a yield approaching 50%. The final product gave a Km of 5.5 mM and a Vmax of 87.5 U/mg with p-nitrophenylphosphate and a Km and Vmax of 0.167 mM and 185 U/mg, respectively, with a phosphotyrosine peptide. The native enzyme purified from Jurkat cells showed comparable Kms with both substrates to the recombinant enzyme but displayed substantially lower Vmax values for both substrates. PMID:8031864

  2. Manifestation of the Se, Cd and Mo levels in different components of the peripheral blood of Sprague-Dawley rats poisoned via the respiratory tract.

    PubMed

    Wang, Dong-Fang; Sun, Xuan; Cao, Bing; Wen, Hua; Zhang, Yu; Liu, Duo-Jian; Yan, Lai-Lai; Liu, Ya-Qiong; Lu, Qing-Bin; Wang, Jing-Yu

    2015-01-01

    This study aimed to explore the effects of exogenous element exposure via the respiratory tract on the Se, Cd and Mo concentrations in different components of the peripheral blood in rats as well as to determine the correlations of the three trace elements concentrations among the components. The Sprague-Dawley rats were randomly divided into a control group and several experimental groups treated with different doses. The rats were exposed to a mixed trace element solution through 10 days of intratracheal instillation. The whole blood of all rats was collected and separated into three parts with Percoll density gradient centrifugation. The Se, Cd and Mo levels in whole blood, plasma, red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) were determined by inductively coupled plasma mass spectrometry. The concentrations of the three trace elements increased together with the increase of the given doses (P<0.05), except Cd and Mo in the PBMCs. The three trace elements lacked linearity with the exposure doses in the PBMCs (r, 0.249-0.508), while the opposite was the case for the other components of the peripheral blood (r, 0.806-0.934). The correlation coefficients were higher (0.842-0.962) among the whole blood, plasma and RBCs than between PBMCs and other components, such as Se (0.376-0.529), Cd (0.495-0.604) and, especially, Mo (0.160-0.257). In conclusion, PBMCs might provide information about endogenous factors, and whole blood could more accurately reflect the effects of exogenous factors compared to other blood components. PMID:26770359

  3. Manifestation of the Se, Cd and Mo levels in different components of the peripheral blood of Sprague-Dawley rats poisoned via the respiratory tract

    PubMed Central

    Wang, Dong-Fang; Sun, Xuan; Cao, Bing; Wen, Hua; Zhang, Yu; Liu, Duo-Jian; Yan, Lai-Lai; Liu, Ya-Qiong; Lu, Qing-Bin; Wang, Jing-Yu

    2015-01-01

    This study aimed to explore the effects of exogenous element exposure via the respiratory tract on the Se, Cd and Mo concentrations in different components of the peripheral blood in rats as well as to determine the correlations of the three trace elements concentrations among the components. The Sprague-Dawley rats were randomly divided into a control group and several experimental groups treated with different doses. The rats were exposed to a mixed trace element solution through 10 days of intratracheal instillation. The whole blood of all rats was collected and separated into three parts with Percoll density gradient centrifugation. The Se, Cd and Mo levels in whole blood, plasma, red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) were determined by inductively coupled plasma mass spectrometry. The concentrations of the three trace elements increased together with the increase of the given doses (P<0.05), except Cd and Mo in the PBMCs. The three trace elements lacked linearity with the exposure doses in the PBMCs (r, 0.249-0.508), while the opposite was the case for the other components of the peripheral blood (r, 0.806-0.934). The correlation coefficients were higher (0.842-0.962) among the whole blood, plasma and RBCs than between PBMCs and other components, such as Se (0.376-0.529), Cd (0.495-0.604) and, especially, Mo (0.160-0.257). In conclusion, PBMCs might provide information about endogenous factors, and whole blood could more accurately reflect the effects of exogenous factors compared to other blood components. PMID:26770359

  4. High levels of TSP1+/CD142+ platelet-derived microparticles characterise young patients with high cardiovascular risk and subclinical atherosclerosis.

    PubMed

    Suades, Rosa; Padró, Teresa; Alonso, Rodrigo; Mata, Pedro; Badimon, Lina

    2015-11-25

    Circulating microparticles (cMPs) play important roles in cellular crosstalk and are messengers of cell activation. We have previously reported that platelet-released microparticles (pMPs) stimulate thrombosis and that lipid-lowering treatment as per guidelines in patients with familial hypercholesterolaemia (FH) is not sufficiently effective in reducing pro-inflammatory cell activation and, consequently, CD45+/CD3+-lymphocyte-derived cMP shedding. FH patients, due to life-long vascular exposure to high LDL-cholesterol levels, are at high cardiovascular risk (HCVR) and develop premature coronary artery disease. Our objectives were to investigate a) whether patients with HCVR have cMPs with a prothrombotic phenotype, and b) whether patients with magnetic resonance imaging (MRI) evidence of lipid-rich atherosclerotic lesions have a specific cMP profile regarding prothrombotic protein cargos. cMPs were isolated from HCVR-patients and from age/gender/treatment-matched control patients. cMP phenotype was characterised by triple-labelling flow cytometry. HCVR--patients have higher numbers of pMPs derived from activated platelets as well as of tissue factor-rich microparticles (TF+-cMPs) than controls (P< 0.0001). TF+-cMPs showed procoagulant activity, which associate with atherosclerotic plaque burden, indicating that TF in the cMPs is functional. In HCVR-patients, overall TF+-cMPs (monocyte-derived [CD142+/CD14+] and platelet-derived [CD142+/TSP1+]) and activated pMPs directly correlate with MRI-detected lipid-rich atherosclerotic plaques while inversely correlate with MRI-detected calcified plaques. C-statistics analysis showed that prothrombotic cMPs add significant prognostic value to a risk factor model for the prediction of lipid-rich plaques. In conclusion, the activation status of blood cells in HCVR-patients differed markedly from controls as shown by higher circulating levels of prothrombotic and TF+-cMPs. Prothrombotic cMP numbers identify subclinical

  5. Downregulation of CD44 reduces doxorubicin resistance of CD44+CD24− breast cancer cells

    PubMed Central

    Van Phuc, Pham; Nhan, Phan Lu Chinh; Nhung, Truong Hai; Tam, Nguyen Thanh; Hoang, Nguyen Minh; Tue, Vuong Gia; Thuy, Duong Thanh; Ngoc, Phan Kim

    2011-01-01

    Background Cells within breast cancer stem cell populations have been confirmed to have a CD44+CD24− phenotype. Strong expression of CD44 plays a critical role in numerous types of human cancers. CD44 is involved in cell differentiation, adhesion, and metastasis of cancer cells. Methods In this study, we reduced CD44 expression in CD44+CD24− breast cancer stem cells and investigated their sensitivity to an antitumor drug. The CD44+CD24− breast cancer stem cells were isolated from breast tumors; CD44 expression was downregulated with siRNAs followed by treatment with different concentrations of the antitumor drug. Results The proliferation of CD44 downregulated CD44+CD24− breast cancer stem cells was decreased after drug treatment. We noticed treated cells were more sensitive to doxorubicin, even at low doses, compared with the control groups. Conclusions It would appear that expression of CD44 is integral among the CD44+CD24− cell population. Reducing the expression level of CD44, combined with doxorubicin treatment, yields promising results for eradicating breast cancer stem cells in vitro. This study opens a new direction in treating breast cancer through gene therapy in conjunction with chemotherapy. PMID:21792314

  6. Fabrication of magnetic hydroxypropyl cellulose-g-poly(acrylic acid) porous spheres via Pickering high internal phase emulsion for removal of Cu(2+) and Cd(2.).

    PubMed

    Zhu, Yongfeng; Zheng, Yian; Zong, Li; Wang, Feng; Wang, Aiqin

    2016-09-20

    A series of magnetic hydroxypropyl cellulose-g-poly(acrylic acid) porous spheres were prepared via O/W Pickering high internal phase emulsions (HIPEs) integrated precipitation polymerization. The structure and composition of modified Fe3O4 and porous structures were characterized by TEM, XRD, TGA and SEM. The results indicated that the silanized Fe3O4 can influence greatly the pore structure of magnetic porous sphere in addition to non-negligible impacts of the proportion of mixed solvent and co-surfactant. The adsorption experiment demonstrated that the adsorption equilibrium can be reached within 40min and the maximal adsorption capacity was 300.00mg/g for Cd(2+) and 242.72mg/g for Cu(2+), suggesting its fast adsorption kinetics and high adsorption capacity. After five adsorption-desorption cycles, no significant changes in the adsorption capacity were observed, suggesting its excellent reusability. The magnetic porous sphere can be easily separated from the solution and then find its potential as a recyclable material for highly efficient removal of heavy metals. PMID:27261748

  7. Development of derived investigation levels for use in internal dosimetry at the West Valley Demonstration Project

    SciTech Connect

    Johnson, P.

    1991-12-31

    The objective was to determine if the routine intemal dosimetry program at the West Valley Demonstration Project is capable of meeting the performance objective of 1 mSv annual effective dose equivalent due to internal contamination. With the use of the computer code REMedy the annual effective dose equivalent is calculated. Some of the radionuclides of concern result in an annual effective dose equivalent that exceeds the performance objective. Although the results exceed the performance objective, in all but two cases they do not exceed the US DOE regulatory limits. In these instances the Th-232 and Am-241 were determined to exceed the committed dose equivalent limit to their limiting tissue. In order to document the potential missed dose for regulatory compliance, Sr-90 is used as an indicator for Th-232. For Am-241 an investigation as to whether or not the minimum detectable amount can be lowered is performed. The derived investigation levels as a result of this project are 4.9E3 Bq/lung count for Co-60, 2.2E4 Bq/lung count for Cs-137, 1.9 Bq/1 for Sr-90 and for radionuclides other than Sr-90 any value greater than or equal to three standard deviations above their net count is considered to require further investigation.

  8. Trogocytosis of multiple B-cell surface markers by CD22 targeting with epratuzumab.

    PubMed

    Rossi, Edmund A; Goldenberg, David M; Michel, Rosana; Rossi, Diane L; Wallace, Daniel J; Chang, Chien-Hsing

    2013-10-24

    Epratuzumab, a humanized anti-CD22 antibody, is currently in clinical trials of B-cell lymphomas and autoimmune diseases, demonstrating therapeutic activity in non-Hodgkin lymphoma (NHL) and systemic lupus erythematosus (SLE). Thus, epratuzumab offers a promising option for CD22-targeted immunotherapy, yet its mechanism of action remains poorly understood. Here we report for the first time that epratuzumab promptly induces a marked decrease of CD22 (>80%), CD19 (>50%), CD21 (>50%), and CD79b (>30%) on the surface of B cells in peripheral blood mononuclear cells (PBMCs) obtained from normal donors or SLE patients, and of NHL cells (Daudi and Raji) spiked into normal PBMCs. Although some Fc-independent loss of CD22 is expected from internalization by epratuzumab, the concurrent and prominent reduction of CD19, CD21, and CD79b is Fc dependent and results from their transfer from epratuzumab-opsonized B cells to FcγR-expressing monocytes, natural killer cells, and granulocytes via trogocytosis. The findings of reduced levels of CD19 are implicative for the efficacy of epratuzumab in autoimmune diseases because elevated CD19 has been correlated with susceptibility to SLE in animal models as well as in patients. This was confirmed herein by the finding that SLE patients receiving epratuzumab immunotherapy had significantly reduced CD19 compared with treatment-naïve patients. PMID:23821660

  9. Estimated association between dwelling soil contamination and internal radiation contamination levels after the 2011 Fukushima Daiichi nuclear accident in Japan

    PubMed Central

    Tsubokura, Masaharu; Nomura, Shuhei; Sakaihara, Kikugoro; Kato, Shigeaki; Leppold, Claire; Furutani, Tomoyuki; Morita, Tomohiro; Oikawa, Tomoyoshi; Kanazawa, Yukio

    2016-01-01

    Objectives Measurement of soil contamination levels has been considered a feasible method for dose estimation of internal radiation exposure following the Chernobyl disaster by means of aggregate transfer factors; however, it is still unclear whether the estimation of internal contamination based on soil contamination levels is universally valid or incident specific. Methods To address this issue, we evaluated relationships between in vivo and soil cesium-137 (Cs-137) contamination using data on internal contamination levels among Minamisoma (10–40 km north from the Fukushima Daiichi nuclear power plant), Fukushima residents 2–3 years following the disaster, and constructed three models for statistical analysis based on continuous and categorical (equal intervals and quantiles) soil contamination levels. Results A total of 7987 people with a mean age of 55.4 years underwent screening of in vivo Cs-137 whole-body counting. A statistically significant association was noted between internal and continuous Cs-137 soil contamination levels (model 1, p value <0.001), although the association was slight (relative risk (RR): 1.03 per 10 kBq/m2 increase in soil contamination). Analysis of categorical soil contamination levels showed statistical (but not clinical) significance only in relatively higher soil contamination levels (model 2: Cs-137 levels above 100 kBq/m2 compared to those <25 kBq/m2, RR=1.75, p value <0.01; model 3: levels above 63 kBq/m2 compared to those <11 kBq/m2, RR=1.45, p value <0.05). Conclusions Low levels of internal and soil contamination were not associated, and only loose/small associations were observed in areas with slightly higher levels of soil contamination in Fukushima, representing a clear difference from the strong associations found in post-disaster Chernobyl. These results indicate that soil contamination levels generally do not contribute to the internal contamination of residents in Fukushima; thus, individual

  10. Cytomegalovirus Replication in Semen Is Associated with Higher Levels of Proviral HIV DNA and CD4+ T Cell Activation during Antiretroviral Treatment

    PubMed Central

    Massanella, Marta; Richman, Douglas D.; Little, Susan J.; Spina, Celsa A.; Vargas, Milenka V.; Lada, Steven M.; Daar, Eric S.; Dube, Michael P.; Haubrich, Richard H.; Morris, Sheldon R.; Smith, Davey M.

    2014-01-01

    ABSTRACT Asymptomatic cytomegalovirus (CMV) replication occurs frequently in the genital tract in untreated HIV-infected men and is associated with increased immune activation and HIV disease progression. To determine the connections between CMV-associated immune activation and the size of the viral reservoir, we evaluated the interactions between (i) asymptomatic seminal CMV replication, (ii) levels of T cell activation and proliferation in blood, and (iii) the size and transcriptional activity of the HIV DNA reservoir in blood from 53 HIV-infected men on long-term antiretroviral therapy (ART) with suppressed HIV RNA in blood plasma. We found that asymptomatic CMV shedding in semen was associated with significantly higher levels of proliferating and activated CD4+ T cells in blood (P < 0.01). Subjects with detectable CMV in semen had approximately five times higher average levels of HIV DNA in blood CD4+ T cells than subjects with no CMV. There was also a trend for CMV shedders to have increased cellular (multiply spliced) HIV RNA transcription (P = 0.068) compared to participants without CMV, but it is unclear if this transcription pattern is associated with residual HIV replication. In multivariate analysis, the presence of seminal plasma CMV (P = 0.04), detectable 2-long terminal repeat (2-LTR), and lower nadir CD4+ (P < 0.01) were independent predictors of higher levels of proviral HIV DNA in blood. Interventions aimed at reducing seminal CMV and associated immune activation may be important for HIV curative strategies. Future studies of anti-CMV therapeutics will help to establish causality and determine the mechanisms underlying these described associations. IMPORTANCE Almost all individuals infected with HIV are also infected with cytomegalovirus (CMV), and the replication dynamics of the two viruses likely influence each other. This study investigated interactions between asymptomatic CMV replication within the male genital tract, levels of inflammation in