Does symptomatic primary HIV-1 infection accelerate progression to CDC stage IV disease, CD4 count below 200 x 10(6)/l, AIDS, and death from AIDS?

PubMed Central

Lindbäck, S.; Broström, C.; Karlsson, A.; Gaines, H.

1994-01-01

OBJECTIVE--To investigate the prognostic significance of symptomatic primary HIV-1 infection. DESIGN--Prospective study of homosexual men seroconverting to HIV in 1985 and 1986. Patients were followed up at least three times yearly with clinical examinations and T cell subset determinations for an average of 7.2 years. SETTING--Research project centred on attenders for treatment and screening for HIV at the Karolinska Institute, Stockholm. SUBJECTS--19 patients presenting with a glandular-fever-like illness associated with seroconversion to HIV and 29 asymptomatic seroconverters. MAIN OUTCOME MEASURES--Progression to Centers for Disease Control and Prevention stage IV disease, CD4 cell count below 200 x 10(6)/l, AIDS, and death from AIDS. RESULTS--Symptomatic seroconverters were significantly more likely to develop Centers for Disease Control and Prevention stage IV disease (95% v 66%), CD4 cell counts below 200 x 10(6)/l (84% v 55%), and AIDS (58% v 28%) and die of AIDS (53% v 7%). CONCLUSION--A glandular-fever-like illness associated with seroconversion to HIV-1 predicts accelerated progression to AIDS and other HIV related diseases. PMID:7819891

Cadmium-Induced Changes in Antioxidative Systems, Hydrogen Peroxide Content, and Differentiation in Scots Pine Roots1

PubMed Central

Schützendübel, Andres; Schwanz, Peter; Teichmann, Thomas; Gross, Kristina; Langenfeld-Heyser, Rosemarie; Godbold, Douglas L.; Polle, Andrea

2001-01-01

To investigate whether Cd induces common plant defense pathways or unspecific necrosis, the temporal sequence of physiological reactions, including hydrogen peroxide (H2O2) production, changes in ascorbate-glutathione-related antioxidant systems, secondary metabolism (peroxidases, phenolics, and lignification), and developmental changes, was characterized in roots of hydroponically grown Scots pine (Pinus sylvestris) seedlings. Cd (50 μm, 6 h) initially increased superoxide dismutase, inhibited the systems involved in H2O2 removal (glutathione/glutathione reductase, catalase [CAT], and ascorbate peroxidase [APX]), and caused H2O2 accumulation. Elongation of the roots was completely inhibited within 12 h. After 24 h, glutathione reductase activities recovered to control levels; APX and CAT were stimulated by factors of 5.5 and 1.5. Cell death was increased. After 48 h, nonspecific peroxidases and lignification were increased, and APX and CAT activities were decreased. Histochemical analysis showed that soluble phenolics accumulated in the cytosol of Cd-treated roots but lignification was confined to newly formed protoxylem elements, which were found in the region of the root tip that normally constitutes the elongation zone. Roots exposed to 5 μm Cd showed less pronounced responses and only a small decrease in the elongation rate. These results suggest that in cells challenged by Cd at concentrations exceeding the detoxification capacity, H2O2 accumulated because of an imbalance of redox systems. This, in turn, may have triggered the developmental program leading to xylogenesis. In conclusion, Cd did not cause necrotic injury in root tips but appeared to expedite differentiation, thus leading to accelerated aging. PMID:11706171

Proton shock acceleration using a high contrast high intensity laser

NASA Astrophysics Data System (ADS)

Gauthier, Maxence; Roedel, Christian; Kim, Jongjin; Aurand, Bastian; Curry, Chandra; Goede, Sebastian; Propp, Adrienne; Goyon, Clement; Pak, Art; Kerr, Shaun; Ramakrishna, Bhuvanesh; Ruby, John; William, Jackson; Glenzer, Siegfried

2015-11-01

Laser-driven proton acceleration is a field of intense research due to the interesting characteristics of this novel particle source including high brightness, high maximum energy, high laminarity, and short duration. Although the ion beam characteristics are promising for many future applications, such as in the medical field or hybrid accelerators, the ion beam generated using TNSA, the acceleration mechanism commonly achieved, still need to be significantly improved. Several new alternative mechanisms have been proposed such as collisionless shock acceleration (CSA) in order to produce a mono-energetic ion beam favorable for those applications. We report the first results of an experiment performed with the TITAN laser system (JLF, LLNL) dedicated to the study of CSA using a high intensity (5x1019W/cm2) high contrast ps laser pulse focused on 55 μm thick CH and CD targets. We show that the proton spectrum generated during the interaction exhibits high-energy mono-energetic features along the laser axis, characteristic of a shock mechanism.

Increased Expression of Complement Regulators CD55 and CD59 on Peripheral Blood Cells in Patients with EAHEC O104:H4 Infection

PubMed Central

Ullrich, Sebastian; Fraedrich, Katharina; Schulze zur Wiesch, Julian; Fründt, Thorben; Tiegs, Gisa; Lohse, Ansgar; Lüth, Stefan

2013-01-01

Background An outbreak of Shiga Toxin 2 (Stx-2) producing enterohemorrhagic and enteroaggregative E.coli (EAHEC) O104H4 infection in May 2011 caused enterocolitis and an unprecedented high 22% rate of hemolytic uremic syndrome (HUS). The monoclonal anti-C5 antibody Eculizumab (ECU) has been used experimentally in EAHEC patients with HUS but treatment efficacy is uncertain. ECU can effectively prevent hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) caused by a lack of complement-regulating CD55 and CD59 on blood cells. We hypothesized a low expression of CD55 and CD59, as seen in PNH, might correlate with HUS development in EAHEC patients. Methods 76 EAHEC patients (34 only gastrointestinal symptoms [GI], 23: HUS, 19: HUS and neurological symptoms [HUS/N]) and 12 healthy controls (HC) were tested for the expression of CD55 and CD59 on erythrocytes and leukocytes retrospectively. Additionally, the effect of Stx-2 on CD55 and CD59 expression on erythrocytes and leukocytes was studied ex vivo. Results CD55 expression on erythrocytes was similar in all patient groups and HC while CD59 showed a significantly higher expression in HUS and HUS/N patients compared to HC and the GI group. CD55 and CD59 expression on leukocytes and their subsets was significantly higher in all patient groups compared to HC regardless of treatment type. However, CD59 expression on erythrocytes was significantly higher in HUS and HUS/N patients treated combined with plasma separation (PS) and ECU compared to HC. Adding Stx-2 ex vivo had no effect on CD55 and CD59 expression on leukocytes from HC or patients. Conclusion HUS evolved independently from CD55 and CD59 expression on peripheral blood cells in EAHEC O104:H4 infected patients. Our data do not support a role for CD55 and CD59 in HUS development during EAHEC O104:H4 infection and point to a different mechanism within the complement system for HUS development in EAHEC patients. PMID:24086391

Single-particle states in ^112Cd probed with the ^111Cd(d,p) reaction

NASA Astrophysics Data System (ADS)

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

2009-10-01

As part of a program of detailed spectroscopy of the Cd isotopes, the single-particle neutron states in ^112Cd have been probed with the ^111Cd(d,p) reaction. Beams of polarized 22 MeV deuterons, obtained from the LMU/TUM Tandem Accelerator, bombarded a target of ^111Cd. The protons from the reaction, corresponding to excitation energies up to 3 MeV in ^112Cd, were momentum analyzed with the Q3D spectrograph. Cross sections and analyzing powers were fit to results of DWBA calculations, and spectroscopic factors were determined. The results from the experiment, and implications for the structure of ^112Cd, will be presented.

Anemia at the time of diagnosis of inflammatory bowel disease: Prevalence and associated factors in adolescent and adult patients.

PubMed

Lucendo, Alfredo J; Arias, Ángel; Roncero, Óscar; Hervías, Daniel; Verdejo, Cristina; Naveas-Polo, Carmen; Bouhmidi, Abdelmouneim; Lorente, Rufo; Alcázar, Luis Miguel; Salueña, Irina; García-Quiñones, Julio A; Carrillo-Ramos, María Jesús

2017-04-01

The prevalence, characteristic and determinants of anemia, at the time of inflammatory bowel disease (IBD) diagnosis have yet to be fully elucidated. Retrospective cross-sectional study. Analytical data and disease characteristics obtained upon diagnosis of 1278 IBD patients [Crohn's disease/ulcerative colitis (CD/UC): 718/560] were collected. Anemia was present in 41.2% of patients at diagnosis (47% and 33.8% of CD and UC patients, respectively; p<0.001), being severe in 5.5%. Iron deficiency anemia represented 69.6% of cases, with no differences between CD and UC. Female sex was the strongest risk factor for anemia in both CD and UC (OR 7.11; 95%CI 4.18-12.10 and 6.55; 95%CI 3.39-12.63, respectively), followed by elevated (≥2mg/dL) C-reactive protein (OR 4.08; 95%CI 2.39-6.97 and 4.58; 95%CI 2.26-9.27, respectively). Current smoking was a risk factor for anemia in CD (OR 2.23; 95%CI 1.24-4.02), but a protective one in UC (OR 0.36; 95%CI 0.14-0.92). A penetrating CD behavior increased the risk of anemia (OR 3.34; 95%CI 1.36-8.21); in UC, anemia increased with disease extension (E2+E3) (OR 1.80; 95%CI 1.13-2.86). Female sex and disease activity are major determinants of anemia at IBD diagnosis. Anemia is associated with disease behavior in CD and with disease extension in UC. Copyright © 2016. Published by Elsevier Ltd.

Tumor necrosis factor-alpha inhibits stem cell factor-induced proliferation of human bone marrow progenitor cells in vitro. Role of p55 and p75 tumor necrosis factor receptors.

PubMed Central

Rusten, L S; Smeland, E B; Jacobsen, F W; Lien, E; Lesslauer, W; Loetscher, H; Dubois, C M; Jacobsen, S E

1994-01-01

Stem cell factor (SCF), a key regulator of hematopoiesis, potently synergizes with a number of hematopoietic growth factors. However, little is known about growth factors capable of inhibiting the actions of SCF. TNF-alpha has been shown to act as a bidirectional regulator of myeloid cell proliferation and differentiation. This study was designed to examine interactions between TNF-alpha and SCF. Here, we demonstrate that TNF-alpha potently and directly inhibits SCF-stimulated proliferation of CD34+ hematopoietic progenitor cells. Furthermore, TNF-alpha blocked all colony formation stimulated by SCF in combination with granulocyte colony-stimulating factor (CSF) or CSF-1. The synergistic effect of SCF observed in combination with GM-CSF or IL-3 was also inhibited by TNF-alpha, resulting in colony numbers similar to those obtained in the absence of SCF. These effects of TNF-alpha were mediated through the p55 TNF receptor, whereas little or no inhibition was signaled through the p75 TNF receptor. Finally, TNF-alpha downregulated c-kit cell-surface expression on CD34+ bone marrow cells, and this was predominantly a p55 TNF receptor-mediated event as well. Images PMID:7518828

CD40 ligation and phagocytosis differently affect the differentiation of monocytes into dendritic cells.

PubMed

Rosenzwajg, Michelle; Jourquin, Frédéric; Tailleux, Ludovic; Gluckman, Jean Claude

2002-12-01

That monocytes can differentiate into macrophages or dendritic cells (DCs) makes them an essential link between innate and adaptive immunity. However, little is known about how interactions with pathogens or T cells influence monocyte engagement toward DCs. We approached this point in cultures where granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4 induced monocytes to differentiate into immature DCs. Activating monocytes with soluble CD40 ligand (CD40L) led to accelerated differentiation toward mature CD83(+) DCs with up-regulated human leukocyte antigen-DR, costimulatory molecules and CD116 (GM-CSF receptor), and down-regulation of molecules involved in antigen capture. Monocytes primed by phagocytosis of antibody-opsonized, killed Escherichia coli differentiated into DCs with an immature phenotype, whereas Zymosan priming yielded active DCs with an intermediate phenotype. Accordingly, DCs obtained from cultures with CD40L or after Zymosan priming had a decreased capacity to endocytose dextran, but only DCs cultured with CD40L had increased capacity to stimulate allogeneic T cells. DCs obtained after E. coli or Zymosan priming of monocytes produced high levels of proinflammatory tumor necrosis factor alpha and IL-6 as well as of regulatory IL-10, but they produced IL-12p70 only after secondary CD40 ligation. Thus, CD40 ligation on monocytes accelerates the maturation of DCs in the presence of GM-CSF/IL-4, whereas phagocytosis of different microorganisms does not alter and even facilitates their potential to differentiate into immature or active DCs, the maturation of which can be completed upon CD40 ligation. In vivo, such differences may correspond to DCs with different trafficking and T helper cell-stimulating capacities that could differently affect induction of adaptive immune responses to infections.

Production of Multiple Transgenic Yucatan Miniature Pigs Expressing Human Complement Regulatory Factors, Human CD55, CD59, and H-Transferase Genes

PubMed Central

Jang, Gun-Hyuk; Jeong, Yeun-Ik; Hwang, In-Sung; Jeong, Yeon-woo; Kim, Yu-Kyung; Shin, Taeyoung; Kim, Nam-Hyung; Hyun, Sang-Hwan; Jeung, Eui-Bae; Hwang, Woo-Suk

2013-01-01

The present study was conducted to generate transgenic pigs coexpressing human CD55, CD59, and H-transferase (HT) using an IRES-mediated polycistronic vector. The study focused on hyperacute rejection (HAR) when considering clinical xenotransplantation as an alternative source for human organ transplants. In total, 35 transgenic cloned piglets were produced by somatic cell nuclear transfer (SCNT) and were confirmed for genomic integration of the transgenes from umbilical cord samples by PCR analysis. Eighteen swine umbilical vein endothelial cells (SUVEC) were isolated from umbilical cord veins freshly obtained from the piglets. We observed a higher expression of transgenes in the transgenic SUVEC (Tg SUVEC) compared with the human umbilical vein endothelial cells (HUVEC). Among these genes, HT and hCD59 were expressed at a higher level in the tested Tg organs compared with non-Tg control organs, but there was no difference in hCD55 expression between them. The transgenes in various organs of the Tg clones revealed organ-specific and spatial expression patterns. Using from 0 to 50% human serum solutions, we performed human complement-mediated cytolysis assays. The results showed that, overall, the Tg SUVEC tested had greater survival rates than did the non-Tg SUVEC, and the Tg SUVEC with higher HT expression levels tended to have more down-regulated α-Gal epitope expression, resulting in greater protection against cytotoxicity. By contrast, several Tg SUVEC with low CD55 expression exhibited a decreased resistance response to cytolysis. These results indicated that the levels of HT expression were inversely correlated with the levels of α-Gal epitope expression and that the combined expression of hCD55, hCD59, and HT proteins in SUVECs markedly enhances a protective response to human serum-mediated cytolysis. Taken together, these results suggest that combining a polycistronic vector system with SCNT methods provides a fast and efficient alternative for the generation of transgenic large animals with multiple genetic modifications. PMID:23704897

Fistulizing pattern in Crohn's disease and pancolitis in ulcerative colitis are independent risk factors for cancer: a single-center cohort study.

PubMed

Biancone, Livia; Zuzzi, Sara; Ranieri, Micaela; Petruzziello, Carmelina; Calabrese, Emma; Onali, Sara; Ascolani, Marta; Zorzi, Francesca; Condino, Giovanna; Iacobelli, Simona; Pallone, Francesco

2012-06-01

The combined role of immunomodulators (IMM) and clinical characteristics of Inflammatory Bowel Disease (IBD) in determining the cancer risk is undefined. The aim was to assess whether clinical characteristics of IBD are independent risk factors for cancer, when considering thiopurines and anti-TNFs use. In a single-center cohort study, clinical characteristics of IBD patients with IBD duration ≥1 year and ≥2 visits from 2000 to 2009 were considered. Tests for crude rates and survival analysis methods were used to assess differences of incidence of cancer between groups. The methods were adjusted for the time interval between diagnosis and immunomodulatory treatments. IBD population included 1222 patients :615 Crohn's disease (CD), 607 ulcerative colitis (UC). Cancer was diagnosed in 51 patients (34 CD,17 UC), with an incidence rate of 4.3/1000 pt/year. The incidence rate of cancer was comparable between CD and UC (4.6/1000 pt/year vs 2.9/1000 pt/year ;p=n.s.). Cancer most frequently involved the breast, the GI tract, the skin. Lymphoma was diagnosed in CD (1HL, 1NHL,0 HSTCL). Risk factors for cancer included older age at diagnosis of IBD (CD: HR 1.25;95%CI 1.08-1.45; UC:HR 1.33;95%CI 1.15-1.55 for an increase by 5 years; p=0.0023; p=0.0002), fistulizing pattern in CD (HR 2.55; 95%CI 1.11-5.86,p=0.0275), pancolitis in UC (HR 2.79;95%CI 1.05-7.40 p=0.0396 vs distal). IMM and anti-TNFs did not increase the cancer risk in CD, neither IMM in UC (anti-TNFs risk in UC not feasible as no cases observed). Fistulizing pattern in CD, pancolitis in UC and older age at diagnosis of IBD are independent risk factors for cancer. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Calibration of an analyzing magnet using the 12C(d, p0)13C nuclear reaction with a thick carbon target

NASA Astrophysics Data System (ADS)

Andrade, E.; Canto, C. E.; Rocha, M. F.

2017-09-01

The absolute energy of an ion beam produced by an accelerator is usually determined by an electrostatic or magnetic analyzer, which in turn must be calibrated. Various methods for accelerator energy calibration are extensively reported in the literature, like nuclear reaction resonances, neutron threshold, and time of flight, among others. This work reports on a simple method to calibrate the magnet associated to a vertical 5.5 MV Van de Graaff accelerator. The method is based on bombarding with deuteron beams a thick carbon target and measuring with a surface barrier detector the particle energy spectra produced. The analyzer magnetic field is measured for each spectrum and the beam energy is deduced by the best fit of the simulation of the spectrum with the SIMNRA code that includes 12C(d,p0)13C nuclear cross sections.

Regional accumulation characteristics of cadmium in vegetables: Influencing factors, transfer model and indication of soil threshold content.

PubMed

Yang, Yang; Chen, Weiping; Wang, Meie; Peng, Chi

2016-12-01

A regional investigation in the Youxian prefecture, southern China, was conducted to analyze the impact of environmental factors including soil properties and irrigation in conjunction with the use of fertilizers on the accumulation of Cd in vegetables. The Cd transfer potential from soil to vegetable was provided by the plant uptake factor (PUF), which varied by three orders of magnitude and was described by a Gaussian distribution model. The soil pH, content of soil organic matter (SOM), concentrations of Zn in the soil, pH of irrigation water and nitrogenous fertilizers contributed significantly to the PUF variations. A path model analysis, however, revealed the principal control of the PUF values resulted from the soil pH, soil Zn concentrations and SOM. Transfer functions were developed using the total soil Cd concentrations, soil pH, and SOM. They explained 56% of the variance for all samples irrespective of the vegetable genotypes. The transfer functions predicted the probability of exceeding China food safety standard concentrations for Cd in four major consumable vegetables under different soil conditions. Poor production practices in the study area involved usage of soil with pH values ≤ 5.5, especially for the cultivation of Raphanus sativus L., even with soil Cd concentrations below the China soil quality standard. We found the soil standard Cd concentrations for cultivating vegetables was not strict enough for strongly acidic (pH ≤ 5.5) and SOM-poor (SOM ≤ 10 g kg -1 ) soils present in southern China. It is thus necessary to address the effect of environmental variables to generate a suitable Cd threshold for cultivated soils. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rescue of CD8+ T cell vaccine memory following sublethal γ irradiation.

PubMed

McFarland, Hugh I; Berkson, Julia D; Lee, Jay P; Elkahloun, Abdel G; Mason, Karen P; Rosenberg, Amy S

2015-07-31

Sublethal γ irradiation eliminates CD8+ T cell mediated memory responses. In this work, we explored how these memory responses could be rescued in the aftermath of such exposure. We utilized two models of CD8+ T cell mediated immunity: a mouse model of Listeria monocytogenes (LM) infection in which CD8+ T cells specific for LM expressed antigens (Listeriolysin O, LLO) can be tracked, and a murine skin graft model in which CD8+ T cells mediate rejection across a MHC class I (D(d)) disparity. In the LM immunized mice, LL0 specific CD8+ T memory cells were lost on irradiation, preserved with rapid revaccination with an attenuated strain 1-3 days post-irradiation (PI), and these mice survived a subsequent wild type LM challenge. A genetic "signature of rescue" identified a group of immune-associated mRNA maintained or upregulated following irradiation and rescue. A number of these factors, including IL-36γ, dectin-2 (Clec4n), and mir101c are upregulated rapidly after exposure of mice to sublethal γ radiation alone and are sustained by early, but not later rescue. Such factors will be evaluated as potential therapeutics to replace individual vaccines for global rescue of CD8+ T memory cell responses following sublethal γ irradiation. The skin allograft model mirrored that of the LM model in that the accelerated D(d) skin allograft rejection response was lost in mice exposed to sublethal γ radiation, but infusion of allogeneic D(d) expressing bone marrow cells 1-4 days PI preserved the CD8+ T memory mediated accelerated rejection response, further suggesting that innate immune responses may not always be essential to rescue of CD8+ memory T cells following γ irradiation. Published by Elsevier Ltd.

Downregulation of membrane complement inhibitors CD55 and CD59 by siRNA sensitises uterine serous carcinoma overexpressing Her2/neu to complement and antibody-dependent cell cytotoxicity in vitro: implications for trastuzumab-based immunotherapy.

PubMed

Bellone, S; Roque, D; Cocco, E; Gasparrini, S; Bortolomai, I; Buza, N; Abu-Khalaf, M; Silasi, D-A; Ratner, E; Azodi, M; Schwartz, P E; Rutherford, T J; Pecorelli, S; Santin, A D

2012-04-24

We evaluated the expression of CD46, CD55 and CD59 membrane-bound complement-regulatory proteins (mCRPs) in primary uterine serous carcinoma (USC) and the ability of small interfering RNA (siRNA) against these mCRPs to sensitise USC to complement-dependent cytotoxicity (CDC) and antibody (trastuzumab)-dependent cellular cytotoxicity (ADCC) in vitro. Membrane-bound complement-regulatory proteins expression was evaluated using real-time PCR (RT-PCR) and flow cytometry, whereas Her2/neu expression and c-erbB2 gene amplification were assessed using immunohistochemistry, flow cytometry and fluorescent in-situ hybridisation. The biological effect of siRNA-mediated knockdown of mCRPs on HER2/neu-overexpressing USC cell lines was evaluated in CDC and ADCC 4-h chromium-release assays. High expression of mCRPs was found in USC cell lines when compared with normal endometrial cells (P<0.05). RT-PCR and FACS analyses demonstrated that anti-mCRP siRNAs were effective in reducing CD46, CD55 and CD59 expression on USC (P<0.05). Baseline complement-dependent cytotoxicity (CDC) against USC cell lines was low (mean ± s.e.m.=6.8 ± 0.9%) but significantly increased upon CD55 and CD59 knockdown (11.6 ± 0.8% and 10.7 ± 0.9%, respectively, P<0.05). Importantly, in the absence of complement, both CD55 and CD59, but not CD46, knockdowns significantly augmented ADCC against USC overexpressing Her2/neu. Uterine serous carcinoma express high levels of the mCRPs CD46, CD55 and CD59. Small interfering RNA inhibition of CD55 and CD59, but not CD46, sensitises USC to both CDC and ADCC in vitro, and if specifically targeted to tumour cells, may significantly increase trastuzumab-mediated therapeutic effect in vivo.

Clinicopathological characteristics of primary gastric T-cell lymphoma.

PubMed

Kawamoto, Kenichiro; Nakamura, Shotaro; Iwashita, Akinori; Watanabe, Jiro; Oshiro, Yumi; Nakayama, Yoshifuku; Nimura, Satoshi; Kimura, Nobuhiro; Aoyagi, Kunihiko; Yao, Takashi; Kuramochi, Shigeru; Matsuyama, Atsuji; Kurihara, Kenji; Ohshima, Koichi; Takeshita, Morishige

2009-12-01

To investigate the clinicopathological characteristics of 20 primary gastric T-cell lymphoma (GTCL) cases without human T-lymphotropic virus type I infection in Japan, a non-endemic area for coeliac disease. Fifteen cases had no history of persistent diarrhoea or severe hypoproteinaemia. Histologically, 13 cases (65%) consisted of large cell lymphoma and seven (35%) were of medium-sized cells. Intraepithelial lymphoma cell invasion was found in three cases (15%). Two of 10 surgical cases (20%) showed intramucosal tumour cell spreading with enteropathy-like features. Helicobacter pylori CagA gene was detected in three of 10 cases (30%). The lymphoma cells of all 20 cases were positive for CD3 and/or TCRbetaF1 and negative for CD56. CD4- and CD8- lymphoma was found in 11 cases (55%), CD4+ lymphoma in seven (35%) and CD8+ lymphoma in two (10%). CD30+, CD5+ and CD25+ lymphomas were detected in nine (45%), 10 (50%) and 11 (55%) cases, respectively. Five-year survival of the 16 available cases was 54%. Early clinical stage and medium-sized cell lymphoma were significantly (P < 0.05) better prognostic factors. Patients with GTCL exhibit distinct clinicopathological findings and prognoses from those with enteropathy-associated T-cell lymphomas. GTCL may be mainly derived from lamina propria and parafollicular T cells.

Effect of Temperature and Moisture on the Development of Concealed Damage in Raw Almonds (Prunus dulcis).

PubMed

Rogel-Castillo, Cristian; Zuskov, David; Chan, Bronte Lee; Lee, Jihyun; Huang, Guangwei; Mitchell, Alyson E

2015-09-23

Concealed damage (CD) is a brown discoloration of nutmeat that appears only after kernels are treated with moderate heat (e.g., roasting). Identifying factors that promote CD in almonds is of significant interest to the nut industry. Herein, the effect of temperature (35 and 45 °C) and moisture (<5, 8, and 11%) on the composition of volatiles in raw almonds (Prunus dulcis var. Nonpareil) was studied using HS-SPME-GC/MS. A CIE LCh colorimetric method was developed to identify raw almonds with CD. A significant increase in CD was demonstrated in almonds exposed to moisture (8% kernel moisture content) at 45 °C as compared to 35 °C. Elevated levels of volatiles related to lipid peroxidation and amino acid degradation were observed in almonds with CD. These results suggest that postharvest moisture exposure resulting in an internal kernel moisture ≥ 8% is a key factor in the development of CD in raw almonds and that CD is accelerated by temperature.

In vivo imaging of the inflammatory receptor CD40 after cerebral ischemia using a fluorescent antibody.

PubMed

Klohs, Jan; Gräfe, Michael; Graf, Kristof; Steinbrink, Jens; Dietrich, Thore; Stibenz, Dietger; Bahmani, Peyman; Kronenberg, Golo; Harms, Christoph; Endres, Matthias; Lindauer, Ute; Greger, Klaus; Stelzer, Ernst H K; Dirnagl, Ulrich; Wunder, Andreas

2008-10-01

Brain inflammation is a hallmark of stroke, where it has been implicated in tissue damage as well as in repair. Imaging technologies that specifically visualize these processes are highly desirable. In this study, we explored whether the inflammatory receptor CD40 can be noninvasively and specifically visualized in mice after cerebral ischemia using a fluorescent monoclonal antibody, which we labeled with the near-infrared fluorescence dye Cy5.5 (Cy5.5-CD40MAb). Wild-type and CD40-deficient mice were subjected to transient middle cerebral artery occlusion. Mice were either intravenously injected with Cy5.5-CD40MAb or control Cy5.5-IgGMAb. Noninvasive and ex vivo near-infrared fluorescence imaging was performed after injection of the compounds. Probe distribution and specificity was further assessed with single-plane illumination microscopy, immunohistochemistry, and confocal microscopy. Significantly higher fluorescence intensities over the stroke-affected hemisphere, compared to the contralateral side, were only detected noninvasively in wild-type mice that received Cy5.5-CD40MAb, but not in CD40-deficient mice injected with Cy5.5-CD40MAb or in wild-type mice that were injected with Cy5.5-IgGMAb. Ex vivo near-infrared fluorescence showed an intense fluorescence within the ischemic territory only in wild-type mice injected with Cy5.5-CD40MAb. In the brains of these mice, single-plane illumination microscopy demonstrated vascular and parenchymal distribution, and confocal microscopy revealed a partial colocalization of parenchymal fluorescence from the injected Cy5.5-CD40MAb with activated microglia and blood-derived cells in the ischemic region. The study demonstrates that a CD40-targeted fluorescent antibody enables specific noninvasive detection of the inflammatory receptor CD40 after cerebral ischemia using optical techniques.

Posttransplant Immune Activation: Innocent Bystander or Insidious Culprit of Posttransplant Accelerated Atherosclerosis.

PubMed

Ducloux, Didier; Bamoulid, Jamal; Crepin, Thomas; Rebibou, Jean-Michel; Courivaud, Cecile; Saas, Philippe

2017-09-01

Cardiovascular disease is a major cause of morbidity, disability, and mortality in kidney transplant patients. Cumulative reports indicate that the excessive risk of cardiovascular events is not entirely explained by the increased prevalence of traditional cardiovascular risk factors. Atherosclerosis is a chronic inflammatory disease, and it has been postulated that posttransplant immune disturbances may explain the gap between the predicted and observed risks of cardiovascular events. Although concordant data suggest that innate immunity contributes to the posttransplant accelerated atherosclerosis, only few arguments plead for a role of adaptive immunity. We report and discuss here consistent data demonstrating that CD8 + T cell activation is a frequent posttransplant immune feature that may have pro-atherogenic effects. Expansion of exhausted/activated CD8 + T cells in kidney transplant recipients is stimulated by several factors including cytomegalovirus infections, lymphodepletive therapy (e.g., antithymocyte globulins), chronic allogeneic stimulation, and a past history of renal insufficiency. This is observed in the setting of decreased thymic activity, a process also found in elderly individuals and reflecting accelerated immune senescence.

Human papillomavirus E6 protein enriches the CD55(+) population in cervical cancer cells, promoting radioresistance and cancer aggressiveness.

PubMed

Leung, Thomas Ho-Yin; Tang, Hermit Wai-Man; Siu, Michelle Kwan-Yee; Chan, David Wai; Chan, Karen Kar-Loen; Cheung, Annie Nga-Yin; Ngan, Hextan Yuen-Sheung

2018-02-01

Accumulating evidence indicates that the human papillomavirus (HPV) E6 protein plays a crucial role in the development of cervical cancer. Subpopulations of cells that reside within tumours are responsible for tumour resistance to cancer therapy and recurrence. However, the identity of such cells residing in cervical cancer and their relationship with the HPV-E6 protein have not been identified. Here, we isolated sphere-forming cells, which showed self-renewal ability, from primary cervical tumours. Gene expression profiling revealed that cluster of differentiation (CD) 55 was upregulated in primary cervical cancer sphere cells. Flow-cytometric analysis detected abundant CD55(+) populations among a panel of HPV-positive cervical cancer cell lines, whereas few CD55(+) cells were found in HPV-negative cervical cancer and normal cervical epithelial cell lines. The CD55(+) subpopulation isolated from the C33A cell line showed significant sphere-forming ability and enhanced tumourigenicity, cell migration, and radioresistance. In contrast, the suppression of CD55 in HPV-positive CaSki cells inhibited tumourigenicity both in vitro and in vivo, and sensitized cells to radiation treatment. In addition, ectopic expression of the HPV-E6 protein in HPV-negative cervical cancer cells dramatically enriched the CD55(+) subpopulation. CRISPR/Cas9 knockout of CD55 in an HPV-E6-overexpressing stable clone abolished the tumourigenic effects of the HPV-E6 protein. Taken together, our data suggest that HPV-E6 protein expression enriches the CD55(+) population, which contributes to tumourigenicity and radioresistance in cervical cancer cells. Targeting CD55 via CRISPR/Cas9 may represent a novel avenue for developing new strategies and effective therapies for the treatment of cervical cancer. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Seismic design parameters - A user guide

USGS Publications Warehouse

Leyendecker, E.V.; Frankel, A.D.; Rukstales, K.S.

2001-01-01

The 1997 NEHRP Recommended Provisions for Seismic Regulations for New Buildings (1997 NEHRP Provisions) introduced seismic design procedure that is based on the explicit use of spectral response acceleration rather than the traditional peak ground acceleration and/or peak ground velocity or zone factors. The spectral response accelerations are obtained from spectral response acceleration maps accompanying the report. Maps are available for the United States and a number of U.S. territories. Since 1997 additional codes and standards have also adopted seismic design approaches based on the same procedure used in the NEHRP Provisions and the accompanying maps. The design documents using the 1997 NEHRP Provisions procedure may be divided into three categories -(1) Design of New Construction, (2) Design and Evaluation of Existing Construction, and (3) Design of Residential Construction. A CD-ROM has been prepared for use in conjunction with the design documents in each of these three categories. The spectral accelerations obtained using the software on the CD are the same as those that would be obtained by using the maps accompanying the design documents. The software has been prepared to operate on a personal computer using a Windows (Microsoft Corporation) operating environment and a point and click type of interface. The user can obtain the spectral acceleration values that would be obtained by use of the maps accompanying the design documents, include site factors appropriate for the Site Class provided by the user, calculate a response spectrum that includes the site factor, and plot a response spectrum. Sites may be located by providing the latitude-longitude or zip code for all areas covered by the maps. All of the maps used in the various documents are also included on the CDROM

Active chinese mistletoe lectin-55 enhances colon cancer surveillance through regulating innate and adaptive immune responses

PubMed Central

Ma, Yan-Hui; Cheng, Wei-Zhi; Gong, Fang; Ma, An-Lun; Yu, Qi-Wen; Zhang, Ji-Ying; Hu, Chao-Ying; Chen, Xue-Hua; Zhang, Dong-Qing

2008-01-01

AIM: To investigate the potential role of Active Chinese mistletoe lectin-55 (ACML-55) in tumor immune surveillance. METHODS: In this study, an experimental model was established by hypodermic inoculating the colon cancer cell line CT26 (5 × 105 cells) into BALB/c mice. The experimental treatment was orally administered with ACML-55 or PBS, followed by the inoculation of colon cancer cell line CT26. Intracellular cytokine staining was used to detect IFN-γ production by tumor antigen specific CD8+ T cells. FACS analysis was employed to profile composition and activation of CD4+, CD8+, γδ T and NK cells. RESULTS: Our results showed, compared to PBS treated mice, ACML-55 treatment significantly delayed colon cancer development in colon cancer -bearing Balb/c mice in vivo. Treatment with ACML-55 enhanced both Ag specific activation and proliferation of CD4+ and CD8+ T cells, and increased the number of tumor Ag specific CD8+ T cells. It was more important to increase the frequency of tumor Ag specific IFN-γ producing-CD8+ T cells. Interestingly, ACML-55 treatment also showed increased cell number of NK, and γδT cells, indicating the role of ACML-55 in activation of innate lymphocytes. CONCLUSION: Our results demonstrate that ACML-55 therapy can enhance function in immune surveillance in colon cancer-bearing mice through regulating both innate and adaptive immune responses. PMID:18785279

Role of transcription factor Sp1 and RNA binding protein HuR in the down-regulation of Dr+ Escherichia coli receptor protein Decay Accelerating Factor (DAF or CD55) by Nitric oxide

PubMed Central

Banadakoppa, Manu; Liebenthal, Daniel; Nowak, David E; Urvil, Petri; Yallampalli, Uma; Wilson, Gerald M; Kishor, Aparna; Yallampalli, Chandra

2012-01-01

We previously reported that nitric oxide (NO) reduces the rate of bacteremia and maternal mortality in pregnant rats with uterine infection by Escherichia coli expressing the Dr Fimbria (Dr+). The epithelial invasion of Dr+ E. coli is dependent on the expression level of its cellular receptor decay accelerating factor (DAF). NO reduces the rate of bacteremia by down-regulating the expression of DAF. In this study, we elucidated the role of transcription factor Sp1 and RNA binding protein HuR in the down-regulation of human DAF by NO. We generated a series of deletion mutant constructs of DAF gene 5′-untranslated region and mapped NO-response region upstream to the core promoter region of the DAF gene. One of the several Sp1 binding sites in the DAF 5′-untranslated region was located within the NO-response region. The binding of Sp1 to this site was inhibited by NO. Furthermore, NO also promoted the degradation of DAF mRNA. The 3′-untranslated region of DAF harbors an AU-rich element and this element destabilized the mRNA transcript. The NO promoted the rapid degradation of DAF mRNA by inhibiting the binding of mRNA stabilizing protein HuR to this AU-rich region. The inhibition of binding of HuR to AU-rich region was due to the S-nitrosylation of one or more cysteine residues by NO. Thus, these data reveal the molecular mediators of transcriptional and post-transcriptional regulation of DAF by NO with implications in pathophysiology related to DAF. PMID:23176121

Role of transcription factor Sp1 and RNA binding protein HuR in the downregulation of Dr+ Escherichia coli receptor protein decay accelerating factor (DAF or CD55) by nitric oxide.

PubMed

Banadakoppa, Manu; Liebenthal, Daniel; Nowak, David E; Urvil, Petri; Yallampalli, Uma; Wilson, Gerald M; Kishor, Aparna; Yallampalli, Chandra

2013-02-01

We previously reported that nitric oxide (NO) reduces the rate of bacteremia and maternal mortality in pregnant rats with uterine infection by Escherichia coli expressing the Dr Fimbria (Dr(+) ). The epithelial invasion of Dr(+) E. coli is dependent on the expression level of its cellular receptor decay accelerating factor (DAF). NO reduces the rate of bacteremia by downregulating the expression of DAF. In this study, we elucidated the role of transcription factor Sp1 and RNA binding protein HuR in the downregulation of human DAF by NO. We generated a series of deletion mutant constructs of DAF gene 5'-untranslated region and mapped the NO-response region upstream to the core promoter region of the DAF gene. One of the several Sp1 binding sites in the DAF 5'-untranslated region was located within the NO-response region. The binding of Sp1 to this site was inhibited by NO. Furthermore, NO also promoted the degradation of DAF mRNA. The 3'-untranslated region of DAF harbors an AU-rich element and this element destabilized the mRNA transcript. NO promoted the rapid degradation of DAF mRNA by inhibiting the binding of mRNA stabilizing protein HuR to this AU-rich region. The inhibition of binding of HuR to the AU-rich region was due to the S-nitrosylation of one or more cysteine residues by NO. Thus, these data reveal the molecular mediators of transcriptional and post-transcriptional regulation of DAF by NO with implications in pathophysiology related to DAF. © 2012 The Authors Journal compilation © 2012 FEBS.

A Paracrine Mechanism Accelerating Expansion of Human Induced Pluripotent Stem Cell-Derived Hepatic Progenitor-Like Cells

PubMed Central

Tsuruya, Kota; Chikada, Hiromi; Ida, Kinuyo; Anzai, Kazuya; Kagawa, Tatehiro; Inagaki, Yutaka; Mine, Tetsuya

2015-01-01

Hepatic stem/progenitor cells in liver development have a high proliferative potential and the ability to differentiate into both hepatocytes and cholangiocytes. In this study, we focused on the cell surface molecules of human induced pluripotent stem (iPS) cell-derived hepatic progenitor-like cells (HPCs) and analyzed how these molecules modulate expansion of these cells. Human iPS cells were differentiated into immature hepatic lineage cells by cytokines. In addition to hepatic progenitor markers (CD13 and CD133), the cells were coimmunostained for various cell surface markers (116 types). The cells were analyzed by flow cytometry and in vitro colony formation culture with feeder cells. Twenty types of cell surface molecules were highly expressed in CD13+CD133+ cells derived from human iPS cells. Of these molecules, CD221 (insulin-like growth factor receptor), which was expressed in CD13+CD133+ cells, was quickly downregulated after in vitro expansion. The proliferative ability was suppressed by a neutralizing antibody and specific inhibitor of CD221. Overexpression of CD221 increased colony-forming ability. We also found that inhibition of CD340 (erbB2) and CD266 (fibroblast growth factor-inducible 14) signals suppressed proliferation. In addition, both insulin-like growth factor (a ligand of CD221) and tumor necrosis factor-like weak inducer of apoptosis (a ligand of CD266) were provided by feeder cells in our culture system. This study revealed the expression profiles of cell surface molecules in human iPS cell-derived HPCs and that the paracrine interactions between HPCs and other cells through specific receptors are important for proliferation. PMID:25808356

A Paracrine Mechanism Accelerating Expansion of Human Induced Pluripotent Stem Cell-Derived Hepatic Progenitor-Like Cells.

PubMed

Tsuruya, Kota; Chikada, Hiromi; Ida, Kinuyo; Anzai, Kazuya; Kagawa, Tatehiro; Inagaki, Yutaka; Mine, Tetsuya; Kamiya, Akihide

2015-07-15

Hepatic stem/progenitor cells in liver development have a high proliferative potential and the ability to differentiate into both hepatocytes and cholangiocytes. In this study, we focused on the cell surface molecules of human induced pluripotent stem (iPS) cell-derived hepatic progenitor-like cells (HPCs) and analyzed how these molecules modulate expansion of these cells. Human iPS cells were differentiated into immature hepatic lineage cells by cytokines. In addition to hepatic progenitor markers (CD13 and CD133), the cells were coimmunostained for various cell surface markers (116 types). The cells were analyzed by flow cytometry and in vitro colony formation culture with feeder cells. Twenty types of cell surface molecules were highly expressed in CD13(+)CD133(+) cells derived from human iPS cells. Of these molecules, CD221 (insulin-like growth factor receptor), which was expressed in CD13(+)CD133(+) cells, was quickly downregulated after in vitro expansion. The proliferative ability was suppressed by a neutralizing antibody and specific inhibitor of CD221. Overexpression of CD221 increased colony-forming ability. We also found that inhibition of CD340 (erbB2) and CD266 (fibroblast growth factor-inducible 14) signals suppressed proliferation. In addition, both insulin-like growth factor (a ligand of CD221) and tumor necrosis factor-like weak inducer of apoptosis (a ligand of CD266) were provided by feeder cells in our culture system. This study revealed the expression profiles of cell surface molecules in human iPS cell-derived HPCs and that the paracrine interactions between HPCs and other cells through specific receptors are important for proliferation.

Relative Contribution of Cellular Complement Inhibitors CD59, CD46, and CD55 to Parainfluenza Virus 5 Inhibition of Complement-Mediated Neutralization

PubMed Central

Li, Yujia; Parks, Griffith D.

2018-01-01

The complement system is a part of the innate immune system that viruses need to face during infections. Many viruses incorporate cellular regulators of complement activation (RCA) to block complement pathways and our prior work has shown that Parainfluenza virus 5 (PIV5) incorporates CD55 and CD46 to delay complement-mediated neutralization. In this paper, we tested the role of a third individual RCA inhibitor CD59 in PIV5 interactions with complement pathways. Using a cell line engineered to express CD59, we show that small levels of functional CD59 are associated with progeny PIV5, which is capable of blocking assembly of the C5b-C9 membrane attack complex (MAC). PIV5 containing CD59 (PIV5-CD59) showed increased resistance to complement-mediated neutralization in vitro comparing to PIV5 lacking regulators. Infection of A549 cells with PIV5 and RSV upregulated CD59 expression. TGF-beta treatment of PIV5-infected cells also increased cell surface CD59 expression and progeny virions were more resistant to complement-mediated neutralization. A comparison of individual viruses containing only CD55, CD46, or CD59 showed a potency of inhibiting complement-mediated neutralization, which followed a pattern of CD55 > CD46 > CD59. PMID:29693588

Co-administration of plasmid-encoded granulocyte-macrophage colony-stimulating factor increases human immunodeficiency virus-1 DNA vaccine-induced polyfunctional CD4+ T-cell responses

PubMed Central

Santana, Vinicius Canato; Almeida, Rafael Ribeiro; Ribeiro, Susan Pereira; Ferreira, Luís Carlos de Souza; Kalil, Jorge; Rosa, Daniela Santoro; Cunha-Neto, Edecio

2015-01-01

T-cell based vaccines against human immunodeficiency virus (HIV) generate specific responses that may limit both transmission and disease progression by controlling viral load. Broad, polyfunctional, and cytotoxic CD4+T-cell responses have been associated with control of simian immunodeficiency virus/HIV-1 replication, supporting the inclusion of CD4+ T-cell epitopes in vaccine formulations. Plasmid-encoded granulocyte-macrophage colony-stimulating factor (pGM-CSF) co-administration has been shown to induce potent CD4+ T-cell responses and to promote accelerated priming and increased migration of antigen-specific CD4+ T-cells. However, no study has shown whether co-immunisation with pGM-CSF enhances the number of vaccine-induced polyfunctional CD4+ T-cells. Our group has previously developed a DNA vaccine encoding conserved, multiple human leukocyte antigen (HLA)-DR binding HIV-1 subtype B peptides, which elicited broad, polyfunctional and long-lived CD4+ T-cell responses. Here, we show that pGM-CSF co-immunisation improved both magnitude and quality of vaccine-induced T-cell responses, particularly by increasing proliferating CD4+ T-cells that produce simultaneously interferon-γ, tumour necrosis factor-α and interleukin-2. Thus, we believe that the use of pGM-CSF may be helpful for vaccine strategies focused on the activation of anti-HIV CD4+ T-cell immunity. PMID:26602876

Potential ecological risk assessment and prediction of soil heavy-metal pollution around coal gangue dump

NASA Astrophysics Data System (ADS)

Jiang, X.; Lu, W. X.; Zhao, H. Q.; Yang, Q. C.; Yang, Z. P.

2014-06-01

The aim of the present study is to evaluate the potential ecological risk and trend of soil heavy-metal pollution around a coal gangue dump in Jilin Province (Northeast China). The concentrations of Cd, Pb, Cu, Cr and Zn were monitored by inductively coupled plasma mass spectrometry (ICP-MS). The potential ecological risk index method developed by Hakanson (1980) was employed to assess the potential risk of heavy-metal pollution. The potential ecological risk in the order of ER(Cd) > ER(Pb) > ER(Cu) > ER(Cr) > ER(Zn) have been obtained, which showed that Cd was the most important factor leading to risk. Based on the Cd pollution history, the cumulative acceleration and cumulative rate of Cd were estimated, then the fixed number of years exceeding the standard prediction model was established, which was used to predict the pollution trend of Cd under the accelerated accumulation mode and the uniform mode. Pearson correlation analysis and correspondence analysis are employed to identify the sources of heavy metals and the relationship between sampling points and variables. These findings provided some useful insights for making appropriate management strategies to prevent or decrease heavy-metal pollution around a coal gangue dump in the Yangcaogou coal mine and other similar areas elsewhere.

Potential ecological risk assessment and prediction of soil heavy metal pollution around coal gangue dump

NASA Astrophysics Data System (ADS)

Jiang, X.; Lu, W. X.; Yang, Q. C.; Yang, Z. P.

2014-03-01

Aim of the present study is to evaluate the potential ecological risk and predict the trend of soil heavy metal pollution around a~coal gangue dump in Jilin Province (Northeast China). The concentrations of Cd, Pb, Cu, Cr and Zn were monitored by inductively coupled plasma mass spectrometry (ICP-MS). The potential ecological risk index method developed by Hakanson (1980) was employed to assess the potential risk of heavy metal pollution. The potential ecological risk in an order of E(Cd) > E(Pb) > E(Cu) > E(Cr) > E(Zn) have been obtained, which showed that Cd was the most important factor led to risk. Based on the Cd pollution history, the cumulative acceleration and cumulative rate of Cd were estimated, and the fixed number of years exceeding standard prediction model was established, which was used to predict the pollution trend of Cd under the accelerated accumulation mode and the uniform mode. Pearson correlation analysis and correspondence analysis are employed to identify the sources of heavy metal, and the relationship between sampling points and variables. These findings provide some useful insights for making appropriate management strategies to prevent and decrease heavy metal pollution around coal gangue dump in Yangcaogou coal mine and other similar areas elsewhere.

Self-discharge mechanism of sealed-type nickel/metal-hydride battery

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

Ikoma, Munehisa; Hoshina, Yasuko; Matsumoto, Isao

1996-06-01

Factors affecting the self-discharge rate of a nickel/metal-hydride (Ni-MH) battery, generally much higher than that of nickel/cadmium (Ni-Cd) battery, are investigated, and the self-discharge mechanism is discussed. Ammonia and amine participate in the shuttle reaction like nitrate ion in the Ni-Cd battery, resulting in acceleration of the self-discharge. When nonwoven fabric made of sulfonated-polypropylene is used as a separator instead of conventional polyamide separator, the self-discharge rate of the Ni-MH battery is strongly depressed, to the same level as that of Ni-Cd battery.

Dendritic cells modulate burn wound healing by enhancing early proliferation.

PubMed

Vinish, Monika; Cui, Weihua; Stafford, Eboni; Bae, Leon; Hawkins, Hal; Cox, Robert; Toliver-Kinsky, Tracy

2016-01-01

Adequate wound healing is vital for burn patients to reduce the risk of infections and prolonged hospitalization. Dendritic cells (DCs) are antigen presenting cells that release cytokines and are central for the activation of innate and acquired immune responses. Studies have showed their presence in human burn wounds; however, their role in burn wound healing remains to be determined. This study investigated the role of DCs in modulating healing responses within the burn wound. A murine model of full-thickness contact burns was used to study wound healing in the absence of DCs (CD11c promoter-driven diphtheria toxin receptor transgenic mice) and in a DC-rich environment (using fms-like tyrosine kinase-3 ligand, FL- a DC growth factor). Wound closure was significantly delayed in DC-deficient mice and was associated with significant suppression of early cellular proliferation, granulation tissue formation, wound levels of TGFβ1 and formation of CD31+ vessels in healing wounds. In contrast, DC enhancement significantly accelerated early wound closure, associated with increased and accelerated cellular proliferation, granulation tissue formation, and increased TGFβ1 levels and CD31+ vessels in healing wounds. We conclude that DCs play an important role in the acceleration of early wound healing events, likely by secreting factors that trigger the proliferation of cells that mediate wound healing. Therefore, pharmacological enhancement of DCs may provide a therapeutic intervention to facilitate healing of burn wounds. © 2016 by the Wound Healing Society.

Paradoxical drop in circulating neutrophil count following granulocyte-colony stimulating factor and stem cell factor administration in rhesus macaques.

PubMed

Gordon, Brent C; Revenis, Amy M; Bonifacino, Aylin C; Sander, William E; Metzger, Mark E; Krouse, Allen E; Usherson, Tatiana N; Donahue, Robert E

2007-06-01

Granulocyte colony-stimulating factor (G-CSF) is frequently used therapeutically to treat chronic or transient neutropenia and to mobilize hematopoietic stem cells. Shortly following G-CSF administration, we observed a dramatic transient drop in circulating neutrophil number. This article characterizes this effect in a rhesus macaque animal model. Hematologic changes were monitored following subcutaneous (SQ) administration of G-CSF. G-CSF was administered as a single SQ dose at 10 microg/kg or 50 microg/kg. It was also administered (10 microg/kg) in combination with stem cell factor (SCF; 200 microg/kg) over 5 days. Flow cytometry was performed on serial blood samples to detect changes in cell surface adhesion protein expression. Neutrophil count dramatically declined 30 minutes after G-CSF administration. This decline was observed whether 10 microg/kg G-CSF was administered in combination with SCF over 5 days, or given as a single 10 microg/kg dose. At a single 50 microg/kg dose, the decline accelerated to 15 minutes. Neutrophil count returned to baseline after 120 minutes and rapidly increased thereafter. An increase in CD11a and CD49d expression coincided with the drop in neutrophil count. A transient paradoxical decline in neutrophil count was observed following administration of G-CSF either alone or in combination with SCF. This decline accelerated with the administration of a higher dose of G-CSF and was associated with an increase in CD11a and CD49d expression. It remains to be determined whether this decline in circulating neutrophils is associated with an increase in endothelial margination and/or entrance into extravascular compartments.

Factors associated with the immune response to hepatitis A vaccination in HIV-infected patients in the era of highly active antiretroviral therapy.

PubMed

Mena, Guillermo; García-Basteiro, Alberto L; Llupià, Anna; Díez, Consolación; Costa, Josep; Gatell, Josep-María; García, Felipe; Bayas, José-María

2013-08-12

HIV seropositivity is considered a risk factor for complications in hepatitis A virus (HAV) infection. HAV vaccination schedules are widely implemented in HIV-infected patients, but the immune response remains impaired. We analysed the response to vaccination (antiHAV titres ≥20IU/l) in 282 HIV-infected patients included in a standard (1440 Elisa Units (EU) at 0, 6 months) or rapidly accelerated schedule (720 EU at 0, 7, 21 days and 6 months) between 1997 and 2009. Factors associated with the response to vaccination were analysed using logistic regression. The overall response rate was 73.4%. Male sex (OR: 0.16, 95% CI 0.05-0.51) and hepatitis C virus co-infection (OR: 0.30, 95% CI 0.14-0.74) were associated with a lower probability of response. Protective antibody response was associated with a higher CD4/CD8 ratio (OR: 3.69, 95% CI 1.3-10.5) and having received two doses of standard schedule (compared with patients receiving only one dose of the same schedule) (OR: 2.51, 95% CI 1.22-5.15). Three doses of the rapidly accelerated schedule were not more effective than a single dose of 1440 EU (OR: 1.32, 95% CI 0.48-3.63). The low responses observed in patients receiving a single dose suggest the need to emphasize adhesion to vaccination protocols to avoid failure. The CD4/CD8 ratio may be considered as an immune status marker which could help to better choose the moment of vaccination. Our findings underscore the importance of identifying strategies that optimize the timing and effectiveness of hepatitis A vaccination in HIV-infected patients and of the need for further studies on individual factors such as sex and hepatitis C co-infection that may affect the response to vaccination. Likewise, the sub-optimal effectiveness of three doses of 720 EU in the rapidly accelerated schedule, if confirmed in future studies, might lead to a revision of the current schedule recommended for HIV-infected travellers. Copyright © 2013 Elsevier Ltd. All rights reserved.

A soluble and active form of Wnt-3a protein is involved in myogenic differentiation after cholesterol depletion.

PubMed

Portilho, Débora M; Martins, Eliane R; Costa, Manoel L; Mermelstein, Cláudia S

2007-12-22

Cholesterol is one of the major lipids of plasma membranes. Recently, we have shown that cholesterol depletion by methyl-beta-cyclodextrin (M beta CD) induces the activation of the Wnt/beta-catenin pathway and enhances myogenic differentiation. Here, we show that M beta CD-conditioned media accelerates myogenesis in a similar way as M beta CD does, suggesting that the effects induced by M beta CD could be caused by soluble factors present in the culture medium. Soluble Wnt-3 protein is significantly enhanced in M beta CD-conditioned medium. Wnt-3a-enriched media induces myogenesis as much as M beta CD does, whereas Wnt-5a-enriched media inhibits. We suggest that Wnt-3a is involved in the myogenic induction observed after cholesterol depletion.

Posttransplant Immune Activation

PubMed Central

Bamoulid, Jamal; Crepin, Thomas; Rebibou, Jean-Michel; Courivaud, Cecile; Saas, Philippe

2017-01-01

Cardiovascular disease is a major cause of morbidity, disability, and mortality in kidney transplant patients. Cumulative reports indicate that the excessive risk of cardiovascular events is not entirely explained by the increased prevalence of traditional cardiovascular risk factors. Atherosclerosis is a chronic inflammatory disease, and it has been postulated that posttransplant immune disturbances may explain the gap between the predicted and observed risks of cardiovascular events. Although concordant data suggest that innate immunity contributes to the posttransplant accelerated atherosclerosis, only few arguments plead for a role of adaptive immunity. We report and discuss here consistent data demonstrating that CD8+ T cell activation is a frequent posttransplant immune feature that may have pro-atherogenic effects. Expansion of exhausted/activated CD8+ T cells in kidney transplant recipients is stimulated by several factors including cytomegalovirus infections, lymphodepletive therapy (e.g., antithymocyte globulins), chronic allogeneic stimulation, and a past history of renal insufficiency. This is observed in the setting of decreased thymic activity, a process also found in elderly individuals and reflecting accelerated immune senescence. PMID:29113470

CD4 T-Cell Memory Generation and Maintenance

PubMed Central

Gasper, David J.; Tejera, Melba Marie; Suresh, M.

2014-01-01

Immunologic memory is the adaptive immune system's powerful ability to remember a previous antigen encounter and react with accelerated vigor upon antigen re-exposure. It provides durable protection against reinfection with pathogens and is the foundation for vaccine-induced immunity. Unlike the relatively restricted immunologic purview of memory B cells and CD8 T cells, the field of CD4 T-cell memory must account for multiple distinct lineages with diverse effector functions, the issue of lineage commitment and plasticity, and the variable distribution of memory cells within each lineage. Here, we discuss the evidence for lineage-specific CD4 T-cell memory and summarize the known factors contributing to memory-cell generation, plasticity, and long-term maintenance. PMID:24940912

Towards the measurement of the13C(d, p)14C cross section using AMS

NASA Astrophysics Data System (ADS)

Murillo-Morales, S.; Barrón-Palos, L.; Chávez, E.; Araujo-Escalona, V.

2017-07-01

A plan to study the total cross section for the13C(d, p)14C nuclear reaction has been developed for energies in the center-of-mass frame between 133 and 400 keV. The proposed experiment will use a deuterium beam (1-3 MeV of energy) from the Instituto de Física-UNAM 5.5 MV Van de Graaff accelerator and the produced14C will be afterwards measured by AMS technique in the LEMA-UNAM (HVEE 1 MV Tandetron). One of the main goals is to study the performance of the LEMA-UNAM facility in the cross section measurement in comparison with other data reported in the literature, measured by other techniques. In this work we present the current status of these studies. The relevance of the13C(d, p)14C reaction in the study of compound nucleus formation as well as in some astrophysics scenarios, and the importance of the development of the AMS technique to measure cross sections of nuclear reactions of astrophysical interest in Mixico are also discussed.

CD55 regulates self-renewal and cisplatin resistance in endometrioid tumors

PubMed Central

Wiechert, Andrew; Rao, Vinay S.; Alluri, Ravi; Thiagarajan, Praveena S.; Hale, James S.; Chumakova, Anastasia; Jarrar, Awad; Parker, Yvonne; Lindner, Daniel J.; Nagaraj, Anil Belur; DiFeo, Analisa; Abdul-Karim, Fadi W.; Rose, Peter G.; DeBernardo, Robert; Mahdi, Haider; McCrae, Keith R.; Lin, Feng

2017-01-01

Effective targeting of cancer stem cells (CSCs) requires neutralization of self-renewal and chemoresistance, but these phenotypes are often regulated by distinct molecular mechanisms. Here we report the ability to target both of these phenotypes via CD55, an intrinsic cell surface complement inhibitor, which was identified in a comparative analysis between CSCs and non-CSCs in endometrioid cancer models. In this context, CD55 functions in a complement-independent manner and required lipid raft localization for CSC maintenance and cisplatin resistance. CD55 regulated self-renewal and core pluripotency genes via ROR2/JNK signaling and in parallel cisplatin resistance via lymphocyte-specific protein tyrosine kinase (LCK) signaling, which induced DNA repair genes. Targeting LCK signaling via saracatinib, an inhibitor currently undergoing clinical evaluation, sensitized chemoresistant cells to cisplatin. Collectively, our findings identify CD55 as a unique signaling node that drives self-renewal and therapeutic resistance through a bifurcating signaling axis and provides an opportunity to target both signaling pathways in endometrioid tumors. PMID:28838952

Difference in Ulex europaeus agglutinin I-binding activity of decay-accelerating factor detected in the stools of patients with colorectal cancer and ulcerative colitis.

PubMed

Okazaki, Hiroaki; Mizuno, Motowo; Nasu, Junichirou; Makidono, Chiho; Hiraoka, Sakiko; Yamamoto, Kazuhide; Okada, Hiroyuki; Fujita, Teizo; Tsuji, Takao; Shiratori, Yasushi

2004-03-01

Expression of decay-accelerating factor (DAF, CD55), a complement-regulatory glycoprotein, is enhanced in colorectal-cancer (CC) cells and colonic epithelium in ulcerative colitis (UC), and stools from these patients contain increased amounts of DAF. Carbohydrate chains of glycoproteins are often altered during malignant transformation or inflammation. In this study, we investigated whether DAF molecules in patients with CC and those with UC differ with respect to oligosaccharide side chains. We analyzed DAF in stools and homogenates of colonic-tissue specimens obtained from patients with CC or UC using solid-phase enzyme-linked assay and Western blotting for reactivity with the lectins Ulex europaeus agglutinin I (UEA-I), wheat-germ agglutinin, peanut agglutinin, and concanavalin A. UEA-I bound to DAF in stools from patients with UC but not in that from the stools of CC patients, as demonstrated on the solid-phase enzyme-linked assay (P <.05, Mann-Whitney U test) and Western blotting. Binding of UEA-I was specifically inhibited by the addition of fucose. The difference in UEA-I reactivity with DAF was observed also in colonic-tissue homogenates from patients with UC and those with CC. DAF expressed in the mucosa and excreted into the stools of UC patients is different from that expressed in CC with regard to UEA-I reactivity. Future studies should be directed toward determining whether a qualitatively unique isoform of DAF is present, of which sugar chains are specific to CC in UC patients.

A comparison of mindfulness, nonjudgmental, and cognitive dissonance-based approaches to mirror exposure.

PubMed

Luethcke, Cynthia A; McDaniel, Leda; Becker, Carolyn Black

2011-06-01

This study compares different versions of mirror exposure (ME), a body image intervention with research support. ME protocols were adapted to maximize control and comparability, and scripted for delivery by research assistants. Female undergraduates (N=168) were randomly assigned to receive mindfulness-based (MB; n=58), nonjudgmental (NJ; n=55), or cognitive dissonance-based (CD, n=55) ME. Participants completed the Body Image Avoidance Questionnaire (BIAQ), Body Checking Questionnaire (BCQ), Satisfaction with Body Parts Scale (SBPS), Beck Depression Inventory-II (BDI-II), and Eating Disorders Examination Questionnaire (EDE-Q) at pre-treatment, post-treatment, and 1-month follow-up. Mixed models ANOVAs revealed a significant main effect of time on all measures, and no significant time by condition interaction for any measures except the SBPS. Post-hoc analysis revealed that only CD ME significantly improved SBPS outcome. Results suggest that all versions of ME reduce eating disorder risk factors, but only CD ME improves body satisfaction. Copyright © 2011 Elsevier Ltd. All rights reserved.

Social-emotional characteristics of gifted accelerated and non-accelerated students in the Netherlands.

PubMed

Hoogeveen, Lianne; van Hell, Janet G; Verhoeven, Ludo

2012-12-01

In the studies of acceleration conducted so far a multidimensional perspective has largely been neglected. No attempt has been made to relate social-emotional characteristics of accelerated versus non-accelerated students in perspective of environmental factors. In this study, social-emotional characteristics of accelerated gifted students in the Netherlands were examined in relation to personal and environmental factors. Self-concept and social contacts of accelerated (n = 148) and non-accelerated (n = 55) gifted students, aged 4 to 27 (M = 11.22, SD = 4.27) were measured. Self-concept and social contacts of accelerated and non-accelerated gifted students were measured using a questionnaire and a diary, and parents of these students evaluated their behavioural characteristics. Gender and birth order were studied as personal factors and grade, classroom, teachers' gender, teaching experience, and the quality of parent-school contact as environmental factors. The results showed minimal differences in the social-emotional characteristics of accelerated and non-accelerated gifted students. The few differences we found favoured the accelerated students. We also found that multiple grade skipping does not have negative effects on social-emotional characteristics, and that long-term effects of acceleration tend to be positive. As regards the possible modulation of personal and environmental factors, we merely found an impact of such factors in the non-accelerated group. The results of this study strongly suggest that social-emotional characteristics of accelerated gifted students and non-accelerated gifted students are largely similar. These results thus do not support worries expressed by teachers about the acceleration of gifted students. Our findings parallel the outcomes of earlier studies in the United States and Germany in that we observed that acceleration does not harm gifted students, not even in the case of multiple grade skipping. On the contrary, there is a suggestion in the data that accelerated students are more socially competent than non-accelerated students. The findings in this study can reassure those parents and teachers who worry about the social-emotional consequences of acceleration in school: If a student is gifted, acceleration seems to be a sound and, in many cases, appropriate measure in gifted education. ©2011 The British Psychological Society.

Temperature-controlled ionic liquid-based ultrasound-assisted microextraction for preconcentration of trace quantity of cadmium and nickel by using organic ligand in artificial saliva extract of smokeless tobacco products

NASA Astrophysics Data System (ADS)

Arain, Sadaf Sadia; Kazi, Tasneem Gul; Arain, Asma Jabeen; Afridi, Hassan Imran; Baig, Jameel Ahmed; Brahman, Kapil Dev; Naeemullah; Arain, Salma Aslam

2015-03-01

A new approach was developed for the preconcentration of cadmium (Cd) and nickel (Ni) in artificial saliva extract of dry snuff (brown and black) products using temperature-controlled ionic liquid-based ultrasound-assisted dispersive liquid-liquid microextraction (TIL-UDLLμE) followed by electrothermal atomic absorption spectrometry (ETAAS). The Cd and Ni were complexed with ammonium pyrrolidinedithiocarbamate (APDC), extracted in ionic liquid drops, 1-butyl-3-methylimidazolium hexafluorophosphate [C4MIM][PF6]. The multivariate strategy was applied to estimate the optimum values of experimental variables influence the % recovery of analytes by TIL-UDLLμE method. At optimum experimental conditions, the limit of detection (3s) were 0.05 and 0.14 μg L-1 while relative standard deviations (% RSD) were 3.97 and 3.55 for Cd and Ni respectively. After extraction, the enhancement factors (EF) were 87 and 79 for Cd and Ni, respectively. The RSD for six replicates of 10 μg L-1 Cd and Ni were 3.97% and 3.55% respectively. To validate the proposed method, certified reference material (CRM) of Virginia tobacco leaves was analyzed, and the determined values of Cd and Ni were in good agreement with the certified values. The concentration of Cd and Ni in artificial saliva extracts corresponds to 39-52% and 21-32%, respectively, of the total contents of both elements in dry brown and black snuff products.

Phytoextraction of 55-year-old wastewater-irrigated soil in a Zn-Pb mine district: effect of plant species and chelators.

PubMed

Tai, YiPing; Yang, YuFen; Li, ZhiAn; Yang, Yang; Wang, JiaXi; Zhuang, Ping; Zou, Bi

2017-07-16

Untreated water from mining sites spreads heavy metal contamination. The present study assessed the phytoextraction performance of heavy metal-accumulating plants and the effects of chemical chelators on cadmium (Cd), lead (Pb), zinc (Zn), and copper (Cu) removal from paddy fields that have been continuously irrigated with mining wastewater from mines for 55 years. Outdoor pot experiments showed that the total Pb, Zn, and Cd content was lower in the rhizosphere soil of Amaranthus hypochondriacus than in that of Sedum alfredii, Solanum nigrum, and Sorghum bicolor. The aboveground biomass (dry weight) and relative growth rate of A. hypochondriacus were significantly higher than that of the other three species (P < .05). However, the total metal accumulation was significantly higher in the A. hypochondriacus system than in the other plants' system (P < .05). The increase in shoot biomass of A. hypochondriacus depended mostly on the chelator type [ethylenediaminetetraacetic acid (EDTA), malate, oxalate, and citrate] and their application frequency. Single application of EDTA significantly increased the shoot biomass of A. hypochondriacus and total metal removal loading from soil (P < .05). In conclusion, A. hypochondriacus may be effective for in situ phytoremediation of heavy metal-contaminated farmland soil and EDTA can accelerate the phytoextraction effect.

Microfiltration: Effect of channel diameter on limiting flux and serum protein removal.

PubMed

Hurt, E E; Adams, M C; Barbano, D M

2015-06-01

Our objective was to determine the limiting flux and serum protein (SP) removal at 8, 9 and 10% true protein (TP) in the retentate recirculation loop using 0.1-µm ceramic graded permeability (GP) microfiltration (MF) membranes with 3mm channel diameters (CD). An additional objective was to compare the limiting flux and SP removal between 0.1-µm ceramic GP membranes with 3mm CD and previous research using 4-mm CD membranes. The MF system was operated at 50°C, using a diluted milk protein concentrate with 85% protein on a total solids basis (MPC85) as the MF feed. The limiting flux for the MF of diluted MPC85 was determined at 8, 9, and 10% TP concentration in the recirculation loop. The experiment using the 3-mm CD membranes was replicated 3 times for a total of 9 runs. On the morning of each run MPC85 was diluted with reverse osmosis water to a MF feed TP concentration of 5.4%. In all runs the starting flux was 55 kg/m2 per hour, the flux was then increased in steps until the limiting flux was reached. For the 3-mm CD membranes, the limiting flux was 128±0.3, 109±4, and 97±0.5 kg/m2 per hour at recirculation loop TP concentrations of 8.1±0.07, 9.2±0.04, and 10.2±0.03%, respectively. For the 3-mm CD membranes, increasing the flux from the starting to the limiting flux decreased the SP removal factor from 0.72±0.02 to 0.67±0.01; however, no difference in SP removal factor among the target recirculation loop TP concentrations was detected. The limiting flux at each recirculation loop target TP concentration was lower for the 3- compared with the 4-mm CD membranes. The differences in limiting fluxes between the 3- and 4-mm CD membranes were explained in part by the difference in cross-flow velocity (5.5±0.03 and 7.0±0.03 m/s for the 3- and 4-mm CD membranes, respectively). The SP removal factor was also lower for the 3- compared with the 4-mm CD membranes, indicating that more membrane fouling may have occurred in the 3- versus 4-mm CD membranes. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[Pre- and perinatal risk factors in autism spectrum disorder and attention deficit/hyperactivity disorder].

PubMed

Schmitz, Johanna C; Cholemkery, Hannah; Medda, Juliane; Freitag, Christine M

2017-01-01

Epidemiological studies indicate the relevance of pre- and perinatal risk factors for the genesis of attention deficit/hyperactivity disorder and autism spectrum disorder. This study compares potential risk factors in a clinical sample of children with ADHD, ASD, the combination of both diseases, ADHD and oppositional defiant or conduct disorder (ADHD & ODD/CD) and examined whether the existence of additional risk factors promotes the occurrence of combined diseases. We compared the pre- and perinatal risk factors of 341 patients (299 boys, 42 girls) from a clinical population, differentiating between children with ADHD (n=80), ASD (n=122), ADHD & ASD (n=55), or ADHD & ODD/CD (n=84). We observed a higher rate of maternal smoking, a higher rate of migration, and lower parental education among the children with ADHD & ODD/CD compared to those with ASD or ADHD. The rate of migration background was higher among the children with ASD compared to children with ADHD. Miscarriage was a specific risk factor for ADHD & ASD. Numerous risk factors described in epidemiological studies occurred only rarely in our clinical sample. The distribution of most risk factors was comparable between the examined diseases.

Generation of induced pluripotent stem cells as a potential source of hematopoietic stem cells for transplant in PNH patients.

PubMed

Phondeechareon, Tanapol; Wattanapanitch, Methichit; U-Pratya, Yaowalak; Damkham, Chanapa; Klincumhom, Nuttha; Lorthongpanich, Chanchao; Kheolamai, Pakpoom; Laowtammathron, Chuti; Issaragrisil, Surapol

2016-10-01

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia caused by lack of CD55 and CD59 on blood cell membrane leading to increased sensitivity of blood cells to complement. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for PNH, however, lack of HLA-matched donors and post-transplant complications are major concerns. Induced pluripotent stem cells (iPSCs) derived from patients are an attractive source for generating autologous HSCs to avoid adverse effects resulting from allogeneic HSCT. The disease involves only HSCs and their progeny; therefore, other tissues are not affected by the mutation and may be used to produce disease-free autologous HSCs. This study aimed to derive PNH patient-specific iPSCs from human dermal fibroblasts (HDFs), characterize and differentiate to hematopoietic cells using a feeder-free protocol. Analysis of CD55 and CD59 expression was performed before and after reprogramming, and hematopoietic differentiation. Patients' dermal fibroblasts expressed CD55 and CD59 at normal levels and the normal expression remained after reprogramming. The iPSCs derived from PNH patients had typical pluripotent properties and differentiation capacities with normal karyotype. After hematopoietic differentiation, the differentiated cells expressed early hematopoietic markers (CD34 and CD43) with normal CD59 expression. The iPSCs derived from HDFs of PNH patients have normal levels of CD55 and CD59 expression and hold promise as a potential source of HSCs for autologous transplantation to cure PNH patients.

Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel Disease in Humans and Mice.

PubMed

Yadav, Pankaj; Ellinghaus, David; Rémy, Gaëlle; Freitag-Wolf, Sandra; Cesaro, Anabelle; Degenhardt, Frauke; Boucher, Gabrielle; Delacre, Myriam; Peyrin-Biroulet, Laurent; Pichavant, Muriel; Rioux, John D; Gosset, Philippe; Franke, Andre; Schumm, L Philip; Krawczak, Michael; Chamaillard, Mathias; Dempfle, Astrid; Andersen, Vibeke

2017-08-01

The role of tobacco smoke in the etiology of inflammatory bowel disease (IBD) is unclear. We investigated interactions between genes and smoking (gene-smoking interactions) that affect risk for Crohn's disease (CD) and ulcerative colitis (UC) in a case-only study of patients and in mouse models of IBD. We used 55 Immunochip-wide datasets that included 19,735 IBD cases (10,856 CD cases and 8879 UC cases) of known smoking status. We performed 3 meta-analyses each for CD, UC, and IBD (CD and UC combined), comparing data for never vs ever smokers, never vs current smokers, and never vs former smokers. We studied the effects of exposure to cigarette smoke in Il10 -/- and Nod2 -/- mice, as well as in Balb/c mice without disruption of these genes (wild-type mice). Mice were exposed to the smoke of 5 cigarettes per day, 5 days a week, for 8 weeks, in a ventilated smoking chamber, or ambient air (controls). Intestines were collected and analyzed histologically and by reverse transcription polymerase chain reaction. We identified 64 single nucleotide polymorphisms (SNPs) for which the association between the SNP and IBD were modified by smoking behavior (meta-analysis Wald test P < 5.0 × 10 -5 ; heterogeneity Cochrane Q test P > .05). Twenty of these variants were located within the HLA region at 6p21. Analysis of classical HLA alleles (imputed from SNP genotypes) revealed an interaction with smoking. We replicated the interaction of a variant in NOD2 with current smoking in relation to the risk for CD (frameshift variant fs1007insC; rs5743293). We identified 2 variants in the same genomic region (rs2270368 and rs17221417) that interact with smoking in relation to CD risk. Approximately 45% of the SNPs that interact with smoking were in close vicinity (≤1 Mb) to SNPs previously associated with IBD; many were located near or within genes that regulate mucosal barrier function and immune tolerance. Smoking modified the disease risk of some variants in opposite directions for CD vs UC. Exposure of Interleukin 10 (il10)-deficient mice to cigarette smoke accelerated development of colitis and increased expression of interferon gamma in the small intestine compared to wild-type mice exposed to smoke. NOD2-deficient mice exposed to cigarette smoke developed ileitis, characterized by increased expression of interferon gamma, compared to wild-type mice exposed to smoke. In an analysis of 55 Immunochip-wide datasets, we identified 64 SNPs whose association with risk for IBD is modified by tobacco smoking. Gene-smoking interactions were confirmed in mice with disruption of Il10 and Nod2-variants of these genes have been associated with risk for IBD. Our findings from mice and humans revealed that the effects of smoking on risk for IBD depend on genetic variants. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

A preliminary study on the role of the complement regulatory protein, cluster of differentiation 55, in mice with diabetic neuropathic pain.

PubMed

Nie, Fachuan; Su, Dong; Shi, Ying; Chen, Jinmei; Wang, Haihui; Qin, Wanxiang; Chen, Yaohua; Wang, Suxia; Li, Lei

2015-03-01

The aim of this study was to investigate the role of the complement regulatory protein cluster of differentiation 55 (CD55) in the pathogenesis of diabetic neuropathic pain (DNP). Healthy adult male C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ) in order to induce DNP. Peripheral blood glucose and protein, and the mRNA expression levels of C3 and CD55 in the spinal cord were determined. In addition, the behaviors of these mice were observed. The results showed that STZ‑treated mice displayed the clinical manifestations of diabetes mellitus, and that their peripheral blood glucose was markedly increased. On the 21st and 28th days following the STZ injection, the mechanical pain threshold and thermal pain threshold of the mice were dramatically reduced (P<0.05). |Additionally, 14 days post‑STZ injection, the mRNA expression of C3 in the spinal cord was significantly increased, which continued for 28 days. On the 21st and 28th days, the number of C3 positive cells in the spinal cord was markedly increased. Seven days after the STZ injection, the number of cells positive for CD55 was markedly reduced in the spinal dorsal horn and subsequently remained at a low level. The mRNA expression of CD55 also was significantly reduced (P<0.05) and remained so for 28 days. The reduction in the expression levels of CD55 occurred earlier than the changes in the expression of C3, suggesting that the downregulation of CD55 expression precedes, and has an important role regarding, the activation of C3 in the occurrence and development of DNP.

Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts

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

Du, Yijun; Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan; Pattnaik, Asit K.

2012-03-01

The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating thatmore » the C-terminal domain of GP4 functions as a GPI anchor. Mutational studies for residues adjacent to the GPI modification site and characterization of respective mutant viruses generated from infectious cDNA clones show that the ability of GP4 for membrane association corresponded to virus viability and growth characteristics. The residues T158 ({omega} - 2, where {omega} is the GPI moiety at E160), P159 ({omega} - 1), and M162 ({omega} + 2) of GP4 were determined to be important for virus replication, with M162 being of particular importance for virus infectivity. The complete removal of the peptide-anchor domain in GP4 resulted in a complete loss of virus infectivity. The depletion of cholesterol from the plasma membrane of cells reduced the virus production, suggesting a role of lipid rafts in PRRSV infection. Remarkably, GP4 was found to co-localize with CD163 in the lipid rafts on the plasma membrane. Since CD163 has been reported as a cellular receptor for PRRSV and GP4 has been shown to interact with this receptor, our data implicates an important role of lipid rafts during entry of the virus.« less

Anti-Inflammatory Properties of Brazilian Green Propolis Encapsulated in a γ-Cyclodextrin Complex in Mice Fed a Western-Type Diet.

PubMed

Rimbach, Gerald; Fischer, Alexandra; Schloesser, Anke; Jerz, Gerold; Ikuta, Naoko; Ishida, Yoshiyuki; Matsuzawa, Ryota; Matsugo, Seiichi; Huebbe, Patricia; Terao, Keiji

2017-05-26

Ageing is often accompanied by chronic inflammation. A fat- and sugar-rich Western-type diet (WTD) may accelerate the ageing phenotype. Cell culture studies have indicated that artepillin C-containing Brazilian green propolis exhibits anti-inflammatory properties. However, little is known regarding its anti-inflammatory potential in mouse liver in vivo. In this study, female C57BL/6NRj wild-type mice were fed a WTD, a WTD supplemented with Brazilian green propolis supercritical extract (GPSE) encapsulated in γ-cyclodextrin (γCD) or a WTD plus γCD for 10 weeks. GPSE-γCD did not affect the food intake, body weight or body composition of the mice. However, mRNA levels of the tumour necrosis factor α were significantly downregulated ( p < 0.05) in these mice compared to those in the WTD-fed controls. Furthermore, the gene expression levels of other pro-inflammatory markers, including serum amyloid P, were significantly ( p < 0.001) decreased following GPSE-γCD treatment. GPSE-γCD significantly induced hepatic ferritin gene expression ( p < 0.01), which may contribute to its anti-inflammatory properties. Conversely, GPSE-γCD did not affect the biomarkers of endogenous antioxidant defence, including catalase, glutathione peroxidase-4, paraoxonase-1, glutamate cysteine ligase and nuclear factor erythroid 2-related factor-2 (Nrf2). Overall, the present data suggest that dietary GPSE-γCD exhibits anti-inflammatory, but not antioxidant activity in mouse liver in vivo. Thus, GPSE-γCD has the potential to serve as a natural hepatoprotective bioactive compound for dietary-mediated strategies against chronic inflammation.

An examination of the parent report version of the inventory of callous-unemotional traits in a community sample of first-grade children.

PubMed

Willoughby, Michael T; Mills-Koonce, W Roger; Waschbusch, Daniel A; Gottfredson, Nisha C

2015-02-01

The Inventory of Callous-Unemotional Traits is a self- and other report questionnaire of callous-unemotional behaviors that is increasingly widely used in research and clinical settings. Nonetheless, questions about the factor structure and validity of scales remain. This study provided the first large-scale (N = 1,078) investigation of the parent report version of the Inventory of Callous-Unemotional Traits in a community sample of school-age (first-grade) children. Confirmatory factor analysis indicated that a two-factor model that distinguished empathic-prosocial (EP) from callous-unemotional (CU) behaviors provided the best fit to the data. EP and CU were moderately to strongly correlated with each other (ϕ = -.67, p < .001) and with oppositional defiant disorder and conduct disorder (ODD/CD) behaviors (ϕODD/CD, EP = -.55; ϕODD/CD, CU = .71, ps < .001). Individual differences in EP and CU behaviors explained unique variation, beyond that attributable to ODD/CD behaviors, in peer-, teacher-, and parent relationship quality. Moreover, whereas EP moderated the effects of ODD/CD in the prediction of student-teacher relationship quality, CU moderated the effects of ODD/CD in the prediction of peer and parent relationship quality. Results are discussed with respect to the use of the ICU with school-age children. © The Author(s) 2014.

Endothelium trans differentiated from Wharton's jelly mesenchymal cells promote tissue regeneration: potential role of soluble pro-angiogenic factors.

PubMed

Aguilera, Valeria; Briceño, Luis; Contreras, Hector; Lamperti, Liliana; Sepúlveda, Esperanza; Díaz-Perez, Francisca; León, Marcelo; Veas, Carlos; Maura, Rafael; Toledo, Jorge Roberto; Fernández, Paulina; Covarrubias, Ambart; Zuñiga, Felipe Andrés; Radojkovic, Claudia; Escudero, Carlos; Aguayo, Claudio

2014-01-01

Mesenchymal stem cells have a high capacity for trans-differentiation toward many adult cell types, including endothelial cells. Feto-placental tissue, such as Wharton's jelly is a potential source of mesenchymal stem cells with low immunogenic capacity; make them an excellent source of progenitor cells with a potential use for tissue repair. We evaluated whether administration of endothelial cells derived from mesenchymal stem cells isolated from Wharton's jelly (hWMSCs) can accelerate tissue repair in vivo. Mesenchymal stem cells were isolated from human Wharton's jelly by digestion with collagenase type I. Endothelial trans-differentiation was induced for 14 (hWMSC-End14d) and 30 (hWMSC-End30d) days. Cell phenotyping was performed using mesenchymal (CD90, CD73, CD105) and endothelial (Tie-2, KDR, eNOS, ICAM-1) markers. Endothelial trans-differentiation was demonstrated by the expression of endothelial markers and their ability to synthesize nitric oxide (NO). hWMSCs can be differentiated into adipocytes, osteocytes, chondrocytes and endothelial cells. Moreover, these cells show high expression of CD73, CD90 and CD105 but low expression of endothelial markers prior to differentiation. hWMSCs-End express high levels of endothelial markers at 14 and 30 days of culture, and also they can synthesize NO. Injection of hWMSC-End30d in a mouse model of skin injury significantly accelerated wound healing compared with animals injected with undifferentiated hWMSC or injected with vehicle alone. These effects were also observed in animals that received conditioned media from hWMSC-End30d cultures. These results demonstrate that mesenchymal stem cells isolated from Wharton's jelly can be cultured in vitro and trans-differentiated into endothelial cells. Differentiated hWMSC-End may promote neovascularization and tissue repair in vivo through the secretion of soluble pro-angiogenic factors.

Expression and distribution of hyaluronic acid and CD44 in unphonated human vocal fold mucosa.

PubMed

Sato, Kiminori; Umeno, Hirohito; Nakashima, Tadashi; Nonaka, Satoshi; Harabuchi, Yasuaki

2009-11-01

The tension caused by phonation (vocal fold vibration) is hypothesized to stimulate vocal fold stellate cells (VFSCs) in the maculae flavae (MFe) to accelerate production of extracellular matrices. The distribution of hyaluronic acid (HA) and expression of CD44 (a cell surface receptor for HA) were examined in human vocal fold mucosae (VFMe) that had remained unphonated since birth. Five specimens of VFMe (3 adults, 2 children) that had remained unphonated since birth were investigated with Alcian blue staining, hyaluronidase digestion, and immunohistochemistry for CD44. The VFMe containing MFe were hypoplastic and rudimentary. The VFMe did not have a vocal ligament, Reinke's space, or a layered structure, and the lamina propria appeared as a uniform structure. In the children, HA was distributed in the VFMe containing MFe. In the adults, HA had decreased in the VFMe containing MFe. In both groups, the VFSCs in the MFe and the fibroblasts in the lamina propria expressed little CD44. This study supports the hypothesis that the tensions caused by vocal fold vibration stimulate the VFSCs in the MFe to accelerate production of extracellular matrices and form the layered structure. Phonation after birth is one of the important factors in the growth and development of the human VFMe.

Growth Factor-Activated Stem Cell Circuits and Stromal Signals Cooperatively Accelerate Non-Integrated iPSC Reprogramming of Human Myeloid Progenitors

PubMed Central

Park, Tea Soon; Huo, Jeffrey S.; Peters, Ann; Talbot, C. Conover; Verma, Karan; Zimmerlin, Ludovic; Kaplan, Ian M.; Zambidis, Elias T.

2012-01-01

Nonviral conversion of skin or blood cells into clinically useful human induced pluripotent stem cells (hiPSC) occurs in only rare fractions (∼0.001%–0.5%) of donor cells transfected with non-integrating reprogramming factors. Pluripotency induction of developmentally immature stem-progenitors is generally more efficient than differentiated somatic cell targets. However, the nature of augmented progenitor reprogramming remains obscure, and its potential has not been fully explored for improving the extremely slow pace of non-integrated reprogramming. Here, we report highly optimized four-factor reprogramming of lineage-committed cord blood (CB) myeloid progenitors with bulk efficiencies of ∼50% in purified episome-expressing cells. Lineage-committed CD33+CD45+CD34− myeloid cells and not primitive hematopoietic stem-progenitors were the main targets of a rapid and nearly complete non-integrated reprogramming. The efficient conversion of mature myeloid populations into NANOG+TRA-1-81+ hiPSC was mediated by synergies between hematopoietic growth factor (GF), stromal activation signals, and episomal Yamanaka factor expression. Using a modular bioinformatics approach, we demonstrated that efficient myeloid reprogramming correlated not to increased proliferation or endogenous Core factor expressions, but to poised expression of GF-activated transcriptional circuits that commonly regulate plasticity in both hematopoietic progenitors and embryonic stem cells (ESC). Factor-driven conversion of myeloid progenitors to a high-fidelity pluripotent state was further accelerated by soluble and contact-dependent stromal signals that included an implied and unexpected role for Toll receptor-NFκB signaling. These data provide a paradigm for understanding the augmented reprogramming capacity of somatic progenitors, and reveal that efficient induced pluripotency in other cell types may also require extrinsic activation of a molecular framework that commonly regulates self-renewal and differentiation in both hematopoietic progenitors and ESC. PMID:22905176

An accelerated test design for use with synchronous orbit. [on Ni-Cd cell degradation behavior

NASA Technical Reports Server (NTRS)

Mcdermott, P. P.; Vasanth, K. L.

1980-01-01

The Naval Weapons Support Center at Crane, Indiana has conducted a large scale accelerated test of 6.0 Ah Ni-Cd cells. Data from the Crane test have been used to develop an equation for the description of Ni-Cd cell behavior in geosynchronous orbit. This equation relates the anticipated time to failure for a cell in synchronous orbit to temperature and overcharge rate sustained by the cell during the light period. A test design is suggested which uses this equation for setting test parameters for future accelerated testing.

Emerging materials for solar cell applications: electrodeposited CdTe. Final report, February 14, 1979-February 14, 1980

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

Rod, R.L.; Bunshah, R.; Stafsudd, O.

1980-05-15

Thin film gold/polycrystalline cadmium telluride Schottky solar cells made by electrodepositing the semiconductor on an ITO-coated glass substrate serving also as an ohmic contact demonstrated an internal efficiency of 4% over 2 mm/sup 2/ areas. During the year being reported upon, Monosolar devoted mator attention to refining the electroplating process and determining the parameters governing CdTe film stoichiometry, grain size, substrate adhesion, and quality. UCLA acting as a Monosolar sub-contractor characterized both the CdTe films themselves and solar cells made from them. Techniques were developed for making measurements on films often less than 1 micron in thickness. The highest valuesmore » achieved for efficiency parameters, not necessarily all in the same cell, were V/sub oc/ = 0.5 V, J/sub sc/ = 11 mA/cm/sup 2/, and fill factor = 0.55 before corrections in the absence of anti-reflection coatings. Typical resistivities for n-CdTe films were 10/sup 5/ ..cap omega..-cm. Lifetimes of about 10/sup -10/ sec were measured. Absorption coefficient of these films is in the order of 10/sup 4/ for lambda < 0.7 ..mu..m. Measured energy gap for these CdTe films is 1.55 eV, sightly higher than the 1.45 eV value for single crystal CdTe. The activation energy of the dominating trap level is 0.55 eV. Trap density is in the order of 10/sup 16//cm/sup 3/. Schottky diodes were of excellent quality and pinhole-free. The measured barrier height varied between 0.75 and 0.85 eV. Rectification ratios of 10/sup 4/ were obtained reproducibly. Films measure about 1 inch square. Indications are that larger and more efficient low cost solar devices can readily be obtained soon using the techniques developed in this program.« less

Piracy of Decay-Accelerating Factor (CD55) Signal Transduction by the Diffusely Adhering Strain Escherichia coli C1845 Promotes Cytoskeletal F-Actin Rearrangements in Cultured Human Intestinal INT407 Cells

PubMed Central

Peiffer, Isabelle; Servin, Alain L.; Bernet-Camard, Marie-Françoise

1998-01-01

Diffusely adhering Escherichia coli (DAEC) C1845 (clinical isolate) harboring the fimbrial adhesin F1845 can infect cultured human differentiated intestinal epithelial cells; this process is followed by the disassembly of the actin network in the apical domain. The aim of this study was to examine the mechanism by which DAEC C1845 promotes F-actin rearrangements. For this purpose, we used a human embryonic intestinal cell line (INT407) expressing the membrane-associated glycosylphosphatidylinositol (GPI) protein-anchored decay-accelerating factor (DAF), the receptor of the F1845 adhesin. We show here that infection of INT407 cells by DAEC C1845 can provoke dramatic F-actin rearrangements without cell entry. Clustering of phosphotyrosines was observed, revealing that the DAEC C1845-DAF interaction involves the recruitment of signal transduction molecules. A pharmacological approach with a subset of inhibitors of signal transduction molecules was used to identify the cascade of signal transduction molecules that are coupled to the DAF, that are activated upon infection, and that promote the F-actin rearrangements. DAEC C1845-induced F-actin rearrangements can be blocked dose dependently by protein tyrosine kinase, phospholipase Cγ, phosphatidylinositol 3-kinase, protein kinase C, and Ca2+ inhibitors. F-actin rearrangements and blocking by inhibitors were observed after infection of the cells with two E. coli recombinants carrying the plasmids containing the fimbrial adhesin F1845 or the fimbrial hemagglutinin Dr, belonging to the same family of adhesins. These findings show that the DAEC Dr family of pathogens promotes alterations in the intestinal cell cytoskeleton by piracy of the DAF-GPI signal cascade without bacterial cell entry. PMID:9712744

A tissue-engineered subcutaneous pancreatic cancer model for antitumor drug evaluation.

PubMed

He, Qingyi; Wang, Xiaohui; Zhang, Xing; Han, Huifang; Han, Baosan; Xu, Jianzhong; Tang, Kanglai; Fu, Zhiren; Yin, Hao

2013-01-01

The traditional xenograft subcutaneous pancreatic cancer model is notorious for its low incidence of tumor formation, inconsistent results for the chemotherapeutic effects of drug molecules of interest, and a poor predictive capability for the clinical efficacy of novel drugs. These drawbacks are attributed to a variety of factors, including inoculation of heterogeneous tumor cells from patients with different pathological histories, and use of poorly defined Matrigel(®). In this study, we aimed to tissue-engineer a pancreatic cancer model that could readily cultivate a pancreatic tumor derived from highly homogenous CD24(+)CD44(+) pancreatic cancer stem cells delivered by a well defined electrospun scaffold of poly(glycolide-co-trimethylene carbonate) and gelatin. The scaffold supported in vitro tumorigenesis from CD24(+)CD44(+) cancer stem cells for up to 7 days without inducing apoptosis. Moreover, CD24(+)CD44(+) cancer stem cells delivered by the scaffold grew into a native-like mature pancreatic tumor within 8 weeks in vivo and exhibited accelerated tumorigenesis as well as a higher incidence of tumor formation than the traditional model. In the scaffold model, we discovered that oxaliplatin-gemcitabine (OXA-GEM), a chemotherapeutic regimen, induced tumor regression whereas gemcitabine alone only capped tumor growth. The mechanistic study attributed the superior antitumorigenic performance of OXA-GEM to its ability to induce apoptosis of CD24(+)CD44(+) cancer stem cells. Compared with the traditional model, the scaffold model demonstrated a higher incidence of tumor formation and accelerated tumor growth. Use of a tiny population of highly homogenous CD24(+)CD44(+) cancer stem cells delivered by a well defined scaffold greatly reduces the variability associated with the traditional model, which uses a heterogeneous tumor cell population and poorly defined Matrigel. The scaffold model is a robust platform for investigating the antitumorigenesis mechanism of novel chemotherapeutic drugs with a special focus on cancer stem cells.

Fc Gamma Receptor 3A Polymorphism and Risk for HIV-Associated Cryptococcal Disease

PubMed Central

Rohatgi, Soma; Gohil, Shruti; Kuniholm, Mark H.; Schultz, Hannah; Dufaud, Chad; Armour, Kathryn L.; Badri, Sheila; Mailliard, Robbie B.; Pirofski, Liise-anne

2013-01-01

ABSTRACT Cryptococcus neoformans is one of the most common causes of fungal disease in HIV-infected persons, but not all of those who are infected develop cryptococcal disease (CD). Although CD4+ T cell deficiency is a risk factor for HIV-associated CD, polymorphisms of phagocytic Fc gamma receptors (FCGRs) have been linked to CD risk in HIV-uninfected persons. To investigate associations between FCGR2A 131 H/R and FCGR3A 158 F/V polymorphisms and CD risk in HIV-infected persons, we performed PCR-based genotyping on banked samples from 164 men enrolled in the Multicenter AIDS Cohort Study (MACS): 55 who were HIV infected and developed CD and a matched control group of 54 who were HIV infected and 55 who were HIV uninfected. Using additive and allelic statistical models for analysis, the high-affinity FCGR3A 158V allele was significantly associated with CD status after adjusting for race/ethnicity (odds ratio [OR], 2.1; P = 0.005), as was the FCGR3A 158 VV homozygous genotype after adjusting for race/ethnicity, rate of CD4+ T cell decline, and nadir CD4+ T cell count (OR, 21; P = 0.005). No associations between CD and FCGR2A 131 H/R polymorphism were identified. In binding studies, human IgG (hIgG)-C. neoformans complexes exhibited more binding to CHO-K1 cells expressing FCGR3A 158V than to those expressing FCGR3A 158F, and in cytotoxicity assays, natural killer (NK) cells expressing FCGR3A 158V induced more C. neoformans-infected monocyte cytotoxicity than those expressing FCGR3A 158F. Together, these results show an association between the FCGR3A 158V allele and risk for HIV-associated CD and suggest that this polymorphism could promote C. neoformans pathogenesis via increased binding of C. neoformans immune complexes, resulting in increased phagocyte cargo and/or immune activation. PMID:23982074

In Vivo, Fatty Acid Translocase (CD36) Critically Regulates Skeletal Muscle Fuel Selection, Exercise Performance, and Training-induced Adaptation of Fatty Acid Oxidation*

PubMed Central

McFarlan, Jay T.; Yoshida, Yuko; Jain, Swati S.; Han, Xioa-Xia; Snook, Laelie A.; Lally, James; Smith, Brennan K.; Glatz, Jan F. C.; Luiken, Joost J. F. P.; Sayer, Ryan A.; Tupling, A. Russell; Chabowski, Adrian; Holloway, Graham P.; Bonen, Arend

2012-01-01

For ∼40 years it has been widely accepted that (i) the exercise-induced increase in muscle fatty acid oxidation (FAO) is dependent on the increased delivery of circulating fatty acids, and (ii) exercise training-induced FAO up-regulation is largely attributable to muscle mitochondrial biogenesis. These long standing concepts were developed prior to the recent recognition that fatty acid entry into muscle occurs via a regulatable sarcolemmal CD36-mediated mechanism. We examined the role of CD36 in muscle fuel selection under basal conditions, during a metabolic challenge (exercise), and after exercise training. We also investigated whether CD36 overexpression, independent of mitochondrial changes, mimicked exercise training-induced FAO up-regulation. Under basal conditions CD36-KO versus WT mice displayed reduced fatty acid transport (−21%) and oxidation (−25%), intramuscular lipids (less than or equal to −31%), and hepatic glycogen (−20%); but muscle glycogen, VO2max, and mitochondrial content and enzymes did not differ. In acutely exercised (78% VO2max) CD36-KO mice, fatty acid transport (−41%), oxidation (−37%), and exercise duration (−44%) were reduced, whereas muscle and hepatic glycogen depletions were accelerated by 27–55%, revealing 2-fold greater carbohydrate use. Exercise training increased mtDNA and β-hydroxyacyl-CoA dehydrogenase similarly in WT and CD36-KO muscles, but FAO was increased only in WT muscle (+90%). Comparable CD36 increases, induced by exercise training (+44%) or by CD36 overexpression (+41%), increased FAO similarly (84–90%), either when mitochondrial biogenesis and FAO enzymes were up-regulated (exercise training) or when these were unaltered (CD36 overexpression). Thus, sarcolemmal CD36 has a key role in muscle fuel selection, exercise performance, and training-induced muscle FAO adaptation, challenging long held views of mechanisms involved in acute and adaptive regulation of muscle FAO. PMID:22584574

PKM2-dependent metabolic reprogramming in CD4+ T cells is crucial for hyperhomocysteinemia-accelerated atherosclerosis.

PubMed

Lü, Silin; Deng, Jiacheng; Liu, Huiying; Liu, Bo; Yang, Juan; Miao, Yutong; Li, Jing; Wang, Nan; Jiang, Changtao; Xu, Qingbo; Wang, Xian; Feng, Juan

2018-06-01

Inflammation mediated by activated T cells plays an important role in the initiation and progression of hyperhomocysteinemia (HHcy)-accelerated atherosclerosis in ApoE -/- mice. Homocysteine (Hcy) activates T cells to secrete proinflammatory cytokines, especially interferon (IFN)-γ; however, the precise mechanisms remain unclear. Metabolic reprogramming is critical for T cell inflammatory activation and effector functions. Our previous study demonstrated that Hcy regulates T cell mitochondrial reprogramming by enhancing endoplasmic reticulum (ER)-mitochondria coupling. In this study, we further explored the important role of glycolysis-mediated metabolic reprogramming in Hcy-activated CD4 + T cells. Mechanistically, Hcy-activated CD4 + T cell increased the protein expression and activity of pyruvate kinase muscle isozyme 2 (PKM2), the final rate-limiting enzyme in glycolysis, via the phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin signaling pathway. Knockdown of PKM2 by small interfering RNA reduced Hcy-induced CD4 + T cell IFN-γ secretion. Furthermore, we generated T cell-specific PKM2 knockout mice by crossing LckCre transgenic mice with PKM2 fl/fl mice and observed that Hcy-induced glycolysis and oxidative phosphorylation were both diminished in PKM2-deficient CD4 + T cells with reduced glucose and lipid metabolites, and subsequently reduced IFN-γ secretion. T cell-depleted apolipoprotein E-deficient (ApoE -/- ) mice adoptively transferred with PKM2-deficient CD4 + T cells, compared to mice transferred with control cells, showed significantly decreased HHcy-accelerated early atherosclerotic lesion formation. In conclusion, this work indicates that the PKM2-dependent glycolytic-lipogenic axis, a novel mechanism of metabolic regulation, is crucial for HHcy-induced CD4 + T cell activation to accelerate early atherosclerosis in ApoE -/- mice. Metabolic reprogramming is crucial for Hcy-induced CD4 + T cell inflammatory activation. Hcy activates the glycolytic-lipogenic pathway in CD4 + T cells via PKM2. Targeting PKM2 attenuated HHcy-accelerated early atherosclerosis in ApoE -/- mice in vivo.

Spanish validation of the 10-item Connor-Davidson Resilience Scale (CD-RISC 10) with non-professional caregivers.

PubMed

Blanco, Vanessa; Guisande, María Adelina; Sánchez, María Teresa; Otero, Patricia; Vázquez, Fernando L

2017-11-08

Despite the importance of resilience in populations under stress, and the fact that the 10-item version Connor-Davidson Resilience Scale (CD-RISC 10) is the shortest instrument for reliable and valid evaluation of resilience, there are no data on their psychometric properties in non-professional caregivers. The aim of this study was to analyze the psychometric properties and factorial structure of the spanish version of the CD-RISC 10 in non-professional caregivers. Independently trained assessors evaluated resilience, self-esteem, social support, emotional distress and depression in a sample of 294 caregivers (89.8% women, mean age 55.3 years). The internal consistency of CD-RISC 10 was α = .86. A single factor was found that accounted for 44.7% of the total variance. Confirmatory factor analysis corroborated this unifactorial model. The CD-RISC 10 was significantly correlated with the self-esteem (r = .416, p < .001) and social support (r = .228, p < .001) scales, and the emotional distress scale (r = -.311, p < .001), though this was an inverse relationship. A score ≤ 23 was a suitable cut-off point for discriminating caregivers with depression (sensitivity = 70.0%, specificity = 68.2%). The CD-RISC 10 is a reliable and valid instrument to evaluate resilience in the caregiver population.

Correlation between CD34 expression and chromosomal abnormalities but not clinical outcome in acute myeloid leukemia.

PubMed

Fruchart, C; Lenormand, B; Bastard, C; Boulet, D; Lesesve, J F; Callat, M P; Stamatoullas, A; Monconduit, M; Tilly, H

1996-11-01

The hemopoietic stem cell marker CD34 has been reported to be a useful predictor of treatment outcome in acute myeloid leukemia (AML). Previous data suggested that CD34 expression may be associated with other poor prognosis factors in AML such as undifferentiated leukemia, secondary AML (SAML), and clonal abnormalities involving chromosome 5 and 7. In order to analyze the correlations between the clinicopathologic features, cytogenetic and CD34 expression in AML, we retrospectively investigated 99 patients with newly diagnosed AML: 85 with de novo disease and 14 with secondary AML (SAML). Eighty-six patients who received the same induction chemotherapy were available for clinical outcome. Defining a case as positive when > or = 20% of bone marrow cells collected at diagnosis expressed the CD34 antigen, forty-five patients were included in the CD34 positive group. Ninety patients had adequate cytogenetic analysis. Thirty-two patients (72%) with CD34 positive AML exhibited an abnormal karyotype whereas 15 patients (28%) with CD34 negative AML had abnormal metaphases (P < 0.01). Monosomy 7/7q- or monosomy 5/5q- occurred in 10 patients and 8 of them expressed the CD34 antigen (P < 0.05). All patients with t(8;21) which is considered as a favorable factor in AML had levels of CD34 >/= 20% (P < 0.05). We did not find any association between CD34 expression and attainment of complete remission, overall survival, or disease-free survival. In conclusion, the variations of CD34 expression in AML are correlated with cytogenetic abnormalities associated both with poor and favorable outcome. The evaluation of the correlations between CD34 antigen and clinical outcome in AML should take into account the results of pretreatment karyotype.

Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma.

PubMed

Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

2014-01-01

The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor.

Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma

PubMed Central

Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

2014-01-01

The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor. PMID:24817962

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

PubMed

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

2017-01-13

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

Electrical and Optical Characterization of Nanowire based Semiconductor Devices

NASA Astrophysics Data System (ADS)

Ayvazian, Talin

This research project is focused on a new strategy for the creation of nanowire based semiconductor devices. The main goal is to understand and optimize the electrical and optical properties of two types of nanoscale devices; in first type lithographically patterned nanowire electrodeposition (LPNE) method has been utilized to fabricate nanowire field effect transistors (NWFET) and second type involved the development of light emitting semiconductor nanowire arrays (NWLED). Field effect transistors (NWFETs) have been prepared from arrays of polycrystalline cadmium selenide (pc-CdSe) nanowires using a back gate configuration. pc-CdSe nanowires were fabricated using the lithographically patterned nanowire electrode- position (LPNE) process on SiO2 /Si substrates. After electrodeposition, pc-CdSe nanowires were thermally annealed at 300 °C x 4 h either with or without exposure to CdCl 2 in methanol a grain growth promoter. The influence of CdCl2 treatment was to increase the mean grain diameter as determined by X-ray diffraction pattern and to convert the crystal structure from cubic to wurtzite. Transfer characteristics showed an increase of the field effect mobility (mu eff) by an order of magnitude and increase of the Ion/I off ratio by a factor of 3-4. Light emitting devices (NW-LED) based on lithographically patterned pc-CdSe nanowire arrays have been investigated. Electroluminescence (EL) spectra of CdSe nanowires under various biases exhibited broad emission spectra centered at 750 nm close to the band gap of CdSe (1.7eV). To enhance the intensity of the emitted light and the external quantum efficiency (EQE), the distance between the contacts were reduced from 5 mum to less than 1 mum which increased the efficiency by an order of magnitude. Also, increasing the annealing temperature of nanowires from 300 °C x4 h to 450 This research project is focused on a new strategy for the creation of nanowire based semiconductor devices. The main goal is to understand and optimize the electrical and optical properties of two types of nanoscale devices; in first type lithographically patterned nanowire electrodeposition (LPNE) method has been utilized to fabricate nanowire field effect transistors (NWFET) and second type involved the development of light emitting semiconductor nanowire arrays (NWLED). Field effect transistors (NWFETs) have been prepared from arrays of polycrystalline cadmium selenide (pc-CdSe) nanowires using a back gate configuration. pc-CdSe nanowires were fabricated using the lithographically patterned nanowire electrode- position (LPNE) process on SiO2 /Si substrates. After electrodeposition, pc-CdSe nanowires were thermally annealed at 300 °C x 4 h either with or without exposure to CdCl2 in methanol- a grain growth promoter. The influence of CdCl2 treatment was to increase the mean grain diameter as determined by X-ray diffraction pattern and to convert the crystal structure from cubic to wurtzite. Transfer characteristics showed an increase of the field effect mobility (mueff<) by an order of magnitude and increase of the Ion/Ioff ratio by a factor of 3-4. Light emitting devices (NW-LED) based on lithographically patterned pc-CdSe nanowire arrays have been investigated. Electroluminescence (EL) spectra of CdSe nanowires under various biases exhibited broad emission spectra centered at 750 nm close to the band gap of CdSe (1.7eV). To enhance the intensity of the emitted light and the external quantum efficiency (EQE), the distance between the contacts were reduced from 5 mum to less than 1 mum which increased the efficiency by an order of magnitude. Also, increasing the annealing temperature of nanowires from 300 °C x4 h to 450 °C x 1h enhanced grain growth confirmed by structural characterization including X-ray diffraction (XRD), Scanning electron microscopy (SEM) and Raman Spectroscopy. Correspondingly the light emission intensity and EQE improved due to this grain growth. Kelvin probe force microscopy (KPFM) was utilized to understand mechanism of light emission in CdSe nanowires. Arrays of CdTe nanowires were electrodeposited using LPNE process where the elec- trodeposition of pc-CdTe was carried out at two temperatures: 20 °C (cold) and 55 °C (hot). Transmission electron microscopy (TEM) and X-ray diffraction (XRD) re- sults revealed higher crystallinity, larger grain size and presence of Te for nanowires prepared at 55°C compared to nanowires deposited at 20°C. Nanowires prepared at 55°C showed higher electrical conductivity and enhanced electroluminescence proper- ties, including higher light emission intensity and improved External Quantum Efficiency (EQE). Electrical conduction mechanism also investigated for CdTe nanowires. Thermionic emission over schottky barrier height was identified as the dominant charge transport mechanism in pc-CdTe nanowires.°C x 1h enhanced grain growth confirmed by structural characterization including X-ray diffraction (XRD), Scanning electron microscopy (SEM) and Raman Spectroscopy. Correspondingly the light emission intensity and EQE improved due to this grain growth. Kelvin probe force microscopy (KPFM) was utilized to understand mechanism of light emission in CdSe nanowires. Arrays of CdTe nanowires were electrodeposited using LPNE process where the electrodeposition of pc-CdTe was carried out at two temperatures: 20 °C (cold) and 55 °C (hot). Transmission electron microscopy (TEM) and X-ray diffraction (XRD) re- sults revealed higher crystallinity, larger grain size and presence of Te for nanowires prepared at 55°C compared to nanowires deposited at 20°C. Nanowires prepared at 55°C showed higher electrical conductivity and enhanced electroluminescence properties, including higher light emission intensity and improved External Quantum Efficiency (EQE). Electrical conduction mechanism also investigated for CdTe nanowires. Thermionic emission over schottky barrier height was identified as the dominant charge transport mechanism in pc-CdTe nanowires.

Regulatory Lymphocytes Are Key Factors in MHC-Independent Resistance to EAE

PubMed Central

Marín, Nieves; Mecha, Miriam; Espejo, Carmen; Mestre, Leyre; Eixarch, Herena; Montalban, Xavier; Álvarez-Cermeño, José C.; Guaza, Carmen; Villar, Luisa M.

2014-01-01

Background and Objectives. Resistant and susceptible mouse strains to experimental autoimmune encephalomyelitis (EAE), an inducible demyelinating experimental disease serving as animal model for multiple sclerosis, have been described. We aimed to explore MHC-independent mechanisms inducing resistance to EAE. Methods. For EAE induction, female C57BL/6 (susceptible strain) and CD1 (resistant outbred strain showing heterogeneous MHC antigens) mice were immunized with the 35–55 peptide of myelin oligodendrocyte glycoprotein (MOG35−55). We studied T cell proliferation, regulatory and effector cell subpopulations, intracellular and serum cytokine patterns, and titers of anti-MOG serum antibodies. Results. Upon immunization with MOG35−55, T lymphocytes from susceptible mice but not that of resistant strain were capable of proliferating when stimulated with MOG35−55. Accordingly, resistant mice experienced a rise in regulatory B cells (P = 0.001) and, to a lower extent, in regulatory T cells (P = 0.02) compared with C57BL/6 susceptible mice. As a consequence, MOG35−55-immunized C57BL/6 mice showed higher percentages of CD4+ T cells producing both IFN-gamma (P = 0.02) and IL-17 (P = 0.009) and higher serum levels of IL-17 (P = 0.04) than resistant mice. Conclusions. Expansion of regulatory B and T cells contributes to the induction of resistance to EAE by an MHC-independent mechanism. PMID:24868560

Cadmium inhibits mouse sperm motility through inducing tyrosine phosphorylation in a specific subset of proteins.

PubMed

Wang, Lirui; Li, Yuhua; Fu, Jieli; Zhen, Linqing; Zhao, Na; Yang, Qiangzhen; Li, Sisi; Li, Xinhong

2016-08-01

Cadmium (Cd) has been reported to impair male fertility, primarily by disrupting sperm motility, but the underlying molecular mechanism remains unclear. Here we investigated the effects of Cd on sperm motility, tyrosine phosphorylation, AMP-activated protein kinase (AMPK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, and ATP levels in vitro. Our results demonstrated that Cd inhibited sperm motility, GAPDH activity, AMPK activity and ATP production, and induced tyrosine phosphorylation of 55-57KDa proteins. Importantly, all the parameters affected by Cd were restored to normal levels when incubated with 10μM Cd in the presence of 30μM ethylene diamine tetraacetic acid (EDTA). Interestingly, changes of tyrosine phosphorylation levels of 55-57KDa proteins are completely contrary to that of other parameters. These results suggest that Cd-induced tyrosine phosphorylation of 55-57KDa proteins might act as an engine to block intracellular energy metabolism and thus decrease sperm motility. Copyright © 2016 Elsevier Inc. All rights reserved.

Does the liposuction method influence the phenotypic characteristic of human adipose-derived stem cells?

PubMed

Bajek, Anna; Gurtowska, Natalia; Gackowska, Lidia; Kubiszewska, Izabela; Bodnar, Magdalena; Marszałek, Andrzej; Januszewski, Rafał; Michalkiewicz, Jacek; Drewa, Tomasz

2015-05-14

Adipose-derived stem cells (ASCs) possess a high differentiation and proliferation potential. However, the phenotypic characterization of ASCs is still difficult. Until now, there is no extensive analysis of ASCs markers depending on different liposuction methods. Therefore, the aim of the present study was to analyse 242 surface markers and determine the differences in the phenotypic pattern between ASCs obtained during mechanical and ultrasound-assisted liposuction. ASCs were isolated from healthy donors, due to mechanical and ultrasound-assisted liposuction and cultured in standard medium to the second passage. Differentiation potential and markers expression was evaluated to confirm the mesenchymal nature of cells. Then, the BD LyoplateTM Human Cell Surface Marker Screening Panel was used. Results shown that both population of ASCs are characterized by high expression of markers specific for ASCs: cluster of differentiation (CD)9, CD10, CD34, CD44, CD49d, CD54, CD55, CD59, CD71 and low expression of CD11a, CD11c and CD144. Moreover, we have noticed significant differences in antigen expression in 58 markers from the 242 studied. Presented study shows for the first time that different liposuction methods are not a significant factor which can influence the expression of human ASCs surface markers. © 2015 The Authors.

The sensitivity of human mesenchymal stem cells to vibration and cold storage conditions representative of cold transportation

PubMed Central

Nikolaev, N. I.; Liu, Y.; Hussein, H.; Williams, D. J.

2012-01-01

In the current study, the mechanical and hypothermic damage induced by vibration and cold storage on human mesenchymal stem cells (hMSCs) stored at 2–8°C was quantified by measuring the total cell number and cell viability after exposure to vibration at 50 Hz (peak acceleration 140 m s−2 and peak displacement 1.4 mm), 25 Hz (peak acceleration 140 m s−2, peak displacement 5.7 mm), 10 Hz (peak acceleration 20 m s−2, peak displacement 5.1 mm) and cold storage for several durations. To quantify the viability of the cells, in addition to the trypan blue exclusion method, the combination of annexin V-FITC and propidium iodide was applied to understand the mode of cell death. Cell granularity and a panel of cell surface markers for stemness, including CD29, CD44, CD105 and CD166, were also evaluated for each condition. It was found that hMSCs were sensitive to vibration at 25 Hz, with moderate effects at 50 Hz and no effects at 10 Hz. Vibration at 25 Hz also increased CD29 and CD44 expression. The study further showed that cold storage alone caused a decrease in cell viability, especially after 48 h, and also increased CD29 and CD44 and attenuated CD105 expressions. Cell death would most likely be the consequence of membrane rupture, owing to necrosis induced by cold storage. The sensitivity of cells to different vibrations within the mechanical system is due to a combined effect of displacement and acceleration, and hMSCs with a longer cold storage duration were more susceptible to vibration damage, indicating a coupling between the effects of vibration and cold storage. PMID:22628214

CMC-544 (inotuzumab ozogamicin), an anti-CD22 immuno-conjugate of calicheamicin, alters the levels of target molecules of malignant B-cells.

PubMed

Takeshita, A; Yamakage, N; Shinjo, K; Ono, T; Hirano, I; Nakamura, S; Shigeno, K; Tobita, T; Maekawa, M; Kiyoi, H; Naoe, T; Ohnishi, K; Sugimoto, Y; Ohno, R

2009-07-01

We studied the effect of CMC-544, the calicheamicin-conjugated anti-CD22 monoclonal antibody, used alone and in combination with rituximab, analyzing the quantitative alteration of target molecules, that is, CD20, CD22, CD55 and CD59, in Daudi and Raji cells as well as in cells obtained from patients with B-cell malignancies (BCM). Antibody inducing direct antiproliferative and apoptotic effect, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) were tested separately. In Daudi and Raji cells, the CDC effect of rituximab significantly increased within 12 h following incubation with CMC-544. The levels of CD22 and CD55 were significantly reduced (P<0.001 in both cells) after incubation with CMC-544, but CD20 level remained constant or increased for 12 h. Similar results were obtained in cells from 12 patients with BCM. The antiproliferative and apoptotic effect of CMC-544 were greater than that of rituximab. The ADCC of rituximab was not enhanced by CMC-544. Thus, the combination of CMC-544 and rituximab increased the in vitro cytotoxic effect in BCM cells, and sequential administration for 12 h proceeded by CMC-544 was more effective. The reduction of CD55 and the preservation of CD20 after incubation with CMC-544 support the rationale for the combined use of CMC-544 and rituximab.

Platinum desensitization in patients with carboplatin hypersensitivity: A single-institution retrospective study.

PubMed

Altwerger, Gary; Gressel, Gregory M; English, Diana P; Nelson, Wendelin K; Carusillo, Nina; Silasi, Dan-Arin; Azodi, Masoud; Santin, Alessandro; Schwartz, Peter E; Ratner, Elena S

2017-01-01

The carboplatin desensitization (CD) protocol presented here allows patients with either a positive skin test or a prior hypersensitivity reaction (HSR) to safely, rapidly and effectively continue with carboplatin infusions. Newly described factors can identify patients at risk for developing adverse events during CD. A retrospective review was performed on patients with gynecologic cancer who underwent CD between 2005 and 2014. The CD protocol uses a four-step dilution process over 3.5h. 129 patients underwent CD and completed a total of 788cycles. The desensitization protocol prevented HSRs in 96% (753 out of 788) of these cycles. Patients achieved an average of 6.1cycles (SD±4.55, range 0-23) with CD. The CD protocol allowed 73% (94 of 129) of the patients to undergo carboplatin infusion without reaction. Patients with moderate to life-threatening HSRs (grade 2 through 4) were 10.5years younger at initial CD than patients with grades 0 or 1 HSRs (52.3 vs. 63, P = 0.0307). One patient death occurred during her thirteenth desensitization cycle. The HSR in this case was complicated by pre-exisiting pulmonary hypertension. This is the largest study of its kind showing a safe, effective and rapid (3.5h) CD protocol. The majority of patients with a history of either carboplatin hypersensitivity reaction or a positive skin test completed the CD protocol without HSRs. Age was identified as a risk factor for HSR severity during CD. Age can be employed along with pre-load dependent cardiac conditions as a way to help risk stratify patients undergoing CD. Copyright © 2016 Elsevier Inc. All rights reserved.

Nanostructured Electron-Selective Interlayer for Efficient Inverted Organic Solar Cells.

PubMed

Song, Jiyun; Lim, Jaehoon; Lee, Donggu; Thambidurai, M; Kim, Jun Young; Park, Myeongjin; Song, Hyung-Jun; Lee, Seonghoon; Char, Kookheon; Lee, Changhee

2015-08-26

We report a unique nanostructured electron-selective interlayer comprising of In-doped ZnO (ZnO:In) and vertically aligned CdSe tetrapods (TPs) for inverted polymer:fullerene bulkheterojunction (BHJ) solar cells. With dimension-controlled CdSe TPs, the direct inorganic electron transport pathway is provided, resulting in the improvement of the short circuit current and fill factor of devices. We demonstrate that the enhancement is attributed to the roles of CdSe TPs that reduce the recombination losses between the active layer and buffer layer, improve the hole-blocking as well as electron-transporting properties, and simultaneously improve charge collection characteristics. As a result, the power conversion efficiency of PTB7:PC70BM based solar cell with nanostructured CdSe TPs increases to 7.55%. We expect this approach can be extended to a general platform for improving charge extraction in organic solar cells.

CD30 expression is rare in myeloid leukemia cutis; a study of 55 cases and implications for routine diagnostic algorithms

PubMed Central

Ogunrinade, Olakunle; Terrano, David; Chiu, April; Pulitzer, Melissa

2016-01-01

Expression of CD30 in blastoid cutaneous infiltrates typically signifies a CD30+ lymphoproliferative disorder, often requiring minimal immunohistochemical work-up, if clinically consonant. However, myeloid and other hematologic malignancies often express CD30. We retrospectively examined the prevalence of CD30 expression in 41 patients (median age 59) and 55 biopsies with the diagnosis of leukemia cutis (LC) to determine whether an extensive immunohistochemical workup is warranted in all large, round cell CD30+ cutaneous infiltrates. Each patient had refractory or recurrent disease, the histologic presence of a large mononuclear cell infiltrate, and varied cytogenetics. CD30+ mononuclear cells within the infiltrate ranged from rare to many in twenty-two biopsies (22/55). In eighteen biopsies, CD30+ cells were interpreted as lymphocytic based on morphology, strong cytoplasmic and Golgi staining for CD30, and negative CD34 and CD117 staining. One case showing 3+ staining of lymphocytes was identified as a post-transplant lymphoproliferative disorder. The second 3+ case was favored to represent a subset CD30-positive AML. Three other cases with 1+ membranous and cytoplasmic staining were interpreted as myeloid leukemia. In conclusion, CD30 positivity in myeloid leukemia in the skin is rare and does not often exhibit the strong membranous (2+ or 3+) and/or Golgi staining seen in reactive lymphocytes. AML or myeloid LC may occasionally show 1+ (and rarely 2-3+) cytoplasmic/membranous or non-specific blush nuclear CD30 labeling. Strong diffuse staining for CD30 should prompt consideration of a reactive lymphoid/lymphoproliferative process, and, when the clinical likelihood of CD30+ leukemia cutis is low, may obviate the need for further immunohistochemistry. PMID:27893466

Comparison of Head Scatter Factor for 6MV and 10MV flattened (FB) and Unflattened (FFF) Photon Beam using indigenously Designed Columnar Mini Phantom.

PubMed

Ashokkumar, Sigamani; Nambi Raj, N Arunai; Sinha, Sujit Nath; Yadav, Girigesh; Thiyagarajan, Rajesh; Raman, Kothanda; Mishra, Manindra Bhushan

2014-07-01

To measure and compare the head scatter factor for flattened (FB) and unflattened (FFF) of 6MV and 10MV photon beam using indigenously designed mini phantom. A columnar mini phantom was designed as recommended by AAPM Task Group 74 with low and high atomic number materials at 10 cm (mini phantom) and at approximately twice the depth of maximum dose water equivalent thickness (brass build-up cap). Scatter in the accelerator (Sc) values of 6MV-FFF photon beams are lesser than that of the 6MV-FB photon beams (0.66-2.8%; Clinac iX, 2300CD) and (0.47-1.74%; True beam) for field sizes ranging from 10 × 10 cm(2) to 40 × 40 cm(2). Sc values of 10MV-FFF photon beams are lesser (0.61-2.19%; True beam) than that of the 10MV-FB photons beams for field sizes ranging from 10 × 10 cm(2) to 40 × 40 cm(2). The SSD had no influence on head scatter for both flattened and unflattened beams and irrespective of head design of the different linear accelerators. The presence of field shaping device influences the Sc values. The collimator exchange effect reveals that the opening of the upper jaw increases Sc irrespective of FB or FFF photon beams and different linear accelerators, and it is less significant in FFF beams. Sc values of 6MV-FB square field were in good agreement with that of AAPM, TG-74 published data for Varian (Clinac iX, 2300CD) accelerator. Our results confirm that the removal of flattening filter decreases in the head scatter factor compared to flattened beam. This could reduce the out-of-field dose in advanced treatment delivery techniques.

Comparison of Head Scatter Factor for 6MV and 10MV flattened (FB) and Unflattened (FFF) Photon Beam using indigenously Designed Columnar Mini Phantom

PubMed Central

Ashokkumar, Sigamani; Nambi Raj, N Arunai; Sinha, Sujit Nath; Yadav, Girigesh; Thiyagarajan, Rajesh; Raman, Kothanda; Mishra, Manindra Bhushan

2014-01-01

To measure and compare the head scatter factor for flattened (FB) and unflattened (FFF) of 6MV and 10MV photon beam using indigenously designed mini phantom. A columnar mini phantom was designed as recommended by AAPM Task Group 74 with low and high atomic number materials at 10 cm (mini phantom) and at approximately twice the depth of maximum dose water equivalent thickness (brass build-up cap). Scatter in the accelerator (Sc) values of 6MV-FFF photon beams are lesser than that of the 6MV-FB photon beams (0.66-2.8%; Clinac iX, 2300CD) and (0.47-1.74%; True beam) for field sizes ranging from 10 × 10 cm2 to 40 × 40 cm2. Sc values of 10MV-FFF photon beams are lesser (0.61-2.19%; True beam) than that of the 10MV-FB photons beams for field sizes ranging from 10 × 10 cm2 to 40 × 40 cm2. The SSD had no influence on head scatter for both flattened and unflattened beams and irrespective of head design of the different linear accelerators. The presence of field shaping device influences the Sc values. The collimator exchange effect reveals that the opening of the upper jaw increases Sc irrespective of FB or FFF photon beams and different linear accelerators, and it is less significant in FFF beams. Sc values of 6MV-FB square field were in good agreement with that of AAPM, TG-74 published data for Varian (Clinac iX, 2300CD) accelerator. Our results confirm that the removal of flattening filter decreases in the head scatter factor compared to flattened beam. This could reduce the out-of-field dose in advanced treatment delivery techniques. PMID:25190997

Immunophenotyping and activation status of maternal peripheral blood leukocytes during pregnancy and labour, both term and preterm.

PubMed

Zhang, Jianhong; Shynlova, Oksana; Sabra, Sally; Bang, Annie; Briollais, Laurent; Lye, Stephen J

2017-10-01

The onset of labour in rodents and in humans is associated with physiological inflammation which is manifested by infiltration of activated maternal peripheral leukocytes (mPLs) into uterine tissues. Here, we used flow cytometry to immunophenotype mPLs throughout gestation and labour, both term and preterm. Peripheral blood was collected from non-pregnant women and pregnant women in the 1st, 2nd and 3rd trimesters. Samples were also collected from women in active labour at term (TL) or preterm (PTL) and compared with women term not-in-labour (TNIL) and preterm not-in-labour (PTNIL). Different leukocyte populations were identified by surface markers such as CD45, CD14, CD15, CD3, CD4, CD8, CD19 and CD56. Their activation status was measured by the expression levels of CD11b, CD44, CD55, CD181 and CD192 proteins. Of all circulating CD45+ leukocytes, we detected significant increases in CD15+ granulocytes (i) in pregnant women versus non-pregnant; (ii) in TL women versus TNIL and versus pregnant women in the 1st/2nd/3rd trimester; (iii) in PTL women versus PTNIL. TL was characterized by (iv) increased expressions of CD11b, CD55 and CD192 on granulocytes; (v) increased mean fluorescent intensity (MFI) of CD55 and CD192 on monocytes; (vi) increased CD44 MFI on CD3+ lymphocytes as compared to late gestation. In summary, we have identified sub-populations of mPLs that are specifically activated in association with gestation (granulocytes) or with the onset of labour (granulocytes, monocytes and lymphocytes). Additionally, beta regression analysis created a set of reference values to rank this association between immune markers of pregnancy and to identify activation status with potential prognostic and diagnostic capability. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Differential clinical efficacy of anti-CD4 monoclonal antibodies in rat adjuvant arthritis is paralleled by differential influence on NF-κB binding activity and TNF-α secretion of T cells

PubMed Central

Pohlers, Dirk; Schmidt-Weber, Carsten B; Franch, Angels; Kuhlmann, Jürgen; Bräuer, Rolf; Emmrich, Frank; Kinne, Raimund W

2002-01-01

The aim of this study was to analyze the differential effects of three anti-CD4 monoclonal antibodies (mAbs) (with distinct epitope specifities) in the treatment of rat adjuvant arthritis (AA) and on T-cell function and signal transduction. Rat AA was preventively treated by intraperitoneal injection of the anti-CD4 mAbs W3/25, OX35, and RIB5/2 (on days -1, 0, 3, and 6, i.e. 1 day before AA induction, on the day of induction [day 0], and thereafter). The effects on T-cell reactivity in vivo (delayed-type hypersensitivity), ex vivo (ConA-induced proliferation), and in vitro (mixed lymphocyte culture) were assessed. The in vitro effects of anti-CD4 preincubation on T-cell receptor (TCR)/CD3-induced cytokine production and signal transduction were also analyzed. While preventive treatment with OX35 and W3/25 significantly ameliorated AA from the onset, treatment with RIB5/2 even accelerated the onset of AA by approximately 2 days (day 10), and ameliorated the arthritis only in the late phase (day 27). Differential clinical effects at the onset of AA were paralleled by a differential influence of the mAbs on T-cell functions, i.e. in comparison with OX35 and W3/25, the 'accelerating' mAb RIB5/2 failed to increase the delayed-type hypersentivity (DTH) to Mycobacterium tuberculosis, increased the in vitro tumor necrosis factor (TNF)-α secretion, and more strongly induced NF-κB binding activity after anti-CD4 preincubation and subsequent TCR/CD3-stimulation. Depending on their epitope specificity, different anti-CD4 mAbs differentially influence individual proinflammatory functions of T cells. This fine regulation may explain the differential efficacy in the treatment of AA and may contribute to the understanding of such treatments in other immunopathologies. PMID:12010568

Spontaneous abortion is associated with elevated systemic C5a and reduced mRNA of complement inhibitory proteins in placenta

PubMed Central

Banadakoppa, M; Chauhan, M S; Havemann, D; Balakrishnan, M; Dominic, J S; Yallampalli, C

2014-01-01

Spontaneous abortion in early pregnancy due to unknown reasons is a common problem. The excess complement activation and consequent placental inflammation and anti-angiogenic milieu is emerging as an important associated factor in many pregnancy-related complications. In the present study we sought to examine the expression of complement inhibitory proteins at the feto–maternal interface and levels of complement split products in the circulation to understand their role in spontaneous abortion. Consenting pregnant women who either underwent elective abortion due to non-clinical reasons (n = 13) or suffered miscarriage (n = 14) were recruited for the study. Systemic levels of complement factors C3a and C5a were measured by enzyme-linked immunosorbent assay (ELISA). Plasma C5 and C3 protein levels were examined by Western blot. Expressions of complement regulatory proteins such as CD46 and CD55 in the decidua were investigated by quantitative polymerase chain reaction (PCR) and Western blot. The median of plasma C3a level was 82·83 ng/ml and 66·17 ng/ml in elective and spontaneous abortion patients, respectively. Medians of plasma C5a levels in elective and spontaneous abortion patients were 0·96 ng/ml and 1·14 ng/ml, respectively. Only plasma C5a levels but not C3a levels showed significant elevation in spontaneous abortion patients compared to elective abortion patients. Further, there was a threefold decrease in the mRNA expressions of complement inhibitory proteins CD46 and CD55 in the decidua obtained from spontaneous abortion patients compared to that of elective abortion patients. These data suggested that dysregulated complement cascade may be associated with spontaneous abortion. PMID:24802103

Nonequilibrium ab initio molecular dynamics determination of Ti monovacancy migration rates in B 1 TiN

NASA Astrophysics Data System (ADS)

Gambino, D.; Sangiovanni, D. G.; Alling, B.; Abrikosov, I. A.

2017-09-01

We use the color diffusion (CD) algorithm in nonequilibrium (accelerated) ab initio molecular dynamics simulations to determine Ti monovacancy jump frequencies in NaCl-structure titanium nitride (TiN), at temperatures ranging from 2200 to 3000 K. Our results show that the CD method extended beyond the linear-fitting rate-versus-force regime [Sangiovanni et al., Phys. Rev. B 93, 094305 (2016), 10.1103/PhysRevB.93.094305] can efficiently determine metal vacancy migration rates in TiN, despite the low mobilities of lattice defects in this type of ceramic compound. We propose a computational method based on gamma-distribution statistics, which provides unambiguous definition of nonequilibrium and equilibrium (extrapolated) vacancy jump rates with corresponding statistical uncertainties. The acceleration-factor achieved in our implementation of nonequilibrium molecular dynamics increases dramatically for decreasing temperatures from 500 for T close to the melting point Tm, up to 33 000 for T ≈0.7 Tm .

CML/CD36 accelerates atherosclerotic progression via inhibiting foam cell migration.

PubMed

Xu, Suining; Li, Lihua; Yan, Jinchuan; Ye, Fei; Shao, Chen; Sun, Zhen; Bao, Zhengyang; Dai, Zhiyin; Zhu, Jie; Jing, Lele; Wang, Zhongqun

2018-01-01

Among the various complications of type 2 diabetes mellitus, atherosclerosis causes the highest disability and morbidity. A multitude of macrophage-derived foam cells are retained in atherosclerotic plaques resulting not only from recruitment of monocytes into lesions but also from a reduced rate of macrophage migration from lesions. Nε-carboxymethyl-Lysine (CML), an advanced glycation end product, is responsible for most complications of diabetes. This study was designed to investigate the mechanism of CML/CD36 accelerating atherosclerotic progression via inhibiting foam cell migration. In vivo study and in vitro study were performed. For the in vivo investigation, CML/CD36 accelerated atherosclerotic progression via promoting the accumulation of macrophage-derived foam cells in aorta and inhibited macrophage-derived foam cells in aorta migrating to the para-aorta lymph node of diabetic apoE -/- mice. For the in vitro investigation, CML/CD36 inhibited RAW264.7-derived foam cell migration through NOX-derived ROS, FAK phosphorylation, Arp2/3 complex activation and F-actin polymerization. Thus, we concluded that CML/CD36 inhibited foam cells of plaque migrating to para-aorta lymph nodes, accelerating atherosclerotic progression. The corresponding mechanism may be via free cholesterol, ROS generation, p-FAK, Arp2/3, F-actin polymerization. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Rate of progression from first use to dependence on cocaine or opioids: a cross-substance examination of associated demographic, psychiatric, and childhood risk factors.

PubMed

Sartor, Carolyn E; Kranzler, Henry R; Gelernter, Joel

2014-02-01

A number of demographic factors, psychiatric disorders, and childhood risk factors have been associated with cocaine dependence (CD) and opioid dependence (OD), but little is known about their relevance to the rate at which dependence develops. Identification of the subpopulations at elevated risk for rapid development of dependence and the risk factors that accelerate the course of dependence is an important public health goal. Data were derived from cocaine dependent (n=6333) and opioid dependent (n=3513) participants in a multi-site study of substance dependence. Mean age was approximately 40 and 40% of participants were women; 51.9% of cocaine dependent participants and 29.5% of opioid dependent participants self-identified as Black/African-American. The time from first use to dependence was calculated for each substance and a range of demographic, psychiatric, and childhood risk factors were entered into ordinal logistic regression models to predict the (categorical) transition time to CD and OD. In both the cocaine and opioid models, conduct disorder and childhood physical abuse predicted rapid development of dependence and alcohol and nicotine dependence diagnoses were associated with slower progression to CD or OD. Blacks/African Americans were at greater risk than European Americans to progress rapidly to OD. Only a subset of factors known to be associated with CD and OD predicted the rate at which dependence developed. Nearly all were common to cocaine and opioids, suggesting that sources of influence on the timing of transitions to dependence are shared across the two substances. © 2013.

Haploinsufficiency of the insulin-like growth factor-1 receptor enhances endothelial repair and favorably modifies angiogenic progenitor cell phenotype.

PubMed

Yuldasheva, Nadira Y; Rashid, Sheikh Tawqeer; Haywood, Natalie J; Cordell, Paul; Mughal, Romana; Viswambharan, Hema; Imrie, Helen; Sukumar, Piruthivi; Cubbon, Richard M; Aziz, Amir; Gage, Matthew; Mbonye, Kamatamu Amanda; Smith, Jessica; Galloway, Stacey; Skromna, Anna; Scott, D Julian A; Kearney, Mark T; Wheatcroft, Stephen B

2014-09-01

Defective endothelial regeneration predisposes to adverse arterial remodeling and is thought to contribute to cardiovascular disease in type 2 diabetes mellitus. We recently demonstrated that the type 1 insulin-like growth factor receptor (IGF1R) is a negative regulator of insulin sensitivity and nitric oxide bioavailability. In this report, we examined partial deletion of the IGF1R as a potential strategy to enhance endothelial repair. We assessed endothelial regeneration after wire injury in mice and abundance and function of angiogenic progenitor cells in mice with haploinsufficiency of the IGF1R (IGF1R(+/-)). Endothelial regeneration after arterial injury was accelerated in IGF1R(+/-) mice. Although the yield of angiogenic progenitor cells was lower in IGF1R(+/-) mice, these angiogenic progenitor cells displayed enhanced adhesion, increased secretion of insulin-like growth factor-1, and enhanced angiogenic capacity. To examine the relevance of IGF1R manipulation to cell-based therapy, we transfused IGF1R(+/-) bone marrow-derived CD117(+) cells into wild-type mice. IGF1R(+/-) cells accelerated endothelial regeneration after arterial injury compared with wild-type cells and did not alter atherosclerotic lesion formation. Haploinsufficiency of the IGF1R is associated with accelerated endothelial regeneration in vivo and enhanced tube forming and adhesive potential of angiogenic progenitor cells in vitro. Partial deletion of IGF1R in transfused bone marrow-derived CD117(+) cells enhanced their capacity to promote endothelial regeneration without altering atherosclerosis. Our data suggest that manipulation of the IGF1R could be exploited as novel therapeutic approach to enhance repair of the arterial wall after injury. © 2014 American Heart Association, Inc.

Estimation and influence of physicochemical properties and chemical fractions of surface sediment on the bioaccessibility of Cd and Hg contaminant in Langat River, Malaysia.

PubMed

Kadhum, Safaa A; Ishak, Mohd Yusoff; Zulkifli, Syaizwan Zahmir

2017-10-01

This study applied the use of sequential extraction technique and simple bioaccessibility extraction test to quantify the bioavailable fractions and the human bioaccessible concentration of metals collected from nine stations in surface sediment of the Langat River. The concentrations of total and bioaccessible metals from different stations were in the range of 0.49-1.04, 0.10-0.32 μg g -1 for T-Cd, Bio-Cd, respectively, and 12.9-128.03, 2.06-8.53 μg kg -1 for T-Hg, Bio-Hg, respectively. The results revealed highest R-Bio-Cd in Banting station (55.3 %), while the highest R-Bio-Hg was in Kajang station (49.61 %). The chemical speciation of Cd in most sampling stations was in the order of oxidisable-organic > residual > exchangeable > acid-reducible, while speciation of Hg was in the order of exchangeable > residual > oxidisable-organic > acid-reducible. The correlation matric of mean content showed that the TOM, particle size and Mg ++ in polluted surface sediments was highly correlated with total mercury. The PCA showed that the main factors influencing the bioaccessibility of Hg in surface sediments were the sediment TOM, F1 (EFLE) and F3 (oxidation-organic), while the factor influencing the bioaccessibility of Cd was the F3 (oxidation-organic) and T-Cd.

TNF/TNFR1 signaling up-regulates CCR5 expression by CD8+ T lymphocytes and promotes heart tissue damage during Trypanosoma cruzi infection: beneficial effects of TNF-alpha blockade.

PubMed

Kroll-Palhares, Karina; Silvério, Jaline Coutinho; Silva, Andrea Alice da; Michailowsky, Vladimir; Marino, Ana Paula; Silva, Neide Maria; Carvalho, Cristiano Marcelo Espinola; Pinto, Luzia Maria de Oliveira; Gazzinelli, Ricardo Tostes; Lannes-Vieira, Joseli

2008-06-01

In Chagas disease, understanding how the immune response controls parasite growth but also leads to heart damage may provide insight into the design of new therapeutic strategies. Tumor necrosis factor-alpha (TNF-alpha) is important for resistance to acute Trypanosoma cruzi infection; however, in patients suffering from chronic T. cruzi infection, plasma TNF-alpha levels correlate with cardiomyopathy. Recent data suggest that CD8-enriched chagasic myocarditis formation involves CCR1/CCR5-mediated cell migration. Herein, the contribution of TNF-alpha, especially signaling through the receptor TNFR1/p55, to the pathophysiology of T. cruzi infection was evaluated with a focus on the development of myocarditis and heart dysfunction. Colombian strain-infected C57BL/6 mice had increased frequencies of TNFR1/p55+ and TNF-alpha+ splenocytes. Although TNFR1-/- mice exhibited reduced myocarditis in the absence of parasite burden, they succumbed to acute infection. Similar to C57BL/6 mice, Benznidazole-treated TNFR1-/- mice survived acute infection. In TNFR1-/- mice, reduced CD8-enriched myocarditis was associated with defective activation of CD44+CD62Llow/- and CCR5+ CD8+ lymphocytes. Also, anti-TNF-alpha treatment reduced the frequency of CD8+CCR5+ circulating cells and myocarditis, though parasite load was unaltered in infected C3H/HeJ mice. TNFR1-/- and anti-TNF-alpha-treated infected mice showed regular expression of connexin-43 and reduced fibronectin deposition, respectively. Furthermore, anti-TNF-alpha treatment resulted in lower levels of CK-MB, a cardiomyocyte lesion marker. Our results suggest that TNF/TNFR1 signaling promotes CD8-enriched myocarditis formation and heart tissue damage, implicating the TNF/TNFR1 signaling pathway as a potential therapeutic target for control of T. cruzi-elicited cardiomyopathy.

Host and Viral Factors in HIV-Mediated Bystander Apoptosis

PubMed Central

Garg, Himanshu; Joshi, Anjali

2017-01-01

Human immunodeficiency virus (HIV) infections lead to a progressive loss of CD4 T cells primarily via the process of apoptosis. With a limited number of infected cells and vastly disproportionate apoptosis in HIV infected patients, it is believed that apoptosis of uninfected bystander cells plays a significant role in this process. Disease progression in HIV infected individuals is highly variable suggesting that both host and viral factors may influence HIV mediated apoptosis. Amongst the viral factors, the role of Envelope (Env) glycoprotein in bystander apoptosis is well documented. Recent evidence on the variability in apoptosis induction by primary patient derived Envs underscores the role of Env glycoprotein in HIV disease. Amongst the host factors, the role of C-C Chemokine Receptor type 5 (CCR5), a coreceptor for HIV Env, is also becoming increasingly evident. Polymorphisms in the CCR5 gene and promoter affect CCR5 cell surface expression and correlate with both apoptosis and CD4 loss. Finally, chronic immune activation in HIV infections induces multiple defects in the immune system and has recently been shown to accelerate HIV Env mediated CD4 apoptosis. Consequently, those factors that affect CCR5 expression and/or immune activation in turn indirectly regulate HIV mediated apoptosis making this phenomenon both complex and multifactorial. This review explores the complex role of various host and viral factors in determining HIV mediated bystander apoptosis. PMID:28829402

Crohn's disease: increased mortality 10 years after diagnosis in a Europe‐wide population based cohort

PubMed Central

Wolters, F L; Russel, M G; Sijbrandij, J; Schouten, L J; Odes, S; Riis, L; Munkholm, P; Bodini, P; O'Morain, C; Mouzas, I A; Tsianos, E; Vermeire, S; Monteiro, E; Limonard, C; Vatn, M; Fornaciari, G; Pereira, S; Moum, B; Stockbrügger, R W

2006-01-01

Background No previous correlation between phenotype at diagnosis of Crohn's disease (CD) and mortality has been performed. We assessed the predictive value of phenotype at diagnosis on overall and disease related mortality in a European cohort of CD patients. Methods Overall and disease related mortality were recorded 10 years after diagnosis in a prospectively assembled, uniformly diagnosed European population based inception cohort of 380 CD patients diagnosed between 1991 and 1993. Standardised mortality ratios (SMRs) were calculated for geographic and phenotypic subgroups at diagnosis. Results Thirty seven deaths were observed in the entire cohort whereas 21.5 deaths were expected (SMR 1.85 (95% CI 1.30–2.55)). Mortality risk was significantly increased in both females (SMR 1.93 (95% CI 1.10–3.14)) and males (SMR 1.79 (95% CI 1.11–2.73)). Patients from northern European centres had a significant overall increased mortality risk (SMR 2.04 (95% CI 1.32–3.01)) whereas a tendency towards increased overall mortality risk was also observed in the south (SMR 1.55 (95% CI 0.80–2.70)). Mortality risk was increased in patients with colonic disease location and with inflammatory disease behaviour at diagnosis. Mortality risk was also increased in the age group above 40 years at diagnosis for both total and CD related causes. Excess mortality was mainly due to gastrointestinal causes that were related to CD. Conclusions This European multinational population based study revealed an increased overall mortality risk in CD patients 10 years after diagnosis, and age above 40 years at diagnosis was found to be the sole factor associated with increased mortality risk. PMID:16150857

Crohn's disease: increased mortality 10 years after diagnosis in a Europe-wide population based cohort.

PubMed

Wolters, F L; Russel, M G; Sijbrandij, J; Schouten, L J; Odes, S; Riis, L; Munkholm, P; Bodini, P; O'Morain, C; Mouzas, I A; Tsianos, E; Vermeire, S; Monteiro, E; Limonard, C; Vatn, M; Fornaciari, G; Pereira, S; Moum, B; Stockbrügger, R W

2006-04-01

No previous correlation between phenotype at diagnosis of Crohn's disease (CD) and mortality has been performed. We assessed the predictive value of phenotype at diagnosis on overall and disease related mortality in a European cohort of CD patients. Overall and disease related mortality were recorded 10 years after diagnosis in a prospectively assembled, uniformly diagnosed European population based inception cohort of 380 CD patients diagnosed between 1991 and 1993. Standardised mortality ratios (SMRs) were calculated for geographic and phenotypic subgroups at diagnosis. Thirty seven deaths were observed in the entire cohort whereas 21.5 deaths were expected (SMR 1.85 (95% CI 1.30-2.55)). Mortality risk was significantly increased in both females (SMR 1.93 (95% CI 1.10-3.14)) and males (SMR 1.79 (95% CI 1.11-2.73)). Patients from northern European centres had a significant overall increased mortality risk (SMR 2.04 (95% CI 1.32-3.01)) whereas a tendency towards increased overall mortality risk was also observed in the south (SMR 1.55 (95% CI 0.80-2.70)). Mortality risk was increased in patients with colonic disease location and with inflammatory disease behaviour at diagnosis. Mortality risk was also increased in the age group above 40 years at diagnosis for both total and CD related causes. Excess mortality was mainly due to gastrointestinal causes that were related to CD. This European multinational population based study revealed an increased overall mortality risk in CD patients 10 years after diagnosis, and age above 40 years at diagnosis was found to be the sole factor associated with increased mortality risk.

Stability of CIGS Solar Cells and Component Materials Evaluated by a Step-Stress Accelerated Degradation Test Method: Preprint

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

Pern, F. J.; Noufi, R.

A step-stress accelerated degradation testing (SSADT) method was employed for the first time to evaluate the stability of CuInGaSe2 (CIGS) solar cells and device component materials in four Al-framed test structures encapsulated with an edge sealant and three kinds of backsheet or moisture barrier film for moisture ingress control. The SSADT exposure used a 15oC and then a 15% relative humidity (RH) increment step, beginning from 40oC/40%RH (T/RH = 40/40) to 85oC/70%RH (85/70) as of the moment. The voluminous data acquired and processed as of total DH = 3956 h with 85/70 = 704 h produced the following results. Themore » best CIGS solar cells in sample Set-1 with a moisture-permeable TPT backsheet showed essentially identical I-V degradation trend regardless of the Al-doped ZnO (AZO) layer thickness ranging from standard 0.12 μm to 0.50 μm on the cells. No clear 'stepwise' feature in the I-V parameter degradation curves corresponding to the SSADT T/RH/time profile was observed. Irregularity in I-V performance degradation pattern was observed with some cells showing early degradation at low T/RH < 55/55 and some showing large Voc, FF, and efficiency degradation due to increased series Rs (ohm-cm2) at T/RH ≥ 70/70. Results of (electrochemical) impedance spectroscopy (ECIS) analysis indicate degradation of the CIGS solar cells corresponded to increased series resistance Rs (ohm) and degraded parallel (minority carrier diffusion/recombination) resistance Rp, capacitance C, overall time constant Rp*C, and 'capacitor quality' factor (CPE-P), which were related to the cells? p-n junction properties. Heating at 85/70 appeared to benefit the CIGS solar cells as indicated by the largely recovered CPE-P factor. Device component materials, Mo on soda lime glass (Mo/SLG), bilayer ZnO (BZO), AlNi grid contact, and CdS/CIGS/Mo/SLG in test structures with TPT showed notable to significant degradation at T/RH ≥ 70/70. At T/RH = 85/70, substantial blistering of BZO layers on CIGS cell pieces was observed that was not seen on BZO/glass, and a CdS/CIGS sample displayed a small darkening and then flaking feature. Additionally, standard AlNi grid contact was less stable than thin Ni grid contact at T/RH ≥ 70/70. The edge sealant and moisture-blocking films were effective to block moisture ingress, as evidenced by the good stability of most CIGS solar cells and device components at T/RH = 85/70 for 704 h, and by preservation of the initial blue color on the RH indicator strips. The SSADT experiment is ongoing to be completed at T/RH = 85/85.« less

Prevalence and management of helminthiasis among underfives living with HIV/AIDS at Amana Hospital, Tanzania.

PubMed

Mwambete, Kennedy D; Tunzo, Jones; Justin-Temu, Mary

2013-01-01

This was a cross-sectional study intended to assess the prevalence and management of helminthiasis (HL) among underfives living with HIV/AIDS (ULHA). Clinical histories of ULHA were scrutinized for HIV/AIDS status, antiretroviral therapy (ART), HL prevalence, and their management. About 364 ULHA were studied, 213 (58.5%) were girls and 151 (41.5%) were boys. Of the 364 ULHA, 171 (47.5%) had HL and 64.3% were treated with albendazole (ABZ). Trichuriasis was ascribed to 23.6% of HL. Majority (72.5%) of ULHA had a CD4 count below 200 cells/mm³. Direct association was observed between CD4 counts and HL. About 55% ULHA were on lamivudine (3TC)-stavudine (d4T)-nevirapine (NVP; LSN) combination therapy. The ABZ-LSN combination was frequently used for HIV/AIDS and HL management. High prevalence of HL and vivid correlation between HIV status and HL were observed. The LSN-ABZ combination was frequently employed for management of HIV/AIDS and HL. We recommended prompt diagnosis of HL to avoid acceleration of HIV infection to AIDS.

Neutron production by stopping 55 MeV deuterons in carbon and heavy water

NASA Astrophysics Data System (ADS)

Lhersonneau, G.; Malkiewicz, T.; Jones, P.; Ketelhut, S.; Trzaska, W. H.

2012-09-01

Neutron production by stopping 55 MeV deuterons in thick carbon and heavy-water targets has been measured by the activation method. The geometry was close to the one defined for the SPIRAL2 uranium-carbide target in the initial phase. A comparative method for obtaining the neutron flux has been used and is presented in detail. The neutron flux generated by 55 MeV deuterons on carbon is 2.3 times the flux at the deuteron energy of 40 MeV. The flux further increases by a factor 1.4 when using a heavy-water target. These results are discussed in the context of an energy upgrade of the SPIRAL2 driver accelerator.

Accelerated cycle life performance for ovonic nickel-metal hydride cells

NASA Technical Reports Server (NTRS)

Otzinger, Burton M.

1991-01-01

Nickel-Metal Hydride (Ni-MH) rechargeable batteries have emerged as the leading candidate for commercial replacement of nickel-cadmium (Ni-Cd) batteries. An important incentive is that the Ni-MH cell provides approximately twice the capacity of a Ni-Cd cell for a given size. A six-cell battery was committed to an accelerated cycle life test to determine the effect of separation type on performance. Results of the test may also show the Ni-MH battery to be a replacement candidate for the aerospace Ni-Cd battery.

Depletion of CD4 T Lymphocytes at the time of infection with M. avium subsp. paratuberculosis does not accelerate disease progression

USDA-ARS?s Scientific Manuscript database

A calf model was used to determine if the depletion of CD4 T cells prior to inoculation of Mycobacterium avium subsp. paratuberculosis (Map) would delay development of an immune response to Map and accelerate disease progression. Ileal cannulas were surgically implanted in 5 bull calves at two month...

PDGF-B Gene Therapy Accelerates Bone Engineering and Oral Implant Osseointegration

PubMed Central

Chang, Po-Chun; Seol, Yang-Jo; Cirelli, Joni A; Pellegrini, Gaia R.; Jin, Qiming; Franco, Lea M.; Goldstein, Steven A.; Chandler, Lois A.; Sosnowski, Barbara; Giannobile, William V.

2009-01-01

Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due in part to transient growth factor bioavailability in vivo. Here, we report that gene delivery of PDGF-B stimulates repair of oral implant extraction socket defects. Alveolar ridge defects were created in rats and were treated at the time of titanium implant installation with a collagen matrix containing an adenoviral (Ad) vector encoding PDGF-B (5.5×108 or 5.5×109 pfu/ml), Ad encoding luciferase (Ad-Luc; 5.5×109 pfu/ml; control) or recombinant human PDGF-BB protein (rhPDGF-BB, 0.3 mg/ml). Bone repair and osseointegration were measured via backscattered SEM, histomorphometry, microcomputed tomography, and biomechanical assessments. Further, a panel of local and systemic safety assessments was performed. Results demonstrated bone repair was accelerated by Ad-PDGF-B and rhPDGF-BB delivery compared to Ad-Luc, with the high dose of Ad-PDGF-B more effective than the low dose. No significant dissemination of the vector construct or alteration of systemic parameters was noted. In summary, gene delivery of Ad-PDGF-B demonstrates regenerative and safety capabilities for bone tissue engineering and osseointegration in alveolar bone defects comparable to rhPDGF-BB protein delivery in vivo. PMID:19741730

Phase I clinical trial of costimulated, IL-4 polarized donor CD4+ T cells as augmentation of allogeneic hematopoietic cell transplantation.

PubMed

Fowler, Daniel H; Odom, Jeanne; Steinberg, Seth M; Chow, Catherine K; Foley, Jason; Kogan, Yelena; Hou, Jeannie; Gea-Banacloche, Juan; Sportes, Claude; Pavletic, Steven; Leitman, Susan; Read, Elizabeth J; Carter, Charles; Kolstad, Arne; Fox, Rebecca; Beatty, Gregory L; Vonderheide, Robert H; Levine, Bruce L; June, Carl H; Gress, Ronald E; Bishop, Michael R

2006-11-01

The primary objective of this clinical trial was to evaluate the safety, feasibility, and biologic effects of administering costimulated, interleukin (IL)-4 polarized donor CD4(+) T cells in the setting of HLA-matched sibling, T cell-replete allogeneic hematopoietic cell transplantation (HCT). Forty-seven subjects with hematologic malignancy received granulocyte colony-stimulating factor-mobilized allogeneic hematopoietic cell transplants and cyclosporine graft-versus-host disease (GVHD) prophylaxis after reduced intensity conditioning. Initial subjects received no additional cells (n = 19); subsequent subjects received additional donor CD4(+) T cells generated ex vivo by CD3/CD28 costimulation in medium containing IL-4 and IL-2 (administered day 1 after HCT at 5, 25, or 125 x 10(6) cells/kg). Studies after HCT included measurement of monocyte IL-1alpha and tumor necrosis factor alpha, detection of T cells with antitumor specificity, and characterization of T cell cytokine phenotype. The culture method generated donor CD4(+) T cells that secreted increased T helper 2 (Th2) cytokines and decreased T helper 1 (Th1) cytokines. Such Th2-like cells were administered without infusional or dose-limiting toxicity. The Th2 cohort had accelerated lymphocyte reconstitution; both cohorts had rapid hematopoietic recovery and alloengraftment. Acute GVHD and overall survival were similar in the Th2 and non-Th2 cohorts. Th2 cell recipients tended to have increased monocyte IL-1alpha and had increased tumor necrosis factor alpha secretion. CD8(+) T cells with antitumor specificity were observed in Th2 and non-Th2 cohorts. Post-transplantation T cells from Th2 cell recipients secreted IL-4 and IL-10 (Th2 cytokines) and IL-2 and interferon gamma (Th1 cytokines). Allograft augmentation with costimulated, IL-4-polarized donor CD4(+) T cells resulted in activated Th1, Th2, and inflammatory cytokine pathways without an apparent increase in GVHD.

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

PubMed

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

2015-10-01

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

Consistency and reproducibility of the VMAT plan delivery using three independent validation methods

PubMed Central

Chandraraj, Varatharaj; Manickam, Ravikumar; Esquivel, Carlos; Supe, Sanjay S; Papanikolaou, Nikos

2010-01-01

The complexity of VMAT delivery requires new methods and potentially new tools for the commissioning of these systems. It appears that great consideration is needed for quality assurance (QA) of these treatments since there are limited devices that are dedicated to the QA of rotational delivery. In this present study, we have evaluated the consistency and reproducibility of one prostate and one lung VMAT plans for 31 consecutive days using three different approaches: 1) MLC DynaLog files, 2) in vivo measurements using the multiwire ionization chamber DAVID, and 3) using PTWseven29 2D ARRAY with the OCTAVIUS phantom at our Varian Clinac linear accelerator. Overall, the three methods of testing the reproducibility and consistency of the VMAT delivery were in agreement with each other. All methods showed minimal daily deviations that contributed to clinically insignificant dose variations from day to day. Based on our results, we conclude that the VMAT delivery using a Varian 2100CD linear accelerator equipped with 120 MLC is highly reproducible. PACS numbers: 87.55.Qr and 87.56.Fc

Mode of Delivery in Previable Births.

PubMed

Rossi, Robert M; DeFranco, Emily A

2018-06-08

 Preterm birth before 23 weeks of gestation typically results in neonatal death (5% survival). Society for Maternal-Fetal Medicine and American College of Obstetricians and Gynecologists published consensus guidelines recommending cesarean delivery (CD) not be performed for fetal indications between 20 and 22 6/7 weeks given the lack of proven benefit. We sought to quantify the previable CD rate and identify characteristics associated with previable CD.  We performed a population-based retrospective cohort study of all live births in Ohio (2006-2015). Frequency of previable CD was stratified by week of gestation, defined as delivery between 16 and < 23 weeks of gestation. Maternal, obstetric, and neonatal characteristics were compared between women who underwent vaginal delivery versus CD. Multivariable logistic regression estimated the relative influence of maternal and fetal factors on the outcome of CD among previable live births.  Of 1,463,506 live births in Ohio during the 10-year study period, 2,865 births (0.2%) occurred during the previable period of 16 to 22 weeks. Nearly 1 in 10 live births at less than 23 weeks was delivered by cesarean ( n  = 273/2,865), CD rate 9.5% (95% confidence interval, 8.5-10.7). At 16 to 22 weeks of gestation, the CD rates were 0, 5.5, 7.6, 3.5, 5.4, 10.1, and 15.1%, respectively. Factors associated with CD included increasing parity, increasing birth weight, maternal corticosteroid administration, and fetal malpresentation. Previable neonates born by CD were more likely to be admitted to the NICU, receive ventilator support, and more likely to be living at the time of birth certificate filing.  Nearly 1 out of 10 births during the previable period was delivered via cesarean. Factors associated with previable CD suggest intent for neonatal interventions, such as NICU admission and supportive therapies. Our findings support that education and adherence with guidelines for care of previable births are a potential area of focus for perinatal quality improvement efforts. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Inflammation Causes Resistance to Anti-CD20-Mediated B Cell Depletion.

PubMed

Laws, L H; Parker, C E; Cherala, G; Koguchi, Y; Waisman, A; Slifka, M K; Oberbarnscheidt, M H; Obhrai, J S; Yeung, M Y; Riella, L V

2016-11-01

B cells play a central role in antibody-mediated rejection and certain autoimmune diseases. However, B cell-targeted therapy such as anti-CD20 B cell-depleting antibody (aCD20) has yielded mixed results in improving outcomes. In this study, we investigated whether an accelerated B cell reconstitution leading to aCD20 depletion resistance could account for these discrepancies. Using a transplantation model, we found that antigen-independent inflammation, likely through toll-like receptor (TLR) signaling, was sufficient to mitigate B cell depletion. Secondary lymphoid organs had a quicker recovery of B cells when compared to peripheral blood. Inflammation altered the pharmacokinetics (PK) and pharmacodynamics (PD) of aCD20 therapy by shortening drug half-life and accelerating the reconstitution of the peripheral B cell pool by bone marrow-derived B cell precursors. IVIG (intravenous immunoglobulin) coadministration also shortened aCD20 drug half-life and led to accelerated B cell recovery. Repeated aCD20 dosing restored B cell depletion and delayed allograft rejection, especially B cell-dependent, antibody-independent allograft rejection. These data demonstrate the importance of further clinical studies of the PK/PD of monoclonal antibody treatment in inflammatory conditions. The data also highlight the disconnect between B cell depletion on peripheral blood compared to secondary lymphoid organs, the deleterious effect of IVIG when given with aCD20 and the relevance of redosing of aCD20 for effective B cell depletion in alloimmunity. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Factors associated with antiretroviral treatment initiation amongst HIV-positive individuals linked to care within a universal test and treat programme: early findings of the ANRS 12249 TasP trial in rural South Africa

PubMed Central

Boyer, Sylvie; Iwuji, Collins; Gosset, Andréa; Protopopescu, Camelia; Okesola, Nonhlanhla; Plazy, Mélanie; Spire, Bruno; Orne-Gliemann, Joanna; McGrath, Nuala; Pillay, Deenan; Dabis, François; Larmarange, Joseph

2016-01-01

Prompt uptake of antiretroviral treatment (ART) is essential to ensure the success of universal test and treat (UTT) strategies to prevent HIV transmission in high-prevalence settings. We describe ART initiation rates and associated factors within an ongoing UTT cluster-randomized trial in rural South Africa. HIV-positive individuals were offered immediate ART in the intervention arm vs. national guidelines recommended initiation (CD4≤350 cells/mm3) in the control arm. We used data collected up to July 2015 among the ART-eligible individuals linked to TasP clinics before January 2015. ART initiation rates at one (M1), three (M3) and six months (M6) from baseline visit were described by cluster and CD4 count strata (cells/mm3) and other eligibility criteria: ≤100; 100–200; 200–350; CD4>350 with WHO stage 3/4 or pregnancy; CD4>350 without WHO stage 3/4 or pregnancy. A Cox model accounting for covariate effect changes over time was used to assess factors associated with ART initiation. The 514 participants had a median [interquartile range] follow-up duration of 1.08 [0.69; 2.07] months until ART initiation or last visit. ART initiation rates at M1 varied substantially (36.9% in the group CD4>350 without WHO stage 3/4 or pregnancy, and 55.2–71.8% in the three groups with CD4≤350) but less at M6 (from 85.3% in the first group to 96.1–98.3% in the three other groups). Factors associated with lower ART initiation at M1 were a higher CD4 count and attending clinics with both high patient load and higher cluster HIV prevalence. After M1, having a regular partner was the only factor associated with higher likelihood of ART initiation. These findings suggest good ART uptake within a UTT setting, even among individuals with high CD4 count. However, inadequate staffing and healthcare professional practices could result in prioritizing ART initiation in patients with the lowest CD4 counts. PMID:27421051

Evidence for naive T-cell repopulation despite thymus irradiation after autologous transplantation in adults with multiple myeloma: role of ex vivo CD34+ selection and age.

PubMed

Malphettes, Marion; Carcelain, Guislaine; Saint-Mezard, Pierre; Leblond, Véronique; Altes, Hester Korthals; Marolleau, Jean-Pierre; Debré, Patrice; Brouet, Jean-Claude; Fermand, Jean-Paul; Autran, Brigitte

2003-03-01

Immunodeficiency following autologous CD34+-purified peripheral blood stem cell (PBSC) transplantation could be related to T-cell depletion of the graft or impaired T-cell reconstitution due to thymus irradiation. Aiming to assess the role of irradiated thymus in T-cell repopulation, we studied 32 adults with multiple myeloma, randomly assigned to receive high-dose therapy including total body irradiation (TBI) followed by autologous transplantation with either unselected or CD34+-selected PBSCs. The median number of reinfused CD3+ cells was lower in the selected group (0.03 versus 14 x 10(6)/kg; P =.002). Lymphocyte subset counts were evaluated from month 3 to 24 after grafting. Naive CD4+ T cells were characterized both by phenotype and by quantification of T-cell receptor rearrangement excision circles (TRECs). The reconstitution of CD3+ and CD4+ T cells was significantly delayed in the CD34+-selected group, but eventually led to counts similar to those found in the unselected group after month 12. Mechanism of reconstitution differed, however, between both groups. Indeed, a marked increase in the naive CD62L+CD45RA+CD4+ subset was observed in the selected group, but not in the unselected group in which half of the CD45RA+CD4+ T cells appear to be CD62L-. Age was identified as an independent adverse factor for CD4+ and CD62L+CD45RA+CD4+ T-cell reconstitution. Our results provide evidence that infusing PBSCs depleted of T cells after TBI in adults delays T-cell reconstitution but accelerates thymic regeneration.

Accumulation of heavy metal in scalp hair of people exposed in Beijing sewage discharge channel sewage irrigation area in Tianjin, China.

PubMed

Wang, Zuwei; Yu, Xiaoman; Geng, Mingshuo; Wang, Zilu; Wang, Qianqian; Zeng, Xiangfeng

2017-05-01

Heavy metal concentrations in soil, wheat, and scalp hair exposed to Beijing sewage discharge channel sewage irrigation area (BSIA) in Tianjin were studied to evaluate the influence of sewage irrigation. Results showed that the continuous application of wastewater has led to an accumulation of heavy metals in the soil, with 55.2 and 8.62% of soil samples accumulating Cd and Zn, respectively, at concentrations exceeding the permissible limits in China. Concentrations of heavy metals in wheat grain from BSIA were higher than these from the clean water irrigation area by 63.2% for Cd, 3.8% for Cu, 100% for Pb, 6.6% for Zn, and 326.7% for Cr. The heavy metal bioaccumulation factor (BAF) of wheat/soil in BSIA showed the following order: Zn > Cd > Cu > Pb > Cr. Interestingly, these accumulation of heavy metals in soil after sewage irrigation could increase the migration ability of heavy metals (particularly Zn and Cd) from soil to wheat. Mean concentrations of heavy metals in the hair of residents followed the decreasing trend of Zn > Cu > Pb > Cr > Cd, which were higher than the control area by 110.0% for Cd, 20.0% for Cu, 55.9% for Zn, 36.6% for Pb, and 64.6% for Cr. Concentrations of heavy metals in male human hair in BSIA were higher than those of females. And the concentrations of heavy metals except for Pb in human hair increased with their increasing ages. The heavy metal BAF values of wheat/soil in BSIA showed the trend of Zn (98.0057) > Pb (7.0162) > Cr (5.5788) > Cu (5.4853) > Cd (3.5584); heavy metals had obvious biological amplification from wheat to human hair. These results indicated that local population health was potentially exposed to the heavy metal risk via wheat consumption.

Bulk Nuclear Hyperpolarization of Inorganic Solids by Relay from the Surface.

PubMed

Björgvinsdóttir, Snædís; Walder, Brennan J; Pinon, Arthur C; Emsley, Lyndon

2018-06-14

NMR is a method of choice to determine structural and electronic features in inorganic materials, and has been widely used in the past, but its application is severely limited by its low relative sensitivity. We show how the bulk of proton-free inorganic solids can be hyperpolarized with a general strategy using impregnation dynamic nuclear polarization through homonuclear spin diffusion between low-γ nuclei. This is achieved either through direct hyperpolarization or with a pulse cooling cross-polarization method, transferring hyperpolarization from protons to heteronuclei at particle surfaces. We demonstrate a factor of 50 gain in overall sensitivity for the 119 Sn spectrum of powdered SnO 2 , corresponding to an acceleration of a factor >2500 in acquisition times. The method is also shown for 31 P spectra of GaP, 113 Cd spectra of CdTe, and 29 Si spectra of α-quartz.

Predictive and prognostic effect of CD133 and cancer-testis antigens in stage Ib-IIIA non-small cell lung cancer.

PubMed

Su, Chunxia; Xu, Ying; Li, Xuefei; Ren, Shengxiang; Zhao, Chao; Hou, Likun; Ye, Zhiwei; Zhou, Caicun

2015-01-01

CD133 and cancer-testis antigens (CTAs) may be potential predicted markers of adjuvant chemotherapy or immune therapy, and they may be the independent prognostic factor of NSCLC. Nowadays, there is still no predictive biomarker identified for the use of adjuvant chemotherapy in non-small cell lung cancer (NSCLC) patients. To clarify the role of CD133 and CTAs as a predictive marker for adjuvant chemotherapy or prognostic factors of overall survival, we performed a retrospective study in 159 stage Ib-IIIA NSCLC patients receiving adjuvant chemotherapy or observe from April 2003 to March 2004 in our institute. Clinical data and gene anaylisis results were collected, while CD133 and three CTAs (MAGE-A4, NY-ESO-1, MAGE-A10) were determined according to their monoclonal antibodies such as CD133, 57B, D8.38 and 3GA11 by immunohistochemistry. All CTAs were more frequently expressed in squamous cell carcinoma (SCC) (50.0%, 26.9%, 34.6%) than in adenocarcinoma (16.2%, 16.2%, 16.2%). CD133 was more frequently found in patients with adenocarcinoma (P=0.044). Negative expression of CD133 was associated with a significantly longer overall survival compared to positive expression of CD133 (62.5 vs. 48.5 months, P=0.035). When combined with MAGEA4, NY-ESO-1or MAGE-A10, patients' OS showed significantly difference among different combination. (CD133-MAGEA4-/CD133-MAGEA4+/CD133+MAGEA4-/CD133+MAGEA4+: 65.6 months vs.51.5 months vs.32.2 months vs.19.8 months, P=0.000, CD133-NY-ESO-1-/ CD133+NY-ESO-1-/CD133-NY-ESO-1+/ CD133+NY-ESO-1+: 57.8 months vs. 55.7 months vs. 44.6 months vs. 28.5 months, P=0.000, CD133-MAGEA10-/CD133+ MAGEA10-/CD133-MAGEA10-/CD133+MAGEA10+: 66.2 months vs. 57.2 months vs. 48.8 months vs. 41.4 months, P=0.001). There is no difference between patients received adjuvant chemotherapy or not, but subgroup analysis showed that the patients with CD133+NY-ESO-1+ expression who received chemotherapy will survive longer than not receive adjuvant chemotherapy (received vs. not received, 52.1 vs. 27.1 months, P=0.020). In the subgroup with EGFR mutation/ALK translocation/Ros1 translocation/Ret fusion, the trend remained but without a statistically significant difference. Multivariate COX regression analysis showed that stage, CD133, CD133-MAGEA4- and CD133-NY-ESO-1- are independent prognostic factors. In conclusion, CTAs (MAGE-A4, NY-ESO-1, MAGE-A10) were more likely expressed in patients with squamous cell carcinoma and when CTAs combined with CD133, they can be better prognostic factors. Patients with CD133+NY-ESO-1+ expression may survive longer when treated with adjuvant chemotherapy, which indicates that the CD133 and CTAs might be a potential marker to guide adjuvant chemotherapy in this population.

Psychosocial and Neurohormonal Predictors of HIV Disease Progression (CD4 Cells and Viral Load): A 4 Year Prospective Study.

PubMed

Ironson, G; O'Cleirigh, C; Kumar, M; Kaplan, L; Balbin, E; Kelsch, C B; Fletcher, M A; Schneiderman, N

2015-08-01

Most studies of psychosocial predictors of disease progression in HIV have not considered norepinephrine (NE), a neurohormone related to emotion and stress, even though NE has been related to accelerated viral replication in vitro and impaired response to antiretroviral therapy (ART). We therefore examined NE, cortisol, depression, hopelessness, coping, and life event stress as predictors of HIV progression in a diverse sample. Participants (n = 177) completed psychological assessment, blood draws [CD4, viral load (VL)], and a 15 h urine sample (NE, cortisol) every 6 months over 4 years. Hierarchical linear modeling (HLM) was used to model slope in CD4 and VL controlling for ART at every time point, gender, age, race, SES, and initial disease status. NE (as well as depression, hopelessness, and avoidant coping) significantly predicted a greater rate of decrease in CD4 and increase in VL. Cortisol was not significantly related to CD4, but predicted VL increase. To our knowledge, this is the first study relating NE, in vivo, to accelerated disease progression over an extended time. It also extends our previous 2 year study by relating depressed mood and coping to accelerated disease progression over 4 years.

Warburg phenotype in renal cell carcinoma: high expression of glucose-transporter 1 (GLUT-1) correlates with low CD8(+) T-cell infiltration in the tumor.

PubMed

Singer, Katrin; Kastenberger, Michael; Gottfried, Eva; Hammerschmied, Christine G; Büttner, Maike; Aigner, Michael; Seliger, Barbara; Walter, Bernhard; Schlösser, Hans; Hartmann, Arndt; Andreesen, Reinhard; Mackensen, Andreas; Kreutz, Marina

2011-05-01

Many tumor cells are characterized by a dysregulated glucose metabolism associated with increased glycolysis in the presence of oxygen ("Warburg Effect"). Here, we analyzed for the first time a possible link between glucose metabolism and immune cell infiltration in renal cell carcinoma (RCC). RCC specimens revealed a highly significant increase in the expression of lactate dehydrogenase A (LDHA) and glucose-transporter 1 (GLUT-1) compared to the corresponding normal kidney tissue on mRNA level. Accordingly, tumor cell lines of different origin such as RCC, melanoma and hepatocellular carcinoma strongly expressed LDHA and GLUT-1 compared to their nonmalignant counterparts. In line with this finding, tumor cells secreted high amounts of lactate. High expression of GLUT-1 and LDH5, a tetramer of 4 LDHA subunits, was confirmed by tissue microarray analysis of 249 RCC specimens. Overall, 55/79 (69.6%) and 46/71 (64.7%) cases of clear cell carcinoma showed a constitutive, but heterogeneous expression of GLUT-1 and LDH5, respectively. The number of CD3(+), CD8(+) and FOXP3(+) T cells was significantly elevated in RCC lesions compared to normal kidney epithelium, but effector molecules such as granzyme B and perforin were decreased in tumor infiltrating T cells. Of interest, further analysis revealed an inverse correlation between GLUT-1 expression and the number of CD8(+) T cells in RCC lesions. Together, our data suggest that an accelerated glucose metabolism in RCC tissue is associated with a low infiltration of CD8(+) effector T cells. Targeting the glucose metabolism may represent an interesting tool to improve the efficacy of specific immunotherapeutic approaches in RCC. Copyright © 2010 UICC.

Gene expression analysis of a Helicobacter pylori-infected and high-salt diet-treated mouse gastric tumor model: identification of CD177 as a novel prognostic factor in patients with gastric cancer

PubMed Central

2013-01-01

Background Helicobacter pylori (H. pylori) infection and excessive salt intake are known as important risk factors for stomach cancer in humans. However, interactions of these two factors with gene expression profiles during gastric carcinogenesis remain unclear. In the present study, we investigated the global gene expression associated with stomach carcinogenesis and prognosis of human gastric cancer using a mouse model. Methods To find candidate genes involved in stomach carcinogenesis, we firstly constructed a carcinogen-induced mouse gastric tumor model combined with H. pylori infection and high-salt diet. C57BL/6J mice were given N-methyl-N-nitrosourea in their drinking water and sacrificed after 40 weeks. Animals of a combination group were inoculated with H. pylori and fed a high-salt diet. Gene expression profiles in glandular stomach of the mice were investigated by oligonucleotide microarray. Second, we examined an availability of the candidate gene as prognostic factor for human patients. Immunohistochemical analysis of CD177, one of the up-regulated genes, was performed in human advanced gastric cancer specimens to evaluate the association with prognosis. Results The multiplicity of gastric tumor in carcinogen-treated mice was significantly increased by combination of H. pylori infection and high-salt diet. In the microarray analysis, 35 and 31 more than two-fold up-regulated and down-regulated genes, respectively, were detected in the H. pylori-infection and high-salt diet combined group compared with the other groups. Quantitative RT-PCR confirmed significant over-expression of two candidate genes including Cd177 and Reg3g. On immunohistochemical analysis of CD177 in human advanced gastric cancer specimens, over-expression was evident in 33 (60.0%) of 55 cases, significantly correlating with a favorable prognosis (P = 0.0294). Multivariate analysis including clinicopathological factors as covariates revealed high expression of CD177 to be an independent prognostic factor for overall survival. Conclusions These results suggest that our mouse model combined with H. pylori infection and high-salt diet is useful for gene expression profiling in gastric carcinogenesis, providing evidence that CD177 is a novel prognostic factor for stomach cancer. This is the first report showing a prognostic correlation between CD177 expression and solid tumor behavior. PMID:23899160

[Effects of Rice Cultivar and Typical Soil Improvement Measures on the Uptake of Cd in Rice Grains].

PubMed

Wang, Mei-e; Peng, Chi; Chen, Wei-ping

2015-11-01

Cadmium pollution of rice is a big problem in agricultural food safety. The accident "Cd rice" occurred last year in Youxian County, Hunan Province caused serious social panic. In this study, trials on "Cd rice" controlling techniques specific to the Cd pollution in paddy soil in Youxian were investigated. It was suggested that the average Cd contents in rice grains of the rice variety "Zhu Liang You 06" in Datongqiao and Wangling were 0.167 and 0.127 mg x kg(-1), respectively, which were only equal to 20% of the contents of other varieties. The trials for stabilizing agents revealed that treatments of lime and mineral fertilizer decreased Cd contents in rice grains to 20-30% of the control. Plastic film-mulched treatment decreased the rice grain Cd to 50%. And combined treatment of plastic film-mulched and biochar and silicon foliar-fertilizer decreased 80% of rice Cd content. Single treatments of silicon foliar-fertilizer and combined treatment of silicon foliar-fertilizer and topdressing fertilizer decreased more than 90% of Cd content. Results of BCR revealed that the percentage of cationic exchangeable and/or carbonate associated Cd fraction was more than 55% for most of the soil samples. Lime treatment significantly decreased the percentage of cationic exchangeable and/or carbonate and oxides of Fe and Mn associated Cd and increased the crystalline structure of clay minerals associated Cd. The change rate reached about 20%. Our results suggested concentration of soil Cd and pH were the two significant factors impacting the uptake of Cd by rice grains.

Nationwide prevalence and drug treatment practices of inflammatory bowel diseases in Hungary: A population-based study based on the National Health Insurance Fund database.

PubMed

Kurti, Zsuzsanna; Vegh, Zsuzsanna; Golovics, Petra A; Fadgyas-Freyler, Petra; Gecse, Krisztina B; Gonczi, Lorant; Gimesi-Orszagh, Judit; Lovasz, Barbara D; Lakatos, Peter L

2016-11-01

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases associated with a substantial healthcare utilization. Our aim was to estimate the national prevalence of inflammatory bowel disease (IBD), CD and UC and to describe current drug treatment practices in CD and UC. Patients and drug dispensing events were identified according to international classification codes for UC and CD in in-patient care, non-primary out-patient care and drug prescription databases (2011-2013) of the National Health Insurance Fund. A total of 55,039 individuals (men: 44.6%) with physician-diagnosed IBD were alive in Hungary in 2013, corresponding to a prevalence of 0.55% (95% CI, 0.55-0.56). The prevalence of CD 0.20% (95% CI, 0.19-0.20), and UC was 0.34% (95% CI, 0.33-0.34). The prevalence both in men and women was the highest in the 20-39 year-olds in CD. Current use of immunosuppressives and biological therapy was highest in the pediatric CD population (44% and 15%) followed by adult CD (33% and 9%), while their use was lowest in elderly patients. Interestingly, current use of 5-ASA (5-aminosalicylates) was high in both UC and CD irrespective of the age group. The Hungarian IBD prevalence based on nationwide database of the National Health Insurance Fund was high. We identified significant differences in the drug prescription practices according to age-groups. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Influence of tea saponin on enhancing accessibility of pyrene and cadmium phytoremediated with Lolium multiflorum in co-contaminated soils.

PubMed

Wang, Qian; Liu, Xiaoyan; Zhang, Xinying; Hou, Yunyun; Hu, Xiaoxin; Liang, Xia; Chen, Xueping

2016-03-01

Tea saponin (TS), a kind of biodegradable surfactant, was chosen to improve the accessible solubilization of pyrene and cadmium (Cd) in co-contaminated soils cultivated Lolium multiflorum. TS obviously improved the accessibility of pyrene and Cd for L. multiflorum to accelerate the process of accumulation and elimination of the pollutants. The chemical forms of Cd was transformed from Fe-Mn oxides and associated to carbonates fractions into exchangeable fractions by adding TS in single Cd and pyrene-Cd contaminated soils. Moreover, the chemical forms of pyrene were transformed from associated fraction into bioaccessible fraction by adding TS in pyrene and pyrene-Cd contaminated soils. In pyrene-Cd contaminated soil, the exchangeable fraction of Cd was hindered in the existence of pyrene, and bioaccessible fraction of pyrene was promoted by the cadmium. Besides, in the process of the pyrene degradation and Cd accumulation, the effect could be improved by the elongation of roots with adding TS, and the microorganism activity was stimulated by TS to accelerate the removal of pollutions. Therefore, Planting L. multiflorum combined with adding TS would be an effective method on the phytoremediation of organics and heavy metals co-contaminated soils.

Activating β-catenin signaling in CD133-positive dermal papilla cells increases hair inductivity

PubMed Central

Zhou, Linli; Yang, Kun; Xu, Mingang; Andl, Thomas; Millar, Sarah; Boyce, Steven; Zhang, Yuhang

2016-01-01

Bioengineering hair follicles using cells isolated from human tissue remains as a difficult task. Dermal papilla (DP) cells are known to guide the growth and cycling activities of hair follicles by interacting with keratinocytes. However, DP cells quickly lose their inductivity during in vitro passaging. Rodent DP cell cultures need external addition of chemical factors, including WNT and BMP molecules, to maintain the hair inductive property. CD133 is expressed by a small subpopulation of DP cells that are capable of inducing hair follicle formation in vivo. We report here that expression of a stabilized form of β-catenin promoted clonal growth of CD133-positive (CD133+) DP cells in in vitro three-dimensional hydrogel culture while maintaining expression of DP markers, including alkaline phosphatase (AP), CD133, and Integrin α8. After a two-week in vitro culture, cultured CD133+ DP cells with up-regulated β-catenin activity led to an accelerated in vivo hair growth in reconstituted skin than control cells. Further analysis showed that matrix cell proliferation and differentiation were significantly promoted in hair follicles when β-catenin signaling was upregulated in CD133+ DP cells. Our data highlight an important role for β-catenin signaling in promoting the inductive capability of CD133+ DP cells for in vitro expansion and in vivo hair follicle regeneration, which could potentially be applied to cultured human DP cells. PMID:27312243

Filgrastim (RHG-CSF) related modulation of the inflammatory response in patients at risk of sepsis or with sepsis.

PubMed

Weiss, M; Gross-Weege, W; Harms, B; Schneider, E M

1996-03-01

Over a period of 14 days a longitudinal analysis was performed on the effects of filgrastim (recombinant human granulocyte colony stimulating factor, rhG-CSF) administered to 20 postoperative/posttraumatic patients at risk of or with sepsis. The following parameters were determined: leukocyte counts, serum cytokine levels and the surface expression of functional antigens and adhesion molecules. Filgrastim (1 mu g/kg.day) was infused continuously on the first 3 days and tapered to 0.5 mu g/kg.day on the following 4 days or until discharge from the surgical intensive care unit. During infusion of filgrastim, G-CSF levels increased in 16 out of the 20 patients within 48 h. In these 16 patients, leukocyte counts increased in 15 out of 16 patients. Expression of CD64 was upregulated within 24 h. The expression of CD32 was upregulated in 8 out of 9 patients with an initial expression < 55%. LAM-1 expression was downregulated in all patients revealing an initial expression of LAM-1 > 40%. Soluble ICAM increased in 9 out of 11 patients. IL-8 decreased in all 6 patients presenting initial values of IL-8 > 90 pg/ml. IL-1RA increased in 10 patients. Filgrastim had no effect on the expression of CD14, CD16 and CD34 and on the levels of TNF-alpha and sTNF-R type I (p55). In conclusion, infusion of filgrastim in postoperative/post traumatic patients at risk of and with sepsis resulted in improved generation and function of neutrophils and appeared to counterregulate hyperactivation of proinflammatory processes.

Effects of umbilical cord blood stem cells on healing factors for diabetic foot injuries.

PubMed

Çil, N; Oğuz, E O; Mete, E; Çetinkaya, A; Mete, G A

2017-01-01

The use of stem or progenitor cells from bone marrow, or peripheral or umbilical cord blood is becoming more common for treatment of diabetic foot problems. These cells promote neovascularization by angiogenic factors and they promote epithelium formation by stimulating cell replication and migration under certain pathological conditions. We investigated the role of CD34 + stem cells from human umbilical cord blood in wound healing using a rat model. Rats were randomly divided into a control group and two groups with diabetes induced by a single dose of 55 mg/kg intraperitoneal streptozocin. Scarred areas 5 mm in diameter were created on the feet of all rats. The diabetic rats constituted the diabetes control group and a diabetes + stem cell group with local injection into the wound site of 0.5 × 106 CD34 + stem cells from human umbilical cord blood. The newly formed skin in the foot wounds following CD34 + stem cell treatment showed significantly improvement by immunohistochemistry and TUNEL staining, and were closer to the wound healing of the control group than the untreated diabetic animals. The increase in FGF expression that accompanied the local injection of CD34 + stem cells indicates that FGF stimulation helped prevent apoptosis. Our findings suggest a promising new treatment approach to diabetic wound healing.

CD151, a novel host factor of nuclear export signaling in influenza virus infection.

PubMed

Qiao, Yongkang; Yan, Yan; Tan, Kai Sen; Tan, Sheryl S L; Seet, Ju Ee; Arumugam, Thiruma Valavan; Chow, Vincent T K; Wang, De Yun; Tran, Thai

2018-05-01

Despite advances in our understanding of the mechanisms of influenza A virus (IAV) infection, the crucial virus-host interactions during the viral replication cycle still remain incomplete. Tetraspanin CD151 is highly expressed in the human respiratory tract, but its pathological role in IAV infection is unknown. We sought to characterize the functional role and mechanisms of action of CD151 in IAV infection of the upper and lower respiratory tracts with H1N1 and H3N2 strains. We used CD151-null mice in an in vivo model of IAV infection and clinical donor samples of in vitro-differentiated human nasal epithelial cells cultured at air-liquid interface. As compared with wild-type infected mice, CD151-null infected mice exhibited a significant reduction in virus titer and improvement in survival that is associated with pronounced host antiviral response and inflammasome activation together with accelerated lung repair. Interestingly, we show that CD151 complexes newly synthesized viral proteins with host nuclear export proteins and stabilizes microtubule complexes, which are key processes necessary for the polarized trafficking of viral progeny to the host plasma membrane for assembly. Our results provide new mechanistic insights into our understanding of IAV infection. We show that CD151 is a critical novel host factor of nuclear export signaling whereby the IAV nuclear export uses it to complement its own nuclear export proteins (a site not targeted by current therapy), making this regulation unique, and holds promise for the development of novel alternative/complementary strategies to reduce IAV severity. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Targeting BRCAness in Gastric Cancer

DTIC Science & Technology

2017-10-01

modified CRISPR system using dCas9-KRAB expressing variants of these cells, and validated them for CRISPRi screening. These reagents will next be... CRISPR activity following transduction with sgRNAs targeting CD55 and FACS staining with the anti-CD55 antibody. Data shown for MKN7 and KATOIII...Oversight, project planning and reporting Patrick O’Leary Postdoctoral Fellow UCSF PH.D. Design, execution, and interpretation of CRISPR experiments

Targeting BRCAness in Gastric Cancer

DTIC Science & Technology

2017-10-01

a modified CRISPR system using dCas9-KRAB expressing variants of these cells, and validated them for CRISPRi screening. These reagents will next be... CRISPR activity following transduction with sgRNAs targeting CD55 and FACS staining with the anti-CD55 antibody. Data shown for MKN7 and KATOIII...Oversight, project planning and reporting Patrick O’Leary Postdoctoral Fellow UCSF PH.D. Design, execution, and interpretation of CRISPR

Spontaneous abortion is associated with elevated systemic C5a and reduced mRNA of complement inhibitory proteins in placenta.

PubMed

Banadakoppa, M; Chauhan, M S; Havemann, D; Balakrishnan, M; Dominic, J S; Yallampalli, C

2014-09-01

Spontaneous abortion in early pregnancy due to unknown reasons is a common problem. The excess complement activation and consequent placental inflammation and anti-angiogenic milieu is emerging as an important associated factor in many pregnancy-related complications. In the present study we sought to examine the expression of complement inhibitory proteins at the feto-maternal interface and levels of complement split products in the circulation to understand their role in spontaneous abortion. Consenting pregnant women who either underwent elective abortion due to non-clinical reasons (n = 13) or suffered miscarriage (n = 14) were recruited for the study. Systemic levels of complement factors C3a and C5a were measured by enzyme-linked immunosorbent assay (ELISA). Plasma C5 and C3 protein levels were examined by Western blot. Expressions of complement regulatory proteins such as CD46 and CD55 in the decidua were investigated by quantitative polymerase chain reaction (PCR) and Western blot. The median of plasma C3a level was 82·83 ng/ml and 66·17 ng/ml in elective and spontaneous abortion patients, respectively. Medians of plasma C5a levels in elective and spontaneous abortion patients were 0·96 ng/ml and 1·14 ng/ml, respectively. Only plasma C5a levels but not C3a levels showed significant elevation in spontaneous abortion patients compared to elective abortion patients. Further, there was a threefold decrease in the mRNA expressions of complement inhibitory proteins CD46 and CD55 in the decidua obtained from spontaneous abortion patients compared to that of elective abortion patients. These data suggested that dysregulated complement cascade may be associated with spontaneous abortion. © 2014 British Society for Immunology.

Dopamine Increases CD14+CD16+ Monocyte Transmigration across the Blood Brain Barrier: Implications for Substance Abuse and HIV Neuropathogenesis.

PubMed

Calderon, Tina M; Williams, Dionna W; Lopez, Lillie; Eugenin, Eliseo A; Cheney, Laura; Gaskill, Peter J; Veenstra, Mike; Anastos, Kathryn; Morgello, Susan; Berman, Joan W

2017-06-01

In human immunodeficiency virus-1 (HIV) infected individuals, substance abuse may accelerate the development and/or increase the severity of HIV associated neurocognitive disorders (HAND). It is proposed that CD14 + CD16 + monocytes mediate HIV entry into the central nervous system (CNS) and that uninfected and infected CD14 + CD16 + monocyte transmigration across the blood brain barrier (BBB) contributes to the establishment and propagation of CNS HIV viral reservoirs and chronic neuroinflammation, important factors in the development of HAND. The effects of substance abuse on the frequency of CD14 + CD16 + monocytes in the peripheral circulation and on the entry of these cells into the CNS during HIV neuropathogenesis are not known. PBMC from HIV infected individuals were analyzed by flow cytometry and we demonstrate that the frequency of peripheral blood CD14 + CD16 + monocytes in HIV infected substance abusers is increased when compared to those without active substance use. Since drug use elevates extracellular dopamine concentrations in the CNS, we examined the effects of dopamine on CD14 + CD16 + monocyte transmigration across our in vitro model of the human BBB. The transmigration of this monocyte subpopulation is increased by dopamine and the dopamine receptor agonist, SKF 38393, implicating D1-like dopamine receptors in the increase in transmigration elicited by this neurotransmitter. Thus, elevated extracellular CNS dopamine may be a novel common mechanism by which active substance use increases uninfected and HIV infected CD14 + CD16 + monocyte transmigration across the BBB. The influx of these cells into the CNS may increase viral seeding and neuroinflammation, contributing to the development of HIV associated neurocognitive impairments.

Detection of paroxysmal nocturnal hemoglobinuria clones in patients with myelodysplastic syndromes and related bone marrow diseases, with emphasis on diagnostic pitfalls and caveats

PubMed Central

Wang, Sa A.; Pozdnyakova, Olga; Jorgensen, Jeffrey L.; Medeiros, L. Jeffrey; Stachurski, Dariusz; Anderson, Mary; Raza, Azra; Woda, Bruce A.

2009-01-01

Background The presence of paroxysmal nocturnal hemoglobinuria clones in the setting of aplastic anemia or myelodysplastic syndrome has been shown to have prognostic and therapeutic implications. However, the status of paroxysmal nocturnal hemoglobinuria clones in various categories of myelodysplastic syndrome and in other bone marrow disorders is not well-studied. Design and Methods By using multiparameter flow cytometry immunophenotypic analysis with antibodies specific for four glycosylphosphatidylinositol-anchored proteins (CD55, CD59, CD16, CD66b) and performing an aerolysin lysis confirmatory test in representative cases, we assessed the paroxysmal nocturnal hemoglobinuria-phenotype granulocytes in 110 patients with myelodysplastic syndrome, 15 with myelodysplastic/myeloproliferative disease, 5 with idiopathic myelofibrosis and 6 with acute myeloid leukemia. Results Paroxysmal nocturnal hemoglobinuria-phenotype granulocytes were detected in nine patients with low grade myelodysplastic syndrome who showed clinicopathological features of bone marrow failure, similar to aplastic anemia. All paroxysmal nocturnal hemoglobinuria-positive cases demonstrated loss of the four glycosylphosphatidylinositol-anchored proteins, with CD16−CD66b− clones being larger than those of CD55−CD59− (p<0.05). Altered glycosylphosphatidylinositol-anchored protein expression secondary to granulocytic hypogranulation, immaturity, and/or immunophenotypic abnormalities was present in a substantial number of cases and diagnostically challenging. Conclusions These results show that routine screening for paroxysmal nocturnal hemoglobinuria clones in patients with an intrinsic bone marrow disease who show no clinical evidence of hemolysis has an appreciable yield in patients with low grade myelodysplastic syndromes. The recognition of diagnostic caveats and pitfalls associated with the underlying intrinsic bone marrow disease is essential in interpreting paroxysmal nocturnal hemoglobinuria testing correctly. In our experience, the CD16/CD66b antibody combination is superior to CD55/CD59 in screening for subclinical paroxysmal nocturnal hemoglobinuria because it detects a large clone size and is less subject to analytical interference. PMID:19001281

Detection of paroxysmal nocturnal hemoglobinuria clones in patients with myelodysplastic syndromes and related bone marrow diseases, with emphasis on diagnostic pitfalls and caveats.

PubMed

Wang, Sa A; Pozdnyakova, Olga; Jorgensen, Jeffrey L; Medeiros, L Jeffrey; Stachurski, Dariusz; Anderson, Mary; Raza, Azra; Woda, Bruce A

2009-01-01

The presence of paroxysmal nocturnal hemoglobinuria clones in the setting of aplastic anemia or myelodysplastic syndrome has been shown to have prognostic and therapeutic implications. However, the status of paroxysmal nocturnal hemoglobinuria clones in various categories of myelodysplastic syndrome and in other bone marrow disorders is not well-studied. By using multiparameter flow cytometry immunophenotypic analysis with antibodies specific for four glycosylphosphatidylinositol-anchored proteins (CD55, CD59, CD16, CD66b) and performing an aerolysin lysis confirmatory test in representative cases, we assessed the paroxysmal nocturnal hemoglobinuria-phenotype granulocytes in 110 patients with myelodysplastic syndrome, 15 with myelodysplastic/myeloproliferative disease, 5 with idiopathic myelofibrosis and 6 with acute myeloid leukemia. Paroxysmal nocturnal hemoglobinuria-phenotype granulocytes were detected in nine patients with low grade myelodysplastic syndrome who showed clinicopathological features of bone marrow failure, similar to aplastic anemia. All paroxysmal nocturnal hemoglobinuria-positive cases demonstrated loss of the four glycosylphosphatidylinositol-anchored proteins, with CD16(-)CD66b(-) clones being larger than those of CD55(-)CD59(-) (p<0.05). Altered glycosylphosphatidylinositol-anchored protein expression secondary to granulocytic hypogranulation, immaturity, and/or immunophenotypic abnormalities was present in a substantial number of cases and diagnostically challenging. These results show that routine screening for paroxysmal nocturnal hemoglobinuria clones in patients with an intrinsic bone marrow disease who show no clinical evidence of hemolysis has an appreciable yield in patients with low grade myelodysplastic syndromes. The recognition of diagnostic caveats and pitfalls associated with the underlying intrinsic bone marrow disease is essential in interpreting paroxysmal nocturnal hemoglobinuria testing correctly. In our experience, the CD16/CD66b antibody combination is superior to CD55/CD59 in screening for subclinical paroxysmal nocturnal hemoglobinuria because it detects a large clone size and is less subject to analytical interference.

Immobilization remediation of Cd-polluted soil with different water condition.

PubMed

Li, Jianrui; Xu, Yingming

2017-05-15

To demonstrate effects of water management on soil Cd immobilization using palygorskite, the investigation evaluated impacts of palygorskite on uptake of Cd present in soils with different water condition by rice plant. Pot experiment results showed that, pH, available Fe and P in untreated soils were higher in continuous flooding than in traditional irrigation and wetting irrigation, which were reasons for lower soil exchangeable Cd and plant Cd in continuous flooding. In control group (untreated soils), compared to traditional irrigation, continuous flooding reduced brown rice Cd by 37.9%, that in wetting irrigation increased by 31.0%. At palygorskite concentrations of 5 g kg -1 , 10 g kg -1 and 15 g kg -1 , brown rice Cd reduced by 16.7%, 44.4% and 55.6% under continuous flooding, 13.8%, 34.5% and 44.8% under traditional irrigation, 13.1%, 36.8% and 47.3% under wetting irrigation (p < 0.05). At the same palygorskite addition, decreasing amplitude of brown rice Cd was higher in continuous flooding than in traditional irrigation and wetting irrigation. Competition for adsorption sites in root coating between Cd 2+ and Fe 2+ was another factor governing plant Cd. In control group, compared to traditional irrigation, root coating Fe(II) increased by 124.5% and root coating Cd reduced by 17.6% upon continuous flooding (p < 0.05). In conclusion, palygorskite addition combined with continuous flooding was an efficacious technique to stabilize Cd in paddy soils. Copyright © 2017 Elsevier Ltd. All rights reserved.

A new method to determine wound age in early vital skin injuries: a probability scoring system using expression levels of Fibronectin, CD62p and Factor VIII in wound hemorrhage.

PubMed

van de Goot, Franklin R W; Korkmaz, H Ibrahim; Fronczek, Judith; Witte, Birgit I; Visser, Rob; Ulrich, Magda M W; Begieneman, Mark P V; Rozendaal, Lawrence; Krijnen, Paul A J; Niessen, Hans W M

2014-11-01

In forensic autopsies it is important to determine the age of early vital skin wounds as accurate as possible. In addition to inflammation, coagulation is also induced in vital wounds. Analysis of blood coagulation markers in wound hemorrhage could therefore be an important additional discriminating factor in wound age determination. The aim of this study was to develop a wound age probability scoring system, based on the immunohistochemical expression levels of Fibronectin, CD62p and Factor VIII in wound hemorrhage. Tissue samples of (A) non injured control skin (n=383), and samples of mechanically induced skin injuries of known wound age, (B) injuries inflicted shortly before death (up to a few minutes old) (n=382), and (C) injuries inflicted 15-30 min before death (n=42) were obtained at autopsy in order to validate wound age estimation. Tissue slides were stained for Fibronectin, CD62p and Factor VIII and were subsequently scored for staining intensity (IHC score) in wound hemorrhage (1=minor, 2=moderate, 3=strong positive). Finally, probability scores of these markers were calculated. In at most 14% of the non-injured control samples, hemorrhage was found, with mean±standard deviation IHC scores of 0.1±0.4, 0.2±0.4 and 0.2±0.5 for Fibronectin, CD62p, and Factor VIII, respectively. Expression of these markers significantly increased to mean IHC scores 1.4±0.8 (Fibronectin), 1.2±0.6 (CD62p), and 1.6±0.8 (Factor VIII) in wounds inflicted shortly before death (few minutes old) and to 2.6±0.5 (Fibronectin), 2.5±0.6 (CD62p), and 2.8±0.4 (Factor VIII) in 15-30 min old wounds. The probabilities that a wound was non vital in case of an IH score 0 were 87%, 88% and 90% for Fibronectin, CD62p, and Factor VIII, respectively. In case of an IHC score 1 or 2, the probabilities that a wound was a few minutes old were 82/90%, 82/83% and 72/93%. Finally, in case of an IHC score 3, the probabilities that a wound was 15-30 min old were 65%, 76% and 55%. Based on the expression of Fibronectin, CD62p and Factor VIII in wound hemorrhage, we developed a probability scoring system that can be used in forensic autopsies to improve wound age estimation in early skin injuries. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Activation of TGF-β1-CD147 positive feedback loop in hepatic stellate cells promotes liver fibrosis.

PubMed

Li, Hai-Yan; Ju, Di; Zhang, Da-Wei; Li, Hao; Kong, Ling-Min; Guo, Yanhai; Li, Can; Wang, Xi-Long; Chen, Zhi-Nan; Bian, Huijie

2015-11-12

Activation of hepatic stellate cells (HSCs) by transforming growth factor-β1 (TGF-β1) initiates HBV-associated fibrogenesis. The mechanism of TGF-β1 modulating HSC activation is not fully uncovered. We hypothesized a positive feedback signaling loop of TGF-β1-CD147 promoting liver fibrogenesis by activation of HSCs. Human HSC cell line LX-2 and spontaneous liver fibrosis model derived from HBV transgenic mice were used to evaluate the activation of molecules in the signaling loop. Wound healing and cell contraction assay were performed to detect the CD147-overexpressed HSC migration and contraction. The transcriptional regulation of CD147 by TGF-β1/Smad4 was determined using dual-luciferase reporter assay and chromatin immunoprecipitation. We found that a positive reciprocal regulation between TGF-β1 and CD147 mediated HSC activation. CD147 over-expression promoted HSC migration and accelerated TGF-β1-induced cell contraction. Phosphorylation of Smad2 and Smad3 in cooperation with Smad4 mediated the TGF-β1-regulated CD147 expression. Smad4 activated the transcription by direct interaction with CD147 promoter. Meanwhile, CD147 modulated the activated phenotype of HSCs through the ERK1/2 and Sp1 which up-regulated α-SMA, collagen I, and TGF-β1 synthesis. These findings indicate that TGF-β1-CD147 loop plays a key role in regulating the HSC activation and combination of TGF-β receptor inhibitor and anti-CD147 antibody might be promised to reverse fibrogenesis.

Activation of TGF-β1-CD147 positive feedback loop in hepatic stellate cells promotes liver fibrosis

PubMed Central

Li, Hai-Yan; Ju, Di; Zhang, Da-Wei; Li, Hao; Kong, Ling-Min; Guo, Yanhai; Li, Can; Wang, Xi-Long; Chen, Zhi-Nan; Bian, Huijie

2015-01-01

Activation of hepatic stellate cells (HSCs) by transforming growth factor-β1 (TGF-β1) initiates HBV-associated fibrogenesis. The mechanism of TGF-β1 modulating HSC activation is not fully uncovered. We hypothesized a positive feedback signaling loop of TGF-β1-CD147 promoting liver fibrogenesis by activation of HSCs. Human HSC cell line LX-2 and spontaneous liver fibrosis model derived from HBV transgenic mice were used to evaluate the activation of molecules in the signaling loop. Wound healing and cell contraction assay were performed to detect the CD147-overexpressed HSC migration and contraction. The transcriptional regulation of CD147 by TGF-β1/Smad4 was determined using dual-luciferase reporter assay and chromatin immunoprecipitation. We found that a positive reciprocal regulation between TGF-β1 and CD147 mediated HSC activation. CD147 over-expression promoted HSC migration and accelerated TGF-β1-induced cell contraction. Phosphorylation of Smad2 and Smad3 in cooperation with Smad4 mediated the TGF-β1-regulated CD147 expression. Smad4 activated the transcription by direct interaction with CD147 promoter. Meanwhile, CD147 modulated the activated phenotype of HSCs through the ERK1/2 and Sp1 which up-regulated α-SMA, collagen I, and TGF-β1 synthesis. These findings indicate that TGF-β1-CD147 loop plays a key role in regulating the HSC activation and combination of TGF-β receptor inhibitor and anti-CD147 antibody might be promised to reverse fibrogenesis. PMID:26559755

An open-label pilot study of granulocyte colony-stimulating factor for the treatment of severe endoscopic postoperative recurrence in Crohn's disease.

PubMed

Dejaco, Clemens; Lichtenberger, Conny; Miehsler, Wolfgang; Oberhuber, Georg; Herbst, Friedrich; Vogelsang, Harald; Gangl, Alfred; Reinisch, Walter

2003-01-01

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) promoted healing of Crohn's disease (CD)-like intestinal lesions in chronic granulomatous disease and glycogen storage disease Ib, both characterized by defective neutrophil functions. We performed a prospective, open-label pilot study with rhG-CSF for the treatment of CD. Five patients with clinically inactive CD, but with severe endoscopic ileitis within 1 year after intestinal resection and ileocolonic anastomosis, received 300 microg of rhG-CSF (Filgrastim; Neupogen) subcutaneously, three times weekly for a total of 12 weeks. Safety was evaluated by assessment of clinical and laboratory data and disease activity. The primary parameter of efficacy was complete mucosal healing, as defined by the Rutgeerts score. Anti-inflammatory mediators were repeatedly measured during treatment. All patients completed the protocol in clinical remission. In 1 subject transient headache resolved after halving the rhG-CSF dosage. Complete mucosal healing was observed in 2 patients: in 1 patient after 12 weeks of therapy and in 1 patient 9 months after treatment cessation. In a single patient, closure of an anovaginal and of a perianal fistula was noted. Neutrophil counts and interleukin-1 receptor antagonist and soluble tumor necrosis factor receptor p55 and p75 levels were found to be increased during drug administration. rhG-CSF seems to be safe, well tolerated, and might provide efficacy in CD. Copyright 2003 S. Karger AG, Basel

Combining contamination indexes, sediment quality guidelines and multivariate data analysis for metal pollution assessment in marine sediments of Cienfuegos Bay, Cuba.

PubMed

Peña-Icart, Mirella; Pereira-Filho, Edenir Rodrigues; Lopes Fialho, Lucimar; Nóbrega, Joaquim A; Alonso-Hernández, Carlos; Bolaños-Alvarez, Yoelvis; Pomares-Alfonso, Mario S

2017-02-01

The purpose of the present work was to combine several tools for assessing metal pollution in marine sediments from Cienfuegos Bay. Fourteen surface sediments collected in 2013 were evaluated. Concentrations of As, Cu, Ni, Zn and V decreased respect to those previous reported. The metal contamination was spatially distributed in the north and south parts of the bay. According to the contamination factor (CF) enrichment factor (EF) and index of geoaccumulation (I geo ), Cd and Cu were classified in that order as the most contaminated elements in most sediment. Comparison of the total metal concentrations with the threshold (TELs) and probable (PELs) effect levels in sediment quality guidelines suggested a more worrisome situation for Cu, of which concentrations were occasional associated with adverse biological effects in thirteen sediments, followed by Ni in nine sediments; while adverse effects were rarely associated with Cd. Probably, Cu could be considered as the most dangerous in the whole bay because it was classified in the high contamination levels by all indexes and, simultaneously, associated to occasional adverse effects in most samples. Despite the bioavailability was partially evaluated with the HCl method, the low extraction of Ni (<3% in all samples) and Cu (<55%, except sample 3) and the relative high extraction of Cd (50% or more, except sample 14) could be considered as an attenuating (Ni and Cu) or increasing (Cd) factor in the risk assessment of those element. Copyright © 2016. Published by Elsevier Ltd.

The effects of gold nanoparticles in wound healing with antioxidant epigallocatechin gallate and α-lipoic acid.

PubMed

Leu, Jyh-Gang; Chen, Siang-An; Chen, Han-Min; Wu, Wen-Mein; Hung, Chi-Feng; Yao, Yeong-Der; Tu, Chi-Shun; Liang, Yao-Jen

2012-07-01

Topical applications of antioxidant agents in cutaneous wounds have attracted much attention. Gold nanoparticles (AuNPs), epigallocatechin gallate (EGCG), and α-lipoic acid (ALA) were shown to have antioxidative effects and could be helpful in wound healing. Their effects in Hs68 and HaCaT cell proliferation and in mouse cutaneous wound healing were studied. Both the mixture of EGCG + ALA (EA) and AuNPs + EGCG + ALA (AuEA) significantly increased Hs68 and HaCaT proliferation and migration. Topical AuEA application accelerated wound healing on mouse skin. Immunoblotting of wound tissue showed significant increase of vascular endothelial cell growth factor and angiopoietin-1 protein expression, but no change of angiopoietin-2 or CD31 after 7 days. After AuEA treatment, CD68 protein expression decreased and Cu/Zn superoxide dismutase increased significantly in the wound area. In conclusion, AuEA significantly accelerated mouse cutaneous wound healing through anti-inflammatory and antioxidation effects. This study may support future studies using other antioxidant agents in the treatment of cutaneous wounds. In this study, topically applied gold nanoparticles with epigallocatechin gallate and alpha-lipoic acid were studied regarding their effects in wound healing in cell cultures. Significant acceleration was demonstrated in wound healing in a murine model. Copyright © 2012 Elsevier Inc. All rights reserved.

Emerging materials for solar cell applications: Electrodeposited CdTe

NASA Astrophysics Data System (ADS)

Rod, R. L.; Basol, B. M.; Stafsudd, O.

1980-09-01

Work was centered about improving electroplating processes and cell fabrication techniques, with emphasis being given to three differing n-CdTe/Au Schottky configurations. The highest values of efficiency related parameters achieved with a simulated solar irradiation of 100 mW/sq cm were 0.57V for open circuit voltage, 0.6 for fill factor, and 6 mA/sq cm for short circuit current. Four important parameters are known to control the quality of the Monosolar electrodeposition process and resultant solar cells. They are electrolyte temperature, Te concentration in the solution at a specific pH, deposition or quasi-rest potential, and flow pattern of the electrolyte (stirring). The first three considerations are believed to be fully understood and optimized. Work is underway to further understand the effects of stirring on the diffusion of ionic components and the effects on CdTe film performance. Work was accelerated during the quarter to increase the short circuit current. Parallel programs using laser irradiation of finished CdTe films, heat treatment, and changes in the electrodeposition process itself to recrystallize films were started.

Targeting BRCAness in Gastric Cancer

DTIC Science & Technology

2017-10-01

inhibitors. We also generated a modified CRISPR system using dCas9-KRAB expressing variants of these cells, and validated them for CRISPRi screening...Figure 2. Validation of CRISPR activity following transduction with sgRNAs targeting CD55 and FACS staining with the anti-CD55 antibody. Data shown...interpretation of CRISPR experiments Morgan Diolaiti Specialist UCSF PH.D. Experimental planning and reporting Jefferson Woods SRA UCSF B.S. Perform drug

Tumor necrosis factor alpha (TNF-alpha)-induced cell adhesion to human endothelial cells is under dominant control of one TNF receptor type, TNF-R55

PubMed Central

1993-01-01

Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine triggering cell responses through two distinct membrane receptors. Stimulation of leukocyte adhesion to the endothelium is one of the many TNF-alpha activities and is explained by the upregulation of adhesion molecules on the endothelial cell surface. Human umbilical vein endothelial cells (HUVEC) were isolated, cultured, and demonstrated to express both TNF receptor types, TNF-R55 and TNF-R75. Cell adhesion to HUVEC was studied using the HL60, U937, and MOLT-4 cell lines. HUVEC were activated by either TNF-alpha, binding to both TNF-R55 and TNF- R75, and by receptor type-specific agonists, binding exclusively to TNF- R55 or to TNF-R75. The TNF-alpha-induced cell adhesion to HUVEC was found to be controlled almost exclusively by TNF-R55. This finding correlated with the exclusive activity of TNF-R55 in the TNF-alpha- dependent regulation of the expression of the intercellular adhesion molecule type 1 (ICAM-1), E-selectin, and vascular cell adhesion molecule type 1 (VCAM-1). The CD44 adhesion molecule in HUVEC was also found to be upregulated through TNF-R55. However, both TNF-R55 and TNF- R75 upregulate alpha 2 integrin expression in HUVEC. The predominant role of TNF-R55 in TNF-alpha-induced adhesion in HUVEC may correlate with its specific control of NF-kappa B activation, since kappa B elements are known to be present in ICAM-1, E-selectin, and VCAM-1 gene regulatory sequences. PMID:8386742

Density increment and decreased survival of rat red blood cells induced by cadmium

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

Kunimoto, M.; Miura, T.

1986-01-01

Male Wistar rats were injected with CdCl/sub 2/ subcutaneously to examine in vivo effects of Cd on density and survival of red blood cells. During the 7 days after administration of 1.0 mg Cd/kg, the following sequence of events occurred: (1) a progressive increase in the amount of more dense red blood cells concomitant with a decrease in that of light red blood cells from the first to the third day; (2) an increase in the spleen weight at the third day; (3) a decrease in the hematocrit value and an increase in the amount of light red blood cellsmore » at the fifth day; and (4) a recovery of the hematocrit value at the seventh day. Five days after administration, the hematocrit value decreased in a dose-dependent mode and the decrease was significant at the 1% level at 1.0 and 1.5 mg Cd/kg. A highly significant splenomegaly was also observed at 0.5 to 1.5 mg Cd/kg. In order to label red blood cells in vivo, (/sup 3/H) diisopropylfluorophosphate ((/sup 3/H)DFP) was injected into rats. At Day 11, Cd at either 0.5 or 1.0 mg/kg was administered to (/sup 3/H)DFP-prelabeled animals. Cd administration accelerated /sup 3/H-labeled red cell clearance from the blood. Six days after Cd administration, the radioactivity of red blood cells was 76 and 68% of the control at 0.5 and 1.0 mg Cd/kg, respectively. In vitro treatment of rat red density and accelerated in vivo clearance of red blood cells from the recipient circulation. These results show that Cd at low dose can cause anemia by increasing red cell density and by accelerating red cell sequestration, presumably in the spleen.« less

Cadmium Accumulation Risk in Vegetables and Rice in Southern China: Insights from Solid-Solution Partitioning and Plant Uptake Factor.

PubMed

Yang, Yang; Wang, Meie; Chen, Weiping; Li, Yanling; Peng, Chi

2017-07-12

Solid-solution partitioning coefficient (K d ) and plant uptake factor (PUF) largely determine the solubility and mobility of soil Cd to food crops. A four-year regional investigation was conducted in contaminated vegetable and paddy fields of southern China to quantify the variability in K d and PUF. The distributions of K d and PUF characterizing transfers of Cd from soil to vegetable and rice are probabilistic in nature. Dynamics in soil pH and soil Zn greatly affected the variations of K d . In addition to soil pH, soil organic matter had a major influence on PUF variations in vegetables. Heavy leaching of soil Mn caused a higher Cd accumulation in rice grain. Dietary ingestion of 85.5% of the locally produced vegetable and rice would have adverse health risks, with rice consumption contributing 97.2% of the risk. A probabilistic risk analysis based on derived transfer function reveals the amorphous Mn oxide content exerts a major influence on Cd accumulation in rice in pH conditions below 5.5. Risk estimation and field experiments show that to limit the Cd concentration in rice grains, soil management strategies should include improving the pH and soil Mn concentration to around 6.0 and 345 mg kg -1 , respectively. Our work illustrates that re-establishing a balance in trace elements in soils' labile pool provides an effective risk-based approach for safer crop practices.

Decreased lipogenesis-promoting factors in adipose tissue in postmenopausal women with overweight on a Paleolithic-type diet.

PubMed

Blomquist, Caroline; Chorell, Elin; Ryberg, Mats; Mellberg, Caroline; Worrsjö, Evelina; Makoveichuk, Elena; Larsson, Christel; Lindahl, Bernt; Olivecrona, Gunilla; Olsson, Tommy

2017-10-26

We studied effects of diet-induced postmenopausal weight loss on gene expression and activity of proteins involved in lipogenesis and lipolysis in adipose tissue. Fifty-eight postmenopausal women with overweight (BMI 32.5 ± 5.5) were randomized to eat an ad libitum Paleolithic-type diet (PD) aiming for a high intake of protein and unsaturated fatty acids or a prudent control diet (CD) for 24 months. Anthropometry, plasma adipokines, gene expression of proteins involved in fat metabolism in subcutaneous adipose tissue (SAT) and lipoprotein lipase (LPL) activity and mass in SAT were measured at baseline and after 6 months. LPL mass and activity were also measured after 24 months. The PD led to improved insulin sensitivity (P < 0.01) and decreased circulating triglycerides (P < 0.001), lipogenesis-related factors, including LPL mRNA (P < 0.05), mass (P < 0.01), and activity (P < 0.001); as well as gene expressions of CD36 (P < 0.05), fatty acid synthase, FAS (P < 0.001) and diglyceride acyltransferase 2, DGAT2 (P < 0.001). The LPL activity (P < 0.05) and gene expression of DGAT2 (P < 0.05) and FAS (P < 0.05) were significantly lowered in the PD group versus the CD group at 6 months and the LPL activity (P < 0.05) remained significantly lowered in the PD group compared to the CD group at 24 months. Compared to the CD, the PD led to a more pronounced reduction of lipogenesis-promoting factors in SAT among postmenopausal women with overweight. This could have mediated the favorable metabolic effects of the PD on triglyceride levels and insulin sensitivity.

PTSD is associated with an increase in aged T cell phenotypes in adults living in Detroit

PubMed Central

Aiello, Allison E.; Dowd, Jennifer B.; Jayabalasingham, Bamini; Feinstein, Lydia; Uddin, Monica; Simanek, Amanda M.; Cheng, Caroline K.; Galea, Sandro; Wildman, Derek E.; Koenen, Karestan; Pawelec, Graham

2016-01-01

Background Psychosocial stress is thought to play a key role in the acceleration of immunological aging. This study investigated the relationship between lifetime and past-year history of post-traumatic stress disorder (PTSD) and the distribution of T cell phenotypes thought to be characteristic of immunological aging. Methods Data were from 85 individuals who participated in the community-based Detroit Neighborhood Health Study. Immune markers assessed included the CD4:CD8 ratio, the ratio of late-differentiated effector (CCR7-CD45RA+CD27-CD28-) to naïve (CCR7+CD45RA+CD27+CD28+) T cells, the percentage of KLRG1-expressing cells, and the percentage of CD57-expressing cells. Results In models adjusted for age, gender, race/ethnicity, education, smoking status, and medication use, we found that past-year PTSD was associated with statistically significant differences in the CD8+ T cell population, including a higher ratio of late-differentiated effector to naïve T cells, a higher percentage of KLRG1+ cells, and a higher percentage of CD57+ cells. The percentage of CD57+ cells in the CD4 subset was also significantly higher and the CD4:CD8 ratio significantly lower among individuals who had experienced past-year PTSD. Lifetime PTSD was also associated with differences in several parameters of immune aging. Conclusions PTSD is associated with an aged immune phenotype and should be evaluated as a potential catalyzer of accelerated immunological aging in future studies. PMID:26894484

A critical role for both CD40 and VLA5 in angiotensin II-mediated thrombosis and inflammation.

PubMed

Senchenkova, Elena Y; Russell, Janice; Vital, Shantel A; Yildirim, Alper; Orr, A Wayne; Granger, D Neil; Gavins, Felicity N E

2018-06-01

Angiotensin II (Ang-II)-induced hypertension is associated with accelerated thrombus formation in arterioles and leukocyte recruitment in venules. The mechanisms that underlie the prothrombotic and proinflammatory responses to chronic Ang-II administration remain poorly understood. We evaluated the role of CD40/CD40 ligand (CD40L) signaling in Ang-II-mediated microvascular responses and assessed whether and how soluble CD40L (sCD40L) contributes to this response. Intravital video microscopy was performed to analyze leukocyte recruitment and dihydrorhodamine-123 oxidation in postcapillary venules. Thrombus formation in cremaster muscle arterioles was induced by using the light/dye endothelial cell injury model. Wild-type (WT), CD40 -/- , and CD40L -/- mice received Ang-II for 14 d via osmotic minipumps. Some mice were treated with either recombinant sCD40L or the VLA5 (very late antigen 5; α5β1) antagonist, ATN-161. Our results demonstrate that CD40 -/- , CD40L -/- , and WT mice that were treated with ATN-161 were protected against the thrombotic and inflammatory effects of Ang-II infusion. Infusion of sCD40L into CD40 -/- or CD40L -/- mice restored the prothrombotic effect of Ang-II infusion. Mice that were treated with ATN-161 and infused with sCD40L were protected against accelerated thrombosis. Collectively, these novel findings suggest that the mechanisms that underlie Ang-II-dependent thrombotic and inflammatory responses link to the signaling of CD40L via both CD40 and VLA5.-Senchenkova, E. Y., Russell, J., Vital, S. A., Yildirim, A., Orr, A. W., Granger, D. N., Gavins, F. N. E. A critical role for both CD40 and VLA5 in angiotensin II-mediated thrombosis and inflammation.

Predicting the influence of liposomal lipid composition on liposome size, zeta potential and liposome-induced dendritic cell maturation using a design of experiments approach.

PubMed

Soema, Peter C; Willems, Geert-Jan; Jiskoot, Wim; Amorij, Jean-Pierre; Kersten, Gideon F

2015-08-01

In this study, the effect of liposomal lipid composition on the physicochemical characteristics and adjuvanticity of liposomes was investigated. Using a design of experiments (DoE) approach, peptide-containing liposomes containing various lipids (EPC, DOPE, DOTAP and DC-Chol) and peptide concentrations were formulated. Liposome size and zeta potential were determined for each formulation. Moreover, the adjuvanticity of the liposomes was assessed in an in vitro dendritic cell (DC) model, by quantifying the expression of DC maturation markers CD40, CD80, CD83 and CD86. The acquired data of these liposome characteristics were successfully fitted with regression models, and response contour plots were generated for each response factor. These models were applied to predict a lipid composition that resulted in a liposome with a target zeta potential. Subsequently, the expression of the DC maturation factors for this lipid composition was predicted and tested in vitro; the acquired maturation responses corresponded well with the predicted ones. These results show that a DoE approach can be used to screen various lipids and lipid compositions, and to predict their impact on liposome size, charge and adjuvanticity. Using such an approach may accelerate the formulation development of liposomal vaccine adjuvants. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Prevalence of Chagas Disease in the Latin American–born Population of Los Angeles

PubMed Central

Forsyth, Colin J.; Soverow, Jonathan; Hernandez, Salvador; Sanchez, Daniel; Montgomery, Susan P.; Traina, Mahmoud

2017-01-01

Abstract Background. According to an estimate from the Centers for Disease Control and Prevention (CDC), Chagas disease (CD) may affect 1.31% of Latin American immigrants in the United States, with >300 000 cases. However, there is a lack of real-world data to support this estimate. Little is known about the actual prevalence of this neglected tropical disease in the United States, and the bulk of those infected are undiagnosed. Methods. From April 2008 to May 2014, we screened 4,755 Latin American–born residents of Los Angeles County. Blood samples were tested for serologic evidence of CD. We collected demographic data and assessed the impact of established risk factors on CD diagnosis, including sex, country of origin, housing materials, family history of CD, and awareness of CD. Results. There were 59 cases of CD, for an overall prevalence of 1.24%. Prevalence was highest among Salvadorans (3.45%). Of the 3,182 Mexican respondents, those from Oaxaca (4.65%) and Zacatecas (2.2%) had the highest CD prevalence. Salvadoran origin (aOR = 6.2; 95% CI = 2.8–13.5; P < .001), prior knowledge of CD (aOR = 2.4; 95% CI = 1.0–5.8; P = .047), and exposure to all 3 at-risk housing types (adobe, mud, and thatched roof) (aOR = 2.5; 95% CI = 1.0–6.4; P = .048) were associated with positive diagnosis. Conclusions. In the largest screening of CD in the United States to date outside of blood banks, we found a CD prevalence of 1.24%. This implies >30 000 people infected in Los Angeles County alone, making CD an important public health concern. Efficient, targeted surveillance of CD may accelerate diagnosis and identify candidates for early treatment. PMID:28329123

Slow-release nitrogen fertilizers can improve yield and reduce Cd concentration in pakchoi (Brassica chinensis L.) grown in Cd-contaminated soil.

PubMed

Zhang, Ran-Ran; Liu, Yue; Xue, Wan-Lei; Chen, Rong-Xin; Du, Shao-Ting; Jin, Chong-Wei

2016-12-01

Cadmium (Cd) pollution in vegetable crops has become a serious problem in recent years. Owing to the limited availability of arable land resources, large areas of Cd-contaminated lands are inevitably being used for the production of vegetables, posing great risks to human health via the food chain. However, strategies to improve yield and reduce Cd concentration in crops grown in contaminated soils are being developed. In the present study, using pot experiments, we investigated the effects of two slow-release nitrogen fertilizers (SRNFs), resin-coated ammonium nitrate (Osmocote 313s ), and resin-coated urea (urea 620 ), on the growth and Cd concentration of the Cd-contaminated pakchoi. The results showed that pakchoi grown in soil containing 5 mg kg -1 of Cd-induced oxidative stress (indicated by malondialdehyde (MDA), H 2 O 2 , and O 2 ·- ) and photosynthesis inhibition, which in turn was restored with the application of SRNFs. However, pakchoi grown in Cd-contaminated soil supplied with Osmocote 313s and urea 620 showed 103 and 203 % increase in fresh weight and 51-55 % and 44-56 % decrease in Cd concentration, respectively, as compared with their controls (pakchoi treated with instant soluble nitrogen fertilizers). On the basis of an increase in their tolerance index (47-238 %) and a decrease in their translocation factor (7.5-21.6 %), we inferred that the plants treated with SRNFs have a stronger tolerance to Cd and a lower efficiency of Cd translocation to edible parts than those treated with instant soluble nitrogen fertilizers. Therefore, in terms of both crop production and food safety, application of SRNFs could be an effective strategy for improving both biomass production and quality in pakchoi grown under Cd stress.

Anterior Cruciate Ligament-Derived Stem Cells Transduced With BMP2 Accelerate Graft-Bone Integration After ACL Reconstruction.

PubMed

Kawakami, Yohei; Takayama, Koji; Matsumoto, Tomoyuki; Tang, Ying; Wang, Bing; Mifune, Yutaka; Cummins, James H; Warth, Ryan J; Kuroda, Ryosuke; Kurosaka, Masahiro; Fu, Freddie H; Huard, Johnny

2017-03-01

Strong graft-bone integration is a prerequisite for successful graft remodeling after reconstruction of the anterior cruciate ligament (ACL) using soft tissue grafts. Novel strategies to accelerate soft tissue graft-bone integration are needed to reduce the need for bone-tendon-bone graft harvest, reduce patient convalescence, facilitate rehabilitation, and reduce total recovery time after ACL reconstruction. The application of ACL-derived stem cells with enhanced expression of bone morphogenetic protein 2 (BMP2) onto soft tissue grafts in the form of cell sheets will both accelerate and improve the quality of graft-bone integration after ACL reconstruction in a rat model. Controlled laboratory study. ACL-derived CD34+ cells were isolated from remnant human ACL tissues, virally transduced to express BMP2, and embedded within cell sheets. In a rat model of ACL injury, bilateral single-bundle ACL reconstructions were performed, in which cell sheets were wrapped around tendon autografts before reconstruction. Four groups containing a total of 48 rats (96 knees) were established (n = 12 rats; 24 knees per group): CD34+BMP2 (100%), CD34+BMP2 (25%), CD34+ (untransduced), and a control group containing no cells. Six rats from each group were euthanized 2 and 4 weeks after surgery, and each graft was harvested for immunohistochemical and histological analyses. The remaining 6 rats in each group were euthanized at 4 and 8 weeks to evaluate in situ tensile load to failure in each femur-graft-tibia complex. In vitro, BMP2 transduction promoted the osteogenic differentiation of ACL-derived CD34+ cells while retaining their intrinsic multipotent capabilities. Osteoblast densities were greatest in the BMP2 (100%) and BMP2 (25%) groups. Bone tunnels in the CD34+BMP2 (100%) and CD34+BMP2 (25%) groups had the smallest cross-sectional areas according to micro-computed tomography analyses. Graft-bone integration occurred most rapidly in the CD34+BMP2 (25%) group. Tensile load to failure was significantly greater in the groups containing stem cells at 4 and 8 weeks after surgery. Tensile strength was greatest in the CD34+BMP2 (100%) group at 4 weeks, and in the CD34+BMP2 (25%) group at 8 weeks. ACL-derived CD34+ cells transduced with BMP2 accelerated graft-bone integration after ACL reconstruction using soft tissue autografts in a rat model, as evidenced by improved histological appearance and graft-bone interface biology along with tensile load to failure at each time point up to 8 weeks after surgery. A primary disadvantage of using soft tissue grafts for ACL reconstruction is the prolonged time required for bony ingrowth, which delays the initiation of midsubstance graft remodeling. The lack of consistent correlation between the appearance of a "healed" ACL on postoperative magnetic resonance imaging and readiness to return to sport results in athletes being released to sport before the graft is ready to handle high-intensity loading. Therefore, it is desirable to identify strategies that accelerate graft-bone integration, which would reduce the time to biologic fixation, improve the reliability of biologic fixation, allow for accelerated rehabilitation, and potentially reduce the incidence of early graft pullout and late midsubstance failure.

Profile and bioconcentration of minerals by King Bolete (Boletus edulis) from the Płocka Dale in Poland.

PubMed

Frankowska, Aneta; Ziółkowska, Joanna; Bielawski, Leszek; Falandysz, Jerzy

2010-01-01

This study aimed to provide basic data on the composition of metallic elements, including toxicologically important Cd and Hg, in popular and prized wild King Bolete mushrooms. We investigated the importance of soil substratum as a source of these metals. ICP-OES and CV-AAS were applied to determine the profile of Al, Ba, Ca, Cd, Cu, Fe, Hg, K, Mg, Mn, Na, Sr and Zn in caps and stipes of King Bolete mushroom and in the surface layer of soil (0-10 cm) from the Płocka Dale area of Poland. Hg, Cu, Cd, Zn, Mg and K exhibited bioconcentration factors (BCF) > 1. Specifically, Hg, Cu and Cd (mean BCFs for caps were 110, 19 and 16, respectively) were efficiently bioconcentrated by King Bolete, while other elements were bioexcluded (BCF < 1). Cadmium was present in the caps at mean levels of 5.5 ± 2.4 mg kg(-1) dry weight (dw) and mercury at levels of 4.9 ± 1.4 mg kg(-1) dw, both occurring at elevated concentrations in those King Bolete mushrooms surveyed.

Analysis of minocycline as a countermeasure against acute radiation syndrome.

PubMed

Mehrotra, Shalini; Pecaut, Michael J; Gridley, Daila S

2012-01-01

To evaluate the impact of an antibiotic, minocycline, on several immune parameters in response to radiation in a mouse model. C57BL/6 mice were treated with minocycline (i.p.) for 5 days, beginning immediately before radiation with 1-3 Gy (60)Co γ-rays. Spleen and blood were collected on day 4 post-irradiation. Cell populations were determined in the blood and spleen. Splenocytes were activated with anti-CD3 antibody for 48 h and cytokines were quantified. Minocycline increased the counts and/or percentages of splenic macrophages, granulocytes, natural killer, T- and CD8(+) T-cells (p<0.05 versus radiation alone). Minocycline significantly increased the expression of interleukin-1α and β, which are radioprotective, as well as the ones of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor, which accelerate neutrophil recovery (p<0.05 versus radiation alone), while suppressing cytokines that could prevent hematopoiesis, e.g. macrophage inflammatory protein-1α, tumor necrosis factor-α and interferon-γ. These data indicate that minocycline should be further tested for use in restoration of the hematopoietic system after radiation exposure.

New Signal Amplification Strategy Using Semicarbazide as Co-reaction Accelerator for Highly Sensitive Electrochemiluminescent Aptasensor Construction.

PubMed

Ma, Meng-Nan; Zhuo, Ying; Yuan, Ruo; Chai, Ya-Qin

2015-11-17

A highly sensitive electrochemiluminescent (ECL) aptasensor was constructed using semicarbazide (Sem) as co-reaction accelerator to promote the ECL reaction rate of CdTe quantum dots (CdTe QDs) and the co-reactant of peroxydisulfate (S2O8(2-)) for boosting signal amplification. The co-reaction accelerator is a species that when it is introduced into the ECL system containing luminophore and co-reactant, it can interact with co-reactant rather than luminophore to promote the ECL reaction rate of luminophore and co-reactant; thus the ECL signal is significantly amplified in comparison with that in which only luminophore and co-reactant are present. In this work, the ECL signal probes were first fabricated by alternately assembling the Sem and Au nanoparticles (AuNPs) onto the surfaces of hollow Au nanocages (AuNCs) via Au-N bond to obtain the multilayered nanomaterials of (AuNPs-Sem)n-AuNCs for immobilizing amino-terminated detection aptamer of thrombin (TBA2). Notably, the Sem with two -NH2 terminal groups could not only serve as cross-linking reagent to assemble AuNPs and AuNCs but also act as co-reaction accelerator to enhance the ECL reaction rate of CdTe QDs and S2O8(2-) for signal amplification. With the sandwich-type format, TBA2 signal probes could be trapped on the CdTe QD-based sensing interface in the presence of thrombin (TB) to achieve a considerably enhanced ECL signal in S2O8(2-) solution. As a result, the Sem in the TBA2 signal probes could accelerate the reduction of S2O8(2-) to produce the more oxidant mediators of SO4(•-), which further boosted the production of excited states of CdTe QDs to emit light. With the employment of the novel co-reaction accelerator Sem, the proposed ECL biosensor exhibited ultrahigh sensitivity to quantify the concentration of TB from 1 × 10(-7) to 1 nM with a detection limit of 0.03 fM, which demonstrated that the co-reaction accelerator could provide a simple, efficient, and low-cost approach for signal amplification and hold great potential for other ECL biosensors construction.

Profound CD4+/CCR5+ T cell expansion is induced by CD8+ lymphocyte depletion but does not account for accelerated SIV pathogenesis

PubMed Central

Okoye, Afam; Park, Haesun; Rohankhedkar, Mukta; Coyne-Johnson, Lia; Lum, Richard; Walker, Joshua M.; Planer, Shannon L.; Legasse, Alfred W.; Sylwester, Andrew W.; Piatak, Michael; Lifson, Jeffrey D.; Sodora, Donald L.; Villinger, Francois; Axthelm, Michael K.; Schmitz, Joern E.

2009-01-01

Depletion of CD8+ lymphocytes during acute simian immunodeficiency virus (SIV) infection of rhesus macaques (RMs) results in irreversible prolongation of peak-level viral replication and rapid disease progression, consistent with a major role for CD8+ lymphocytes in determining postacute-phase viral replication set points. However, we report that CD8+ lymphocyte depletion is also associated with a dramatic induction of proliferation among CD4+ effector memory T (TEM) cells and, to a lesser extent, transitional memory T (TTrM) cells, raising the question of whether an increased availability of optimal (activated/proliferating), CD4+/CCR5+ SIV “target” cells contributes to this accelerated pathogenesis. In keeping with this, depletion of CD8+ lymphocytes in SIV− RMs led to a sustained increase in the number of potential CD4+ SIV targets, whereas such depletion in acute SIV infection led to increased target cell consumption. However, we found that the excess CD4+ TEM cell proliferation of CD8+ lymphocyte–depleted, acutely SIV-infected RMs was completely inhibited by interleukin (IL)-15 neutralization, and that this inhibition did not abrogate the rapidly progressive infection in these RMs. Moreover, although administration of IL-15 during acute infection induced robust CD4+ TEM and TTrM cell proliferation, it did not recapitulate the viral dynamics of CD8+ lymphocyte depletion. These data suggest that CD8+ lymphocyte function has a larger impact on the outcome of acute SIV infection than the number and/or activation status of target cells available for infection and viral production. PMID:19546246

Pancreatic cancer cells express CD44 variant 9 and multidrug resistance protein 1 during mitosis.

PubMed

Kiuchi, Shizuka; Ikeshita, Shunji; Miyatake, Yukiko; Kasahara, Masanori

2015-02-01

Pancreatic cancer is one of the most lethal cancers with high metastatic potential and strong chemoresistance. Its intractable natures are attributed to high robustness in tumor cells for their survival. We demonstrate here that pancreatic cancer cells (PCCs) with an epithelial phenotype upregulate cell surface expression of CD44 variant 9 (CD44v9), an important cancer stem cell marker, during the mitotic phases of the cell cycle. Of five human CD44(+) PCC lines examined, three cell lines, PCI-24, PCI-43 and PCI-55, expressed E-cadherin and CD44 variants, suggesting that they have an epithelial phenotype. By contrast, PANC-1 and MIA PaCa-2 cells expressed vimentin and ZEB1, suggesting that they have a mesenchymal phenotype. PCCs with an epithelial phenotype upregulated cell surface expression of CD44v9 in prophase, metaphase, anaphase and telophase and downregulated CD44v9 expression in late-telophase, cytokinesis and interphase. Sorted CD44v9-negative PCI-55 cells resumed CD44v9 expression when they re-entered the mitotic stage. Interestingly, CD44v9(bright) mitotic cells expressed multidrug resistance protein 1 (MDR1) intracellularly. Upregulated expression of CD44v9 and MDR1 might contribute to the intractable nature of PCCs with high proliferative activity. Copyright © 2014 Elsevier Inc. All rights reserved.

Associations between NRAMP1 Polymorphisms and Susceptibility to Ulcerative Colitis/Crohn's Disease: A Meta-Analysis.

PubMed

Sun, Manyi; Zhang, Li; Shi, Songli

2016-01-01

Multiple environmental and genetic factors contribute to the risks of ulcerative colitis (UC) and Crohn's disease (CD). Several allelic variants have been identified in natural resistance associated macrophage protein 1 (NRAMP1) gene; however, their association with UC/CD remains conflicting. The purpose of this study was to evaluate whether NRAMP1 polymorphisms are associated with the susceptibility to UC/CD. A meta-analysis on the association between the NRAMP1 polymorphisms and susceptibility to UC/CD was performed. Relevant studies were retrieved from the databases. After eligible data were extracted, Mantel-Haenszel statistics and random/fixed effects model were applied to calculate the pooled odds radio (OR) and 95% confidence interval (95% CI). Seven articles containing 536 UC cases, 997 CD cases, and 1361 controls were collected. No significant association between allele 2 frequency of NRAMP1 and susceptibility to UC/CD was detected in overall population (all p > 0.05). However, increased UC/CD risk for allele 3 was observed in Caucasian population (OR = 1.27, 95% CI = 1.08~1.50, p = 0.04), whereas decreased UC/CD risk was detected in non-Caucasian population (OR = 0.72, 95% CI = 0.60~0.87, p < 0.001), under "allele 3 vs. other alleles" model. Moreover, a significant increase in CD risk for T carrier frequency of -237 C/T (OR = 0.44, 95% CI, 0.26~0.75, p = 0.003) was detected, but not 274 C/T and 1729+55del4 (TGTG) +/del. The polymorphism of -237 C/T is related to the risk of CD; and the association of allele 3 with UC/CD risk differs in Caucasian and non-Caucasian population, which might be the potential biomarkers for clinical diagnosis of UC/CD.

Repair of astrocytes, blood vessels, and myelin in the injured brain: possible roles of blood monocytes

PubMed Central

2013-01-01

Inflammation in injured tissue has both repair functions and cytotoxic consequences. However, the issue of whether brain inflammation has a repair function has received little attention. Previously, we demonstrated monocyte infiltration and death of neurons and resident microglia in LPS-injected brains (Glia. 2007. 55:1577; Glia. 2008. 56:1039). Here, we found that astrocytes, oligodendrocytes, myelin, and endothelial cells disappeared in the damage core within 1–3 d and then re-appeared at 7–14 d, providing evidence of repair of the brain microenvironment. Since round Iba-1+/CD45+ monocytes infiltrated before the repair, we examined whether these cells were involved in the repair process. Analysis of mRNA expression profiles showed significant upregulation of repair/resolution-related genes, whereas proinflammatory-related genes were barely detectable at 3 d, a time when monocytes filled injury sites. Moreover, Iba-1+/CD45+ cells highly expressed phagocytic activity markers (e.g., the mannose receptors, CD68 and LAMP2), but not proinflammatory mediators (e.g., iNOS and IL1β). In addition, the distribution of round Iba-1+/CD45+ cells was spatially and temporally correlated with astrocyte recovery. We further found that monocytes in culture attracted astrocytes by releasing soluble factor(s). Together, these results suggest that brain inflammation mediated by monocytes functions to repair the microenvironment of the injured brain. PMID:23758980

Size distribution, characteristics and sources of heavy metals in haze episode in Beijing.

PubMed

Duan, Jingchun; Tan, Jihua; Hao, Jiming; Chai, Fahe

2014-01-01

Size segragated samples were collected during high polluted winter haze days in 2006 in Beijing, China. Twenty nine elements and 9 water soluble ions were determined. Heavy metals of Zn, Pb, Mn, Cu, As, Cr, Ni, V and Cd were deeply studied considering their toxic effect on human being. Among these heavy metals, the levels of Mn, As and Cd exceeded the reference values of National Ambient Air Quality Standard (GB3095-2012) and guidelines of World Health Organization. By estimation, high percentage of atmospheric heavy metals in PM2.5 indicates it is an effective way to control atmospheric heavy metals by PM2.5 controlling. Pb, Cd, and Zn show mostly in accumulation mode, V, Mn and Cu exist mostly in both coarse and accumulation modes, and Ni and Cr exist in all of the three modes. Considering the health effect, the breakthrough rates of atmospheric heavy metals into pulmonary alveoli are: Pb (62.1%) > As (58.1%) > Cd (57.9%) > Zn (57.7%) > Cu (55.8%) > Ni (53.5%) > Cr (52.2%) > Mn (49.2%) > V (43.5%). Positive matrix factorization method was applied for source apportionment of studied heavy metals combined with some marker elements and ions such as K, As, SO4(2-) etc., and four factors (dust, vehicle, aged and transportation, unknown) are identified and the size distribution contribution of them to atmospheric heavy metals are discussed.

Monocyte alterations in rheumatoid arthritis are dominated by preterm release from bone marrow and prominent triggering in the joint.

PubMed

Smiljanovic, Biljana; Radzikowska, Anna; Kuca-Warnawin, Ewa; Kurowska, Weronika; Grün, Joachim R; Stuhlmüller, Bruno; Bonin, Marc; Schulte-Wrede, Ursula; Sörensen, Till; Kyogoku, Chieko; Bruns, Anne; Hermann, Sandra; Ohrndorf, Sarah; Aupperle, Karlfried; Backhaus, Marina; Burmester, Gerd R; Radbruch, Andreas; Grützkau, Andreas; Maslinski, Wlodzimierz; Häupl, Thomas

2018-02-01

Rheumatoid arthritis (RA) accompanies infiltration and activation of monocytes in inflamed joints. We investigated dominant alterations of RA monocytes in bone marrow (BM), blood and inflamed joints. CD14 + cells from BM and peripheral blood (PB) of patients with RA and osteoarthritis (OA) were profiled with GeneChip microarrays. Detailed functional analysis was performed with reference transcriptomes of BM precursors, monocyte blood subsets, monocyte activation and mobilisation. Cytometric profiling determined monocyte subsets of CD14 ++ CD16 - , CD14 ++ CD16 + and CD14 + CD16 + cells in BM, PB and synovial fluid (SF) and ELISAs quantified the release of activation markers into SF and serum. Investigation of genes differentially expressed between RA and OA monocytes with reference transcriptomes revealed gene patterns of early myeloid precursors in RA-BM and late myeloid precursors along with reduced terminal differentiation to CD14 + CD16 + monocytes in RA-PB. Patterns associated with tumor necrosis factor/lipopolysaccharide (TNF/LPS) stimulation were weak and more pronounced in RA-PB than RA-BM. Cytometric phenotyping of cells in BM, blood and SF disclosed differences related to monocyte subsets and confirmed the reduced frequency of terminally differentiated CD14 + CD16 + monocytes in RA-PB. Monocyte activation in SF was characterised by the predominance of CD14 ++ CD16 ++ CD163 + HLA-DR + cells and elevated concentrations of sCD14, sCD163 and S100P. Patterns of less mature and less differentiated RA-BM and RA-PB monocytes suggest increased turnover with accelerated monocytopoiesis, BM egress and migration into inflamed joints. Predominant activation in the joint indicates the action of local and primary stimuli, which may also promote adaptive immune triggering through monocytes, potentially leading to new diagnostic and therapeutic strategies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Genetic Adjuvantation of Recombinant MVA with CD40L Potentiates CD8 T Cell Mediated Immunity

PubMed Central

Lauterbach, Henning; Pätzold, Juliane; Kassub, Ronny; Bathke, Barbara; Brinkmann, Kay; Chaplin, Paul; Suter, Mark; Hochrein, Hubertus

2013-01-01

Modified vaccinia Ankara (MVA) is a safe and promising viral vaccine vector that is currently investigated in several clinical and pre-clinical trials. In contrast to inactivated or sub-unit vaccines, MVA is able to induce strong humoral as well as cellular immune responses. In order to further improve its CD8 T cell inducing capacity, we genetically adjuvanted MVA with the coding sequence of murine CD40L, a member of the tumor necrosis factor superfamily. Immunization of mice with this new vector led to strongly enhanced primary and memory CD8 T cell responses. Concordant with the enhanced CD8 T cell response, we could detect stronger activation of dendritic cells and higher systemic levels of innate cytokines (including IL-12p70) early after immunization. Interestingly, acquisition of memory characteristics (i.e., IL-7R expression) was accelerated after immunization with MVA-CD40L in comparison to non-adjuvanted MVA. Furthermore, the generated cytotoxic T-lymphocytes (CTLs) also showed improved functionality as demonstrated by intracellular cytokine staining and in vivo killing activity. Importantly, the superior CTL response after a single MVA-CD40L immunization was able to protect B cell deficient mice against a fatal infection with ectromelia virus. Taken together, we show that genetic adjuvantation of MVA can change strength, quality, and functionality of innate and adaptive immune responses. These data should facilitate a rational vaccine design with a focus on rapid induction of large numbers of CD8 T cells able to protect against specific diseases. PMID:23986761

Effects of a common variant in the CD38 gene on social processing in an oxytocin challenge study: possible links to autism.

PubMed

Sauer, Carina; Montag, Christian; Wörner, Christiane; Kirsch, Peter; Reuter, Martin

2012-05-01

The intranasal application of oxytocin (OT) has been shown to influence behavioral and neural correlates of social processing. These effects are probably mediated by genetic variations within the OT system. One potential candidate could be the CD38 gene, which codes for a transmembrane protein engaged in OT secretion processes. A common variation in this gene (rs3796863) was recently found to be associated with autism spectrum disorders (ASD). Using an imaging genetics approach, we studied differential effects of an intranasal OT application on neural processing of social stimuli in 55 healthy young men depending on their CD38 gene variant in a double-blind placebo-controlled crossover design. Genotype had a significant influence on both behavioral and neuronal measures of social processing. Homozygotic risk allele carriers showed slower reaction times (RT) and higher activation of left fusiform gyrus during visual processing of social stimuli. Under OT activation differences between genotypes were more evident (though not statistically significantly increased) and RT were accelerated in homozygotic risk allele carriers. According to our data, rs3796863 mainly influences fusiform gyrus activation, an area which has been widely discussed in ASD research. OT seems to modulate this effect by enhancing activation differences between allele groups, which suggests an interaction between genetic makeup and OT availability on fusiform gyrus activation. These results support recent approaches to apply OT as a pharmacological treatment of ASD symptoms.

Fuzhengpaidu granule regulates immune activation molecules CD38 and human leukocyte antigen-D related on CD4+ and CD8+ T cells in patients with acquired immunodeficiency syndrome/human immunodeficiency virus.

PubMed

Jiang, Feng; Zhang, Rongxin; Gu, Zhenfang; Zhang, Huailing; Guo, Huijun; Deng, Xin; Liang, Jian

2013-08-01

To evaluate the effect of Fuzhengpaidu granule (FZPDG) on immune activation molecules CD38 and human leukocyte antigen-D related (HLA-DR) on CD4+ and CD8+ cells in HIV/AIDS patients, and to explore the underlying mechanism of this therapy. Plasma changes in CD3+, CD4+, CD8+, CD3 + CD4 + CD38 +, CD3 + CD4 + HLA-DR+, CD3 + CD8+CD38+, and CD3+CD8+HLA-DR+ levels in HIV/ AIDS patients treated with FZPDG for six months were examined by flow cytometry and compared with levels in healthy controls. The clinical trial included 34 outpatients with HIV/AIDS. Before treatment, plasma levels of CD38+ and HLA-DR+ on CD4/CD8 cells were higher than those in 28 health controls (P < 0.05). There were no significant changes in serum levels of CD3+, CD4+, and CD8+ T cells between pretreatment baseline versus after treatment, which were 82.85% +/- 5.41%, 14.57% +/- 10.31% and 54.55% +/- 11.43% before treatment and 79.15% +/- 8.21%, 19.96% +/- 9.58% and 56.36% +/- 11.67% after treatment, respectively (P > 0.05). Plasma levels of CD3+ CD4+CD38+ and CD3+CD4+HLA-DR+ were 2.3% +/-2.2% and 7.8% +/- 5.5% before treatment and 1.2% +/-0.8% and 2.6% +/- 1.0% after treatment, respectively. Plasma levels of CD3+CD8+CD38+ and CD3+CD8+ HLA-DR+ were 41.4% +/- 13.4% and 17.8% +/- 11.3% before treatment, which changed to 27.1% +/- 10.2% and 3.8% +/- 2.4% after treatment, respectively (P < 0.05). HIV/AIDS patients exhibited an immune activation profile following FZPDG treatment. A potential mechanism of action for FZPDG appears to lie in its ability to up-regulate CD38 and HLA-DR levels on CD4+ T cells, and down-regulate them on CD8+ cells, thereby modulating immune activation of CD4+and CD8+T cells.

Evaluation of humoral and cell-mediated inducible immunity to Haemophilus ducreyi in an animal model of chancroid.

PubMed Central

Desjardins, M; Filion, L G; Robertson, S; Kobylinski, L; Cameron, D W

1996-01-01

To study the mechanisms of inducible immunity to Haemophilus ducreyi infection in the temperature-dependent rabbit model of chancroid, we conducted passive immunization experiments and characterized the inflammatory infiltrate of chancroidal lesions. Polyclonal immunoglobulin G was purified from immune sera raised against H. ducreyi 35000 whole-cell lysate or a pilus preparation and from naive control rabbits. Rabbits were passively immunized with 24 or 48 mg of purified polyclonal immunoglobulin G intravenously, followed 24 h after infusion by homologous titered infectious challenge. Despite titratable antibody, no significant difference in infection or disease was observed. We then evaluated the immunohistology of lesions produced by homologous-strain challenge in sham-immunized rabbits and those protectively vaccinated by pilus preparation immunization. Immunohistochemical stains for CD5 and CD4 T-lymphocyte markers were performed on lesion sections 4, 10, 15, and 21 days from infection. Lesions of pilus preparation vaccinees compared with those of controls had earlier infiltration with significantly more T lymphocytes (CD5+) and with a greater proportion of CD4+ T lymphocytes at day 4 (33% +/- 55% versus 9.7% +/- 2%; P = 0.002), corroborating earlier sterilization (5.0 +/- 2 versus 13.7 +/- 0.71 days; P < 0.001) and lesion resolution. Intraepithelial challenge of pilus-vaccinated rabbits with 100 micrograms of the pilus preparation alone produced indurated lesions within 48 h with lymphoid and plasmacytoid infiltration, edema, and extravasation of erythrocytes. We conclude that passive immunization may not confer a vaccine effect in this model and that active vaccination with a pilus preparation induces a delayed-type hypersensitivity skin test response and confers protection through cell-mediated immunity seen as an amplified lymphocytic infiltrate and accelerated maturation of the T-lymphocyte response. PMID:8613391

Evaluation of rapid progressors in HIV infection as an extreme phenotype.

PubMed

Olson, Ashley D; Guiguet, Marguerite; Zangerle, Robert; Gill, John; Perez-Hoyos, Santiago; Lodi, Sara; Ghosn, Jade; Dorrucci, Maria; Johnson, Anne; Sannes, Mette; Moreno, Santiago; Porter, Kholoud

2014-09-01

Rapid CD4 cell loss represents an HIV phenotype used to identify causal variants of accelerated disease progression. The optimal rate and threshold for identifying this extreme phenotype in recently infected individuals is unclear. Using a cohort of patients with known dates of HIV-1 seroconversion (SC), CASCADE (Concerted Action on SeroConversion on AIDS and Death in Europe), we identified proportions experiencing nadir CD4 cell levels within 1 year of SC, and assessed their mean AIDS-free survival time at 10-year follow-up and hazard of AIDS/death, compared with those whose CD4 remained >500 cells per cubic millimeter. Follow-up was censored at December 31, 1996 to avoid bias due to combination antiretroviral therapy initiation. Of 4876 individuals, 2.8%, 7.3%, and 24.9% experienced ≥1 CD4 <100, 200, and 350 cells per cubic millimeter, respectively, within 1 year of SC. Minimum CD4 levels of 30, 166, 231, and 506 cells per cubic millimeter were experienced during this period by 1%, 5%, 10%, and 50% of individuals, respectively. Mean (95% confidence interval) AIDS-free survival at 10 years follow-up was 2.9 (2.3 to 3.6), 5.5 (5.0 to 6.1), 6.7 (6.5 to 7.0), 7.4 (7.2 to 7.6), and 8.1 (7.9 to 8.3), for those with minimum counts ≤100, 100-200, 200-350, 350-500, >500 cells per cubic millimeter, respectively. Using counts of >500 cells per cubic millimeter as reference, the hazard ratios (95% confidence interval) of AIDS/death were 15.0 (11.9 to 18.9), 3.6 (2.9 to 4.5), 2.1 (1.8 to 2.4), and 1.5 (1.3 to 1.7), respectively. The hazard ratio increased to 37.5 (26.5 to 53.1) when a minimum CD4 count <100 was confirmed within 1 year of SC. At least 1 CD4 ≤100 cells per cubic millimeter within the first year of SC identifies a rare group of individuals at high risk of disease progression and could form the basis for defining the rapid progressor phenotype.

Comfort Contours: Inter-Axis Equivalence

NASA Astrophysics Data System (ADS)

Griefahn, B.; Bröde, P.

1997-07-01

Inter-axis equivalence for sinusoidal vibrations as stipulated by ISO/DIS 2631 for seated persons was studied by adjusting the acceleration of a horizontal sinusoidal test vibration (x∨y) until it caused equal sensation as a vertical sinusoidal reference motion of the same frequency. The reference vibrations consisted of sine waves ranging from 1·6 to 12·5Hz and were presented with three weighted accelerations ofazw=0·3, 0·6 and 1·2ms-2r.m.s. (reference contours). 26 subjects (15 men, 11 women, 20-55yrs, 153-187cm) participated in the respective experiments. Based on the three reference contours, predicted values for horizontal motions were calculated by using the weighting factors provided in ISO/DIS 2631. The International standard was confirmed insofar as the shape of the contours determined for horizontal motions was independent from vibration magnitudes as sensitivity to fore-and-aft and to lateral motions was similar. However, the accelerations adjusted for horizontal vibrations were considerably lower than predicted, suggesting that the weighing factors provided in ISO/DIS 2631 need to be corrected.

Subdivision design and stewardship affect bird and mammal use of conservation developments.

PubMed

Farr, Cooper M; Pejchar, Liba; Reed, Sarah E

2017-06-01

Developing effective tools for conservation on private lands is increasingly important for global biodiversity conservation; private lands are located in more productive and biologically diverse areas, and they face accelerated rates of land conversion. One strategy is conservation development (CD) subdivisions, which cluster houses in a small portion of a property and preserve the remaining land as protected open space. Despite widespread use, the characteristics that make CD more or less effective at achieving biodiversity conservation are not well understood. We investigated CD's ability to successfully protect animal populations by examining bird and mammal occurrences in 14 CD subdivisions and four undeveloped areas (range: 14-432 ha) in northern Colorado, USA. Using point count and camera trap data in an occupancy modeling framework, we evaluated the relative importance of nine subdivision design factors (e.g., housing density, proportion of CD protected) and 14 stewardship factors (e.g., presence of livestock, percent native vegetation cover) in influencing the overall community composition and the probability of use by 16 birds and six mammals. We found that habitat use by 75% of birds and 83% of mammals was associated with design characteristics that maximized the natural or undisturbed land area both within and near the development (e.g., proportion of CD protected, total area of protected open space, proportion of natural land cover in the surrounding landscape). These factors were also associated with an increasing dominance of human-sensitive bird species, larger-bodied mammals, and mammals with larger home ranges. Habitat use by birds was also influenced by local land use composition and quality, and use by several bird and mammal species decreased with increased localized disturbances. We found few differences in habitat use between sampling sites in undeveloped areas and in CD subdivisions. These similarities indicate that, if CDs are large enough or located within a matrix of undeveloped land, they can provide habitat that supports similar use patterns as protected areas without housing development. By incorporating characteristics that promote the persistence of sensitive birds and mammals on private lands, CDs have potential to preserve native biodiversity in areas threatened by expanding residential development. © 2017 by the Ecological Society of America.

The apoptotic members CD95, BclxL, and Bcl-2 cooperate to promote cell migration by inducing Ca2+ flux from the endoplasmic reticulum to mitochondria

PubMed Central

Fouqué, A; Lepvrier, E; Debure, L; Gouriou, Y; Malleter, M; Delcroix, V; Ovize, M; Ducret, T; Li, C; Hammadi, M; Vacher, P; Legembre, P

2016-01-01

Metalloprotease-processed CD95L (cl-CD95L) is a soluble cytokine that implements a PI3K/Ca2+ signaling pathway in triple-negative breast cancer (TNBC) cells. Accordingly, high levels of cl-CD95L in TNBC women correlate with poor prognosis, and administration of this ligand in an orthotopic xenograft mouse model accelerates the metastatic dissemination of TNBC cells. The molecular mechanism underlying CD95-mediated cell migration remains unknown. Here, we present genetic and pharmacologic evidence that the anti-apoptotic molecules BclxL and Bcl-2 and the pro-apoptotic factors BAD and BID cooperate to promote migration of TNBC cells stimulated with cl-CD95L. BclxL was distributed in both endoplasmic reticulum (ER) and mitochondrion membranes. The mitochondrion-localized isoform promoted cell migration by interacting with voltage-dependent anion channel 1 to orchestrate Ca2+ transfer from the ER to mitochondria in a BH3-dependent manner. Mitochondrial Ca2+ uniporter contributed to this flux, which favored ATP production and cell migration. In conclusion, this study reveals a novel molecular mechanism controlled by BclxL to promote cancer cell migration and supports the use of BH3 mimetics as therapeutic options not only to kill tumor cells but also to prevent metastatic dissemination in TNBCs. PMID:27367565

Cadmium sulfide thin films growth by chemical bath deposition

NASA Astrophysics Data System (ADS)

Hariech, S.; Aida, M. S.; Bougdira, J.; Belmahi, M.; Medjahdi, G.; Genève, D.; Attaf, N.; Rinnert, H.

2018-03-01

Cadmium sulfide (CdS) thin films have been prepared by a simple technique such as chemical bath deposition (CBD). A set of samples CdS were deposited on glass substrates by varying the bath temperature from 55 to 75 °C at fixed deposition time (25 min) in order to investigate the effect of deposition temperature on CdS films physical properties. The determination of growth activation energy suggests that at low temperature CdS film growth is governed by the release of Cd2+ ions in the solution. The structural characterization indicated that the CdS films structure is cubic or hexagonal with preferential orientation along the direction (111) or (002), respectively. The optical characterization indicated that the films have a fairly high transparency, which varies between 55% and 80% in the visible range of the optical spectrum, the refractive index varies from 1.85 to 2.5 and the optical gap value of which can reach 2.2 eV. It can be suggested that these properties make these films perfectly suitable for their use as window film in thin films based solar cells.

[Evolution of paroxysmal nocturnal hemoglobinuria clone during an hemolytic crisis in a patient with aplastic anemia. Flow cytometry study].

PubMed

Canalejo, K; Galassi, N; Riera, N; Bengió, R; Aixalá, M

2001-01-01

The expansion of paroxysmal nocturnal hemoglobinuria (PHN) clone was evaluated in a patient with aplastic anemia (AA) of 18 years of evolution during an hemolytic crisis. On day 0, Ham and Sucrosa tests were positive and hematological parameters were altered. Low hemoglobin (Hb) levels and erythrocyte and leukocyte counts were found and continued decreasing on days 7 and 24 (last day of study). High LDH levels, indirect bilirubin and reticulocyte counts were detected throughout. We evaluated CD55 and CD59 on erythrocytes by flow cytometry. Our results showed low CD55 expression with respect to the normal pattern. Since day 0, CD59 staining detected two red cell populations: PNH I (48%), cells with positive fluorescence similar to normal and PNH III (52%), negative cells (PNH clone). These negative cells increased, reaching 70% on day 24. Other membrane anchored leukocyte proteins were also absent (CD14) or decreased (CD16). We found a good correlation between clinical observations, evolution of the laboratory values and expansion of the PNH clone.

Profound CD4+/CCR5+ T cell expansion is induced by CD8+ lymphocyte depletion but does not account for accelerated SIV pathogenesis.

PubMed

Okoye, Afam; Park, Haesun; Rohankhedkar, Mukta; Coyne-Johnson, Lia; Lum, Richard; Walker, Joshua M; Planer, Shannon L; Legasse, Alfred W; Sylwester, Andrew W; Piatak, Michael; Lifson, Jeffrey D; Sodora, Donald L; Villinger, Francois; Axthelm, Michael K; Schmitz, Joern E; Picker, Louis J

2009-07-06

Depletion of CD8(+) lymphocytes during acute simian immunodeficiency virus (SIV) infection of rhesus macaques (RMs) results in irreversible prolongation of peak-level viral replication and rapid disease progression, consistent with a major role for CD8(+) lymphocytes in determining postacute-phase viral replication set points. However, we report that CD8(+) lymphocyte depletion is also associated with a dramatic induction of proliferation among CD4(+) effector memory T (T(EM)) cells and, to a lesser extent, transitional memory T (T(TrM)) cells, raising the question of whether an increased availability of optimal (activated/proliferating), CD4(+)/CCR5(+) SIV "target" cells contributes to this accelerated pathogenesis. In keeping with this, depletion of CD8(+) lymphocytes in SIV(-) RMs led to a sustained increase in the number of potential CD4(+) SIV targets, whereas such depletion in acute SIV infection led to increased target cell consumption. However, we found that the excess CD4(+) T(EM) cell proliferation of CD8(+) lymphocyte-depleted, acutely SIV-infected RMs was completely inhibited by interleukin (IL)-15 neutralization, and that this inhibition did not abrogate the rapidly progressive infection in these RMs. Moreover, although administration of IL-15 during acute infection induced robust CD4(+) T(EM) and T(TrM) cell proliferation, it did not recapitulate the viral dynamics of CD8(+) lymphocyte depletion. These data suggest that CD8(+) lymphocyte function has a larger impact on the outcome of acute SIV infection than the number and/or activation status of target cells available for infection and viral production.

Transient CD15-positive endothelial phenotype in the human placenta correlates with physiological and pathological fetoplacental immaturity.

PubMed

Seidmann, L; Suhan, T; Unger, R; Gerein, V; Kirkpatrick, C J

2014-09-01

Placental growth and villous maturation are critical parameters of placental function at the end of pregnancy. A failure in these processes leads to the development of placental dysfunction, as well as fetal and neonatal mortality and morbidity. The aim of the study was to determine the relevant diagnostic markers associated with pathological placental development. Forty tissue samples from normal placentas of different gestational age and 68 pathological term placentas with defective villous maturation (GDM, idiopathic IUFD, preeclamsia, HELLP syndrome) comprised the comparative immunohistochemical study (CD15, CD45 and CD34). Positive immunohistochemical reactions were quantitatively assessed in the chorionic plate and vessels of the villi of different histological type. Physiologically immature placentas of the first and second trimester and pathologically immature term placentas were characterized by marked endothelial CD15-immunostaining. A significant loss of CD15-positive endothelium of the placentas was associated with a physiological and accelerated villous maturity. A spatio-temporal correlation was shown for CD15+ endothelial cells (ECs) and the number of CD45+ stromal cells (SCs). A negative temporal correlation was shown for CD15+ ECs and CD15+ myelomonocytes in the fetal blood. CD34 expression in the ECs was stable during the pregnancy. A correlation between a transient CD15-positive endothelial phenotype and a physiological and pathological fetoplacental immaturity was demonstrated. Physiological and accelerated placental maturation was accompanied by a significant disappearance of CD15-positive endothelium. We propose that "immature" CD15+ endothelium is an important diagnostic marker of the physiological and pathological fetoplacental immaturity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Comparison of DNA aneuploidy, chromosome 1 abnormalities, MYCN amplification and CD44 expression as prognostic factors in neuroblastoma.

PubMed

Christiansen, H; Sahin, K; Berthold, F; Hero, B; Terpe, H J; Lampert, F

1995-01-01

A comparison of the prognostic impact of five molecular variables in a large series was made, including tests of their nonrandom association and multivariate analysis. Molecular data were available for 377 patients and MYCN amplification, cytogenetic chromosome 1p deletion, loss of chromosome 1p heterozygosity, DNA ploidy and CD44 expression were investigated. Their interdependence and influence on event-free survival was tested uni- and multivariately using Pearson's chi 2-test, Kaplan-Meier estimates, log rank tests and the Cox's regression model. MYCN amplification was present in 18% (58/322) of cases and predicted poorer prognosis in localised (P < 0.001), metastatic (P = 0.002) and even 4S (P = 0.040) disease. CD44 expression was found in 86% (127/148) of cases, and was a marker for favourable outcome in patients with neuroblastoma stages 1-3 (P = 0.003) and 4 (P = 0.017). Chromosome 1p deletion was cytogenetically detected in 51% (28/55), and indicated reduced event-free survival in localised neuroblastoma (P = 0.020). DNA ploidy and loss of heterozygosity on chromosome 1p were of less prognostic value. Most factors of prognostic significance were associated with each other. By multivariate analysis, MYCN was selected as the only relevant factor. Risk estimation of high discriminating power is, therefore, possible for patients with localised and metastatic neuroblastoma using stage and MYCN.

T cell-depleted splenocytes from mice pre-immunized with neuroantigen in incomplete Freund's adjuvant involved in protection from experimental autoimmune encephalomyelitis.

PubMed

Zheng, Hui; Zhang, Han; Liu, Feng; Qi, Yuanyuan; Jiang, Hong

2014-01-01

Mice immunized with neuroantigens in incomplete Freund's adjuvant (IFA) are resistant to subsequent induction of experimental autoimmune encephalomyelitis (EAE). The mechanisms involved in this protection are complex. Studies on relevant CD4(+) or CD8(+) T cells, including effective and regulatory T cells, have been performed by others. In this work, the effects of CD4(-)-, CD8(-)- splenocytes on protection from EAE in C57BL/6 mice which were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG)35-55 in IFA were evaluated. We observed that MOG-reactive CD4(+) T cells failed to be activated and proliferate when CD4(-)-, CD8(-)- splenocytes from MOG/IFA-immunized mice were regarded as antigen-presenting cells (APC). It was shown that these APC expressed lower levels of major histocompatibility complex class II (MHC-II), CD80, and CD86 than naïve cells. In addition, CD4(-)-, CD8(-)- splenocytes from MOG/IFA-immunized mice showed significantly higher levels of IL-10 mRNA expression. When the immunized-mice were induced to develop EAE, these cells secreted significantly higher levels of IL-10 and produced lower levels of IL-6, leading to decreased secretion of IL-17 and IFN-γ from MOG-specific CD4(+) T cells. The transfer of CD4(-)-, CD8(-)- splenocytes from MOG/IFA-immunized mice was able to ameliorate the subsequent induction of EAE in recipient mice. Thus, MOG/IFA immunization can modulate CD4(-)-, CD8(-)- splenocytes by reducing the expression of antigen-presenting molecules and altering the levels of secreted cytokines. Our study reveals an additional mechanism involved in the protective effects of MOG/IFA pre-immunization in an EAE model. Copyright © 2013 Elsevier B.V. All rights reserved.

Effector/memory CD8+ T cells synergize with co-stimulation competent macrophages to trigger autoimmune peripheral neuropathy.

PubMed

Yang, Mu; Shi, Xiang Qun; Peyret, Corentin; Oladiran, Oladayo; Wu, Sonia; Chambon, Julien; Fournier, Sylvie; Zhang, Ji

2018-04-05

Autoimmune peripheral neuropathy (APN) such as Guillain Barre Syndrome (GBS) is a debilitating illness and sometimes life threatening. The molecular and cellular mechanisms remain elusive but exposure to environmental factors including viral/bacterial infection and injury is highly associated with disease incidence. We demonstrated previously that both male and female B7.2 (CD86) transgenic L31 and L31/CD4KO mice develop spontaneous APN. Here we further reveal that CD8 + T cells in these mice exhibit an effector/memory phenotype, which bears a resemblance to the CD8 + T cell response following persistent cytomegalovirus (CMV) infection in humans and mice, whilst CMV has been considered as one of the most relevant pathogens in APN development. These activated, peripheral myelin Ag specific CD8 + T cells are required for the disease initiation. While an injury to a peripheral nerve results in Wallerian degeneration in control littermates, the same injury accelerates the development of APN in other non-injured nerves of L31 mice which have a predisposed inflammatory background consisting of effector/memory CD8 + T (CD8 + T EM ) cells. However, CD8 + T EM cells alone are not sufficient. A certain threshold of B7.2 expression on nerve macrophages is an additional requisite. Our findings reveal that indeed, the synergism between CD8 + T EM cells and co-stimulation competent macrophages is crucial in inducing autoimmune-mediated peripheral neuropathy. The identification of decisive molecular/cellular players connecting environmental triggers and the occurrence of APN provides opportunities to prevent disease onset, reduce relapses and develop new therapeutic strategies. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Alloimmune responses and atherosclerotic disease after kidney transplantation.

PubMed

Ducloux, Didier; Courivaud, Cécile; Bamoulid, Jamal; Bisaccia, Vincent; Roubiou, Caroline; Crepin, Thomas; Gaugler, Béatrice; Laheurte, Caroline; Rebibou, Jean-Michel; Chalopin, Jean-Marc; Saas, Philippe

2015-01-01

Chronic exposure to exogenous antigens causes accumulation of proinflammatory CD57(+)CD28(-) hyperactivated CD8(+) T cells that may promote atherosclerosis. We hypothesized that persistent alloimmune responses may induce immune activation and contribute to posttransplant atherosclerosis. This hypothesis was tested in a single-center cohort of 577 kidney transplant patients. Propensity score analysis was performed to address potential confounding variables by indication. Immune exhaustion was studied in subcohort of 103 patients. Five hundred seventy-seven consecutive renal transplant recipients were included. Seventy-seven atherosclerotic events (AE) (12.3%) occurred during a mean follow-up of 7 years. The cumulative incidence of AE increased with the number of human leukocyte antigen (HLA) mismatches (18%, 10%, and 5% in patients with 5-6, 3-4, and 0-2 mismatches, respectively; P=0.012). Human leukocyte antigen mismatch number (hazards ratio, 1.35; 95% confidence interval, 1.10-1.66, for each supplementary mismatch; P=0.005) was an independent risk factor for AE. In the propensity score match analysis, having received a well-matched kidney conferred a reduced risk of AE (hazards ratio, 0.22; 95% confidence interval, 0.05-0.95; P=0.044). We observed a significant correlation between HLA mismatch numbers and circulating CD57(+)CD28(-) CD8(+) T cells (R=0.31; P=0.017). These CD8(+) T cells were more frequent in patients with more HLA mismatches (P<0.0001). Overall, our results suggest that chronic allogeneic stimulation participates to accelerated atherosclerosis observed after transplantation.

Physical reasons of emission transformation in infrared CdSeTe/ZnS quantum dots at bioconjugation

NASA Astrophysics Data System (ADS)

Torchynska, T. V.

2015-04-01

The core/shell CdSeTe/ZnS quantum dots (QDs) with emission at 780-800 nm (1.55-1.60 eV) have been studied by means of photoluminescence (PL) and Raman scattering methods in the nonconjugated state and after conjugation to different antibodies (Ab): (i) mouse monoclonal [8C9] human papilloma virus Ab, anti-HPV 16-E7 Ab, (ii) mouse monoclonal [C1P5] human papilloma virus HPV16 E6+HPV18 E6 Ab, and (iii) pseudo rabies virus (PRV) Ab. The transformations of PL and Raman scattering spectra of QDs, stimulated by conjugated antibodies, have been revealed and discussed. The energy band diagram of core/shell CdSeTe/ZnS QDs has been designed that helps to analyze the PL spectra and their transformations at the bioconjugation. It is shown that the core in CdSeTe/ZnS QDs is complex and including the type II quantum well. The last fact permits to explain the nature of infrared (IR) optical transitions (1.55-1.60 eV) and the high energy PL band (1.88-1.94 eV) in the nonconjugated and bioconjugated QDs. A set of physical reasons has been analyzed with the aim to explain the transformation of PL spectra in bioconjugated QDs. Finally it is shown that two factors are responsible for the PL spectrum transformation at bioconjugation to charged antibodies: (i) the change of energy band profile in QDs and (ii) the shift of QD energy levels in the strong quantum confinement case. The effect of PL spectrum transformation is useful for the study of QD bioconjugation to specific antibodies and can be a powerful technique for early medical diagnostics.

Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells

PubMed Central

Kobayashi, Hideki; Butler, Jason M.; O'Donnell, Rebekah; Kobayashi, Mariko; Ding, Bi-Sen; Bonner, Bryant; Chiu, Vi K.; Nolan, Daniel J.; Shido, Koji; Benjamin, Laura; Rafii, Shahin

2010-01-01

Endothelial cells establish an instructive vascular niche that reconstitutes haematopoietic stem and progenitor cells (HSPCs) through release of specific paracrine growth factors, known as angiocrine factors. However, the mechanism by which endothelial cells balance the rate of proliferation and lineage-specific differentiation of HSPCs is unknown. Here, we demonstrate that Akt activation in endothelial cells, through recruitment of mTOR, but not the FoxO pathway, upregulates specific angiocrine factors that support expansion of CD34−Flt3− KLS HSPCs with long-term haematopoietic stem cell (LT-HSC) repopulation capacity. Conversely, co-activation of Akt-stimulated endothelial cells with p42/44 MAPK shifts the balance towards maintenance and differentiation of the HSPCs. Selective activation of Akt1 in the endothelial cells of adult mice increased the number of colony forming units in the spleen and CD34−Flt3− KLS HSPCs with LT-HSC activity in the bone marrow, accelerating haematopoietic recovery. Therefore, the activation state of endothelial cells modulates reconstitution of HSPCs through the upregulation of angiocrine factors, with Akt–mTOR-activated endothelial cells supporting the self-renewal of LT-HSCs and expansion of HSPCs, whereas MAPK co-activation favours maintenance and lineage-specific differentiation of HSPCs. PMID:20972423

Plasmacytoid dendritic cell and functional HIV Gag p55-specific T cells before treatment interruption can inform set-point plasma HIV viral load after treatment interruption in chronically suppressed HIV-1(+) patients.

PubMed

Papasavvas, Emmanouil; Foulkes, Andrea; Yin, Xiangfan; Joseph, Jocelin; Ross, Brian; Azzoni, Livio; Kostman, Jay R; Mounzer, Karam; Shull, Jane; Montaner, Luis J

2015-07-01

The identification of immune correlates of HIV control is important for the design of immunotherapies that could support cure or antiretroviral therapy (ART) intensification-related strategies. ART interruptions may facilitate this task through exposure of an ART partially reconstituted immune system to endogenous virus. We investigated the relationship between set-point plasma HIV viral load (VL) during an ART interruption and innate/adaptive parameters before or after interruption. Dendritic cell (DC), natural killer (NK) cell and HIV Gag p55-specific T-cell functional responses were measured in paired cryopreserved peripheral blood mononuclear cells obtained at the beginning (on ART) and at set-point of an open-ended interruption from 31 ART-suppressed chronically HIV-1(+) patients. Spearman correlation and linear regression modeling were used. Frequencies of plasmacytoid DC (pDC), and HIV Gag p55-specific CD3(+)  CD4(-)  perforin(+)  IFN-γ(+) cells at the beginning of interruption associated negatively with set-point plasma VL. Inclusion of both variables with interaction into a model resulted in the best fit (adjusted R(2)  = 0·6874). Frequencies of pDC or HIV Gag p55-specific CD3(+)  CD4(-)  CSFE(lo)  CD107a(+) cells at set-point associated negatively with set-point plasma VL. The dual contribution of pDC and anti-HIV T-cell responses to viral control, supported by our models, suggests that these variables may serve as immune correlates of viral control and could be integrated in cure or ART-intensification strategies. © 2015 John Wiley & Sons Ltd.

Determination of small field synthetic single-crystal diamond detector correction factors for CyberKnife, Leksell Gamma Knife Perfexion and linear accelerator.

PubMed

Veselsky, T; Novotny, J; Pastykova, V; Koniarova, I

2017-12-01

The aim of this study was to determine small field correction factors for a synthetic single-crystal diamond detector (PTW microDiamond) for routine use in clinical dosimetric measurements. Correction factors following small field Alfonso formalism were calculated by comparison of PTW microDiamond measured ratio M Qclin fclin /M Qmsr fmsr with Monte Carlo (MC) based field output factors Ω Qclin,Qmsr fclin,fmsr determined using Dosimetry Diode E or with MC simulation itself. Diode measurements were used for the CyberKnife and Varian Clinac 2100C/D linear accelerator. PTW microDiamond correction factors for Leksell Gamma Knife (LGK) were derived using MC simulated reference values from the manufacturer. PTW microDiamond correction factors for CyberKnife field sizes 25-5 mm were mostly smaller than 1% (except for 2.9% for 5 mm Iris field and 1.4% for 7.5 mm fixed cone field). The correction of 0.1% and 2.0% for 8 mm and 4 mm collimators, respectively, needed to be applied to PTW microDiamond measurements for LGK Perfexion. Finally, PTW microDiamond M Qclin fclin /M Qmsr fmsr for the linear accelerator varied from MC corrected Dosimetry Diode data by less than 0.5% (except for 1 × 1 cm 2 field size with 1.3% deviation). Regarding low resulting correction factor values, the PTW microDiamond detector may be considered an almost ideal tool for relative small field dosimetry in a large variety of stereotactic and radiosurgery treatment devices. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Increased red cell turnover in a line of CD22-deficient mice is caused by Gpi1c: a model for hereditary haemolytic anaemia.

PubMed

Walker, Jennifer A; Hall, Andrew M; Kotsopoulou, Ekaterini; Espeli, Marion; Nitschke, Lars; Barker, Robert N; Lyons, Paul A; Smith, Kenneth G C

2012-12-01

CD22, an inhibitory co-receptor of the BCR, has been identified as a potential candidate gene for the development of autoimmune haemolytic anaemia in mice. In this study, we have examined Cd22(tm1Msn) CD22-deficient mice and identified an increase in RBC turnover and stress erythropoiesis, which might be consistent with haemolysis. We then, however, eliminated CD22 deficiency as the cause of accelerated RBC turnover and established that enhanced RBC turnover occurs independently of B cells and anti-RBC autoanti-bodies. Accelerated RBC turnover in this particular strain of CD22-deficient mice is red cell intrinsic and appears to be the consequence of a defective allele of glucose phosphate isomerase, Gpi1(c). This form of Gpi1 was originally derived from wild mice and results in a substantial reduction in enzyme activity. We have identified the polymorphism that causes impaired catalytic activity in the Gpi1(c) allele, and biochemically confirmed an approximate 75% reduction of GPI1 activity in Cd22(-/-) RBCs. The Cd22(-/-).Gpi1(c) congenic mouse provides a novel animal model of GPI1-deficiency, which is one of the most common causes of chronic non-spherocytic haemolytic anaemia in humans. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Infantile hemangioma-like vascular lesion in a 26-year-old woman after abortion.

PubMed

Lu, Yang; Wang, Shu Jun; Li, Xin; Hu, Li; Zhang, Wen Jie; Li, Wei

2014-01-01

A 26-year-old woman (G2P1A1) presented with a 5-week history of multiple red marks on her body after a therapeutic abortion. A physical examination found 15 palpable red marks on her head, neck, chest, arms and legs. Proliferating endothelial cells, which expressed CD31, CD34, von Willebrand factor, but not Glut-1 and merosin, were observed in the lesional area by histopathological analyses. Histocompatibility antigen typing of 2 lesions was identical to a sample from peripheral blood. Accelerated regression was observed in 2 lesions treated by intralesional injection of betamethasone, while spontaneous regression was observed within 9 months in the remaining lesions without any treatment. Rapid growth, spontaneous regression and histological analyses in this case support the diagnosis of 'infantile hemangioma-like vascular lesion'.

Chronic alcohol increases CD8+ T-cell immunosenescence in simian immunodeficiency virus-infected rhesus macaques.

PubMed

Katz, Paige S; Siggins, Robert W; Porretta, Connie; Armstrong, Megan L; Zea, Arnold H; Mercante, Donald E; Parsons, Christopher; Veazey, Ronald S; Bagby, Gregory J; Nelson, Steve; Molina, Patricia E; Welsh, David A

2015-12-01

Activated CD8+ T-cells correlate with viral load and may foretell antiretroviral therapy (ART) failure. HIV infection has been suggested to accelerate immunosenescence through chronic persistent inflammation. Alcohol-use disorders (AUD) are prevalent in persons living with HIV/AIDS (PLWHA). We tested the hypothesis that hazardous alcohol consumption accelerates immune activation and immunosenescence. Immune activation and immunosenescence were examined in CD8+ T lymphocytes (CD3+CD4-CD8+) isolated from intestinal biopsies, axillary lymph nodes, and peripheral blood mononuclear cells (PBMCs) of chronic binge alcohol (CBA)-consuming simian immunodeficiency virus (SIV)-infected male rhesus macaques with and without antiretroviral therapy (ART; CBA/ART+, CBA/ART-) and in PBMCs isolated from a cohort of PLWHA. Polychromatic flow cytometry was used to phenotype cells isolated from intestinal biopsies, lymph nodes, and peripheral blood from rhesus macaques and PLWHA. The Alcohol Use Disorders Identification Test (AUDIT) identified hazardous alcohol drinking in PLWHA. Viral load was determined by RT-qPCR and telomere length was measured using qPCR. PBMC CD8+ T-cell activation (CD38+HLA-DR+) and immunosenescence (CD28-) were increased over baseline levels (857% ± 334, p < 0.05; 398% ± 80, p < 0.05, respectively) only in CBA animals not receiving ART. Viral load correlated with CD8+ T-cell immunosenescence in macaque PBMCs (r(s) = 0.49, p = 0.02). Activated immunosenescent T-cell (CD8+CD38+CD28-) frequencies in PBMCs from PLWHA significantly correlated with AUDIT scores (r(s) = 0.75, p = 0.001), while no correlation was observed with CD4+ T-cell and AUDIT scores (r(s) = -0.24, p = 0.38). Activated immunosenescent T-cells had shorter telomeres than CD8+ T-cells (CD8+CD28+) from PLWHA. Our results suggest that CBA and AUD augment immune activation and immunosenescence in SIV-infected macaques and PLWHA. Copyright © 2015 Elsevier Inc. All rights reserved.

The Dosepix detector—an energy-resolving photon-counting pixel detector for spectrometric measurements

NASA Astrophysics Data System (ADS)

Zang, A.; Anton, G.; Ballabriga, R.; Bisello, F.; Campbell, M.; Celi, J. C.; Fauler, A.; Fiederle, M.; Jensch, M.; Kochanski, N.; Llopart, X.; Michel, N.; Mollenhauer, U.; Ritter, I.; Tennert, F.; Wölfel, S.; Wong, W.; Michel, T.

2015-04-01

The Dosepix detector is a hybrid photon-counting pixel detector based on ideas of the Medipix and Timepix detector family. 1 mm thick cadmium telluride and 300 μm thick silicon were used as sensor material. The pixel matrix of the Dosepix consists of 16 x 16 square pixels with 12 rows of (200 μm)2 and 4 rows of (55 μm)2 sensitive area for the silicon sensor layer and 16 rows of pixels with 220 μm pixel pitch for CdTe. Besides digital energy integration and photon-counting mode, a novel concept of energy binning is included in the pixel electronics, allowing energy-resolved measurements in 16 energy bins within one acquisition. The possibilities of this detector concept range from applications in personal dosimetry and energy-resolved imaging to quality assurance of medical X-ray sources by analysis of the emitted photon spectrum. In this contribution the Dosepix detector, its response to X-rays as well as spectrum measurements with Si and CdTe sensor layer are presented. Furthermore, a first evaluation was carried out to use the Dosepix detector as a kVp-meter, that means to determine the applied acceleration voltage from measured X-ray tubes spectra.

Association Between Cd Exposure and Risk of Prostate Cancer: A PRISMA-Compliant Systematic Review and Meta-Analysis.

PubMed

Ju-Kun, Song; Yuan, Dong-Bo; Rao, Hao-Fu; Chen, Tian-Fei; Luan, Bo-Shi; Xu, Xiao-Ming; Jiang, Fu-Neng; Zhong, Wei-De; Zhu, Jian-Guo

2016-02-01

Several observational studies on the association between Cd exposure and risk of prostate cancer have yielded inconsistent results. To address this issue, we conducted a meta-analysis to evaluate the correlation between Cd exposure and risk of prostate cancer.Relevant studies in PubMed and Embase databases were retrieved until October 2015. We compared the highest and lowest meta-analyses to quantitatively evaluate the relationship between Cd exposure and risk of prostate cancer. Summary estimates were obtained using a random-effects model.In the general population, high Cd exposure was not associated with increased prostate cancer (OR 1.21; 95% CI 0.91-1.64), whereas the combined standardized mortality ratio of the association between Cd exposure and risk of prostate cancer was 1.66 (95% CI 1.10-2.50) in populations exposed to occupational Cd. In addition, high D-Cd intake (OR 1.07; 95% CI 0.96-1.20) and U-Cd concentration (OR 0.86; 95% CI 0.48-1.55) among the general population was not related to the increased risk of prostate cancer. In the dose analysis, the summary relative risk was 1.07 (95% CI 0.73-1.57) for each 0.5 μg/g creatinine increase in U-Cd and 1.02 (95% CI 0.99-1.06) for each 10 μg/day increase of dietary Cd intake. However, compared with nonoccupational exposure, high occupational Cd exposure may be associated with the increased risk of prostate cancer.This meta-analysis suggests high Cd exposure as a risk factor for prostate cancer in occupational rather than nonoccupational populations. However, these results should be carefully interpreted because of the significant heterogeneity among studies. Additional large-scale and high-quality prospective studies are needed to confirm the association between Cd exposure and risk of prostate cancer.

Association Between Cd Exposure and Risk of Prostate Cancer

PubMed Central

Ju-Kun, Song; Yuan, Dong-Bo; Rao, Hao-Fu; Chen, Tian-Fei; Luan, Bo-Shi; Xu, Xiao-Ming; Jiang, Fu-Neng; Zhong, Wei-De; Zhu, Jian-Guo

2016-01-01

Abstract Several observational studies on the association between Cd exposure and risk of prostate cancer have yielded inconsistent results. To address this issue, we conducted a meta-analysis to evaluate the correlation between Cd exposure and risk of prostate cancer. Relevant studies in PubMed and Embase databases were retrieved until October 2015. We compared the highest and lowest meta-analyses to quantitatively evaluate the relationship between Cd exposure and risk of prostate cancer. Summary estimates were obtained using a random-effects model. In the general population, high Cd exposure was not associated with increased prostate cancer (OR 1.21; 95% CI 0.91–1.64), whereas the combined standardized mortality ratio of the association between Cd exposure and risk of prostate cancer was 1.66 (95% CI 1.10–2.50) in populations exposed to occupational Cd. In addition, high D-Cd intake (OR 1.07; 95% CI 0.96–1.20) and U-Cd concentration (OR 0.86; 95% CI 0.48–1.55) among the general population was not related to the increased risk of prostate cancer. In the dose analysis, the summary relative risk was 1.07 (95% CI 0.73–1.57) for each 0.5 μg/g creatinine increase in U-Cd and 1.02 (95% CI 0.99–1.06) for each 10 μg/day increase of dietary Cd intake. However, compared with nonoccupational exposure, high occupational Cd exposure may be associated with the increased risk of prostate cancer. This meta-analysis suggests high Cd exposure as a risk factor for prostate cancer in occupational rather than nonoccupational populations. However, these results should be carefully interpreted because of the significant heterogeneity among studies. Additional large-scale and high-quality prospective studies are needed to confirm the association between Cd exposure and risk of prostate cancer. PMID:26871808

Measurements of 55Fe activity in activated steel samples with GEMPix

NASA Astrophysics Data System (ADS)

Curioni, A.; Dinar, N.; La Torre, F. P.; Leidner, J.; Murtas, F.; Puddu, S.; Silari, M.

2017-03-01

In this paper we present a novel method, based on the recently developed GEMPix detector, to measure the 55Fe content in samples of metallic material activated during operation of CERN accelerators and experimental facilities. The GEMPix, a gas detector with highly pixelated read-out, has been obtained by coupling a triple Gas Electron Multiplier (GEM) to a quad Timepix ASIC. Sample preparation, measurements performed on 45 samples and data analysis are described. The calibration factor (counts per second per unit specific activity) has been obtained via measurements of the 55Fe activity determined by radiochemical analysis of the same samples. Detection limit and sensitivity to the current Swiss exemption limit are calculated. Comparison with radiochemical analysis shows inconsistency for the sensitivity for only two samples, most likely due to underestimated uncertainties of the GEMPix analysis. An operative test phase of this technique is already planned at CERN.

Analysis of adenovirus-induced immunity to infection with Listeria monocytogenes: Fading protection coincides with declining CD8 T cell numbers and phenotypic changes.

PubMed

Jahn, Marie Louise; Steffensen, Maria Abildgaard; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

2018-05-11

Defining correlates of T cell mediated protection is important in order to accelerate the development of efficient T cell based vaccines conferring long-term immunity. Extensive studies have provided important insight regarding the characteristics and functional properties of the effector and memory CD8 T cells induced by viral vector based vaccines. However, long-term protection has been difficult to achieve with T cell inducing vaccines, and the determinants underlying this loss in protection over time are still not fully defined. In this study we analyzed different parameters of the CD8 T cell response as a function of time after vaccination with a human serotype 5 adenovector expressing the glycoprotein (GP) of LCMV tethered to the MHC class II-associated invariant chain. Using this vector we have previously found that CD8 T cells mediate protection from challenge with GP-expressing Listeria monocytogenes at 60 days post vaccination, but only little protection after further 60 days, and we now confirm this observation. A comparison of vaccine-primed CD8 T cells early and late after vaccination revealed a minor decline in the overall numbers of antigen specific memory CD8 T cells during this interval. More importantly, we also observed phenotypic changes over time with a distinct decline in the frequency and number of KLRG1 + CD8 T cells, and, notably, adoptive transfer studies confirmed that memory CD8 T cells expressing KLRG1 are central to protection from systemic L. monocytogenes infection. Together these findings imply that multiple factors including changes in memory T cell numbers and phenotypic composition over time influence the longevity of CD8 T-cell mediated protection. Copyright © 2018 Elsevier Ltd. All rights reserved.

Temperature enhances the affinity of soil alkaline phosphatase to Cd.

PubMed

Tan, Xiangping; Machmuller, Megan B; Wang, Ziquan; Li, Xudong; He, Wenxiang; Cotrufo, M Francesca; Shen, Weijun

2018-04-01

Both elevated temperature and heavy metal contamination can have profound effects on microbial function and soil biogeochemical cycling. However, the interactive effects of heavy metal toxicity and temperature on microbial activity have been poorly understood. The aim of this study was to quantify the effect of temperature and cadmium (Cd) toxicity on alkaline phosphatase (ALP) produced by microbes to acquire phosphorus. To determine whether these effects were dependent on soil properties, we utilized 11 soil types from cropland throughout China. We measured ALP activities and kinetics across a temperature (17, 27, 37, and 47 °C) and Cd concentration gradient (0, 0.6, 5, 25, 50, 100, 200, 300, and 500 mg kg -1 ). We found that the half saturation constant (K m ) and the velocity constant (k) of ALP increased nonlinearly with temperature across all soil types. However, the maximum reaction velocity (V max ) increased linearly with temperature. Regardless of soil type and temperature, Cd had a non-competitive inhibitory mechanism. Soil pH, TOC, and clay content were the major factors controlling the affinity of ALP for Cd (K i ). The ecology dose (ED 50 ) for V max and k, and K i were negatively related to temperature, indicating that the toxicity of Cd on ALP is temperature-dependent. Additionally, higher temperatures led to more inhibition of Cd on ALP activity in alkaline soils than that in acidic and neutral soils. Our results suggest that global warming might accelerate the deficiency of available phosphorus in Cd contaminated soils due to higher inhibition of Cd on ALP activity, particularly in alkaline soils. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased prevalence of psychopathology and maladaptive personality traits after long-term cure of Cushing's disease.

PubMed

Tiemensma, Jitske; Biermasz, Nienke R; Middelkoop, Huub A M; van der Mast, Roos C; Romijn, Johannes A; Pereira, Alberto M

2010-10-01

Psychopathology and maladaptive personality traits are often observed during the active phase of Cushing's disease (CD). We hypothesized that patients with long-term cure of CD show persistent psychopathology and maladaptive personality traits. Four questionnaires on frequently occurring psychopathology in somatic illnesses were used, including the Apathy Scale, Irritability Scale, Hospital Anxiety and Depression Scale, and Mood and Anxiety Symptoms Questionnaire short-form. Personality was assessed using the Dimensional Assessment of Personality Pathology short-form (DAPPs). We included 51 patients cured of CD (16% men, 53 ± 13 yr) and 51 matched controls. In addition, we included 55 patients treated for nonfunctioning pituitary macroadenomas (55% men, 62 ± 10 yr), and 55 matched controls. Mean duration of remission was 11 yr (range 1-32 yr). Compared with matched controls, patients cured from CD scored significantly worse on virtually all questionnaires. Compared with nonfunctioning pituitary macroadenoma patients, patients treated for CD scored worse on apathy (P < 0.001), irritability (P < 0.001), anxiety (P < 0.001), negative affect and lack of positive affect (P < 0.001 on both scales), somatic arousal (P < 0.001), and 11 of 18 subscales of the Dimensional Assessment of Personality Pathology short-form (P < 0.05). Patients with long-term cured CD show an increased prevalence of psychopathology and maladaptive personality traits. These observations suggest irreversible effects of previous glucocorticoid excess on the central nervous system rather than an effect of pituitary tumors and/or their treatment in general. This may also be of relevance for patients treated with high doses of exogenous glucocorticoids.

Identification of Smoking-Associated Differentially Methylated Regions Using Reduced Representation Bisulfite Sequencing and Cell type-Specific Enhancer Activation and Gene Expression.

PubMed

Wan, Ma; Bennett, Brian D; Pittman, Gary S; Campbell, Michelle R; Reynolds, Lindsay M; Porter, Devin K; Crowl, Christopher L; Wang, Xuting; Su, Dan; Englert, Neal A; Thompson, Isabel J; Liu, Yongmei; Bell, Douglas A

2018-04-27

Cigarette smoke is a causal factor in cancers and cardiovascular disease. Smoking-associated differentially methylated regions (SM-DMRs) have been observed in disease studies, but the causal link between altered DNA methylation and transcriptional change is obscure. Our objectives were to finely resolve SM-DMRs and to interrogate the mechanistic link between SM-DMRs and altered transcription of enhancer noncoding RNA (eRNA) and mRNA in human circulating monocytes. We integrated SM-DMRs identified by reduced representation bisulfite sequencing (RRBS) of circulating CD14+ monocyte DNA collected from two independent human studies [ n =38 from Clinical Research Unit (CRU) and n =55 from the Multi-Ethnic Study of Atherosclerosis (MESA), about half of whom were active smokers] with gene expression for protein-coding genes and noncoding RNAs measured by RT-PCR or RNA sequencing. Candidate SM-DMRs were compared with RRBS of purified CD4+ T cells, CD8+ T cells, CD15+ granulocytes, CD19+ B cells, and CD56+ NK cells ( n =19 females, CRU). DMRs were validated using pyrosequencing or bisulfite amplicon sequencing in up to 85 CRU volunteers, who also provided saliva DNA. RRBS identified monocyte SM-DMRs frequently located in putative gene regulatory regions. The most significant monocyte DMR occurred at a poised enhancer in the aryl-hydrocarbon receptor repressor gene ( AHRR ) and it was also detected in both granulocytes and saliva DNA. To our knowledge, we identify for the first time that SM-DMRs in or near AHRR , C5orf55-EXOC-AS , and SASH1 were associated with increased noncoding eRNA as well as mRNA in monocytes. Functionally, the AHRR SM-DMR appeared to up-regulate AHRR mRNA through activating the AHRR enhancer, as suggested by increased eRNA in the monocytes, but not granulocytes, from smokers compared with nonsmokers. Our findings suggest that AHRR SM-DMR up-regulates AHRR mRNA in a monocyte-specific manner by activating the AHRR enhancer. Cell type-specific activation of enhancers at SM-DMRs may represent a mechanism driving smoking-related disease. https://doi.org/10.1289/EHP2395.

Identification of a CD8 T cell that can independently mediate autoimmune diabetes development in the complete absence of CD4 T cell helper functions.

PubMed

Graser, R T; DiLorenzo, T P; Wang, F; Christianson, G J; Chapman, H D; Roopenian, D C; Nathenson, S G; Serreze, D V

2000-04-01

Previous work has indicated that an important component for the initiation of autoimmune insulin-dependent diabetes mellitus (IDDM) in the NOD mouse model entails MHC class I-restricted CD8 T cell responses against pancreatic beta cell Ags. However, unless previously activated in vitro, such CD8 T cells have previously been thought to require helper functions provided by MHC class II-restricted CD4 T cells to exert their full diabetogenic effects. In this study, we show that IDDM development is greatly accelerated in a stock of NOD mice expressing TCR transgenes derived from a MHC class I-restricted CD8 T cell clone (designated AI4) previously found to contribute to the earliest preclinical stages of pancreatic beta cell destruction. Importantly, these TCR transgenic NOD mice (designated NOD.AI4alphabeta Tg) continued to develop IDDM at a greatly accelerated rate when residual CD4 helper T cells were eliminated by introduction of the scid mutation or a functionally inactivated CD4 allele. In a previously described stock of NOD mice expressing TCR transgenes derived from another MHC class I-restricted beta cell autoreactive T cell clone, IDDM development was retarded by elimination of residual CD4 T cells. Hence, there is variability in the helper dependence of CD8 T cells contributing to the development of autoimmune IDDM. The AI4 clonotype represents the first CD8 T cell with a demonstrated ability to progress from a naive to functionally activated state and rapidly mediate autoimmune IDDM development in the complete absence of CD4 T cell helper functions.

Modulation of CD4(+) T cell-dependent specific cytotoxic CD8(+) T cells differentiation and proliferation by the timing of increase in the pathogen load.

PubMed

Tzelepis, Fanny; Persechini, Pedro M; Rodrigues, Mauricio M

2007-04-25

Following infection with viruses, bacteria or protozoan parasites, naïve antigen-specific CD8(+) T cells undergo a process of differentiation and proliferation to generate effector cells. Recent evidences suggest that the timing of generation of specific effector CD8(+) T cells varies widely according to different pathogens. We hypothesized that the timing of increase in the pathogen load could be a critical parameter governing this process. Using increasing doses of the protozoan parasite Trypanosoma cruzi to infect C57BL/6 mice, we observed a significant acceleration in the timing of parasitemia without an increase in mouse susceptibility. In contrast, in CD8 deficient mice, we observed an inverse relationship between the parasite inoculum and the timing of death. These results suggest that in normal mice CD8(+) T cells became protective earlier, following the accelerated development of parasitemia. The evaluation of specific cytotoxic responses in vivo to three distinct epitopes revealed that increasing the parasite inoculum hastened the expansion of specific CD8(+) cytotoxic T cells following infection. The differentiation and expansion of T. cruzi-specific CD8(+) cytotoxic T cells is in fact dependent on parasite multiplication, as radiation-attenuated parasites were unable to activate these cells. We also observed that, in contrast to most pathogens, the activation process of T. cruzi-specific CD8(+) cytotoxic T cells was dependent on MHC class II restricted CD4(+) T cells. Our results are compatible with our initial hypothesis that the timing of increase in the pathogen load can be a critical parameter governing the kinetics of CD4(+) T cell-dependent expansion of pathogen-specific CD8(+) cytotoxic T cells.

Soil biogeochemistry, plant physiology and phytoremediation of cadmium contaminated soils

USDA-ARS?s Scientific Manuscript database

Cadmium (Cd) loading in soil and the environment has been accelerated worldwide due to enhanced industrialization and intensified agricultural production, particularly in the developing countries. Soil Cd pollution, resulting from both anthropogenic and geogenic sources, has posed an increasing chal...

HTLV-1 bZIP factor protein targets the Rb/E2F-1 pathway to promote proliferation and apoptosis of primary CD4+ T cells

PubMed Central

Kawatsuki, A; Yasunaga, J-i; Mitobe, Y; Green, PL; Matsuoka, M

2016-01-01

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that induces a fatal T-cell malignancy, adult T-cell leukemia (ATL). Among several regulatory/accessory genes in HTLV-1, HTLV-1 bZIP factor (HBZ) is the only viral gene constitutively expressed in infected cells. Our previous study showed that HBZ functions in two different molecular forms, HBZ protein and HBZ RNA. In this study, we show that HBZ protein targets retinoblastoma protein (Rb), which is a critical tumor suppressor in many types of cancers. HBZ protein interacts with the Rb/E2F-1 complex and activates the transcription of E2F-target genes associated with cell cycle progression and apoptosis. Mouse primary CD4+ T cells transduced with HBZ show accelerated G1/S transition and apoptosis, and importantly, T cells from HBZ transgenic (HBZ-Tg) mice also demonstrate enhanced cell proliferation and apoptosis. To evaluate the functions of HBZ protein alone in vivo, we generated a new transgenic mouse strain that expresses HBZ mRNA altered by silent mutations but encoding intact protein. In these mice, the numbers of effector/memory and Foxp3+ T cells were increased, and genes associated with proliferation and apoptosis were upregulated. This study shows that HBZ protein promotes cell proliferation and apoptosis in primary CD4+ T cells through activation of the Rb/E2F pathway, and that HBZ protein also confers onto CD4+ T-cell immunophenotype similar to those of ATL cells, suggesting that HBZ protein has important roles in dysregulation of CD4+ T cells infected with HTLV-1. PMID:26804169

Cross-sectional, descriptive study of Chagas disease among citizens of Bolivian origin living in Munich, Germany

PubMed Central

Navarro, Miriam; Berens-Riha, Nicole; Hohnerlein, Stefan; Seiringer, Peter; von Saldern, Charlotte; Garcia, Sarah; Blasco-Hernández, Teresa; Navaza, Bárbara; Shock, Jonathan; Bretzel, Gisela; Hoelscher, Michael; Löscher, Thomas; Albajar-Viñas, Pedro; Pritsch, Michael

2017-01-01

Purpose Chagas disease (CD) has become a global health issue mainly due to migration. Germany lacks surveillance data and is home to a large Latin American immigrant population. Recognising that Bolivia is the country with the highest CD prevalence in Latin America, this cross-sectional, descriptive pilot study investigated CD and associated factors among citizens of Bolivian origin living in Munich, Germany. Methods Participants completed a questionnaire in order to collect socioeconomic and health-related data. In addition, serology was performed. In case of positive serological tests, PCR diagnostic and clinical staging together with disease management was initiated. Qualitative research was conducted to identify personal and community barriers as well as strategies to increase CD awareness among the population at risk. Results Between June 2013 and June 2014, 43 people from Bolivia (or descendants) were enrolled. A total of 9.3% (4/43), of whom two women were of childbearing age, tested seropositive (ELISA and IFAT), and one also by PCR. For 2/4 positive participants, clinical evaluation was performed and the indeterminate form of CD was diagnosed. Knowledge about CD symptoms and ways of transmission were completely absent among 55.8% (24/43, 2/4 with CD) and 30.2% (13/43, 1/4 with CD) of participants, respectively. A total of 27.9% (12/43, 0/4 with CD) of participants had donated blood prior to the study, whereas 62.8% (27/43, 3/4 with CD) were motivated to donate blood in the future. The qualitative research identified lack of knowledge as well as stigma and fears related to CD. Conclusions Despite the small number of participants, the prevalence of CD as well as the potential risk of non-vectorial transmission was alarming. Campaigns adapted for Latin American migrants as well as control strategies should be developed and put in place in order to prevent non-vectorial transmission and actively detect cases of CD in Germany. PMID:28093440

CD30 expression in malignant vascular tumors and its diagnostic and clinical implications: a study of 146 cases.

PubMed

Alimchandani, Meghna; Wang, Zeng-Feng; Miettinen, Markku

2014-01-01

Angiosarcoma (AS) is a rare malignant vascular tumor, whereas epithelioid hemangioendothelioma (EHE) is a vascular tumor of low-grade malignancy. CD30 is a member of the tumor necrosis factor receptor superfamily, member 8 (TNFRSF8). Although the expression of CD30 is most commonly associated with lymphoid malignancies or germ cell tumors, occasional ASs have been reported as CD30 positive. However, there are limited data to evaluate its role definitively in malignant vascular tumors. In this study, we evaluated 91 ASs, 30 EHEs from various sites, and 25 Kaposi sarcomas. Overall, CD30 was expressed in 31/91 cases (34%) of AS, in 7/30 cases (30%) of EHE, but in none of the Kaposi sarcomas. CD30 was expressed in a membranous staining pattern and positivity in tumor cells varied from focal to diffuse. The positive ASs included vasoformative more differentiated tumors and also solid, undifferentiated, lymphoma-like examples, one of which was classified as lymphoma before the era of immunohistochemistry. The CD30 expression was seen in >50% of tumor cells in a majority of ASs but only in 7% of EHEs. None of the 55 ASs studied were immunohistochemically positive for TIA-1 or Granzyme B, antigens used as more specific markers for anaplastic large-cell lymphoma. Compared with AS, normal vascular endothelia of capillaries and muscular vessels showed variable positivity. Among hemangiomas, cavernous and spindle cell hemangiomas showed most frequent endothelial CD30 positivity, whereas in most other hemangiomas, CD30 positivity was scant. In conclusion, CD30 expression occurs in a significant subset of ASs and EHEs and needs to be included in the differential diagnosis with other CD30-positive malignancies to avoid a diagnostic pitfall. It remains to be determined whether patients with strongly CD30-positive ASs could be candidates for targeted therapy using the recently introduced CD30 antibody drug conjugates.

[Heavy metal pollution characteristics and ecological risk analysis for soil in Phyllostachys praecox stands of Lin'an].

PubMed

Fang, Xiao-bo; Shi, Han; Liao, Xin-feng; Lou, Zhong; Zhou, Lyu-yan; Yu, Hai-xia; Yao, Lin; Sun, Li-ping

2015-06-01

An investigation was carried out in an attempt to reveal the characteristics of heavy metals contamination in the soils of Phyllostachys praecox forest in Lin' an. Based on the concentrations of Hg, As, Cu, Pb, Zn, Cd, Cr, Ni, Co and Mn in 160 topsoil samples, the pollution status and ecological risks of heavy metals in the soils were assessed by single factor pollution index, Nemerow integrated pollution index and Hankanson potential ecological risk index. The spatial variability of heavy metal concentrations in the soils closely related to the distribution of traffic, industrial and livestock pollution sources. The average concentrations of Hg, As, Cu, Pb, Zn, Cd, Cr, Ni, Co and Mn in the soils were 0.16, 7.41, 34.36, 87.98, 103.98, 0.26, 59.12, 29.56, 11.44 and 350.26 mg · kg(-1), respectively. Pb, Cd, Zn and Cu concentrations were as 2.89, 1.70, 1.12 and 1.12 times as the background values of soil in Zhejiang Province, respectively. But their concentrations were all lower than the threshold values of the National Environmental Quality Standard for Soil (GB 15618-1995). The average single factor pollution index revealed that the level of heavy metal pollution in the soils was in order of Pb>Cd>Cu= Zn>Hg>As>Ni>Co>Cr>Mn. Pb pollution was of moderate level while Cd, Cu and Zn pollutions were slight. There was no soil pollution caused by the other heavy metals. However, the Nemerow integrated pollution index showed that all the 160 soil samples were contaminated by heavy metals to a certain extent. Among total 160 soil samples, slight pollution level, moderate pollution level and heavy pollution level accounted for 55.6%, 29.4% and 15.0%, respectively. The average single factor potential ecological risk index (Er(i)) implied that the potential ecological risk related to Cd reached moderate level, while the others were of slight level. Furthermore, Cd and Hg showed higher potential ecological risk indices which reached up to 256.82 and 187.33 respectively, indicating Cd and Hg had a strong ecological risk and therefore might pose the most serious ecological risk in the soils of P. praecox standsin Lin' an. In addition, the integrated factor potential ecological risk analysis suggested a slight risk to local ecosystem originated from heavy metal contamination in the soils of P. praecox stands in Lin'an.

Cadmium-1,4-cyclohexanedicarboxylato coordination polymers bearing different di-alkyl-2,2'-bipyridines: syntheses, crystal structures and photoluminescence studies.

PubMed

Rosales-Vázquez, Luis D; Sánchez-Mendieta, Víctor; Dorazco-González, Alejandro; Martínez-Otero, Diego; García-Orozco, Iván; Morales-Luckie, Raúl A; Jaramillo-Garcia, Jonathan; Téllez-López, Antonio

2017-09-26

Four coordination polymers have been synthesized using self-assembly solution reactions under ambient conditions, reacting Cd(ii) ions with 1,4-cyclohexanedicarboxylic acid in the presence of different 2,2'-bipyridine co-ligands: {[Cd(H 2 O)(e,a-cis-1,4-chdc)(2,2'-bpy)]·H 2 O} n (1); [Cd 2 (H 2 O) 2 (e,a-cis-1,4-chdc) 2 (4,4'-dmb) 2 ] n (2); {[Cd(e,a-cis-1,4-chdc)(5,5'-dmb)]·H 2 O·CH 3 OH} n (3) and {[Cd(e,e-trans-1,4-chdc)(4,4'-dtbb)]·CH 3 OH} n (4), where 1,4-chdc = 1,4-cyclohexanedicarboxylato, 2,2'-bpy = 2,2'-bipyridine, 4,4'-dmb = 4,4'-dimethyl-2,2'-bipyridine, 5,5'-dmb = 5,5'-dimethyl-2,2'-bipyridine and 4,4'-dtbb = 4,4'-di-tert-butyl-2,2'-bipyridine. Crystallographic studies show that compound 1 has a 1D structure propagating along the crystallographic b-axis; the Cd ion in 1 is six-coordinated with a distorted-octahedral coordination sphere. Compound 2 has two crystallographic different Cd ions and both are six-coordinated with a distorted-octahedral coordination sphere. Compound 3 exhibits a seven-coordinated Cd ion having a distinctive distorted-monocapped trigonal prismatic geometry. In compound 4, the Cd ion is also seven-coordinated in a distorted monocapped octahedral geometry. Compounds 2, 3 and 4 possess rhombic-shaped dinuclear units (Cd 2 O 2 ) as nodes to generate larger cycles made up of four dinuclear units, a Cd 4 motif, bridged by four 1,4-chdc ligands, accomplishing, thus, 2D structures. Remarkably, in compound 4 the 1,4-chdc ligand conformation changes to the equatorial, equatorial trans, unlike the other compounds where the bridging ligand conformation is the more typical equatorial, axial cis. The solid state luminescence properties of 1-4 were investigated; polymers 3 and 4 exhibited a strong blue emission (λ em = 410-414 nm) compared to 1 and 2; structure-related photoluminescence is attributed to the degree of hydration of the compounds. Furthermore, Cd-polymer 3 suspended in acetone allows the fluorescence selective sensing of acetonitrile over common organic solvents such as alcohols and DMF, based on turn-on fluorescence intensity with a limit of 53 μmol L -1 .

CD4 Count in HIV- Brain-Dead Donors: Insight into Donor Risk Assessment for HIV+ Donors.

PubMed

Serrano, Oscar Kenneth; Kerwin, Scott; Payne, William D; Pruett, Timothy L

2017-04-01

The Human Immunodeficiency Virus (HIV) Organ Policy Equity Act allows for transplantation of organs from HIV-infected individuals (HIV+), provided it is performed under a research protocol. The safety assessment of an organ for transplantation is an essential element of the donation process. The risk for HIV-associated opportunistic infections increases as circulating CD4+ lymphocytes decrease to less than 200 cells/μL; however, the numbers of circulating CD4+ cells in the HIV-negative (HIV-) brain-dead donor (BDD) is not known. Circulating T-lymphocyte subset profiles in conventional HIV- BDD were measured in 20 BDD in a clinical laboratory. The mean age of the BDD cohort was 48.7 years, 95% were white and 45% were women. The average body mass index was 29.2 kg/m. Cerebrovascular accident (40%) was the most prevalent cause of death. Sixteen (80%) subjects had a CD4 count ≤441 cells/μL (lower limit of normal) and 11 (55%) had a CD4 count less than 200 cells/μL; 11 (55%) subjects had a CD8 count ≤125 cells/μL (lower limit of normal). CD4/CD8 ratio was below normal in 3 patients (normal, 1.4-2.6). No recipient had a recognized donor-associated adverse event. Absolute numbers of CD4 and CD8 T-lymphocytes are commonly reduced after brain death in HIV- individuals. Thus, CD4 absolute numbers are an inconsistent metric for assessing organ donor risk, irrespective of HIV status.

Origin discrimination of defatted pork via trace elements profiling, stable isotope ratios analysis, and multivariate statistical techniques.

PubMed

Park, Yu Min; Lee, Cheong Mi; Hong, Joon Ho; Jamila, Nargis; Khan, Naeem; Jung, Jong-Hyun; Jung, Young-Chul; Kim, Kyong Su

2018-09-01

This study verified the origin of 346 defatted Korean and non-Korean pork samples via trace elements profiling, and C and N stable isotope ratios analysis. The analyzed elements were 6 Li, 7 Li, 10 B, 11 B, 51 V , 50 Cr, 52 Cr, 53 Cr, 55 Mn, 58 Ni, 60 Ni, 59 Co, 63 Cu, 65 Cu, 64 Zn, 66 Zn, 69 Ga, 71 Ga, 75 As, 82 Se, 84 Sr, 86 Sr, 87 Sr, 88 Sr, 85 Rb, 94 Mo, 95 Mo, 97 Mo, 107 Ag, 109 Ag, 110 Cd, 111 Cd, 113 Cd, 112 Cd, 114 Cd, 116 Cd, 133 Cs, 206 Pb, 207 Pb, and 208 Pb. Content (mg/kg) of 51 V (0.012), 50 Cr (0.882), 75 As (0.017), 85 Rb (57.7), and 87 Sr (46.3) were high in Korean pork samples whereas 6 Li, 7 Li, 59 Co, 55 Mn, 58 Ni, 84 Sr, 86 Sr, 88 Sr, 111 Cd, and 133 Cs were found higher in non-Korean samples. The results of discriminant analysis showed that the trace elements content and stable isotope ratios were significant for the discrimination of geographical origins with a perfect discrimination rate of 100%. Copyright © 2018 Elsevier Ltd. All rights reserved.

Loss of Sirt3 accelerates arterial thrombosis by increasing formation of neutrophil extracellular traps and plasma tissue factor activity

PubMed Central

Gaul, Daniel S; Weber, Julien; van Tits, Lambertus J; Sluka, Susanna; Pasterk, Lisa; Reiner, Martin F; Calatayud, Natacha; Lohmann, Christine; Klingenberg, Roland; Pahla, Jürgen; Vdovenko, Daria; Tanner, Felix C; Camici, Giovanni G; Eriksson, Urs; Auwerx, Johan; Mach, François; Windecker, Stephan; Rodondi, Nicolas; Lüscher, Thomas F; Winnik, Stephan; Matter, Christian M

2018-01-01

Abstract Aims Sirtuin 3 (Sirt3) is a mitochondrial, nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that reduces oxidative stress by activation of superoxide dismutase 2 (SOD2). Oxidative stress enhances arterial thrombosis. This study investigated the effects of genetic Sirt3 deletion on arterial thrombosis in mice in an inflammatory setting and assessed the clinical relevance of these findings in patients with ST-elevation myocardial infarction (STEMI). Methods and results Using a laser-induced carotid thrombosis model with lipopolysaccharide (LPS) challenge, in vivo time to thrombotic occlusion in Sirt3−/− mice (n = 6) was reduced by half compared to Sirt3+/+ wild-type (n = 8, P < 0.01) controls. Ex vivo analyses of whole blood using rotational thromboelastometry revealed accelerated clot formation and increased clot stability in Sirt3−/− compared to wild-type blood. rotational thromboelastometry of cell-depleted plasma showed accelerated clotting initiation in Sirt3−/− mice, whereas overall clot formation and firmness remained unaffected. Ex vivo LPS-induced neutrophil extracellular trap formation was increased in Sirt3−/− bone marrow-derived neutrophils. Plasma tissue factor (TF) levels and activity were elevated in Sirt3−/− mice, whereas plasma levels of other coagulation factors and TF expression in arterial walls remained unchanged. SOD2 expression in bone marrow -derived Sirt3−/− neutrophils was reduced. In STEMI patients, transcriptional levels of Sirt3 and its target SOD2 were lower in CD14+ leukocytes compared with healthy donors (n = 10 each, P < 0.01). Conclusions Sirt3 loss-of-function enhances experimental thrombosis in vivo via an increase of neutrophil extracellular traps and elevation of TF suggesting thrombo-protective effects of endogenous Sirt3. Acute coronary thrombosis in STEMI patients is associated with lower expression levels of SIRT3 and SOD2 in CD14+ leukocytes. Therefore, enhancing SIRT3 activity by pan-sirtuin activating NAD+-boosters may provide a novel therapeutic target to prevent or treat thrombotic arterial occlusion in myocardial infarction or stroke. PMID:29444200

Immune Cell-Mediated Protection against Vaginal Candidiasis: Evidence for a Major Role of Vaginal CD4+ T Cells and Possible Participation of Other Local Lymphocyte Effectors

PubMed Central

Santoni, Giorgio; Boccanera, Maria; Adriani, Daniela; Lucciarini, Roberta; Amantini, Consuelo; Morrone, Stefania; Cassone, Antonio; De Bernardis, Flavia

2002-01-01

The protective roles of different lymphocyte subsets were investigated in a rat vaginal candidiasis model by adoptive transfer of vaginal lymphocytes (VL) or sorted, purified CD3+ T cells, CD4+ or CD8+ T cells, or CD3− CD5+ B cells from the vaginas of naïve or immune rats following three rounds of Candida albicans infection. The adoptive transfer of total VL from nonimmune animals did not alter the course of vaginal candidiasis of the recipient rats. In contrast, the animals receiving total VL or CD3+ T cells from immune rats showed a highly significant acceleration of fungus clearance compared with animals which received nonimmune VL. The animals with vaginal CD3− CD5+ B cells transferred from immune rats also had fewer Candida CFU than the controls, but fungal clearance was significantly retarded with respect to the animals administered immune T cells. Sorted, purified CD4+ and CD8+ vaginal T cells from immune rats were also adoptively transferred to naïve animals. Although both populations were seen to accelerate the clearance of the fungus from the vagina, CD4+ T cells were much more effective than CD8+ T cells. Overall, there was no difference between the antifungal effects of immune vaginal CD4+ T cells and those achievable with the transfer of whole, immune VL. Histological observations of the vaginal tissues of rats with adoptively transferred immune T cells demonstrated a remarkable accumulation of lymphocytes in the subepithelial lamina propria and also infiltrating the mucosal epithelium. These results strongly suggest that distinct vaginal lymphocyte subsets participate in the adaptive anti-Candida immunity at the vaginal level, with the vaginal CD4+ T cells probably playing a major role. PMID:12183521

Bio-nano complexes of ZVFeNPs/Fe-s-M13 and Cd (II)/Cd-s-M13 accelerate Cd (II) reduction by FeNPs through dual dispersing and separate deposition

NASA Astrophysics Data System (ADS)

Zhang, Shuai; Nakano, Kazuhiko; Yu, Huimin; Shen, Zhongyao

2014-03-01

Reduction of Cd (II) in liquor by solid zero valent Fe nanoparticles (ZVFeNPs) is a liquid-solid biphasic reaction in which the reduction efficiency was often lowered by either aggregation of ZVFeNPs or coating of the generated ZVCd. In light of the filamentous nanostructure of bacteriophage M13 with ˜2700 copies of pVIII protein in delicate distribution at the coat, a novel dual dispersing reduction route was designed by introducing two different kinds of M13 with Fe-binding specificity (Fe-s-M13) and Cd-binding specificity (Cd-s-M13) to disperse ZVFeNPs and Cd (II) ions, respectively. The Fe-s-M13 was used for synthesis of the ZVFeNPs/Fe-s-M13 complex, where ZVFeNPs were uniformly dispersed into small nanoparticles (5-10 nm) on Fe-s-M13. The engineered Cd-s-M13, constructed by genetic recombination of pVIII through inserting the gene of a biopanned 7-mer Cd-specific peptide (SCPICPG) into the N-terminus of pVIII gene, was used for Cd (II) dispersion before reduction. The dispersed complex of Cd(II)/Cd-s-M13 was rapidly reduced by complex of ZVFeNPs/Fe-s-M13. Kinetics results showed that the initial reduction rate and final reduction ratio of Cd (II) increased by 35.7% and 16.4%, respectively, through dispersion of ZVFeNPs by Fe-s-M13; they improved again by 53.6% and 37.0%, respectively, through further dispersion of Cd (II) by Cd-s-M13. TEM and EDS results revealed that the acceleration effect of the dual dispersing reduction was arising from uniform dispersion of the small ZVFeNPs and separate deposition of the reduced ZVCd on the two different M13 phages.

From Blood Islands to Blood Vessels: Morphologic Observations and Expression of Key Molecules during Hyaloid Vascular System Development

PubMed Central

McLeod, D. Scott; Hasegawa, Takuya; Baba, Takayuki; Grebe, Rhonda; Galtier d'Auriac, Ines; Merges, Carol; Edwards, Malia; Lutty, Gerard A.

2012-01-01

Purpose. The mode of development of the human hyaloid vascular system (HVS) remains unclear. Early studies suggested that these blood vessels formed by vasculogenesis, while the current concept seems to favor angiogenesis as the mode of development. We examined embryonic and fetal human HVS using a variety of techniques to gain new insights into formation of this vasculature. Methods. Embryonic and fetal human eyes from 5.5 to 12 weeks gestation (WG) were prepared for immunohistochemical analysis or for light and electron microscopy. Immunolabeling of sections with a panel of antibodies directed at growth factors, transcription factors, and hematopoietic stem cell markers was employed. Results. Light microscopic examination revealed free blood islands (BI) in the embryonic vitreous cavity (5.5–7 WG). Giemsa stain revealed that BI were aggregates of mesenchymal cells and primitive nucleated erythroblasts. Free cells were also observed. Immunolabeling demonstrated that BI were composed of mesenchymal cells that expressed hemangioblast markers (CD31, CD34, C-kit, CXCR4, Runx1, and VEGFR2), erythroblasts that expressed embryonic hemoglobin (Hb-ε), and cells that expressed both. Few cells were proliferating as determined by lack of Ki67 antigen. As development progressed (12 WG), blood vessels became more mature structurally with pericyte investment and basement membrane formation. Concomitantly, Hb-ε and CXCR4 expression was down-regulated and von Willebrand factor expression was increased with the formation of Weibel-Palade bodies. Conclusions. Our results support the view that the human HVS, like the choriocapillaris, develops by hemo-vasculogenesis, the process by which vasculogenesis, erythropoiesis, and hematopoiesis occur simultaneously from common precursors, hemangioblasts. PMID:23092923

Ubiquitinated CD36 sustains insulin-stimulated Akt activation by stabilizing insulin receptor substrate 1 in myotubes.

PubMed

Sun, Shishuo; Tan, Pengcheng; Huang, Xiaoheng; Zhang, Wei; Kong, Chen; Ren, Fangfang; Su, Xiong

2018-02-16

Both the magnitude and duration of insulin signaling are important in executing its cellular functions. Insulin-induced degradation of insulin receptor substrate 1 (IRS1) represents a key negative feedback loop that restricts insulin signaling. Moreover, high concentrations of fatty acids (FAs) and glucose involved in the etiology of obesity-associated insulin resistance also contribute to the regulation of IRS1 degradation. The scavenger receptor CD36 binds many lipid ligands, and its contribution to insulin resistance has been extensively studied, but the exact regulation of insulin sensitivity by CD36 is highly controversial. Herein, we found that CD36 knockdown in C2C12 myotubes accelerated insulin-stimulated Akt activation, but the activated signaling was sustained for a much shorter period of time as compared with WT cells, leading to exacerbated insulin-induced insulin resistance. This was likely due to enhanced insulin-induced IRS1 degradation after CD36 knockdown. Overexpression of WT CD36, but not a ubiquitination-defective CD36 mutant, delayed IRS1 degradation. We also found that CD36 functioned through ubiquitination-dependent binding to IRS1 and inhibiting its interaction with cullin 7, a key component of the multisubunit cullin-RING E3 ubiquitin ligase complex. Moreover, dissociation of the Src family kinase Fyn from CD36 by free FAs or Fyn knockdown/inhibition accelerated insulin-induced IRS1 degradation, likely due to disrupted IRS1 interaction with CD36 and thus enhanced binding to cullin 7. In summary, we identified a CD36-dependent FA-sensing pathway that plays an important role in negative feedback regulation of insulin activation and may open up strategies for preventing or managing type 2 diabetes mellitus. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Natural History of Aging in Cornelia de Lange Syndrome

PubMed Central

KLINE, ANTONIE D.; GRADOS, MARCO; SPONSELLER, PAUL; LEVY, HOWARD P.; BLAGOWIDOW, NATALIE; SCHOEDEL, CHRISTIANNE; RAMPOLLA, JONI; CLEMENS, DOUGLAS K.; KRANTZ, IAN; KIMBALL, AMY; PICHARD, CARMEN; TUCHMAN, DAVID

2016-01-01

Observations about the natural history of aging in Cornelia de Lange syndrome (CdLS) are made, based on 49 patients from a multidisciplinary clinic for adolescents and adults. The mean age was 17 years. Although most patients remain small, obesity may develop. Gastroesophageal reflux persists or worsens, and there are early long-term sequelae, including Barrett esophagus in 10%; other gastrointestinal findings include risk for volvulus, rumination, and chronic constipation. Submucous cleft palate was found in 14%, most undetected before our evaluation. Chronic sinusitis was noted in 39%, often with nasal polyps. Blepharitis improves with age; cataracts and detached retina may occur. Decreased bone density is observed, with occasional fractures. One quarter have leg length discrepancy and 39% scoliosis. Most females have delayed or irregular menses but normal gynecologic exams and pap smears. Benign prostatic hypertrophy occurred in one male prior to 40 years. The phenotype is variable, but there is a distinct pattern of facial changes with aging. Premature gray hair is frequent; two patients had cutis verticis gyrata. Behavioral issues and specific psychiatric diagnoses, including self-injury, anxiety, attention-deficit disorder, autistic features, depression, and obsessive-compulsive behavior, often worsen with age. This work presents some evidence for accelerated aging in CdLS. Of 53% with mutation analysis, 55% demonstrate a detectable mutation in NIPBL or SMC1A. Although no specific genotype–phenotype correlations have been firmly established, individuals with missense mutations in NIPBL and SMC1A appear milder than those with other mutations. Based on these observations, recommendations for clinical management of adults with CdLS are made. PMID:17640042

Platelet-Rich Fibrin Accelerates Skin Wound Healing in Diabetic Mice.

PubMed

Ding, Yinjia; Cui, Lei; Zhao, Qiming; Zhang, Weiqiang; Sun, Huafeng; Zheng, Lijun

2017-09-01

Diabetic foot ulcers (DFUs) are associated with an increased risk of secondary infection and amputation. Platelet-rich fibrin (PRF), a platelet and leukocyte concentrate containing several cytokines and growth factors, is known to promote wound healing. However, the effect of PRF on diabetic wound healing has not been adequately investigated. The aim of the study was to investigate the effect of PRF on skin wound healing in a diabetic mouse model. Platelet-rich fibrin was prepared from whole blood of 8 healthy volunteers. Two symmetrical skin wounds per mouse were created on the back of 16 diabetic nude mice. One of the 2 wounds in each mouse was treated with routine dressings (control), whereas the other wound was treated with PRF in addition to routine dressings (test), each for a period of 14 days. Skin wound healing rate was calculated.Use of PRF was associated with significantly improved skin wound healing in diabetic mice. On hematoxylin and eosin and CD31 staining, a significant increase in the number of capillaries and CD31-positive cells was observed, suggesting that PRF may have promoted blood vessel formation in the skin wound. In this study, PRF seemed to accelerate skin wound healing in diabetic mouse models, probably via increased blood vessel formation.

Clinical Significance of Soluble Hemoglobin Scavenger Receptor CD163 (sCD163) in Sepsis, a Prospective Study

PubMed Central

Feng, Lin; Zhou, Xin; Su, Long-Xiang; Feng, Dan; Jia, Yan-Hong; Xie, Li-Xin

2012-01-01

Objective We investigated serum soluble CD163 (sCD163) levels for use in the diagnosis, severity assessment, and prognosis of sepsis in the critical ill patients and compared sCD163 with other infection-related variables. Methods During july 2010 and April 2011, serum was obtained from 102 sepsis patients (days 1, 3, 5, 7, and 10 after admission to an ICU) and 30 systemic inflammatory response syndrome (SIRS) patients with no sepsis diagnosed. Serum levels of sCD163, procalcitonon (PCT), and C reactive protein (CRP) were determined respectively. Sequential organ failure assessment (SOFA) scores for sepsis patients were also recorded. Then evaluated their roles in sepsis. Results The sCD163 levels were 0.88(0.78–1.00)ug/mL for SIRS patients, 1.50(0.92–2.00)ug/mL for moderate sepsis patients, and 2.95(2.18–5.57)ug/mL for severe sepsis patients on day1. The areas under the ROC curves for sCD163, CRP, and PCT for the diagnosis of sepsis were, respectively, 0.856(95%CI: 0.791–0.921), 0.696(95%CI: 0.595–0.797), and 0.629(95%CI: 0.495–0.763), At the recommended cut-off 1.49 ug/mL for sCD163, the sensitivity is 74.0% with 93.3% specificity. Based on 28-day survivals, sCD163 levels in the surviving group stay constant, while they tended to gradually increase in the non-surviving group.The area under the ROC curve for sCD163 for sepsis prognosis was 0.706(95%CI 0.558–0.804). Levels of sCD163 with cut-off point >2.84 ug/mL have sensitivity of 55.8.0%, specificity 80.4%.Common risk factors for death and sCD163 were included in multivariate logistic regression analysis; the odds ratios (OR) for sCD163 and SOFA scores for sepsis prognosis were 1.173 and 1.396, respectively (P<0.05). Spearman rank correlation analysis showed that sCD163 was weakly, but positively correlated with CRP, PCT, and SOFA scores (0.2< r <0.4, P<0.0001), but not with leukocyte counts (r <0.2, P = 0.450). Conclusion Serum sCD163 is superior to PCT and CRP for the diagnosis of sepsis and differentiate the severity of sepsis. sCD163 levels were more sensitive for dynamic evaluations of sepsis prognosis. Serum sCD163 and SOFA scores are prognostic factors for sepsis. Trial Registration www.chictr.org ChiCTR-ONC-10000812 PMID:22911680

Advanced Glycation End Products Enhance Macrophages Polarization into M1 Phenotype through Activating RAGE/NF-κB Pathway

PubMed Central

Jin, Xian; Yao, Tongqing; Zhou, Zhong'e; Zhu, Jian; Zhang, Song; Hu, Wei; Shen, Chengxing

2015-01-01

Atherosclerotic lesions are accelerated in patients with diabetes. M1 (classically activated in contrast to M2 alternatively activated) macrophages play key roles in the progression of atherosclerosis. Since advanced glycation end products (AGEs) are major pathogenic factors and active inflammation inducers in diabetes mellitus, this study assessed the effects of AGEs on macrophage polarization. The present study showed that AGEs significantly promoted macrophages to express IL-6 and TNF-α. M1 macrophage markers such as iNOS and surface markers including CD11c and CD86 were significantly upregulated while M2 macrophage markers such as Arg1 and CD206 remained unchanged after AGEs stimulation. AGEs significantly increased RAGE expression in macrophages and activated NF-κB pathway, and the aforementioned effects were partly abolished by administration of anti-RAGE antibody or NF-κB inhibitor PDTC. In conclusion, our results suggest that AGEs enhance macrophage differentiation into proinflammatory M1 phenotype at least partly via RAGE/NF-κB pathway activation. PMID:26114112

Immunomodulatory effects of Longdan Xiegan Tang on CD4+/CD8+ T cells and associated inflammatory cytokines in rats with experimental autoimmune uveitis.

PubMed

Tang, Kai; Guo, Dadong; Zhang, Lian; Guo, Junguo; Zheng, Fengming; Si, Junkang; Bi, Hongsheng

2016-09-01

Longdan Xiegan Tang (LXT) is a mixture of herbal extracts commonly used in traditional Chinese medicine that may exert immunomodulatory effects for the treatment of autoimmune diseases. However, the detailed mechanisms that mediate the actions of LXT are unclear. The present study induced an experimental autoimmune uveitis (EAU) model in Lewis rats via injection of IRBP1177‑1191 emulsion. The model was used to investigate the effects of LXT on EAU rats and assess the efficacy of LXT by measuring clinical manifestations and histopathological changes caused by EAU. Additionally, alterations in the ratio of CD4+/CD8+‑T cells were determined by flow cytometry, and the expression of interferon (IFN)‑γ, interleukin (IL)‑17, IL‑10 and tumor necrosis factor (TNF)‑α were measured using reverse transcription‑quantitative polymerase chain reaction and enzyme‑linked immunosorbent assay analysis. The results of the present study demonstrate that LXT can efficiently alleviate the symptoms of EAU, inhibit the differentiation of uveitogenic CD4+ T cells and reduce the expression of proinflammatory cytokines, including IFN‑γ, IL‑17 and TNF‑α. Furthermore, LXT promotes the production of IL‑10 and accelerates the recovery of EAU, indicating that the immunomodulatory effects of LXT may potentially be used for the treatment of uveitis.

Three-year chemical dependency and mental health treatment outcomes among adolescents: the role of continuing care.

PubMed

Sterling, Stacy; Chi, Felicia; Campbell, Cynthia; Weisner, Constance

2009-08-01

Few studies have examined the effects of treatment factors, including the types of services [chemical dependency (CD), psychiatric, or both], on long-term outcomes among adolescents following CD treatment, and whether receiving continuing care may contribute to better outcomes. This study examines the effect of the index CD and ongoing CD and psychiatric treatment episodes, 12-step participation, and individual characteristics such as CD and mental health (MH) severity and gender, age, and ethnicity, on 3-year CD and MH outcomes. Participants were 296 adolescents aged 13 to 18 seeking treatment at 4 CD programs of a nonprofit, managed care, integrated health system. We surveyed participants at intake, 1 year, and 3 years, and examined survey and administrative data, and CD and psychiatric utilization. At 3 years, 29.7% of the sample reported total abstinence from both alcohol and drugs (excluding tobacco). Compared with girls, boys had only half the odds of being abstinent (OR = 0.46, p = 0.0204). Gender also predicted Externalizing severity at 3 years (coefficients 18.42 vs. 14.77, p < 0.01). CD treatment readmission in the second and third follow-up years was related to abstinence at 3 years (OR = 0.24, p = 0.0066 and OR = 3.33, p = 0.0207, respectively). Abstinence at 1 year predicted abstinence at 3 years (OR = 4.11, p < 0.0001). Those who were abstinent at 1 year also had better MH outcomes (both lower Internalizing and Externalizing scores) than those who were not (11.75 vs. 15.55, p = 0.0012 and 15.13 vs. 18.06, p = 0.0179, respectively). A CD treatment episode resulting in good 1-year CD outcomes may contribute significantly to both CD and MH outcomes 3 years later. The findings also point to the value of providing a continuing care model of treatment for adolescents.

Positive matrix factorization as source apportionment of soil lead and cadmium around a battery plant (Changxing County, China).

PubMed

Xue, Jian-long; Zhi, Yu-you; Yang, Li-ping; Shi, Jia-chun; Zeng, Ling-zao; Wu, Lao-sheng

2014-06-01

Chemical compositions of soil samples are multivariate in nature and provide datasets suitable for the application of multivariate factor analytical techniques. One of the analytical techniques, the positive matrix factorization (PMF), uses a weighted least square by fitting the data matrix to determine the weights of the sources based on the error estimates of each data point. In this research, PMF was employed to apportion the sources of heavy metals in 104 soil samples taken within a 1-km radius of a lead battery plant contaminated site in Changxing County, Zhejiang Province, China. The site is heavily contaminated with high concentrations of lead (Pb) and cadmium (Cd). PMF successfully partitioned the variances into sources related to soil background, agronomic practices, and the lead battery plants combined with a geostatistical approach. It was estimated that the lead battery plants and the agronomic practices contributed 55.37 and 29.28%, respectively, for soil Pb of the total source. Soil Cd mainly came from the lead battery plants (65.92%), followed by the agronomic practices (21.65%), and soil parent materials (12.43%). This research indicates that PMF combined with geostatistics is a useful tool for source identification and apportionment.

Accelerated lymphocyte recovery after alemtuzumab does not predict multiple sclerosis activity.

PubMed

Kousin-Ezewu, Onajite; Azzopardi, Laura; Parker, Richard A; Tuohy, Orla; Compston, Alastair; Coles, Alasdair; Jones, Joanne

2014-06-17

To test the hypothesis that accelerated peripheral blood mononuclear cell recovery after alemtuzumab treatment of multiple sclerosis is associated with recurrent disease activity and to investigate the claim that CD4 counts greater than 388.5 × 10(6) cells/mL at 12 months can be used to identify patients who may benefit from further treatment. A total of 108 patients were followed for a median of 99 months post alemtuzumab. Patients were classified as active or nonactive after each cycle of treatment based on clinical relapse, increasing disability, or new T2/enhancing MRI lesions. These outcomes were correlated with CD4, CD8, CD19, CD56+ NK, and monocyte counts. Of 108 patients, 56 (52%) relapsed at some point during follow-up. Mean annualized relapse rate after alemtuzumab was 0.17 vs 1.67 prior to treatment (equating to a 90% reduction). Of 108 patients, 28 (26%) met the criteria for sustained accumulation of disability. Median time to the lower limit of normal for CD19, CD8, and CD4 was 3, 19.5, and 32 months, respectively. There was no significant difference in the recovery of any cell population between patients with and without disease activity or accumulation of disability after treatment. This study does not support the use of cell counts as biomarkers for identifying patients at greater risk of active disease following treatment with alemtuzumab. © 2014 American Academy of Neurology.

Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn’s disease

PubMed Central

Gathungu, Grace; Zhang, Yuanhao; Tian, Xinyu; Bonkowski, Erin; Rowehl, Leahana; Krumsiek, Julia; Nix, Billy; Chalk, Claudia; Trapnell, Bruce; Zhu, Wei; Newberry, Rodney; Denson, Lee; Li, Ellen

2018-01-01

AIM To examine the relationship between elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) auto-antibodies (Ab) level and time to surgical recurrence after initial surgery for Crohn’s disease (CD). METHODS We reviewed 412 charts from a clinical database at tertiary academic hospital. Patients included in the study had ileal or ileocolonic CD and surgical resection of small bowel or ileocecal region for management of disease. Serum samples were analyzed for serological assays including GM-CSF cytokine, GM-CSF Ab, ASCA IgG and IgA, and genetic markers including SNPs rs2066843, rs2066844, rs2066845, rs2076756 and rs2066847 in NOD2, rs2241880 in ATG16L1, and rs13361189 in IRGM. Cox proportional-hazards models were used to assess the predictors of surgical recurrence. RESULTS Ninety six percent of patients underwent initial ileocecal resection (ICR) or ileal resection (IR) and subsequently 40% of patients required a second ICR/IR for CD. GM-CSF Ab level was elevated at a median of 3.81 mcg/mL. Factors predicting faster time to a second surgery included elevated GM-CSF Ab [hazard ratio (HR) 3.52, 95%CI: 1.45-8.53, P = 0.005] and elevated GM-CSF cytokine (HR = 2.48, 95%CI: 1.31-4.70, P = 0.005). Factors predicting longer duration between first and second surgery included use of Immunomodulators (HR = 0.49, 95%CI: 0.31-0.77, P = 0.002), the interaction effect of low GM-CSF Ab levels and smoking (HR = 0.60, 95%CI: 0.45-0.81, P = 0.001) and the interaction effect of low GM-CSF cytokine levels and ATG16L1 (HR = 0.65, 95%CI: 0.49-0.88, P = 0.006). CONCLUSION GM-CSF bioavailability plays a critical role in maintaining intestinal homeostasis. Decreased bioavailability coupled with the genetic risk markers and/or smoking results in aggressive CD behavior. PMID:29434451

Significantly Reduced Genoprevalence of Vaccine-Type HPV-16/18 Infections among Vaccinated Compared to Non-Vaccinated Young Women 5.5 Years after a Bivalent HPV-16/18 Vaccine (Cervarix®) Pilot Project in Uganda

PubMed Central

Berggren, Vanja; Wabinga, Henry; Lillsunde-Larsson, Gabriella; Helenius, Gisela; Kaliff, Malin; Karlsson, Mats; Kirimunda, Samuel; Musubika, Caroline; Andersson, Sören

2016-01-01

The objective of this study was to determine the prevalence and some predictors for vaccine and non-vaccine types of HPV infections among bivalent HPV vaccinated and non-vaccinated young women in Uganda. This was a comparative cross sectional study 5.5 years after a bivalent HPV 16/18 vaccination (Cervarix®, GlaxoSmithKline, Belgium) pilot project in western Uganda. Cervical swabs were collected between July 2014-August 2014 and analyzed with a HPV genotyping test, CLART® HPV2 assay (Genomica, Madrid Spain) which is based on PCR followed by microarray for determination of genotype. Blood samples were also tested for HIV and syphilis infections as well as CD4 and CD8 lymphocyte levels. The age range of the participants was 15–24 years and mean age was 18.6(SD 1.4). Vaccine-type HPV-16/18 strains were significantly less prevalent among vaccinated women compared to non-vaccinated women (0.5% vs 5.6%, p 0.006, OR 95% CI 0.08(0.01–0.64). At type-specific level, significant difference was observed for HPV16 only. Other STIs (HIV/syphilis) were important risk factors for HPV infections including both vaccine types and non-vaccine types. In addition, for non-vaccine HPV types, living in an urban area, having a low BMI, low CD4 count and having had a high number of life time sexual partners were also significant risk factors. Our data concurs with the existing literature from other parts of the world regarding the effectiveness of bivalent HPV-16/18 vaccine in reducing the prevalence of HPV infections particularly vaccine HPV- 16/18 strains among vaccinated women. This study reinforces the recommendation to vaccinate young girls before sexual debut and integrate other STI particularly HIV and syphilis interventions into HPV vaccination packages. PMID:27482705

Quality‐Quantity Control Culture Enhances Vasculogenesis and Wound Healing Efficacy of Human Diabetic Peripheral Blood CD34+ Cells

PubMed Central

Masuda, Haruchika; Fujimura, Satoshi; Ito‐Hirano, Rie; Arita, Kayo; Kakinuma, Yusuke; Hagiwara, Hiroko; Kado, Makiko; Hayashi, Ayato; Mita, Tomoya; Ogawa, Takasuke; Watada, Hirotaka; Mizuno, Hiroshi; Sawada, Naoki; Asahara, Takayuki

2018-01-01

Abstract Autologous endothelial progenitor cell (EPC) therapy is commonly used to stimulate angiogenesis in ischemic repair and wound healing. However, low total numbers and functional deficits of EPCs make autologous EPC therapy ineffective in diabetes. Currently, no known ex vivo culture techniques can expand and/or ameliorate the functional deficits of EPCs for clinical usage. Recently, we showed that a quality‐quantity culture (QQc) system restores the vasculogenic and wound‐healing efficacy of murine diabetic EPCs. To validate these results and elucidate the mechanism in a translational study, we evaluated the efficacy of this QQc system to restore the vasculogenic potential of diabetic human peripheral blood (PB) CD34+ cells. CD34+ cells purified from PB of diabetic and healthy patients were subjected to QQc. Gene expression, vascular regeneration, and expression of cytokines and paracrine mediators were analyzed. Pre‐ or post‐QQc diabetic human PB‐CD34+ cells were transplanted into wounded BALB/c nude mice and streptozotocin‐induced diabetic mice to assess functional efficacy. Post‐QQc diabetic human PB‐CD34+ cell therapy significantly accelerated wound closure, re‐epithelialization, and angiogenesis. The higher therapeutic efficacy of post‐QQc diabetic human PB‐CD34+ cells was attributed to increased differentiation ability of diabetic CD34+ cells, direct vasculogenesis, and enhanced expression of angiogenic factors and wound‐healing genes. Thus, QQc can significantly enhance the therapeutic efficacy of human PB‐CD34+ cells in diabetic wounds, overcoming the inherent limitation of autologous cell therapy in diabetic patients, and could be useful for treatment of not only wounds but also other ischemic diseases. Stem Cells Translational Medicine 2018;7:428–438 PMID:29573563

Accelerated Thermal Cycling and Failure Mechanisms for BGA and CSP Assemblies

NASA Technical Reports Server (NTRS)

Ghaffarian, Reza

2000-01-01

This paper reviews the accelerated thermal cycling test methods that are currently used by industry to characterize the interconnect reliability of commercial-off-the-shelf (COTS) ball grid array (BGA) and chip scale package (CSP) assemblies. Acceleration induced failure mechanisms varied from conventional surface mount (SM) failures for CSPs. Examples of unrealistic life projections for other CSPs are also presented. The cumulative cycles to failure for ceramic BGA assemblies performed under different conditions, including plots of their two Weibull parameters, are presented. The results are for cycles in the range of -30 C to 100 C, -55 C to 100 C, and -55 C to 125 C. Failure mechanisms as well as cycles to failure for thermal shock and thermal cycling conditions in the range of -55 C to 125 C were compared. Projection to other temperature cycling ranges using a modified Coffin-Manson relationship is also presented.

Germline Variation in Complement Genes and Event-Free Survival in Follicular and Diffuse Large B-Cell Lymphoma

PubMed Central

Charbonneau, Bridget; Maurer, Matthew J.; Fredericksen, Zachary S.; Zent, Clive S.; Link, Brian K.; Novak, Anne J.; Ansell, Stephen M.; Weiner, George J.; Wang, Alice H.; Witzig, Thomas E.; Dogan, Ahmet; Slager, Susan L.; Habermann, Thomas M.; Cerhan, James R.

2013-01-01

The complement pathway plays a central role in innate immunity, and also functions as a regulator of the overall immune response. We evaluated whether polymorphisms in complement genes are associated with event-free survival (EFS) in follicular (FL) and diffuse large B-cell (DLBCL) lymphoma. We genotyped 167 single nucleotide polymorphisms (SNPs) from 30 complement pathway genes in a prospective cohort study of newly diagnosed FL (N=107) and DLBCL (N=82) patients enrolled at the Mayo Clinic from 2002–2005. Cox regression was used to estimate Hazard Ratios (HRs) for individual SNPs with EFS, adjusting for FLIPI or IPI and treatment. For gene-level analyses, we used a principal components based gene-level test. In gene-level analyses for FL EFS, CFH (p=0.009), CD55 (p=0.006), CFHR5 (p=0.01), C9 (p=0.02), CFHR1 (p=0.03), and CD46 (p=0.03) were significant at p<0.05, and these genes remained noteworthy after accounting for multiple testing (q<0.15). SNPs in CFH, CFHR1, and CFHR5 showed stronger associations among patients receiving any rituximab, while SNPs from CD55 and CD46 showed stronger associations among patients who were observed. For DLBCL, only CLU (p=0.001) and C7 (p=0.03) were associated with EFS, but did not remain noteworthy after accounting for multiple testing (q>0.15). Genes from the Regulators of Complement Activation (CFH, CD55, CFHR1, CFHR5, CD46) at 1q32-q32.1, along with C9, were associated with FL EFS after adjusting for clinical variables, and if replicated, these findings add further support for the role of host innate immunity in FL prognosis. PMID:22718493

Age-related decline of the cytochrome c oxidase subunit expression in the auditory cortex of the mimetic aging rat model associated with the common deletion.

PubMed

Zhong, Yi; Hu, Yujuan; Peng, Wei; Sun, Yu; Yang, Yang; Zhao, Xueyan; Huang, Xiang; Zhang, Honglian; Kong, Weijia

2012-12-01

The age-related deterioration in the central auditory system is well known to impair the abilities of sound localization and speech perception. However, the mechanisms involved in the age-related central auditory deficiency remain unclear. Previous studies have demonstrated that mitochondrial DNA (mtDNA) deletions accumulated with age in the auditory system. Also, a cytochrome c oxidase (CcO) deficiency has been proposed to be a causal factor in the age-related decline in mitochondrial respiratory activity. This study was designed to explore the changes of CcO activity and to investigate the possible relationship between the mtDNA common deletion (CD) and CcO activity as well as the mRNA expression of CcO subunits in the auditory cortex of D-galactose (D-gal)-induced mimetic aging rats at different ages. Moreover, we explored whether peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) were involved in the changes of nuclear- and mitochondrial-encoded CcO subunits in the auditory cortex during aging. Our data demonstrated that d-gal-induced mimetic aging rats exhibited an accelerated accumulation of the CD and a gradual decline in the CcO activity in the auditory cortex during the aging process. The reduction in the CcO activity was correlated with the level of CD load in the auditory cortex. The mRNA expression of CcO subunit III was reduced significantly with age in the d-gal-induced mimetic aging rats. In contrast, the decline in the mRNA expression of subunits I and IV was relatively minor. Additionally, significant increases in the mRNA and protein levels of PGC-1α, NRF-1 and TFAM were observed in the auditory cortex of D-gal-induced mimetic aging rats with aging. These findings suggested that the accelerated accumulation of the CD in the auditory cortex may induce a substantial decline in CcO subunit III and lead to a significant decline in the CcO activity progressively with age despite compensatory increases of PGC-1α, NRF-1 and TFAM. Therefore, CcO may be a specific intramitochondrial site of age-related deterioration in the auditory cortex, and CcO subunit III might be a target in the development of presbycusis. Copyright © 2012 Elsevier B.V. All rights reserved.

Accelerating the dissolution of enteric coatings in the upper small intestine: evolution of a novel pH 5.6 bicarbonate buffer system to assess drug release.

PubMed

Varum, Felipe J O; Merchant, Hamid A; Goyanes, Alvaro; Assi, Pardis; Zboranová, Veronika; Basit, Abdul W

2014-07-01

Despite rapid dissolution in compendial phosphate buffers, gastro resistant (enteric coated) products can take up to 2 h to disintegrate in the human small intestine, which clearly highlights the inadequacy of the in vitro test method to predict in vivo behaviour of these formulations. The aim of this study was to establish the utility of a novel pH 5.6 bicarbonate buffer, stabilized by an Auto pH™ System, as a better surrogate of the conditions of the proximal small intestine to investigate the dissolution behaviour of standard and accelerated release enteric double coating formulations. Prednisolone tablets were coated with 3 or 5 mg/cm(2) of partially neutralized EUDRAGIT(®) L 30 D-55, HP-55 or HPMC adjusted to pH 6 or 8. An outer layer of EUDRAGIT(®) L 30 D-55 was applied at 5mg/cm(2). For comparison purposes, a standard single layer of EUDRAGIT(®) L 30 D-55 was applied to the tablets. Dissolution was carried out using USP II apparatus in 0.1 M HCl for 2 h, followed by pH 5.6 bicarbonate buffer. EUDRAGIT(®) L 30 D-55 single-coated tablets showed a slow drug release with a lag time of 75 min in buffer, whereas release from the EUDRAGIT(®) L 30 D-55 double-coated tablets was accelerated. These in vitro lag times closely match the in vivo disintegration times for these coated tablets reported previously. Drug release was further accelerated from modified double coatings, particularly in the case of coatings with a thinner inner layer of HP-55 or HPMC (pH 8 and KH2PO4). This study confirms that the pH 5.6 bicarbonate buffer system offers significant advantages during the development of dosage forms designed to release the drug in the upper small intestine. Copyright © 2014. Published by Elsevier B.V.

Particle drag history in a subcritical post-shock flow - data analysis method and uncertainty

NASA Astrophysics Data System (ADS)

Ding, Liuyang; Bordoloi, Ankur; Adrian, Ronald; Prestridge, Kathy; Arizona State University Team; Los Alamos National Laboratory Team

2017-11-01

A novel data analysis method for measuring particle drag in an 8-pulse particle tracking velocimetry-accelerometry (PTVA) experiment is described. We represented the particle drag history, CD(t) , using polynomials up to the third order. An analytical model for continuous particle position history was derived by integrating an equation relating CD(t) with particle velocity and acceleration. The coefficients of CD(t) were then calculated by fitting the position history model to eight measured particle locations in the sense of least squares. A preliminary test with experimental data showed that the new method yielded physically more reasonable particle velocity and acceleration history compared to conventionally adopted polynomial fitting. To fully assess and optimize the performance of the new method, we performed a PTVA simulation by assuming a ground truth of particle motion based on an ensemble of experimental data. The results indicated a significant reduction in the RMS error of CD. We also found that for particle locating noise between 0.1 and 3 pixels, a range encountered in our experiment, the lowest RMS error was achieved by using the quadratic CD(t) model. Furthermore, we will also discuss the optimization of the pulse timing configuration.

Non-CD34+ cells, especially CD8+ cytotoxic T cells and CD56+ natural killer cells, rather than CD34 cells, predict early engraftment and better transplantation outcomes in patients with hematologic malignancies after allogeneic peripheral stem cell transplantation.

PubMed

Kim, Dong Hwan; Won, Dong Il; Lee, Nan Young; Sohn, Sang Kyun; Suh, Jang Soo; Lee, Kyu Bo

2006-07-01

The effect of the transplant dose of each cell subset on engraftment kinetics and transplantation outcomes was evaluated in HLA-identical allogeneic peripheral blood stem cell transplantation (PBSCT). Sixty-nine patients were included in this retrospective study. Engraftment kinetics, transplantation outcomes, and immune reconstitution up to 1 year after transplantation were analyzed according to the transplant dose of CD34+ and non-CD34+ cells, including natural killer (NK) cells and CD8+ cytotoxic T (Tc) cells. An accelerated neutrophil engraftment was strongly associated with a higher transplant dose of NK cells (12 versus 16 days, P < .001) and Tc cells (13 versus 16 days, P < .001) but not CD34+ cells (P = .442). Survival analyses revealed a favorable prognosis for patients who received a higher dose of non-CD34+ cell subsets, rather than CD34+ cells, in terms of overall survival (OS; P = .024 for NK cells and .050 for Tc cells) and nonrelapse mortality (NRM; P = .005 for NK cells, .060 for Tc cells). In addition, a higher transplant dose of NK and Tc cells was correlated with a faster lymphoid reconstitution. In multivariate analyses, rapid neutrophil engraftment was correlated with a higher transplant dose of NK cells (P = .001) and Tc cells (P = .004). Moreover, an increased OS was associated with the NK cell dose (P = .007) and chronic graft-versus-host disease (P = .009), whereas a decreased NRM was associated with the NK dose (P = .024). In conclusion, in a PBSCT setting, a higher transplant dose of NK and Tc cells accelerated neutrophil engraftment, improved the immune reconstitution, and decreased NRM, thereby increasing OS after allogeneic PBSCT.

Conventional medical management of inflammatory bowel disease.

PubMed

Burger, Daniel; Travis, Simon

2011-05-01

Conventional therapies for ulcerative colitis and Crohn's disease (CD) include aminosalicylates, corticosteroids, thiopurines, methotrexate, and anti-tumor necrosis factor agents. A time-structured approach is required for appropriate management. Traditional step-up therapy has been partly replaced during the last decade by potent drugs and top-down therapies, with an accelerated step-up approach being the most appropriate in the majority of patients. When patients are diagnosed with CD or ulcerative colitis, physicians should consider the probable pattern of disease progression so that effective therapy is not delayed. This can be achieved by setting arbitrary time limits for administration of biological therapies, changing therapy from mesalamine in patients with active ulcerative colitis, or using rescue therapy for acute severe colitis. In this review, we provide algorithms with a time-structured approach for guidance of therapy. Common mistakes in conventional therapy include overprescription of mesalamine for CD; inappropriate use of steroids (for perianal CD, when there is sepsis, or for maintenance); delayed introduction or underdosing with azathioprine, 6-mercaptopurine, or methotrexate; and failure to consider timely surgery. The paradox of anti-tumor necrosis factor therapy is that although it too is used inappropriately (when patients have sepsis or fibrostenotic strictures) or too frequently (for diseases that would respond to less-potent therapy), it is also often introduced too late in disease progression. Conventional drugs are the mainstay of current therapy for inflammatory bowel diseases, but drug type, timing, and context must be optimized to manage individual patients effectively. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Seroprevalence of Brucellosis in Human Immunodeficiency Virus Infected Patients in Hamadan, Iran

PubMed Central

Keramat, Fariba; Majzobi, Mohammad Mehdi; Poorolajal, Jalal; Ghane, Zohreh Zarei; Adabi, Maryam

2017-01-01

Objectives Brucellosis is a systemic disease with a wide spectrum of clinical manifestations. This study aimed to determine the seroprevalence of brucellosis in human immunodeficiency virus (HIV) infected patients in Hamadan Province in the west of Iran. Methods A total of 157 HIV-infected patients were screened through standard serological tests, including Wright’s test, Coombs’ Wright test, and 2-mercaptoethanol Brucella agglutination test (2ME test), blood cultures in Castaneda media, and CD4 counting. Data were analyzed using Stata version 11. Results Wright and Coombs’ Wright tests were carried out, and only 5 (3.2%) patients had positive serological results. However, all patients had negative 2ME results, and blood cultures were negative for Brucella spp. Moreover, patients with positive serology and a mean CD4 count of 355.8 ± 203.11 cells/μL had no clinical manifestations of brucellosis, and, and the other patients had a mean CD4 count of 335.55 ± 261.71 cells/μL. Conclusion Results of this study showed that HIV infection is not a predisposing factor of acquiring brucellosis. PMID:28904852

Synergetic Influences of Mixed-Host Emitting Layer Structures and Hole Injection Layers on Efficiency and Lifetime of Simplified Phosphorescent Organic Light-Emitting Diodes.

PubMed

Han, Tae-Hee; Kim, Young-Hoon; Kim, Myung Hwan; Song, Wonjun; Lee, Tae-Woo

2016-03-09

We used various nondestructive analyses to investigate various host material systems in the emitting layer (EML) of simple-structured, green phosphorescent organic light-emitting diodes (OLEDs) to clarify how the host systems affect its luminous efficiency (LE) and operational stability. An OLED that has a unipolar single-host EML with conventional poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) ( PSS) showed high operating voltage, low LE (∼26.6 cd/A, 13.7 lm/W), and short lifetime (∼4.4 h @ 1000 cd/m(2)). However, the combined use of a gradient mixed-host EML and a molecularly controlled HIL that has increased surface work function (WF) remarkably decreased operating voltage and improved LE (∼68.7 cd/A, 77.0 lm/W) and lifetime (∼70.7 h @ 1000 cd/m(2)). Accumulated charges at the injecting interfaces and formation of a narrow recombination zone close to the interfaces are the major factors that accelerate degradation of charge injection/transport and electroluminescent properties of OLEDs, so achievement of simple-structured OLEDs with high efficiency and long lifetime requires facilitating charge injection and balanced transport into the EML and distributing charge carriers and excitons in EML.

Emerging materials for solar cell applications: electrodeposited CdTe. Second quarter report, May 16-August 15, 1980

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

Basol, B.; Stafsudd, O.

1980-09-10

Work was centered about improving electroplating processes and cell fabrication techniques, with emphasis being given to three differing n-CdTe/Au Schottky configurations. The highest values of efficiency-related parmeters achieved with a simulated solar irradiation of 100 mW/cm/sup 2/ were 0.57V for open circuit voltage, 0.6 for fill factor, and 6 mA/cm/sup 2/ for short circuit current. Four important parameters are known to control the quality of the Monosolar electrodeposition process and resultant solar cells. They are electrolyte temperature, Te concentration in the solution at a specific pH, deposition or quasi-rest potential, and flow pattern of the electrolyte (stirring). The first threemore » considerations are believed to be fully understood and optimized. Work is underway to further understand the effects of stirring on the diffusion of ionic components and the effects on CdTe film performance. Work was accelerated during the quarter to increase the short circuit current. Parallel programs using laser irradiation of finished CdTe films, heat treatment, and changes in the electrodeposition process itself to recrystallize films were started. The surface etching technique has been highly refined, while the entire cell manufacturing process is now reproducible when defect-free substrates are used.« less

A short term quality control tool for biodegradable microspheres.

PubMed

D'Souza, Susan; Faraj, Jabar A; Dorati, Rossella; DeLuca, Patrick P

2014-06-01

Accelerated in vitro release testing methodology has been developed as an indicator of product performance to be used as a discriminatory quality control (QC) technique for the release of clinical and commercial batches of biodegradable microspheres. While product performance of biodegradable microspheres can be verified by in vivo and/or in vitro experiments, such evaluation can be particularly challenging because of slow polymer degradation, resulting in extended study times, labor, and expense. Three batches of Leuprolide poly(lactic-co-glycolic acid) (PLGA) microspheres having varying morphology (process variants having different particle size and specific surface area) were manufactured by the solvent extraction/evaporation technique. Tests involving in vitro release, polymer degradation and hydration of the microspheres were performed on the three batches at 55°C. In vitro peptide release at 55°C was analyzed using a previously derived modification of the Weibull function termed the modified Weibull equation (MWE). Experimental observations and data analysis confirm excellent reproducibility studies within and between batches of the microsphere formulations demonstrating the predictability of the accelerated experiments at 55°C. The accelerated test method was also successfully able to distinguish the in vitro product performance between the three batches having varying morphology (process variants), indicating that it is a suitable QC tool to discriminate product or process variants in clinical or commercial batches of microspheres. Additionally, data analysis utilized the MWE to further quantify the differences obtained from the accelerated in vitro product performance test between process variants, thereby enhancing the discriminatory power of the accelerated methodology at 55°C.

Monte Carlo study of neutron-ambient dose equivalent to patient in treatment room.

PubMed

Mohammadi, A; Afarideh, H; Abbasi Davani, F; Ghergherehchi, M; Arbabi, A

2016-12-01

This paper presents an analytical method for the calculation of the neutron ambient dose equivalent H* (10) regarding patients, whereby the different concrete types that are used in the surrounding walls of the treatment room are considered. This work has been performed according to a detailed simulation of the Varian 2300C/D linear accelerator head that is operated at 18MV, and silver activation counter as a neutron detector, for which the Monte Carlo MCNPX 2.6 code is used, with and without the treatment room walls. The results show that, when compared to the neutrons that leak from the LINAC, both the scattered and thermal neutrons are the major factors that comprise the out-of field neutron dose. The scattering factors for the limonite-steel, magnetite-steel, and ordinary concretes have been calculated as 0.91±0.09, 1.08±0.10, and 0.371±0.01, respectively, while the corresponding thermal factors are 34.22±3.84, 23.44±1.62, and 52.28±1.99, respectively (both the scattering and thermal factors are for the isocenter region); moreover, the treatment room is composed of magnetite-steel and limonite-steel concretes, so the neutron doses to the patient are 1.79 times and 1.62 times greater than that from an ordinary concrete composition. The results also confirm that the scattering and thermal factors do not depend on the details of the chosen linear accelerator head model. It is anticipated that the results of the present work will be of great interest to the manufacturers of medical linear accelerators. Copyright © 2016. Published by Elsevier Ltd.

Matrix metalloproteinase-10 (MMP-10) interaction with tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2: binding studies and crystal structure.

PubMed

Batra, Jyotica; Robinson, Jessica; Soares, Alexei S; Fields, Alan P; Radisky, Derek C; Radisky, Evette S

2012-05-04

Matrix metalloproteinase 10 (MMP-10, stromelysin-2) is a secreted metalloproteinase with functions in skeletal development, wound healing, and vascular remodeling; its overexpression is also implicated in lung tumorigenesis and tumor progression. To understand the regulation of MMP-10 by tissue inhibitors of metalloproteinases (TIMPs), we have assessed equilibrium inhibition constants (K(i)) of putative physiological inhibitors TIMP-1 and TIMP-2 for the active catalytic domain of human MMP-10 (MMP-10cd) using multiple kinetic approaches. We find that TIMP-1 inhibits the MMP-10cd with a K(i) of 1.1 × 10(-9) M; this interaction is 10-fold weaker than the inhibition of the similar MMP-3 (stromelysin-1) catalytic domain (MMP-3cd) by TIMP-1. TIMP-2 inhibits the MMP-10cd with a K(i) of 5.8 × 10(-9) M, which is again 10-fold weaker than the inhibition of MMP-3cd by this inhibitor (K(i) = 5.5 × 10(-10) M). We solved the x-ray crystal structure of TIMP-1 bound to the MMP-10cd at 1.9 Å resolution; the structure was solved by molecular replacement and refined with an R-factor of 0.215 (R(free) = 0.266). Comparing our structure of MMP-10cd·TIMP-1 with the previously solved structure of MMP-3cd·TIMP-1 (Protein Data Bank entry 1UEA), we see substantial differences at the binding interface that provide insight into the differential binding of stromelysin family members to TIMP-1. This structural information may ultimately assist in the design of more selective TIMP-based inhibitors tailored for specificity toward individual members of the stromelysin family, with potential therapeutic applications.

Dietary α-cyclodextrin modifies gut microbiota and reduces fat accumulation in high-fat-diet-fed obese mice.

PubMed

Nihei, Nanako; Okamoto, Hinako; Furune, Takahiro; Ikuta, Naoko; Sasaki, Kengo; Rimbach, Gerald; Yoshikawa, Yutaka; Terao, Keiji

2018-05-07

We investigated the effect of α-cyclodextrin (α-CD) on the bacterial populations of gut microbiota, production of organic acids, and short-chain fatty acids (SCFAs), and lipid metabolism in obese mice induced by feeding a high-fat diet (HFD). Male C57BL/6J mice were assigned to three diet groups: normal diet (ND) (5% [w/w] fat), HFD (35% [w/w] fat), and HFD (35% [w/w] fat) + 5.5% (w/w) α-CD for 16 weeks. Increases in body and epididymal adipose tissue weights were observed in the HFD group compared with the ND group, which were attenuated in the HFD+α-CD group. The supplementation of α-CD increased the total number of bacteria, Bacteroides, Bifidobacterium, and Lactobacillus that were decreased in gut microbiota of mice by feeding the HFD. Importantly, α-CD administration increased the concentrations of lactic acid and SCFAs, such as acetic, propionic, and butyric acids, and decreased glucose concentrations in cecal contents. Furthermore, supplementation of α-CD upregulated the gene expression of peroxisome proliferator-activated receptor (PPAR)γ involved in adipocyte differentiation and PPARα involved in energy expenditure and downregulated that of sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase involved in fatty acid and triglyceride synthesis in adipose tissue. This study revealed that the alteration in gut microbiota and increased production of lactic acid and SCFAs by supplementation of α-CD have beneficial antiobesity effects via modulating the expression of genes related to lipid metabolism, indicating a prebiotic property of α-CD. © 2018 BioFactors, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis

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

Xiong, Shanshan; Pan, Xiujie; Xu, Long

Purpose: Radiation-induced pulmonary fibrosis results from thoracic radiation therapy and severely limits radiation therapy approaches. CD4{sup +}CD25{sup +}FoxP3{sup +} regulatory T cells (Tregs) as well as epithelium-to-mesenchyme transition (EMT) cells are involved in pulmonary fibrosis induced by multiple factors. However, the mechanisms of Tregs and EMT cells in irradiation-induced pulmonary fibrosis remain unclear. In the present study, we investigated the influence of Tregs on EMT in radiation-induced pulmonary fibrosis. Methods and Materials: Mice thoraxes were irradiated (20 Gy), and Tregs were depleted by intraperitoneal injection of a monoclonal anti-CD25 antibody 2 hours after irradiation and every 7 days thereafter. Mice were treated onmore » days 3, 7, and 14 and 1, 3, and 6 months post irradiation. The effectiveness of Treg depletion was assayed via flow cytometry. EMT and β-catenin in lung tissues were detected by immunohistochemistry. Tregs isolated from murine spleens were cultured with mouse lung epithelial (MLE) 12 cells, and short interfering RNA (siRNA) knockdown of β-catenin in MLE 12 cells was used to explore the effects of Tregs on EMT and β-catenin via flow cytometry and Western blotting. Results: Anti-CD25 antibody treatment depleted Tregs efficiently, attenuated the process of radiation-induced pulmonary fibrosis, hindered EMT, and reduced β-catenin accumulation in lung epithelial cells in vivo. The coculture of Tregs with irradiated MLE 12 cells showed that Tregs could promote EMT in MLE 12 cells and that the effect of Tregs on EMT was partially abrogated by β-catenin knockdown in vitro. Conclusions: Tregs can promote EMT in accelerating radiation-induced pulmonary fibrosis. This process is partially mediated through β-catenin. Our study suggests a new mechanism for EMT, promoted by Tregs, that accelerates radiation-induced pulmonary fibrosis.« less

Pre-transplant and post-transplant soluble CD30 for prediction and diagnosis of acute kidney allograft rejection.

PubMed

Nafar, Mohsen; Farrokhi, Farhat; Vaezi, Mohammad; Entezari, Amir-Ebrahim; Pour-Reza-Gholi, Fatemeh; Firoozan, Ahmad; Eniollahi, Behzad

2009-01-01

Serum levels of soluble CD30 (sCD30) have been considered as a predictor of acute kidney allograft rejection. We have evaluated the pre-transplant and post-transplant levels of sCD30 with the aim of determining its value in predicting and diagnosing kidney rejection. We measured sCD30 serum levels before kidney transplantation, 5 days post-operatively, and at creatinine elevation episodes. The predictive value of sCD30 for diagnosing acute rejection (AR) within the first 6 post-operative months was assessed in 203 kidney recipients from living donors. Pre-transplant and post-operative levels of serum sCD30 were 58.10 +/- 52.55 and 51.55 +/- 49.65 U/ml, respectively (P = 0.12). Twenty-three patients experienced biopsy-proven acute rejection, and 28 had acute allograft dysfunction due to non-immunologic diseases. The pre-transplant sCD30 level was not different between patients with and without AR. However, post-transplant sCD30 was higher in the AR group. The median serum level of post-transplant sCD30 was 52 U/ml in the AR group and 26.3 U/ml in a control group (P < 0.001). The relative changes of sCD30 on day 5 were higher in patients with AR (P = 0.003). Based on post-transplant sCD30 levels, we were able to differentiate between kidney recipients who experienced an AR within 6 months post-surgery and those without an AR (cutoff value 41 U/ml; sensitivity 70%; specificity 71.7%). The level of sCD30 during periods of elevated serum creatinine was not independently associated with the diagnosis of AR. Post-transplant sCD30 levels and their relative changes are higher in patients experiencing AR. We propose further studies on the post-transplant trend of this marker for the prediction of AR.

Role of Complement in Red Cell Dysfunction in Trauma

DTIC Science & Technology

2013-12-01

fragmentation 2. Erythrocyte membrane has there major components: 1) membrane proteins, that are either transmembrane or attached to the plasma membrane...through GPI- or lipid-anchors (glycophorins, CD47, CR1, band 3, CD55, CD59, flotillin, stomatin etc.) 2) skeletal proteins, located below the plasma ...glycophorin C with spectrin skeleton 3. More recently, adducin and dematin have also been implicated in linking plasma membrane protein Glut-1

Role of Complement in Red Cell Dysfunction in Trauma

DTIC Science & Technology

2012-12-01

there major components: 1) membrane proteins, that are either transmembrane or attached to the plasma membrane through GPI- or lipid-anchors...glycophorins, CD47, CR1, band 3, CD55, CD59, flotillin, stomatin etc.) 2) skeletal proteins, located below the plasma membrane, conferring the erythrocyte...skeleton 3. More recently, adducin and dematin have also been implicated in linking plasma membrane protein Glut-1 (glucose transporter-1) to spectrin 4

Neutrophils prime a long-lived effector macrophage phenotype that mediates accelerated helminth expulsion

USDA-ARS?s Scientific Manuscript database

The innate immune cell populations that mediate metazoan parasite expulsion remain largely undefined. We examined the role of innate cells in the immune response to the nematode parasite Nippostrongylus brasiliensis hypothesizing that they may mediate the markedly accelerated CD4+ T cell-independen...

Chloride-induced corrosion of steel in cracked concrete – Part I: Experimental studies under accelerated and natural marine environments

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

Otieno, M., E-mail: Mike.Otieno@wits.ac.za; Beushausen, H.; Alexander, M.

Parallel corrosion experiments were carried out for 2¼ years by exposing one half of 210 beam specimens (120 × 130 × 375 mm long) to accelerated laboratory corrosion (cyclic wetting and drying) while the other half underwent natural corrosion in a marine tidal zone. Experimental variables were crack width w{sub cr} (0, incipient crack, 0.4, 0.7 mm), cover c (20, 40 mm), binder type (PC, PC/GGBS, PC/FA) and w/b ratio (0.40, 0.55). Results show that corrosion rate (i{sub corr}) was affected by the experimental variables in the following manner: i{sub corr} increased with increase in crack width, and decreased withmore » increase in concrete quality and cover depth. The results also show that the corrosion performance of concretes in the field under natural corrosion cannot be inferred from its performance in the laboratory under accelerated corrosion. Other factors such as corrosion process should be taken into account.« less

Release of metals from metal-amended soil treated with a sulfosuccinamate surfactant: effects of surfactant concentration, soil/solution ratio, and pH.

PubMed

Hernández-Soriano, Maria del Carmen; Peña, Aránzazu; Dolores Mingorance, Ma

2010-01-01

Anionic surfactants, mainly sulfosuccinamates, can be found in soils as the result of sludge application, wastewater irrigation, and remediation processes. Relatively high concentrations of surfactants together with multimetals can represent an environmental risk. A study was performed to assess the potential of the anionic surfactant Aerosol 22 (A22) for release of Cd, Cu, Pb, and Zn from a metal-amended soil representative of a Mediterranean area. Metal desorption was performed by batch experiments and release kinetics were assessed. Response surface methodology was applied to determine the influence of A22 concentration and the surfactant/soil ratio, as extraction key factors. An increase in solution/soil ratio to 100 (mL g(-1)) caused higher metal release. Leaching predictions found Pb to have the lowest and Cd the highest hazard. Metal release was highly dependent on pH. When extraction was made at pH less than 7, low or negligible amounts of metals were leached, whereas an increase to pH 7 caused desorption rates of 50 to 55% for Cd, Cu, and Zn but only 35% for Pb. Complexed metal-carboxylic groups from A22 were mainly responsible for its higher extractive capacity, especially of Cd and Cu.

Investigation of Gallium Nitride Transistor Reliability through Accelerated Life Testing and Modeling

DTIC Science & Technology

2011-12-01

Carbon Cd Cadmium CdS Cadmium Sulfide CMOS Complementary Metal Oxide Semiconductor DC Direct Current DoD Department of Defense EBL Electron...Crane Division [NAVSEA Crane], Crane, Indiana ) are Section 4.1and Section 4.3, Condition 2. Eight devices were stressed for over 1000 hours each and

A theoretical investigation of the structural and electronic properties of 55-atom nanoclusters: The examples of Y-Tc and Pt.

PubMed

Batista, Krys E A; Piotrowski, Maurício J; Chaves, Anderson S; Da Silva, Juarez L F

2016-02-07

Several studies have found that the Pt55 nanocluster adopts a distorted reduced core structure, DRC55, in which there are 8-11 atoms in the core and 47-44 atoms in the surface, instead of the compact and high-symmetry icosahedron structure, ICO55, with 13 and 42 atoms in the core and surface, respectively. The DRC structure has also been obtained as the putative global minimum configuration (GMC) for the Zn55 (3d), Cd55 (4d), and Au55 (5d) systems. Thus, the DRC55 structure has been reported only for systems with a large occupation of the d-states, where the effects of the occupation of the valence anti-bonding d-states might play an important role. Can we observe the DRC structure for 55-atom transition-metal systems with non-occupation of the anti-bonding d-states? To address this question, we performed a theoretical investigation of the Y 55, Zr55, Nb55, Mo55, Tc55, and Pt55 nanoclusters, employing density functional theory calculations. For the putative GMCs, we found that the Y 55 adopts the ICO55 structure, while Nb55 and Mo55 adopt a bulk-like fragment based on the hexagonal close-packed structure and Tc55 adopts a face-centered cubic fragment; however, Zr55 adopts a DRC55 structure, like Zn55, Cd55, Pt55, and Au55. Thus we can conclude that the preference for DRC55 structure is not related to the occupation of the anti-bonding d-states, but to a different effect, in fact, a combination of structural and electronic effects. Furthermore, we obtained that the binding energy per atom follows the occupation of the bonding and anti-bonding model, i.e., the stability of the studied systems increases from Y to Tc with a small oscillation for Mo, which also explains the equilibrium bond lengths. We obtained a larger magnetic moment for Y 55 (31 μB) which can be explained by the localization of the d-states in Y at nanoscale, which is not observed for the remaining systems (0-1 μB).

Low-Intensity Vibration Improves Angiogenesis and Wound Healing in Diabetic Mice

PubMed Central

Weinheimer-Haus, Eileen M.; Judex, Stefan; Ennis, William J.; Koh, Timothy J.

2014-01-01

Chronic wounds represent a significant health problem, especially in diabetic patients. In the current study, we investigated a novel therapeutic approach to wound healing – whole body low-intensity vibration (LIV). LIV is anabolic for bone, by stimulating the release of growth factors, and modulating stem cell proliferation and differentiation. We hypothesized that LIV improves the delayed wound healing in diabetic mice by promoting a pro-healing wound environment. Diabetic db/db mice received excisional cutaneous wounds and were subjected to LIV (0.4 g at 45 Hz) for 30 min/d or a non-vibrated sham treatment (controls). Wound tissue was collected at 7 and 15 d post-wounding and wound healing, angiogenesis, growth factor levels and wound cell phenotypes were assessed. LIV increased angiogenesis and granulation tissue formation at day 7, and accelerated wound closure and re-epithelialization over days 7 and 15. LIV also reduced neutrophil accumulation and increased macrophage accumulation. In addition, LIV increased expression of pro-healing growth factors and chemokines (insulin-like growth factor-1, vascular endothelial growth factor and monocyte chemotactic protein-1) in wounds. Despite no evidence of a change in the phenotype of CD11b+ macrophages in wounds, LIV resulted in trends towards a less inflammatory phenotype in the CD11b− cells. Our findings indicate that LIV may exert beneficial effects on wound healing by enhancing angiogenesis and granulation tissue formation, and these changes are associated with increases in pro-angiogenic growth factors. PMID:24618702

Taking Control of Castleman Disease: Leveraging Precision Medicine Technologies to Accelerate Rare Disease Research.

PubMed

Newman, Samantha Kass; Jayanthan, Raj K; Mitchell, Grant W; Carreras Tartak, Jossie A; Croglio, Michael P; Suarez, Alexander; Liu, Amy Y; Razzo, Beatrice M; Oyeniran, Enny; Ruth, Jason R; Fajgenbaum, David C

2015-12-01

Castleman disease (CD) is a rare and heterogeneous disorder characterized by lymphadenopathy that may occur in a single lymph node (unicentric) or multiple lymph nodes (multicentric), the latter typically occurring secondary to excessive proinflammatory hypercytokinemia. While a cohort of multicentric Castleman disease (MCD) cases are caused by Human Herpes Virus-8 (HHV-8), the etiology of HHV-8 negative, idiopathic MCD (iMCD), remains unknown. Breakthroughs in "omics" technologies that have facilitated the development of precision medicine hold promise for elucidating disease pathogenesis and identifying novel therapies for iMCD. However, in order to leverage precision medicine approaches in rare diseases like CD, stakeholders need to overcome several challenges. To address these challenges, the Castleman Disease Collaborative Network (CDCN) was founded in 2012. In the past 3 years, the CDCN has worked to transform the understanding of the pathogenesis of CD, funded and initiated genomics and proteomics research, and united international experts in a collaborative effort to accelerate progress for CD patients. The CDCN's collaborative structure leverages the tools of precision medicine and serves as a model for both scientific discovery and advancing patient care.

Neonatal microbial colonization in mice promotes prolonged dominance of CD11b(+)Gr-1(+) cells and accelerated establishment of the CD4(+) T cell population in the spleen.

PubMed

Kristensen, Matilde B; Metzdorff, Stine B; Bergström, Anders; Damlund, Dina S M; Fink, Lisbeth N; Licht, Tine R; Frøkiær, Hanne

2015-09-01

To assess the microbial influence on postnatal hematopoiesis, we examined the role of early life microbial colonization on the composition of leukocyte subsets in the neonatal spleen. A high number of CD11b(+)Gr-1(+) splenocytes present perinatally was sustained for a longer period in conventionally colonized (CONV) mice than in mono-colonized (MC) and germfree (GF) mice, and the CD4(+) T cell population established faster in CONV mice. At the day of birth, compared to GF mice, the expression of Cxcl2 was up-regulated and Arg1 down-regulated in livers of CONV mice. This coincided with lower abundance of polylobed cells in the liver of CONV mice. An earlier peak in the expression of the genes Tjp1, Cdh1, and JamA in intestinal epithelial cells of CONV mice indicated an accelerated closure of the epithelial barrier. In conclusion, we have identified an important microbiota-dependent neonatal hematopoietic event, which we suggest impacts the subsequent development of the T cell population in the murine spleen.

Early Course of Inflammatory Bowel Disease in a Population-Based Inception Cohort Study From 8 Countries in Asia and Australia.

PubMed

Ng, Siew C; Zeng, Zhirong; Niewiadomski, Ola; Tang, Whitney; Bell, Sally; Kamm, Michael A; Hu, Pinjin; de Silva, H Janaka; Niriella, Madunil A; Udara, W S A A Yasith; Ong, David; Ling, Khoon Lin; Ooi, Choon Jin; Hilmi, Ida; Lee Goh, Khean; Ouyang, Qin; Wang, Yu Fang; Wu, Kaichun; Wang, Xin; Pisespongsa, Pises; Manatsathit, Sathaporn; Aniwan, Satimai; Limsrivilai, Julajak; Gunawan, Jeffri; Simadibrata, Marcellus; Abdullah, Murdani; Tsang, Steve W C; Lo, Fu Hang; Hui, Aric J; Chow, Chung Mo; Yu, Hon Ho; Li, Mo Fong; Ng, Ka Kei; Ching, Jessica Y L; Chan, Victor; Wu, Justin C Y; Chan, Francis K L; Chen, Minhu; Sung, Joseph J Y

2016-01-01

The incidence of inflammatory bowel disease (IBD) is increasing in Asia, but little is known about disease progression in this region. The Asia-Pacific Crohn's and Colitis Epidemiology Study was initiated in 2011, enrolling subjects from 8 countries in Asia (China, Hong Kong, Indonesia, Sri Lanka, Macau, Malaysia, Singapore, and Thailand) and Australia. We present data from this ongoing study. We collected data on 413 patients diagnosed with IBD (222 with ulcerative colitis [UC], 181 with Crohn's disease [CD], 10 with IBD unclassified; median age, 37 y) from 2011 through 2013. We analyzed the disease course and severity and mortality. Risks for medical and surgical therapies were assessed using Kaplan-Meier analysis. The cumulative probability that CD would change from inflammatory to stricturing or penetrating disease was 19.6%. The cumulative probabilities for use of immunosuppressants or anti-tumor necrosis factor agents were 58.9% and 12.0% for patients with CD, and 12.7% and 0.9% for patients with UC, respectively. Perianal CD was associated with an increased risk of anti-tumor necrosis factor therapy within 1 year of its diagnosis (hazard ratio, 2.97; 95% confidence interval, 1.09-8.09). The cumulative probabilities for surgery 1 year after diagnosis were 9.1% for patients with CD and 0.9% for patients with UC. Patients with CD and penetrating disease had a 7-fold increase for risk of surgery, compared with patients with inflammatory disease (hazard ratio, 7.67; 95% confidence interval, 3.93-14.96). The overall mortality for patients with IBD was 0.7%. In a prospective population-based study, we found that the early course of disease in patients with IBD in Asia was comparable with that of the West. Patients with CD frequently progress to complicated disease and have accelerated use of immunosuppressants. Few patients with early stage UC undergo surgery in Asia. Increasing our understanding of IBD progression in different populations can help optimize therapy and improve outcomes. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation

PubMed Central

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-01-01

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant. PMID:28368030

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation.

PubMed

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-04-03

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant.

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation

NASA Astrophysics Data System (ADS)

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-04-01

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant.

Extensive characterization of the immunophenotype and pattern of cytokine production by distinct subpopulations of normal human peripheral blood MHC II+/lineage− cells

PubMed Central

Almeida, J; Bueno, C; Alguero, M C; Sanchez, M L; Cañizo, M C; Fernandez, M E; Vaquero, J M; Laso, F J; Escribano, L; San Miguel, J F; Orfao, A

1999-01-01

Dendritic cells (DC) represent the most powerful professional antigen-presenting cells (APC) in the immune system. The aim of the present study was to analyse, on a single-cell basis by multiparametric flow cytometry with simultaneous four-colour staining and a two-step acquisition procedure, the immunophenotypic profile and cytokine production of DC from 67 normal whole peripheral blood (PB) samples. Two clearly different subsets of HLA-II+/lineage− were identified on the basis of their distinct phenotypic characteristics: one DC subset was CD33strong+ and CD123dim+ (0.16 ± 0.06% of the PB nucleated cells and 55.9 ± 11.9% of all PB DC) and the other, CD33dim+ and CD123strong+ (0.12 ± 0.04% of PB nucleated cells and 44.53 ± 11.5% of all PB DC). Moreover, the former DC subpopulation clearly showed higher expression of the CD13 myeloid-associated antigen, the CD29 and CD58 adhesion molecules, the CD2, CD5 and CD86 costimulatory molecules, the CD32 IgG receptor and the CD11c complement receptor. In addition, these cells showed stronger HLA-DR and HLA-DQ expression and a higher reactivity for the IL-6 receptor α-chain (CD126) and for CD38. In contrast, the CD123strong+/CD33dim+ DC showed a stronger reactivity for the CD4 and CD45RA molecules, whereas they did not express the CD58, CD5, CD11c and CD13 antigens. Regarding cytokine production, our results show that while the CD33strong+/CD123dim+ DC are able to produce significant amounts of inflammatory cytokines, such as IL-1β (97 ± 5% of positive cells), IL-6 (96 ± 1.1% of positive cells), IL-12 (81.5 ± 15.5% of positive cells) and tumour necrosis factor-alpha (TNF-α) (84 ± 22.1% of positive cells) as well as chemokines such as IL-8 (99 ± 1% of positive cells), the functional ability of the CD123strong+/CD33dim+ DC subset to produce cytokines under the same conditions was almost null. Our results therefore clearly show the presence of two distinct subsets of DC in normal human PB, which differ not only in their immunophenotype but also in their functionality, as regards cytokine production. PMID:10594557

Clinical and demographic factors associated with low viral load in early untreated HIV infection in the INSIGHT Strategic Timing of AntiRetroviral Treatment trial

PubMed Central

Law, Matthew G; Achhra, Amit; Deeks, Steven G; Gazzard, Brian; Migueles, Stephen A; Novak, Richard M; Ristola, Matti

2014-01-01

Objectives A small subset of HIV-positive adults have low HIV RNA in the absence of therapy, sometimes for years. Clinical factors associated with low HIV RNA in early infection have not been well defined. Methods We assessed factors associated with low plasma HIV RNA level at study entry in the Strategic Timing of AntiRetroviral Treatment (START) trial. All START participants had a baseline HIV RNA assessment within 60 days prior to randomisation. The key covariables considered for this analysis were race, hepatitis B virus (HBV) and hepatitis C virus (HCV) status. We assessed factors associated with HIV RNA ≤50 and ≤400 copies/mL using logistic regression. Because of the strong association between region of randomisation and baseline low HIV RNA, analyses were stratified by region. Results We found that of 4676 eligible participants randomised in START with a baseline HIV RNA assessment, 113 (2.4%) had HIV RNA ≤50 copies/mL at baseline, and a further 257 (5.5%) between 51 and 400 copies/mL. We found that HIV exposure routes other than male homosexual contact, higher HDL levels, higher CD4 cell counts, and higher CD4:CD8 ratio were associated with increased odds of low HIV RNA. HCV antibody positivity was borderline statistically significantly associated with low HIV RNA. Race and HBV surface antigen positivity were not significantly associated with low HIV RNA. Conclusion In a modern cohort of early untreated HIV infection we found that HIV exposure routes other than male homosexual contact and higher HDL were associated with increased odds of low HIV RNA. PMID:25711322

Peripheral mRNA expression of pluripotency markers in bipolar disorder and the effect of long-term lithium treatment.

PubMed

Ferensztajn-Rochowiak, Ewa; Tarnowski, Maciej; Samochowiec, Jerzy; Michalak, Michal; Ratajczak, Mariusz Z; Rybakowski, Janusz K

2016-10-01

The aim was to evaluate the peripheral mRNA expression of pluripotency master transcriptional factors such as octamer-binding transcription factor 4 (Oct4), sex-determining region Y-box 2 (Sox2) and homeobox protein Nanog, in patients with bipolar disorder (BD), and the effect of long-term lithium treatment. Fifteen BD patients (aged 53±7years) not treated with lithium, with duration of illness>10years, 15 BD patients (aged 55±6years) treated with lithium for 8-40 years (mean 16years) and 15 control subjects (aged 50±5years) were included. Assessment of the mRNA levels of pluripotency markers (Oct-4, Sox 2 and Nanog) was performed, using the Real-time quantitative reverse transcription PCR (RQ-PCR) procedure, and the number of CD34+ very small embryonic-like stem cells (VSELs) was measured by flow cytometric analysis. In those BD patients not treated with lithium the expression of all three pluripotency genes was significantly higher than that in the control subjects. Oct-4, Sox2 and Nanog also positively correlated with the number of CD34+ VSELs/[ul] in this group. In the lithium-treated patients the mRNA levels of Nanog were significantly higher than in the control individuals and correlated with the number and % of CD34+ VSELs. The overexpression of the pluripotency master transcriptional factors in patients with a long duration of BD not treated with lithium, may contribute to the pathogenesis of the illness and make them potential biological markers of BD. Long-term lithium treatment may attenuate these excessive regenerative processes, especially in relation to the transcription factors Oct-4 and Sox2. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Epigenetic Aging and Immune Senescence in Women With Insomnia Symptoms: Findings From the Women's Health Initiative Study.

PubMed

Carroll, Judith E; Irwin, Michael R; Levine, Morgan; Seeman, Teresa E; Absher, Devin; Assimes, Themistocles; Horvath, Steve

2017-01-15

Insomnia symptoms are associated with vulnerability to age-related morbidity and mortality. Cross-sectional data suggest that accelerated biological aging may be a mechanism through which sleep influences risk. A novel method for determining age acceleration using epigenetic methylation to DNA has demonstrated predictive utility as an epigenetic clock and prognostic of age-related morbidity and mortality. We examined the association of epigenetic age and immune cell aging with sleep in the Women's Health Initiative study (N = 2078; mean 64.5 ± 7.1 years of age) with assessment of insomnia symptoms (restlessness, difficulty falling asleep, waking at night, trouble getting back to sleep, and early awakenings), sleep duration (short sleep 5 hours or less; long sleep greater than 8 hours), epigenetic age, naive T cell (CD8+CD45RA+CCR7+), and late differentiated T cells (CD8+CD28-CD45RA-). Insomnia symptoms were related to advanced epigenetic age (β ± SE = 1.02 ± 0.37, p = .005) after adjustments for covariates. Insomnia symptoms were also associated with more late differentiated T cells (β ± SE = 0.59 ± 0.21, p = .006), but not with naive T cells. Self-reported short and long sleep duration were unrelated to epigenetic age. Short sleep, but not long sleep, was associated with fewer naive T cells (p < .005) and neither was related to late differentiated T cells. Symptoms of insomnia were associated with increased epigenetic age of blood tissue and were associated with higher counts of late differentiated CD8+ T cells. Short sleep was unrelated to epigenetic age and late differentiated cell counts, but was related to a decline in naive T cells. In this large population-based study of women in the United States, insomnia symptoms are implicated in accelerated aging. Copyright © 2016. Published by Elsevier Inc.

Benefits of plasma rich in growth factors (PRGF) in skin photodamage: clinical response and histological assessment.

PubMed

Díaz-Ley, B; Cuevast, J; Alonso-Castro, L; Calvo, M I; Ríos-Buceta, L; Orive, G; Anitua, E; Jaén, P

2015-01-01

Skin ageing is characterized by small and fine wrinkles, roughness, laxity, and pigmentation as a result of epidermal thinning, collagen degradation, dermal atrophy, and fewer fibroblasts. Plasma rich in growth factors (PRGF) is an autologous plasma preparation enriched in proteins obtained from patient's own blood aimed at accelerating tissue repair and regeneration. To evaluate the benefits of PRGF in skin photodamage, 10 healthy volunteers were treated with three consecutive intradermal injections of PRGF in the facial area. Clinical outcomes and histological analysis were performed. A statistically significant increase in the epidermis and papillary dermis thickness was seen after PRGF treatment (p < 0.001). Skin thickening was observed in all patients studied, being more intense in the group of patients with photodamage (p < 0.001). After PRGF treatment, a reduction of the average area fraction of solar elastosis was observed in patients with clinical and histological signs of skin photodamage (p < 0.05).No changeswere observed in the number of CD31, XIIIa factor, cKit, CD10, nor p53-positive cells. The improvement score after PRGF use was 0.75 (9/12) for the group of patients with signs of skin photodamage. Intradermal PRGF infiltration appears to be an effective treatment for the photodamaged skin. © 2015 Wiley Periodicals, Inc.

Traumatic stress and accelerated DNA methylation age: A meta-analysis.

PubMed

Wolf, Erika J; Maniates, Hannah; Nugent, Nicole; Maihofer, Adam X; Armstrong, Don; Ratanatharathorn, Andrew; Ashley-Koch, Allison E; Garrett, Melanie; Kimbrel, Nathan A; Lori, Adriana; Va Mid-Atlantic Mirecc Workgroup; Aiello, Allison E; Baker, Dewleen G; Beckham, Jean C; Boks, Marco P; Galea, Sandro; Geuze, Elbert; Hauser, Michael A; Kessler, Ronald C; Koenen, Karestan C; Miller, Mark W; Ressler, Kerry J; Risbrough, Victoria; Rutten, Bart P F; Stein, Murray B; Ursano, Robert J; Vermetten, Eric; Vinkers, Christiaan H; Uddin, Monica; Smith, Alicia K; Nievergelt, Caroline M; Logue, Mark W

2018-06-01

Recent studies examining the association between posttraumatic stress disorder (PTSD) and accelerated aging, as defined by DNA methylation-based estimates of cellular age that exceed chronological age, have yielded mixed results. We conducted a meta-analysis of trauma exposure and PTSD diagnosis and symptom severity in association with accelerated DNA methylation age using data from 9 cohorts contributing to the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (combined N = 2186). Associations between demographic and cellular variables and accelerated DNA methylation age were also examined, as was the moderating influence of demographic variables. Meta-analysis of regression coefficients from contributing cohorts revealed that childhood trauma exposure (when measured with the Childhood Trauma Questionnaire) and lifetime PTSD severity evidenced significant, albeit small, meta-analytic associations with accelerated DNA methylation age (ps = 0.028 and 0.016, respectively). Sex, CD4T cell proportions, and natural killer cell proportions were also significantly associated with accelerated DNA methylation age (all ps < 0.02). PTSD diagnosis and lifetime trauma exposure were not associated with advanced DNA methylation age. There was no evidence of moderation of the trauma or PTSD variables by demographic factors. Results suggest that traumatic stress is associated with advanced epigenetic age and raise the possibility that cells integral to immune system maintenance and responsivity play a role in this. This study highlights the need for additional research into the biological mechanisms linking traumatic stress to accelerated DNA methylation age and the importance of furthering our understanding of the neurobiological and health consequences of PTSD. Published by Elsevier Ltd.

Hyperforin/HP-β-Cyclodextrin Enhances Mechanosensitive Ca2+ Signaling in HaCaT Keratinocytes and in Atopic Skin Ex Vivo Which Accelerates Wound Healing.

PubMed

Takada, Hiroya; Yonekawa, Jun; Matsumoto, Masami; Furuya, Kishio; Sokabe, Masahiro

2017-01-01

Cutaneous wound healing is accelerated by mechanical stretching, and treatment with hyperforin, a major component of a traditional herbal medicine and a known TRPC6 activator, further enhances the acceleration. We recently revealed that this was due to the enhancement of ATP-Ca 2+ signaling in keratinocytes by hyperforin treatment. However, the low aqueous solubility and easy photodegradation impede the topical application of hyperforin for therapeutic purposes. We designed a compound hydroxypropyl- β -cyclodextrin- (HP- β -CD-) tetracapped hyperforin, which had increased aqueous solubility and improved photoprotection. We assessed the physiological effects of hyperforin/HP- β -CD on wound healing in HaCaT keratinocytes using live imaging to observe the ATP release and the intracellular Ca 2+ increase. In response to stretching (20%), ATP was released only from the foremost cells at the wound edge; it then diffused to the cells behind the wound edge and activated the P2Y receptors, which caused propagating Ca 2+ waves via TRPC6. This process might facilitate wound closure, because the Ca 2+ response and wound healing were inhibited in parallel by various inhibitors of ATP-Ca 2+ signaling. We also applied hyperforin/HP- β -CD on an ex vivo skin model of atopic dermatitis and found that hyperforin/HP- β -CD treatment for 24 h improved the stretch-induced Ca 2+ responses and oscillations which failed in atopic skin.

Hyperforin/HP-β-Cyclodextrin Enhances Mechanosensitive Ca2+ Signaling in HaCaT Keratinocytes and in Atopic Skin Ex Vivo Which Accelerates Wound Healing

PubMed Central

Takada, Hiroya; Yonekawa, Jun; Matsumoto, Masami; Sokabe, Masahiro

2017-01-01

Cutaneous wound healing is accelerated by mechanical stretching, and treatment with hyperforin, a major component of a traditional herbal medicine and a known TRPC6 activator, further enhances the acceleration. We recently revealed that this was due to the enhancement of ATP-Ca2+ signaling in keratinocytes by hyperforin treatment. However, the low aqueous solubility and easy photodegradation impede the topical application of hyperforin for therapeutic purposes. We designed a compound hydroxypropyl-β-cyclodextrin- (HP-β-CD-) tetracapped hyperforin, which had increased aqueous solubility and improved photoprotection. We assessed the physiological effects of hyperforin/HP-β-CD on wound healing in HaCaT keratinocytes using live imaging to observe the ATP release and the intracellular Ca2+ increase. In response to stretching (20%), ATP was released only from the foremost cells at the wound edge; it then diffused to the cells behind the wound edge and activated the P2Y receptors, which caused propagating Ca2+ waves via TRPC6. This process might facilitate wound closure, because the Ca2+ response and wound healing were inhibited in parallel by various inhibitors of ATP-Ca2+ signaling. We also applied hyperforin/HP-β-CD on an ex vivo skin model of atopic dermatitis and found that hyperforin/HP-β-CD treatment for 24 h improved the stretch-induced Ca2+ responses and oscillations which failed in atopic skin. PMID:28210627

Efficacy and Safety of Vedolizumab in Ulcerative Colitis and Crohn's Disease Patients Stratified by Age.

PubMed

Yajnik, Vijay; Khan, Nabeel; Dubinsky, Marla; Axler, Jeffrey; James, Alexandra; Abhyankar, Brihad; Lasch, Karen

2017-02-01

The efficacy and safety of vedolizumab, a gut-selective α 4 β 7 integrin antibody, were demonstrated in the GEMINI 1 and GEMINI 2 clinical trials of adults aged 18-80 years. We investigated the efficacy and safety of vedolizumab in patients stratified by age from the GEMINI trials. Safety and efficacy, including clinical response, clinical remission, and corticosteroid-free remission, at week 6 and/or 52 were determined post hoc in patients aged <35, 35 to <55, and ≥55 years. At baseline, 353, 412, and 130 ulcerative colitis (UC) and 582, 443, and 90 Crohn's disease (CD) patients were aged <35, 35 to <55, and ≥55. Of these patients, 56 were aged ≥65 years (UC: 33, CD: 23). Trends favoring vedolizumab over placebo were observed for most efficacy endpoints irrespective of patient age; some variability between subgroups was observed. Safety profiles of vedolizumab and placebo were similar in all age groups. Vedolizumab-treated patients aged ≥55 had the lowest incidence of serious infections (0.9 per 100 person-years) and adverse events leading to hospitalization (14.8 per 100 person-years). There were no age-related differences in the incidence of adverse hematological events, malignancy, or death. The safety and efficacy of vedolizumab in patients with UC or CD were similar for all age groups. The number of patients in the oldest age group in these analyses was small; thus further studies of vedolizumab in larger cohorts of elderly patients are warranted. Millennium Pharmaceuticals, Inc. (d/b/a Takeda Pharmaceuticals International Co.).

Cross-sectional, descriptive study of Chagas disease among citizens of Bolivian origin living in Munich, Germany.

PubMed

Navarro, Miriam; Berens-Riha, Nicole; Hohnerlein, Stefan; Seiringer, Peter; von Saldern, Charlotte; Garcia, Sarah; Blasco-Hernández, Teresa; Navaza, Bárbara; Shock, Jonathan; Bretzel, Gisela; Hoelscher, Michael; Löscher, Thomas; Albajar-Viñas, Pedro; Pritsch, Michael

2017-01-16

Chagas disease (CD) has become a global health issue mainly due to migration. Germany lacks surveillance data and is home to a large Latin American immigrant population. Recognising that Bolivia is the country with the highest CD prevalence in Latin America, this cross-sectional, descriptive pilot study investigated CD and associated factors among citizens of Bolivian origin living in Munich, Germany. Participants completed a questionnaire in order to collect socioeconomic and health-related data. In addition, serology was performed. In case of positive serological tests, PCR diagnostic and clinical staging together with disease management was initiated. Qualitative research was conducted to identify personal and community barriers as well as strategies to increase CD awareness among the population at risk. Between June 2013 and June 2014, 43 people from Bolivia (or descendants) were enrolled. A total of 9.3% (4/43), of whom two women were of childbearing age, tested seropositive (ELISA and IFAT), and one also by PCR. For 2/4 positive participants, clinical evaluation was performed and the indeterminate form of CD was diagnosed. Knowledge about CD symptoms and ways of transmission were completely absent among 55.8% (24/43, 2/4 with CD) and 30.2% (13/43, 1/4 with CD) of participants, respectively. A total of 27.9% (12/43, 0/4 with CD) of participants had donated blood prior to the study, whereas 62.8% (27/43, 3/4 with CD) were motivated to donate blood in the future. The qualitative research identified lack of knowledge as well as stigma and fears related to CD. Despite the small number of participants, the prevalence of CD as well as the potential risk of non-vectorial transmission was alarming. Campaigns adapted for Latin American migrants as well as control strategies should be developed and put in place in order to prevent non-vectorial transmission and actively detect cases of CD in Germany. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Significant IFNγ responses of CD8+ T cells in CMV-seropositive individuals with autoimmune arthritis.

PubMed

Almanzar, Giovanni; Schmalzing, Marc; Trippen, Raimund; Höfner, Kerstin; Weißbrich, Benedikt; Geissinger, Eva; Meyer, Thomas; Liese, Johannes; Tony, Hans-Peter; Prelog, Martina

2016-04-01

Latent Cytomegalovirus (CMV) infection accelerates immunosenescence in elderly with reactivations reported in Rheumatoid Arthritis (RA) and abnormal responses towards CMV in Juvenile Idiopathic Arthritis (JIA). Considering the signs of premature T-cell immunosenescence in arthritis patients, the known effect of CMV latency on speeding up many of these signs in an age-dependent manner and the role of CMV on IFNγ-mediated inflammation in healthy elderly and RA, we hypothesized that latent CMV infection accelerates TCR repertoire restriction, loss of CD28, peripheral T-cell proliferation and aberrant IFNγ responses in arthritis patients. Unspecific and CMVpp65-specific IFNγ responses were investigated in peripheral CD8+ T-cells in RA or JIA patients and healthy, age-matched controls. Despite higher prevalence and concentrations of IgG-anti-CMV, arthritis patients showed lower unspecific IFNγ production, lower CD69-mediated activation and lower CD8+ T-cell proliferation. CMV-seropositive RA patients showed higher intracellular IFNγ production and increased proportions of CD28-CD8+ T-cells after specific CMVpp65 long-term stimulation which was not altered by in vitro blockade of TNFα or IL-6. A skewed TCR repertoire towards oligoclonality and less polyclonality was found in JIA. CMVpp65-specific IFNγ production with expansion of CD28-CD8+ T-cells suggests an efficient control of latent CMV regardless of immunosuppressive therapy or in vitro blockade of TNFα or IL-6 in CMV-seropositive arthritis patients. Increased IgG-anti-CMV antibody concentrations and increased proportions of intracellular IFNγ-producing CMVpp65-specific CD8+ T-cells in long-term cultures propose a possibly role of endogenous CMV reactivations boosting antibody levels and a higher possibly CMV-driven IFNγ-mediated inflammatory potential of CD8+ T-cells in arthritis patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Incidence of short-term complications and associated factors after primary trabeculectomy in Chiang Mai University Hospital.

PubMed

Leeungurasatien, Thidarat; Khunsongkiet, Preeyanuch; Pathanapitoon, Kassara; Wiwatwongwana, Damrong

2016-10-01

To determine the incidence of early postoperative complications and associated factors after primary trabeculectomy in Thai glaucoma patients. This was a retrospective observational study performed in Chiang Mai University Hospital. One hundred and eighteen glaucoma patients participated in the study. All glaucoma patients underwent primary trabeculectomy with mitomycin C (MMC) using fornix-based conjunctival flap technique between December 2011 and May 2013. Surgical complications during the first 3 months of follow-up were recorded, and associated risk factors were analyzed. The incidence of posttrabeculectomy complications was the main outcome measure. One hundred and eighteen eyes of 118 patients were included. Early postoperative complications developed in 55 eyes (56.7%). Complications included hypotony (25 eyes, 27.2%), serous choroidal detachment (CD) (14 eyes, 15.6%), subconjunctival hemorrhage (12 eyes, 13.0%), hyphema (11 eyes, 12.4%), bleb leak (8 eyes, 8.8%), encapsulated bleb (2 eyes, 2.2%), aqueous misdirection (1 eyes, 1.1%), corneal epithelial defect (1 eyes, 1.1%), and overfiltration (1 eyes, 1.1%). There were no reported cases of endophthalmitis or blebitis. Hypotony was associated with serous CD (P = 0.006), and hyphema was associated with neovascular glaucoma (NVG) patients (P = 0.009). NVG was not associated with the increased rate of surgical failure (P = 0.083). The incidence of early complications after first-time trabeculectomy with MMC was high (56.7%) in this Thai clinic setting, but most were transient and self-limited conditions. The correlations between hypotony and CD as well as hyphema and NVG were compatible with the previous studies.

Prevalence of- and risk factors for work disability in Dutch patients with inflammatory bowel disease.

PubMed

Spekhorst, Lieke M; Oldenburg, Bas; van Bodegraven, Ad A; de Jong, Dirk J; Imhann, Floris; van der Meulen-de Jong, Andrea E; Pierik, Marieke J; van der Woude, Janneke C; Dijkstra, Gerard; D'Haens, Geert; Löwenberg, Mark; Weersma, Rinse K; Festen, Eleonora A M

2017-12-14

To determine the prevalence of work disability in inflammatory bowel disease (IBD), and to assess risk factors associated with work disability. For this retrospective cohort study, we retrieved clinical data from the Dutch IBD Biobank on July 2014, containing electronic patient records of 3388 IBD patients treated in the eight University Medical Centers in the Netherlands. Prevalence of work disability was assessed in 2794 IBD patients and compared with the general Dutch population. Multivariate analyses were performed for work disability (sick leave, partial and full disability) and long-term full work disability (> 80% work disability for > 2 years). Prevalence of work disability was higher in Crohn's disease (CD) (29%) and ulcerative colitis (UC) (19%) patients compared to the general Dutch population (7%). In all IBD patients, female sex, a lower education level, and extra-intestinal manifestations, were associated with work disability. In CD patients, an age > 40 years at diagnosis, disease duration > 15 years, smoking, surgical interventions, and anti-TNFα use were associated with work disability. In UC patients, an age > 55 years, and immunomodulator use were associated with work disability. In CD patients, a lower education level (OR = 1.62, 95%CI: 1.02-2.58), and in UC patients, disease complications (OR = 3.39, 95%CI: 1.09-10.58) were associated with long-term full work disability. The prevalence of work disability in IBD patients is higher than in the general Dutch population. Early assessment of risk factors for work disability is necessary, as work disability is substantial among IBD patients.

TPL-2 restricts Ccl24-dependent immunity to Heligmosomoides polygyrus

PubMed Central

Kannan, Yashaswini; Entwistle, Lewis J.; Pelly, Victoria S.; Perez-Lloret, Jimena; Ley, Steven C.

2017-01-01

TPL-2 (COT, MAP3K8) kinase activates the MEK1/2-ERK1/2 MAPK signaling pathway in innate immune responses following TLR, TNFR1 and IL-1R stimulation. TPL-2 contributes to type-1/Th17-mediated autoimmunity and control of intracellular pathogens. We recently demonstrated TPL-2 reduces severe airway allergy to house dust mite by negatively regulating type-2 responses. In the present study, we found that TPL-2 deficiency resulted in resistance to Heligmosomoides polygyrus infection, with accelerated worm expulsion, reduced fecal egg burden and reduced worm fitness. Using co-housing experiments, we found resistance to infection in TPL-2 deficient mice (Map3k8–/–) was independent of microbiota alterations in H. polygyrus infected WT and Map3k8–/–mice. Additionally, our data demonstrated immunity to H. polygyrus infection in TPL-2 deficient mice was not due to dysregulated type-2 immune responses. Genome-wide analysis of intestinal tissue from infected TPL-2-deficient mice identified elevated expression of genes involved in chemotaxis and homing of leukocytes and cells, including Ccl24 and alternatively activated genes. Indeed, Map3k8–/–mice had a significant influx of eosinophils, neutrophils, monocytes and Il4GFP+ T cells. Conditional knockout experiments demonstrated that specific deletion of TPL-2 in CD11c+ cells, but not Villin+ epithelial cells, LysM+ myeloid cells or CD4+ T cells, led to accelerated resistance to H. polygyrus. In line with a central role of CD11c+ cells, CD11c+ CD11b+ cells isolated from TPL-2-deficient mice had elevated Ccl24. Finally, Ccl24 neutralization in TPL-2 deficient mice significantly decreased the expression of Arg1, Retnla, Chil3 and Ear11 correlating with a loss of resistance to H. polygyrus. These observations suggest that TPL-2-regulated Ccl24 in CD11c+CD11b+ cells prevents accelerated type-2 mediated immunity to H. polygyrus. Collectively, this study identifies a previously unappreciated role for TPL-2 controlling immune responses to H. polygyrus infection by restricting Ccl24 production. PMID:28759611

Curcuma oil attenuates accelerated atherosclerosis and macrophage foam-cell formation by modulating genes involved in plaque stability, lipid homeostasis and inflammation.

PubMed

Singh, Vishal; Rana, Minakshi; Jain, Manish; Singh, Niharika; Naqvi, Arshi; Malasoni, Richa; Dwivedi, Anil Kumar; Dikshit, Madhu; Barthwal, Manoj Kumar

2015-01-14

In the present study, the anti-atherosclerotic effect and the underlying mechanism of curcuma oil (C. oil), a lipophilic fraction from turmeric (Curcuma longa L.), was evaluated in a hamster model of accelerated atherosclerosis and in THP-1 macrophages. Male golden Syrian hamsters were subjected to partial carotid ligation (PCL) or FeCl3-induced arterial oxidative injury (Ox-injury) after 1 week of treatment with a high-cholesterol (HC) diet or HC diet plus C. oil (100 and 300 mg/kg, orally). Hamsters fed with the HC diet were analysed at 1, 3 and 5 weeks following carotid injury. The HC diet plus C. oil-fed group was analysed at 5 weeks. In hyperlipidaemic hamsters with PCL or Ox-injury, C. oil (300 mg/kg) reduced elevated plasma and aortic lipid levels, arterial macrophage accumulation, and stenosis when compared with those subjected to arterial injury alone. Similarly, elevated mRNA transcripts of matrix metalloproteinase-2 (MMP-2), MMP-9, cluster of differentiation 45 (CD45), TNF-α, interferon-γ (IFN-γ), IL-1β and IL-6 were reduced in atherosclerotic arteries, while those of transforming growth factor-β (TGF-β) and IL-10 were increased after the C. oil treatment (300 mg/kg). The treatment with C. oil prevented HC diet- and oxidised LDL (OxLDL)-induced lipid accumulation, decreased the mRNA expression of CD68 and CD36, and increased the mRNA expression of PPARα, LXRα, ABCA1 and ABCG1 in both hyperlipidaemic hamster-derived peritoneal and THP-1 macrophages. The administration of C. oil suppressed the mRNA expression of TNF-α, IL-1β, IL-6 and IFN-γ and increased the expression of TGF-β in peritoneal macrophages. In THP-1 macrophages, C. oil supplementation prevented OxLDL-induced production of TNF-α and IL-1β and increased the levels of TGF-β. The present study shows that C. oil attenuates arterial injury-induced accelerated atherosclerosis, inflammation and macrophage foam-cell formation.

Design and Performance Data for 81 Ah FNC Cells

NASA Technical Reports Server (NTRS)

Cohen, F.; Anderman, Menahem

1997-01-01

Design and performance data for 81 Ah FNC cells are given. The conclusions are: that a sealed Ni-Cd cells are not limited to 50 Ah with the FNC design; energy densities of 40 Wh/kg in a conservative high Cd, high electrolyte design have been demonstrated; uniform ATP data and LEO cycling performance is being demonstrated; internal cell pressures remain low under all conditions; and no conditioning is necessary under any LEO profile; accelerated LEO cycling exhibits performance well beyond traditional space Ni-Cd cells.

Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120.

PubMed

deCamp, Allan C; Rolland, Morgane; Edlefsen, Paul T; Sanders-Buell, Eric; Hall, Breana; Magaret, Craig A; Fiore-Gartland, Andrew J; Juraska, Michal; Carpp, Lindsay N; Karuna, Shelly T; Bose, Meera; LePore, Steven; Miller, Shana; O'Sullivan, Annemarie; Poltavee, Kultida; Bai, Hongjun; Dommaraju, Kalpana; Zhao, Hong; Wong, Kim; Chen, Lennie; Ahmed, Hasan; Goodman, Derrick; Tay, Matthew Z; Gottardo, Raphael; Koup, Richard A; Bailer, Robert; Mascola, John R; Graham, Barney S; Roederer, Mario; O'Connell, Robert J; Michael, Nelson L; Robb, Merlin L; Adams, Elizabeth; D'Souza, Patricia; Kublin, James; Corey, Lawrence; Geraghty, Daniel E; Frahm, Nicole; Tomaras, Georgia D; McElrath, M Juliana; Frenkel, Lisa; Styrchak, Sheila; Tovanabutra, Sodsai; Sobieszczyk, Magdalena E; Hammer, Scott M; Kim, Jerome H; Mullins, James I; Gilbert, Peter B

2017-01-01

Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 sequences from vaccine recipients were significantly more distant from the subtype B vaccine insert than sequences from placebo recipients (P = 0.01, Q-value = 0.12). These vaccine effects were associated with signatures mapping to CD4 binding site and CD4-induced monoclonal antibody footprints. These results suggest either (i) no vaccine efficacy to block acquisition of any viral genotype but vaccine-accelerated Env evolution post-acquisition; or (ii) vaccine efficacy against HIV-1s with Env sequences closest to the vaccine insert combined with increased acquisition due to other factors, potentially including the vaccine vector.

Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120

PubMed Central

Edlefsen, Paul T.; Sanders-Buell, Eric; Hall, Breana; Magaret, Craig A.; Fiore-Gartland, Andrew J.; Juraska, Michal; Carpp, Lindsay N.; Karuna, Shelly T.; Bose, Meera; LePore, Steven; Miller, Shana; O'Sullivan, Annemarie; Poltavee, Kultida; Bai, Hongjun; Dommaraju, Kalpana; Zhao, Hong; Wong, Kim; Chen, Lennie; Ahmed, Hasan; Goodman, Derrick; Tay, Matthew Z.; Gottardo, Raphael; Koup, Richard A.; Bailer, Robert; Mascola, John R.; Graham, Barney S.; Roederer, Mario; O’Connell, Robert J.; Michael, Nelson L.; Robb, Merlin L.; Adams, Elizabeth; D’Souza, Patricia; Kublin, James; Corey, Lawrence; Geraghty, Daniel E.; Frahm, Nicole; Tomaras, Georgia D.; McElrath, M. Juliana; Frenkel, Lisa; Styrchak, Sheila; Tovanabutra, Sodsai; Sobieszczyk, Magdalena E.; Hammer, Scott M.; Kim, Jerome H.; Mullins, James I.; Gilbert, Peter B.

2017-01-01

Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 sequences from vaccine recipients were significantly more distant from the subtype B vaccine insert than sequences from placebo recipients (P = 0.01, Q-value = 0.12). These vaccine effects were associated with signatures mapping to CD4 binding site and CD4-induced monoclonal antibody footprints. These results suggest either (i) no vaccine efficacy to block acquisition of any viral genotype but vaccine-accelerated Env evolution post-acquisition; or (ii) vaccine efficacy against HIV-1s with Env sequences closest to the vaccine insert combined with increased acquisition due to other factors, potentially including the vaccine vector. PMID:29149197

Synthesis and characterization of low-molecular-weight π-conjugated polymers covered by persilylated β-cyclodextrin

PubMed Central

Resmerita, Ana-Maria; Stefanache, Andreea; Balan, Mihaela; Harabagiu, Valeria

2012-01-01

Summary The paper reports the preparation of a poly[2,7-(9,9-dioctylfluorene)-alt-5,5'-bithiophene/PS-βCD] (PDOF-BTc) polyrotaxane copolymer, through a Suzuki coupling reaction between the 5,5'-dibromo-2,2'-bithiophene (BT) inclusion complex with persilylated β-cyclodextrin (PS-βCD), and 9,9-dioctylfluorene-2,7-bis(trimethylene borate) (DOF) as the blocking group. The chemical structure and the thermal and morphological properties of the resulting polyrotaxane were investigated by using NMR and FT-IR spectroscopy, TGA, DSC and AFM analysis. The encapsulation of BT inside the PS-βCD cavity results in improvements in the solubility, as well as in different surface morphology and thermal properties of the PDOF-BTc rotaxane copolymer compared to its noncomplexed PDOF-BT homologue. In contrast, the number-average molecular weight (M n) of PDOF-BTc rotaxane copolymer indicated lower values suggesting that the condensation reaction is subjected to steric effects of the bulkier silylated groups, affecting the ability of the diborate groups from the DOF molecule to partially penetrate the PS-βCD cavity. PMID:23019485

CD44 variant isoform 9 emerges in response to injury and contributes to the regeneration of the gastric epithelium

PubMed Central

Bertaux-Skeirik, Nina; Wunderlich, Mark; Teal, Emma; Chakrabarti, Jayati; Biesiada, Jacek; Mahe, Maxime; Sundaram, Nambirajan; Gabre, Joel; Hawkins, Jennifer; Jian, Gao; Engevik, Amy C.; Yang, Li; Wang, Jiang; Goldenring, James R.; Qualls, Joseph E.; Medvedovic, Mario; Helmrath, Michael A.; Diwan, Tayyab; Mulloy, James C.; Zavros, Yana

2017-01-01

The CD44 gene encodes several protein isoforms due to alternative splicing and post translational modifications. Given that CD44 variant isoform 9 (CD44v9) is expressed within Spasmolytic Polypeptide/TFF2-Expressing Metaplasia (SPEM) glands during repair, CD44v9 may be play a functional role during the process of regeneration of the gastric epithelium. Here we hypothesize that CD44v9 marks a regenerative cell lineage responsive to infiltrating macrophages during regeneration of the gastric epithelium. Ulcers were induced in CD44-decient (CD44KO) and C57BL/6 (BL6) mice by a localized application of acetic acid to the serosal surface of the stomach. Gastric organoids expressing CD44v9 were derived from mouse stomachs and transplanted at the ulcer site of CD44KO mice. Ulcers, CD44v9 expression, proliferation and histology were measured 1, 3, 5 and 7-days post-injury. Human-derived gastric organoids were generated from stomach tissue collected from elderly (>55 years) or young (14–20 years) patients. Organoids were transplanted into the stomachs of NOD scid gamma (NSG) mice at the site of injury. Gastric injury was induced in NRG-SGM3 (NRGS) mice harboring human-derived immune cells (hnNRGS) and the immune profile analyzed by CyTOF. CD44v9 expression emerged within regenerating glands the ulcer margin in response to injury. While ulcers in BL6 mice healed within 7-days post-injury, CD44KO mice exhibited loss of repair and epithelial regeneration. Ulcer healing was promoted in CD44KO mice by transplanted CD55v9-expressing gastric organoids. NSG mice exhibited loss of CD44v9 expression and gastric repair. Transplantation of human-derived gastric organoids from young, but not aged stomachs promoted repair in NSG mouse stomachs in response to injury. Finally, compared to NRGS mice, huNRGS animals exhibited reduced ulcer sizes, an infiltration of human CD162+ macrophages and an emergence of CD44v9 expression in SPEM. Thus, during repair of the gastric epithelium CD44v9 emerges within a regenerative cell lineage t hat coincides with macrophage infiltration within the injured mucosa. PMID:28497484

Selective expression of a splice variant of decay-accelerating factor in c-erbB-2-positive mammary carcinoma cells showing increased transendothelial invasiveness

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

Brandt, Burkhard; Mikesch, Jan-Hendrik; Simon, Ronald

2005-04-01

By differential-display-PCR a subclone of the SK-BR-3 cell line with high in vitro transendothelial invasiveness was identified to express increased levels of a new alternative splice variant of decay-accelerating factor (DAF). DAF seems to play an important role in some malignant tumours since on the one hand the expression of complement inhibitors on the surface of tumour cells prevents the accumulation of complement factors and in consequence cell lysis. On the other hand, DAF has been identified as a ligand for the CD97 surface receptor which induces cell migration. Immunofluorescence procedures, Western blot analyses, and cDNA clone sequencing were employedmore » to confirm the expression of DAF restricted to invasive tumour cells. Using a radioactive RNA-in situ hybridisation on freshly frozen tissue microarrays and RT-PCR on native tumour tissue, the expression of alternative spliced DAF mRNA was demonstrated in invasive breast cancer. Due to the fact that it could thereby not be detected in normal mammary tissues, it has to be confirmed in larger studies that the DAF splice variant might be a specific tumour marker for invasive breast cancer.« less

Comparison of remicade to curcumin for the treatment of Crohn's disease: A systematic review.

PubMed

Schneider, Allaire; Hossain, Ivy; VanderMolen, Julia; Nicol, Kara

2017-08-01

The aim of this study was to review the literature to assess if there is evidence to support the use of Curcumin as a safe complementary therapy in treating Crohn's Disease (CD) in conjunction with Remicade. Systematic searches were performed by three researchers using electronic databases (ProQuest Medical Library, CINAHL Complete, and PUBMED) to locate and identify articles to meet a predetermined set of inclusion criteria. Specifically full text, peer-reviewed articles published after 2007 were included if they studied human participants 18 years or older. Tumor necrosis factor-alpha (TNF-a) and Interleukin-1 (IL-1) levels increase in CD patients. Remicade reduces TNF-a in adults with CD. The issues are eventual loss of response (LOR) once IL-1 increases, and severe risks such as malignancy. CD patients using Curcumin saw a 55 point mean reduction in the Crohn's Disease Activity Index, reducing IL-1 and Crp. Plus it reduced TNF-a and PPMTase which improved colorectal cancer outcomes. LOR of Remicade occurs when IL-1 increases, and it can cause malignancy. Research shows Curcumin reduces IL-1 and improves cancer outcomes. Future research, using both Remicade and Curcumin, would have to be done, but preliminary data would suggest using both would reduce LOR. Curcumin, even by itself, was found to be a cheap and safe way to reduce CD symptoms and inflammatory markers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diagnostic value of CD10 and Bcl2 expression in distinguishing cutaneous basal cell carcinoma from squamous cell carcinoma and seborrheic keratosis.

PubMed

Gaballah, Mohammad A; Ahmed, Rehab-Allah

2015-12-01

The distinction between cutaneous basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and seborrheic keratosis (SK), which are common entities in clinical practice, can be difficult clinically and histologically. CD10 and Bcl2 antigens are important factors in tumor growth, survival and spread. The aim of the present study is to define the frequency of CD10 and Bcl2 expression in such cutaneous tumors and its relation to the clinicopathological characteristics as well as their possible diagnostic utility. CD10 and Bcl2 immunohistochemistry was performed on 30 BCC, 20 SCC and 15 SK. 93.3% of SK cases and 53.3% of BCC cases showed significant expression of CD10 in tumor cells when compared either with each other or with SCC cases (100% negative). Stromal CD10 expression was positive in 50% of BCC cases and 75% of SCC cases. Stromal CD10 expression was significantly higher in high risk BCC and BCC with infiltrating deep margins; furthermore, it showed a significant positive correlation with grade of SCC. A significant inverse correlation between CD10 expression in stromal and tumor cells of BCC was present. Bcl2 was significantly expressed in 93.3% of SK cases and 80% of BCC cases when compared with SCC cases (100% negative). It was found that for distinguishing BCC from SK, only CD10 expression in tumor cells provided a high diagnostic value with positive likelihood ratio (PLR) was 7.00. In addition, CD10 and Bcl2 expression in tumor cells could give convincing diagnostic value to distinguish SCC from SK (PLR=15.00 for each marker). Moreover, for differentiating BCC from SCC, only Bcl2 in the tumor cells could provide a high diagnostic value (PLR=5.5). In conclusion, CD10 and Bcl2 can help in differentiating cutaneous BCC from SK and SCC. The overexpression of CD10 in the stromal cells of SCC and some variants of BCC suggests the invasive properties of such tumors. Copyright © 2015 Elsevier GmbH. All rights reserved.

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

PubMed

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

2013-08-15

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

Lipopolysaccharide stimulates HepG2 human hepatoma cells in the presence of lipopolysaccharide-binding protein via CD14.

PubMed

Nanbo, A; Nishimura, H; Muta, T; Nagasawa, S

1999-02-01

Lipopolysaccharide (LPS)-binding protein (LBP), an opsonin for activation of macrophages by bacterial LPS, is synthesized in hepatocytes and is known to be an acute phase protein. Recently, cytokine-induced production of LBP was reported to increase 10-fold in hepatocytes isolated from LPS-treated rats, compared with those from normal rats. However, the mechanism by which the LPS treatment enhances the effect of cytokines remains to be clarified. In the present study, we examined whether LPS alone or an LPS/LBP complex directly stimulates the hepatocytes, leading to acceleration of the cytokine-induced LBP production. HepG2 cells (a human hepatoma cell line) were shown to express CD14, a glycosylphosphatidylinositol-anchored LPS receptor, by both RT/PCR and flow cytometric analyses. An LPS/LBP complex was an effective stimulator for LBP and CD14 production in HepG2 cells, but stimulation of the cells with either LPS or LBP alone did not significantly accelerate the production of these proteins. The findings were confirmed by semiquantitative RT/PCR analysis of mRNA levels of LBP and CD14 in HepG2 cells after stimulation with LPS alone and an LPS/LBP complex. In addition, two monoclonal antibodies (mAbs) to CD14 (3C10 and MEM-18) inhibited LPS/LBP-induced cellular responses of HepG2 cells. Furthermore, prestimulation of HepG2 cells with LPS/LBP augmented cytokine-induced production and gene expression of LBP and CD14. All these findings suggest that an LPS/LBP complex, but not free LPS, stimulates HepG2 cells via CD14 leading to increased basal and cytokine-induced LBP and CD14 production.

Intake of Boron, Cadmium, and Molybdenum enhances rat thyroid cell transformation.

PubMed

Luca, Emilia; Fici, Laura; Ronchi, Anna; Marandino, Ferdinando; Rossi, Esther Diana; Caristo, Maria Emiliana; Malandrino, Pasqualino; Russo, Marco; Pontecorvi, Alfredo; Vigneri, Riccardo; Moretti, Fabiola

2017-06-02

Epidemiologic data in volcanic areas suggest that environmental factors might be involved in the increase of thyroid cancer (TC) incidence. Recent reports indicate that several heavy metals and metalloids are increased in volcanic areas. This study aims to evaluate the combined effect of three of these elements Boron (B), Cadmium (Cd), and Molybdenum (Mo) - all increased in the volcanic area of Mt. Etna, in Italy - on thyroid tumorigenesis in the rat. Female Wistar rats prone to develop thyroid tumors by low-iodine diet and methimazole treatment received ad libitum drinking water supplemented with B, Cd, and Mo at concentrations in the range found in the urine samples of residents of the volcanic area. At 5 and 10 months animals were euthanized, and their thyroid analysed. Statistical analysis was performed with a 2-way unpaired t-test. No toxic effect of the three elements on the growth of the animals was observed. A significant increase of histological features of transformation was observed in thyroid follicular cells of rats treated with B, Cd, and Mo compared with those of control group. These abnormalities were associated with decreased iodine content in the thyroid. This study provides the evidence that slightly increased environmental concentrations of B, Cd, and Mo can accelerate the appearance of transformation marks in the thyroid gland of hypothyroid rats.

Enhancement of death-receptor induced caspase-8-activation in the death-inducing signalling complex by uncoupling of oxidative phosphorylation.

PubMed

Vier, Juliane; Gerhard, Monika; Wagner, Hermann; Häcker, Georg

2004-01-01

Signalling through the death receptor CD95 induces apoptosis by formation of a signalling complex at the cell membrane and subsequent caspase-8 and caspase-3-activation. Treatment of Jurkat T cells with protonophores across the mitochondrial membrane such as 2,4-dinitrophenol (DNP) enhances the death-inducing capacity of CD95. In this study, we show that this enhancement is due to the specific acceleration of caspase-8-processing and activation at the CD95-receptor. DNP-treatment did not affect NF-kappaB-induction by CD95. Immunoprecipitation experiments showed that the amounts of the adapter FADD/MORT1 and pro-caspase-8 at the CD95-receptor were not altered by DNP. Subcellular fractionation studies revealed that the amount of mature caspase-8 but not pro-caspase at the membrane was increased following CD95-stimulation in the presence of DNP. As a consequence of caspase-activation, c-FLIP-levels in the cytosol decreased. In Jurkat cells overexpressing c-FLIPS, DNP was still able to enhance caspase-activation. The enhancing capacity of DNP was seen in some cell lines (Jurkat, CEM and HeLa) but not in SKW6 cells and was also found in mitogen-stimulated human T cells. Furthermore, the enhancement extended to TRAIL-induced caspase-activation. Thus, a mechanism exists by which caspase-8-activation can be accelerated at death receptors and this mechanism can be triggered by targeting mitochondrial oxidative phosphorylation.

Combinatorial chemical bath deposition of CdS contacts for chalcogenide photovoltaics

DOE PAGES

Mokurala, Krishnaiah; Baranowski, Lauryn L.; de Souza Lucas, Francisco W.; ...

2016-08-01

Contact layers play an important role in thin film solar cells, but new material development and optimization of its thickness is usually a long and tedious process. A high-throughput experimental approach has been used to accelerate the rate of research in photovoltaic (PV) light absorbers and transparent conductive electrodes, however the combinatorial research on contact layers is less common. Here, we report on the chemical bath deposition (CBD) of CdS thin films by combinatorial dip coating technique and apply these contact layers to Cu(In,Ga)Se 2 (CIGSe) and Cu 2ZnSnSe 4 (CZTSe) light absorbers in PV devices. Combinatorial thickness steps ofmore » CdS thin films were achieved by removal of the substrate from the chemical bath, at regular intervals of time, and in equal distance increments. The trends in the photoconversion efficiency and in the spectral response of the PV devices as a function of thickness of CdS contacts were explained with the help of optical and morphological characterization of the CdS thin films. The maximum PV efficiency achieved for the combinatorial dip-coating CBD was similar to that for the PV devices processed using conventional CBD. Finally, the results of this study lead to the conclusion that combinatorial dip-coating can be used to accelerate the optimization of PV device performance of CdS and other candidate contact layers for a wide range of emerging absorbers.« less

Outcomes of Primary Transsphenoidal Surgery in Cushing Disease: Experience of a Tertiary Center.

PubMed

Keskin, Fatma Ela; Ozkaya, Hande Mefkure; Bolayirli, Murat; Erden, Secil; Kadioglu, Pınar; Tanriover, Necmettin; Gazioglu, Nurperi

2017-10-01

To report the initial and long-term remission rates and related factors, secondary treatments, and outcomes of a series of patients with Cushing disease (CD). We included 147 consecutive adult patients with CD who underwent primary transsphenoidal surgery (TSS) between 1998 and 2014 in this study. Eighty-two were followed up in the Cerrahpasa Medical Faculty Endocrinology and Metabolism outpatient clinic. Patients were requested to attend a long-term remission assessment; 55 could be contacted, and data for the remaining 27 patients' last visit to the outpatient clinics were reviewed for early and late remission. Six patients were excluded from the study. Magnetic resonance imaging (MRI) findings and pathologic results including mitosis, Ki-67 levels, and P53 in immunostaining of all patients were evaluated. Data of 82 patients with CD with an average age of 36 years [interquartile range: 29-47] were analyzed with a mean follow-up of 7.5 years [interquartile range: 5-10]. Overall initial remission rates were 72.3% after TSS. Among the 82 patients, 16 patients had Gamma Knife radiosurgery and 7 patients underwent adrenalectomy. After these additional treatments, the long-term remission rate was found as 69.7%. The highest remission rates were with microadenomas. Recurrence was most frequently seen in patients without tumor evidence on MRI. Patients with high Ki-67 levels had higher recurrence rates in long-term follow-up (P = 0.02). Life-long follow-up for patients with CD seems essential. Undetectable tumors on MRI before TSS and high Ki-67 immunopositivity were found as risk factors for tumor recurrence. Copyright © 2017 Elsevier Inc. All rights reserved.

A case of non-Hodgkin lymphoma in a patient with chronic myeloid leukemia.

PubMed

Găman, Amelia Maria; Dobrea, Camelia; Rotaru, Ionela

2013-01-01

Chronic myeloid leukemia is a clonal expansion of hematopoietic progenitor cells characterized by exaggerated proliferation of granulocytic lineage, with chronic phase, accelerated phase and blast crisis. Accelerated phase and blast crisis may be associated with extramedulary disease. Extramedullary transformation of CML can be determined both in nodal and extranodal sites. Non-Hodgkin lymphoma is rare in chronic myeloid leukemia and may be misdiagnosed as an extramedullary lymphoid blast transformation; the majorities are T-cell lymphomas with an immature thymic phenotype, while peripheral B-cell lymphomas are rarer. We report the case of a 79-year-old woman carrier Ph+ chronic myeloid leukemia who developed at eight months of diagnosis an accelerated phase of CML associated simultaneous with a tumor of soft palate, which was initial considering an extramedullary disease. The patient was treated with specific chemotherapy for accelerated phase of CML (Cytosinarabinoside) + Anagrelide, and reversed to secondary chronic phase of CML, but soft palate tumor persists. The immunohistochemical findings of bone marrow trephine biopsy examination showed chronic phase of CML (negativity for immature cells such as CD34, Tdt) and the biopsy of soft palate tumor and immunohistochemical findings revealed a primitive non-Hodgkin lymphoma (NHL) with medium B-cells (CD20, CD79a positive) and excluding an extramedullary blast crisis (CD34 negative, Tdt negative). Cytogenetic analysis in tumor revealed absence of Philadelphia chromosome. The patient was treated with local radiotherapy for NHL, with a favorable evolution and Hydroxyurea 1 g/day for CML with hematological remission. A localized lymphoid neoplasm may be an extramedullary localized blast crisis of CML or a distinct malignancy, with distinguished therapy and prognosis. A correct diagnosis based on a complex investigation: immunohistochemistry, conventional cytogenetic analysis and fluorescence in situ hybridization (FISH), molecular analysis (Southern blot and RT-PCR) is necessary. Further studies are required to clarify the pathogenetic relationship between chronic myeloid leukemia and non-Hodgkin lymphomas.

Risk assessment, spatial distribution, and source apportionment of heavy metals in Chinese surface soils from a typically tobacco cultivated area.

PubMed

Liu, Haiwei; Wang, Haiyun; Zhang, Yan; Yuan, Jumin; Peng, Yaodong; Li, Xiuchun; Shi, Yi; He, Kuanxin; Zhang, Qiming

2018-06-01

The heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in the surface soils of tobacco (Nicotiana tabacum L.) fields in Jiangxi Province were analyzed, and the mean heavy metal concentrations were 3.55, 0.19, 25.89, 14.96, 0.25, 10.89, 27.80, and 44.00 mg/kg, respectively. Spatial distribution analysis showed that the highest concentrations were recorded in the north-western, south-western, and mid-eastern parts of the study area. The index of geo-accumulation and pollution index indicated modest enrichment with Cd and Hg, which were the only two metals posing a potentially high ecological risk to the local agricultural environment. The health risk assessment showed no considerable non-carcinogenic or carcinogenic risks for children and adults from these elements. The principal component analysis (PCA) and cluster analysis (CA) found that the variations in the Cr and Ni concentrations were largely on account of the soil parent rocks, but the As, Cd, Cu, and Hg variations in the soil were largely owing to agricultural practices of years. However, the main factor influencing Pb and Zn was atmospheric deposition.

Systematic design and research on a series of cadmium coordination polymers assembled due to tetracarboxylate ligands

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

Lü, Lei; Mu, Bao; Li, Chang-Xia

A series of metal-organic frameworks (MOFs) have been prepared by tetracarboxylate ligands and Cd(II) ions under the hydrothermal or solvothermal conditions with the formulas of {[Cd_2(L_1)(H_2O)_4]·H_2O}{sub n} (1), {[(CH_3)_2NH_2]_2[Cd(L_1)]}{sub n} (2), [Cd(L{sub 2}){sub 0.5}(H{sub 2}O)]{sub n} (3), {[(CH_3)_2NH_2]_2 [Cd(L_2)]·2DMF}{sub n} (4), [Cd(L{sub 3}){sub 0.5}(H{sub 2}O)]{sub n} (5), {[Cd(L_3)_0_._5(H_2O)]·CH_3OH}{sub n} (6), {[(CH_3)_2NH_2]_2[Cd_3(L_4)_2]}{sub n} (7) (H{sub 4}L{sub 1}=[1,1′:4′,1″-terphenyl]-2,2″,5,5″-tetracarboxylic acid; H{sub 4}L{sub 2}=[1,1′:4′,1″-terphenyl]-2′,4,4″,5′-tetracarboxylic acid; H{sub 4}L{sub 3}=[1,1′:3′,1″-terphenyl]-2′,3,3″,5′-tetracarboxylic acid; H{sub 4}L{sub 4}=[1,1′:4′,1″-terphenyl]-3,3″,5,5″-tetracarboxylic acid), which are characterized by single-crystal X-ray diffraction, elemental analyses, IR, TGA and PXRD. Complex 1 exhibits a three-dimensional (3D) supramolecular framework based on two-dimensional (2D) coordination networks. Complexes 2 and 4more » possess 3D framework based on the 1D right-handed helix channels. Complexes 3 and 7 are a 3D architecture containing two different channels. Isostructural complexes 5 and 6 display 3D framework. The different synthetic methods and coordination modes of the tetracarboxylates ligands have effect on formation of various MOFs. Moreover, the luminescent properties and N{sub 2} adsorption behaviors have been reported. - Graphical abstract: A series of cadmium(II) high-dimensional coordination polymers constructed from four different kinds of tetracarboxylate ligands have been successfully prepared under hydrothermal or solvothermal conditions. The effect of solvents, the coordination modes of the tetracarboxylates and positions of carboxylate groups on the architectures of complexes 1–7 have been investigated in detail. The luminescent properties of the part of complexes, N{sub 2} adsorption behaviors of complexes 2, 4–7 have also been studied. - Highlights: • Tetracarboxylate ligands based on terphenyl moiety have been used. • Several factors that influenced the architecture have been discussed. • Luminescent properties have been investigated.« less

Synthesis, crystal structure and electronic structure of the binary phase Rh2Cd5

NASA Astrophysics Data System (ADS)

Koley, Biplab; Chatterjee, S.; Jana, Partha P.

2017-02-01

A new phase in the Rh-Cd binary system - Rh2Cd5 has been identified and characterized by single crystal X-ray diffraction and Energy dispersive X-ray analysis. The stoichiometric compound Rh2Cd5 crystallizes with a unit cell containing 14 atoms, in the orthorhombic space group Pbam (55). The crystal structure of Rh2Cd5 can be described as a defect form of the In3Pd5 structure with ordered vacancies, formed of two 2D atomic layers with the stacking sequence: ABAB. The A type layers consist of (3.6.3.6)-Kagomé nets of Cd atoms while the B type layers consist of (35) (37)- nets of both Cd and Rh atoms. The stability of this line phase is investigated by first principle electronic structure calculations on the model of ordered Rh2Cd5.

Risk Factors for Vitamin D Deficiency and Impact of Repletion in a Tertiary Care Inflammatory Bowel Disease Population.

PubMed

Zullow, Samantha; Jambaulikar, Guruprasad; Rustgi, Ankur; Quezada, Sandra; Cross, Raymond K

2017-08-01

Many patients with inflammatory bowel disease (IBD) are vitamin D deficient. The purpose of our study was to identify risk factors for vitamin D deficiency in IBD and to assess the impact of vitamin D repletion on disease activity and quality of life (QOL). Patients with at least one 25-OH vitamin D level measured between 2004 and 2011 were included. Patients with a level <30 ng/ml at baseline were followed until the time of repletion. QOL and disease activity scores were measured at baseline and repletion. A total of 255 patients were identified. 33, 29, and 39% had a vitamin D level of ≥30, 20-29, and <20 ng/ml, respectively. When adjusting for disease type and duration, gender, smoking, and race, non-Caucasians had 5.3 (2.3-12.3) and UC patients had a 0.59 (0.33-1.03) odds of having a vitamin D <30 ng/ml. Women were 1.7 times more likely to have a 25-OH vitamin D level <20 ng/ml than men. 55 patients underwent repletion. In CD patients, the HBI and SIBDQ prior to repletion was 5.5 ± 4.9 and 44.3 ± 16.4, respectively; these improved to 3.6 ± 3.4 and 48.6 ± 14.2 after repletion (p = 0.0154 and p = 0.0684). In this tertiary care IBD cohort, the majority of patients have low vitamin D levels. Non-Caucasian race and female gender are associated with low vitamin D. UC was associated with lower risk of vitamin D insufficiency. In CD, vitamin D repletion is associated with decreased disease activity and increased QOL.

Acid-Labile Poly(glycidyl methacrylate)-Based Star Gene Vectors.

PubMed

Yang, Yan-Yu; Hu, Hao; Wang, Xing; Yang, Fei; Shen, Hong; Xu, Fu-Jian; Wu, De-Cheng

2015-06-10

It was recently reported that ethanolamine-functionalized poly(glycidyl methacrylate) (PGEA) possesses great potential applications in gene therapy due to its good biocompatibility and high transfection efficiency. Importing responsivity into PGEA vectors would further improve their performances. Herein, a series of responsive star-shaped vectors, acetaled β-cyclodextrin-PGEAs (A-CD-PGEAs) consisting of a β-CD core and five PGEA arms linked by acid-labile acetal groups, were proposed and characterized as therapeutic pDNA vectors. The A-CD-PGEAs owned abundant hydroxyl groups to shield extra positive charges of A-CD-PGEAs/pDNA complexes, and the star structure could decrease charge density. The incorporation of acetal linkers endowed A-CD-PGEAs with pH responsivity and degradation. In weakly acidic endosome, the broken acetal linkers resulted in decomposition of A-CD-PGEAs and morphological transformation of A-CD-PGEAs/pDNA complexes, lowering cytotoxicity and accelerating release of pDNA. In comparison with control CD-PGEAs without acetal linkers, A-CD-PGEAs exhibited significantly better transfection performances.

Evaluation of Dutch guideline for just-in-time addition of plerixafor to stem cell mobilization in patients who fail with granulocyte-colony-stimulating factor.

PubMed

Bilgin, Yavuz M; Visser, Otto; Beckers, Erik A M; te Boome, Liane C J; Huisman, Cynthia; Ypma, Paula F; Croockewit, Alexandra J; Netelenbos, Tanja; Kramer, Ellen P A; de Greef, Georgine E

2015-05-01

Plerixafor in combination with granulocyte-colony-stimulating factor (G-CSF) is approved for the use of stem cell collection in patients who fail to mobilize on G-CSF. In 2009 the Stem Cell Working Party of the Dutch-Belgian Cooperative Trial group for Hematology Oncology (HOVON) composed a guideline for the use of plerixafor. According to this guideline it is recommended to add plerixafor to G-CSF in patients with circulating CD34+ cell counts of fewer than 20 × 10(6) /L on 2 consecutive days accompanied by increasing white blood cells. In this analysis we evaluated retrospectively the outcome of the use of this guideline in the Netherlands. In total 111 patients received plerixafor with a median one administration (range, one to four administrations). Of these patients 55.8% had non-Hodgkin lymphoma, 31.5% multiple myeloma, 8.1% Hodgkin lymphoma, and 4.5% nonhematologic malignancies. In 63.9% patients sufficient numbers of CD34+ cells were collected. In patients with multiple myeloma more successful mobilizations with plerixafor were observed compared to patients with non-Hodgkin lymphoma (71.4% vs. 61.3%). In patients with circulating CD34+ cell counts of at least 2.0 × 10(6) /L before administration of plerixafor a successful mobilization was achieved in 76.5%, and in the patients with very low (0-1 × 10(6) /L) circulating CD34+ cell counts the success rate was 44.2%. Application of the HOVON guideline on the just-in-time administration of plerixafor is effective for mobilization of hematopoietic stem cells in the majority of patients. Stem cell yield in patients with non-Hodgkin lymphoma was lower compared to patients with multiple myeloma. Also patients with very low circulating CD34+ cells before addition of plerixafor might benefit from this approach. © 2014 AABB.

CD14+ CD15- HLA-DR- myeloid-derived suppressor cells impair antimicrobial responses in patients with acute-on-chronic liver failure.

PubMed

Bernsmeier, Christine; Triantafyllou, Evangelos; Brenig, Robert; Lebosse, Fanny J; Singanayagam, Arjuna; Patel, Vishal C; Pop, Oltin T; Khamri, Wafa; Nathwani, Rooshi; Tidswell, Robert; Weston, Christopher J; Adams, David H; Thursz, Mark R; Wendon, Julia A; Antoniades, Charalambos Gustav

2018-06-01

Immune paresis in patients with acute-on-chronic liver failure (ACLF) accounts for infection susceptibility and increased mortality. Immunosuppressive mononuclear CD14 + HLA-DR - myeloid-derived suppressor cells (M-MDSCs) have recently been identified to quell antimicrobial responses in immune-mediated diseases. We sought to delineate the function and derivation of M-MDSC in patients with ACLF, and explore potential targets to augment antimicrobial responses. Patients with ACLF (n=41) were compared with healthy subjects (n=25) and patients with cirrhosis (n=22) or acute liver failure (n=30). CD14 + CD15 - CD11b + HLA-DR - cells were identified as per definition of M-MDSC and detailed immunophenotypic analyses were performed. Suppression of T cell activation was assessed by mixed lymphocyte reaction. Assessment of innate immune function included cytokine expression in response to Toll-like receptor (TLR-2, TLR-4 and TLR-9) stimulation and phagocytosis assays using flow cytometry and live cell imaging-based techniques. Circulating CD14 + CD15 - CD11b + HLA-DR - M-MDSCs were markedly expanded in patients with ACLF (55% of CD14+ cells). M-MDSC displayed immunosuppressive properties, significantly decreasing T cell proliferation (p=0.01), producing less tumour necrosis factor-alpha/interleukin-6 in response to TLR stimulation (all p<0.01), and reduced bacterial uptake of Escherichia coli (p<0.001). Persistently low expression of HLA-DR during disease evolution was linked to secondary infection and 28-day mortality. Recurrent TLR-2 and TLR-4 stimulation expanded M-MDSC in vitro. By contrast, TLR-3 agonism reconstituted HLA-DR expression and innate immune function ex vivo. Immunosuppressive CD14 + HLA-DR - M-MDSCs are expanded in patients with ACLF. They were depicted by suppressing T cell function, attenuated antimicrobial innate immune responses, linked to secondary infection, disease severity and prognosis. TLR-3 agonism reversed M-MDSC expansion and innate immune function and merits further evaluation as potential immunotherapeutic agent. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cancer Immunosurveillance by Tissue-resident Innate Lymphoid Cells and Innate-like T Cells

PubMed Central

Dadi, Saïda; Chhangawala, Sagar; Whitlock, Benjamin M.; Franklin, Ruth A.; Luo, Chong T.; Oh, Soyoung A.; Toure, Ahmed; Pritykin, Yuri; Huse, Morgan; Leslie, Christina S.; Li, Ming O.

2016-01-01

Summary Malignancy can be suppressed by the immune system in a process termed immunosurveillance. However, to what extent immunosurveillance occurs in spontaneous cancers and the composition of participating cell types remain obscure. Here we show that cell transformation triggers a tissue-resident lymphocyte response in oncogene-induced murine cancer models. Non-circulating cytotoxic lymphocytes, derived from innate, TCRαβ and TCRγδ lineages, expand in early tumors. Characterized by high expression of NK1.1, CD49a and CD103, these cells share a gene expression signature distinct from those of conventional NK cells, T cells and invariant NKT cells. Generation of these lymphocytes is dependent on the cytokine IL-15, but not the transcription factor Nfil3 that is required for the differentiation of tumor-infiltrating NK cells, and IL-15, but not Nfil3, deficiency results in accelerated tumor growth. These findings reveal a tumor-elicited immunosurveillance mechanism that engages unconventional type 1-like innate lymphoid cells and type 1 innate-like T cells. PMID:26806130

Association Between Changes in Air Pollution Levels During the Beijing Olympics and Biomarkers of Inflammation and Thrombosis in Healthy Young Adults

PubMed Central

Rich, David Q.; Kipen, Howard M.; Huang, Wei; Wang, Guangfa; Wang, Yuedan; Zhu, Ping; Ohman-Strickland, Pamela; Hu, Min; Philipp, Claire; Diehl, Scott R.; Lu, Shou-En; Tong, Jian; Gong, Jicheng; Thomas, Duncan; Zhu, Tong; Zhang, Junfeng (Jim)

2014-01-01

Context Air pollution is a risk factor for cardiovascular diseases (CVD), but the underlying biological mechanisms are not well understood. Objective To determine whether markers related to CVD pathophysiological pathways (biomarkers for systemic inflammation and thrombosis, heart rate, and blood pressure) are sensitive to changes in air pollution. Design, Setting, and Participants Using a quasi-experimental opportunity offered by greatly restricted air pollution emissions during the Beijing Olympics, we measured pollutants daily and the outcomes listed below in 125 healthy young adults before, during, and after the 2008 Olympics (June 2-October 30). We used linear mixed-effects models to estimate the improvement in outcome levels during the Olympics and the anticipated reversal of outcome levels after pollution controls ended to determine whether changes in outcome levels were associated with changes in pollutant concentrations. Main Outcome Measures C-reactive protein (CRP), fibrinogen, von Willebrand factor, soluble CD40 ligand (sCD40L), soluble P-selectin (sCD62P) concentrations; white blood cell count (WBC); heart rate; and blood pressure. Results Concentrations of particulate and gaseous pollutants decreased substantially (−13% to −60%) from the pre-Olympic period to the during-Olympic period. Using 2-sided tests conducted at the .003 level, we observed statistically significant improvements in sCD62P levels by −34.0% (95% CI, −38.4% to −29.2%; P<.001) from a pre-Olympic mean of 6.29 ng/mL to a during-Olympic mean of 4.16 ng/mL and von Willebrand factor by −13.1% (95% CI, −18.6% to −7.5%; P<.001) from 106.4% to 92.6%. After adjustments for multiple comparisons, changes in the other outcomes were not statistically significant. In the post-Olympic period when pollutant concentrations increased, most outcomes approximated pre-Olympic levels, but only sCD62P and systolic blood pressure were significantly worsened from the during-Olympic period. The fraction of above-detection-limit values for CRP (percentage ≥0.3 mg/L) was reduced from 55% in the pre-Olympic period to 46% in the during-Olympic period and reduced further to 36% in the post-Olympic period. Interquartile range increases in pollutant concentrations were consistently associated with statistically significant increases in fibrinogen, von Wille-brand factor, heart rate, sCD62P, and sCD40L concentrations. Conclusions Changes in air pollution levels during the Beijing Olympics were associated with acute changes in biomarkers of inflammation and thrombosis and measures of cardiovascular physiology in healthy young persons. These findings are of uncertain clinical significance. PMID:22665106

Biochar and Glomus caledonium Influence Cd Accumulation of Upland Kangkong (Ipomoea aquatica Forsk.) Intercropped with Alfred Stonecrop (Sedum alfredii Hance)

NASA Astrophysics Data System (ADS)

Hu, Junli; Wu, Fuyong; Wu, Shengchun; Lam, Cheung Lung; Lin, Xiangui; Wong, Ming Hung

2014-04-01

Both biochar application and mycorrhizal inoculation have been proposed to improve plant growth and alter bioaccumulation of toxic metals. A greenhouse pot trial was conducted to investigate growth and Cd accumulation of upland kangkong (Ipomoea aquatica Forsk.) intercropped with Alfred stonecrop (Sedum alfredii Hance) in a Cd-contaminated soil inoculated with Glomus caledonium and/or applied with biochar. Compared with the monocultural control, intercropping with stonecrop (IS) decreased kangkong Cd acquisition via rhizosphere competition, and also decreased kangkong yield. Gc inoculation (+M) accelerated growth and Cd acquisition of stonecrop, and hence resulted in further decreases in kangkong Cd acquisition. Regardless of IS and +M, biochar addition (+B) increased kangkong yield via elevating soil available P, and decreased soil Cd phytoavailability and kangkong Cd concentration via increasing soil pH. Compared with the control, the treatment of IS + M + B had a substantially higher kangkong yield (+25.5%) with a lower Cd concentration (-62.7%). Gc generated additive effects on soil alkalinization and Cd stabilization to biochar, causing lower DTPA-extractable (phytoavailable) Cd concentrations and post-harvest transfer risks.

The effect of freeze-dried antibody concentrations on its stability in the presence of trehalose and hydroxypropyl-β-cyclodextrin: a Box-Behnken statistical design.

PubMed

Faghihi, Homa; Khalili, Fatemeh; Amini, Mohsen; Vatanara, Alireza

2017-09-01

The present study aimed at preparation and optimization of stable freeze-dried immunoglobulin G (IgG) applying proper amount of antibody with efficient combination of trehalose and hydroxypropyl-β-cyclodextrin (HPβCD). Response surface methodology was employed through a three-factor, three-level Box-Behnken design. Amounts of IgG (X 1 ), trehalose (X 2 ) and HPβCD (X 3 ) were independent variables. Aggregation following process (Y 1 ), after one month at 45 °C (Y 2 ), upon two month at 45 °C (Y 3 ) and beta-sheet content of IgG (Y 4 ) were determined as dependent variables. Results were fitted to quadratic models (except for beta-sheet content), describing the inherent relationship between main factors. Optimized formulation composed of 55.85 mg IgG, 52.51 mg trehalose and 16.01 mg HPβCD was prepared. The calculated responses of the optimized formulation were as follows: Y 1  = 0.19%, Y 2  = 0.78%, Y 3  = 1.88% and Y 4  = 68.60%, respectively. The thermal analysis confirmed the amorphous nature of optimum formulation and the integrity of IgG was shown to be favorably preserved. Validation of the optimization study demonstrated high degree of prognostic ability. The DOE study successfully predicted the optimum values of antibody as well as stabilizers for desirable process and storage stabilization of freeze-dried IgG.

Maternal and neonatal scalp hair concentrations of zinc, copper, cadmium, and lead: relationship to some lifestyle factors.

PubMed

Razagui, Ibrahim B-A; Ghribi, Ibrahim

2005-07-01

Postpartum scalp hair samples from 82 term-pregnancy mother/ neonate pairs were analyzed for their concentrations of zinc (Zn), copper (Cu), cadmium (Cd), and lead (Pb), using inductively coupled plasma-mass spectrometry. Maternal and neonatal Zn concentrations had geometric means (and 99% confidence intervals) of 122.5 microg/g (117.9--131.5 microg/g) and 146.9 microg (141.5--156.7 microg/g) respectively. Corresponding Cu values were 18.4 microg/g (17.6--23.8 microg/g) and 6.7 microg/g (6.3--7.6 microg/g). Those of Cd were 0.49 microg/g (0.47--0.69 microg/g) in the mothers and 0.57 microg/g (0.55--0.86 microg/g) in the neonates. For Pb, they were 7.95 microg/g (7.60--9.32 microg/g) and 4.56 microg/g (4.39--5.56 microg/g). Cigarette smoking, despite its relatively low prevalence (19.5%), was associated with lower Zn and higher Cd and Pb concentrations and in lower Zn/Cd and Zn/Pb molar concentration ratios. Smoking also altered interelemental relationships, particularly those of Zn with Cd and Pb and those between Cd and Pb. Smoking frequency appeared to show negative dose-response effects on maternal and neonatal Zn concentrations, Zn/Pb molar concentration ratios, and birth weight. Mothers with a history of oral contraceptive (OC) usage had significantly higher Cu concentrations and lower Zn/Cu molar concentration ratios than non users, with the highest Cu concentrations and lowest Zn/Cu values being associated with third-generation OCs. No similar effects were elicited in the respective neonatal Cu concentrations. Neither alcohol consumption nor prenatal supplementation with iron and/or folic acid had discernible effects on the maternal or neonatal elemental concentrations. The data from this study suggest that in a given population of term-pregnancy mothers and neonates, significant interindividual variations in hair trace element concentrations can occur, irrespective of commonality of general environment, and that lifestyle factors, including cigarette smoking and OC usage history, can be significant contributory factors to such variations. The data are discussed in relation to the effects of smoking-associated exposure to Cd and Pb exposure on Zn availability for placental transfer, as well as on the quantitative maternal Zn supply levels to the fetus resulting from the known tendency of smokers to have lower dietary intakes of Zn.

Maternal and postnatal high-fat diets with high ?6:?3 ratios affect the reproductive performance of male offspring in the mouse.

PubMed

Bianconi, S; Stutz, G; Solís, M R; Martini, A C; Vincenti, L M; Ponzio, M F; Luque, E; Avendaño, C; Quiroga, P; Santillán, M E

2018-05-24

High-fat diets (HFDs) are an acknowledged risk factor for male subfertility, but the underlying mechanisms remain unclear. In the present study we compared the effects of two HFDs with different ω6:ω3 ratios, one enriched with soy oil (SOD; ω6:ω3=9.62) and another enriched with sunflower oil (SFOD; ω6:ω3=51.55), with those of a commercial diet (CD; ω6:ω3=19.87), supplied from pregnancy to adulthood, on morphometric parameters and reproductive performance in adult male mice (recommended ω6:ω3 for rodents=1-6). Bodyweight was significantly higher in the SFOD than CD group, and relative testicular weight was significantly lower in the SFOD than the other two groups. SFOD altered sperm performance: it reduced sperm viability (mean±s.e.m.; 76.00±1.35% vs 82.50±1.45% and 80.63±1.00% in the SFOD vs CD and SOD groups respectively; P<0.05) and increased the percentage of immature spermatozoa (71.88±7.17% vs 51.38±5.87% and 48.00±5.72% in the SFOD vs CD and SOD groups respectively; P<0.05). The epididymal ω6:ω3 ratio was higher in the SFOD versus CD and SOD groups, whereas the unsaturation index was higher in the SOD and SFOD groups than in CD group. Sperm membrane integrity was diminished in both the SOD and SFOD groups, but there was no difference in sperm reactive oxygen species production in these two groups compared with the CD group. The fertilisation rate was lower in the SFOD compared with the CD and SOD groups. In conclusion, although both HFDs affected sperm quality, the fertilising ability was more altered by the excessive dietary ω6:ω3 ratio than by the net ω6 content.

Beneficial effect of pistachio consumption on glucose metabolism, insulin resistance, inflammation, and related metabolic risk markers: a randomized clinical trial.

PubMed

Hernández-Alonso, Pablo; Salas-Salvadó, Jordi; Baldrich-Mora, Mònica; Juanola-Falgarona, Martí; Bulló, Mònica

2014-11-01

To examine whether a pistachio-rich diet reduces the prediabetes stage and improves its metabolic risk profile. Prediabetic subjects were recruited to participate in this Spanish randomized clinical trial between 20 September 2011 and 4 February 2013. In a crossover manner, 54 subjects consumed two diets, each for 4 months: a pistachio-supplemented diet (PD) and a control diet (CD). A 2-week washout period separated study periods. Diets were isocaloric and matched for protein, fiber, and saturated fatty acids. A total of 55% of the CD calories came from carbohydrates and 30% from fat, whereas for the PD, these percentages were 50 and 35%, respectively (including 57 g/day of pistachios). Fasting glucose, insulin, and HOMA of insulin resistance decreased significantly after the PD compared with the CD. Other cardiometabolic risk markers such as fibrinogen, oxidized LDL, and platelet factor 4 significantly decreased under the PD compared with the CD (P < 0.05), whereas glucagon-like peptide-1 increased. Interleukin-6 mRNA and resistin gene expression decreased by 9 and 6%, respectively, in lymphocytes after the pistachio intervention (P < 0.05, for PD vs. CD). SLC2A4 expression increased by 69% in CD (P = 0.03, for PD vs. CD). Cellular glucose uptake by lymphocytes decreased by 78.78% during the PD (P = 0.01, PD vs. CD). Chronic pistachio consumption is emerging as a useful nutritional strategy for the prediabetic state. Data suggest that pistachios have a glucose- and insulin-lowering effect, promote a healthier metabolic profile, and reverse certain metabolic deleterious consequences of prediabetes. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Etiology of inflammatory bowel disease: A unified hypothesis

PubMed Central

Qin, Xiaofa

2012-01-01

Inflammatory bowel disease (IBD), including both ulcerative colitis (UC) and Crohn’s disease (CD), emerged and dramatically increased for about a century. Despite extensive research, its cause remains regarded as unknown. About a decade ago, a series of findings made me suspect that saccharin may be a key causative factor for IBD, through its inhibition on gut bacteria and the resultant impaired inactivation of digestive proteases and over digestion of the mucus layer and gut barrier (the Bacteria-Protease-Mucus-Barrier hypothesis). It explained many puzzles in IBD such as its emergence and temporal changes in last century. Recently I further found evidence suggesting sucralose may be also linked to IBD through a similar mechanism as saccharin and have contributed to the recent worldwide increase of IBD. This new hypothesis suggests that UC and CD are just two symptoms of the same morbidity, rather than two different diseases. They are both caused by a weakening in gut barrier and only differ in that UC is mainly due to increased infiltration of gut bacteria and the resultant recruitment of neutrophils and formation of crypt abscess, while CD is mainly due to increased infiltration of antigens and particles from gut lumen and the resultant recruitment of macrophages and formation of granulomas. It explained the delayed appearance but accelerated increase of CD over UC and many other phenomena. This paper aims to provide a detailed description of a unified hypothesis regarding the etiology of IBD, including the cause and mechanism of IBD, as well as the relationship between UC and CD. PMID:22553395

Degradation of Leakage Currents and Reliability Prediction for Tantalum Capacitors

NASA Technical Reports Server (NTRS)

Teverovsky, Alexander

2016-01-01

Two types of failures in solid tantalum capacitors, catastrophic and parametric, and their mechanisms are described. Analysis of voltage and temperature reliability acceleration factors reported in literature shows a wide spread of results and requires more investigation. In this work, leakage currents in two types of chip tantalum capacitors were monitored during highly accelerated life testing (HALT) at different temperatures and voltages. Distributions of degradation rates were approximated using a general log-linear Weibull model and yielded voltage acceleration constants B = 9.8 +/- 0.5 and 5.5. The activation energies were Ea = 1.65 eV and 1.42 eV. The model allows for conservative estimations of times to failure and was validated by long-term life test data. Parametric degradation and failures are reversible and can be annealed at high temperatures. The process is attributed to migration of charged oxygen vacancies that reduce the barrier height at the MnO2/Ta2O5 interface and increase injection of electrons from the MnO2 cathode. Analysis showed that the activation energy of the vacancies' migration is 1.1 eV.

Mobility of selected trace elements in Mediterranean red soil amended with phosphogypsum: experimental study.

PubMed

Kassir, Lina Nafeh; Darwish, Talal; Shaban, Amin; Ouaini, Naim

2012-07-01

Soil amendment by phosphogypsum (PG) application becomes of increasing importance in agriculture. This may lead, however, to soil, plant, and groundwater contamination with trace elements (TEs) inherently present in PG. Monitoring of selected TEs (Pb, Zn, Cu, and Cd) distribution and mobility in a Mediterranean red soil profile has been performed in soil parcels applied with PG over a 16-month period. Concentrations were measured in soil and plant samples collected from various depth intervals at different points in time. TEs sequential extraction was performed on soil and PG samples. Results showed soil profile enrichment peaked 5 months after PG application for Cd, and 12 months for Pb, Zn, and Cu. Rainwater, pH, total organic carbon, and cationic exchange capacity were the main controlling factors in TEs accumulation in soils. Cd was transferred to a soil depth of about 20 cm. Zn exhibited mobility towards deeper layers. Pb and Cu were accumulated in around 20-55-cm-deep layers. PG increased the solubility of the studied TEs; PG-applied soils contained TEs bound to exchangeable and acid-soluble fractions in higher percentages than reference soil. Pb, Zn, and Cu were sorbed into mineral soil phases, while Cd was mainly found in the exchangeable (bio-available) form. The order of TEs decreasing mobility was Zn > Cd > Pb > Cu. Roots and leaves of existed plants, Cichorium intybus L., accumulated high concentrations of Cd (1-2.4 mg/kg), exceeding recommended tolerable levels, and thus signifying potential health threats through contaminated crops. It was therefore recommended that PG should be applied in carefully established, monitored, and controlled quantities to agricultural soils.

Differentiation potential of human CD133 positive hematopoietic stem cells into motor neuron- like cells, in vitro.

PubMed

Moghaddam, Sepideh Alavi; Yousefi, Behnam; Sanooghi, Davood; Faghihi, Faezeh; Hayati Roodbari, Nasim; Bana, Nikoo; Joghataei, Mohammad Taghi; Pooyan, Paria; Arjmand, Babak

2017-12-01

Spinal cord injuries and motor neuron-related disorders impact on life of many patients around the world. Since pharmacotherapy and surgical approaches were not efficient to regenerate these types of defects; stem cell therapy as a good strategy to restore the lost cells has become the focus of interest among the scientists. Umbilical cord blood CD133 + hematopoietic stem cells (UCB- CD133 + HSCs) with self- renewal property and neural lineage differentiation capacity are ethically approved cell candidate for use in regenerative medicine. In this regard the aim of this study was to quantitatively evaluate the capability of these cells to differentiate into motor neuron-like cells (MNL), in vitro. CD133 + HSCs were isolated from human UCB using MACS system. After cell characterization using flow cytometry, the cells were treated with a combination of Retinoic acid, Sonic hedgehog, Brain derived neurotrophic factor, and B27 through a 2- step procedure for two weeks. The expression of MN-specific markers was examined using qRT- PCR, flow cytometry and immunocytochemistry. By the end of the two-week differentiation protocol, CD133 + cells acquired unipolar MNL morphology with thin and long neurites. The expression of Isl-1(62.15%), AChE (41.83%), SMI-32 (21.55%) and Nestin (17.46%) was detected using flow cytometry and immunocytochemistry. The analysis of the expression of PAX6, ISL-1, ACHE, CHAT and SMI-32 revealed that MNLs present these neural markers at levels comparable with undifferentiated cells. In Conclusion Human UCB- CD133 + HSCs are remarkably potent cell candidates to transdifferentiate into motor neuron-like cells, in vitro. Copyright © 2017. Published by Elsevier B.V.

Cd(II)-coordination polymers based on tetracarboxylic acid and diverse bis(imidazole) ligands: Synthesis, structural diversity and photoluminescence properties

NASA Astrophysics Data System (ADS)

Arıcı, Mürsel; Yeşilel, Okan Zafer; Taş, Murat

2017-01-01

Three new Cd(II)-coordination polymers, namely, {[Cd2(μ6-ao2btc)(μ-1,5-bipe)2]·2H2O}n (1), {[Cd2(μ6-ao2btc)(μ-1,4-bix)2]n·2DMF} (2) and {[Cd2(μ8-abtc)(μ-1,4-betix)]·DMF·H2O}n (3) (ao2btc=di-oxygenated form of 3,3‧,5,5‧-azobenzenetetracarboxylate, 1,5-bipe: 1,5-bis(imidazol-1yl)pentane, 1,4-bix=1,4-bis(imidazol-1ylmethyl)benzene, 1,4-betix=1,4-bis(2-ethylimidazol-1ylmethyl)benzene) were synthesized with 3,3‧,5,5‧-azobenzenetetracarboxylic acid and flexible, semi-flexible and semi-flexible substituted bis(imidazole) linkers. They were characterized by IR spectroscopy, elemental analysis, single-crystal X-ray diffraction, powder X-ray diffractions (PXRD) and thermal analyses (TG/DTA). Complexes 1-3 exhibited structural diversities depending on flexible, semi-flexible and semi-flexible substituted bis(imidazole) ligands. Complex 1 was 2D structure with 3,6L18 topology. Complex 2 had a 3D pillar-layered framework with the rare sqc27 topology. When semi-flexible substituted bis(imidazole) linker was used, 3D framework of complex 3 was obtained with the paddlewheel Cd2(CO2)4-type binuclear SBU. Moreover, thermal and photoluminescence properties of the complexes were determined in detailed.

Expansion of inflammatory innate lymphoid cells in patients with common variable immune deficiency.

PubMed

Cols, Montserrat; Rahman, Adeeb; Maglione, Paul J; Garcia-Carmona, Yolanda; Simchoni, Noa; Ko, Huai-Bin M; Radigan, Lin; Cerutti, Andrea; Blankenship, Derek; Pascual, Virginia; Cunningham-Rundles, Charlotte

2016-04-01

Common variable immunodeficiency (CVID) is an antibody deficiency treated with immunoglobulin; however, patients can have noninfectious inflammatory conditions that lead to heightened morbidity and mortality. Modular analyses of RNA transcripts in whole blood previously identified an upregulation of many interferon-responsive genes. In this study we sought the cell populations leading to this signature. Lymphoid cells were measured in peripheral blood of 55 patients with CVID (31 with and 24 without inflammatory/autoimmune complications) by using mass cytometry and flow cytometry. Surface markers, cytokines, and transcriptional characteristics of sorted innate lymphoid cells (ILCs) were defined by using quantitative PCR. Gastrointestinal and lung biopsy specimens of subjects with inflammatory disease were stained to seek ILCs in tissues. The linage-negative, CD127(+), CD161(+) lymphoid population containing T-box transcription factor, retinoic acid-related orphan receptor (ROR) γt, IFN-γ, IL-17A, and IL-22, all hallmarks of type 3 innate lymphoid cells, were expanded in the blood of patients with CVID with inflammatory conditions (mean, 3.7% of PBMCs). ILCs contained detectable amounts of the transcription factors inhibitor of DNA binding 2, T-box transcription factor, and RORγt and increased mRNA transcripts for IL-23 receptor (IL-23R) and IL-26, demonstrating inflammatory potential. In gastrointestinal and lung biopsy tissues of patients with CVID, numerous IFN-γ(+)RORγt(+)CD3(-) cells were identified, suggesting a role in these mucosal inflammatory states. An expansion of this highly inflammatory ILC population is a characteristic of patients with CVID with inflammatory disease; ILCs and the interferon signature are markers for the uncontrolled inflammatory state in these patients. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Core/shell colloidal quantum dot exciplex states for the development of highly efficient quantum-dot-sensitized solar cells.

PubMed

Wang, Jin; Mora-Seró, Iván; Pan, Zhenxiao; Zhao, Ke; Zhang, Hua; Feng, Yaoyu; Yang, Guang; Zhong, Xinhua; Bisquert, Juan

2013-10-23

Searching suitable panchromatic QD sensitizers for expanding the light-harvesting range, accelerating charge separation, and retarding charge recombination is an effective way to improve power conversion efficiency (PCE) of quantum-dot-sensitized solar cells (QDSCs). One possible way to obtain a wide absorption range is to use the exciplex state of a type-II core/shell-structured QDs. In addition, this system could also provide a fast charge separation and low charge-recombination rate. Herein, we report on using a CdTe/CdSe type-II core/shell QD sensitizer with an absorption range extending into the infrared region because of its exciplex state, which is covalently linked to TiO2 mesoporous electrodes by dropping a bifunctional linker molecule mercaptopropionic acid (MPA)-capped QD aqueous solution onto the film electrode. High loading and a uniform distribution of QD sensitizer throughout the film electrode thickness have been confirmed by energy dispersive X-ray (EDX) elemental mapping. The accelerated electron injection and retarded charge-recombination pathway in the built CdTe/CdSe QD cells in comparison with reference CdSe QD-based cells have been confirmed by impedance spectroscopy, fluorescence decay, and intensity-modulated photocurrent/photovoltage spectroscopy (IMPS/IMVS) analysis. With the combination of the high QD loading and intrinsically superior optoelectronic properties of type-II core/shell QD (wide absorption range, fast charge separation, and slow charge recombination), the resulting CdTe/CdSe QD-based regenerative sandwich solar cells exhibit a record PCE of 6.76% (J(sc) = 19.59 mA cm(-2), V(oc) = 0.606 V, and FF = 0.569) with a mask around the active film under a full 1 sun illumination (simulated AM 1.5), which is the highest reported to date for liquid-junction QDSCs.

[Clinical features of imbalance between Th1 and Th22 cells and its association with disease progression in patients with liver cirrhosis].

PubMed

Wu, H Q; Zhao, J J; Li, H W; Zhang, Z

2017-10-20

Objective: To investigate the clinical features of imbalance between Th1 and Th22 cells and its association with disease progression in patients with liver cirrhosis, and to explore immune therapeutic strategies for targeted therapy for liver cirrhosis. Methods: In vitro peripheral blood mononucleated cells (PBMCs) were collected by centrifugation. CD3-BV500 and CD8-PerCP-Cy5.5 staining was performed for these cells. IFNγ-PE-Cy7, IL-17a-APC, IL-22-PE, or the corresponding isotype control was added, and then PBMCs were fixed with 1% polyoxymethylene after being washed once by permeabilization-wash buffer. Flowjo software was used for the analysis of T lymphocyte subsets and cytokines. Th1 (CD4+IFNγ(+)), Th17 (CD4+IL-17a(+)), Th22 (CD4+IL-22(+)), Tc1 (CD8+IFNγ(+)), Tc17 (CD8+IL-17a(+)), and Tc22 (CD8+IL-22(+)) subsets were defined and the secretions of interferon-γ (IFN-γ), interleukin-17a (IL-17a), and interleukin-22 (IL-22) were measured for all subsets. LX-2 cells were cultured in a serum-free medium and different concentrations of recombinant human IL-22 protein (25, 50, 100 ng/ml) were added; 24 hours later, the activation marker α-smooth muscle actin (α-SMA) was used to measure LX-2 activation. Fetal bovine serum with a volume fraction of 10% was used as a positive control. Enzyme-linked immunosorbent assay (chemiluminescence) was used to measure the concentrations of hyaluronic acid, type III precollagen, and type IV collagen in supernatant. A one-way analysis of variance, the non-parametric Mann-Whitney U test, and the non-parametric Kruskal-wallis H test were used for statistical analysis based on data type. Results: Compared with the health control group, the liver cirrhosis groups with various causes had significant increases in peripheral Tc1, Th17, and Th22 cells. The percentage of Th17 cells in the liver cirrhosis group was 1.64 times that in the control group (4.25%±2.45% vs 2.59%±1.36%, P < 0.05), and the mean percentage of Th22 cells in the liver cirrhosis group was 2.18 times that in the control group (4.17%±2.55% vs 1.31%±0.64%, P < 0.05). The percentages of Th17 (5.89%±3.44%) and Th22 cells (5.32%±3.67%) in the patients with alcoholic cirrhosis were 1.27 and 3.06 times those in the control group ( P < 0.05). The patients with alcoholic cirrhosis had a significant increase in Th22 cells. The patients with different types of liver cirrhosis had a significant reduction in the ratio between anti-fibrotic and pro-fibrotic factors (Th1/Th22), which was positively correlated with the severity of liver cirrhosis and was a common immunological feature of liver cirrhosis with different causes. In addition, IL-22 activated hepatic stellate cells and promoted the production of collagen. Conclusion: The imbalance between anti-fibrotic and pro-fibrotic factors (Th1/Th22) is a common feature of the progression of liver fibrosis with various causes and may contribute to the progression of liver fibrosis.

UPTAKE OF LIPOPHILIC CADMIUM COMPLEXES BY THREE GREEN ALGAE: INFLUENCE OF HUMIC ACID AND ITS pH DEPENDENCE(1).

PubMed

Boullemant, Amiel; Le Faucheur, Séverine; Fortin, Claude; Campbell, Peter G C

2011-08-01

Cadmium forms neutral, lipophilic CdL2 (0) complexes with diethyldithiocarbamate (L = DDC) and with ethylxanthate (L = XANT). In a synthetic solution and in the absence of natural dissolved organic matter (DOM), for a given total Cd concentration, uptake of these complexes by unicellular algae is much faster than the uptake of the free Cd(2+) cation. The objective of the present study was to determine how this enhanced uptake of the lipophilic CdL2 (0) complexes was affected by the presence of natural DOM (Suwannee River humic acid, SRHA). Experiments were performed with Cd(DDC)2 (0) and Cd(XANT)2 (0) at two pH values (7.0 and 5.5) and with the three chlorophytes [Chlamydomonas reinhardtii P. A. Dang., Pseudokirchneriella subcapitata (Korshikov) Hindák, Chlorella fusca var. vacuolata Shihira et R. W. Krauss]. Short-term uptake (30-40 min) of the CdL2 (0) complexes was followed in the absence and presence of SRHA (6.5 mg C · L(-1) ). Acidification from pH 7.0 to 5.5 decreased CdL2 (0) uptake by the three algae, in the presence or absence of humic acid (HA). The dominant effect of the HA was to decrease Cd uptake, due to its interaction with the CdL2 (0) complexes in solution. However, if uptake of the free CdL2 (0) complexes was compared in the presence and absence of HA, in four of eight cases initial uptake rate constants (ki ) were significantly higher (P < 0.05) in the presence of the HA, suggesting the operation of an interfacial effect of the HA at the algal cell membrane, favoring uptake of CdL2 (0) . Overall, the experimental results suggest that neutral metal complexes will be less bioavailable in natural waters than they are in synthetic laboratory media in the absence of natural DOM. © 2011 Phycological Society of America.

Gamma Interferon-Induced T-Cell Loss in Virulent Mycobacterium avium Infection

PubMed Central

Flórido, Manuela; Pearl, John E.; Solache, Alejandra; Borges, Margarida; Haynes, Laura; Cooper, Andrea M.; Appelberg, Rui

2005-01-01

Infection by virulent Mycobacterium avium caused progressive severe lymphopenia in C57BL/6 mice due to increased apoptosis rates. T-cell depletion did not occur in gamma interferon (IFN-γ)-deficient mice which showed increased T-cell numbers and proliferation; in contrast, deficiency in nitric oxide synthase 2 did not prevent T-cell loss. Although T-cell loss was IFN-γ dependent, expression of the IFN-γ receptor on T cells was not required for depletion. Similarly, while T-cell loss was optimal if the T cells expressed IFN-γ, CD8+ T-cell depletion could occur in the absence of T-cell-derived IFN-γ. Depletion did not require that the T cells be specific for mycobacterial antigen and was not affected by deficiencies in the tumor necrosis factor receptors p55 or p75, the Fas receptor (CD95), or the respiratory burst enzymes or by forced expression of bcl-2 in hematopoietic cells. PMID:15908387

Effect of Chemicals on Morphology and Luminescence of CdSe Quantum Dots.

PubMed

Zhang, Xiao; Li, Xiaoyu; Zhang, Ruili; Yang, Ping

2015-04-01

CdSe quantum dots (QDs) with several morphologies were fabricated using various reaction sys- tems. In a trioctylamine (TOA) and octadecylphosphonic acid (ODPA) system, yellow-emitting (a photoluminescence (PL) peak wavelength of 583 nm) CdSe QDs revealed rod morphology and nar- row size distribution. When ODPA was replaced by tetradecylphosphonic acid (TDPA), red-emitting CdSe rods (a PL peak wavelength of 653 nm) with broad size distribution were fabricated. This is ascribed that the short carbon chain accelerated the growth of CdSe QDs. As a result, the use of ODPA resulted in CdSe QDs with high PL efficiency (3.1%). Furthermore, cubic-like CdSe QDs were created in a stearic acid (SA) and octadecene (ODE) reaction system. The PL efficiency of the QDs is low (0.2%). When hexadecylamine (HDA) was added in such SA and ODE reaction system, spherical CdSe QDs with narrow size distribution and high PL efficiency (3.4%) were prepared.

Highly Efficient White Organic Light Emitting Diodes Using New Blue Fluorescence Emitter.

PubMed

Kim, Seungho; Kim, Beomjin; Lee, Jaehyun; Yu, Young-Jun; Park, Jongwook

2015-07-01

Two different emitting compounds, 1-[1,1';3',1"]Terphenyl-5'-yl-6-(10-[1,1';3',1"]terpheny-5'-yl- anthracen-9-yl)-pyrene (TP-AP-TP) and Poly-phenylene vinylene derivative (PDY 132) were used to white OLED device. By incorporating adjacent blue and yellow emitting layers in a multi-layered structure, highly efficient white emission has been attained. The device was fabricated with a hybrid configuration structure: ITO/PEDOT (40 nm)/PDY-132 (8-50 nm)/ NPB (10 nm)/TP-AP-TP (30 nm)/Alq3 (20 nm)/LiF (1 nm)/Al (200 nm). After fixing TP-AP-TP thickness of 30 nm by evaporation, PDY-132 thickness varied with 8, 15, 35, and 50 nm by spin coating in device. The luminance efficiency of the white devices at 10 mA/cm2 were 2.93 cd/A-6.55 cd/A. One of white devices showed 6.55 cd/A and white color of (0.290, 0.331).

Abdominal {gamma}-Radiation Induces an Accumulation of Function-Impaired Regulatory T Cells in the Small Intestine

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

Billiard, Fabienne; Buard, Valerie; Benderitter, Marc

Purpose: To assess the frequency and the functional characteristics of one major component of immune tolerance, the CD4{sup +}FoxP3{sup +} regulatory T cells (Tregs) in a mouse model of abdominal irradiation. Methods and Materials: Mice were exposed to a single abdominal dose of {gamma}-radiation (10 Gy). We evaluated small intestine Treg infiltration by Foxp3 immunostaining and the functional suppressive activity of Tregs isolated from mesenteric lymph nodes. Results: Foxp3 immunostaining showed that radiation induced a long-term infiltration of the intestine by Tregs (levels 5.5 times greater than in controls). Co-culture of Tregs from mesenteric lymph nodes with CD4{sup +} effectormore » cells showed that the Tregs had lost their suppressive function. This loss was associated with a significant decrease in the levels of Foxp3, TGF-{beta}, and CTLA-4 mRNA, all required for optimal Treg function. At Day 90 after irradiation, Tregs regained their suppressive activity as forkhead box P3 (Foxp3), transforming growth factor beta (TGF-{beta}), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression returned to normal. Analysis of the secretory function of mesenteric lymph node Tregs, activated in vitro with anti-CD3/anti-CD28 Abs, showed that this dysfunction was independent of a defect in interleukin-10 secretion. Conclusion: Radiation caused a long-term accumulation of function-impaired Foxp3{sup +}CD4{sup +} Tregs in the intestine. Our study provides new insights into how radiation affects the immune tolerance in peripheral tissues.« less

A facile and green preparation of high-quality CdTe semiconductor nanocrystals at room temperature

NASA Astrophysics Data System (ADS)

Liu, Yan; Shen, Qihui; Yu, Dongdong; Shi, Weiguang; Li, Jixue; Zhou, Jianguang; Liu, Xiaoyang

2008-06-01

One chemical reagent, hydrazine hydrate, was discovered to accelerate the growth of semiconductor nanocrystals (cadmium telluride) instead of additional energy, which was applied to the synthesis of high-quality CdTe nanocrystals at room temperature and ambient conditions within several hours. Under this mild condition the mercapto stabilizers were not destroyed, and they guaranteed CdTe nanocrystal particle sizes with narrow and uniform distribution over the largest possible range. The CdTe nanocrystals (photoluminescence emission range of 530-660 nm) synthesized in this way had very good spectral properties; for instance, they showed high photoluminescence quantum yield of up to 60%. Furthermore, we have succeeded in detecting the living Borrelia burgdorferi of Lyme disease by its photoluminescence image using CdTe nanocrystals.

Amount of cadmium associated with Cd-binding protein in roots of young plants. [Agrostis gigantea

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

Rauser, W.E.

1986-04-01

The partitioning of Cd between roots and shoots was determined for young plants exposed to Cd in nutrient solution. The intentionally high concentration of 3 ..mu..m Cd was used to assess the role of root Cd-binding protein (Cd-BP) in Cd detoxification. The roots of tomatoes exposed to Cd retained 60-84% of the plant Cd from day 2 through day 9 without toxicity symptoms evident. Cd-BP did not contribute to Cd retention over the initial 4 days, only 1-4% of the root Cd was in this protein fraction. Maize roots retained 59-66% of the plant Cd from day 1 through daymore » 7. The Cd-BP fraction bound 8-19% of the root Cd on day 1 and 31-55% by day 7. Cd toxicity symptoms occurred in leaves by 4 days. In the grass Agrostis gigantea the roots retained 73-85% of the seedling Cd after 1 day and for another 6 days. A high proportion of the root Cd(34-68%) was in the Cd-BP fraction after one day and continued to be so to day 7 (46-64%). No Cd toxicity symptoms were evident. Only the specific pattern of rapid, early and sustained production of Cd-BP observed in Agrostis was consistent with the putative detoxification role for Cd-BP.« less

Enhanced levels of soluble CD40 ligand exacerbate platelet aggregation and thrombus formation through a CD40-dependent tumor necrosis factor receptor-associated factor-2/Rac1/p38 mitogen-activated protein kinase signaling pathway.

PubMed

Yacoub, Daniel; Hachem, Ahmed; Théorêt, Jean-François; Gillis, Marc-Antoine; Mourad, Walid; Merhi, Yahye

2010-12-01

CD40 ligand is a thromboinflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40 ligand (sCD40L), which has been shown to influence platelet activation, although its exact functional impact on platelets and the underlying mechanisms remain undefined. We aimed to determine the impact and the signaling mechanisms of sCD40L on platelets. sCD40L strongly enhances platelet activation and aggregation. Human platelets treated with a mutated form of sCD40L that does not bind CD40, and CD40(-/-) mouse platelets failed to elicit such responses. Furthermore, sCD40L stimulation induces the association of the tumor necrosis factor receptor-associated factor-2 with platelet CD40. Notably, sCD40L primes platelets through activation of the small GTPase Rac1 and its downstream target p38 mitogen-activated protein kinase, which leads to platelet shape change and actin polymerization. Moreover, sCD40L exacerbates thrombus formation and leukocyte infiltration in wild-type mice but not in CD40(-/-) mice. sCD40L enhances agonist-induced platelet activation and aggregation through a CD40-dependent tumor necrosis factor receptor-associated factor-2/Rac1/p38 mitogen-activated protein kinase signaling pathway. Thus, sCD40L is an important platelet primer predisposing platelets to enhanced thrombus formation in response to vascular injury. This may explain the link between circulating levels of sCD40L and cardiovascular diseases.

A theoretical investigation of the structural and electronic properties of 55-atom nanoclusters: The examples of Y–Tc and Pt

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

Batista, Krys E. A.; Piotrowski, Maurício J., E-mail: mauriciomjp@gmail.com; Chaves, Anderson S.

2016-02-07

Several studies have found that the Pt{sub 55} nanocluster adopts a distorted reduced core structure, DRC{sub 55}, in which there are 8–11 atoms in the core and 47–44 atoms in the surface, instead of the compact and high-symmetry icosahedron structure, ICO{sub 55}, with 13 and 42 atoms in the core and surface, respectively. The DRC structure has also been obtained as the putative global minimum configuration (GMC) for the Zn{sub 55} (3d), Cd{sub 55} (4d), and Au{sub 55} (5d) systems. Thus, the DRC{sub 55} structure has been reported only for systems with a large occupation of the d-states, where themore » effects of the occupation of the valence anti-bonding d-states might play an important role. Can we observe the DRC structure for 55-atom transition-metal systems with non-occupation of the anti-bonding d-states? To address this question, we performed a theoretical investigation of the Y {sub 55}, Zr{sub 55}, Nb{sub 55}, Mo{sub 55}, Tc{sub 55}, and Pt{sub 55} nanoclusters, employing density functional theory calculations. For the putative GMCs, we found that the Y {sub 55} adopts the ICO{sub 55} structure, while Nb{sub 55} and Mo{sub 55} adopt a bulk-like fragment based on the hexagonal close-packed structure and Tc{sub 55} adopts a face-centered cubic fragment; however, Zr{sub 55} adopts a DRC{sub 55} structure, like Zn{sub 55}, Cd{sub 55}, Pt{sub 55}, and Au{sub 55}. Thus we can conclude that the preference for DRC{sub 55} structure is not related to the occupation of the anti-bonding d-states, but to a different effect, in fact, a combination of structural and electronic effects. Furthermore, we obtained that the binding energy per atom follows the occupation of the bonding and anti-bonding model, i.e., the stability of the studied systems increases from Y to Tc with a small oscillation for Mo, which also explains the equilibrium bond lengths. We obtained a larger magnetic moment for Y {sub 55} (31 μ{sub B}) which can be explained by the localization of the d-states in Y at nanoscale, which is not observed for the remaining systems (0–1 μ{sub B})« less

High altitude gust acceleration environment as experienced by a supersonic airplane

NASA Technical Reports Server (NTRS)

Ehernberger, L. J.; Love, B. J.

1975-01-01

High altitude turbulence experienced at supersonic speeds is described in terms of gust accelerations measured on the YF-12A airplane. The data were obtained during 90 flights at altitudes above 12.2 kilometers (40,000 feet). Subjective turbulence intensity ratings were obtained from air crew members. The air crew often rated given gust accelerations as being more intense during high altitude supersonic flight than during low altitude subsonic flight. The portion of flight distance in turbulence ranged from 6 percent to 8 percent at altitudes between 12.2 kilometers and 16.8 kilometers (40,000 feet and 55,000 feet) to less than 1 percent at altitudes above 18.3 kilometers (60,000 feet). The amount of turbulence varied with season, increasing by a factor of 3 or more from summer to winter. Given values of gust acceleration were less frequent, on the basis of distance traveled, for supersonic flight of the YF-12A airplane at altitudes above 12.2 kilometers (40,000 feet) than for subsonic flight of a jet passenger airplane at altitudes below 12.2 kilometers (40,000 feet). The median thickness of high altitude turbulence patches was less than 400 meters (1300 feet); the median length was less than 16 kilometers (10 miles). The distribution of the patch dimensions tended to be log normal.

Vacuum-assisted closure therapy increases local interleukin-8 and vascular endothelial growth factor levels in traumatic wounds.

PubMed

Labler, Ludwig; Rancan, Mario; Mica, Ladislav; Härter, Luc; Mihic-Probst, Daniela; Keel, Marius

2009-03-01

Clinical observations are suggesting accelerated granulation tissue formation in traumatic wounds treated with vacuum-assisted closure (VAC). Aim of this study was to determine the impact of VAC therapy versus alternative Epigard application on local inflammation and neovascularization in traumatic soft tissue wounds. Thirty-two patients with traumatic wounds requiring temporary coverage (VAC n = 16; Epigard n = 16) were included. At each change of dressing, samples of wound fluid and serum were collected (n = 80). The cytokines interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 were measured by ELISA. Wound biopsies were examined histologically for inflammatory cells and degree of neovascularization present. All cytokines were found to be elevated in wound fluids during both VAC and Epigard treatment, whereas serum concentrations were negligible or not detectable. In wound fluids, significantly higher IL-8 (p < 0.001) and VEGF (p < 0.05) levels were detected during VAC therapy. Furthermore, histologic examination revealed increased neovascularization (p < 0.05) illustrated by CD31 and von Willebrand factor immunohistochemistry in wound biopsies of VAC treatment. In addition, there was an accumulation of neutrophils as well as an augmented expression of VEGF (p < 0.005) in VAC wound biopsies. This study suggests that VAC therapy of traumatic wounds leads to increased local IL-8 and VEGF concentrations, which may trigger accumulation of neutrophils and angiogenesis and thus, accelerate neovascularization.

A 16-year retrospective study of dacryocystitis in adult patients in the Moldavia Region, Romania.

PubMed

Costea, Claudia Florida; Dumitrescu, Gabriela FlorenŢa; Turliuc, Mihaela Dana; Dimitriu, Gabriela; Chihaia, Mădălina Adriana; Indrei, Lucia; Dumitrescu, Nicoleta; Cucu, Andrei; Cărăuleanu, Alexandru; Gavrilescu, Cristina Maria; Costache, Irina Iuliana

2017-01-01

Chronic dacryocystitis (CD) is an inflammation of the lacrimal sac and nasolacrimal duct with a long-standing evolution. The aims of this study were to analyze the epidemiology and to evaluate the histopathological features and the chronic inflammation score (CIS) system of chronic dacryocystitis in the region of Moldavia, Romania, over a period of 16 years. We conducted a retrospective descriptive analysis of all pathological reports of chronic dacryocystitis from the Department of Pathology, "Prof. Dr. Nicolae Oblu" Emergency Clinical Hospital, Iasi, Romania, between January 1, 1999 and December 31, 2015, with the final application of CIS. We also recorded the demographic information of patients and lesion localizations. Eighteen cases of CD were identified, with a female:male ratio of 8:1. Patient median age was 66.27 years (range 33-83 years), 55.55% being in their eighth and ninth decade of life. A non-systemized growth trend starting with 2002 could be identified. Microscopically, several histopathological features were identified, some of them being associated: epithelial lining hyperplasia with pseudopapillary folds (77.77% of the cases), epithelial invaginations in the submucosa (11.11%), squamous metaplasia (16.66%) or partial denudation (33.33%). The sac wall revealed chronic diffusion (88.88%) or nodular lymphocytic inflammation (11.11%). 5.55% of cases presented fibrosis in the lacrimal sac wall with few lymphocytes. Applying CIS system, the majority of cases (13 patients, 72.22%) were identified with moderate chronic inflammation, only one case (5.55%) pointed out a mild degree of inflammation with a CIS<3, but four (22.22%) cases showed severe inflammatory changes with a CIS>6. In our region, CD is more frequent in senior women, probably due to their deficient immune system. Histological specimens of CD are not commonly found in practice of pathologists, but when the histological sections are analyzed they reflect a multitude of aspects that need to be known in order to guide ophthalmologists in their practice. In our region, CD is more frequent in senior women, probably due to their deficient immune system and to the specific anatomy of their nasolacrimal duct. The histological appearances varied from patient to patient and even in the same patient varied from one area to another. There were histopathological changes indicating adaptive changes, which could lead to the development of malignant tumors at this level. Therefore, there is a need for patient education with CD both in terms of ophthalmic hygiene and in what regards possible complications in the absence of a regular presentation to the ophthalmologist.

GalT-KO pig lungs are highly susceptible to acute vascular rejection in baboons, which may be mitigated by transgenic expression of hCD47 on porcine blood vessels.

PubMed

Watanabe, Hironosuke; Sahara, Hisashi; Nomura, Shunichiro; Tanabe, Tatsu; Ekanayake-Alper, Dilrukshi K; Boyd, Lennan K; Louras, Nathan J; Asfour, Arsenoi; Danton, Makenzie A; Ho, Siu-Hong; Arn, Scott J; Hawley, Robert J; Shimizu, Akira; Nagayasu, Takeshi; Ayares, David; Lorber, Marc I; Sykes, Megan; Sachs, David H; Yamada, Kazuhiko

2018-03-12

Despite recent progress in survival times of xenografts in non-human primates, there are no reports of survival beyond 5 days of histologically well-aerated porcine lung grafts in baboons. Here, we report our initial results of pig-to-baboon xeno-lung transplantation (XLTx). Eleven baboons received genetically modified porcine left lungs from either GalT-KO alone (n = 3), GalT-KO/humanCD47(hCD47)/hCD55 (n = 3), GalT-KO/hD47/hCD46 (n = 4), or GalT-KO/hCD39/hCD46/hCD55/TBM/EPCR (n = 1) swine. The first 2 XLTx procedures were performed under a non-survival protocol that allowed a 72-hour follow-up of the recipients with general anesthesia, while the remaining 9 underwent a survival protocol with the intention of weaning from ventilation. Lung graft survivals in the 2 non-survival animals were 48 and >72 hours, while survivals in the other 9 were 25 and 28 hours, at 5, 5, 6, 7, >7, 9, and 10 days. One baboon with graft survival >7 days, whose entire lung graft remained well aerated, was euthanized on POD 7 due to malfunction of femoral catheters. hCD47 expression of donor lungs was detected in both alveoli and vessels only in the 3 grafts surviving >7, 9, and 10 days. All other grafts lacked hCD47 expression in endothelial cells and were completely rejected with diffuse hemorrhagic changes and antibody/complement deposition detected in association with early graft loss. To our knowledge, this is the first evidence of histologically viable porcine lung grafts beyond 7 days in baboons. Our results indicate that GalT-KO pig lungs are highly susceptible to acute humoral rejection and that this may be mitigated by transgenic expression of hCD47. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An IFNG SNP with an estrogen-like response element selectively enhances promoter expression in peripheral but not lamina propria T cells.

PubMed

Gonsky, R; Deem, R L; Bream, J H; Young, H A; Targan, S R

2006-07-01

This study examines mucosa-specific regulatory pathways involved in modulation of interferon-gamma (IFN-gamma) in lamina propria T cells. Previous studies identified mucosa-specific CD2 cis-elements within the -204 to -108 bp IFNG promoter. Within this region, a single-site nucleotide polymorphism, -179G/T, imparts tumor necrosis factor-alpha stimulation of IFNG in peripheral blood lymphocytes, and is linked with accelerated AIDS progression. We discovered a putative estrogen response element (ERE) introduced by the -179T, which displays selective activation in peripheral blood mononuclear cells (PBMC) vs lamina propria mononuclear cells (LPMC). Transfection of PBMC with constructs containing the -179G or -179T site revealed CD2-mediated enhancement of the -179T compared to -179G allele, although, in LPMC, a similar level of expression was detected. Electrophoretic mobility shift assay (EMSA) analysis demonstrated CD2-mediated nucleoprotein binding to the -179T but not the -179G in PBMC. In LPMC, binding is constitutive to both -179G and -179T regions. Sequence and EMSA analysis suggests that the -179T allele creates an ERE-like binding site capable of binding recombinant estrogen receptor. Estrogen response element transactivation is enhanced by CD2 signaling, but inhibited by estrogen in PBMC but not in LPMC, although expression of estrogen receptor was similar. This is the first report to describe a potential molecular mechanism responsible for selectively controlling IFN-gamma production in LPMC.

Evaluation of a CdTe semiconductor based compact γ camera for sentinel lymph node imaging.

PubMed

Russo, Paolo; Curion, Assunta S; Mettivier, Giovanni; Esposito, Michela; Aurilio, Michela; Caracò, Corradina; Aloj, Luigi; Lastoria, Secondo

2011-03-01

The authors assembled a prototype compact gamma-ray imaging probe (MediPROBE) for sentinel lymph node (SLN) localization. This probe is based on a semiconductor pixel detector. Its basic performance was assessed in the laboratory and clinically in comparison with a conventional gamma camera. The room-temperature CdTe pixel detector (1 mm thick) has 256 x 256 square pixels arranged with a 55 microm pitch (sensitive area 14.08 x 14.08 mm2), coupled pixel-by-pixel via bump-bonding to the Medipix2 photon-counting readout CMOS integrated circuit. The imaging probe is equipped with a set of three interchangeable knife-edge pinhole collimators (0.94, 1.2, or 2.1 mm effective diameter at 140 keV) and its focal distance can be regulated in order to set a given field of view (FOV). A typical FOV of 70 mm at 50 mm skin-to-collimator distance corresponds to a minification factor 1:5. The detector is operated at a single low-energy threshold of about 20 keV. For 99 mTc, at 50 mm distance, a background-subtracted sensitivity of 6.5 x 10(-3) cps/kBq and a system spatial resolution of 5.5 mm FWHM were obtained for the 0.94 mm pinhole; corresponding values for the 2.1 mm pinhole were 3.3 x 10(-2) cps/kBq and 12.6 mm. The dark count rate was 0.71 cps. Clinical images in three patients with melanoma indicate detection of the SLNs with acquisition times between 60 and 410 s with an injected activity of 26 MBq 99 mTc and prior localization with standard gamma camera lymphoscintigraphy. The laboratory performance of this imaging probe is limited by the pinhole collimator performance and the necessity of working in minification due to the limited detector size. However, in clinical operative conditions, the CdTe imaging probe was effective in detecting SLNs with adequate resolution and an acceptable sensitivity. Sensitivity is expected to improve with the future availability of a larger CdTe detector permitting operation at shorter distances from the patient skin.

Biochar and Glomus caledonium Influence Cd Accumulation of Upland Kangkong (Ipomoea aquatica Forsk.) Intercropped with Alfred Stonecrop (Sedum alfredii Hance)

PubMed Central

Hu, Junli; Wu, Fuyong; Wu, Shengchun; Lam, Cheung Lung; Lin, Xiangui; Wong, Ming Hung

2014-01-01

Both biochar application and mycorrhizal inoculation have been proposed to improve plant growth and alter bioaccumulation of toxic metals. A greenhouse pot trial was conducted to investigate growth and Cd accumulation of upland kangkong (Ipomoea aquatica Forsk.) intercropped with Alfred stonecrop (Sedum alfredii Hance) in a Cd-contaminated soil inoculated with Glomus caledonium and/or applied with biochar. Compared with the monocultural control, intercropping with stonecrop (IS) decreased kangkong Cd acquisition via rhizosphere competition, and also decreased kangkong yield. Gc inoculation (+M) accelerated growth and Cd acquisition of stonecrop, and hence resulted in further decreases in kangkong Cd acquisition. Regardless of IS and +M, biochar addition (+B) increased kangkong yield via elevating soil available P, and decreased soil Cd phytoavailability and kangkong Cd concentration via increasing soil pH. Compared with the control, the treatment of IS + M + B had a substantially higher kangkong yield (+25.5%) with a lower Cd concentration (−62.7%). Gc generated additive effects on soil alkalinization and Cd stabilization to biochar, causing lower DTPA-extractable (phytoavailable) Cd concentrations and post-harvest transfer risks. PMID:24728157

Alterations in expression pattern of splicing factors in epithelial ovarian cancer and its clinical impact.

PubMed

Iborra, Severine; Hirschfeld, Marc; Jaeger, Markus; Zur Hausen, Axel; Braicu, Iona; Sehouli, Jalid; Gitsch, Gerald; Stickeler, Elmar

2013-07-01

Alternative splicing represents an important nuclear mechanism in the posttranscriptional regulation of gene expression, which is frequently altered during tumorigenesis. Previously, we described marked changes in alternative splicing of the CD44 gene in ovarian and breast cancer as well as specific induction of distinct splicing factors during tumor development. The present study was focused on the expression profiles of different splicing factors, including classical serine-arginine (SR) proteins including ASF/SF2, hTra2β1, hTra2α, and Y-box-binding protein (YB-1) in physiological and malignant epithelial ovarian tissue to evaluate their expression pattern with regard to tumor development and disease progression. Expression levels of the different splicing factors were analyzed in physiological epithelial ovarian tissue samples, primary tumors, and metastatic samples of patients with a diagnosis of epithelial ovarian cancer using quantified reverse transcription polymerase chain reaction analysis. We examined more closely the splicing factor hTra2β1 using Western blot analysis and immunohistochemistry. The analysis revealed a marked and specific induction of ASF/SF2, SRp20, hTra2β1, and YB-1 in primary tumors as well as in their metastatic sites. However, in our patient cohort, no induction was seen for the other investigated splicing factors SRp55, SRp40, and hTra2α. Our results suggest a specific induction of distinct splicing factors in ovarian cancer tumorigenesis. The involvement of hTra2β1, YB-1, SRp20, and ASF/SF2 in exon recognition and alternative splicing may be important for gene regulation of alternatively spliced genes like CD44 with potential functional consequences in this tumor type leading to progression and metastasis.

Insufficient interleukin-2 production from splenic CD4+ T cells causes impaired cell proliferation and early apoptosis in SAMP1, a strain of senescence-accelerated mouse

PubMed Central

Nishimura, Yasumitsu; Hosokawa, Tomohide; Hosono, Masamichi; Baba, Mitsuo; Hosokawa, Masanori

2002-01-01

We examined the proliferative and cytokine-producing activities of CD4+ T cells from young mice of the senescence-accelerated mouse strain SAMP1, which had shown markedly low T-dependent antibody-producing responses. When splenic T cells were cultured with concanavalin A (Con A), the percentage of CD4+ cells decreased earlier in SAMP1 than in C3H/He mice. At 40 hr of culture, the percentage of BrdU-labelled proliferating CD4+ cells increased strongly in C3H/He, but only slightly in SAMP1. When purified CD4+ T cells were cultured with Con A, the percentage of 5-bromo-2′-deoxyuridine (BrdU)-labelled cells peaked at around 48 hr of culture in both strains, but decreased significantly at 64 hr in SAMP1. The production of interleukin (IL)-2 but not IL-4 or interferon-γ (IFN-γ) was significantly lower in SAMP1 than in C3H/He at 48 hr of culture. IL-2 production was also markedly low in SAMP1, even under the stimulation of anti-CD3 with anti-CD28 antibodies. The frequency of cells producing IL-2 was significantly lower in SAMP1 than in C3H/He at 6–24 hr of culture with Con A. The percentage of annexin-positive and propidium iodide (PI)-negative apoptotic cells was significantly higher in SAMP1 than in C3H/He at 96 hr of culture. Exogenous IL-2 prevented the decrease in BrdU-labelled cells and the increase in apoptotic cells in the SAMP1 cell culture. These results indicate that SAMP1 CD4+ T cells cannot produce IL-2 at levels sufficient to support cell proliferation and survival. This may account for the weak T-dependent antibody response in SAMP1 mice. PMID:12383198

Data base for early postfire succession in Northern Rocky Mountain forests

Treesearch

Peter F. Stickney; Robert B. Campbell

2000-01-01

Web site and CD-ROM include 21 pages of text plus electronic data for 55 succession sites including color plates, tables, and figures. Provides data on quantitative postfire changes of plant species and forest vegetation components for up to the first 25 years of secondary plant succession for 55 forest sites in northern Idaho and northwestern Montana. Cover (aerial...

Statolith formation in Cnidaria: effects of cadmium on Aurelia statoliths

NASA Technical Reports Server (NTRS)

Spangenberg, D. B.

1986-01-01

Statolith formation in Cnidaria was reviewed with an emphasis on Aurelia statoliths. The review provides information on the chemical composition, mechanisms of initiation of mineralization, and effects of environmental factors on Cnidarian statolith formation. Environmental factors discussed included modified sea water ingredients, X-irradiation, clinostat rotation, and petroleum oil ingredients. A detailed account of the effects of cadmium on mineralization and demineralization of Aurelia statoliths is given. Cadmium at dosages of 2 to 4 micromoles significantly reduces statolith numbers in developing ephyrae. At a dosage of 3 micromoles, cadmium accelerates statolith loss in unfed ephyrae studied at 4 and 8 days following ephyrae release from strobilae. Cadmium, therefore, is shown to reduce statolith numbers in developing ephyrae and to cause greater reduction of statolith numbers in unfed ephyrae after 4 and 8 days than occurred in controls. Supplementation of Cd(2+)-containing artificial sea water (ASW) with calcium (3X and 5X ASW calcium content) results in higher numbers of statoliths at day 4 as compared with cadmium-treated ephyrae. At 8 days only the 5X calcium supplemented ASW is effective in enhancing statolith numbers in Cd(2+)-treated ephyrae. These results suggest that cadmium competes in some manner with calcium at the mineralizing sites of Aurelia.

Anti-inflammatory effects of probiotic yogurt in inflammatory bowel disease patients

PubMed Central

Lorea Baroja, M; Kirjavainen, P V; Hekmat, S; Reid, G

2007-01-01

Our aim was to assess anti-inflammatory effects on the peripheral blood of subjects with inflammatory bowel disease (IBD) who consumed probiotic yogurt for 1 month. We studied 20 healthy controls and 20 subjects with IBD, 15 of whom had Crohn's disease and five with ulcerative colitis. All the subjects consumed Lactobacillus rhamnosus GR-1 and L. reuteri RC-14 supplemented yogurt for 30 days. The presence of putative regulatory T (Treg) cells (CD4+ CD25high) and cytokines in T cells, monocytes and dendritic cells (DC) was determined by flow cytometry from peripheral blood before and after treatment, with or without ex vivo stimulation. Serum and faecal cytokine concentrations were determined by enzyme-linked immunosorbent assays. The proportion of CD4+ CD25high T cells increased significantly (P = 0.007) in IBD patients, mean (95% confidence interval: CI) 0.84% (95% CI 0.55–1.12) before and 1.25% (95% CI 0.97–1.54) after treatment, but non-significantly in controls. The basal proportion of tumour necrosis factor (TNF)-α+/interleukin (IL)-12+ monocytes and myeloid DC decreased in both subject groups, but of stimulated cells only in IBD patients. Also serum IL-12 concentrations and proportions of IL-2+ and CD69+ T cells from stimulated cells decreased in IBD patients. The increase in CD4+ CD25high T cells correlated with the decrease in the percentage of TNF-α- or IL-12-producing monocytes and DC. The effect of the probiotic yogurt was confirmed by a follow-up study in which subjects consumed the yogurt without the probiotic organisms. Probiotic yogurt intake was associated with significant anti-inflammatory effects that paralleled the expansion of peripheral pool of putative Treg cells in IBD patients and with few effects in controls. PMID:17590176

Association of six CpG-SNPs in the inflammation-related genes with coronary heart disease.

PubMed

Chen, Xiaomin; Chen, Xiaoying; Xu, Yan; Yang, William; Wu, Nan; Ye, Huadan; Yang, Jack Y; Hong, Qingxiao; Xin, Yanfei; Yang, Mary Qu; Deng, Youping; Duan, Shiwei

2016-07-25

Chronic inflammation has been widely considered to be the major risk factor of coronary heart disease (CHD). The goal of our study was to explore the possible association with CHD for inflammation-related single nucleotide polymorphisms (SNPs) involved in cytosine-phosphate-guanine (CpG) dinucleotides. A total of 784 CHD patients and 739 non-CHD controls were recruited from Zhejiang Province, China. Using the Sequenom MassARRAY platform, we measured the genotypes of six inflammation-related CpG-SNPs, including IL1B rs16944, IL1R2 rs2071008, PLA2G7 rs9395208, FAM5C rs12732361, CD40 rs1800686, and CD36 rs2065666). Allele and genotype frequencies were compared between CHD and non-CHD individuals using the CLUMP22 software with 10,000 Monte Carlo simulations. Allelic tests showed that PLA2G7 rs9395208 and CD40 rs1800686 were significantly associated with CHD. Moreover, IL1B rs16944, PLA2G7 rs9395208, and CD40 rs1800686 were shown to be associated with CHD under the dominant model. Further gender-based subgroup tests showed that one SNP (CD40 rs1800686) and two SNPs (FAM5C rs12732361 and CD36 rs2065666) were associated with CHD in females and males, respectively. And the age-based subgroup tests indicated that PLA2G7 rs9395208, IL1B rs16944, and CD40 rs1800686 were associated with CHD among individuals younger than 55, younger than 65, and over 65, respectively. In conclusion, all the six inflammation-related CpG-SNPs (rs16944, rs2071008, rs12732361, rs2065666, rs9395208, and rs1800686) were associated with CHD in the combined or subgroup tests, suggesting an important role of inflammation in the risk of CHD.

Estimating rangeland runoff, soil erosion, and salt mobility and transport processes

USDA-ARS?s Scientific Manuscript database

Over 55% of sediment and salts entering the Colorado River are derived from accelerated soil erosion from federal rangelands with damages estimated to be $385 million per year. About 55% of the loading is derived from rangelands. This suggests a significant potential to reduce dissolved-solids loa...

PD-L1, B7-H3, and PD-1 expression in immunocompetent vs. immunosuppressed patients with cutaneous squamous cell carcinoma.

PubMed

Varki, Vinod; Ioffe, Olga B; Bentzen, Soren M; Heath, Jon; Cellini, Ashley; Feliciano, Josephine; Zandberg, Dan P

2018-05-01

To characterize the expression of co-signaling molecules PD-L1, PD-1, and B7-H3 in cutaneous squamous cell carcinoma (cSCC) by immune status. We retrospectively analyzed 66 cases of cSCC treated with surgical resection from 2012 to 2015. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 (Tum-PD-L1%), B7-H3 (Tum-B7-H3%), density of peri and intratumoral CD8 T cells (CD8 density), proportion of CD8 T cells expressing PD-1 (CD8-PD-1%) and of tumor-infiltrating immune cells (TII) expressing PD-L1 (TII-PD-L1%). Of 66 cases, 42 were immunocompetent, 24 immunosuppressed (13 organ transplant, 8 HIV+, 3 other). Defining positive expression at > 5%, 26% of tumors were positive for PD-L1, 85% for B7-H3, 80% had CD8 T cells that expressed PD-1 and 55% had TII that expressed PD-L1. Tum-B7-H3% was significantly higher (median 60 vs. 28%, p = 0.025) in immunocompetent vs. immunosuppressed patients, including when factoring in cause of immunosuppression. No significant difference in Tum-PD-L1%, TII-PD-L1%, CD8 density, or CD8-PD-1% was observed. Tumors from HIV+ patients lacked PD-L1 expression, and had lower B7-H3% (median 2.5 vs. 60%, p = 0.007), and higher CD8 density (median 75% vs. 40%, p = 0.04) compared to immunocompetent patients. Higher tumor grade (R s  = 0.34, p = 0.006) and LVI (R s  = 0.61, p < 0.001) were both associated with higher Tum-PD-L1%. cSCC showed expression of PD-L1 on tumor in 26% of cases, and high tumor B7-H3 expression (85%) and PD-1 expression on CD8 TILs (80%). Tumor B7-H3 expression was significantly higher in immunocompetent vs. immunosuppressed patients, largely driven by very low expression in HIV+ patients.

The Robo4 cytoplasmic domain is dispensable for vascular permeability and neovascularization.

PubMed

Zhang, Feng; Prahst, Claudia; Mathivet, Thomas; Pibouin-Fragner, Laurence; Zhang, Jiasheng; Genet, Gael; Tong, Raymond; Dubrac, Alexandre; Eichmann, Anne

2016-11-24

Vascular permeability and neovascularization are implicated in many diseases including retinopathies and diabetic wound healing. Robo4 is an endothelial-specific transmembrane receptor that stabilizes the vasculature, as shown in Robo4 -/- mice that develop hyperpermeability, but how Robo4 signals remained unclear. Here we show that Robo4 deletion enhances permeability and revascularization in oxygen-induced retinopathy (OIR) and accelerates cutaneous wound healing. To determine Robo4 signalling pathways, we generated transgenic mice expressing a truncated Robo4 lacking the cytoplasmic domain (Robo4ΔCD). Robo4ΔCD expression is sufficient to prevent permeability, and inhibits OIR revascularization and wound healing in Robo4 -/- mice. Mechanistically, Robo4 does not affect Slit2 signalling, but Robo4 and Robo4ΔCD counteract Vegfr2-Y949 (Y951 in human VEGFR2) phosphorylation by signalling through the endothelial UNC5B receptor. We conclude that Robo4 inhibits angiogenesis and vessel permeability independently of its cytoplasmic domain, while activating VEGFR2-Y951 via ROBO4 inhibition might accelerate tissue revascularization in retinopathy of prematurity and in diabetic patients.

Euler force actuation mechanism for siphon valving in compact disk-like microfluidic chips.

PubMed

Deng, Yongbo; Fan, Jianhua; Zhou, Song; Zhou, Teng; Wu, Junfeng; Li, Yin; Liu, Zhenyu; Xuan, Ming; Wu, Yihui

2014-03-01

Based on the Euler force induced by the acceleration of compact disk (CD)-like microfluidic chip, this paper presents a novel actuation mechanism for siphon valving. At the preliminary stage of acceleration, the Euler force in the tangential direction of CD-like chip takes the primary place compared with the centrifugal force to function as the actuation of the flow, which fills the siphon and actuates the siphon valving. The Euler force actuation mechanism is demonstrated by the numerical solution of the phase-field based mathematical model for the flow in siphon valve. In addition, experimental validation is implemented in the polymethylmethacrylate-based CD-like microfluidic chip manufactured using CO2 laser engraving technique. To prove the application of the proposed Euler force actuation mechanism, whole blood separation and plasma extraction has been conducted using the Euler force actuated siphon valving. The newly introduced actuation mechanism overcomes the dependence on hydrophilic capillary filling of siphon by avoiding external manipulation or surface treatments of polymeric material. The sacrifice for highly integrated processing in pneumatic pumping technique is also prevented by excluding the volume-occupied compressed air chamber.

Trace metals solubility in rainwater: evaluation of rainwater quality at a watershed area, Istanbul.

PubMed

Başak, Bertan; Alagha, Omar

2010-08-01

In this study, 79 bulk precipitation samples were collected at two sampling sites near Büyükçekmece Lake, one of the important drinking water sources of Istanbul, for the period of October 2001 to July 2002. The study comprised the determination of trace and toxic metals concentrations in rain water. The concentrations of the metals in this study were found to be higher than those reported by other researchers around the world. The solubility of toxic metals was found in the order of Cd>Cu>V>Zn>Ni>Pb>Cr. Solubility of metals under acidic conditions (pH<5.5) was approximately five times higher than those under neutral conditions with Cd as the most soluble metal (50% soluble). Statistical evaluations including seasonal variations, crustal enrichment factors, and correlation matrix were discussed to identify the possible sources of these pollutants. The study revealed that anthropogenic elements were highly enriched especially for Cd>Cu>Pb which were found to be highly enriched. Significant portion of Cu and Pb could be increased by the effect of local sources like cement industry in the area; however, the rest of the investigated trace metals could be brought to the sampling site by long-range transport to the Büyükçekmece Lake watershed area.

Endocytosed factor V is trafficked to CD42b+ proplatelet extensions during differentiation of human umbilical cord blood-derived megakaryocytes.

PubMed

Gertz, Jacqueline M; McLean, Kelley C; Bouchard, Beth A

2018-05-15

Plasma- and platelet-derived factor Va are essential for thrombin generation catalyzed by the prothrombinase complex; however, several observations demonstrate that the platelet-derived cofactor, which is formed following megakaryocyte endocytosis and modification of the plasma procofactor, factor V, is more hemostatically relevant. Factor V endocytosis, as a function of megakaryocyte differentiation and proplatelet formation, was assessed by flow cytometry and microscopy in CD34 + hematopoietic progenitor cells isolated from human umbilical cord blood and cultured for 12 days in the presence of cytokines to induce ex vivo differentiation into megakaryocytes. Expression of an early marker of megakaryocyte differentiation, CD41, endocytosis of factor V, and the percentage of CD41 + cells that endocytosed factor V increased from days 6 to 12 of differentiation. In contrast, statistically significant decreases in expression of the stem cell marker, CD34, and in the percentage of CD34 + cells that endocytosed factor V were observed. A statistically significant increase in the expression of CD42b, a late marker of megakaryocyte differentiation, was also observed over time, such that by Day 12, all CD42b + cells endocytosed factor V and expressed CD41. This endocytosed factor V was trafficked to proplatelet extensions and was localized in a punctate pattern in the cytoplasm consistent with its storage in α-granules. In conclusion, loss of CD34 and expression of CD42b define cells capable of factor V endocytosis and trafficking to proplatelet extensions during differentiation of megakaryocytes ex vivo from progenitor cells isolated from umbilical cord blood. © 2018 Wiley Periodicals, Inc.

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

PubMed Central

2010-01-01

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

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

PubMed

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

2010-08-04

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

Purification of Bone Marrow Clonal Cells from Patients with Myelodysplastic Syndrome via IGF-IR

PubMed Central

He, Qi; Chang, Chun-Kang; Xu, Feng; Zhang, Qing-Xia; Shi, Wen-Hui; Li, Xiao

2015-01-01

Malignant clonal cells purification can greatly benefit basic and clinical studies in myelodysplastic syndrome (MDS). In this study, we investigated the potential of using type 1 insulin-like growth factor receptor (IGF-IR) as a marker for purification of malignant bone marrow clonal cells from patients with MDS. The average percentage of IGF-IR expression in CD34+ bone marrow cells among 15 normal controls was 4.5%, 70% of which also express the erythroid lineage marker CD235a. This indicates that IGF-IR mainly express in erythropoiesis. The expression of IGF-IR in CD34+ cells of 55 MDS patients was significantly higher than that of cells from the normal controls (54.0 vs. 4.5%). Based on the pattern of IGF-IR expression in MDS patients and normal controls, sorting of IGF-IR-positive and removal of CD235a-positive erythroid lineage cells with combination of FISH detection were performed on MDS samples with chromosomal abnormalities. The percentage of malignant clonal cells significantly increased after sorting. The enrichment effect was more significant in clonal cells with a previous percentage lower than 50%. This enrichment effect was present in samples from patients with +8, 5q-/-5, 20q-/-20 or 7q-/-7 chromosomal abnormalities. These data suggest that IGF-IR can be used as a marker for MDS bone marrow clonal cells and using flow cytometry for positive IGF-IR sorting may effectively purify MDS clonal cells. PMID:26469401

Cryopreservation of cord blood CD34+ cells before or after thrombopoietin expansion differentially affects early platelet recovery in NOD SCID mice.

PubMed

van Hensbergen, Yvette; van der Garde, Mark; Brand, Anneke; Slot, Manon C; de Graaf-Dijkstra, Alice; Watt, Suzanne; Zwaginga, Jaap Jan

2015-07-01

Expansion of human cord blood (CB) CD34+ cells with thrombopoietin (TPO) can accelerate delayed platelet (PLT) recovery after transplantation into immunodeficient mice. Clinical implementation, however, will depend on practical and effective protocols. The best timing of TPO expansion in relation to cryopreservation in this respect is unknown. In this study, we evaluated whether the order of cryopreservation and TPO expansion affected the expansion rate and numbers of clonogenic hematopoietic progenitor cells in vitro or PLT and longer-term hematopoietic repopulation in NOD SCID mice in vivo. Our results demonstrate higher expansion rates and the generation of higher numbers of multilineage and megakaryocytic progenitors (granulocyte, erythrocyte, monocyte, megakaryocyte colony-forming units and megakaryocyte colony-forming units) in vitro when freshly isolated CB CD34+ cells are first cultured with TPO and then cryopreserved and thawed as compared to TPO expansion after CD34+ cell cryopreservation. In contrast, the cells produced with the latter strategy showed higher expression of CD62L and a superior stromal cell-derived factor-1α-mediated migration. This might play a role in an also observed superior early PLT recovery after transplantation of these cells into NOD SCID mice. The hematopoietic engraftment in the marrow 6 weeks after transplantation was not different between the two strategies. Although TPO expansion before cryopreservation would yield higher nucleated cell and clonogenic myeloid and megakaryocyte cell numbers and enable earlier availability, CB TPO expansion after cryopreservation is likely to be clinically more effective, despite the lower number of cells obtained after expansion. Moreover, the latter strategy is logistically more feasible. © 2015 AABB.

Development of poly(lactic-co-glycolic) acid nanoparticles-embedded hyaluronic acid-ceramide-based nanostructure for tumor-targeted drug delivery.

PubMed

Park, Ju-Hwan; Lee, Jae-Young; Termsarasab, Ubonvan; Yoon, In-Soo; Ko, Seung-Hak; Shim, Jae-Seong; Cho, Hyun-Jong; Kim, Dae-Duk

2014-10-01

A hyaluronic acid-ceramide (HACE) nanostructure embedded with docetaxel (DCT)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) was fabricated for tumor-targeted drug delivery. NPs with a narrow size distribution and negative zeta potential were prepared by embedding DCT-loaded PLGA NPs into a HACE nanostructure (DCT/PLGA/HACE). DCT-loaded PLGA and DCT/PLGA/HACE NPs were characterized by solid-state techniques, including Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). A sustained drug release pattern from the NPs developed was observed and negligible cytotoxicity was seen in NIH3T3 cells (normal fibroblast, CD44 receptor negative) and MDA-MB-231 cells (breast cancer cells, CD44 receptor positive). PLGA/HACE NPs containing coumarin 6, used as a fluorescent dye, exhibited improved cellular uptake efficiency, based on the HA-CD44 receptor interaction, compared to plain PLGA NPs. Cyanine 5.5 (Cy5.5)-labeled PLGA/HACE NPs were injected intravenously into a MDA-MB-231 tumor xenograft mouse model and demonstrated enhanced tumor targetability, compared with Cy5.5-PLGA NPs, according to a near-infrared fluorescence (NIRF) imaging study. Considering these experimental results, the DCT/PLGA/HACE NPs developed may be useful as a tumor-targeted drug delivery system. Copyright © 2014 Elsevier B.V. All rights reserved.

p85α recruitment by the CD300f phosphatidylserine receptor mediates apoptotic cell clearance required for autoimmunity suppression

NASA Astrophysics Data System (ADS)

Tian, Linjie; Choi, Seung-Chul; Murakami, Yousuke; Allen, Joselyn; Morse, Herbert C., III; Qi, Chen-Feng; Krzewski, Konrad; Coligan, John E.

2014-01-01

Apoptotic cell (AC) clearance is essential for immune homeostasis. Here we show that mouse CD300f (CLM-1) recognizes outer membrane-exposed phosphatidylserine, and regulates the phagocytosis of ACs. CD300f accumulates in phagocytic cups at AC contact sites. Phosphorylation within CD300f cytoplasmic tail tyrosine-based motifs initiates signals that positively or negatively regulate AC phagocytosis. Y276 phosphorylation is necessary for enhanced CD300f-mediated phagocytosis through the recruitment of the p85α regulatory subunit of phosphatidylinositol-3-kinase (PI3K). CD300f-PI3K association leads to activation of downstream Rac/Cdc42 GTPase and mediates changes of F-actin that drive AC engulfment. Importantly, primary macrophages from CD300f-deficient mice have impaired phagocytosis of ACs. The biological consequence of CD300f deficiency is predisposition to autoimmune disease development, as FcγRIIB-deficient mice develop a systemic lupus erythematosus-like disease at a markedly accelerated rate if CD300f is absent. In this report we identify the mechanism and role of CD300f in AC phagocytosis and maintenance of immune homeostasis.

Predictive factors for long-term engraftment of autologous blood stem cells.

PubMed

Duggan, P R; Guo, D; Luider, J; Auer, I; Klassen, J; Chaudhry, A; Morris, D; Glück, S; Brown, C B; Russell, J A; Stewart, D A

2000-12-01

Data from 170 consecutive patients aged 19-66 years (median age 46 years) who underwent unmanipulated autologous blood stem cell transplant (ASCT) were analyzed to determine if total CD34+ cells/kg infused, CD34+ subsets (CD34+41+, CD34+90+, CD34+33-, CD34+38-, CD34+38-DR-), peripheral blood CD34+ cell (PBCD34+) count on first apheresis day, or various clinical factors were associated with low blood counts 6 months post ASCT. Thirty-four patients were excluded from analysis either because of death (n = 17) or re-induction chemotherapy prior to 6 months post ASCT (n = 13), or because of lack of follow-up data (n = 4). Of the remaining 136 patients, 46% had low WBC ( < 4 x 10(9)/l), 41% low platelets (<150 x 10(9)/l), and 34% low hemoglobin ( < 120 g/l) at a median of 6 months following ASCT. By Spearman's rank correlation, both the total CD34+ cell dose/kg and the PBCD34+ count correlated with 6 month blood counts better than any subset of CD34+ cells or any clinical factor. The PBCD34+ count was overall a stronger predictor of 6 month blood counts than was the total CD34+ cells/kg infused. Both factors retained their significance in multivariate analysis, controlling for clinical factors. In conclusion, subsets of CD34+ cells and clinical factors are inferior to the total CD34+ cell dose/kg and PBCD34+ count in predicting 6 month blood counts following ASCT.

CD271 regulates the proliferation and motility of hypopharyngeal cancer cells.

PubMed

Mochizuki, Mai; Tamai, Keiichi; Imai, Takayuki; Sugawara, Sayuri; Ogama, Naoko; Nakamura, Mao; Matsuura, Kazuto; Yamaguchi, Kazunori; Satoh, Kennichi; Sato, Ikuro; Motohashi, Hozumi; Sugamura, Kazuo; Tanaka, Nobuyuki

2016-07-29

CD271 (p75 neurotrophin receptor) plays both positive and negative roles in cancer development, depending on the cell type. We previously reported that CD271 is a marker for tumor initiation and is correlated with a poor prognosis in human hypopharyngeal cancer (HPC). To clarify the role of CD271 in HPC, we established HPC cell lines and knocked down the CD271 expression using siRNA. We found that CD271-knockdown completely suppressed the cells' tumor-forming capability both in vivo and in vitro. CD271-knockdown also induced cell-cycle arrest in G0 and suppressed ERK phosphorylation. While treatment with an ERK inhibitor only partially inhibited cell growth, CDKN1C, which is required for maintenance of quiescence, was strongly upregulated in CD271-depleted HPC cells, and the double knockdown of CD271 and CDKN1C partially rescued the cells from G0 arrest. In addition, either CD271 depletion or the inhibition of CD271-RhoA signaling by TAT-Pep5 diminished the in vitro migration capability of the HPC cells. Collectively, CD271 initiates tumor formation by increasing the cell proliferation capacity through CDKN1C suppression and ERK-signaling activation, and by accelerating the migration signaling pathway in HPC.

CD271 regulates the proliferation and motility of hypopharyngeal cancer cells

PubMed Central

Mochizuki, Mai; Tamai, Keiichi; Imai, Takayuki; Sugawara, Sayuri; Ogama, Naoko; Nakamura, Mao; Matsuura, Kazuto; Yamaguchi, Kazunori; Satoh, Kennichi; Sato, Ikuro; Motohashi, Hozumi; Sugamura, Kazuo; Tanaka, Nobuyuki

2016-01-01

CD271 (p75 neurotrophin receptor) plays both positive and negative roles in cancer development, depending on the cell type. We previously reported that CD271 is a marker for tumor initiation and is correlated with a poor prognosis in human hypopharyngeal cancer (HPC). To clarify the role of CD271 in HPC, we established HPC cell lines and knocked down the CD271 expression using siRNA. We found that CD271-knockdown completely suppressed the cells’ tumor-forming capability both in vivo and in vitro. CD271-knockdown also induced cell-cycle arrest in G0 and suppressed ERK phosphorylation. While treatment with an ERK inhibitor only partially inhibited cell growth, CDKN1C, which is required for maintenance of quiescence, was strongly upregulated in CD271-depleted HPC cells, and the double knockdown of CD271 and CDKN1C partially rescued the cells from G0 arrest. In addition, either CD271 depletion or the inhibition of CD271-RhoA signaling by TAT-Pep5 diminished the in vitro migration capability of the HPC cells. Collectively, CD271 initiates tumor formation by increasing the cell proliferation capacity through CDKN1C suppression and ERK-signaling activation, and by accelerating the migration signaling pathway in HPC. PMID:27469492

Wrinkle-free atomically thin CdS nanosheets for photocatalytic hydrogen evolution

NASA Astrophysics Data System (ADS)

Pan, Ziwei; Li, Junnan; Zhou, Kebin

2018-05-01

Two-dimensional (2D) nanosheets of atomic thickness have attracted extensive research interest recently. In this work, atomically thin (0.7 nm) flat CdS (F-CdS) nanosheets of several tens of micrometers in lateral size were synthesized by a solvent-thermal method. The as-synthesized F-CdS could maintain flat morphology well in solution, while irreversible wrinkles could be generated after drying, forming wrinkled CdS (W-CdS) samples. It was revealed that the formation of wrinkles could reduce light absorbance, narrow the band gap, move down the conduction band position and accelerate electron–hole recombination. As photocatalysts, the F-CdS achieved a photocatalytic H2 evolution rate of 138.7 mmol g‑1 h‑1 without any co-catalyst under visible light, which was much higher than that of the W-CdS sample (with an H2 evolution rate of only 52.8 mmol g‑1 h‑1). This work demonstrates that great attention should be paid to the wrinkles in 2D materials as photocatalysts.

Surface and interface of epitaxial CdTe film on CdS buffered van der Waals mica substrate

NASA Astrophysics Data System (ADS)

Yang, Y.-B.; Seewald, L.; Mohanty, Dibyajyoti; Wang, Y.; Zhang, L. H.; Kisslinger, K.; Xie, Weiyu; Shi, J.; Bhat, I.; Zhang, Shengbai; Lu, T.-M.; Wang, G.-C.

2017-08-01

Single crystal CdTe films are desirable for optoelectronic device applications. An important strategy of creating films with high crystallinity is through epitaxial growth on a proper single crystal substrate. We report the metalorganic chemical vapor deposition of epitaxial CdTe films on the CdS/mica substrate. The epitaxial CdS film was grown on a mica surface by thermal evaporation. Due to the weak van der Waals forces, epitaxy is achieved despite the very large interface lattice mismatch between CdS and mica (∼21-55%). The surface morphology of mica, CdS and CdTe were quantified by atomic force microscopy. The near surface structures, orientations and texture of CdTe and CdS films were characterized by the unique reflection high-energy electron diffraction surface pole figure technique. The interfaces of CdTe and CdS films and mica were characterized by X-ray pole figure technique and transmission electron microscopy. The out-of-plane and in-plane epitaxy of the heteroepitaxial films stack are determined to be CdTe(111)//CdS(0001)//mica(001) and [1 bar2 1 bar]CdTe//[ 1 bar100]CdS//[010]mica, respectively. The measured photoluminescence (PL), time resolved PL, photoresponse, and Hall mobility of the CdTe/CdS/mica indicate quality films. The use of van der Waals surface to grow epitaxial CdTe/CdS films offers an alternative strategy towards infrared imaging and solar cell applications.

Long-term Results and Recurrence-Related Risk Factors for Crohn Disease in Patients Undergoing Side-to-Side Isoperistaltic Strictureplasty.

PubMed

Fazi, Marilena; Giudici, Francesco; Luceri, Cristina; Pronestì, Micaela; Tonelli, Francesco

2016-05-01

Side-to-side isoperistaltic strictureplasty (SSIS) is useful in patients undergoing surgery for Crohn disease (CD) to avoid wide small-bowel resections. To our knowledge, there are no definitive data regarding its recurrence risk factors. To evaluate the results obtained in a monocentric population of patients with CD who have undergone SSIS. From August 1996 to March 2010, 91 patients with CD underwent SSIS in our center. In this prospective observational study, side-to-side isoperistaltic strictureplasty was according the Michelassi technique in 69 patients and the Tonelli technique in 22 patients. Factors relating to the patient and the CD, surgery, and pharmacological therapy during the preoperative and perioperative periods were evaluated in association with medical or surgical recurrence. Side-to-side isoperistaltic strictureplasty. The recurrence-free curve was estimated using Kaplan-Meier analysis. Patients were stratified into cohorts in relation to the considered categorical variables and data were compared by using the Mantel-Cox log-rank test. Cox proportional hazard regression analysis was used to set up a predictive model simultaneously exploring the effects of all independent variables on a dichotomous outcome recurrence in relation to time. Among the 91 patients, the mean (SD) age was 39.5 (11.2) years and preoperative disease duration was 97.9 (85.8) months; 83 patients (91.2%) were followed up, of whom 37 (44.58%) experienced a recurrence at a mean (SD) of 55.46 (36.79) months after surgery (range, 9-140 months). The recurrence in the SSIS site at a mean (SD) of 48.25 (29.94) months after surgery affected 24 of 83 patients (28.9%), 9 being medical and 15 being surgical recurrence. Recurrence in the SSIS was statistically significantly associated with the time elapsed between diagnosis and surgery (P = .03). A borderline association between family history of CD and surgical recurrence (P = .054) was also found. Multivariate analysis identified the age at diagnosis (χ2 = 5.56; P = .02) and at surgery (χ2 = 7.77; P = .005), family history (χ2 = 6.26; P = .01), and smoking habit (χ2 = 10.06; P = .007) as independent risk factors for recurrence. In the short-term, SSIS leads to a resolution of symptoms in more than 90% of cases and the recurrence rate in the SSIS area is acceptable, even after long-term follow-up.

Spatiotemporal analysis of putative notochordal cell markers reveals CD24 and keratins 8, 18, and 19 as notochord‐specific markers during early human intervertebral disc development

PubMed Central

Rodrigues‐Pinto, Ricardo; Berry, Andrew; Piper‐Hanley, Karen; Hanley, Neil; Richardson, Stephen M.

2016-01-01

ABSTRACT In humans, the nucleus pulposus (NP) is composed of large vacuolated notochordal cells in the fetus but, soon after birth, becomes populated by smaller, chondrocyte‐like cells. Although animal studies indicate that notochord‐derived cells persist in the adult NP, the ontogeny of the adult human NP cell population is still unclear. As such, identification of unique notochordal markers is required. This study was conducted to determine the spatiotemporal expression of putative human notochordal markers to aid in the elucidation of the ontogeny of adult human NP cells. Human embryos and fetuses (3.5–18 weeks post‐conception (WPC)) were microdissected to isolate the spine anlagens (notochord and somites/sclerotome). Morphology of the developing IVD was assessed using hematoxylin and eosin. Expression of keratin (KRT) 8, KRT18, KRT19, CD24, GAL3, CD55, BASP1, CTGF, T, CD90, Tie2, and E‐cadherin was assessed using immunohistochemistry. KRT8, KRT18, KRT19 were uniquely expressed by notochordal cells at all spine levels at all stages studied; CD24 was expressed at all stages except 3.5 WPC. While GAL3, CD55, BASP1, CTGF, and T were expressed by notochordal cells at specific stages, they were also co‐expressed by sclerotomal cells. CD90, Tie2, and E‐cadherin expression was not detectable in developing human spine cells at any stage. This study has identified, for the first time, the consistent expression of KRT8, KRT18, KRT19, and CD24 as human notochord‐specific markers during early IVD development. Thus, we propose that these markers can be used to help ascertain the ontogeny of adult human NP cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 34:1327–1340, 2016. PMID:26910849

Spatiotemporal analysis of putative notochordal cell markers reveals CD24 and keratins 8, 18, and 19 as notochord-specific markers during early human intervertebral disc development.

PubMed

Rodrigues-Pinto, Ricardo; Berry, Andrew; Piper-Hanley, Karen; Hanley, Neil; Richardson, Stephen M; Hoyland, Judith A

2016-08-01

In humans, the nucleus pulposus (NP) is composed of large vacuolated notochordal cells in the fetus but, soon after birth, becomes populated by smaller, chondrocyte-like cells. Although animal studies indicate that notochord-derived cells persist in the adult NP, the ontogeny of the adult human NP cell population is still unclear. As such, identification of unique notochordal markers is required. This study was conducted to determine the spatiotemporal expression of putative human notochordal markers to aid in the elucidation of the ontogeny of adult human NP cells. Human embryos and fetuses (3.5-18 weeks post-conception (WPC)) were microdissected to isolate the spine anlagens (notochord and somites/sclerotome). Morphology of the developing IVD was assessed using hematoxylin and eosin. Expression of keratin (KRT) 8, KRT18, KRT19, CD24, GAL3, CD55, BASP1, CTGF, T, CD90, Tie2, and E-cadherin was assessed using immunohistochemistry. KRT8, KRT18, KRT19 were uniquely expressed by notochordal cells at all spine levels at all stages studied; CD24 was expressed at all stages except 3.5 WPC. While GAL3, CD55, BASP1, CTGF, and T were expressed by notochordal cells at specific stages, they were also co-expressed by sclerotomal cells. CD90, Tie2, and E-cadherin expression was not detectable in developing human spine cells at any stage. This study has identified, for the first time, the consistent expression of KRT8, KRT18, KRT19, and CD24 as human notochord-specific markers during early IVD development. Thus, we propose that these markers can be used to help ascertain the ontogeny of adult human NP cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 34:1327-1340, 2016. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc.

Dendritic cells regulate angiogenesis associated with liver fibrogenesis.

PubMed

Blois, Sandra M; Piccioni, Flavia; Freitag, Nancy; Tirado-González, Irene; Moschansky, Petra; Lloyd, Rodrigo; Hensel-Wiegel, Karin; Rose, Matthias; Garcia, Mariana G; Alaniz, Laura D; Mazzolini, Guillermo

2014-01-01

During liver fibrogenesis the immune response and angiogenesis process are fine-tuned resulting in activation of hepatic stellate cells that produce an excess of extracellular matrix proteins. Dendritic cells (DC) play a central role modulating the liver immunity and have recently been implicated to favour fibrosis regression; although their ability to influence the development of fibrogenesis is unknown. Therefore, we explored whether the depletion of DC during early stages of liver injury has an impact in the development of fibrogenesis. Using the CD11c.DTR transgenic mice, DC were depleted in two experimental models of fibrosis in vivo. The effect of anti-angiogenic therapy was tested during early stages of liver fibrogenesis. DC depletion accelerates the development of fibrosis and as a consequence, the angiogenesis process is boosted. We observed up-regulation of pro-angiogenic factors together with an enhanced vascular endothelial growth factor (VEGF) bioavailability, mainly evidenced by the decrease of anti-angiogenic VEGF receptor 1 (also known as sFlt-1) levels. Interestingly, fibrogenesis process enhanced the expression of Flt-1 on hepatic DC and administration of sFlt-1 was sufficient to abrogate the acceleration of fibrogenesis upon DC depletion. Thus, DC emerge as novel players during the development of liver fibrosis regulating the angiogenesis process and thereby influencing fibrogenesis.

[Dectection of G3BP and CD44v6 in the tissues of laryngeal squamous cell carcinoma and their clinical significance].

PubMed

Luo, Dahu; Lou, Weihua

2017-07-01

Objective To study the expressions of RNA-binding Ras-GAP SH3 binding protein (G3BP) and tumor stem cell marker CD44v6 in laryngeal squamous cell carcinoma and their correlations with angiogenesis. Methods We collected the cancer tissues and corresponding paracancerous tissues from 56 patients with laryngeal squamous cell carcinoma. The expressions of G3BP and CD44v6 proteins were detected by Western blotting in cancer tissues and corresponding paracancerous tissues; the expressions of G3BP, CD44v6 and vascular endothelial growth factor A (VEGF-A) were tested by immunohistochemistry. Thereafter, we compared the positive expression rates of G3BP and CD44v6 between in cancer tissues and in normal tissues, analyzed the correlations between the expressions of G3BP, CD44v6 and the laryngeal squamous cell carcinoma features as well as their correlations with microvessel density (MVD) that was determined by FVIIIAg immunohistochemistry. Results Western blotting showed that the expressions of G3BP and CD44v6 proteins in the laryngeal squamous cell carcinoma were higher than those in the paracancerous tissues. Immunohistochemistry showed that compared with the paracancerous tissues, G3BP, CD44v6 and VEGF-A expressions (the positive rates are 58.9%, 53.6%, 46.4%, respectively) were higher in cancer tissues. The positive rates of G3BP and CD44v6 in cancer tissues were related with the clinical stage, recurrence or metastasis, and lymph node metastasis of laryngeal squamous cell carcinoma, but had nothing to do with patients' age and tumor size. Pearson correlation analysis showed the expressions of both G3BP and CD44v6 were positively correlated with VEGF-A (r=0.741, r=0.756). MVD values were significantly higher in the G3BP and CD44v6 positive cases than in paracancerous tissues, but there was no difference in MVD between those without G3BP and CD44v6 positive expressions and the paracancerous tissues. Conclusion The positive expression rates of G3BP and CD44v6 in laryngeal squamous cell carcinoma tissues are very high, and they have a close relationship with the clinical prognosis. They may raise the VEGF-A expression so as to promote angiogenesis, and then accelerate the development of the laryngeal squamous cell carcinoma.

Association Between HIV-1 RNA Level and CD4 Cell Count Among Untreated HIV-Infected Individuals

PubMed Central

Lima, Viviane D.; Fink, Valeria; Yip, Benita; Hogg, Robert S.; Harrigan, P. Richard

2009-01-01

Objectives. We examined the significance of plasma HIV-1 RNA levels (or viral load alone) in predicting CD4 cell decline in untreated HIV-infected individuals. Methods. Data were obtained from the British Columbia Centre for Excellence in HIV/AIDS. Participants included all residents who ever had a viral load determination in the province and who had never taken antiretroviral drugs (N = 890). We analyzed a total of 2074 viral load measurements and 2332 CD4 cell counts. Linear mixed-effects models were used to predict CD4 cell decline over time. Results. Longitudinal viral load was strongly associated with CD4 cell decline over time; an average of 1 log10 increase in viral load was associated with a 55-cell/mm3 decrease in CD4 cell count. Conclusions. Our results support the combined use of CD4 cell count and viral load as prognostic markers in HIV-infected individuals before the introduction of antiretroviral therapy. PMID:19218172

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

Not Available

The Accelerator Research Studies program at the University of Maryland, sponsored by the Department of Energy under grant number DE-FG05-91ER40642, is currently in the second year of a three-year funding cycle. The program consists of the following three tasks: TASK A, ``Study of Transport and Longitudinal Compression of Intense, High-Brightness Beams,`` (P.I., M. Reiser); TASK B, ``Study of Collective Ion Acceleration by Intense Electron Beams and Pseudospark Produced High Brightness Electron Beams,`` (Co-P.I.`s, W.W. Destler, M. Reiser, M.J. Rhee, and C.D. Striffler); TASK C, ``Study of a Gyroklystron High-Power Microwave Source for Linear Colliders,`` (Co-P.I.`s, V.L. Granatstein, W. Lawson, M.more » Reiser, and C.D. Striffler). In this report we document the progress that has been made during the past year for each of the three tasks.« less

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

Not Available

The Accelerator Research Studies program at the University of Maryland, sponsored by the Department of Energy under grant number DE-FG05-91ER40642, is currently in the second year of a three-year funding cycle. The program consists of the following three tasks: TASK A, Study of Transport and Longitudinal Compression of Intense, High-Brightness Beams,'' (P.I., M. Reiser); TASK B, Study of Collective Ion Acceleration by Intense Electron Beams and Pseudospark Produced High Brightness Electron Beams,'' (Co-P.I.'s, W.W. Destler, M. Reiser, M.J. Rhee, and C.D. Striffler); TASK C, Study of a Gyroklystron High-Power Microwave Source for Linear Colliders,'' (Co-P.I.'s, V.L. Granatstein, W. Lawson, M.more » Reiser, and C.D. Striffler). In this report we document the progress that has been made during the past year for each of the three tasks.« less

Study of binary and ternary organic hybrid CdSe quantum dot photodetector

NASA Astrophysics Data System (ADS)

Ramar, M.; Kajal, S.; Pal, Prabir; Srivastava, R.; Suman, C. K.

2015-09-01

The hybrid binary and ternary photodetectors (PDs) were fabricated from P3HT-PC71BM with CdSe quantum dot (QD) materials. The absorption spectra of P3HT:PC71BM (named as B1), P3HT:CdSe (B2) and P3HT:CdSe:PC71BM (T) active blended material were analyzed in the wavelength range from 350 to 800 nm. The current density-voltage characteristics of the device were measured in dark and under illumination for study of detector detectivities and the contact with electrode. The ratio at -0.5 V for PDs B1, B2 and T is 1.1 × 102, 1.9 × 102 and 1.8 × 103, respectively. The values of detectivity for B1, B2 and T are 1 × 1010, 2 × 1010 and 7 × 1011 Jones, respectively. The for PD T is ten times in comparison with B1 and B2 PDs. The linear dynamic range (LDR) value for ternary device is more than double to both binary PDs. The absorption by CdSe QD increases the photon efficiency in the ternary detector, and at the same time the ternary detectors have high detectivity in broad spectral range. The responsivity of current to the light intensity exponent θ for detector B1, B2 and T is ~0.55, 0.55 and 0.62, respectively, which represents a complex process of electron hole generation, recombination and trapping within active material.

Effect of PGE2 on the cell surface molecule expression in PMA treated thymocytes.

PubMed

Daculsi, R; Vaillier, D; Carron, J C; Gualde, N

1998-02-01

PGE2 is produced by cells of the thymic microenvironment. The effects of PGE2 are mediated by cAMP through binding to its intracellular receptor protein kinase A (PKA). Phorbol 12-myristate 13-acetate (PMA) is known to modulate CD molecule expression on thymocytes, probably through activation of protein kinase C (PKC). We have hypothesized that cross-talk between these two signalling pathways may affect modulation of the CD molecules on the cell surface of thymocytes. For this purpose, we compare the effects of PMA alone or combined with PGE2 on CD3, CD4 and CD8 expression on mouse thymocytes by flow-cytometric analysis. PMA treatment almost completely abolished CD4 expression and slightly decreased CD3 and CD8 expression. PGE2 alone did not change the CD3, CD4 and CD8 molecule expression. Combined with PMA, PGE2 can overcome the decrease induced by PMA of the CD3 expression and partially reduced the disappearance of the CD4 molecule. On the other hand PGE2 accelerated the loss of CD8 molecule expression. These events occurred only in CD4+ CD8+ immature thymocytes. An analogue of cAMP (dibutyryl cAMP) mimics the effect of PGE2, but not Br-cGMP. This differential regulation by PGE2 of the CD molecule expression on immature thymocytes may provide additional evidence on the role of PGE2 during the process of thymic differentiation.

Particle size distribution and characteristics of heavy metals in road-deposited sediments from Beijing Olympic Park.

PubMed

Li, Haiyan; Shi, Anbang; Zhang, Xiaoran

2015-06-01

Due to rapid urbanization and industrialization, heavy metals in road-deposited sediments (RDSs) of parks are emitted into the terrestrial, atmospheric, and water environment, and have a severe impact on residents' and tourists' health. To identify the distribution and characteristic of heavy metals in RDS and to assess the road environmental quality in Chinese parks, samples were collected from Beijing Olympic Park in the present study. The results indicated that particles with small grain size (<150 μm) were the dominant fraction. The length of dry period was one of the main factors affecting the particle size distribution, as indicated by the variation of size fraction with the increase of dry days. The amount of heavy metal (i.e., Cu, Zn, Pb and Cd) content was the largest in particles with small size (<150 μm) among all samples. Specifically, the percentage of Cu, Zn, Pb and Cd in these particles was 74.7%, 55.5%, 56.6% and 71.3%, respectively. Heavy metals adsorbed in sediments may mainly be contributed by road traffic emissions. The contamination levels of Pb and Cd were higher than Cu and Zn on the basis of the mean heavy metal contents. Specifically, the geoaccumulation index (Igeo) decreased in the order: Cd>Pb>Cu>Zn. This study analyzed the mobility of heavy metals in sediments using partial sequential extraction with the Tessier procedure. The results revealed that the apparent mobility and potential metal bioavailability of heavy metals in the sediments, based on the exchangeable and carbonate fractions, decreased in the order: Cd>Zn≈Pb>Cu. Copyright © 2015. Published by Elsevier B.V.

The N-butyl alcohol extract from Hibiscus rosa-sinensis L. flowers enhances healing potential on rat excisional wounds.

PubMed

Shen, Hui-Min; Chen, Chun; Jiang, Ji-Yang; Zheng, Yi-Lin; Cai, Wen-Feng; Wang, Bin; Ling, Zhen; Tang, Liu; Wang, Yuan-Hang; Shi, Gang-Gang

2017-02-23

Hibiscus rosa-sinensis L. (HRS), a folk medicine named Zhujin in China, possess anti-tumor, antioxidant, antibacterial, low density lipoprotein oxidation prevention and macrophage death prevention effects. The leaves and red flowers of HRS have been traditionally used to treat with furuncle and ulceration. To investigate the efficacy and possible mechanism of the N-butyl alcohol extract of HRS (NHRS) red flowers in wound healing by analyzing the collagen fiber deposition, angiogenic activity and macrophages action of the NHRS. In an excisional wound healing model in rats, different concentrations of NHRS, or recombinant bovine basic fibroblast growth factor (rbFGF), were respectively applied twice daily for 9 days. Histopathology was assessed on day 9 via hematoxylin and eosin (HE) and Masson's trichrome (MT) staining, and immunohistochemistry for vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1) and CD68. Immunomodulation by NHRS was evaluated by a carbon clearance test in mice. Wound healing post-surgery was greater in the rbFGF-control, NHRS-M and MHRS-H groups than in the model and 5% dimethylsulfoxide (DMSO)-control groups after the third day. By the sixth day the wound contraction of NHRS-M and MHRS-H groups was much higher than the rbFGF-control group. HE and MT staining revealed that epithelialization, fibroblast distribution, collagen deposition of NHRS-M- and NHRS-H-control groups were significantly higher than the model group. Moreover, immunohistochemistry showed more intense staining of VEGF, TGF-β1 and CD68 in the rbFGF- and NHRS-control groups, compared to that in model and 5% DMSO-control groups. The clearance and phagocytic indices of NHRS-M- and NHRS-H-control groups were significantly higher than that of the carboxyl methyl cellulose (CMC) group in mice. NHRS accelerates wound repair via enhancing the macrophages activity, accelerating angiogenesis and collagen fiber deposition response mediated by VEGF and TGF-β1. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Short-term acute hypercapnia affects cellular responses to trace metals in the hard clams Mercenaria mercenaria.

PubMed

Ivanina, Anna V; Beniash, Elia; Etzkorn, Markus; Meyers, Tiffany B; Ringwood, Amy H; Sokolova, Inna M

2013-09-15

Estuarine and coastal habitats experience large fluctuations of environmental factors such as temperature, salinity, partial pressure of CO2 ( [Formula: see text] ) and pH; they also serve as the natural sinks for trace metals. Benthic filter-feeding organisms such as bivalves are exposed to the elevated concentrations of metals in estuarine water and sediments that can strongly affect their physiology. The effects of metals on estuarine organisms may be exacerbated by other environmental factors. Thus, a decrease in pH caused by high [Formula: see text] (hypercapnia) can modulate the effects of trace metals by affecting metal bioavailability, accumulation or binding. To better understand the cellular mechanisms of interactions between [Formula: see text] and trace metals in marine bivalves, we exposed isolated mantle cells of the hard clams (Mercenaria mercenaria) to different levels of [Formula: see text] (0.05, 1.52 and 3.01 kPa) and two major trace metal pollutants - cadmium (Cd) and copper (Cu). Elevated [Formula: see text] resulted in a decrease in intracellular pH (pHi) of the isolated mantle cells from 7.8 to 7.4. Elevated [Formula: see text] significantly but differently affected the trace metal accumulation by the cells. Cd uptake was suppressed at elevated [Formula: see text] levels while Cu accumulation has greatly accelerated under hypercapnic conditions. Interestingly, at higher extracellular Cd levels, labile intracellular Cd(2+) concentration remained the same, while intracellular levels of free Zn(2+) increased suggesting that Cd(2+) substitutes bound Zn(2+) in these cells. In contrast, Cu exposure did not affect intracellular Zn(2+) but led to a profound increase in the intracellular levels of labile Cu(2+) and Fe(2+). An increase in the extracellular concentrations of Cd and Cu led to the elevated production of reactive oxygen species under the normocapnic conditions (0.05 kPa [Formula: see text] ); surprisingly, this effect was mitigated in hypercapnia (1.52 and 3.01 kPa). Overall, our data reveal complex and metal-specific interactions between the cellular effects of trace metals and [Formula: see text] in clams and indicate that variations in environmental [Formula: see text] may modulate the biological effects of trace metals in marine organisms. Copyright © 2013 Elsevier B.V. All rights reserved.

DPPIV promotes endometrial carcinoma cell proliferation, invasion and tumorigenesis

PubMed Central

Yang, Xiaoqing; Zhang, Xinhua; Wu, Rongrong; Huang, Qicheng; Jiang, Yao; Qin, Jianbing; Yao, Feng; Jin, Guohua; Zhang, Yuquan

2017-01-01

Dipeptidyl peptidase IV (DPPIV), also known as CD26, is a 110-kDa cell surface glycoprotein expressed in various tissues. DPPIV reportedly plays a direct role in the progression of several human malignancies. DPPIV specific inhibitors are employed as antidiabetics and could potentially be repurposed to enhance anti-tumor immunotherapies. In the present study, we investigated the correlation between DPPIV expression and tumor progression in endometrial carcinoma (EC). DPPIV overexpression altered cell morphology and stimulated cell proliferation, invasion and tumorigenesis in vitro and in vivo. These effects were abrogated by DPPIV knockdown or pharmacological inhibition using sitagliptin. DPPIV overexpression increased hypoxia-inducible factor 1a (HIF-1a) and vascular endothelial growth factor A (VEGFA) expression to promote HIF-1a-VEGFA signaling. Our results indicated that DPPIV accelerated endometrial carcinoma progression and that sitagliptin may be an effective anti-EC therapeutic. PMID:28060721

DPPIV promotes endometrial carcinoma cell proliferation, invasion and tumorigenesis.

PubMed

Yang, Xiaoqing; Zhang, Xinhua; Wu, Rongrong; Huang, Qicheng; Jiang, Yao; Qin, Jianbing; Yao, Feng; Jin, Guohua; Zhang, Yuquan

2017-01-31

Dipeptidyl peptidase IV (DPPIV), also known as CD26, is a 110-kDa cell surface glycoprotein expressed in various tissues. DPPIV reportedly plays a direct role in the progression of several human malignancies. DPPIV specific inhibitors are employed as antidiabetics and could potentially be repurposed to enhance anti-tumor immunotherapies. In the present study, we investigated the correlation between DPPIV expression and tumor progression in endometrial carcinoma (EC). DPPIV overexpression altered cell morphology and stimulated cell proliferation, invasion and tumorigenesis in vitro and in vivo. These effects were abrogated by DPPIV knockdown or pharmacological inhibition using sitagliptin. DPPIV overexpression increased hypoxia-inducible factor 1a (HIF-1a) and vascular endothelial growth factor A (VEGFA) expression to promote HIF-1a-VEGFA signaling. Our results indicated that DPPIV accelerated endometrial carcinoma progression and that sitagliptin may be an effective anti-EC therapeutic.

Thermodynamic Analyses of the LCLS-II Cryogenic Distribution System

DOE PAGES

Dalesandro, Andrew; Kaluzny, Joshua; Klebaner, Arkadiy

2016-12-29

The Linac Coherent Light Source (LCLS) at Stanford Linear Accelerator Center (SLAC) is in the process of being upgraded to a superconducting radio frequency (SRF) accelerator and renamed LCLS-II. This upgrade requires thirty-five 1.3 GHz SRF cryomodules (CM) and two 3.9 GHz CM. A cryogenic distribution system (CDS) is in development by Fermi National Accelerator Laboratory to interconnect the CM Linac with the cryogenic plant (CP). The CDS design utilizes cryogenic helium to support the CM operations with a high temperature thermal shield around 55 K, a low temperature thermal intercepts around 5 K, and a SRF cavity liquid heliummore » supply and sub-atmospheric vapor return both around 2 K. Additionally the design must accommodate a Linac consisting of two parallel cryogenic strings, supported by two independent CP utilizing CDS components such as distribution boxes, transfer lines, feed caps and endcaps. In this paper, we describe the overall layout of the cryogenic distribution system and the major thermodynamic factors which influence the CDS design including heat loads, pressure drops, temperature profiles, and pressure relieving requirements. In addition the paper describes how the models are created to perform the analyses.« less

Bacterial pneumonia, HIV therapy, and disease progression among HIV-infected women in the HIV epidemiologic research (HER) study.

PubMed

Kohli, Rakhi; Lo, Yungtai; Homel, Peter; Flanigan, Timothy P; Gardner, Lytt I; Howard, Andrea A; Rompalo, Anne M; Moskaleva, Galina; Schuman, Paula; Schoenbaum, Ellie E

2006-07-01

To determine the rate and predictors of community-acquired bacterial pneumonia and its effect on human immunodeficiency virus (HIV) disease progression in HIV-infected women, we performed a multiple-site, prospective study of HIV-infected women in 4 cities in the United States. During the period of 1993-2000, we observed 885 HIV-infected and 425 HIV-uninfected women with a history of injection drug use or high-risk sexual behavior. Participants underwent semiannual interviews, and CD4+ lymphocyte count and viral load were assessed in HIV-infected subjects. Data regarding episodes of bacterial pneumonia were ascertained from medical record reviews. The rate of bacterial pneumonia among 885 HIV-infected women was 8.5 cases per 100 person-years, compared with 0.7 cases per 100 person-years in 425 HIV-uninfected women (P < .001). In analyses limited to follow-up after 1 January 1996, highly active antiretroviral therapy (HAART) and trimethoprim-sulfamethoxazole (TMP-SMX) use were associated with a decreased risk of bacterial pneumonia. Among women who had used TMP-SMX for 12 months, each month of HAART decreased bacterial pneumonia risk by 8% (adjusted hazard ratio [HR(adj)], 0.92; 95% confidence interval [CI], 0.89-0.95). Increments of 50 CD4+ cells/mm3 decreased the risk (HR(adj), 0.88; 95% CI, 0.84-0.93), and smoking doubled the risk (HR(adj), 2.12; 95% CI, 1.26-3.55). Bacterial pneumonia increased mortality risk (HR(adj), 5.02; 95% CI, 2.12-11.87), with adjustment for CD4+ lymphocyte count and duration of HAART and TMP-SMX use. High rates of bacterial pneumonia persist among HIV-infected women. Although HAART and TMP-SMX treatment decreased the risk, bacterial pneumonia was associated with an accelerated progression to death. Interventions that improve HAART utilization and promote smoking cessation among HIV-infected women are warranted.

Photonuclear reactions on the cadmium isotopes {sup 106,108}Cd at the bremsstrahlung endpoint energy of 55.5 MeV

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

Belyshev, S. S.; Kuznetsov, A. A.; Stopani, K. A., E-mail: hatta@depni.sinp.msu.ru

The gamma-activation technique was used to measure the absolute yields of photonuclear reactions on the cadmium isotopes {sup 106,108}Cd. The results obtained in this way were compared with the results of the calculations based on the statistical model. For reactions on the isotope {sup 108}Cd, agreement between these theoretical and experimental results is good, but the experimental ratio of the yields of photoproton and photoneutron reactions on the isotope {sup 106}Cd differs substantially from its theoretical counterpart. The results of our present study are discussed from the point of view of the production of bypassed nuclei in the p-process ofmore » nucleosynthesis.« less

Cd(II)-coordination polymers based on tetracarboxylic acid and diverse bis(imidazole) ligands: Synthesis, structural diversity and photoluminescence properties

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

Arıcı, Mürsel, E-mail: marici@ogu.edu.tr; Yeşilel, Okan Zafer; Taş, Murat

Three new Cd(II)-coordination polymers, namely, ([Cd{sub 2}(μ{sub 6}-ao{sub 2}btc)(μ-1,5-bipe){sub 2}]·2H{sub 2}O){sub n} (1), ([Cd{sub 2}(μ{sub 6}-ao{sub 2}btc)(μ-1,4-bix){sub 2}]{sub n}·2DMF) (2) and ([Cd{sub 2}(μ{sub 8}-abtc)(μ-1,4-betix)]·DMF·H{sub 2}O){sub n} (3) (ao{sub 2}btc=di-oxygenated form of 3,3′,5,5′-azobenzenetetracarboxylate, 1,5-bipe: 1,5-bis(imidazol-1yl)pentane, 1,4-bix=1,4-bis(imidazol-1ylmethyl)benzene, 1,4-betix=1,4-bis(2-ethylimidazol-1ylmethyl)benzene) were synthesized with 3,3′,5,5′-azobenzenetetracarboxylic acid and flexible, semi-flexible and semi-flexible substituted bis(imidazole) linkers. They were characterized by IR spectroscopy, elemental analysis, single-crystal X-ray diffraction, powder X-ray diffractions (PXRD) and thermal analyses (TG/DTA). Complexes 1–3 exhibited structural diversities depending on flexible, semi-flexible and semi-flexible substituted bis(imidazole) ligands. Complex 1 was 2D structure with 3,6L18 topology. Complex 2 had a 3D pillar-layered framework with the raremore » sqc27 topology. When semi-flexible substituted bis(imidazole) linker was used, 3D framework of complex 3 was obtained with the paddlewheel Cd{sub 2}(CO{sub 2}){sub 4}-type binuclear SBU. Moreover, thermal and photoluminescence properties of the complexes were determined in detailed. - Graphical abstract: In this study, three novel Cd(II)-coordination polymers were synthesized with 3,3′,5,5′-azobenzenetetracarboxylic acid and flexible, semi-flexible and semi-flexible substituted bis(imidazole) linkers. They were characterized by IR spectroscopy, elemental analysis, single-crystal X-ray diffraction, powder X-ray diffractions (PXRD) and thermal analyses (TG/DTA). Complexes 1–3 exhibited structural diversities depending on flexible, semi-flexible and semi-flexible substituted bis(imidazole) ligands. Complex 1 was 2D structure with 3,6L18 topology. Complex 2 had a 3D pillar-layered framework with the rare sqc27 topology. When semi-flexible substituted bis(imidazole) linker was used, 3D framework of complex 3 was obtained with the paddlewheel Cd{sub 2}(CO{sub 2}){sub 4}-type binuclear SBU. - Highlights: • Three new Cd(II)-coordination polymers with azobenzenetetracarboxylic acid and diverse bis(imidazole) linkers. • Complex 1 is 2D structure with 3,6L18 topology. • 3D pillar-layered framework of 2 with the rare sqc27 topology. • 3D framework of 3 with the paddlewheel Cd{sub 2}(CO{sub 2}){sub 4}-type SBU.« less

The ThPOK transcription factor differentially affects the development and function of self-specific CD8(+) T cells and regulatory CD4(+) T cells.

PubMed

Twu, Yuh-Ching; Teh, Hung-Sia

2014-03-01

The zinc finger transcription factor ThPOK plays a crucial role in CD4 T-cell development and CD4/CD8 lineage decision. In ThPOK-deficient mice, developing T cells expressing MHC class II-restricted T-cell receptors are redirected into the CD8 T-cell lineage. In this study, we investigated whether the ThPOK transgene affected the development and function of two additional types of T cells, namely self-specific CD8 T cells and CD4(+) FoxP3(+) T regulatory cells. Self-specific CD8 T cells are characterized by high expression of CD44, CD122, Ly6C, 1B11 and proliferation in response to either IL-2 or IL-15. The ThPOK transgene converted these self-specific CD8 T cells into CD4 T cells. The converted CD4(+) T cells are no longer self-reactive, lose the characteristics of self-specific CD8 T cells, acquire the properties of conventional CD4 T cells and survive poorly in peripheral lymphoid organs. By contrast, the ThPOK transgene promoted the development of CD4(+) FoxP3(+) regulatory T cells resulting in an increased recovery of CD4(+) FoxP3(+) regulatory T cells that expressed higher transforming growth factor-β-dependent suppressor activity. These studies indicate that the ThPOK transcription factor differentially affects the development and function of self-specific CD8 T cells and CD4(+) FoxP3(+) regulatory T cells. © 2013 John Wiley & Sons Ltd.

Expression of a transmembrane phosphotyrosine phosphatase inhibits cellular response to platelet-derived growth factor and insulin-like growth factor-1.

PubMed

Mooney, R A; Freund, G G; Way, B A; Bordwell, K L

1992-11-25

Tyrosine phosphorylation is a mechanism of signal transduction shared by many growth factor receptors and oncogene products. Phosphotyrosine phosphatases (PTPases) potentially modulate or counter-regulate these signaling pathways. To test this hypothesis, the transmembrane PTPase CD45 (leukocyte common antigen) was expressed in the murine cell line C127. Hormone-dependent autophosphorylation of the platelet-derived growth factor (PDGF) and insulin-like growth factor-1 (IGF-1) receptors was markedly reduced in cells expressing the transmembrane PTPase. Tyrosine phosphorylation of other PDGF-dependent phosphoproteins (160, 140, and 55 kDa) and IGF-1-dependent phosphoproteins (145 kDa) was similarly decreased. Interestingly, the pattern of growth factor-independent tyrosine phosphorylations was comparable in cells expressing the PTPase and control cells. This suggests a selectivity or accessibility of the PTPase limited to a subset of cellular phosphotyrosyl proteins. The maximum mitogenic response to PDGF and IGF-1 in cells expressing the PTPase was decreased by 67 and 71%, respectively. These results demonstrate that a transmembrane PTPase can both affect the tyrosine phosphorylation state of growth factor receptors and modulate proximal and distal cellular responses to the growth factors.

Dynamic Modulation of Expression of Lentiviral Restriction Factors in Primary CD4+ T Cells following Simian Immunodeficiency Virus Infection.

PubMed

Rahmberg, Andrew R; Rajakumar, Premeela A; Billingsley, James M; Johnson, R Paul

2017-04-01

Although multiple restriction factors have been shown to inhibit HIV/SIV replication, little is known about their expression in vivo Expression of 45 confirmed and putative HIV/SIV restriction factors was analyzed in CD4 + T cells from peripheral blood and the jejunum in rhesus macaques, revealing distinct expression patterns in naive and memory subsets. In both peripheral blood and the jejunum, memory CD4 + T cells expressed higher levels of multiple restriction factors compared to naive cells. However, relative to their expression in peripheral blood CD4 + T cells, jejunal CCR5 + CD4 + T cells exhibited significantly lower expression of multiple restriction factors, including APOBEC3G , MX2 , and TRIM25 , which may contribute to the exquisite susceptibility of these cells to SIV infection. In vitro stimulation with anti-CD3/CD28 antibodies or type I interferon resulted in upregulation of distinct subsets of multiple restriction factors. After infection of rhesus macaques with SIVmac239, the expression of most confirmed and putative restriction factors substantially increased in all CD4 + T cell memory subsets at the peak of acute infection. Jejunal CCR5 + CD4 + T cells exhibited the highest levels of SIV RNA, corresponding to the lower restriction factor expression in this subset relative to peripheral blood prior to infection. These results illustrate the dynamic modulation of confirmed and putative restriction factor expression by memory differentiation, stimulation, tissue microenvironment and SIV infection and suggest that differential expression of restriction factors may play a key role in modulating the susceptibility of different populations of CD4 + T cells to lentiviral infection. IMPORTANCE Restriction factors are genes that have evolved to provide intrinsic defense against viruses. HIV and simian immunodeficiency virus (SIV) target CD4 + T cells. The baseline level of expression in vivo and degree to which expression of restriction factors is modulated by conditions such as CD4 + T cell differentiation, stimulation, tissue location, or SIV infection are currently poorly understood. We measured the expression of 45 confirmed and putative restriction factors in primary CD4 + T cells from rhesus macaques under various conditions, finding dynamic changes in each state. Most dramatically, in acute SIV infection, the expression of almost all target genes analyzed increased. These are the first measurements of many of these confirmed and putative restriction factors in primary cells or during the early events after SIV infection and suggest that the level of expression of restriction factors may contribute to the differential susceptibility of CD4 + T cells to SIV infection. Copyright © 2017 American Society for Microbiology.

Current sheet characteristics of a parallel-plate electromagnetic plasma accelerator operated in gas-prefilled mode

NASA Astrophysics Data System (ADS)

Liu, Shuai; Huang, Yizhi; Guo, Haishan; Lin, Tianyu; Huang, Dong; Yang, Lanjun

2018-05-01

The axial characteristics of a current sheet in a parallel-plate electromagnetic plasma accelerator operated in gas-prefilled mode are reported. The accelerator is powered by a fourteen stage pulse forming network. The capacitor and inductor in each stage are 1.5 μF and 300 nH, respectively, and yield a damped oscillation square wave of current with a pulse width of 20.6 μs. Magnetic probes and photodiodes are placed at various axial positions to measure the behavior of the current sheet. Both magnetic probe and photodiode signals reveal a secondary breakdown when the current reverses the direction. An increase in the discharge current amplitude and a decrease in pressure lead to a decrease in the current shedding factor. The current sheet velocity and thickness are nearly constant during the run-down phase under the first half-period of the current. The current sheet thicknesses are typically in the range of 25 mm to 40 mm. The current sheet velocities are in the range of 10 km/s to 45 km/s when the discharge current is between 10 kA and 55 kA and the gas prefill pressure is between 30 Pa and 800 Pa. The experimental velocities are about 75% to 90% of the theoretical velocities calculated with the current shedding factor. One reason for this could be that the idealized snowplow analysis model ignores the surface drag force.

Manufacture of endothelial colony-forming progenitor cells from steady-state peripheral blood leukapheresis using pooled human platelet lysate.

PubMed

Siegel, Georg; Fleck, Erika; Elser, Stefanie; Hermanutz-Klein, Ursula; Waidmann, Marc; Northoff, Hinnak; Seifried, Erhard; Schäfer, Richard

2018-05-01

Endothelial colony-forming progenitor cells (ECFCs) are promising candidates for cell therapies. However, ECFC translation to the clinic requires optimized isolation and manufacture technologies according to good manufacturing practice (GMP). ECFCs were manufactured from steady-state peripheral blood (PB) leukapheresis (11 donors), using GMP-compliant technologies including pooled human platelet (PLT) lysate, and compared to human umbilical cord endothelial cells, human aortic endothelial cells, and human cerebral microvascular endothelial cells. Specific variables assessed were growth kinetics, phenotype, trophic factors production, stimulation of tube formation, and Dil-AcLDL uptake. ECFCs could be isolated from PB leukapheresis units with mean processed volume of 5411 mL and mean white blood cell (WBC) concentration factor of 8.74. The mean frequency was 1.44 × 10 -8 ECFCs per WBC, corresponding to a mean of 177.8 ECFCs per apheresis unit. Expandable for up to 12 cumulative population doublings, calculated projection showed that approximately 730 × 10 3 ECFCs could be manufactured from 1 apheresis unit. ECFCs produced epidermal growth factor, hepatocyte growth factor, vascular endothelial growth factor (VEGF)-A, PLT-derived growth factor-B, interleukin-8, and monocyte chemoattractant protein-1, featured high potential for capillary-like tubes formation, and showed no telomerase activity. They were characterized by CD29, CD31, CD44, CD105, CD117, CD133, CD144, CD146, and VEGF-R2 expression, with the most common subpopulation CD34+CD117-CD133-. Compared to controls, ECFCs featured greater Dil-AcLDL uptake and higher expression of CD29, CD31, CD34, CD44, CD144, and VEGF-R2. Here we show that isolation of ECFCs with proangiogenic profile from steady-state PB leukapheresis is feasible, marking a first step toward ECFC product manufacture according to GMP. © 2018 AABB.

Thrombopoietin treatment of one graft in a double cord blood transplant provides early platelet recovery while contributing to long-term engraftment in NSG mice.

PubMed

van der Garde, Mark; van Hensbergen, Yvette; Brand, Anneke; Slot, Manon C; de Graaf-Dijkstra, Alice; Mulder, Arend; Watt, Suzanne M; Zwaginga, Jaap Jan

2015-01-01

Human cord blood (CB) hematopoietic stem cell (HSC) transplants demonstrate delayed early neutrophil and platelet recovery and delayed longer term immune reconstitution compared to bone marrow and mobilized peripheral blood transplants. Despite advances in enhancing early neutrophil engraftment, platelet recovery after CB transplantation is not significantly altered when compared to contemporaneous controls. Recent studies have identified a platelet-biased murine HSC subset, maintained by thrombopoietin (TPO), which has enhanced capacity for short- and long-term platelet reconstitution, can self-renew, and can give rise to myeloid- and lymphoid-biased HSCs. In previous studies, we have shown that transplantation of human CB CD34(+) cells precultured in TPO as a single graft accelerates early platelet recovery as well as yielding long-term repopulation in immune-deficient mice. In this study, using a double CB murine transplant model, we investigated whether TPO cultured human CB CD34(+) cells have a competitive advantage or disadvantage over untreated human CB CD34(+) cells in terms of (1) short-term and longer term platelet recovery and (2) longer term hematological recovery. Our studies demonstrate that the TPO treated graft shows accelerated early platelet recovery without impairing the platelet engraftment of untreated CD34(+) cells. Notably, this was followed by a dominant contribution to platelet production through the untreated CD34(+) cell graft over the intermediate to longer term. Furthermore, although the contribution of the TPO treated graft to long-term hematological engraftment was reduced, the TPO treated and untreated grafts both contributed significantly to long-term chimerism in vivo.

Accelerated approval of oncology products: the food and drug administration experience.

PubMed

Johnson, John R; Ning, Yang-Min; Farrell, Ann; Justice, Robert; Keegan, Patricia; Pazdur, Richard

2011-04-20

We reviewed the regulatory history of the accelerated approval process and the US Food and Drug Administration (FDA) experience with accelerated approval of oncology products from its initiation in December 11, 1992, to July 1, 2010. The accelerated approval regulations allowed accelerated approval of products to treat serious or life-threatening diseases based on surrogate endpoints that are reasonably likely to predict clinical benefit. Failure to complete postapproval trials to confirm clinical benefit with due diligence could result in removal of the accelerated approval indication from the market. From December 11, 1992, to July 1, 2010, the FDA granted accelerated approval to 35 oncology products for 47 new indications. Clinical benefit was confirmed in postapproval trials for 26 of the 47 new indications, resulting in conversion to regular approval. The median time between accelerated approval and regular approval of oncology products was 3.9 years (range = 0.8-12.6 years) and the mean time was 4.7 years, representing a substantial time savings in terms of earlier availability of drugs to cancer patients. Three new indications did not show clinical benefit when confirmatory postapproval trials were completed and were subsequently removed from the market or had restricted distribution plans implemented. Confirmatory trials were not completed for 14 new indications. The five longest intervals from receipt of accelerated approval to July 1, 2010, without completion of trials to confirm clinical benefit were 10.5, 6.4, 5.5, 5.5, and 4.7 years. The five longest intervals between accelerated approval and successful conversion to regular approval were 12.6, 9.7, 8.1, 7.5, and 7.4 years. Trials to confirm clinical benefit should be part of the drug development plan and should be in progress at the time of an application seeking accelerated approval to prevent an ineffective drug from remaining on the market for an unacceptable time.

Pyroglutamic acid-induced metabolic acidosis: a case report.

PubMed

Luyasu, S; Wamelink, M M C; Galanti, L; Dive, A

2014-06-01

High anion gap metabolic acidosis due to pyroglutamic acid (5-oxoproline) is a rare complication of acetaminophen treatment (which depletes glutathione stores) and is often associated with clinically moderate to severe encephalopathy. Acquired 5-oxoprolinase deficiency (penicillins) or the presence of other risk factors of glutathione depletion such as malnutrition or sepsis seems to be necessary for symptoms development. We report the case of a 55-year-old women who developed a symptomatic overproduction of 5-oxoproline during flucloxacillin treatment for severe sepsis while receiving acetaminophen for fever control. Hemodialysis accelerated the clearance of the accumulated organic acid, and was followed by a sustained clinical improvement.

Visible-light-driven Efficient Photocatalytic Reduction of Organic Azides to Amines over CdS Sheet-rGO Nanocomposite.

PubMed

Singha, Krishnadipti; Mondal, Aniruddha; Ghosh, Subhash Chandra; Panda, Asit Baran

2018-02-02

CdS sheet-rGO nanocomposite as a heterogeneous photocatalyst enables visible-light-induced photocatalytic reduction of aromatic, heteroaromatic, aliphatic and sulfonyl azides to the corresponding amines using hydrazine hydrate as a reductant. The reaction shows excellent conversion and chemoselectivity towards the formation of the amine without self-photoactivated azo compounds. In the adopted strategy, CdS not only accelerates the formation of nitrene through photoactivation of azide but also enhances the decomposition of azide to a certain extent, which entirely suppressed formation of the azo compound. The developed CdS sheet-rGO nanocomposite catalyst is very active, providing excellent results under irradiation with a 40 W simple household CFL lamp. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Body mass index is a practical preoperative nutritional index for postoperative infectious complications after intestinal resection in patients with Crohn's disease

PubMed Central

Zhu, Yibin; Zhou, Wei; Qi, Weilin; Liu, Wei; Chen, Mingyu; Zhu, Hepan; Xiang, Jianjian; Xie, Qingwen; Chen, Pengpeng

2017-01-01

Abstract The patients with Crohn's disease (CD) are often accompanied with nutritional deficiencies. Compared with other intestinal benign disease, patients with CD have the higher risk of developing postoperative complications following intestinal resection. The aim of this study was to investigate the risk factors for postoperative infectious complications (PICs) after intestinal resection for CD, as well as search a practical preoperative nutritional index for PICs in patients with CD. A total of 122 patients who underwent intestinal resection for CD during 2011 to 2015 were retrospectively analyzed. After operation, 28 (22.95%) patients experienced PICs. Compared with the non-PICs group, the patients with PICs have the lower preoperative body mass index (BMI) (16.96 ± 2.33 vs 19.53 ± 2.49 kg/m2, P < .001), lower albumin (ALB) (33.64 ± 5.58 vs 36.55 ± 5.69 g/L, P = .013), higher C-reactive protein (CRP) level (30.44 ± 37.06 vs 15.99 ± 33.30 mg/L, P = .052), and longer hospital stay (22.64 ± 9.93 vs 8.90 ± 4.32 days, P < .001). By analyzing the receiver-operating characteristic (ROC) curve, BMI have better value in predicting the occurrence of PICs than ALB. The areas under the ROC curves of BMI for PICs was 0.784 (95% confidence interval 0.690–0.878, P < .001) with an optimal diagnostic cut-off value of 17.5 kg/m2. In the univariate and multivariate analysis, BMI < 17.5 kg/m2 (P = .001), ALB < 33.6 g/L (P = .024), CRP ≥ 10 mg/L (P = .026) were risk factors for PICs. Patients with a lower preoperative BMI (BMI < 17.5 kg/m2) had a 7.35 times greater risk of PICs. Therefore, preoperative BMI could be regarded as a practical preoperative nutritional index for evaluating the nutritional preparation sufficiency before CD operations. Preoperative treatment with the aim of reducing CRP level and improving the patient's nutritional status may be helpful to reduce the rate of PICs. PMID:28591060

C-Reactive Protein (CRP), Interferon Gamma-Inducible Protein 10 (IP-10), and Lipopolysaccharide (LPS) Are Associated with Risk of Tuberculosis after Initiation of Antiretroviral Therapy in Resource-Limited Settings

PubMed Central

Tenforde, Mark W.; Gupte, Nikhil; Dowdy, David W.; Asmuth, David M.; Balagopal, Ashwin; Pollard, Richard B.; Sugandhavesa, Patcharaphan; Lama, Javier R.; Pillay, Sandy; Cardoso, Sandra W.; Pawar, Jyoti; Santos, Breno; Riviere, Cynthia; Mwelase, Noluthando; Kanyama, Cecilia; Kumwenda, Johnstone; Hakim, James G.; Kumarasamy, Nagalingeswaran; Bollinger, Robert; Semba, Richard D.; Campbell, Thomas B.; Gupta, Amita

2015-01-01

Objective The association between pre-antiretroviral (ART) inflammation and immune activation and risk for incident tuberculosis (TB) after ART initiation among adults is uncertain. Design Nested case-control study (n = 332) within ACTG PEARLS trial of three ART regimens among 1571 HIV-infected, treatment-naïve adults in 9 countries. We compared cases (participants with incident TB diagnosed by 96 weeks) to a random sample of controls (participants who did not develop TB, stratified by country and treatment arm). Methods We measured pre-ART C-reactive protein (CRP), EndoCab IgM, ferritin, interferon gamma (IFN-γ), interleukin 6 (IL-6), interferon gamma-inducible protein 10 (IP-10), lipopolysaccharide (LPS), soluble CD14 (sCD14), tumor necrosis factor alpha (TNF-α), and CD4/DR+/38+ and CD8/DR+/38+ T cells. Markers were defined according to established cutoff definitions when available, 75th percentile of measured values when not, and detectable versus undetectable for LPS. Using logistic regression, we measured associations between biomarkers and incident TB, adjusting for age, sex, study site, treatment arm, baseline CD4 and log10 viral load. We assessed the discriminatory value of biomarkers using receiver operating characteristic (ROC) analysis. Results Seventy-seven persons (4.9%) developed incident TB during follow-up. Elevated baseline CRP (aOR 3.25, 95% CI: 1.55–6.81) and IP-10 (aOR 1.89, 95% CI: 1.05–3.39), detectable plasma LPS (aOR 2.39, 95% CI: 1.13–5.06), and the established TB risk factors anemia and hypoalbuminemia were independently associated with incident TB. In ROC analysis, CRP, albumin, and LPS improved discrimination only modestly for TB risk when added to baseline routine patient characteristics including CD4 count, body mass index, and prior TB. Conclusion Incident TB occurs commonly after ART initiation. Although associated with higher post-ART TB risk, baseline CRP, IP-10, and LPS add limited value to routine patient characteristics in discriminating who develops active TB. Besides determining ideal cutoffs for these biomarkers, additional biomarkers should be sought that predict TB disease in ART initiators. PMID:25719208

Age at menopause and menopause-related symptoms in human immunodeficiency virus-infected Thai women.

PubMed

Boonyanurak, Pongrak; Bunupuradah, Torsak; Wilawan, Kittisak; Lueanyod, Aksorn; Thongpaeng, Parawee; Chatvong, Duangjai; Sophonphan, Jiratchaya; Saeloo, Siriporn; Ananworanich, Jintanat; Chaithongwongwatthana, Surasith

2012-07-01

There are limited data for age at menopause (AM) and menopause-related symptoms in human immunodeficiency virus (HIV)-infected Asian women. We investigated AM and menopause-related symptoms in HIV-infected Thai women. HIV-infected Thai women 40 years or older who did not receive any hormone therapy in the 8-week period preceding the study were enrolled. Participants completed the Menopause-Specific Quality of Life survey for their symptoms in the past 30 days. Menopause was defined as having the last menstrual period more than 1 year ago. Multivariate Cox proportional hazard regression analysis was used to identify factors associated with menopause. Two hundred sixty-eight HIV-infected women were enrolled; their median age was 44.6 (41.8-48.7) years, and the ratio of their Centers for Disease Control and Prevention clinical classifications (A:B:C) was 53%:34%:13%; 95% were using highly active antiretroviral therapy. The median (interquartile range [IQR]) CD4 count was 575 (437-758) cells/μL, and 93% had HIV-RNA of less than 1.7log10 copies/mL. Among the 55 women who had reached menopause, the mean (SD) AM was 47.3 (5.1) years. The mean (SD) AM in our study was earlier than the previous report of 49.5 (3.6) years in non-HIV-infected Thai women (difference, -2.2 y; 95% CI, -3.2 to -1.2, P < 0.01). Postmenopausal women had more symptoms, including night sweats (P = 0.03), change in sexual desire (P = 0.01), and avoiding intimacy (P = 0.01), compared with nonpostmenopausal women. No differences in psychosocial or physical domains between groups were found. Factors associated with menopause were Centers for Disease Control and Prevention clinical classification B or C (hazard ratio, 1.7; 95% CI, 1.0-3.03, P = 0.04), and no sexual act in the past month (hazard ratio, 4.9; 95% CI, 1.5-16.0, P = 0.01). No associations of later age of menarche, parity, marital status, educational level, income, body mass index, CD4 count, and HIV-RNA with menopause were found. AM in HIV-infected Thai women was 47.3 years, which is significantly earlier than the findings of a previous AM report on non-HIV-infected women. Postmenopausal HIV-infected women had more vasomotor and sexual symptoms. More studies are needed to investigate the cause and appropriate interventions for accelerated menopause in HIV-infected women.

Surface and interface of epitaxial CdTe film on CdS buffered van der Waals mica substrate

DOE PAGES

Yang, Y. -B.; Seewald, L.; Mohanty, Dibyajyoti; ...

2017-03-31

We report single crystal CdTe films are desirable for optoelectronic device applications. An important strategy of creating films with high crystallinity is through epitaxial growth on a proper single crystal substrate. We report the metalorganic chemical vapor deposition of epitaxial CdTe films on the CdS/mica substrate. The epitaxial CdS film was grown on a mica surface by thermal evaporation. Due to the weak van der Waals forces, epitaxy is achieved despite the very large interface lattice mismatch between CdS and mica (~21–55%). The surface morphology of mica, CdS and CdTe were quantified by atomic force microscopy. The near surface structures, orientations and texture of CdTe and CdS films were characterized by the unique reflection high-energy electron diffraction surface pole figure technique. The interfaces of CdTe and CdS films and mica were characterized by X-ray pole figure technique and transmission electron microscopy. The out-of-plane and in-plane epitaxy of the heteroepitaxial films stack are determined to be CdTe(111)//CdS(0001)//mica(001) and [more » $$\\overline{1}2\\overline{1}$$] CdTe//[$$\\overline{1}100$$] CdS//[010] mica, respectively. The measured photoluminescence (PL), time resolved PL, photoresponse, and Hall mobility of the CdTe/CdS/mica indicate quality films. Finally, the use of van der Waals surface to grow epitaxial CdTe/CdS films offers an alternative strategy towards infrared imaging and solar cell applications.« less

Surface and interface of epitaxial CdTe film on CdS buffered van der Waals mica substrate

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

Yang, Y. -B.; Seewald, L.; Mohanty, Dibyajyoti

We report single crystal CdTe films are desirable for optoelectronic device applications. An important strategy of creating films with high crystallinity is through epitaxial growth on a proper single crystal substrate. We report the metalorganic chemical vapor deposition of epitaxial CdTe films on the CdS/mica substrate. The epitaxial CdS film was grown on a mica surface by thermal evaporation. Due to the weak van der Waals forces, epitaxy is achieved despite the very large interface lattice mismatch between CdS and mica (~21–55%). The surface morphology of mica, CdS and CdTe were quantified by atomic force microscopy. The near surface structures, orientations and texture of CdTe and CdS films were characterized by the unique reflection high-energy electron diffraction surface pole figure technique. The interfaces of CdTe and CdS films and mica were characterized by X-ray pole figure technique and transmission electron microscopy. The out-of-plane and in-plane epitaxy of the heteroepitaxial films stack are determined to be CdTe(111)//CdS(0001)//mica(001) and [more » $$\\overline{1}2\\overline{1}$$] CdTe//[$$\\overline{1}100$$] CdS//[010] mica, respectively. The measured photoluminescence (PL), time resolved PL, photoresponse, and Hall mobility of the CdTe/CdS/mica indicate quality films. Finally, the use of van der Waals surface to grow epitaxial CdTe/CdS films offers an alternative strategy towards infrared imaging and solar cell applications.« less

Biomimetic transport and rational drug delivery.

PubMed

Ranney, D F

2000-01-15

Medicine and pharmaceutics are encountering critical needs and opportunities for transvascular drug delivery that improves site targeting and tissue permeation by mimicking natural tissue addressing and transport mechanisms. This is driven by the accelerated development of genomic agents requiring targeted controlled release. Although rationally designed for in vitro activity, such agents are not highly effective in vivo, due to opsonization and degradation by plasma constituents, and failure to transport across the local vascular endothelium and tissue matrix. A growing knowledge of the addresses of the body can be applied to engineer "Bio-Logically" staged delivery systems with sequential bioaddressins complementary to the discontinuous compartments encountered--termed discontinuum pharmaceutics. Effective tissue targeting is accomplished by leukocytes, bacteria, and viruses. We are increasingly able to mimic their bioaddressins by genomic means. Approaches described in this commentary include: (a) endothelial-directed adhesion mediated by oligosaccharides and carbohydrates (e.g. dermatan sulfate as a mimic of sulfated CD44) and peptidomimetics interacting with adhesins, selectins, integrins, hyaluronans, and locally induced growth factors (e.g. vascular endothelial growth factor, VEGF) and coagulation factors (e.g. factor VIII antigen); (b) improved tissue permeation conferred by hydrophilically "cloaked" carrier systems; (c) "uncloaking" by matrix dilution or selective triggering near the target cells; and (d) target binding-internalization by terminally exposed hydrophobic moieties, cationic polymers, and receptor-binding lectins, peptides, or carbohydrates. This commentary also describes intermediate technology solutions (e.g. "hybrid drugs"), and highlights the high-resolution, dynamic magnetic resonance imaging and radiopharmaceutical imaging technologies plus the groups and organizations capable of accelerating these important initiatives.

Effects of environmental biomass-producing factors on Cd uptake in two Swedish ecotypes of Pinus sylvestris.

PubMed

Ekvall, Lars; Greger, Maria

2003-01-01

A factorial design was used to study direct effects of external biomass-producing factors such as light, temperature and photoperiod on cadmium (Cd) uptake and indirect effects, via change in biomass production in two ecotypes of Scots pine (Pinus silvestris). The aim was to find out if the external factors affect the Cd uptake directly or via change in biomass production, and if the effect differs between ecotypes. Seedlings were grown under 10 combinations of external factors, i.e. temperature (15 and 20 degrees C), light intensity (50 and 200 micromol photons m(-2) S(-1)), photoperiod (18 h light/8 h darkness and continuous light) and external Cd concentration (totally 1.88 and 7.50 micromol). The treatment lasted for 18 days and Cd concentrations in roots and shoots were determined by AAS. The results showed that an increased biomass production increased the total Cd uptake but had a dilution effect on the Cd concentration, especially in the root tissues. The external factors tested did not have any direct effects on the Cd untake, only in the case of Cd translocation to the shoot did the higher temperature show a direct increase, but only in the southern ecotype. The two ecotypes reacted differently in Cd uptake and translocation to the external factors studied. The relative Cd uptake creased with increasing photoperiod in the northern but not in the southern ecotype. The southern ecotype decreased the Cd concentration in the shoot with increased light intensity caused by a dilution effect due to extensive shoot growth of this ecotype. The conclusion is that the uptake in pine seedlings is mainly regulated via biomass production, and not directly by light and temperature and that resulting plant Cd contents to a certain extent depend on plant origin.

Calcineurin inhibitor-induced complement system activation via ERK1/2 signalling is inhibited by SOCS-3 in human renal tubule cells.

PubMed

Loeschenberger, Beatrix; Niess, Lea; Würzner, Reinhard; Schwelberger, Hubert; Eder, Iris E; Puhr, Martin; Guenther, Julia; Troppmair, Jakob; Rudnicki, Michael; Neuwirt, Hannes

2018-02-01

One factor that significantly contributes to renal allograft loss is chronic calcineurin inhibitor (CNI) nephrotoxicity (CIN). Among other factors, the complement (C-) system has been proposed to be involved CIN development. Hence, we investigated the impact of CNIs on intracellular signalling and the effects on the C-system in human renal tubule cells. In a qPCR array, CNI treatment upregulated C-factors and downregulated SOCS-3 and the complement inhibitors CD46 and CD55. Additionally, ERK1/-2 was required for these regulations. Following knock-down and overexpression of SOCS-3, we found that SOCS-3 inhibits ERK1/-2 signalling. Finally, we assessed terminal complement complex formation, cell viability and apoptosis. Terminal complement complex formation was induced by CNIs. Cell viability was significantly decreased, whereas apoptosis was increased. Both effects were reversed under complement component-depleted conditions. In vivo, increased ERK1/-2 phosphorylation and SOCS-3 downregulation were observed at the time of transplantation in renal allograft patients who developed a progressive decline of renal function in the follow-up compared to stable patients. The progressive cohort also had lower total C3 levels, suggesting higher complement activity at baseline. In conclusion, our data suggest that SOCS-3 inhibits CNI-induced ERK1/-2 signalling, thereby blunting the negative control of C-system activation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simian immunodeficiency virus infection induces severe loss of intestinal central memory T cells which impairs CD4+ T-cell restoration during antiretroviral therapy.

PubMed

Verhoeven, D; Sankaran, S; Dandekar, S

2007-08-01

Simian immunodeficiency virus (SIV) infection leads to severe loss of intestinal CD4(+) T cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (ART). Mechanisms for this delay have not been examined in context of which specific CD4(+) memory subsets or lost and fail to regenerate during ART. Fifteen rhesus macaques were infected with SIV, five of which received ART (FTC/PMPA) for 30 weeks. Viral loads were measured by real-time PCR. Flow cytometric analysis determined changes in T-cell subsets and their proliferative state. Changes in proliferative CD4(+) memory subsets during infection accelerated their depletion. This reduced the central memory CD4(+) T-cell pool and contributed to slow CD4(+) T-cell restoration during ART. There was a lack of restoration of the CD4(+) central memory and effector memory T-cell subsets in gut-associated lymphoid tissue during ART, which may contribute to the altered intestinal T-cell homeostasis in SIV infection.

Heavy metal pollution and spatial distribution in surface sediments of Mustafakemalpaşa stream located in the world's largest borate basin (Turkey).

PubMed

Omwene, Philip Isaac; Öncel, Mehmet Salim; Çelen, Meltem; Kobya, Mehmet

2018-06-07

Mining activities in addition to the geology of Mustafakemalpaşa catchment have for long been linked to its deteriorating water and sediment quality. This study assessed contamination levels of heavy metals and other major elements (Pb, As, B, Cd, Zn, Cr, Mo, Co, Ni, Cu, and Ag) in surface sediments of the area, and identified possible pollution sources. Sediment quality indicators, such as contamination factor (CF), enrichment factor (EF), geo-accumulation index (I geo ) and sediment quality guidelines were used, in addition to multivariate statistical technics; Pearson Correlation Matrix (PCM), Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA). The highest contamination (annual average > 110 mg kg -1 ) was revealed by B, Cr, Ni, Zn and As. Moreover, As, Cd and Ni levels exceeded their respective probable effect concentrations (PEC), posing a potential negative impact to biota. The highest I geo values were recorded for Cr, B, Ni, As and Zn, and occurred near urban settlements and mining sites, particularly of coal and chromium. The present study also suggests use of site rank index (SRI) as an alternative to pollution load index (PLI), since the former is derived from the data of interest and eliminates arbitrary classifications. The sources of heavy metals in the sediments were attributed to fly ashes of coal-powered plants, urban waste leachate and weathering of sulfide ore minerals for Pb, Zn and Cu; urban-industrial wastes and mining wastes for Ni. Although Cr, As, Cd and B were ascribed to natural occurrence, their presences in river sediment is accelerated by mining. Copyright © 2018 Elsevier Ltd. All rights reserved.

Integrated micro-biochemical approach for phytoremediation of cadmium and zinc contaminated soils.

PubMed

Mani, Dinesh; Kumar, Chitranjan; Patel, Niraj Kumar

2015-01-01

The integrated potential of oilcake manure (OM), elemental sulphur (S(0)), Glomus fasciculatum and Pseudomonas putida by growing Helianthus annuus L for phytoremediation of cadmium and zinc contaminated soils was investigated under pot experiment. The integrated treatment (2.5 g kg(-1) OM, 0.8 g kg(-1) S(0) and co-inoculation with G. fasciculatum and P. putida promoted the dry biomass of the plant. The treatment was feasible for enhanced cadmium accumulation up to 6.56 and 5.25 mg kg(-1) and zinc accumulation up to 45.46 and 32.56 mg kg(-1) in root and shoot, respectively, which caused maximum remediation efficiency (0.73 percent and 0.25 percent) and bioaccumulation factor (2.39 and 0.83) for Cd and Zn, respectively showing feasible uptake (in mg kg(-1) dry biomass) of Cd (5.55) and Zn (35.51) at the contaminated site. Thus, authors conclude to integrate oilcake manure, S(0) and microbial co-inoculation for enhanced clean-up of cadmium and zinc-contaminated soils. Copyright © 2014 Elsevier Inc. All rights reserved.

Exercise Training Modifies Ghrelin and Adiponectin Concentrations and Is Related to Inflammation in Older Adults

PubMed Central

Carrillo, Andres E.; Timmerman, Kyle L.; Jennings, Kristofer; Coen, Paul M.; Pence, Brandt D.; Flynn, Michael G.

2014-01-01

The purpose of this study was to observe exercise training–induced effects on adiponectin, leptin, and ghrelin. Twenty-nine older, healthy participants were classified as physically active (comparison group: N = 15, 70.9±1.2 years) or physically inactive (exercise group: N = 14, 70.5±1.4 years). Exercise group participants completed 12 weeks of combined aerobic and resistance exercise training, whereas comparison group participants maintained their current level of exercise and served as a physically active comparison group. Monocyte phenotype, as well as serum ghrelin, leptin, adiponectin, and soluble tumor necrosis factor receptor II were analyzed prior to and following the 12-week period. Ghrelin and adiponectin increased 47% and 55%, respectively, in exercise group participants following exercise training. Percent change in ghrelin (post and pre) was negatively correlated with the percent change in CD14+CD16+ monocytes (post and pre) in exercise group participants. Despite no changes in body mass, these data contribute to evidence for the anti-inflammatory effects of exercise. PMID:24013674

Rapid immune reconstitution of SCID-X1 canines after G-CSF/AMD3100 mobilization and in vivo gene therapy

PubMed Central

Humbert, Olivier; Chan, Frieda; Rajawat, Yogendra S.; Torgerson, Troy R.; Burtner, Christopher R.; Hubbard, Nicholas W.; Humphrys, Daniel; Norgaard, Zachary K.; O’Donnell, Patricia; Adair, Jennifer E.; Trobridge, Grant D.; Scharenberg, Andrew M.; Felsburg, Peter J.; Rawlings, David J.

2018-01-01

Hematopoietic stem-cell gene therapy is a promising treatment of X-linked severe combined immunodeficiency disease (SCID-X1), but currently, it requires recipient conditioning, extensive cell manipulation, and sophisticated facilities. With these limitations in mind, we explored a simpler therapeutic approach to SCID-X1 treatment by direct IV administration of foamy virus (FV) vectors in the canine model. FV vectors were used because they have a favorable integration site profile and are resistant to serum inactivation. Here, we show improved efficacy of our in vivo gene therapy platform by mobilization with granulocyte colony-stimulating factor (G-CSF) and AMD3100 before injection of an optimized FV vector incorporating the human phosphoglycerate kinase enhancerless promoter. G-CSF/AMD3100 mobilization before FV vector delivery accelerated kinetics of CD3+ lymphocyte recovery, promoted thymopoiesis, and increased immune clonal diversity. Gene-corrected T lymphocytes exhibited a normal CD4:CD8 ratio and a broad T-cell receptor repertoire and showed restored γC-dependent signaling function. Treated animals showed normal primary and secondary antibody responses to bacteriophage immunization and evidence for immunoglobulin class switching. These results demonstrate safety and efficacy of an accessible, portable, and translatable platform with no conditioning regimen for the treatment of SCID-X1 and other genetic diseases. PMID:29720491

Simian immunodeficiency virus selectively infects proliferating CD4+ T cells in neonatal rhesus macaques.

PubMed

Wang, Xiaolei; Xu, Huanbin; Pahar, Bapi; Alvarez, Xavier; Green, Linda C; Dufour, Jason; Moroney-Rasmussen, Terri; Lackner, Andrew A; Veazey, Ronald S

2010-11-18

Infants infected with HIV have a more severe course of disease and persistently higher viral loads than HIV-infected adults. However, the underlying pathogenesis of this exacerbation remains obscure. Here we compared the rate of CD4(+) and CD8(+) T-cell proliferation in intestinal and systemic lymphoid tissues of neonatal and adult rhesus macaques, and of normal and age-matched simian immunodeficiency virus (SIV)-infected neonates. The results demonstrate infant primates have much greater rates of CD4(+) T-cell proliferation than adult macaques, and that these proliferating, recently "activated" CD4(+) T cells are infected in intestinal and other lymphoid tissues of neonates, resulting in selective depletion of proliferating CD4(+) T cells in acute infection. This depletion is accompanied by a marked increase in CD8(+) T-cell activation and production, particularly in the intestinal tract. The data indicate intestinal CD4(+) T cells of infant primates have a markedly accelerated rate of proliferation and maturation resulting in more rapid and sustained production of optimal target cells (activated memory CD4(+) T cells), which may explain the sustained "peak" viremia characteristic of pediatric HIV infection. Eventual failure of CD4(+) T-cell turnover in intestinal tissues may indicate a poorer prognosis for HIV-infected infants.

Age of onset and the subclassification of conduct/dissocial disorder

PubMed Central

Silberg, Judy; Moore, Ashlee A.; Rutter, Michael

2015-01-01

Background Conduct Disorder (CD) is a markedly heterogeneous psychiatric condition. Moffitt (1993) proposed that subclassification of CD should be according to age of onset. Our goals were to compare childhood-onset and adolescent-onset CD in terms of differences in phenotypic risk factors, genetic analyses, and factors associated with the persistence of antisocial behavior into young adulthood. Methods The data are from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and Young Adult Follow-Up (YAFU). Childhood-onset CD was defined as CD beginning at or before age 11. Adolescent-onset CD was defined as having CD onset between ages 14 and 17. These subgroups were compared on ADHD, young adult antisocial behavior (ASB), family dysfunction, and parental depression. Genetic analyses compare childhood-onset and adolescent-onset CD, as well as their cooccurrence with ADHD and ASB. Finally, predictors of persistence were examined. Results Childhood-onset CD was significantly associated with ADHD, ASB, family dysfunction, and parental depression. Adolescent-onset CD was marginally associated with parental depression (p = .05) but not with any of the other risk factors. Univariate genetic models showed that both childhood-onset and adolescent-onset CD involve a large genetic liability accounting for 62% and 65% of the variance, respectively. A common genetic factor (as well as an ADHD-specific factor) accounted for the cooccurence of childhood-onset CD and ADHD. The cooccurrence of childhood-onset CD and ASB are reflected by a common genetic factor with genetic specific effects on ASB. There was no etiological link between adolescent-onset CD and either ADHD or ASB. Both ADHD and family dysfunction were significantly associated with the persistence of antisocial behavior into young adulthood. Conclusions Phenotypic findings differentiated between childhood-onset and adolescent-onset CD. ADHD and family dysfunction predicted persistence of antisocial behavior into young adulthood. PMID:25359313

Age of onset and the subclassification of conduct/dissocial disorder.

PubMed

Silberg, Judy; Moore, Ashlee A; Rutter, Michael

2015-07-01

Conduct Disorder (CD) is a markedly heterogeneous psychiatric condition. Moffitt (1993) proposed that subclassification of CD should be according to age of onset. Our goals were to compare childhood-onset and adolescent-onset CD in terms of differences in phenotypic risk factors, genetic analyses, and factors associated with the persistence of antisocial behavior into young adulthood. The data are from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and Young Adult Follow-Up (YAFU). Childhood-onset CD was defined as CD beginning at or before age 11. Adolescent-onset CD was defined as having CD onset between ages 14 and 17. These subgroups were compared on ADHD, young adult antisocial behavior (ASB), family dysfunction, and parental depression. Genetic analyses compare childhood-onset and adolescent-onset CD, as well as their cooccurrence with ADHD and ASB. Finally, predictors of persistence were examined. Childhood-onset CD was significantly associated with ADHD, ASB, family dysfunction, and parental depression. Adolescent-onset CD was marginally associated with parental depression (p = .05) but not with any of the other risk factors. Univariate genetic models showed that both childhood-onset and adolescent-onset CD involve a large genetic liability accounting for 62% and 65% of the variance, respectively. A common genetic factor (as well as an ADHD-specific factor) accounted for the cooccurrence of childhood-onset CD and ADHD. The cooccurrence of childhood-onset CD and ASB are reflected by a common genetic factor with genetic specific effects on ASB. There was no etiological link between adolescent-onset CD and either ADHD or ASB. Both ADHD and family dysfunction were significantly associated with the persistence of antisocial behavior into young adulthood. Phenotypic findings differentiated between childhood-onset and adolescent-onset CD. ADHD and family dysfunction predicted persistence of antisocial behavior into young adulthood. © 2014 Association for Child and Adolescent Mental Health.

[CD22 signal abnormalities in the pathogenesis of immune related pancytopenia].

PubMed

Wu, Xiaojing; Shao, Zonghong; Ruan, Erbao; Fu, Rong; Wang, Guojin; Liu, Hong; Wu, Yuhong; Song, Jia; Xing, Limin; Qu, Wen; Cuan, Jing; Li, Lijuan; Wang, Xiaoming; Liu, Hui; Wang, Yihao; Wang, Huaquan

2015-07-14

To investigate the expression of CD22 and its downstream signal molecule spleen tyrosine kinase (SYK) and their phosphorylation of B lymphocytes in patients with immune related pancytopenia(IRP), and to explore the role of CD22 in pathogenesis of IRP. The expression of CD22, SYK and their phosphorylation, along with the expression of IgG and IgM, which obtained from B lymphocytes in peripheral blood of 46 patients with IRP(22 new diagnosed and 24 remitted patients returned to normal after treatment), 22 healthy controls and 12 chronic lymphocytic leukemia(CLL) patients from February to December 2014 were analyzed by flow cytometry. And the mRNA expression of CD22 in peripheral blood mononuclear cell was determined by real-time quantitative PCR. The ratios of CD22+ cells and phosphorylated CD22(pCD22)+ cells of B lymphocytes in new diagnosed group (60. 03% ± 20. 94% 71. 32% ± 11. 16%) were significantly higher than those in remission group (46. 92% ± 20. 04%, 55. 82% ± 14. 42%), normal control group (46. 86% ± 17. 78%, 53. 28% ± 14. 76%) and CLL group (39. 74% ± 18. 96%, 59. 07% ± 17.09%) (all P <0.05). The ratios of phosphorylated SYK( pSYK) + cells in the four groups had the same trend (all P <0. 05). The ratio of pCD22+ cells/pSYK+ cells in new diagnosed group was significantly lower than that in normal control group and CLL group (27. 39 (5. 06 - 102. 70) vs 55. 95 (15. 25 - 298. 53), 56. 92(5. 60 - 228. 96), both P <0. 05), and pCD22+ cells positively correlated to pSYK+ cells ( r = 0. 341, P < 0. 05). The expression of IgG in new diagnosed group and remission group was significantly higher than that in normal control group, and the expression of IgM in new diagnosed group was significantly higher than that in normal control group and CLL group (all P <0. 05). The expression levels of CD22 mRNA in new diagnosed group was significantly higher than that in remission group, normal control group and CLL group (all P <0. 05). The BCR signal pathway of B lymphocyte in IRP patients is enhanced, and the quantity and function of CD22 are increased, while which are still insufficient to inhibit B cell proliferation, and these may have some relationships with the pathogenesis of IRP. [Key words] Pancytopenia; Antigens, CD22; Immune related pancytopenia; Spleen tyrosine kinase; Phosphorylation

Effects of High Intensity Training and High Volume Training on Endothelial Microparticles and Angiogenic Growth Factors

PubMed Central

Achtzehn, Silvia; Schmitz, Theresa; Bloch, Wilhelm; Mester, Joachim; Werner, Nikos

2014-01-01

Aims Endothelial microparticles (EMP) are complex vesicular structures shed from activated or apoptotic endothelial cells. As endurance exercise affects the endothelium, the objective of the study was to examine levels of EMP and angiogenic growth factors following different endurance exercise protocols. Methods 12 subjects performed 3 different endurance exercise protocols: 1. High volume training (HVT; 130 min at 55% peak power output (PPO); 2. 4×4 min at 95% PPO; 3. 4×30 sec all-out. EMPs were quantified using flow cytometry after staining platelet-poor-plasma. Events positive for Annexin-V and CD31, and negative for CD42b, were classified as EMPs. Vascular endothelial growth factor (VEGF), migratory inhibiting factor (MIF) and hepatocyte growth factor (HGF) were determined by ELISA technique. For all these measurements venous blood samples were taken pre, 0′, 30′, 60′ and 180′ after each intervention. Furthermore, in vitro experiments were performed to explore the effect of collected sera on target endothelial functions and MP uptake capacities. Results VEGF and HGF significantly increased after HIT interventions. All three interventions caused a significant decrease in EMP levels post exercise compared to pre values. The sera taken after exercise increased the uptake of EMP in target endothelial cells compared to sera taken under resting conditions, which was shown to be phosphatidylserin-dependent. Increased EMP uptake was associated with an improved protection of target cells against apoptosis. Sera taken prior and after exercise promoted target endothelial cell migration, which was abrogated after inhibition of VEGF. Conclusion Physical exercise leads to decreased EMP levels and promotes a phosphatidylserin-dependent uptake of EMP into target endothelial cells, which is associated with a protection of target cells against apoptosis. PMID:24770423

Health-related quality of life among military HIV patients on antiretroviral therapy.

PubMed

Emuren, Leonard; Welles, Seth; Evans, Alison A; Polansky, Marcia; Okulicz, Jason F; Macalino, Grace; Agan, Brian K

2017-01-01

The aims of this study were: (i) to determine the factors associated with HRQOL at baseline in our cohort, and (ii) to evaluate if there are differences in baseline HRQOL measures by antiretroviral treatment. The Short Form 36 (SF-36) was administered between 2006 and 2010 among members of the United States HIV Natural History Study cohort (NHS), and participants who completed the SF-36 were included in the study. Physical component summary (PCS) and mental component summary (MCS) scores were computed based on standard algorithms. Multivariate linear regression models were constructed for PCS and MCS to estimate the association between selected variables and HRQOL scores. Antiretroviral therapy (ART) was not independently associated with HRQOL scores. Factors associated with PCS were CD4+ count < 200 cells/mm3 (β = -5.84, 95% CI: -7.63, -4.06), mental comorbidity (β = -2.82, 95% CI: -3.79, -1.85), medical comorbidity (β = -2.51, 95% CI: -3.75, -1.27), AIDS diagnosis (β = -2.38, 95% CI: -3.79, -0.98). Others were gender, military rank, marital status, and age. Factors independently associated with MCS were CD4+ count < 200 cells/mm3 (β = -1.93, 95% CI: -3.85, -0.02), mental comorbidity (β = -6.25, 95% CI: -7.25, -5.25), age (β = 0.37, 95% CI: 0.14, 0.60), and being African American (β = 1.55, 95% CI: 0.63, 2.47). Among military active duty and beneficiaries with HIV, modifiable factors associated with HRQOL measures included advanced HIV disease, and mental or medical comorbidity. Addressing these factors may improve quality of life of HIV-infected individuals in the NHS cohort.

Trends in and correlates of CD4+ cell count at antiretroviral therapy initiation after changes in national ART guidelines in Rwanda

PubMed Central

Mutimura, Eugene; Addison, Diane; Anastos, Kathryn; Hoover, Donald; Dusingize, Jean Claude; Karenzie, Ben; Izimukwiye, Isabelle; Mutesa, Leo; Nsanzimana, Sabin; Nashi, Denis

2015-01-01

Background Initiation of antiretroviral therapy (ART) in the advanced stages of HIV infection remains a major challenge in sub-Saharan Africa. This study was conducted to better understand barriers and enablers to timely ART initiation in Rwanda where ART coverage is high and national ART eligibility guidelines first expanded in 2007–2008. Methods Using data on 6326 patients (≥15 years) at five Rwandan clinics, we assessed trends and correlates of CD4+ cell count at ART initiation and the proportion initiating ART with advanced HIV disease (CD4+ <200 cells/µl or WHO stage IV). Results Out of 6326 patients, 4486 enrolling in HIV care initiated ART with median CD4+ cell count of 211 cells/µl [interquartile range: 131–300]. Median CD4+ cell counts at ART initiation increased from 183 cells/µl in 2007 to 293 cells/µl in 2011–2012, and the proportion with advanced HIV disease decreased from 66.2 to 29.4%. Factors associated with a higher odds of advanced HIV disease at ART initiation were male sex [adjusted odds ratios (AOR) = 1.7; 95% confidence interval (CI): 1.3–2.1] and older age (AOR46–55+ vs. <25 = 2.3; 95% CI: 1.2–4.3). Among those initiating ART more than 1 year after enrollment in care, those who had a gap in care of 12 or more months prior to ART initiation had higher odds of advanced HIV disease (AOR = 5.2; 95% CI: 1.2–21.1). Conclusion Marked improvements in the median CD4+ cell count at ART initiation and proportion initiating ART with advanced HIV disease were observed following the expansion of ART eligibility criteria in Rwanda. However, sex disparities in late treatment initiation persisted through 2011–2012, and appeared to be driven by later diagnosis and/or delayed linkage to care among men. PMID:25562492

Improved survival after transplantation of more donor plasmacytoid dendritic or naïve T cells from unrelated-donor marrow grafts: results from BMTCTN 0201.

PubMed

Waller, Edmund K; Logan, Brent R; Harris, Wayne A C; Devine, Steven M; Porter, David L; Mineishi, Shin; McCarty, John M; Gonzalez, Corina E; Spitzer, Thomas R; Krijanovski, Oleg I; Linenberger, Michael L; Woolfrey, Ann; Howard, Alan; Wu, Juan; Confer, Dennis L; Anasetti, Claudio

2014-08-01

To characterize relationships between specific immune cell subsets in bone marrow (BM) or granulocyte colony-stimulating factor-mobilized peripheral blood (PB) stem cells collected from unrelated donors and clinical outcomes of patients undergoing transplantation in BMTCTN 0201. Fresh aliquots of 161 BM and 147 PB stem-cell allografts from North American donors randomly assigned to donate BM or PB stem cells and numbers of transplanted cells were correlated with overall survival (OS), relapse, and graft-versus-host disease (GvHD). Patients with evaluable grafts were similar to all BMTCTN 0201 patients. The numbers of plasmacytoid dendritic cells (pDCs) and naïve T cells (Tns) in BM allografts were independently associated with OS in multivariable analyses including recipient and donor characteristics, such as human leukocyte antigen mismatch, age, and use of antithymocyte globulin. BM recipients of > median number of pDCs, naïve CD8(+) T cells (CD8Tns), or naïve CD4(+) T cells (CD4Tns) had better 3-year OS (pDCs, 56% v 35%; P = .025; CD8Tns, 56% v 37%; P = .012; CD4Tns, 55% v 37%; P = .009). Transplantation of more BM Tns was associated with less grade 3 to 4 acute GvHD but similar rates of relapse. Transplantation of more BM pDCs was associated with fewer deaths resulting from GvHD or from graft rejection. Analysis of PB grafts did not identify a donor cell subset significantly associated with OS, relapse, or GvHD. Donor immune cells in BM but not PB stem-cell grafts were associated with survival after unrelated-donor allogeneic hematopoietic stem-cell transplantation. The biologic activity of donor immune cells in allogeneic transplantation varied between graft sources. Donor grafts with more BM-derived Tns and pDCs favorably regulated post-transplantation immunity in allogeneic hematopoietic stem-cell transplantation. © 2014 by American Society of Clinical Oncology.

Euler force actuation mechanism for siphon valving in compact disk-like microfluidic chips

PubMed Central

Deng, Yongbo; Fan, Jianhua; Zhou, Song; Zhou, Teng; Wu, Junfeng; Li, Yin; Liu, Zhenyu; Xuan, Ming; Wu, Yihui

2014-01-01

Based on the Euler force induced by the acceleration of compact disk (CD)-like microfluidic chip, this paper presents a novel actuation mechanism for siphon valving. At the preliminary stage of acceleration, the Euler force in the tangential direction of CD-like chip takes the primary place compared with the centrifugal force to function as the actuation of the flow, which fills the siphon and actuates the siphon valving. The Euler force actuation mechanism is demonstrated by the numerical solution of the phase-field based mathematical model for the flow in siphon valve. In addition, experimental validation is implemented in the polymethylmethacrylate-based CD-like microfluidic chip manufactured using CO2 laser engraving technique. To prove the application of the proposed Euler force actuation mechanism, whole blood separation and plasma extraction has been conducted using the Euler force actuated siphon valving. The newly introduced actuation mechanism overcomes the dependence on hydrophilic capillary filling of siphon by avoiding external manipulation or surface treatments of polymeric material. The sacrifice for highly integrated processing in pneumatic pumping technique is also prevented by excluding the volume-occupied compressed air chamber. PMID:24753736

High-speed rail turnout literature review : final report.

DOT National Transportation Integrated Search

2016-08-01

High-speed rail (HSR) turnout design criteria generally address unbalanced lateral acceleration or cant deficiency (CD), cant deficiency change rate (CDCR), and entry and exit jerk. Various countries have adopted different design values for their HSR...

Charge transfer in photorefractive CdTe:Ge at different wavelengths

NASA Astrophysics Data System (ADS)

Shcherbin, K.; Odoulov, S.; Ramaz, F.; Farid, B.; Briat, B.; von Bardeleben, H. J.; Delaye, P.; Roosen, G.

2001-10-01

The charge transfer processes in photorefractive CdTe:Ge were modeled using the data of optical absorption, magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR) spectroscopies. Within the developed model the variations in the photorefractive properties of different CdTe:Ge samples are explained by differences in the relative concentrations of donor and trap centers. The existence of two different centers of comparable concentrations, each in two charge states, allows charge redistribution between them and gives rise to optical sensitization of some CdTe:Ge samples for photorefractive recording under an auxiliary illumination. In the present article we follow the proposal of pseudo-3D presentation of light-induced absorption to distinguish the main charge transfer processes at different excitation energies and explain the sensitization of CdTe:Ge for photorefractive recording at 1.06, 1.32 and 1.55 μm by light with appropriate wavelength.

TOMOX : An X-rays tomographer for planetary exploration

NASA Astrophysics Data System (ADS)

Marinangeli, Lucia; Pompilio, Loredana; Chiara Tangari, Anna; Baliva, Antonio; Alvaro, Matteo; Chiara Domeneghetti, Maria; Frau, Franco; Melis, Maria Teresa; Bonanno, Giovanni; Consolata Rapisarda, Maria; Petrinca, Paolo; Menozzi, Oliva; Lasalvia, Vasco; Pirrotta, Simone

2017-04-01

The TOMOX instrument has recently been founded under the ASI DC-EOS-2014-309 call. The TOMOX objective is to acquire both X-ray fluorescence and diffraction measurements from a sample in order to: a) achieve its chemical and mineralogical composition; b) reconstruct a 3D tomography of the sample exposed surface; c) give hints regarding the sample age. Nevertheless, this technique has applicability in several disciplines other than planetary geology, especially archaeology. The word 'tomography' is nowadays used for many 3D imaging methods, not just for those based on radiographic projections, but also for a wider range of techniques that yield 3D images. Fluorescence tomography is based on the signal produced on an energy-sensitive detector, generally placed in the horizontal plane at some angle with respect to the incident beam caused by photons coming from fluorescence emission. So far, a number of setups have been designed in order to acquire X-rays fluorescence tomograms of several different sample types. The proposed instrument is based on the MARS-XRD heritage, an ultra miniaturised XRD and XRF instrument developed for the ESA ExoMars mission. The general idea of TOMOX is to distribute both sources and detectors along a moving hemispherical support around the target sample. As a result, both sources move integrally with the detectors while the sample is observed from a fixed position, thus preserving the geometry of observation. In that way, the whole sample surface is imagined and XRD and XRF measurements are acquired continuously along all the scans. We plan to irradiate the target sample with X-rays emitted from 55Fe and 109Cd radioactive sources. 55Fe and 109Cd radioisotopes are commonly used as X-ray sources for analysis of metals in soils and rocks. The excitation energies of 55Fe and 109Cd are 5.9 keV, and 22.1 and 87.9 keV, respectively. Therefore, the elemental analysis ranges are Al to Mn with K lines excited with 55Fe; Ca to Rh, with K lines excited with 109Cd. 55Fe will be primarily dedicated to XRD measurements, as it has been already tested for the MARS-XRD development. 109Cd will be used to reinforce the efficiency of 55Fe source in the production of fluorescent X-rays generated in the sample as a consequence of irradiation and to extend the analytical range of elements. Two different detectors will be used in order to increase the total amount of events collected and allow the spatial distribution of events to be recorded as well. The detectors we plan to use are SDD (Silicon Drift Detector) and stand-alone CCD (Coupled Charge Detector). SDD has higher count rate and stability and has been successfully used for XRF applications. CCD is able to record the spatial position of each event of X-ray emission, together with its energy. Therefore, we plan to dedicate this detector to XRD measurements, where the spatial position of the event is directly correlated to the type of crystal through the Bragg's law. A prototype of the instrument will be likely completed by the end of this year.

CD16+ monocytes control T-cell subset development in immune thrombocytopenia

PubMed Central

Zhong, Hui; Bao, Weili; Li, Xiaojuan; Miller, Allison; Seery, Caroline; Haq, Naznin; Bussel, James

2012-01-01

Immune thrombocytopenia (ITP) results from decreased platelet production and accelerated platelet destruction. Impaired CD4+ regulatory T-cell (Treg) compartment and skewed Th1 and possibly Th17 responses have been described in ITP patients. The trigger for aberrant T-cell polarization remains unknown. Because monocytes have a critical role in development and polarization of T-cell subsets, we explored the contribution of monocyte subsets in control of Treg and Th development in patients with ITP. Unlike circulating classic CD14hiCD16− subpopulation, the CD16+ monocyte subset was expanded in ITP patients with low platelet counts on thrombopoietic agents and positively correlated with T-cell CD4+IFN-γ+ levels, but negatively with circulating CD4+CD25hiFoxp3+ and IL-17+ Th cells. Using a coculture model, we found that CD16+ ITP monocytes promoted the expansion of IFN-γ+CD4+ cells and concomitantly inhibited the proliferation of Tregs and IL-17+ Th cells. Th-1–polarizing cytokine IL-12, secreted after direct contact of patient T-cell and CD16+ monocytes, was responsible for the inhibitory effect on Treg and IL-17+CD4+ cell proliferation. Our findings are consistent with ITP CD16+ monocytes promoting Th1 development, which in turn negatively regulates IL-17 and Treg induction. This underscores the critical role of CD16+ monocytes in the generation of potentially pathogenic Th responses in ITP. PMID:22915651

Childhood Psychiatric Disorders as Risk Factor for Subsequent Substance Abuse: A Meta-Analysis.

PubMed

Groenman, Annabeth P; Janssen, Tieme W P; Oosterlaan, Jaap

2017-07-01

To assess the prospective risk of developing substance-related disorders after childhood mental health disorders (i.e., attention-deficit/hyperactivity disorder [ADHD], oppositional defiant disorder [ODD] or conduct disorder [CD], anxiety disorder, and depression) using meta-analysis. PubMed, Embase, and PsycInfo were searched for relevant longitudinal studies that described childhood (<18 years old) ADHD, ODD or CD, anxiety, or depression in relation to later alcohol-, nicotine-, or drug-related disorders or substance use disorders (SUDs) published in peer-reviewed journals in the English language from 1986 to May 2016. Two researchers conducted all review stages. Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. Thirty-seven studies including more than 762,187 participants were identified for quantitative analyses. These studies included 22,029 participants with ADHD, 434 participants with ODD or CD, 1,433 participants with anxiety disorder, and 2,451 participants with depression. Ninety-seven effects sizes were extracted for analyses. Meta-analysis showed a significantly increased risk for addiction in ADHD (n = 23, odds ratio [OR] 2.27, 95% CI 1.98-3.67; OR alcohol 2.15, 95% CI 1.56-2.97; OR drugs 1.52, 95% CI 1.52-5.27; OR nicotine 2.52, 95% CI 2.01-3.15; OR SUDs 2.61, 95% CI 1.77-3.84), ODD or CD (n = 8, OR 3.18, 95% CI 1.97-5.80; OR alcohol 1.73, 95% CI 1.51-2.00; OR drugs 4.24, 95% CI 1.3.21.5.59; OR nicotine 4.22, 95% CI 3.21-5.55; OR SUDs 4.86, 95% CI 3.09-7.56), and depression (n = 13, OR 2.03, 95% CI 1.47-2.81; OR alcohol 1.10, 95% CI 1.02-1.19; OR nicotine 2.56, 95% CI 1.89-3.48; OR SUDs 2.20, 95% CI 1.41-3.43), but not for anxiety disorders (n = 15, OR 1.34, 95% CI 0.90-1.55, not significant). Childhood ADHD, ODD, CD, and depression increase the risk of developing substance-related disorders. Anxiety disorders do not seem to increase the risk for future substance-related disorders, although the findings are highly heterogeneous. These findings emphasize the need for early detection and intervention to prevent debilitating substance-related disorders in later life. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Technetium-99m-HMPAO labeled leukocyte single photon emission computerized tomography (SPECT) for assessing Crohn's disease extent and intestinal infiltration.

PubMed

Biancone, L; Schillaci, O; Capoccetti, F; Bozzi, R M; Fina, D; Petruzziello, C; Geremia, A; Simonetti, G; Pallone, F

2005-02-01

Scintigraphy using radiolabeled leukocytes is a useful technique for assessing intestinal infiltration in Crohn's disease (CD). However, limits of planar images include overlapping activity in other organs and low specificity. To investigate the usefulness of (99m)Tc-HMPAO (hexametyl propylene amine oxime) labeled leukocyte single photon emission computerized tomography (SPECT) for assessing CD lesions, in comparison with planar images. Twenty-two inflammatory bowel disease patients (19 CD; 2 ulcerative colitis, UC; 1 ileal pouch) assessed by conventional endoscopy or radiology were enrolled. Leukocytes were labeled with (99m)Tc-HMPAO. SPECT images were acquired at 2 h and planar images at 30 min and 2 h. Bowel uptake was quantitated in nine regions (score 0-3). Both SPECT and planar images detected a negative scintigraphy (score 0) in the UC patient with no pouchitis and a positive scintigraphy (score 1-3) in the 21 patients showing active inflammation by conventional techniques. SPECT showed a higher global score than planar images (0.71 +/- 0.09 vs 0.30 +/- 0.05; p < 0.001), and in particular in the right iliac fossa (p= 0.003), right and left flank (p < 0.001; p= 0.02), hypogastrium (p= 0.002), and mesogastrium (p < 0.001). SPECT provided a better visualization and a higher uptake than planar images in patients with ileal and ileocolonic CD (6.45 +/- 0.82 vs 2.8 +/- 0.55, p < 0.001; 5.5 +/- 1.6 vs 2.6 +/- 0.7, p= 0.03), and with perianal CD (6.6 +/- 1.6 vs 3.4 +/- 1.2; p= 0.03). (99m)Tc-HMPAO labeled leukocyte SPECT provides a more detailed visualization of CD lesions than planar images. This technique may better discriminate between intestinal and bone marrow uptake, thus being useful for assessing CD lesions within the pelvis, including perianal disease.

[The usefullness of hyaluronate injection in patients with RA].

PubMed

Saito, Seiji

2003-06-01

In this seminar, we reported the usefulness of hyaluronate injection in clinical application with patients of RA. In basic research areas, however, the mechanisms responsible for the reported beneficial clinical effects of these treatments remain unclear. There is accumulating experimental evidence to show that the receptors of HA, eg, CD-44, accelerate the inflammation of joint. Administration high molecular weight HA may modulate CD-44 sensitive macromolecular in joint inflammation in part to reduce the activity of proteinases such as MMP-9.

Preeclampsia in autologous and oocyte donation pregnancy: is there a different pathophysiology?

PubMed

Lashley, Lisa E E L O; Buurma, Aletta; Swings, Godelieve M J S; Eikmans, Michael; Anholts, Jacqueline D H; Bakker, Jaap A; Claas, Frans H J

2015-06-01

Oocyte donation (OD) is a specific method of artificial reproductive technology that is accompanied by a higher risk of preeclampsia during pregnancy. The pathophysiological mechanism underlying preeclampsia in OD pregnancies is thought to differ from preeclampsia in autologous pregnancies. As preeclampsia in autologous pregnancies is suggested to be associated with complement activation, we studied C4d deposition, circulating complement components and placental complement regulatory proteins in preeclamptic OD pregnancies. Women with uncomplicated and preeclamptic pregnancies after OD or spontaneous conception were selected. We stained the placentas for C4d, marker for complement activation, measured complement factors C1q, C3 and C4 in maternal sera and quantified the placental mRNA expression of complement regulatory proteins CD46, CD55 and CD59. A significantly (p < 0.03) higher incidence of C4d deposition was observed in placentas from women with preeclampsia compared with uncomplicated pregnancies, both OD and autologous. The level of complement factors in serum did not differ between the groups. Children born in the autologous preeclampsia group were significantly lower in birth weight (p < 10th percentile) compared with the preeclamptic OD group. In addition, the placental mRNA expression level of complement regulatory proteins was significantly lower in uncomplicated and preeclamptic OD compared with the autologous pregnancies. In line with autologous preeclampsia pregnancies, there is excessive activation of complement in preeclamptic OD pregnancies. However, in contrast to autologous pregnancies this is not associated with counterbalancing upregulation of complement regulatory proteins. Furthermore, C4d deposition in OD pregnancies is not related to the severity of preeclampsia, suggesting another trigger or regulatory mechanism of placental C4d deposition in preeclamptic OD pregnancies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

CD19+CD21low B cells and CD4+CD45RA+CD31+ T cells correlate with first diagnosis of chronic graft-versus-host disease.

PubMed

Greinix, Hildegard T; Kuzmina, Zoya; Weigl, Roman; Körmoczi, Ulrike; Rottal, Arno; Wolff, Daniel; Kralj, Mateja; Kalhs, Peter; Mitterbauer, Margit; Rabitsch, Werner; Edinger, Matthias; Holler, Ernst; Pickl, Winfried F

2015-02-01

Chronic graft-versus-host disease (cGVHD) is a serious and frequent complication of allogeneic hematopoietic stem cell transplantation (HCT). Currently, no biomarkers for prediction and diagnosis of cGVHD are available. We performed a large prospective study focusing on noninvasive biomarkers for National Institutes of Health-defined cGVHD patients (n = 163) in comparison to time-matched HCT recipients who never experienced cGVHD (n = 64), analyzed from day 100 after HCT. In logistic regression analysis, CD19(+)CD21(low) B cells (P = .002; hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.53 to 7.17) and CD4(+)CD45RA(+)CD31(+) T cells (P < .001; HR, 3.88; 95% CI, 1.88 to 7.99) assessed on day 100 after HCT were significantly associated with subsequent development of cGVHD, independent of clinical parameters. A significant association with diagnosis of cGVHD was only observed for CD19(+)CD21(low) B cells (P = .008; HR, 3.00; 95% CI, 1.33 to 6.75) and CD4(+)CD45RA(+)CD31(+) T cells (P = .017; HR, 2.80; 95% CI, 1.19 to 6.55). CD19(+)CD21(low) B cells were found to have the highest discriminatory value with an area under the receiver operating curve of .77 (95% CI, .64 to .90). Our results demonstrate that CD19(+)CD21(low) B cells and CD4(+)CD45RA(+)CD31(+) T cells are significantly elevated in patients with newly diagnosed cGVHD. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Thin-film photovoltaic partnership -- Apollo{reg{underscore}sign} thin film process development: Phase 1 Technical Report, May 1998--April 1999

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

Cunningham, D.W.; Skinner, D.E.

1999-10-26

The objective of this Phase 1 subcontract was to establish an efficient production plating system capable of depositing thin-film CdTe and CdS on substrates up to 0.55 m{sup 2}. This baseline would then be used to build on and extend deposition areas to 0.94 m{sup 2} in the next two phases. The following achievements have been demonstrated: {sm{underscore}bullet} Chemical-bath deposition of CdS and electrochemical deposition of CdTe was demonstrated on 0.55 m{sup 2} substrates. The films were characterized using optical and electrical techniques, to increase the understanding of the materials and aid in loss analysis. {sm{underscore}bullet} A stand-alone, prototype CdTemore » reaction tank was built and commissioned, allowing the BP Solar team to perform full-scale trials as part of this subcontract. {sm{underscore}bullet} BP Solar installed two outdoor systems for reliability and performance testing. {sm{underscore}bullet} The 2-kW, ground-mounted, grid-connected system contains seventy-two 0.43-m{sup 2} Apollo{reg{underscore}sign} module interconnects. {sm{underscore}bullet} Two modules have been supplied to NREL for evaluation on their Performance and Energy Rating Test bed (PERT) for kWh evaluation. {sm{underscore}bullet} BP Solar further characterized the process waste stream with the aim to close-loop the system. Currently, various pieces of equipment are being investigated for suitability of particle and total organic compound removal.« less

Tbo-Filgrastim versus Filgrastim during Mobilization and Neutrophil Engraftment for Autologous Stem Cell Transplantation.

PubMed

Elayan, Mohammed M; Horowitz, Justin G; Magraner, Jose M; Shaughnessy, Paul J; Bachier, Carlos

2015-11-01

There are limited data available supporting the use of the recombinant granulocyte colony-stimulating factor (G-CSF), tbo-filgrastim, rather than traditionally used filgrastim to mobilize peripheral blood stem cells (PBSC) or to accelerate engraftment after autologous stem cell transplantation (ASCT). We sought to compare the efficacy and cost of tbo-filgrastim to filgrastim in these settings. Patients diagnosed with lymphoma or plasma cell disorders undergoing G-CSF mobilization, with or without plerixafor, were included in this retrospective analysis. The primary outcome was total collected CD34(+) cells/kg. Secondary mobilization endpoints included peripheral CD34(+) cells/μL on days 4 and 5 of mobilization, adjunctive use of plerixafor, CD34(+) cells/kg collected on day 5, number of collection days and volumes processed, number of collections reaching 5 million CD34(+) cells/kg, and percent reaching target collection goal in 1 day. Secondary engraftment endpoints included time to neutrophil and platelet engraftment, number of blood product transfusions required before engraftment, events of febrile neutropenia, and length of stay. A total of 185 patients were included in the final analysis. Patients receiving filgrastim (n = 86) collected a median of 5.56 × 10(6) CD34(+) cells/kg, compared with a median of 5.85 × 10(6) CD34(+) cells/kg in the tbo-filgrastim group (n = 99; P = .58). There were no statistically significant differences in all secondary endpoints with the exception of apheresis volumes processed (tbo-filgrastim, 17.0 liters versus filgrastim, 19.7 liters; P < .01) and mean platelet transfusions (tbo-filgrastim, 1.7 units versus filgrastim, 1.4 units; P = .04). In conclusion, tbo-filgrastim demonstrated similar CD34(+) yield compared with filgrastim in mobilization and post-transplantation settings, with no clinically meaningful differences in secondary efficacy and safety endpoints. Furthermore, tbo-filgrastim utilization was associated with cost savings of approximately $1406 per patient utilizing average wholesale price. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Incidence rate of Kaposi sarcoma in HIV-infected patients on antiretroviral therapy in Southern Africa: a prospective multi-cohort study

PubMed Central

Rohner, Eliane; Valeri, Fabio; Maskew, Mhairi; Prozesky, Hans; Rabie, Helena; Garone, Daniela; Dickinson, Diana; Chimbetete, Cleophas; Lumano-Mulenga, Priscilla; Sikazwe, Izukanji; Wyss, Natascha; Clough-Gorr, Kerri M.; Egger, Matthias; Chi, Benjamin H.; Bohlius, Julia

2014-01-01

Background The risk of Kaposi sarcoma (KS) among HIV-infected persons on antiretroviral therapy (ART) is not well defined in resource-limited settings. We studied KS incidence rates and associated risk factors in children and adults on ART in Southern Africa. Methods We included patient data of six ART programs in Botswana, South Africa, Zambia, and Zimbabwe. We estimated KS incidence rates in patients on ART measuring time from 30 days after ART initiation to KS diagnosis, last follow-up visit, or death. We assessed risk factors (age, sex, calendar year, WHO stage, tuberculosis, and CD4 counts) using Cox models. Findings We analyzed data from 173,245 patients (61% female, 8% children aged <16 years) who started ART between 2004 and 2010. 564 incident cases were diagnosed during 343,927 person-years (pys). KS incidence rate overall was 164/100,000 pys (95% confidence interval [CI] 151–178). The incidence rate was highest 30 to 90 days after ART initiation (413/100,000 pys; 95% CI 342–497) and declined thereafter (86/100,000 pys[95% CI 71–105]>2 years after ART initiation). Male sex (adjusted hazard ratio [HR] 1.34; 95% CI 1.12–1.61), low current CD4 counts (≥500 cells/µL versus <50 cells/µL, adjusted HR 0.36; 95% CI 0.23–0.55) and age (5 to 9 years versus 30 to 39 years, adjusted HR 0.20; 95% CI 0.05–0.79) were relevant risk factors for developing KS. Interpretation Despite ART, KS risk in HIV-infected persons in Southern Africa remains high. Early HIV testing and maintaining high CD4 counts is needed to further reduce KS-related morbidity and mortality. PMID:25393941

Involvement of nuclear factor κB in platelet CD40 signaling.

PubMed

Hachem, Ahmed; Yacoub, Daniel; Zaid, Younes; Mourad, Walid; Merhi, Yahye

2012-08-17

CD40 ligand (CD40L) is a thrombo-inflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40L (sCD40L), which has been shown to potentiate platelet activation and aggregation, in a CD40-dependent manner, via p38 mitogen activated protein kinase (MAPK) and Rac1 signaling. In many cells, the CD40L/CD40 dyad also induces activation of nuclear factor kappa B (NF-κB). Given that platelets contain NF-κB, we hypothesized that it may be involved in platelet CD40 signaling and function. In human platelets, sCD40L induces association of CD40 with its adaptor protein the tumor necrosis factor receptor associated factor 2 and triggers phosphorylation of IκBα, which are abolished by CD40L blockade. Inhibition of IκBα phosphorylation reverses sCD40L-induced IκBα phosphorylation without affecting p38 MAPK phosphorylation. On the other hand, inhibition of p38 MAPK phosphorylation has no effect on IκBα phosphorylation, indicating a divergence in the signaling pathway originating from CD40 upon its ligation. In functional studies, inhibition of IκBα phosphorylation reverses sCD40L-induced platelet activation and potentiation of platelet aggregation in response to a sub-threshold concentration of collagen. This study demonstrates that the sCD40L/CD40 axis triggers NF-κB activation in platelets. This signaling pathway plays a critical role in platelet activation and aggregation upon sCD40L stimulation and may represent an important target against thrombo-inflammatory disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

Crammed signaling motifs in the T-cell receptor.

PubMed

Borroto, Aldo; Abia, David; Alarcón, Balbino

2014-09-01

Although the T cell antigen receptor (TCR) is long known to contain multiple signaling subunits (CD3γ, CD3δ, CD3ɛ and CD3ζ), their role in signal transduction is still not well understood. The presence of at least one immunoreceptor tyrosine-based activation motif (ITAM) in each CD3 subunit has led to the idea that the multiplication of such elements essentially serves to amplify signals. However, the evolutionary conservation of non-ITAM sequences suggests that each CD3 subunit is likely to have specific non-redundant roles at some stage of development or in mature T cell function. The CD3ɛ subunit is paradigmatic because in a relatively short cytoplasmic sequence (∼55 amino acids) it contains several docking sites for proteins involved in intracellular trafficking and signaling, proteins whose relevance in T cell activation is slowly starting to be revealed. In this review we will summarize our current knowledge on the signaling effectors that bind directly to the TCR and we will propose a hierarchy in their response to TCR triggering. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of cadmium on absorption, excretion, and distribution of nickel in rats.

PubMed

Li, Zhan; Gu, Jun-Ying; Wang, Xian-Wen; Fan, Qiao-Hui; Geng, Yan-Xia; Jiao, Zong-Xian; Hou, Yi-Ping; Wu, Wang-Suo

2010-06-01

The effects of cadmium (Cd (II)) on absorption, excretion, and distribution of nickel (Ni (II)) were studied in rats using (63)Ni-NiCl(2) as radiotracer in the presence and absence of CdCl(2), through intraperitoneal injection (i.p.). The time-concentration curves in the blood were fitted with a two-compartment model. The peak time (t ((peak))) is 0.31 h in the absence of Cd (II), and it is 5.5 h in the presence of Cd (II). The levels of nickels were higher at 3 h and lower (close to zero) at 24 h in all organs of interest, except kidneys, in the absence of Cd (II). There still residue Ni (II) at 72 h post-injection in the presence of Cd (II). The Cd (II) did effect the total Ni (II) excretion 24 h post-injection. Our study showed that cadmium has a competitive effect on the absorption of nickel and an inhibitory effect on the elimination of it, so cadmium may induce the bioaccumulation of nickel in the body.

Human CD34(lo)CD133(lo) fetal liver cells support the expansion of human CD34(hi)CD133(hi) hematopoietic stem cells.

PubMed

Yong, Kylie Su Mei; Keng, Choong Tat; Tan, Shu Qi; Loh, Eva; Chang, Kenneth Te; Tan, Thiam Chye; Hong, Wanjin; Chen, Qingfeng

2016-09-01

We have recently discovered a unique CD34(lo)CD133(lo) cell population in the human fetal liver (FL) that gives rise to cells in the hepatic lineage. In this study, we further characterized the biological functions of FL CD34(lo)CD133(lo) cells. Our findings show that these CD34(lo)CD133(lo) cells express markers of both endodermal and mesodermal lineages and have the capability to differentiate into hepatocyte and mesenchymal lineage cells by ex vivo differentiation assays. Furthermore, we show that CD34(lo)CD133(lo) cells express growth factors that are important for human hematopoietic stem cell (HSC) expansion: stem cell factor (SCF), insulin-like growth factor 2 (IGF2), C-X-C motif chemokine 12 (CXCL12), and factors in the angiopoietin-like protein family. Co-culture of autologous FL HSCs and allogenic HSCs derived from cord blood with CD34(lo)CD133(lo) cells supports and expands both types of HSCs.These findings are not only essential for extending our understanding of the HSC niche during the development of embryonic and fetal hematopoiesis but will also potentially benefit adult stem cell transplantations in clinics because expanded HSCs demonstrate the same capacity as primary cells to reconstitute the human immune system and mediate long-term hematopoiesis in vivo. Together, CD34(lo)CD133(lo) cells not only serve as stem/progenitor cells for liver development but are also an essential component of the HSC niche in the human FL.

T-cell differentiation and CD56+ levels in polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.

PubMed

Subhi, Yousif; Nielsen, Marie Krogh; Molbech, Christopher Rue; Oishi, Akio; Singh, Amardeep; Nissen, Mogens Holst; Sørensen, Torben Lykke

2017-11-20

Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (AMD) are prevalent age-related diseases characterized by exudative changes in the macula. Although they share anatomical and clinical similarities, they are also distinctly characterized by their own features, e.g. vascular abnormalities in PCV and drusen-mediated progression in neovascular AMD. PCV remains etiologically uncharacterized, and ongoing discussion is whether PCV and neovascular AMD share the same etiology or constitute two substantially different diseases. In this study, we investigated T-cell differentiation and aging profile in human patients with PCV, patients with neovascular AMD, and age-matched healthy control individuals. Fresh venous blood was prepared for flow cytometry to investigate CD4 + and CD8 + T-cell differentiation (naïve, central memory, effector memory, effector memory CD45ra + ), loss of differentiation markers CD27 and CD28, and expression of aging marker CD56. Patients with PCV were similar to the healthy controls in all aspects. In patients with neovascular AMD we found significantly accelerated T-cell differentiation (more CD28 - CD27 - cells) and aging (more CD56 + cells) in the CD8 + T-cell compartment. These findings suggest that PCV and neovascular AMD are etiologically different in terms of T cell immunity, and that neovascular AMD is associated with T-cell immunosenescence.

Fission-Fusion: A new reaction mechanism for nuclear astrophysics based on laser-ion acceleration

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

Thirolf, P. G.; Gross, M.; Allinger, K.

We propose to produce neutron-rich nuclei in the range of the astrophysical r-process around the waiting point N = 126 by fissioning a dense laser-accelerated thorium ion bunch in a thorium target (covered by a CH{sub 2} layer), where the light fission fragments of the beam fuse with the light fission fragments of the target. Via the 'hole-boring' mode of laser Radiation Pressure Acceleration using a high-intensity, short pulse laser, very efficiently bunches of {sup 232}Th with solid-state density can be generated from a Th target and a deuterated CD{sub 2} foil, both forming the production target assembly. Laser-accelerated Thmore » ions with about 7 MeV/u will pass through a thin CH{sub 2} layer placed in front of a thicker second Th foil (both forming the reaction target) closely behind the production target and disintegrate into light and heavy fission fragments. In addition, light ions (d,C) from the CD{sub 2} layer of the production target will be accelerated as well, inducing the fission process of {sup 232}Th also in the second Th layer. The laser-accelerated ion bunches with solid-state density, which are about 10{sup 14} times more dense than classically accelerated ion bunches, allow for a high probability that generated fission products can fuse again. The high ion beam density may lead to a strong collective modification of the stopping power, leading to significant range and thus yield enhancement. Using a high-intensity laser as envisaged for the ELI-Nuclear Physics project in Bucharest (ELI-NP), order-of-magnitude estimates promise a fusion yield of about 10{sup 3} ions per laser pulse in the mass range of A = 180-190, thus enabling to approach the r-process waiting point at N = 126.« less

Histologic findings in skin biopsy in a JMML rash: a case report and review of literature.

PubMed

Gupta, Rajib K; Qureshi, Amna; Choi, John K

2014-01-01

Juvenile myelomonocytic leukemia (JMML), belonging to the category of myeloproliferative/myelodysplastic syndromes, is a rare pediatric hematologic malignancy with frequent skin manifestations commonly in the form of rashes. However, these rashes are not always biopsied and their immunophenotype studied in details. We report one such case in a 2-year-old boy who presented with a 1-month history of nonresolving fever, fatigue, and pallor along with a generalized maculopapular skin rash. The child also had mild hepatomegaly. A complete blood count with differential revealed a hemoglobin value of 8.6 g/L, leukocytosis (white blood cell count of 55.3 × 109/L), absolute monocytosis (27 × 109/L), immature granulocytes, and a platelet count of 126 × 109/L. The bone marrow aspirate showed a hypercellular marrow with trilineage hematopoiesis, 10% blasts (including promonocytes), increased monocytes (46%), and dysplastic changes in the erythroid and myeloid cell lines. These findings along with absence of a BCR-ABL1 fusion gene and a hemoglobin F level of 3.4% were consistent with the diagnosis of JMML, which was confirmed by subsequent positive granulocyte macrophage-colony stimulating factor hypersensitivity and NRAS mutation studies. A skin biopsy of the rash revealed a dermal infiltrate composed predominantly of atypical monocytic cells that were positive for CD68, myeloperoxidase, and lysozyme and negative for CD117, CD1a, and S100, consistent with JMML.

Boosting airway T-regulatory cells by gastrointestinal stimulation as a strategy for asthma control.

PubMed

Strickland, D H; Judd, S; Thomas, J A; Larcombe, A N; Sly, P D; Holt, P G

2011-01-01

The hallmark of atopic asthma is transient airways hyperresponsiveness (AHR) preceded by aeroallergen-induced Th-cell activation. This is preceded by upregulation of CD86 on resident airway dendritic cells (DCs) that normally lack competence in T-cell triggering. Moreover, AHR duration is controlled via T-regulatory (Treg) cells, which can attenuate CD86 upregulation on DC. We show that airway mucosal Treg/DC interaction represents an accessible therapeutic target for asthma control. Notably, baseline airway Treg activity in sensitized rats can be boosted by microbe-derived stimulation of the gut, resulting in enhanced capacity to control CD86 expression on airway DC triggered by aeroallergen and accelerated resolution of AHR.

Study of polarization phenomena in Schottky CdTe diodes using infrared light illumination

NASA Astrophysics Data System (ADS)

Sato, Goro; Fukuyama, Taro; Watanabe, Shin; Ikeda, Hirokazu; Ohta, Masayuki; Ishikawa, Shin'nosuke; Takahashi, Tadayuki; Shiraki, Hiroyuki; Ohno, Ryoichi

2011-10-01

Schottky CdTe diode detectors suffer from a polarization phenomenon, which is characterized by degradation of the spectral properties over time following exposure to high bias voltage. This is considered attributable to charge accumulation at deep acceptor levels. A Schottky CdTe diode was illuminated with an infrared light for a certain period during a bias operation, and two opposite behaviors emerged. The detector showed a recovery when illuminated after the bias-induced polarization had completely progressed. Conversely, when the detector was illuminated before the emergence of bias-induced polarization, the degradation of the spectral properties was accelerated. Interpretation of these effects and discussion on the energy level of deep acceptors are presented.

Cadmium Exposure and Cancer Mortality in a Prospective Cohort: The Strong Heart Study

PubMed Central

Pollan, Marina; Tellez-Plaza, Maria; Francesconi, Kevin A.; Goessler, Walter; Guallar, Eliseo; Umans, Jason G.; Yeh, Jeunliang; Best, Lyle G.; Navas-Acien, Ana

2014-01-01

Background: Cadmium (Cd) is a toxic metal classified as a human carcinogen by the International Agency for Research on Cancer. Objective: We evaluated the association of long-term Cd exposure, as measured in urine, with cancer mortality in American Indians from Arizona, Oklahoma, and North and South Dakota who participated in the Strong Heart Study during 1989–1991. Methods: The Strong Heart Study was a prospective cohort study of 3,792 men and women 45–74 years of age who were followed for up to 20 years. Baseline urinary Cd (U-Cd) was measured using inductively coupled plasma mass spectrometry. We assessed cancer events by annual mortality surveillance. Results: The median (interquintile range) U-Cd concentration was 0.93 (0.55, 1.63) μg/g creatinine. After adjusting for sex, age, smoking status, cigarette pack-years, and body mass index, the adjusted hazard ratios (HRs) comparing the 80th versus the 20th percentiles of U-Cd were 1.30 (95% CI: 1.09, 1.55) for total cancer, 2.27 (95% CI: 1.58, 3.27) for lung cancer, and 2.40 (95% CI: 1.39, 4.17) for pancreatic cancer mortality. For all smoking-related cancers combined, the corresponding HR was 1.56 (95% CI: 1.24, 1.96). Cd was not significantly associated with liver, esophagus and stomach, colon and rectum, breast, prostate, kidney, or lymphatic and hematopoietic cancer mortality. On the basis of mediation analysis, we estimated that the percentage of lung cancer deaths due to tobacco smoking that could be attributed to Cd exposure was 9.0% (95% CI: 2.8, 21.8). Conclusions: Low-to-moderate Cd exposure was prospectively associated with total cancer mortality and with mortality from cancers of the lung and pancreas. The implementation of population-based preventive measures to decrease Cd exposure could contribute to reducing the burden of cancer. Citation: García-Esquinas E, Pollan M, Tellez-Plaza M, Francesconi KA, Goessler W, Guallar E, Umans JG, Yeh J, Best LG, Navas-Acien A. 2014. Cadmium exposure and cancer mortality in a prospective cohort: the Strong Heart Study. Environ Health Perspect 122:363–370; http://dx.doi.org/10.1289/ehp.1306587 PMID:24531129

Study of the key factors affecting the triple grid lifetime of the LIPS-300 ion thruster

NASA Astrophysics Data System (ADS)

Mingming, SUN; Liang, WANG; Juntai, YANG; Xiaodong, WEN; Yongjie, HUANG; Meng, WANG

2018-04-01

In order to ascertain the key factors affecting the lifetime of the triple grids in the LIPS-300 ion thruster, the thermal deformation, upstream ion density and component lifetime of the grids are simulated with finite element analysis, fluid simulation and charged-particle tracing simulation methods on the basis of a 1500 h short lifetime test. The key factor affecting the lifetime of the triple grids in the LIPS-300 ion thruster is obtained and analyzed through the test results. The results show that ion sputtering erosion of the grids in 5 kW operation mode is greater than in the case of 3 kW. In 5 kW mode, the decelerator grid shows the most serious corrosion, the accelerator grid shows moderate corrosion, and the screen grid shows the least amount of corrosion. With the serious corrosion of the grids in 5 kW operation mode, the intercept current of the acceleration and deceleration grids increases substantially. Meanwhile, the cold gap between the accelerator grid and the screen grid decreases from 1 mm to 0.7 mm, while the cold gap between the accelerator grid and the decelerator grid increases from 1 mm to 1.25 mm after 1500 h of thruster operation. At equilibrium temperature with 5 kW power, the finite element method (FEM) simulation results show that the hot gap between the screen grid and the accelerator grid reduces to 0.2 mm. Accordingly, the hot gap between the accelerator grid and the decelerator grid increases to 1.5 mm. According to the fluid method, the plasma density simulated in most regions of the discharge chamber is 1 × 1018‑8 × 1018 m‑3. The upstream plasma density of the screen grid is in the range 6 × 1017‑6 × 1018 m‑3 and displays a parabolic characteristic. The charged particle tracing simulation method results show that the ion beam current without the thermal deformation of triple grids has optimal perveance status. The ion sputtering rates of the accelerator grid hole and the decelerator hole are 5.5 × 10‑14 kg s‑1 and 4.28 × 10‑14 kg s‑1, respectively, while after the thermal deformation of the triple grids, the ion beam current has over-perveance status. The ion sputtering rates of the accelerator grid hole and the decelerator hole are 1.41 × 10‑13 kg s‑1 and 4.1 × 10‑13 kg s‑1, respectively. The anode current is a key factor for the triple grid lifetime in situations where the structural strength of the grids does not change with temperature variation. The average sputtering rates of the accelerator grid and the decelerator grid, which were measured during the 1500 h lifetime test in 5 kW operating conditions, are 2.2 × 10‑13 kg s‑1 and 7.3 × 10‑13 kg s‑1, respectively. These results are in accordance with the simulation, and the error comes mainly from the calculation distribution of the upstream plasma density of the grids.

A Meta-Analysis of Genome-Wide Association Scans Identifies IL18RAP, PTPN2, TAGAP, and PUS10 As Shared Risk Loci for Crohn's Disease and Celiac Disease

PubMed Central

Boucher, Gabrielle; Beauchamp, Claudine; Trynka, Gosia; Dubois, Patrick C.; Lagacé, Caroline; Stokkers, Pieter C. F.; Hommes, Daan W.; Barisani, Donatella; Palmieri, Orazio; Annese, Vito; van Heel, David A.; Weersma, Rinse K.; Daly, Mark J.; Wijmenga, Cisca; Rioux, John D.

2011-01-01

Crohn's disease (CD) and celiac disease (CelD) are chronic intestinal inflammatory diseases, involving genetic and environmental factors in their pathogenesis. The two diseases can co-occur within families, and studies suggest that CelD patients have a higher risk to develop CD than the general population. These observations suggest that CD and CelD may share common genetic risk loci. Two such shared loci, IL18RAP and PTPN2, have already been identified independently in these two diseases. The aim of our study was to explicitly identify shared risk loci for these diseases by combining results from genome-wide association study (GWAS) datasets of CD and CelD. Specifically, GWAS results from CelD (768 cases, 1,422 controls) and CD (3,230 cases, 4,829 controls) were combined in a meta-analysis. Nine independent regions had nominal association p-value <1.0×10−5 in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value <1×10−2 in CelD and <1×10−3 in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37×10−8 and 6.39×10−9, respectively, in the meta-analysis. The other seven had not been reported as shared loci and thus were tested in additional CelD (3,149 cases and 4,714 controls) and CD (1,835 cases and 1,669 controls) cohorts. Two of these loci, TAGAP and PUS10, showed significant evidence of replication (Bonferroni corrected p-values <0.0071) in the combined CelD and CD replication cohorts and were firmly established as shared risk loci of genome-wide significance, with overall combined p-values of 1.55×10−10 and 1.38×10−11 respectively. Through a meta-analysis of GWAS data from CD and CelD, we have identified four shared risk loci: PTPN2, IL18RAP, TAGAP, and PUS10. The combined analysis of the two datasets provided the power, lacking in the individual GWAS for single diseases, to detect shared loci with a relatively small effect. PMID:21298027

CD44 deficiency enhanced Streptococcus equi ssp. zooepidemicus dissemination and inflammation response in a mouse model.

PubMed

Fu, Qiang; Xiao, Pingping; Chen, Yaosheng; Wei, Zigong; Liu, Xiaohong

2017-12-01

Streptococcus equi ssp. zooepidemicus (S. zooepidemicus) is responsible for peritonitis, septicemia, meningitis, arthritis and several other serious diseases in various species. Recent studies have demonstrated that CD44 is implicated in the process of host defense against pathogenic microorganisms. In the present study, the role of CD44 in the host response to S. zooepidemicus infection was investigated in a mouse model. Upon intraperitoneal infection with S. zooepidemicus, the expression of CD44 on the peritoneal exudate cells from wild-type (WT) mice was increased. CD44 deficiency accelerated mortality, which was accompanied by increased peritoneal bacterial growth and dissemination to distant body sites. CD44 knock-out (KO) mice showed enhanced early inflammatory cell recruitment into the peritoneal fluid on S. zooepidemicus infection. In line with this, the expression of proinflammatory cytokines, chemokines in peritoneal exudate cells and peritoneal macrophages of CD44 KO mice were increased compared with those of WT mice. In addition, CD44 deficiency was associated with reduced expression of A20, a negative regulator in TLR signaling. Overall, the present study suggests that CD44 plays a protective role in antibacterial defense against S. zooepidemicus in mice. Copyright © 2017. Published by Elsevier Ltd.

CD147 overexpression promotes tumorigenicity in Chinese hamster ovary cells.

PubMed

Yong, Yu-Le; Liao, Cheng-Gong; Wei, Ding; Chen, Zhi-Nan; Bian, Huijie

2016-04-01

CD147 overexpresses in many epithelium-originated tumors and plays an important role in tumor migration and invasion. Most studies aim at the role of CD147 in tumor progression using tumor cell models. However, the influence of abnormal overexpression of CD147 on neoplastic transformation of normal cells is unknown. Here, the role of CD147 in malignant phenotype transformation in CHO cells was investigated. Three CHO cell lines that stably overexpressed CD147 (CHO-CD147), EGFP-CD147 (CHO-EGFP-CD147), and EGFP (CHO-EGFP) were generated by transfection of plasmids containing human CD147, EGFP-human CD147, and EGFP genes into CHO cells. Cell migration and invasion were detected by wound healing and transwell matrix penetration assay. Trypan blue exclusion, MTT, cell cycle analysis, and BrdU cell proliferation assay were used to detect cell viability and cell proliferation. Annexin V-FITC analysis was performed to detect apoptosis. We found that CD147 overexpression promoted the migration and invasion of CHO cells. CD147 accelerated the G1 to S phase transition and enhanced the CHO cell proliferation. Overexpression of CD147 inhibited both early- and late-stages of apoptosis of CHO-CD147 cells, which is caused by serum deprivation. CHO-EGFP-CD147 cells showed an increased anchorage-independent growth compared with CHO-EGFP cells as detected by soft-agar colony formation assay. The tumors formed by CHO-CD147 cells in nude mice were larger and coupled with higher expression of proliferating cell nuclear antigen and Ki-67 than that of CHO cells. In conclusion, human CD147 overexpression induces malignant phenotype in CHO cells. © 2015 International Federation for Cell Biology.

An increase in circulating B cell-activating factor in childhood-onset ocular myasthenia gravis.

PubMed

Motobayashi, Mitsuo; Inaba, Yuji; Nishimura, Takafumi; Kobayashi, Norimoto; Nakazawa, Yozo; Koike, Kenichi

2015-04-01

Myasthenia gravis is a B cell-mediated autoimmune disorder. The pathophysiology of childhood-onset ocular myasthenia gravis remains unclear. We investigated serum B cell-activating factor levels and other immunological parameters in child patients with ocular myasthenia gravis. Blood samples were obtained from 9 children with ocular myasthenia gravis and 20 age-matched controls. We assayed serum concentrations of B cell-activating factor, anti-acetylcholine receptor antibody titers, 7 types of cytokines (interleukins-2, -4, -6, -10, and -17A; interferon-γ; tumor necrosis factor-α) as well as the percentages of peripheral blood CD4+, CD8+, and CD19+ cells. Serum B cell-activating factor levels were significantly higher before immunosuppressive therapy in patients with childhood-onset ocular myasthenia gravis than in controls and decreased after immunosuppressive therapy. A significant positive correlation was observed between serum B cell-activating factor levels and anti-acetylcholine receptor antibody titers in patients with myasthenia gravis. Serum B cell-activating factor concentrations did not correlate with the percentages of CD4+, CD8+, and CD19+ cells or the CD4+/CD8+ ratio. No significant differences were observed in the levels of the 7 different types of cytokines examined, including interleukin-17A, between preimmunosuppressive therapy myasthenia gravis patients and controls. Circulating B cell-activating factor may play a key role in the pathophysiology of childhood-onset ocular myasthenia gravis. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of a CdTe semiconductor based compact gamma camera for sentinel lymph node imaging

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

Russo, Paolo; Curion, Assunta S.; Mettivier, Giovanni

2011-03-15

Purpose: The authors assembled a prototype compact gamma-ray imaging probe (MediPROBE) for sentinel lymph node (SLN) localization. This probe is based on a semiconductor pixel detector. Its basic performance was assessed in the laboratory and clinically in comparison with a conventional gamma camera. Methods: The room-temperature CdTe pixel detector (1 mm thick) has 256x256 square pixels arranged with a 55 {mu}m pitch (sensitive area 14.08x14.08 mm{sup 2}), coupled pixel-by-pixel via bump-bonding to the Medipix2 photon-counting readout CMOS integrated circuit. The imaging probe is equipped with a set of three interchangeable knife-edge pinhole collimators (0.94, 1.2, or 2.1 mm effective diametermore » at 140 keV) and its focal distance can be regulated in order to set a given field of view (FOV). A typical FOV of 70 mm at 50 mm skin-to-collimator distance corresponds to a minification factor 1:5. The detector is operated at a single low-energy threshold of about 20 keV. Results: For {sup 99m}Tc, at 50 mm distance, a background-subtracted sensitivity of 6.5x10{sup -3} cps/kBq and a system spatial resolution of 5.5 mm FWHM were obtained for the 0.94 mm pinhole; corresponding values for the 2.1 mm pinhole were 3.3x10{sup -2} cps/kBq and 12.6 mm. The dark count rate was 0.71 cps. Clinical images in three patients with melanoma indicate detection of the SLNs with acquisition times between 60 and 410 s with an injected activity of 26 MBq {sup 99m}Tc and prior localization with standard gamma camera lymphoscintigraphy. Conclusions: The laboratory performance of this imaging probe is limited by the pinhole collimator performance and the necessity of working in minification due to the limited detector size. However, in clinical operative conditions, the CdTe imaging probe was effective in detecting SLNs with adequate resolution and an acceptable sensitivity. Sensitivity is expected to improve with the future availability of a larger CdTe detector permitting operation at shorter distances from the patient skin.« less

A proinflammatory CD4+ T cell phenotype in gestational diabetes mellitus.

PubMed

Sheu, Angela; Chan, Yixian; Ferguson, Angela; Bakhtyari, Mohammad B; Hawke, Wendy; White, Chris; Chan, Yuk Fun; Bertolino, Patrick J; Woon, Heng G; Palendira, Umaimainthan; Sierro, Frederic; Lau, Sue Mei

2018-07-01

Numerous adaptations of the maternal immune system are necessary during pregnancy to maintain immunological tolerance to the semi-allogeneic fetus. Several complications of pregnancy have been associated with dysregulation of these adaptive mechanisms. While gestational diabetes mellitus (GDM) has been associated with upregulation of circulating inflammatory factors linked to innate immunity, polarisation of the adaptive immune system has not been extensively characterised in this condition. We aimed to characterise pro- and anti-inflammatory CD4 + (T helper [Th]) T cell subsets in women with GDM vs women without GDM (of similar BMI), during and after pregnancy, and examine the relationship between CD4 + subsets and severity of GDM. This is a prospective longitudinal case-control study of 55 women with GDM (cases) and 65 women without GDM (controls) at a tertiary maternity hospital. Quantification of proinflammatory (Th17, Th17.1, Th1) and anti-inflammatory (regulatory T cell [Treg]) CD4 + T cell subsets was performed on peripheral blood at 37 weeks gestation and 7 weeks postpartum, and correlated with clinical characteristics and measures of blood glucose. Women with GDM had a significantly greater percentage of Th17 (median 2.49% [interquartile range 1.62-4.60] vs 1.85% [1.13-2.98], p = 0.012) and Th17.1 (3.06% [1.30-4.33] vs 1.55% [0.65-3.13], p = 0.006) cells compared with the control group of women without GDM. Women with GDM also had higher proinflammatory cell ratios (Th17:Treg, Th17.1:Treg and Th1:Treg) in pregnancy compared with the control group of women without GDM. In the control group, there was a statistically significant independent association between 1 h glucose levels in the GTT and Th17 cell percentages, and also between 2 h glucose levels and percentage of Th17 cells. The percentage of Th17 cells and the Th17:Treg ratio declined significantly after delivery in women with GDM, whereas this was not the case with the control group of women. Nevertheless, a milder inflammatory phenotype persisted after delivery (higher Th17:Treg ratio) in women with GDM vs women without. Dysregulation of adaptive immunity supports a novel paradigm of GDM that extends beyond hyperglycaemia and altered innate immunity.

Exploring the clonal evolution of CD133/aldehyde-dehydrogenase-1 (ALDH1)-positive cancer stem-like cells from primary to recurrent high-grade serous ovarian cancer (HGSOC). A study of the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium.

PubMed

Ruscito, Ilary; Cacsire Castillo-Tong, Dan; Vergote, Ignace; Ignat, Iulia; Stanske, Mandy; Vanderstichele, Adriaan; Ganapathi, Ram N; Glajzer, Jacek; Kulbe, Hagen; Trillsch, Fabian; Mustea, Alexander; Kreuzinger, Caroline; Benedetti Panici, Pierluigi; Gourley, Charlie; Gabra, Hani; Kessler, Mirjana; Sehouli, Jalid; Darb-Esfahani, Silvia; Braicu, Elena Ioana

2017-07-01

High-grade serous ovarian cancer (HGSOC) causes 80% of all ovarian cancer (OC) deaths. In this setting, the role of cancer stem-like cells (CSCs) is still unclear. In particular, the evolution of CSC biomarkers from primary (pOC) to recurrent (rOC) HGSOCs is unknown. Aim of this study was to investigate changes in CD133 and aldehyde dehydrogenase-1 (ALDH1) CSC biomarker expression in pOC and rOC HGSOCs. Two-hundred and twenty-four pOC and rOC intrapatient paired tissue samples derived from 112 HGSOC patients were evaluated for CD133 and ALDH1 expression using immunohistochemistry (IHC); pOCs and rOCs were compared for CD133 and/or ALDH1 levels. Expression profiles were also correlated with patients' clinicopathological and survival data. Some 49.1% of the patient population (55/112) and 37.5% (42/112) pOCs were CD133+ and ALDH1+ respectively. CD133+ and ALDH1+ samples were detected in 33.9% (38/112) and 36.6% (41/112) rOCs. CD133/ALDH1 coexpression was observed in 23.2% (26/112) and 15.2% (17/112) of pOCs and rOCs respectively. Pairwise analysis showed a significant shift of CD133 staining from higher (pOCs) to lower expression levels (rOCs) (p < 0.0001). Furthermore, all CD133 + pOC patients were International Federation of Gynaecology and Obstetrics (FIGO)-stage III/IV (p < 0.0001) and had significantly worse progression-free interval (PFI) (p = 0.04) and overall survival (OS) (p = 0.02). On multivariate analysis, CD133/ALDH1 coexpression in pOCs was identified as independent prognostic factor for PFI (HR: 1.64; 95% CI: 1.03-2.60; p = 0.036) and OS (HR: 1.71; 95% CI: 1.01-2.88; p = 0.045). Analysis on 52 pts patients with known somatic BRCA status revealed that BRCA mutations did not influence CSC biomarker expression. The study showed that CD133/ALDH1 expression impacts HGSOC patients' survival and first suggests that CSCs might undergo phenotypic change during the disease course similarly to non stem-like cancer cells, providing also a first evidence that there is no correlation between CSCs and BRCA status. Copyright © 2017 Elsevier Ltd. All rights reserved.

Optimization of electrostatic dual-grid beam-deflection system

NASA Technical Reports Server (NTRS)

Hudson, W. R.; Lathem, W. C.; Power, J. L.; Banks, B. A.

1972-01-01

Tests were performed to minimize accelerator grid erosion of a 5-cm diameter Kaufman ion thruster due to direct beam impingement. Several different screen hole diameters, pillow-shape-square screen holes, and dished screen grids were tried. The optimization was accomplished by copper plating the accelerator grid before testing each grid configuration on a thruster for a 2-hour run. The thruster beam sputtered copper and molybdenum from the accelerator grid where the beam impinged. The observed erosion patterns and measured accelerator currents were used to determine how to modify the accelerator system. The lowest erosion was obtained for a 50-percent open area pillow-shape-square-aperture screen grid, dished 0.043 centimeter convex toward the accelerator grid, which was positioned with the center of the screen grid 0.084 centimeter from the accelerator grid. During this investigation the accelerator current was reduced from 120 to 55 microamperes and was also more uniformly distributed over the area of the accelerator grid.

Unimpaired Autoreactive T-Cell Traffic Within the Central Nervous System During Tumor Necrosis Factor Receptor-Mediated inhibition of Experimental Autoimmune Encephalomyelitis

NASA Astrophysics Data System (ADS)

Korner, Heinrich; Goodsall, Anna L.; Lemckert, Frances A.; Scallon, Bernard J.; Ghrayeb, John; Ford, Andrew L.; Sedgwick, Jonathon D.

1995-11-01

The critical role of tumor necrosis factor (TNF) as a mediator in autoimmune inflammatory processes is evident from in vivo studies with TNF-blocking agents. However, the mechanisms by which TNF, and possibly also its homologue lymphotoxin α, contributes to development of pathology in rheumatoid arthritis and Crohn disease and in animal models like experimental autoimmune encephalomyelitis is unclear. Possibilities include regulation of vascular adhesion molecules enabling leukocyte movement into tissues or direct cytokine-mediated effector functions such as mediation of tissue damage. Here we show that administration of a TNF receptor (55 kDa)-IgG fusion protein prevented clinical signs of actively induced experimental autoimmune encephalomyelitis. Significantly, the total number of CD4^+ T lymphocytes isolated from the central nervous system of clinically healthy treated versus diseased control animals was comparable. By using a CD45 congenic model of passively transferred experimental autoimmune encephalomyelitis to enable tracking of myelin basic protein-specific effector T lymphocytes, prevention of clinical signs of disease was again demonstrated in treated animals but without quantitative or qualitative impediment to the movement of autoreactive T lymphocytes to and within the central nervous system. Thus, despite the uninterrupted movement of specific T lymphocytes into the target tissue, subsequent disease development was blocked. This provides compelling evidence for a direct effector role of TNF/lymphotoxin α in autoimmune tissue damage.

Secreted Klotho Attenuates Inflammation-Associated Aortic Valve Fibrosis in Senescence-Accelerated Mice P1.

PubMed

Chen, Jianglei; Fan, Jun; Wang, Shirley; Sun, Zhongjie

2018-05-01

Senescence-accelerated mice P1 (SAMP1) is an aging model characterized by shortened lifespan and early signs of senescence. Klotho is an aging-suppressor gene. The purpose of this study is to investigate whether in vivo expression of secreted klotho ( Skl ) gene attenuates aortic valve fibrosis in SAMP1 mice. SAMP1 mice and age-matched (AKR/J) control mice were used. SAMP1 mice developed obvious fibrosis in aortic valves, namely fibrotic aortic valve disease. Serum level of Skl was decreased drastically in SAMP1 mice. Expression of MCP-1 (monocyte chemoattractant protein 1), ICAM-1 (intercellular adhesion molecule 1), F4/80, and CD68 was increased in aortic valves of SAMP1 mice, indicating inflammation. An increase in expression of α-smooth muscle actin (myofibroblast marker), transforming growth factorβ-1, and scleraxis (a transcription factor of collagen synthesis) was also found in aortic valves of SAMP1 mice, suggesting that accelerated aging is associated with myofibroblast transition and collagen gene activation. We constructed adeno-associated virus 2 carrying mouse Skl cDNA for in vivo expression of Skl. Skl gene delivery effectively increased serum Skl of SAMP1 mice to the control level. Skl gene delivery inhibited inflammation and myofibroblastic transition in aortic valves and attenuated fibrotic aortic valve disease in SAMP1 mice. It is concluded that senescence-related fibrotic aortic valve disease in SAMP1 mice is associated with a decrease in serum klotho leading to inflammation, including macrophage infiltration and transforming growth factorβ-1/scleraxis-driven myofibroblast differentiation in aortic valves. Restoration of serum Skl levels by adeno-associated virus 2 carrying mouse Skl cDNA effectively suppresses inflammation and myofibroblastic transition and attenuates aortic valve fibrosis. Skl may be a potential therapeutic target for fibrotic aortic valve disease. © 2018 American Heart Association, Inc.

Regulatory T Cells in Patients with Idiopathic Thrombocytopenic Purpura.

PubMed

Akyol Erikçi, Alev; Karagöz, Bülent; Bilgi, Oğuz

2016-06-05

Immune thrombocytopenic purpura (ITP) is an immune-mediated bleeding disorder in which platelets are opsonized by autoantibodies and destroyed by an Fc receptor-mediated phagocytosis by the reticuloendothelial system within the spleen. Autoimmune processes are also considered in the pathogenesis of this disorder. CD4+CD25+FoxP3+ regulatory T (Treg) cells and CD8+CD28- Treg cells have roles in autoimmune diseases. We investigated these regulatory cells in ITP patients. We included 22 ITP patients and 16 age-matched healthy subjects. CD4+CD25+FoxP3+ Treg cells and CD8+CD28- cells were investigated by three-color flow cytometry. The ratios of these cell populations to total lymphocytes were calculated. Statistical analysis was carried out with the Mann-Whitney U test. CD4+CD25+ Treg cells were 9.69±3.70% and 12.99±5.58% in patients with ITP and controls, respectively. CD4+CD25highFoxP3+ cells were 27.72±19.74% and 27.55±23.98% in ITP patients and controls, respectively. The percentages of both of these cell types were not statistically significant when compared to the control group. We did not find any differences in ratios of CD4+CD25+FoxP3+ Treg cells or CD8+CD28- T cells in lymphocytes between patients and healthy subjects. We conclude that these circulatory cells are not different in ITP, but further studies are needed to explore the putative roles of these regulatory cells.

The Antagonistic Effect of Selenium on Cadmium-Induced Damage and mRNA Levels of Selenoprotein Genes and Inflammatory Factors in Chicken Kidney Tissue.

PubMed

Wang, Xinyue; Bao, Rongkun; Fu, Jing

2018-02-01

Selenium (Se) is a necessary trace mineral in the diet of humans and animals. Cadmium (Cd) is a toxic heavy metal that can damage animal organs, especially the kidneys. Antagonistic interactions between Se and Cd have been reported in previous studies. However, little is known about the effects of Se against Cd toxicity and on the mRNA levels of 25 selenoprotein genes and inflammatory factors in chicken kidneys. In the current study, we fed chickens with a Se-treated, Cd-treated, or Se/Cd treated diet for 90 days. We then analyzed the mRNA expression of inflammatory factors (including prostaglandin E synthase (PTGES), nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2)) and 25 selenoprotein genes (Gpx1, Gpx2, Gpx3, Gpx4, Txnrd1, Txnrd2, Txnrd3, Dio1, Dio2, Dio3, SPS2, Sepp1, SelPb, Sep15, Selh, Seli, Selm, Selo, Sels, Sepx1, Selu, Selk, Selw, Seln, Selt). The results demonstrated that Cd exposure increased the Cd content in the chicken kidneys, renal tubular epithelial cells underwent denaturation and necrosis, and the tubules became narrow or disappeared. However, Se supplementation reduced the Cd content in chicken kidneys and induced normal development of renal tubular epithelial cells. In addition, we also observed that Se alleviated the Cd-induced increase in the mRNA levels of inflammatory factors and ameliorated the Cd-induced downtrend in the mRNA levels of 25 selenoprotein genes in chicken kidneys.

Predictors of CD4:CD8 ratio normalization and its effect on health outcomes in the era of combination antiretroviral therapy.

PubMed

Leung, Victor; Gillis, Jennifer; Raboud, Janet; Cooper, Curtis; Hogg, Robert S; Loutfy, Mona R; Machouf, Nima; Montaner, Julio S G; Rourke, Sean B; Tsoukas, Chris; Klein, Marina B

2013-01-01

HIV leads to CD4:CD8 ratio inversion as immune dysregulation progresses. We examined the predictors of CD4:CD8 normalization after combination antiretroviral therapy (cART) and determined whether normalization is associated with reduced progression to AIDS-defining illnesses (ADI) and death. A Canadian cohort of HIV-positive adults with CD4:CD8<1.2 prior to starting cART from 2000-2010 were analyzed. Predictors of (1) reaching a CD4:CD8 ≥ 1.2 on two separate follow-up visits >30 days apart, and (2) ADI and death from all causes were assessed using adjusted proportional hazards models. 4206 patients were studied for a median of 2.77 years and 306 (7.2%) normalized their CD4:CD8 ratio. Factors associated with achieving a normal CD4:CD8 ratio were: baseline CD4+ T-cells >350 cells/mm(3), baseline CD8+ T-cells <500 cells/mm(3), time-updated HIV RNA suppression, and not reporting sex with other men as a risk factor. There were 213 ADIs and 214 deaths in 13476 person-years of follow-up. Achieving a normal CD4:CD8 ratio was not associated with time to ADI/death. In our study, few individuals normalized their CD4:CD8 ratios within the first few years of initiating modern cART. This large study showed no additional short-term predictive value of the CD4:CD8 ratio for clinical outcomes after accounting for other risk factors including age and HIV RNA.

Age-related skeletal muscle decline is similar in HIV-infected and uninfected individuals.

PubMed

Yarasheski, Kevin E; Scherzer, Rebecca; Kotler, Donald P; Dobs, Adrian S; Tien, Phyllis C; Lewis, Cora E; Kronmal, Richard A; Heymsfield, Steven B; Bacchetti, Peter; Grunfeld, Carl

2011-03-01

Skeletal muscle (SM) mass decreases with advanced age and with disease in HIV infection. It is unknown whether age-related muscle loss is accelerated in the current era of antiretroviral therapy and which factors might contribute to muscle loss among HIV-infected adults. We hypothesized that muscle mass would be lower and decline faster in HIV-infected adults than in similar-aged controls. Whole-body (1)H-magnetic resonance imaging was used to quantify regional and total SM in 399 HIV-infected and 204 control men and women at baseline and 5 years later. Multivariable regression identified associated factors. At baseline and Year 5, total SM was lower in HIV-infected than control men. HIV-infected women were similar to control women at both time points. After adjusting for demographics, lifestyle factors, and total adipose tissue, HIV infection was associated with lower Year 5 SM in men and higher SM in women compared with controls. Average overall 5-year change in total SM was small and age related, but rate of change was similar in HIV-infected and control men and women. CD4 count and efavirenz use in HIV-infected participants were associated with increasing SM, whereas age and stavudine use were associated with decreasing SM. Muscle mass was lower in HIV-infected men compared with controls, whereas HIV-infected women had slightly higher SM than control women after multivariable adjustment. We found evidence against substantially faster SM decline in HIV infected versus similar-aged controls. SM gain was associated with increasing CD4 count, whereas stavudine use may contribute to SM loss.

An Evil Backstage Manipulator: Psychological Factors Correlated with Health-Related Quality of Life in Chinese Patients with Crohn's Disease

PubMed Central

Liu, Song; Hong, Zhiwu; Li, Xiaoting; Yao, Min; Yan, Dongsheng; Ren, Huajian; Wu, Xiuwen; Wang, Gefei; Gu, Guosheng; Xia, Qiuyuan; Han, Gang; Li, Jieshou

2013-01-01

Health-related quality of life (HRQoL) is recommended as one of essential parameters to evaluate treatment effect and clinical outcome in patients with Crohn's disease (CD). Recent studies reported that psychological factors might play a role in HRQoL in Western and American CD patients. Sufficient evidences in Chinese CD patients are still unavailable. This study is dedicated to investigate the correlation of various psychological factors with HRQoL in Chinese CD patients. We prospectively collected 40 active and 40 quiescent CD patients in China and found that psychological factors, especially neuroticism and anxiety, significantly correlate with and affect HRQoL in both active and quiescent CD groups. This is the first report revealing correlation between psychological factors and HRQoL in Chinese CD patients. Therefore, we assume that our results can contribute to a better understanding of etiology and tailoring of management in Chinese patients with Crohn's disease and are beneficial to our colleagues to compare the heterogeneous characteristics of Crohn's disease in different ethnic groups. PMID:24453858

Central memory CD8+ T lymphocytes mediate lung allograft acceptance

PubMed Central

Krupnick, Alexander Sasha; Lin, Xue; Li, Wenjun; Higashikubo, Ryuiji; Zinselmeyer, Bernd H.; Hartzler, Hollyce; Toth, Kelsey; Ritter, Jon H.; Berezin, Mikhail Y.; Wang, Steven T.; Miller, Mark J.; Gelman, Andrew E.; Kreisel, Daniel

2014-01-01

Memory T lymphocytes are commonly viewed as a major barrier for long-term survival of organ allografts and are thought to accelerate rejection responses due to their rapid infiltration into allografts, low threshold for activation, and ability to produce inflammatory mediators. Because memory T cells are usually associated with rejection, preclinical protocols have been developed to target this population in transplant recipients. Here, using a murine model, we found that costimulatory blockade–mediated lung allograft acceptance depended on the rapid infiltration of the graft by central memory CD8+ T cells (CD44hiCD62LhiCCR7+). Chemokine receptor signaling and alloantigen recognition were required for trafficking of these memory T cells to lung allografts. Intravital 2-photon imaging revealed that CCR7 expression on CD8+ T cells was critical for formation of stable synapses with antigen-presenting cells, resulting in IFN-γ production, which induced NO and downregulated alloimmune responses. Thus, we describe a critical role for CD8+ central memory T cells in lung allograft acceptance and highlight the need for tailored approaches for tolerance induction in the lung. PMID:24569377

Using corona discharge-ion mobility spectrometry for detection of 2,4,6-Trichloroanisole.

PubMed

Lichvanová, Zuzana; Ilbeigi, Vahideh; Sabo, Martin; Tabrizchi, Mahmoud; Matejčík, Stefan

2014-09-01

In this work possible application of the corona discharge-ion mobility spectrometer (CD-IMS) for detection of 2,4,6-Trichloroanisole (TCA) has been investigated. We applied CD-IMS interfaced with orthogonal acceleration time of flight mass spectrometer (CD-IMS-oaTOF) to study the ion processes within the CD-IMS technique. The CD-IMS instrument was operated in two modes, (i) standard and (ii) reverse flow modes resulting in different chemical ionisation schemes by NO3(-)(HNO3)n (n=0,1,2) and O2(-)(H2O)n (n=0,1,2), respectively. The O2(-)(H2O)n ionisation was associated with formation of Cl(-) and (TCA-CH3)(-) ions from TCA. The NO3(-)(HNO3)n ionisation, resulted in formation of NO3(-)(HNO3)(TCA-Cl) adduct ions. Limit of detection (LOD) for TCA was determined in gas (100 ppb) and solid phases (150 ng). Copyright © 2014 Elsevier B.V. All rights reserved.

Comparative Analysis of Cellular and Growth Factor Composition in Bone Marrow Aspirate Concentrate and Platelet-Rich Plasma.

PubMed

Sugaya, Hisashi; Yoshioka, Tomokazu; Kato, Toshiki; Taniguchi, Yu; Kumagai, Hiroshi; Hyodo, Kojiro; Ohneda, Osamu; Yamazaki, Masashi; Mishima, Hajime

2018-01-01

The purpose of this study was to quantify the stem cell and growth factor (GF) contents in the bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) prepared from whole blood using a protocol established in our laboratory. We examined 10 patients with osteonecrosis of the femoral head who were treated by autologous BMAC transplantation at our hospital between January 2015 and June 2015. We quantified CD34+ and CD31-CD45-CD90+CD105+ cells in BMAC and PRP by flow cytometry. Additionally, we measured various GFs, that is, basic fibroblast growth factor (b-FGF), platelet-derived growth factor-BB (PDGF-BB), vascular endothelial growth factor (VEGF), transforming growth factor- β 1 (TGF- β 1), and bone morphogenetic protein-2 (BMP-2) in BMAC and PRP using enzyme-linked immunosorbent assays and statistical analyses. CD34+ and CD31-45-90+105+ cells accounted for approximately 1.9% and 0.03% of cells in BMAC and no cells in PRP. The concentration of b-FGF was higher in BMAC than in PRP ( P < 0.001), whereas no significant differences in the levels of PDGF-BB, VEGF, TGF- β 1, and BMP-2 were observed between the two types of sample. BMAC had an average of 1.9% CD34+ and 0.03% CD31-45-90+105+ cells and higher levels of b-FGF than those of PRP.

Potential of Taraxacum mongolicum Hand-Mazz for accelerating phytoextraction of cadmium in combination with eco-friendly amendments.

PubMed

Wei, Shuhe; Wang, Shanshan; Zhou, Qixing; Zhan, Jie; Ma, Lihui; Wu, Zhijie; Sun, Tieheng; Prasad, M N V

2010-09-15

Phytoextraction and phytostabilization are well-established sub-processes of phytoremediation that are being followed for in situ remediation of soils contaminated with toxic metals. Taraxacum mongolicum Hand-Mazz, a newly reported Cd accumulator has shown considerable potential for phytoextracting Cd. This paper investigated the effects of urea and chicken manure on T. mongolicum phytoextracting Cd from soil using pot culture experiments. The results showed that urea application did not affect the Cd concentrations in root, leaf, inflorescence and shoot of T. mongolicum, but chicken manure significantly decreased them (p<0.05) by 23.5%, 31.5%, 24.8% and 30.4% owing to decreased extractable Cd. Urea and chicken manure significantly increased (p<0.05) the phytoextraction capacities (microg pot(-1)) of T. mongolicum to Cd by 3-5-fold due to the increase in shoot biomass (increased 4-7 folds). Further, addition of urea and chicken manure increased organic matter, nitrogen, phosphorus and potassium, the microorganism count, urease and phosphatase activities of soil indicating their eco-friendly function. Urea is ideal for optimizing phytoextraction of T. mongolicum to Cd, while chicken manure is appropriate for phytostabilization. Copyright 2010 Elsevier B.V. All rights reserved.

Synthesis, crystal structure and electronic structure of the binary phase Rh{sub 2}Cd{sub 5}

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

Koley, Biplab; Chatterjee, S.; Jana, Partha P., E-mail: ppj@chem.iitkgp.ernet.in

2017-02-15

A new phase in the Rh-Cd binary system - Rh{sub 2}Cd{sub 5} has been identified and characterized by single crystal X-ray diffraction and Energy dispersive X-ray analysis. The stoichiometric compound Rh{sub 2}Cd{sub 5} crystallizes with a unit cell containing 14 atoms, in the orthorhombic space group Pbam (55). The crystal structure of Rh{sub 2}Cd{sub 5} can be described as a defect form of the In{sub 3}Pd{sub 5} structure with ordered vacancies, formed of two 2D atomic layers with the stacking sequence: ABAB. The A type layers consist of (3.6.3.6)-Kagomé nets of Cd atoms while the B type layers consist ofmore » (3{sup 5}) (3{sup 7})- nets of both Cd and Rh atoms. The stability of this line phase is investigated by first principle electronic structure calculations on the model of ordered Rh{sub 2}Cd{sub 5}. - Graphical abstract: (3.6.3.6)-Kagomé nets of cadmium atoms (top) and (3{sup 5}) (3{sup 7})- nets of both cadmium and rhodium atoms (bottom) in the structure of Rh{sub 2}Cd{sub 5}.« less

A Critical Role for CD200R Signaling in Limiting the Growth and Metastasis of CD200+ Melanoma.

PubMed

Liu, Jin-Qing; Talebian, Fatemeh; Wu, Lisha; Liu, Zhihao; Li, Ming-Song; Wu, Laichu; Zhu, Jianmin; Markowitz, Joseph; Carson, William E; Basu, Sujit; Bai, Xue-Feng

2016-08-15

CD200 is a cell surface glycoprotein that functions through engaging CD200R on cells of the myeloid lineage and inhibits their functions. Expression of CD200 was implicated in a variety of human cancer cells, including melanoma cells; however, its roles in tumor growth and immunity are not clearly understood. In this study, we used CD200R-deficient mice and the B16 tumor model to evaluate this issue. We found that CD200R-deficient mice exhibited accelerated growth of CD200(+), but not CD200(-), B16 tumors. Strikingly, CD200R-deficient mice receiving CD200(+) B16 cells i.v. exhibited massive tumor growth in multiple organs, including liver, lung, kidney, and peritoneal cavity, whereas the growth of the same tumors in wild-type mice was limited. CD200(+) tumors grown in CD200R-deficient mice contained higher numbers of CD11b(+)Ly6C(+) myeloid cells, exhibited increased expression of VEGF and HIF1α genes with increased angiogenesis, and showed significantly reduced infiltration of CD4(+) and CD8(+) T cells, presumably as the result of reduced expression of T cell chemokines, such as CXCL9 and CXCL16. The liver from CD200R-deficient mice, under metastatic growth of CD200(+) tumors, contained significantly increased numbers of CD11b(+)Gr1(-) myeloid cells and Foxp3(+) regulatory T cells and reduced numbers of NK cells. Liver T cells also had a reduced capacity to produce IFN-γ or TNF-α. Taken together, we revealed a critical role for CD200R signaling in limiting the growth and metastasis of CD200(+) tumors. Thus, targeting CD200R signaling may potentially interfere with the metastatic growth of CD200(+) tumors, like melanoma. Copyright © 2016 by The American Association of Immunologists, Inc.

Involvement of nuclear factor {kappa}B in platelet CD40 signaling

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

Hachem, Ahmed; Yacoub, Daniel; Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1

Highlights: Black-Right-Pointing-Pointer sCD40L induces TRAF2 association to CD40 and NF-{kappa}B activation in platelets. Black-Right-Pointing-Pointer I{kappa}B{alpha} phosphorylation downstream of CD40L/CD40 signaling is independent of p38 MAPK phosphorylation. Black-Right-Pointing-Pointer I{kappa}B{alpha} is required for sCD40L-induced platelet activation and potentiation of aggregation. -- Abstract: CD40 ligand (CD40L) is a thrombo-inflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40L (sCD40L), which has been shown to potentiate platelet activation and aggregation, in a CD40-dependent manner, via p38 mitogen activated protein kinase (MAPK) and Rac1 signaling. In many cells, the CD40L/CD40 dyad also induces activation of nuclear factor kappa B (NF-{kappa}B). Givenmore » that platelets contain NF-{kappa}B, we hypothesized that it may be involved in platelet CD40 signaling and function. In human platelets, sCD40L induces association of CD40 with its adaptor protein the tumor necrosis factor receptor associated factor 2 and triggers phosphorylation of I{kappa}B{alpha}, which are abolished by CD40L blockade. Inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced I{kappa}B{alpha} phosphorylation without affecting p38 MAPK phosphorylation. On the other hand, inhibition of p38 MAPK phosphorylation has no effect on I{kappa}B{alpha} phosphorylation, indicating a divergence in the signaling pathway originating from CD40 upon its ligation. In functional studies, inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced platelet activation and potentiation of platelet aggregation in response to a sub-threshold concentration of collagen. This study demonstrates that the sCD40L/CD40 axis triggers NF-{kappa}B activation in platelets. This signaling pathway plays a critical role in platelet activation and aggregation upon sCD40L stimulation and may represent an important target against thrombo-inflammatory disorders.« less

Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells

PubMed Central

Libro, Rosaliana; Scionti, Domenico; Diomede, Francesca; Marchisio, Marco; Grassi, Gianpaolo; Pollastro, Federica; Piattelli, Adriano; Bramanti, Placido; Mazzon, Emanuela; Trubiani, Oriana

2016-01-01

Human Gingival Mesenchymal Stem Cells (hGMSCs) are multipotential cells that can expand and differentiate in culture under specific and standardized conditions. In the present study, we have investigated whether in vitro pre-treatment of hGMSCs with Cannabidiol (CBD) can influence their expression profile, improving the therapeutic potential of this cell culture. Following CBD treatment (5 μM) for 24 h, gene expression analysis through Next Generation Sequencing (NGS) has revealed several genes differentially expressed between CBD-treated hGMSCs (CBD-hGMSCs) and control cells (CTR-hGMSCs) that were linked to inflammation and apoptosis. In particular, we have demonstrated that CBD treatment in hGMSCs prevented the activation of the NALP3-inflammasome pathway by suppressing the levels of NALP3, CASP1, and IL18, and in parallel, inhibited apoptosis, as demonstrated by the suppression of Bax. CBD treatment was also able to modulate the expression of the well-known mesenchymal stem cell markers (CD13, CD29, CD73, CD44, CD90, and CD166), and other surface antigens. Specifically, CBD led to the downregulation of genes codifying for antigens involved in the activation of the immune system (CD109, CD151, CD40, CD46, CD59, CD68, CD81, CD82, CD99), while it led to the upregulation of those implicated in the inhibition of the immune responses (CD47, CD55, CD276). In conclusion, the present study will provide a new simple and reproducible method for preconditioning hGMSCs with CBD, before transplantation, as an interesting strategy for improving the hGMSCs molecular phenotype, reducing the risk of immune or inflammatory reactions in the host, and in parallel, for increasing their survival and thus, their long-term therapeutic efficacy. PMID:27932991

Psychometric properties of Connor-Davidson Resilience Scale in a Spanish sample of entrepreneurs.

PubMed

Manzano-García, Guadalupe; Ayala Calvo, Juan Carlos

2013-01-01

The literature regarding entrepreneurship suggests that the resilience of entrepreneurs may help to explain entrepreneurial success, but there is no resilience measure widely accepted by researchers. This study analyzes the psychometric properties of the Connor and Davidson Resilience Scale (CD-RISC) in a sample of Spanish entrepreneurs. A telephone survey research method was used. The participants were entrepreneurs operating in the business services sector. Interviewers telephoned a total of 900 entrepreneurs of whom 783 produced usable questionnaires. The CD-RISC was used as data collection instrument. We used principal component analysis factor and confirmatory factor analysis to determine the factor structure of the CD-RISC. Confirmatory factor analysis failed to verify the original five-factor structure of the CD-RISC, whereas principal component analysis factor yielded a 3-factor structure of resilience (hardiness, resourcefulness and optimism). In this research, 47.48% of the total variance was accounted for by three factors, and the obtained factor structure was verified through confirmatory factor analysis. The CD-RISC has been shown to be a reliable and valid tool for measuring entrepreneurs' resilience.

The relationship between proton pump inhibitor use and longitudinal change in bone mineral density: a population-based study [corrected] from the Canadian Multicentre Osteoporosis Study (CaMos).

PubMed

Targownik, Laura E; Leslie, William D; Davison, K Shawn; Goltzman, David; Jamal, Sophie A; Kreiger, Nancy; Josse, Robert G; Kaiser, Stephanie M; Kovacs, Christopher S; Prior, Jerilynn C; Zhou, Wei

2012-09-01

Proton pump inhibitor (PPI) use has been identified as a risk factor for hip and vertebral fractures. Evidence supporting a relationship between PPI use and osteoporosis remains scant. Demonstrating that PPIs are associated with accelerated bone mineral density (BMD) loss would provide supportive evidence for a mechanism through which PPIs could increase fracture risk. We used the Canadian Multicentre Osteoporosis Study data set, which enrolled a population-based sample of Canadians who underwent BMD testing of the femoral neck, total hip, and lumbar spine (L1-L4) at baseline, and then again at 5 and 10 years. Participants also reported drug use and exposure to risk factors for osteoporosis and fracture. Multivariate linear regression was used to determine the independent association of PPI exposure and baseline BMD, and on change in BMD at 5 and 10 years. In all, 8,340 subjects were included in the baseline analysis, with 4,512 (55%) undergoing year 10 BMD testing. After adjusting for potential confounders, PPI use was associated with significantly lower baseline BMD at the femoral neck and total hip. PPI use was not associated with a significant acceleration in covariate-adjusted BMD loss at any measurement site after 5 and 10 years of follow-up. PPI users had lower BMD at baseline than PPI non-users, but PPI use over 10 years did not appear to be associated with accelerated BMD loss. The reasons for discordant findings between PPI use at baseline and during follow-up require further study.

Accelerated Aging Test for Plastic Scintillator Gamma Ray Detectors

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

Kouzes, Richard T.

Polyvinyl toluene (PVT) and polystyrene (PS), collectively referred to as “plastic scintillator,” are synthetic polymer materials used to detect gamma radiation, and are commonly used in instrumentation. Recent studies have revealed that plastic scintillator undergoes an environmentally related material degradation that adversely affects performance under certain conditions and histories. A significant decrease in gamma ray sensitivity has been seen in some detectors in systems as they age. The degradation of sensitivity of plastic scintillator over time is due to a variety of factors, and the term “aging” is used to encompass all factors. Some plastic scintillator samples show no agingmore » effects (no significant change in sensitivity over more than 10 years), while others show severe aging (significant change in sensitivity in less than 5 years). Aging effects arise from weather (variations in heat and humidity), chemical exposure, mechanical stress, light exposure, and loss of volatile components. The damage produced by these various causes can be cumulative, causing observable damage to increase over time. Damage may be reversible up to some point, but becomes permanent under some conditions. It has been demonstrated that exposure of plastic scintillator in an environmental chamber to 30 days of high temperature and humidity (90% relative humidity and 55°C) followed by a single cycle to cold temperature (-30°C) will produce severe fogging in all PVT samples. This thermal cycle will be referred to as the “Accelerated Aging Test.” This document describes the procedure for performing this Accelerated Aging Test.« less

Does an Alzheimer's disease susceptibility gene influence the cognitive effects of cancer therapy?

PubMed

Caselli, Richard J

2014-10-01

The apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor for Alzheimer's disease (AD). APOE e4 carriers suffer greater morbidity from head trauma, stroke, and carbon monoxide poisoning, yet possible interactions between APOE genotype and cancer therapy on cognition are unclear. Neuropathological and biomarker studies of young asymptomatic APOE e4 carriers that show elevated neocortical amyloid and medial temporal neurofibrillary tangles and longitudinal neuropsychological studies that show accelerated memory decline beginning around age 55-60 years define preclinical AD and have set the stage for assessing the potential adverse cognitive effects of cancer therapy in APOE e4 carriers. © 2013 Wiley Periodicals, Inc.

Investigation of charge stripping scheme for uranium ions at 1-20 MeV/nucleon

NASA Astrophysics Data System (ADS)

Kuboki, Hironori; Harada, Hiroyuki; Saha, Pranab K.

2018-05-01

We investigated a possibility to obtain charge distributions of uranium ions under the conditions to meet the requirements of the booster synchrotron proposed for heavy ion acceleration at J-PARC. The charge distribution is expected to have a width as narrow as possible to realize multi-charge acceleration. The main candidate of stripping material is a carbon foil because we can obtain narrower distributions than gas stripper and a lot of data is available. Besides that, the thickness of the stripping material should be less than 142 μg cm-2 because the energy loss in the stripping material would be compensated by an auxiliary accelerating cavity in the synchrotron ring. We studied the impact energy with which the charge distribution attains equilibrium within this thickness and has the narrowest width. The width is estimated over 1-20 MeV/nucleon by the calculation using the ionization and electron capture cross sections. Scaling factors are introduced to reproduce the experimental data and are determined to be 2.0 and 0.08 for the cross sections of ionization and electron capture, respectively. We concluded that the narrowest width can be obtained at 5.5 MeV/nucleon with a 109-μg cm-2-thick carbon foil.

Cd immobilization and reduced tissue Cd accumulation of rice (Oryza sativa wuyun-23) in the presence of heavy metal-resistant bacteria.

PubMed

Li, Ya; Pang, Hai-Dong; He, Lin-Yan; Wang, Qi; Sheng, Xia-Fang

2017-04-01

Two metal-resistant Bacillus megaterium H3 and Neorhizobium huautlense T1-17 were investigated for their immobilization of Cd in solution and tissue Cd accumulation of rice (Oryza sativa wuyun-23) in the Cd-contaminated soil. Strains H3 and T1-17 decreased 79-96% of water-soluble Cd in solution and increased grain biomass in the high Cd-contaminated soil. Inoculation with H3 and T1-17 significantly decreased the root (ranging from 25% to 58%), above-ground tissue (ranging from 13% to 34%), and polished rice (ranging from 45% to 72%) Cd contents as well as Cd bioconcentration factor of the rice compared to the controls. Furthermore, H3 and T1-17 significantly reduced the exchangeable Cd content of the rhizosphere soils compared with the controls. Notably, strain T1-17 had significantly higher ability to reduce Cd bioconcentration factor and polished rice Cd uptake than strain H3. The results demonstrated that H3 and T1-17 decreased the tissue (especially polished rice) Cd uptake by decreasing Cd availability in soil and Cd bioconcentration factor and the effect on the reduced polished rice Cd uptake was dependent on the strains. The results may provide an effective synergistic bioremediation of Cd-contaminated soils in the bacteria and rice plants and bacterial-assisted safe production of rice in Cd-contaminated soils. Copyright © 2016 Elsevier Inc. All rights reserved.

Bean Metal-Responsive Element-Binding Transcription Factor Confers Cadmium Resistance in Tobacco1

PubMed Central

Sun, Na; Liu, Meng; Zhang, Wentao; Yang, Wanning; Bei, Xiujuan; Ma, Hui; Qiao, Fan; Qi, Xiaoting

2015-01-01

Cadmium (Cd) is highly toxic to plants. Modulation of Cd-responsive transcription is an important way for Cd detoxification in plants. Metal-responsive element (MRE) is originally described in animal metallothionein genes. Although functional MREs also exist in Cd-regulated plant genes, specific transcription factors that bind MRE to regulate Cd tolerance have not been identified. Previously, we showed that Cd-inducible bean (Phaseolus vulgaris) stress-related gene2 (PvSR2) produces a short (S) PvSR2 transcript (S-PvSR2) driven by an intronic promoter. Here, we demonstrate that S-PvSR2 encodes a bean MRE-binding transcription factor1 (PvMTF-1) that confers Cd tolerance in tobacco (Nicotiana tabacum). PvMTF-1 expression was up-regulated by Cd at the levels of RNA and protein. Importantly, expression of PvMTF-1 in tobacco enhanced Cd tolerance, indicating its role in regulating Cd resistance in planta. This was achieved through direct regulation of a feedback-insensitive Anthranilate Synthase α-2 chain gene (ASA2), which catalyzes the first step for tryptophan biosynthesis. In vitro and in vivo DNA-protein interaction studies further revealed that PvMTF-1 directly binds to the MRE in the ASA2 promoter, and this binding depends on the zinc finger-like motif of PvMTF-1. Through modulating ASA2 up-regulation by Cd, PvMTF-1 increased free tryptophan level and subsequently reduced Cd accumulation, thereby enhancing Cd tolerance of transgenic tobacco plants. Consistent with this observation, tobacco transiently overexpressing ASA2 also exhibited increased tolerance to Cd. We conclude that PvMTF-1 is a zinc finger-like transcription factor that links MRE to Cd resistance in transgenic tobacco through activation of tryptophan biosynthesis. PMID:25624396

IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

PubMed Central

Sebina, Ismail; James, Kylie R.; Soon, Megan S. F.; Best, Shannon E.; Montes de Oca, Marcela; Amante, Fiona H.; Thomas, Bryce S.; Beattie, Lynette; Souza-Fonseca-Guimaraes, Fernando; Smyth, Mark J.; Hertzog, Paul J.; Hill, Geoffrey R.; Engwerda, Christian R.

2016-01-01

Parasite-specific antibodies protect against blood-stage Plasmodium infection. However, in malaria-endemic regions, it takes many months for naturally-exposed individuals to develop robust humoral immunity. Explanations for this have focused on antigenic variation by Plasmodium, but have considered less whether host production of parasite-specific antibody is sub-optimal. In particular, it is unclear whether host immune factors might limit antibody responses. Here, we explored the effect of Type I Interferon signalling via IFNAR1 on CD4+ T-cell and B-cell responses in two non-lethal murine models of malaria, P. chabaudi chabaudi AS (PcAS) and P. yoelii 17XNL (Py17XNL) infection. Firstly, we demonstrated that CD4+ T-cells and ICOS-signalling were crucial for generating germinal centre (GC) B-cells, plasmablasts and parasite-specific antibodies, and likewise that T follicular helper (Tfh) cell responses relied on B cells. Next, we found that IFNAR1-signalling impeded the resolution of non-lethal blood-stage infection, which was associated with impaired production of parasite-specific IgM and several IgG sub-classes. Consistent with this, GC B-cell formation, Ig-class switching, plasmablast and Tfh differentiation were all impaired by IFNAR1-signalling. IFNAR1-signalling proceeded via conventional dendritic cells, and acted early by limiting activation, proliferation and ICOS expression by CD4+ T-cells, by restricting the localization of activated CD4+ T-cells adjacent to and within B-cell areas of the spleen, and by simultaneously suppressing Th1 and Tfh responses. Finally, IFNAR1-deficiency accelerated humoral immune responses and parasite control by boosting ICOS-signalling. Thus, we provide evidence of a host innate cytokine response that impedes the onset of humoral immunity during experimental malaria. PMID:27812214

Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

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

Fang, Zhong-Ze; Department of Toxicology, School of Public Health, Tianjin Medical University, Tianjin; Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian

Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showedmore » that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4{sup +} naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. - Highlights: • CPT-11 is an effective anticancer drug, but induced toxicity limits its application in the clinic. • CPT-11 decreased IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes. • CPT-11 altered the composition of bile acid metabolites, notably DCA and TDCA in liver, bile and intestine. • DCA and TDCA potentiated CPT-11-induced suppression of IL-10 secretion by active CD4{sup +} naive T cells.« less

Coupling complement regulators to immunoglobulin domains generates effective anti-complement reagents with extended half-life in vivo

PubMed Central

HARRIS, C L; WILLIAMS, A S; LINTON, S M; MORGAN, B P

2002-01-01

Complement activation and subsequent generation of inflammatory molecules and membrane attack complex contributes to the pathology of a number of inflammatory and degenerative diseases, including arthritis, glomerulonephritis and demyelination. Agents that specifically inhibit complement activation might prove beneficial in the treatment of these diseases. Soluble recombinant forms of the naturally occurring membrane complement regulatory proteins (CRP) have been exploited for this purpose. We have undertaken to design better therapeutics based on CRP. Here we describe the generation of soluble, recombinant CRP comprising rat decay accelerating factor (DAF) or rat CD59 expressed as Fc fusion proteins, antibody-like molecules comprising two CRP moieties in place of the antibody Fab arms (CRP-Ig). Reagents bearing DAF on each arm (DAF-Ig), CD59 on each arm (CD59-Ig) and a hybrid reagent containing both DAF and CD59 were generated. All three reagents inhibited C activation in vitro. Compared with soluble CRP lacking Fc domains, activity was reduced, but was fully restored by enzymatic release of the regulator from the Ig moiety, implicating steric constraints in reducing functional activity. In vivo studies showed that DAF-Ig, when compared to soluble DAF, had a much extended half-life in the circulation in rats and concomitantly caused a sustained reduction in plasma complement activity. When given intra-articularly to rats in a model of arthritis, DAF-Ig significantly reduced severity of disease. The data demonstrate the potential of CRP-Ig as reagents for sustained therapy of inflammatory disorders, including arthritis, but emphasize the need for careful design of fusion proteins to retain function. PMID:12165074

Granulocyte-colony stimulating factor and stem cell factor are the crucial factors in long-term culture of human primitive hematopoietic cells supported by a murine stromal cell line.

PubMed

Nishi, N; Ishikawa, R; Inoue, H; Nishikawa, M; Kakeda, M; Yoneya, T; Tsumura, H; Ohashi, H; Yamaguchi, Y; Motoki, K; Sudo, T; Mori, K J

1996-09-01

The findings that murine marrow stromal cell line MS-5 supported the proliferation of human lineage-negative (Lin-) CD34+CD38- bone marrow cells in long-term culture have been reported. In this study, we analyzed this proliferating activity of MS-5-conditioned medium (CM) on human primitive hematopoietic cells. When Lin-CD34+CD38- cells of normal human cord blood cells were co-cultured with MS-5, colony forming cells (CFCs) were maintained over 7 weeks in vitro. Prevention of contact between MS-5 and Lin-CD34+CD38- cells by using membrane filter (0.45 micron) was negligible for this activity. This indicated that the activity of MS-5 on human primitive hematopoietic cells is a soluble factor(s) secreted from MS-5, which is not induced by the contact between MS-5 and Lin-CD34+CD38- cells. We tried to purify this soluble activity. An active material with a molecular weight of about 150 kDa, determined by gel filtration chromatography, solely supported the growth of Lin-CD34+CD38- cells and Mo7e, a human megakaryocytic cell line. This activity not only reacted with anti-mouse stem cell factor (mSCF) antibody on Western blots, but it was also neutralized in the presence of anti-mSCF antibody. Another active material with a molecular weight of about 20-30 kDa synergized with mSCF to stimulate the growth of Lin-CD34+CD38- cells but failed to do so alone, although this synergy was inhibited in the presence of soluble mouse granulocyte-colony stimulating factor (mG-CSF) receptor, which is a chimeric protein consisting of the extracellular domain of mG-CSF receptor and the Fe region of human IgG1. In addition, the latter molecule supported the growth of the G-CSF dependent cell line FD/GR3, which is a murine myeloid leukemia cell line, FDC-P2, transfected with mG-CSF receptor cDNA. Adding of anti-mSCF antibody and soluble mG-CSF receptor to the culture completely abrogated the activity of MS-5-CM. Recombinant (r) mSCF and rmG-CSF had synergistic activity on the growth of Lin-CD34+CD38- cells. These results indicated that the activity on Lin-CD34+CD38- cells included in MS-5-CM is based upon the synergistic effects of mSCF and mG-CSF.

The development of human mast cells. An historical reappraisal

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

Ribatti, Domenico, E-mail: domenico.ribatti@uniba.it

2016-03-15

The understanding of mast cell (MC) differentiation is derived mainly from in vitro studies of different stages of stem and progenitor cells. The hematopoietic lineage development of human MCs is unique compared to other myeloid-derived cells. Human MCs originate from CD34{sup +}/CD117{sup +}/CD13{sup +}multipotent hematopoietic progenitors, which undergo transendothelial recruitment into peripheral tissues, where they complete differentiation. Stem cell factor (SCF) is a major chemotactic factor for MCs and their progenitors. SCF also elicits cell-cell and cell-substratum adhesion, facilitates the proliferation, and sustains the survival, differentiation, and maturation, of MCs. Because MC maturation is influenced by local microenvironmental factors, differentmore » MC phenotypes can develop in different tissues and organs. - Highlights: • Human mast cells originate from CD34/CD117/CD13 positive multipotent hematopoietic progenitors. • Stem cell factor is a major chemotactic factor for mast cells and their progenitors. • Different mast cell phenotypes can develop in different tissues and organs.« less

Single Particle Tracking reveals two distinct environments for CD4 receptors at the surface of living T lymphocytes

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

Mascalchi, Patrice; Lamort, Anne Sophie; Salome, Laurence

2012-01-06

Highlights: Black-Right-Pointing-Pointer We studied the diffusion of single CD4 receptors on living lymphocytes. Black-Right-Pointing-Pointer This study reveals that CD4 receptors have either a random or confined diffusion. Black-Right-Pointing-Pointer The dynamics of unconfined CD4 receptors was accelerated by a temperature raise. Black-Right-Pointing-Pointer The dynamics of confined CD4 receptors was unchanged by a temperature raise. Black-Right-Pointing-Pointer Our results suggest the existence of two different environments for CD4 receptors. -- Abstract: We investigated the lateral diffusion of the HIV receptor CD4 at the surface of T lymphocytes at 20 Degree-Sign C and 37 Degree-Sign C by Single Particle Tracking using Quantum Dots. Wemore » found that the receptors presented two major distinct behaviors that were not equally affected by temperature changes. About half of the receptors showed a random diffusion with a diffusion coefficient increasing upon raising the temperature. The other half of the receptors was permanently or transiently confined with unchanged dynamics on raising the temperature. These observations suggest that two distinct subpopulations of CD4 receptors with different environments are present at the surface of living T lymphocytes.« less

CD4 T Follicular Helper Cells and HIV Infection: Friends or Enemies?

PubMed

Moukambi, Félicien; Rodrigues, Vasco; Fortier, Yasmina; Rabezanahary, Henintsoa; Borde, Chloé; Krust, Bernard; Andreani, Guadalupe; Silvestre, Ricardo; Petrovas, Constantinos; Laforge, Mireille; Estaquier, Jérôme

2017-01-01

Follicular T helper (Tfh) cells, a subset of CD4 T lymphocytes, are essential for memory B cell activation, survival, and differentiation and assist B cells in the production of antigen-specific antibodies. Work performed in recent years pointed out the importance of Tfh cells in the context of HIV and SIV infections. The importance of tissue distribution of Tfh is also an important point since their frequency differs between peripheral blood and lymph nodes compared to the spleen, the primary organ for B cell activation, and differentiation. Our recent observations indicated an early and profound loss of splenic Tfh cells. The role of transcriptional activator and repressor factors that control Tfh differentiation is also discussed in the context of HIV/SIV infection. Because Tfh cells are important for B cell differentiation and antibody production, accelerating the Tfh responses early during HIV/SIV infection could be promising as novel immunotherapeutic approach or alternative vaccine strategies. However, because Tfh cells are infected during the HIV/SIV infection and represent a reservoir, this may interfere with HIV vaccine strategy. Thus, Tfh represent the good and bad guys during HIV infection.

CD4 T Follicular Helper Cells and HIV Infection: Friends or Enemies?

PubMed Central

Moukambi, Félicien; Rodrigues, Vasco; Fortier, Yasmina; Rabezanahary, Henintsoa; Borde, Chloé; Krust, Bernard; Andreani, Guadalupe; Silvestre, Ricardo; Petrovas, Constantinos; Laforge, Mireille; Estaquier, Jérôme

2017-01-01

Follicular T helper (Tfh) cells, a subset of CD4 T lymphocytes, are essential for memory B cell activation, survival, and differentiation and assist B cells in the production of antigen-specific antibodies. Work performed in recent years pointed out the importance of Tfh cells in the context of HIV and SIV infections. The importance of tissue distribution of Tfh is also an important point since their frequency differs between peripheral blood and lymph nodes compared to the spleen, the primary organ for B cell activation, and differentiation. Our recent observations indicated an early and profound loss of splenic Tfh cells. The role of transcriptional activator and repressor factors that control Tfh differentiation is also discussed in the context of HIV/SIV infection. Because Tfh cells are important for B cell differentiation and antibody production, accelerating the Tfh responses early during HIV/SIV infection could be promising as novel immunotherapeutic approach or alternative vaccine strategies. However, because Tfh cells are infected during the HIV/SIV infection and represent a reservoir, this may interfere with HIV vaccine strategy. Thus, Tfh represent the good and bad guys during HIV infection. PMID:28265271

UV-CD12: synchrotron radiation circular dichroism beamline at ANKA

PubMed Central

Bürck, Jochen; Roth, Siegmar; Windisch, Dirk; Wadhwani, Parvesh; Moss, David; Ulrich, Anne S.

2015-01-01

Synchrotron radiation circular dichroism (SRCD) is a rapidly growing technique for structure analysis of proteins and other chiral biomaterials. UV-CD12 is a high-flux SRCD beamline installed at the ANKA synchrotron, to which it had been transferred after the closure of the SRS Daresbury. The beamline covers an extended vacuum-UV to near-UV spectral range and has been open for users since October 2011. The current end-station allows for temperature-controlled steady-state SRCD spectroscopy, including routine automated thermal scans of microlitre volumes of water-soluble proteins down to 170 nm. It offers an excellent signal-to-noise ratio over the whole accessible spectral range. The technique of oriented circular dichroism (OCD) was recently implemented for determining the membrane alignment of α-helical peptides and proteins in macroscopically oriented lipid bilayers as mimics of cellular membranes. It offers improved spectral quality <200 nm compared with an OCD setup adapted to a bench-top instrument, and accelerated data collection by a factor of ∼3. In addition, it permits investigations of low hydrated protein films down to 130 nm using a rotatable sample cell that avoids linear dichroism artifacts. PMID:25931105

No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity

PubMed Central

Garcia-Etxebarria, Koldo; Bracho, María Alma; Galán, Juan Carlos; Pumarola, Tomàs; Castilla, Jesús; Ortiz de Lejarazu, Raúl; Rodríguez-Dominguez, Mario; Quintela, Inés; Bonet, Núria; Garcia-Garcerà, Marc; Domínguez, Angela; González-Candelas, Fernando; Calafell, Francesc

2015-01-01

While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10−8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course. PMID:26379185

Expansion of CD11b+Ly6Ghigh and CD11b+CD49d+ myeloid cells with suppressive potential in mice with chronic inflammation and light-at-night-induced circadian disruption.

PubMed

Perfilyeva, Yuliya V; Abdolla, Nurshat; Ostapchuk, Yekaterina O; Tleulieva, Raikhan; Krasnoshtanov, Vladimir C; Belyaev, Nikolai N

2017-08-01

Myeloid-derived suppressor cells (MDSCs) are important negative regulators of immune processes in cancer and other pathological conditions. We suggested that MDSCs play a key role in pathogenesis of chronic inflammation, which precedes and, to a certain extent, induces carcinogenesis. The present study aimed at investigation of MDSCs arising during chronic inflammation and light-at-night (LN)-induced stress, which is shown to accelerate chronic diseases. 67 CD-1 mice and in vitro MDSC cultures. Adjuvant arthritis was induced by a subdermal injection of complete Freund's adjuvant. LN was induced by illumination of 750 lx at night. Flow cytometry for evaluation of cell phenotypes and MTT standard test for cell proliferation were used. Increased levels of splenic CD11b + Ly6G high and CD11b + CD49d + myeloid cells possessing suppressive potential in mice with adjuvant arthritis are shown. LN amplifies the process of CD11b + Ly6G high expansion in mice with adjuvant arthritis. Expression of CD62L and CD195 is elevated on the myeloid cells during exposure to LN. Our study raises the possibility that CD11b + Ly6G high and CD11b + CD49d + MDSCs play an important role in the induction of immunosuppressive environment typical for chronic inflammation. Also, LN can affect immune responses during chronic inflammation through recruitment of MDSCs from the bone marrow.

Conformational Ensemble of the Poliovirus 3CD Precursor Observed by MD Simulations and Confirmed by SAXS: A Strategy to Expand the Viral Proteome?

PubMed

Moustafa, Ibrahim M; Gohara, David W; Uchida, Akira; Yennawar, Neela; Cameron, Craig E

2015-11-23

The genomes of RNA viruses are relatively small. To overcome the small-size limitation, RNA viruses assign distinct functions to the processed viral proteins and their precursors. This is exemplified by poliovirus 3CD protein. 3C protein is a protease and RNA-binding protein. 3D protein is an RNA-dependent RNA polymerase (RdRp). 3CD exhibits unique protease and RNA-binding activities relative to 3C and is devoid of RdRp activity. The origin of these differences is unclear, since crystal structure of 3CD revealed "beads-on-a-string" structure with no significant structural differences compared to the fully processed proteins. We performed molecular dynamics (MD) simulations on 3CD to investigate its conformational dynamics. A compact conformation of 3CD was observed that was substantially different from that shown crystallographically. This new conformation explained the unique properties of 3CD relative to the individual proteins. Interestingly, simulations of mutant 3CD showed altered interface. Additionally, accelerated MD simulations uncovered a conformational ensemble of 3CD. When we elucidated the 3CD conformations in solution using small-angle X-ray scattering (SAXS) experiments a range of conformations from extended to compact was revealed, validating the MD simulations. The existence of conformational ensemble of 3CD could be viewed as a way to expand the poliovirus proteome, an observation that may extend to other viruses.

CD147 reinforces [Ca2+]i oscillations and promotes oncogenic progression in hepatocellular carcinoma.

PubMed

Tang, Juan; Guo, Yun-Shan; Yu, Xiao-Ling; Huang, Wan; Zheng, Ming; Zhou, Ying-Hui; Nan, Gang; Wang, Jian-Chao; Yang, Hai-Jiao; Yu, Jing-Min; Jiang, Jian-Li; Chen, Zhi-Nan

2015-10-27

Oscillations in intracellular Ca2+ concentrations ([Ca2+]i) mediate various cellular function. Although it is known that [Ca2+]i oscillations are susceptible to dysregulation in tumors, the tumor-specific regulators of [Ca2+]i oscillations are poorly characterized. We discovered that CD147 promotes hepatocellular carcinoma (HCC) metastasis and proliferation by enhancing the amplitude and frequency of [Ca2+]i oscillations in HCC cells. CD147 activates two distinct signaling pathways to regulate [Ca2+]i oscillations. By activating FAK-Src-IP3R1 signaling pathway, CD147 promotes Ca2+ release from endoplasmic reticulum (ER) and enhances the amplitude of [Ca2+]i oscillations. Furthermore, CD147 accelerates ER Ca2+refilling and enhances the frequency of [Ca2+]i oscillations through activating CaMKP-PAK1-PP2A-PLB-SERCA signaling pathway. Besides, CD147-promoted ER Ca2+ release and refilling are tightly regulated by changing [Ca2+]i. CD147 may activate IP3R1 channel under low [Ca2+]i conditions and CD147 may activate SERCA pump under high [Ca2+]i conditions. CD147 deletion suppresses HCC tumorigenesis and increases the survival rate of liver-specific CD147 knockout mice by regulating [Ca2+]i oscillations in vivo. Together, these results reveal that CD147 functions as a critical regulator of ER-dependent [Ca2+]i oscillations to promote oncogenic progression in HCC.

CD147 reinforces [Ca2+]i oscillations and promotes oncogenic progression in hepatocellular carcinoma

PubMed Central

Zheng, Ming; Zhou, Ying-Hui; Nan, Gang; Wang, Jian-Chao; Yang, Hai-Jiao; Yu, Jing-Min; Jiang, Jian-Li; Chen, Zhi-Nan

2015-01-01

Oscillations in intracellular Ca2+ concentrations ([Ca2+]i) mediate various cellular function. Although it is known that [Ca2+]i oscillations are susceptible to dysregulation in tumors, the tumor-specific regulators of [Ca2+]i oscillations are poorly characterized. We discovered that CD147 promotes hepatocellular carcinoma (HCC) metastasis and proliferation by enhancing the amplitude and frequency of [Ca2+]i oscillations in HCC cells. CD147 activates two distinct signaling pathways to regulate [Ca2+]i oscillations. By activating FAK-Src-IP3R1 signaling pathway, CD147 promotes Ca2+ release from endoplasmic reticulum (ER) and enhances the amplitude of [Ca2+]i oscillations. Furthermore, CD147 accelerates ER Ca2+ refilling and enhances the frequency of [Ca2+]i oscillations through activating CaMKP-PAK1-PP2A-PLB-SERCA signaling pathway. Besides, CD147-promoted ER Ca2+ release and refilling are tightly regulated by changing [Ca2+]i. CD147 may activate IP3R1 channel under low [Ca2+]i conditions and CD147 may activate SERCA pump under high [Ca2+]i conditions. CD147 deletion suppresses HCC tumorigenesis and increases the survival rate of liver-specific CD147 knockout mice by regulating [Ca2+]i oscillations in vivo. Together, these results reveal that CD147 functions as a critical regulator of ER-dependent [Ca2+]i oscillations to promote oncogenic progression in HCC. PMID:26498680

Humic substances as a washing agent for Cd-contaminated soils.

PubMed

Meng, Fande; Yuan, Guodong; Wei, Jing; Bi, Dongxue; Ok, Yong Sik; Wang, Hailong

2017-08-01

Cost-effective and eco-friendly washing agents are in demand for Cd contaminated soils. Here, we used leonardite-derived humic substances to wash different types of Cd-contaminated soils, namely, a silty loam (Soil 1), a silty clay loam (Soil 2), and a sandy loam (Soil 3). Washing conditions were investigated for their effects on Cd removal efficiency. Cadmium removal was enhanced by a high humic substance concentration, long washing time, near neutral pH, and large solution/soil ratio. Based on the tradeoff between efficiency and cost, an optimum working condition was established as follows: humic substance concentration (3150 mg C/L), solution pH (6.0), washing time (2 h) and a washing solution/soil ratio (5). A single washing removed 0.55 mg Cd/kg from Soil 1 (1.33 mg Cd/kg), 2.32 mg Cd/kg from Soil 2 (6.57 mg Cd/kg), and 1.97 mg Cd/kg from Soil 3 (2.63 mg Cd/kg). Cd in effluents was effectively treated by adding a small dose of calcium hydroxide, reducing its concentration below the discharge limit of 0.1 mg/L in China. Being cost-effective and safe, humic substances have a great potential to replace common washing agents for the remediation of Cd-contaminated soils. Besides being environmentally benign, humic substances can improve soil physical, chemical, and biological properties. Copyright © 2017 Elsevier Ltd. All rights reserved.

Brentuximab vedotin: clinical updates and practical guidance

PubMed Central

Yi, Jun Ho; Kim, Seok Jin

2017-01-01

Brentuximab vedotin (BV), a potent antibody-drug conjugate, targets the CD30 antigen. Owing to the remarkable efficacy shown in CD30-positive lymphomas, such as Hodgkin's lymphoma and systemic anaplastic large-cell lymphoma, BV was granted accelerated approval in 2011 by the US Food and Drug Administration. Thereafter, many large-scale trials in various situations have been performed, which led to extensions of the original indication. The aim of this review was to describe the latest updates on clinical trials of BV and the in-practice guidance for the use of BV. PMID:29333400

Experimental evidence of impact ignition: 100-fold increase of neutron yield by impactor collision.

PubMed

Azechi, H; Sakaiya, T; Watari, T; Karasik, M; Saito, H; Ohtani, K; Takeda, K; Hosoda, H; Shiraga, H; Nakai, M; Shigemori, K; Fujioka, S; Murakami, M; Nagatomo, H; Johzaki, T; Gardner, J; Colombant, D G; Bates, J W; Velikovich, A L; Aglitskiy, Y; Weaver, J; Obenschain, S; Eliezer, S; Kodama, R; Norimatsu, T; Fujita, H; Mima, K; Kan, H

2009-06-12

We performed integrated experiments on impact ignition, in which a portion of a deuterated polystyrene (CD) shell was accelerated to about 600 km/s and was collided with precompressed CD fuel. The kinetic energy of the impactor was efficiently converted into thermal energy generating a temperature of about 1.6 keV. We achieved a two-order-of-magnitude increase in the neutron yield by optimizing the timing of the impact collision, demonstrating the high potential of impact ignition for fusion energy production.

Epstein-Barr virus effect on frequency of functionally distinct T cell subsets in children with infectious mononucleosis.

PubMed

Sulik, Artur; Oldak, Elzbieta; Kroten, Anna; Lipska, Alina; Radziwon, Piotr

2014-09-01

Epstein-Barr virus is a common human pathogen which infects the great majority of population worldwide. A striking proliferation of CD8⁺ T cells is an immune response to EBV invasion of B lymphocytes during infectious mononucleosis. The aim of the study was to analyze frequencies of CD28⁺CD95⁻, CD28⁺CD95⁺, CD28⁻CD95⁺ T cell subsets putative naïve (T(N)), central (T(CM)) and effector memory (T(EM)) T cells in children with infectious mononucleosis. Multiparameter flow cytometric analysis of CD4⁺ and CD8⁺ T cell subsets was performed in 19 children with acute infectious mononucleosis. The CD4⁺/CD8⁺ ratio was found to be decreased (0.53) in children with infectious mononucleosis. Median T(N), T(CM), T(EM) frequencies were estimated to be 3.7, 4.5, 15.1% of CD8⁺ and 23, 59.3, 5.5% of CD4⁺ T cells, respectively. In the present study we demonstrated negative correlations between CD8⁺CD28⁺CD95⁺ and CD8⁺CD28⁻CD95⁺ T cells and both VCA IgM antibody titers and disease duration. However, no such correlation was found when subset of CD4⁺ T cells or CD8⁺CD28⁺CD95⁻ cells was compared. We conclude that there is a rapid decrease in the number of memory CD8⁺ T cells in early acute stage of infectious mononucleosis. Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Immune Response to Hepatitis B Vaccine in HIV-Infected Subjects Using Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) as a Vaccine Adjuvant: ACTG Study 5220

PubMed Central

Overton, ET; Kang, M; Peters, MG; Umbleja, T; Alston-Smith, BL; Bastow, B; Demarco-Shaw, D; Koziel, MJ; Mong-Kryspin, L; Sprenger, HL; Yu, JY; Aberg, JA

2010-01-01

HIV-infected persons are at risk for HBV co-infection which is associated with increased morbidity and mortality. Unfortunately, protective immunity following HBV vaccination in HIV-infected persons is poor. This randomized, phase II, open label study aimed to evaluate efficacy and safety of 40 mcg HBV vaccine with or without 250 mcg GM-CSF administered at day 0, weeks 4 and 12. HIV-infected individuals ≥18 years of age, CD4 count ≥200 cells/mm3, seronegative for HBV and HCV, and naïve to HBV vaccination were eligible. Primary endpoints were quantitative HBsAb titers and adverse events. The study enrolled 48 subjects. Median age and baseline CD4 were 41 years and 446 cells/mm3, 37 were on ART, and 26 subjects had undetectable VL. Vaccination was well tolerated. Seven subjects in the GM-CSF group reported transient Grade ≥2 signs/symptoms (six Grade 2, one Grade 3), mostly aches and nausea. GM-CSF had no significant effect on VL or CD4. Four weeks after vaccination, 26 subjects (59%) developed a protective antibody response (HBsAb ≥10mIU/mL; 52% in the GM-CSF arm and 65% in the control arm) without improved Ab titer in the GM-CSF versus control arm (median 11 mIU/mL vs. 92 mIU/mL, respectively). Response was more frequent in those with CD4 ≥350 cells/mm3 (64%) than with CD4 <350 cells/mm3 (50%), though not statistically significant. GM-CSF as an adjuvant did not improve the Ab titer or the development of protective immunity to HBV vaccination in those receiving an accelerated vaccine schedule. Given the common routes of transmission for HIV and HBV, additional HBV vaccine research is warranted. PMID:20600512

Boosting the efficiency of quantum dot sensitized solar cells through modulation of interfacial charge transfer.

PubMed

Kamat, Prashant V

2012-11-20

The demand for clean energy will require the design of nanostructure-based light-harvesting assemblies for the conversion of solar energy into chemical energy (solar fuels) and electrical energy (solar cells). Semiconductor nanocrystals serve as the building blocks for designing next generation solar cells, and metal chalcogenides (e.g., CdS, CdSe, PbS, and PbSe) are particularly useful for harnessing size-dependent optical and electronic properties in these nanostructures. This Account focuses on photoinduced electron transfer processes in quantum dot sensitized solar cells (QDSCs) and discusses strategies to overcome the limitations of various interfacial electron transfer processes. The heterojunction of two semiconductor nanocrystals with matched band energies (e.g., TiO(2) and CdSe) facilitates charge separation. The rate at which these separated charge carriers are driven toward opposing electrodes is a major factor that dictates the overall photocurrent generation efficiency. The hole transfer at the semiconductor remains a major bottleneck in QDSCs. For example, the rate constant for hole transfer is 2-3 orders of magnitude lower than the electron injection from excited CdSe into oxide (e.g., TiO(2)) semiconductor. Disparity between the electron and hole scavenging rate leads to further accumulation of holes within the CdSe QD and increases the rate of electron-hole recombination. To overcome the losses due to charge recombination processes at the interface, researchers need to accelerate electron and hole transport. The power conversion efficiency for liquid junction and solid state quantum dot solar cells, which is in the range of 5-6%, represents a significant advance toward effective utilization of nanomaterials for solar cells. The design of new semiconductor architectures could address many of the issues related to modulation of various charge transfer steps. With the resolution of those problems, the efficiencies of QDSCs could approach those of dye sensitized solar cells (DSSC) and organic photovoltaics.

Separator Qualification for Aerospace Nickel-cadmium Cells

NASA Technical Reports Server (NTRS)

Milden, M. J.

1984-01-01

The development plans for a new separator for nickel cadmium (NiCd) cells is described. Research includes acceptance testing, operation in a charge/discharge characterization matrix, and life testing in low earth orbit (LEO) and geosynchronous (GEO) orbit under real time and accelerated conditions.

Galectin-7 promotes proliferation and Th1/2 cells polarization toward Th1 in activated CD4+ T cells by inhibiting The TGFβ/Smad3 pathway.

PubMed

Luo, Zhenlong; Ji, Yudong; Tian, Dean; Zhang, Yong; Chang, Sheng; Yang, Chao; Zhou, Hongmin; Chen, Zhonghua Klaus

2018-06-08

Galectin-7 (Gal-7) has been associated with cell proliferation and apoptosis. It is known that Gal-7 antagonises TGFβ-mediated effects in hepatocytes by interacting with Smad3. Previously, we have demonstrated that Gal-7 is related to CD4+ T cells responses; nevertheless, its effect and functional mechanism on CD4+ T cells responses remain unclear. The murine CD4+ T cells were respectively cultured with Gal-7, anti-CD3/CD28 mAbs, or with anti-CD3/CD28 mAbs & Gal-7. The effects of Gal-7 on proliferation and the phenotypic changes in CD4+ T cells were assessed by flow cytometry. The cytokines from CD4+ T cells were analysed by quantitative real-time PCR. Subcellular localisation and expression of Smad3 were determined by immunofluorescence staining and Western blot, respectively. Gal-7 enhanced the proliferation of activated CD4+ T cells in a dose- and β-galactoside-dependent manner. Additionally, Gal-7 treatment did not change the ratio of Th2 cells in activated CD4+ T cells, while it increased the ratio of Th1 cells. Gal-7 also induced activated CD4+ T cells to produce a higher level of IFN-γ and TNF-α and a lower level of IL-10. Moreover, Gal-7 treatment significantly accelerated nuclear export of Smad3 in activated CD4+ T cells. These results revealed a novel role of Gal-7 in promoting proliferation and Th1/2 cells polarization toward Th1 in activated CD4+ T cells by inhibiting the TGFβ/Smad3 pathway. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nitric oxide modulates cadmium influx during cadmium-induced programmed cell death in tobacco BY-2 cells.

PubMed

Ma, Wenwen; Xu, Wenzhong; Xu, Hua; Chen, Yanshan; He, Zhenyan; Ma, Mi

2010-07-01

Nitric oxide (NO) is a bioactive gas and functions as a signaling molecule in plants exposed to diverse biotic and abiotic stresses including cadmium (Cd(2+)). Cd(2+) is a non-essential and toxic heavy metal, which has been reported to induce programmed cell death (PCD) in plants. Here, we investigated the role of NO in Cd(2+)-induced PCD in tobacco BY-2 cells (Nicotiana tabacum L. cv. Bright Yellow 2). In this work, BY-2 cells exposed to 150 microM CdCl(2) underwent PCD with TUNEL-positive nuclei, significant chromatin condensation and the increasing expression of a PCD-related gene Hsr203J. Accompanied with the occurring of PCD, the production of NO increased significantly. The supplement of NO by sodium nitroprusside (SNP) had accelerated the PCD, whereas the NO synthase inhibitor Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME) and NO-specific scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) alleviated this toxicity. To investigate the mechanism by which NO exerted its function, Cd(2+) concentration was measured subsequently. SNP led more Cd(2+) content than Cd(2+) treatment alone. By contrast, the prevention of NO by L-NAME decreased Cd(2+) accumulation. Using the scanning ion-selective electrode technique, we analyzed the pattern and rate of Cd(2+) fluxes. This analysis revealed the promotion of Cd(2+) influxes into cells by application of SNP, while L-NAME and cPTIO reduced the rate of Cd(2+) uptake or even resulted in net Cd(2+) efflux. Based on these founding, we concluded that NO played a positive role in CdCl(2)-induced PCD by modulating Cd(2+) uptake and thus promoting Cd(2+) accumulation in BY-2 cells.

Partition coefficient of cadmium between organic soils and bean and oat plants

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

Siddqui, M.F.R.; Courchesne, F.; Kennedy, G.

Environmental fate models require the partition coefficient data of contaminants among two or more environmental compartments. The bioaccumulation of cadmium (Cd) by bean and oat plants grown on organic soils in a controlled growth chamber was investigated to validate the plant/soil partition coefficient. Total Cd was measured in the soils and in the different parts of the plants. The mean total Cd concentrations for soil cultivated with beans and oats were 0.86 and 0.69 {micro}g/g, respectively. Selective extractants (BaCl{sub 2}, Na-pyrophosphate and HNO{sub 3}-hydroxy) were used to evaluate solid phase Cd species in the soil. In the soil cultivated withmore » bean, BaCl{sub 2} exchangeable, Na-pyrophosphate extractable and HNO{sub 3}-NH{sub 2}OH extractable Cd represented 1.2, 1.6 and 50.9% of total soil Cd, respectively. For the soil cultivated with oats, the same extractants gave values of 1.1, 1.8 and 61.9%. Cd concentration levels in bean plants followed the sequence roots > fruits = stems > leaves (p < 0.01) while the following sequence was observed for oat plants: roots > fruits > stems > leaves (p < 0.05). The partition coefficient for total Cd (Cd{sub Plant tissue}/Cd{sub Soil}) was in the range of 0.28--0.55 for bean plants and 1.03--1.86 for oat plants.« less

Effect of CdS nanocrystals on charge transport mechanism in poly(3-hexylthiophene)

NASA Astrophysics Data System (ADS)

Khan, Mohd Taukeer; Almohammedi, Abdullah

2017-08-01

The present manuscript demonstrates the optical and electrical characteristics of poly(3-hexylthiophene) (P3HT) and cadmium sulphide (CdS) hybrid nanocomposites. Optical results suggest that there is a formation of charge transfer complex (CTC) between host P3HT and guest CdS nanocrystals (NCs). Electrical properties of P3HT and P3HT-CdS thin films have been studied in hole only device configurations at different temperatures (290 K-150 K), and results were analysed by the space charge limited conduction mechanism. Density of traps and characteristic trap energy increase on incorporation of inorganic NCs in the polymer matrix, which might be due to the additional favourable energy states created by CdS NCs in the band gap of P3HT. These additional trap states assist charge carriers to move quicker which results in enhancement of hole mobility from 7 × 10-6 to 5.5 × 10-5 cm2/V s in nanocomposites. These results suggest that the P3HT-CdS hybrid system has desirable optical and electrical properties for its applications to photovoltaics devices.

Various types of stem cells, including a population of very small embryonic-like stem cells, are mobilized into peripheral blood in patients with Crohn's disease.

PubMed

Marlicz, Wojciech; Zuba-Surma, Ewa; Kucia, Magda; Blogowski, Wojciech; Starzynska, Teresa; Ratajczak, Mariusz Z

2012-09-01

Developmentally early cells, including hematopoietic stem progenitor cells (HSPCs), mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), and very small embryonic-like stem cells (VSELs), are mobilized into peripheral blood (PB) in response to tissue/organ injury. We sought to determine whether these cells are mobilized into PB in patients with Crohn's disease (CD). Twenty-five patients with active CD, 20 patients in clinical remission, and 25 age-matched controls were recruited and PB samples harvested. The circulating CD133+/Lin-/CD45+ and CD34+/Lin-/CD45+ cells enriched for HSPCs, CD105+/STRO-1+/CD45- cells enriched for MSCs, CD34+/KDR+/CD31+/CD45-cells enriched for EPCs, and small CXCR4+CD34+CD133+ subsets of Lin-CD45- cells that correspond to the population of VSELs were counted by fluorescence-activated cell sorting (FACS) and evaluated by direct immunofluorescence staining for pluripotency embryonic markers and by reverse-transcription polymerase chain reaction (RT-PCR) for expression of messenger (m)RNAs for a panel of genes expressed in intestine epithelial stem cells. The serum concentration of factors involved in stem cell trafficking, such as stromal derived factor-1 (SDF-1), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) were measured by enzyme-linked immunosorbent assay (ELISA). Our data indicate that cells expressing markers for MSCs, EPCs, and small Oct-4+Nanog+SSEA-4+CXCR4+lin-CD45- VSELs are mobilized into PB in CD. The mobilized cells also expressed at the mRNA level genes playing a role in development and regeneration of gastrointestinal epithelium. All these changes were accompanied by increased serum concentrations of VEGF and HGF. CD triggers the mobilization of MSCs, EPCs, and VSELs, while the significance and precise role of these mobilized cells in repair of damaged intestine requires further study. Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.

Garlic (Allium sativum L.) as a potential antidote for cadmium and lead intoxication: cadmium and lead distribution and analysis in different mice organs.

PubMed

Massadeh, A M; Al-Safi, S A; Momani, I F; Alomary, A A; Jaradat, Q M; AlKofahi, A S

2007-01-01

Analysis and distribution of Pb and Cd in different mice organs including liver, kidney, spleen, heart and blood were evaluated after treatment with different aqueous concentrations of garlic (12.5-100 mg/l). Atomic absorption spectrometry (AAS) was used for analysis of Pb and Cd in these organs. Treatment of Cd-Pb exposed mice with garlic (12.5-100 mg/l) reduced Pb concentrations by 44.65, 42.61, 38.4, 47.56, and 66.62% in liver, kidney, heart, spleen and blood respectively. Moreover, garlic reduced Cd levels by 72.5, 87.7, 92.6, 95.6, and 71.7% in liver, kidney, heart, spleen and blood respectively. The suppressed immune responses in mice pretreated with Cd-Pb mixture were reversed by 48.85, 55.82, 81.4 and 90.7 in the presence of 100, 50, 25, and 12.5 mg/ml of garlic extract.

Outcomes after an excisional procedure for cervical intraepithelial neoplasia in HIV-infected women

PubMed Central

Reimers, Laura L.; Sotardi, Susan; Daniel, David; Chiu, Lydia G.; Arsdale, Anne Van; Wieland, Daryl L.; Leider, Jason M.; Xue, Xiaonan; Strickler, Howard D.; Garry, David J.; Goldberg, Gary L.; Einstein, Mark H.

2011-01-01

Objective To determine predictors of treatment failure and recurrence after surgical excisional procedures for CIN in HIV-infected women. Methods A retrospective cohort study was conducted in which 136 eligible HIV-infected women treated for CIN between 1999 and 2005 were included. Data were abstracted from charts and computer databases. Treatment failures were defined as the presence of CIN 1+ at initial follow-up. Recurrences were defined as the presence of CIN 1+ subsequent to initial normal follow-up. Results Treatment failure at initial follow-up was common, occurring in 51% of CIN 1 and 55% of CIN 2+. Most lesions detected at treatment failure were high grade (>70%), regardless of the grade of initial lesion. Significant risk factors for treatment failure were loop electrosurgical excision procedure (LEEP) compared to cold knife conization (RR=1.76; 95% CI: 1.15–2.64), and low CD4+ count (p = 0.04). Among those with an initial normal clinical evaluation, 55% eventually recurred. As with treatment failure, most lesions detected at recurrence were high grade. Risk factors for recurrence included use of LEEP (hazard ratio [HR] = 3.38; 95% CI: 1.55–7.39), higher HIV RNA level, and the presence of positive margins at treatment (HR = 6.12; 95% CI: 1.90–19.73). Conclusions Most CIN treatment of HIV-infected women studied either failed or resulted in recurrence. Of particular concern, many of these subsequent lesions were high grade. Conization, however, was associated with significantly less failure/recurrence than LEEP. Clinicians treating CIN in HIV-infected women should avoid raising expectations of cure and instead focus on the achievable goal of cancer prevention until there are better therapies for this patient population. PMID:20605046

The Immune Interaction between HIV-1 Infection and Mycobacterium tuberculosis.

PubMed

Du Bruyn, Elsa; Wilkinson, Robert John

2016-12-01

The modulation of tuberculosis (TB)-induced immunopathology caused by human immunodeficiency virus (HIV)-1 coinfection remains incompletely understood but underlies the change seen in the natural history, presentation, and prognosis of TB in such patients. The deleterious combination of these two pathogens has been dubbed a "deadly syndemic," with each favoring the replication of the other and thereby contributing to accelerated disease morbidity and mortality. HIV-1 is the best-recognized risk factor for the development of active TB and accounts for 13% of cases globally. The advent of combination antiretroviral therapy (ART) has considerably mitigated this risk. Rapid roll-out of ART globally and the recent recommendation by the World Health Organization (WHO) to initiate ART for everyone living with HIV at any CD4 cell count should lead to further reductions in HIV-1-associated TB incidence because susceptibility to TB is inversely proportional to CD4 count. However, it is important to note that even after successful ART, patients with HIV-1 are still at increased risk for TB. Indeed, in settings of high TB incidence, the occurrence of TB often remains the first presentation of, and thereby the entry into, HIV care. As advantageous as ART-induced immune recovery is, it may also give rise to immunopathology, especially in the lower-CD4-count strata in the form of the immune reconstitution inflammatory syndrome. TB-immune reconstitution inflammatory syndrome will continue to impact the HIV-TB syndemic.

Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8α+ conventional dendritic cells

PubMed Central

Edelson, Brian T.; KC, Wumesh; Juang, Richard; Kohyama, Masako; Benoit, Loralyn A.; Klekotka, Paul A.; Moon, Clara; Albring, Jörn C.; Ise, Wataru; Michael, Drew G.; Bhattacharya, Deepta; Stappenbeck, Thaddeus S.; Holtzman, Michael J.; Sung, Sun-Sang J.; Murphy, Theresa L.; Hildner, Kai

2010-01-01

Although CD103-expressing dendritic cells (DCs) are widely present in nonlymphoid tissues, the transcription factors controlling their development and their relationship to other DC subsets remain unclear. Mice lacking the transcription factor Batf3 have a defect in the development of CD8α+ conventional DCs (cDCs) within lymphoid tissues. We demonstrate that Batf3−/− mice also lack CD103+CD11b− DCs in the lung, intestine, mesenteric lymph nodes (MLNs), dermis, and skin-draining lymph nodes. Notably, Batf3−/− mice displayed reduced priming of CD8 T cells after pulmonary Sendai virus infection, with increased pulmonary inflammation. In the MLNs and intestine, Batf3 deficiency resulted in the specific lack of CD103+CD11b− DCs, with the population of CD103+CD11b+ DCs remaining intact. Batf3−/− mice showed no evidence of spontaneous gastrointestinal inflammation and had a normal contact hypersensitivity (CHS) response, despite previous suggestions that CD103+ DCs were required for immune homeostasis in the gut and CHS. The relationship between CD8α+ cDCs and nonlymphoid CD103+ DCs implied by their shared dependence on Batf3 was further supported by similar patterns of gene expression and their shared developmental dependence on the transcription factor Irf8. These data provide evidence for a developmental relationship between lymphoid organ–resident CD8α+ cDCs and nonlymphoid CD103+ DCs. PMID:20351058

Genetically engineered Pseudomonas putida X3 strain and its potential ability to bioremediate soil microcosms contaminated with methyl parathion and cadmium.

PubMed

Zhang, Rong; Xu, Xingjian; Chen, Wenli; Huang, Qiaoyun

2016-02-01

A multifunctional Pseudomonas putida X3 strain was successfully engineered by introducing methyl parathion (MP)-degrading gene and enhanced green fluorescent protein (EGFP) gene in P. putida X4 (CCTCC: 209319). In liquid cultures, the engineered X3 strain utilized MP as sole carbon source for growth and degraded 100 mg L(-1) of MP within 24 h; however, this strain did not further metabolize p-nitrophenol (PNP), an intermediate metabolite of MP. No discrepancy in minimum inhibitory concentrations (MICs) to cadmium (Cd), copper (Cu), zinc (Zn), and cobalt (Co) was observed between the engineered X3 strain and its host strain. The inoculated X3 strain accelerated MP degradation in different polluted soil microcosms with 100 mg MP kg(-1) dry soil and/or 5 mg Cd kg(-1) dry soil; MP was completely eliminated within 40 h. However, the presence of Cd in the early stage of remediation slightly delayed MP degradation. The application of X3 strain in Cd-contaminated soil strongly affected the distribution of Cd fractions and immobilized Cd by reducing bioavailable Cd concentrations with lower soluble/exchangeable Cd and organic-bound Cd. The inoculated X3 strain also colonized and proliferated in various contaminated microcosms. Our results suggested that the engineered X3 strain is a potential bioremediation agent showing competitive advantage in complex contaminated environments.

Apollo(R) Thin Film Process Development: Final Technical Report, April 1998 - April 2002

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

Cunningham, D.W.

2002-10-01

BP Solar first started investigative work on CdTe photovoltaics in 1986. The module product name chosen for the CdTe devices is Apollo. The deposition method chosen was electrochemical deposition due to its simplicity and good control of stoichiometric composition. The window layer used is CdS, produced from a chemical-bath deposition. Initial work focused on increasing photovoltaic cell size from a few mm2 to 900 cm2. At BP Solar's Fairfield plant, work is focused on increasing semiconductor deposition to 1 m2. The primary objective of this subcontract is to establish the conditions required for the efficient plating of CdS/CdTe on large-area,more » transparent conducting tin-oxide-coated glass superstrate. The initial phase concentrates on superstrate sizes up to 0.55 m2. Later phases will include work on 0.94 m2 superstrates. The tasks in this subcontract have been split into four main categories: (1) CdS and CdTe film studies; (2) Enhanced laser processing; (3) Outdoor testing program for the Apollo module; and (4) Production waste abatement and closed loop study.« less

Human Uterine Leiomyoma Stem/Progenitor Cells Expressing CD34 and CD49b Initiate Tumors In Vivo

PubMed Central

Ono, Masanori; Moravek, Molly B.; Coon, John S.; Navarro, Antonia; Monsivais, Diana; Dyson, Matthew T.; Druschitz, Stacy A.; Malpani, Saurabh S.; Serna, Vanida A.; Qiang, Wenan; Chakravarti, Debabrata; Kim, J. Julie; Bulun, Serdar E.

2015-01-01

Context: Uterine leiomyoma is the most common benign tumor in reproductive-age women. Using a dye-exclusion technique, we previously identified a side population of leiomyoma cells exhibiting stem cell characteristics. However, unless mixed with mature myometrial cells, these leiomyoma side population cells did not survive or grow well in vitro or in vivo. Objective: The objective of this study was to identify cell surface markers to isolate leiomyoma stem/progenitor cells. Design: Real-time PCR screening was used to identify cell surface markers preferentially expressed in leiomyoma side population cells. In vitro colony-formation assay and in vivo tumor-regeneration assay were used to demonstrate functions of leiomyoma stem/progenitor cells. Results: We found significantly elevated CD49b and CD34 gene expression in side population cells compared with main population cells. Leiomyoma cells were sorted into three populations based on the expression of CD34 and CD49b: CD34+/CD49b+, CD34+/CD49b−, and CD34−/CD49b− cells, with the majority of the side population cells residing in the CD34+/CD49b+ fraction. Of these populations, CD34+/CD49b+ cells expressed the lowest levels of estrogen receptor-α, progesterone receptor, and α-smooth muscle actin, but the highest levels of KLF4, NANOG, SOX2, and OCT4, confirming their more undifferentiated status. The stemness of CD34+/CD49b+ cells was also demonstrated by their strongest in vitro colony-formation capacity and in vivo tumor-regeneration ability. Conclusions: CD34 and CD49b are cell surface markers that can be used to enrich a subpopulation of leiomyoma cells possessing stem/progenitor cell properties; this technique will accelerate efforts to develop new therapies for uterine leiomyoma. PMID:25658015

Sex Differences in the Blood Concentration of Tacrolimus in Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients with CYP3A5*3/*3.

PubMed

Ito, Ayano; Okada, Yuko; Hashita, Tadahiro; Aomori, Tohru; Hiromura, Keiju; Nojima, Yoshihisa; Nakamura, Tomonori; Araki, Takuya; Yamamoto, Koujirou

2017-06-01

The purpose of this study was to describe the impact of sex and cytochrome P450 3A5 (CYP3A5) variant on the blood concentration of tacrolimus in patients with systemic lupus erythematosus or rheumatoid arthritis. The blood concentration of tacrolimus (ng/mL) divided by the daily dose of tacrolimus (mg/day) and the patient's weight (kg) (C/D) was obtained from 55 patients. The C/D value was analysed according to genetic variation in CYP3A5 or ATP binding cassette subfamily B member 1 (ABCB1), sex, and age. The C/D value in the CYP3A5*3/*3 group was significantly higher than in the CYP3A5*1/*1 and *1/*3 groups (p < 0.05, effect size: d = 1.40). In the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in men than in women (p < 0.05, effect size: d = 1.78). Furthermore, in the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in women aged over 50 years than in women aged under 50 years (p < 0.05, effect size: d = 1.18). In contrast, ABCB1 genetic variations did not show any significant effect on the C/D value. Since the blood concentration of tacrolimus in patients with CYP3A5*3/*3 varies depending on sex and age, these factors should be considered when studying the difference of sex in CYP3A.

A Highly Sensitive Multi-Element HgCdTe E-APD Detector for IPDA Lidar Applications

NASA Technical Reports Server (NTRS)

Beck, Jeff; Welch, Terry; Mitra, Pradip; Reiff, Kirk; Sun, Xiaoli; Abshire, James

2014-01-01

An HgCdTe electron avalanche photodiode (e-APD) detector has been developed for lidar receivers, one application of which is integrated path differential absorption lidar measurements of such atmospheric trace gases as CO2 and CH4. The HgCdTe APD has a wide, visible to mid-wave-infrared, spectral response, high dynamic range, substantially improved sensitivity, and an expected improvement in operational lifetime. A demonstration sensor-chip assembly consisting of a 4.3 lm cutoff HgCdTe 4 9 4 APD detector array with 80 micrometer pitch pixels and a custom complementary metal-oxide-semiconductor readout integrated circuit was developed. For one typical array the APD gain was 654 at 12 V with corresponding gain normalized dark currents ranging from 1.2 fA to 3.2 fA. The 4 9 4 detector system was characterized at 77 K with a 1.55 micrometer wavelength, 1 microsecond wide, laser pulse. The measured unit gain detector photon conversion efficiency was 91.1%. At 11 V bias the mean measured APD gain at 77 K was 307.8 with sigma/mean uniformity of 1.23%. The average, noise-bandwidth normalized, system noise-equivalent power (NEP) was 1.04 fW/Hz(exp 1/2) with a sigma/mean of 3.8%. The measured, electronics-limited, bandwidth of 6.8 MHz was more than adequate for 1 microsecond pulse detection. The system had an NEP (3 MHz) of 0.4 fW/Hz(exp 1/2) at 12 V APD bias and a linear dynamic range close to 1000. A gain-independent quantum-limited SNR of 80% of full theoretical was indicative of a gain-independent excess noise factor very close to 1.0 and the expected APD mode quantum efficiency.

[Distribution of Urban Soil Heavy Metal and Pollution Evaluation in Different Functional Zones of Yinchuan City].

PubMed

Wang, You-qi; Bai, Yi-ru; Wang, Jian-yu

2016-02-15

Surface soil samples (0-20 cm) from eight different functional areas in Yinchuan city were collected. There were 10 samples respectively in each functional area. The urban soil heavy metals (Zn, Cd, Pb, Mn, Cu and Cr) pollution characteristics and sources in eight different functional areas were evaluated by mathematical statistics and geostatistical analysis method. Meanwhile, the spatial distributions of heavy metals based on the geography information system (GIS) were plotted. The average values of total Zn, Cd, Pb, Mn, Cu and Cr were 74.87, 0.15, 29.02, 553.55, 40.37 and 80.79 mg x kg(-1), respectively. The results showed that the average value of soil heavy metals was higher than the soil background value of Ningxia, which indicated accumulation of the heavy metals in urban soil. The single factor pollution index of soil heavy metals was in the sequence of Cu > Pb > Zn > Cr > Cd > Mn. The average values of total Zn, Cd, Pb and Cr were higher in north east, south west and central city, while the average values of Mn and Cu were higher in north east and central city. There was moderate pollution in road and industrial area of Yinchuan, while the other functional areas showed slight pollution according to Nemoro synthesis index. The pollution degree of different functional areas was as follows: road > industrial area > business district > medical treatment area > residential area > public park > development zone > science and education area. The results indicated that the soil heavy metal pollution condition in Yinchuan City has been affected by human activities with the development of economy.

Metal phytoremediation potential of naturally growing plants on fly ash dumpsite of Patratu thermal power station, Jharkhand, India.

PubMed

Pandey, Shikha Kumari; Bhattacharya, Tanushree; Chakraborty, Sukalyan

2016-01-01

Three naturally growing plants Ipomoea carnea, Lantana camara, and Solanum surattense were found in fly ash dumpsite of Patratu thermal power station, Jharkhand, India. They were assessed for their metal uptake potential. The fly ash was slightly alkaline with very less nitrogen and organic carbon but enriched with phosphorus and heavy metals. Lantana camara and Ipomoea carnea showed good translocation from root to shoot for most of the metals except Mn and Pb. The order of metal accumulation in stem of both the plants were Fe(205mg/kg)>Mn(65mg/kg)>Cu(22.35mg/kg)>Pb(6.6mg/kg)>Cr(3.05mg/kg)>Ni(1 mg/kg)>Cd(0.5 mg/kg) and Fe(741 mg/kg)>Mn(154.05 mg/kg)>Cu(20.75 mg/kg)>Pb(6.75 mg/kg)>Ni(4.0 mg/kg)>Cr(3.3mg/kg)>Cd(0.05mg/kg), respectively. But Solanum surattense accumulated most of the metals in roots. The order was in the following order, Mn (382.2mg/kg) >Fe (264.1mg/kg) > Cu (25.35mg/kg) >Pb (5.95 mg/kg) > Ni (1.9 mg/kg) > Cr (1.8mg/kg) > Cd (0.55 mg/kg). The order of Bioconcentration factor (BCF) in root and shoot followed almost the same order as, Mn>Fe>Ni>Pb>Cu>Cr≈ Cd in all the three species. ANOVA showed significant variation in metal accumulation by root and stem between the species. Finally, it can be concluded that Solanum surattense can be used as phytostabilizer and other two species as phytoextractor of metal for fly ash dumpsite reclamation.

Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor

PubMed Central

1994-01-01

Interleukin 15 (IL-15) is a novel cytokine that has recently been cloned and expressed. Whereas it has no sequence homology with IL-2, IL- 15 interacts with components of the IL-2 receptor (IL-2R). In the present study we performed a functional analysis of recombinant IL-15 on phenotypically and functionally distinct populations of highly purified human natural killer (NK) cells. The CD56bright subset of human NK cells constitutively expresses the high affinity IL-2R and exhibits a brisk proliferative response after the binding of picomolar amounts of IL-2. Using a proliferation assay, IL-15 demonstrated a very steep dose-response curve that was distinct from the dose-response curve for IL-2. The proliferative effects of IL-15 could be abrogated by anti-IL-2R beta (p75), but not by anti-IL-2R alpha (p55). The proliferative effects of IL-2 on CD56bright NK cells could be inhibited by both antibodies. CD56dim NK cells express the intermediate affinity IL-2R in the absence of the high affinity IL-2R. Activation of CD56dim NK cells by IL-15 was similar to that of IL-2 as measured by enhanced NK cytotoxic activity, antibody-dependent cellular cytotoxicity, and NK cell production of interferon gamma, tumor necrosis factor alpha, and granulocyte/macrophage colony-stimulating factor. The IL-15-enhanced NK cytotoxic activity could be completely blocked by anti-IL-2R beta monoclonal antibody. The binding of radiolabeled IL-2 and IL-15 to CD56dim NK cells was inhibited in the presence of anti-IL-2R beta. Scatchard analysis of radiolabeled IL-15 and IL-2 binding to NK- enriched human lymphocytes revealed the presence of high and intermediate affinity receptors for both ligands. IL-15 is a ligand that activates human NK cells through components of the IL-2R in a pattern that is similar but not identical to that of IL-2. Unlike IL-2, IL-15 is produced by activated monocytes/macrophages. The discovery of IL-15 may increase our understanding of how monocytes/macrophages participate in the regulation of NK cell function. PMID:7523571

Factor structure and individual patterns of DSM-IV conduct disorder criteria in adolescent psychiatric inpatients.

PubMed

Janson, Harald; Kjelsberg, Ellen

2006-01-01

We investigated the factor structure of the DSM-IV conduct disorder (CD) diagnostic criteria and typical individual patterns of CD subscales in an adolescent inpatient population using detailed hospital records of a Norwegian nationwide sample of 1087 adolescent psychiatric inpatients scored for the 15 DSM-IV CD criteria. Varimax rotated principal components and full-information factor analyses of 12 CD criteria were carried out separately for boys and girls employing two methods. Standardized values on three subscales of CD criteria were subjected to Ward's method of hierarchical cluster analyses followed by k-means relocation employing a double cross-replication design. Similar factor structures emerged regardless of factoring method and gender. With the exception of Criteria 8 ("Fire setting") and 14 ("Run away from home") the factor loadings for both genders were in accordance with Loeber's tripartite model, with Aggression, Delinquency, and Rule Breaking factors largely corresponding to Loeber's overt, covert and authority conflict pathways. A five-cluster solution proved highly replicable and interpretable. One cluster gathered adolescents without CD, and the remaining four described groups with different conceptually meaningful constellations of CD criteria, which were not equally prevalent in each gender. Delinquency appeared in all symptomatic clusters. The cluster analytic results highlighted typical forms of expressions of conduct problems, and the fact that these forms may not be equally prevalent in girls and boys even while the underlying structure of conduct problems may be similar across genders. Future research should address the prediction of specific outcomes from CD criteria subscales or constellations.

In vivo NIRF imaging-guided delivery of a novel NGR-VEGI fusion protein for targeting tumor vasculature.

PubMed

Ma, Wenhui; Li, Guoquan; Wang, Jing; Yang, Weidong; Zhang, Yingqi; Conti, Peter S; Chen, Kai

2014-12-01

Pathological angiogenesis is crucial in tumor growth, invasion and metastasis. Previous studies demonstrated that the vascular endothelial growth inhibitor (VEGI), a member of the tumor necrosis factor superfamily, can be used as a potent endogenous inhibitor of tumor angiogenesis. Molecular probes containing the asparagine-glycine-arginine (NGR) sequence can specifically bind to CD13 receptor which is overexpressed on neovasculature and several tumor cells. Near-infrared fluorescence (NIRF) optical imaging for targeting tumor vasculature offers a noninvasive method for early detection of tumor angiogenesis and efficient monitoring of response to anti-tumor vasculature therapy. The aim of this study was to develop a new NIRF imaging probe on the basis of an NGR-VEGI protein for the visualization of tumor vasculature. The NGR-VEGI fusion protein was prepared from prokaryotic expression, and its function was characterized in vitro. The NGR-VEGI protein was then labeled with a Cy5.5 fluorophore to afford Cy5.5-NGR-VEGI probe. Using the NIRF imaging technique, we visualized and quantified the specific delivery of Cy5.5-NGR-VEGI protein to subcutaneous HT-1080 fibrosarcoma tumors in mouse xenografts. The Cy5.5-NGR-VEGI probe exhibited rapid HT-1080 tumor targeting, and highest tumor-to-background contrast at 8 h post-injection (pi). Tumor specificity of Cy5.5-NGR-VEGI was confirmed by effective blocking of tumor uptake in the presence of unlabeled NGR-VEGI (20 mg/kg). Ex vivo NIRF imaging further confirmed in vivo imaging findings, demonstrating that Cy5.5-NGR-VEGI displayed an excellent tumor-to-muscle ratio (18.93 ± 2.88) at 8 h pi for the non-blocking group and significantly reduced ratio (4.92 ± 0.75) for the blocking group. In conclusion, Cy5.5-NGR-VEGI provided highly sensitive, target-specific, and longitudinal imaging of HT-1080 tumors. As a novel theranostic protein, Cy5.5-NGR-VEGI has the potential to improve cancer treatment by targeting tumor vasculature.

Socioeconomic Risk Factors for Celiac Disease Burden and Symptoms.

PubMed

Oza, Sveta S; Akbari, Mona; Kelly, Ciarán P; Hansen, Joshua; Theethira, Thimmaiah; Tariq, Sohaib; Dennis, Melinda; Leffler, Daniel A

2016-04-01

Celiac disease (CD) affects approximately 1% of the population and negatively affects aspects of life including physical and social function. The relationship between socioeconomic (SE) factors, symptom severity, and perceived burden of living with CD is not well understood. The objective of this study was to assess the relationships between income, symptoms, and perceived burden of CD. In this survey study conducted at a tertiary care center, 773 patients 18 years of age or more with biopsy confirmed CD were eligible to participate. Patients completed a survey with information on SE data, the validated Celiac Symptom Index (CSI), and visual analog scales (VAS) assessing overall health, CD-related health, difficulty in following a gluten-free diet (GFD), and importance of following a GFD. Three hundred forty one patients completed the survey. Higher income predicted better overall health, better CD related health, and fewer symptoms. In the logistic regression model, low income was associated with greater CD symptoms (odds ratio=6.04, P=0.002). Other factors associated with greater symptoms were younger age, poor overall health state, and more physician visits. Factors associated with increased burden of CD included hospitalizations, more symptoms, poor overall health state, and burden of following a GFD. Patients with lower incomes have worse CD-related health and greater symptoms. Those with low income had 6 times the odds of greater symptoms compared with those with high income. Our data suggest that income is associated with perceived overall health, CD-related health, and CD symptoms.

Effect of Cytomegalovirus Co-Infection on Normalization of Selected T-Cell Subsets in Children with Perinatally Acquired HIV Infection Treated with Combination Antiretroviral Therapy

PubMed Central

Kapetanovic, Suad; Aaron, Lisa; Montepiedra, Grace; Anthony, Patricia; Thuvamontolrat, Kasalyn; Pahwa, Savita; Burchett, Sandra; Weinberg, Adriana; Kovacs, Andrea

2015-01-01

Background We examined the effect of cytomegalovirus (CMV) co-infection and viremia on reconstitution of selected CD4+ and CD8+ T-cell subsets in perinatally HIV-infected (PHIV+) children ≥ 1-year old who participated in a partially randomized, open-label, 96-week combination antiretroviral therapy (cART)-algorithm study. Methods Participants were categorized as CMV-naïve, CMV-positive (CMV+) viremic, and CMV+ aviremic, based on blood, urine, or throat culture, CMV IgG and DNA polymerase chain reaction measured at baseline. At weeks 0, 12, 20 and 40, T-cell subsets including naïve (CD62L+CD45RA+; CD95-CD28+), activated (CD38+HLA-DR+) and terminally differentiated (CD62L-CD45RA+; CD95+CD28-) CD4+ and CD8+ T-cells were measured by flow cytometry. Results Of the 107 participants included in the analysis, 14% were CMV+ viremic; 49% CMV+ aviremic; 37% CMV-naïve. In longitudinal adjusted models, compared with CMV+ status, baseline CMV-naïve status was significantly associated with faster recovery of CD8+CD62L+CD45RA+% and CD8+CD95-CD28+% and faster decrease of CD8+CD95+CD28-%, independent of HIV VL response to treatment, cART regimen and baseline CD4%. Surprisingly, CMV status did not have a significant impact on longitudinal trends in CD8+CD38+HLA-DR+%. CMV status did not have a significant impact on any CD4+ T-cell subsets. Conclusions In this cohort of PHIV+ children, the normalization of naïve and terminally differentiated CD8+ T-cell subsets in response to cART was detrimentally affected by the presence of CMV co-infection. These findings may have implications for adjunctive treatment strategies targeting CMV co-infection in PHIV+ children, especially those that are now adults or reaching young adulthood and may have accelerated immunologic aging, increased opportunistic infections and aging diseases of the immune system. PMID:25794163

Nuclear factor-kappaB activation and postischemic inflammation are suppressed in CD36-null mice after middle cerebral artery occlusion.

PubMed

Kunz, Alexander; Abe, Takato; Hochrainer, Karin; Shimamura, Munehisa; Anrather, Josef; Racchumi, Gianfranco; Zhou, Ping; Iadecola, Costantino

2008-02-13

CD36, a class-B scavenger receptor involved in multiple functions, including inflammatory signaling, may also contribute to ischemic brain injury through yet unidentified mechanisms. We investigated whether CD36 participates in the molecular events underlying the inflammatory reaction that accompanies cerebral ischemia and may contribute to the tissue damage. We found that activation of nuclear factor-kappaB, a transcription factor that coordinates postischemic gene expression, is attenuated in CD36-null mice subjected to middle cerebral artery occlusion. The infiltration of neutrophils and the glial reaction induced by cerebral ischemia were suppressed. Treatment with an inhibitor of inducible nitric oxide synthase, an enzyme that contributes to the tissue damage, reduced ischemic brain injury in wild-type mice, but not in CD36 nulls. In contrast to cerebral ischemia, the molecular and cellular inflammatory changes induced by intracerebroventricular injection of interleukin-1beta were not attenuated in CD36-null mice. The findings unveil a novel role of CD36 in early molecular events leading to nuclear factor-kappaB activation and postischemic inflammation. Inhibition of CD36 signaling may be a valuable therapeutic approach to counteract the deleterious effects of postischemic inflammation.

Aminoacid N-substituted 1,4,7-triazacyclononane and 1,4,7,10-tetraazacyclododecane Zn2+, Cd2+ and Cu2+ complexes. A preparative, potentiometric titration and NMR spectroscopic study.

PubMed

Plush, Sally E; Lincoln, Stephen F; Wainwright, Kevin P

2004-05-07

The pK(a)s and Zn2+, Cd2+ and Cu2+ complexation constants (K) for 1,4,7-tris[(2''S)-acetamido-2''-(methyl-3''-phenylpropionate)]-1,4,7-triazacyclononane, 1, 1,4,7-tris[(2''S)-acetamido-2''-(1''-carboxy-3''-phenylpropane)]-1,4,7-triazacyclononane, H(3)2, 1,4,7-tris[(2''S)-acetamido-2''-(methyl-3''-(1H-3-indolyl)propionate)]-1,4,7-triazacyclononane, 3, and 1,4,7,10-tetrakis[(2''S)-acetamido-2''-(methyl-3''-phenylpropionate)]-1,4,7,10-tetraazacyclododecane, 4, 1,4,7,10-tetrakis[(2''S)-acetamido-2''-(1''-carboxy-3''-phenylpropane)]-1,4,7,10-tetraazacyclododecane, H(4)5, in 20 : 80 v/v water-methanol solution are reported. The pK(a)s within the potentiometric detection range for H(3)1(3+) = 8.69 and 3.59, for H(6)2(3+) = 9.06, 6.13, 4.93 and 4.52, H(3)3(3+) = 8.79 and 3.67, H(4)4(4+) = 8.50, 5.62 and 3.77 and for H(8)5(4+) = 9.89, 7.06, 5.53, 5.46, 4.44 and 4.26 where each tertiary amine nitrogen is protonated. The complexes of 1: [Zn(1)]2+(9.00), [Cd(1)]2+ (6.49), [Cd(H1)]3+ (4.54) and [Cu(1)]2+ (10.01) are characterized by the log(K/dm3 mol(-1)) values shown in parentheses. Analogous complexes are formed by 3 and 4: [Zn(3)]2+ (10.19), [Cd(3)]2+ (8.54), [Cu(3)]2+ (10.77), [Zn(4)]2+ (11.41) [Cd(4)]2+ (9.16), [Cd(H4)]3+ (6.16) and [Cu(4)]2+ (11.71). The tricarboxylic acid H(3)2 generates a greater variety of complexes as exemplified by: [Zn(2)-] (10.68) [Zn(H2)] (6.60) [Zn(H(2)2)+] (5.15), [Cd(2)](-) (4.99), [Cd(H2)] (4.64), [Cd(H2(2))]+ (3.99), [Cd(H(3)2)]2+ (3.55), [Cu(2)](-) (12.55) [Cu(H2)] (7.66), [Cu(H(2)2)]+ (5.54) and [Cu(2)2](4-) (3.23). The complexes of H(4)5 were insufficiently soluble to study in this way. The 1H and 13C NMR spectra of the ligands are consistent with formation of a predominant Zn2+ and Cd2+ Delta or Lambda diastereomer. The preparations of the new pendant arm macrocycles H(3)2, 3, 4 and H(4)5 are reported.

Impact of different feedstocks derived biochar amendment with cadmium low uptake affinity cultivar of pak choi (Brassica rapa ssb. chinensis L.) on phytoavoidation of Cd to reduce potential dietary toxicity.

PubMed

Yasmin Khan, Kiran; Ali, Barkat; Cui, Xiaoqiang; Feng, Ying; Yang, Xiaoe; Joseph Stoffella, Peter

2017-07-01

Biochar has become eco-friendly amendment used for phytoavoidation with low cadmium (Cd) accumulating cultivars of crops to ensure food safety in Cd contaminated soils. In this study, biochar with different waste feedstock material were evaluated for their effectiveness on essential trace metals mobility, Cd bioavailability and its accumulation in two contrasting Cd accumulating cultivars of pak choi (Brassica rapa ssp. chinensis L.) grown in Cd contaminated Mollisol soil. A greenhouse experiment was conducted with plants grown in Cd contaminated soil that had been amended with biochar derived from barley straw, tomato green waste, chicken manure, duck manure and swine manure at application rate of 0%, 2.5% and 5.0% (w/w). The results showed that soil pH was significantly increased by all treatments. Biochar increased plant dry biomass, micronutrients bioavailability with significant differences in the Cd sorption capacity, with the effectiveness higher with increasing biochar application rate. However, tomato green waste (TGW) and chicken manure (CM) derived biochar were more effective than the other biochar in reducing Cd mobilization in soil by 35-54% and 26-43% and reduced its accumulation in shoots of pak choi cultivars by 34-76% and 33-72% in low Cd accumulator cultivar and 64-85% and 55-80% in high Cd accumulator cultivar than the control. Overall, results indicate that TGW and CM biochar can efficiently immobilize Cd, thereby reducing bioavailability in Cd contaminated Mollisol soil to ensure food safety. Copyright © 2017 Elsevier Inc. All rights reserved.

Overtraining and immune system: a prospective longitudinal study in endurance athletes.

PubMed

Gabriel, H H; Urhausen, A; Valet, G; Heidelbach, U; Kindermann, W

1998-07-01

A prospective longitudinal study investigated for 19 +/- 3) months whether immunophenotypes of peripheral leukocytes were altered in periods of severe training. Leukocyte membrane antigens (CD3, CD4, CD8, CD14, CD16, CD19, CD45, CD45RO, and CD56) of endurance athletes were immunophenotyped (dual-color flow cytometry) and list mode data analyzed by a self-learning classification system in a state of an overtraining syndrome (OT; N = 15) and several occasions without symptoms of staleness (NS; N = 70). Neither at physical rest nor after a short-term highly intensive cycle ergometer exercise session at 110% of the individual anaerobic threshold did cell counts of neutrophils, T, B, and natural killer cells differ between OT and NS. Eosinophils were lower during OT, activated T cells (CD3+HLA/DR+) showed slight increases (NS: 5.5 +/- 2.7; OT 7.3 +/- 2.4% CD3+ of cells; means +/- SD; P < 0.01) during OT without reaching pathological ranges. The cell-surface expression of CD45RO (P < 0.001) on T cells, but not cell concentrations of CD45RO+ T cells, were higher during OT. OT could be classified with high specificities (92%) and sensitivities (93%). It is concluded that OT does not lead to clinically relevant alterations of immunophenotypes in peripheral blood and especially that an immunosuppressive effect cannot be detected. Immunophenotyping may provide help with the diagnosis of OT in future, but the diagnostic approach presented here requires improvements before use in sports medicine practice is enabled.

Cadmium distribution in field-grown fruit trees

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

Korcak, R.F.

The effect of soil applied Cd on Cd distribution in and growth of five species of fruit trees was investigated. Cadmium was applied at three rates (0, 5, and 10 mg kg{sup {minus}1} soil) as CdSO{sub 4} to orchard plots established at two pH levels, low (5.5) and high (6.5). Five fruit tree types were planted: Gala apple (Malus domestica Borkh.) budded on M.26 (dwarfing) or MM.111 (semistandard) rootstocks, Redskin peach (Prunus persica L.) on Lovell rootstock, Stanley plum (Prunus domestica L.) on Myrobalon rootstock, and Seckel pear (Pyrus communis L.) on seedling rootstock. The trees were grown for 6more » yr, 7 yr in the case of pear, and leaf, bark, wood, fruit, and root Cd concentrations were monitored. Gala apple on both rootstocks accumulated very small concentrations of Cd, usually 0.1 mg kg{sup {minus}1} dry wt. in all tissues tested. Peach and plum were intermediate in Cd accumulation, but both still relatively low. Seckel pear had high Cd concentrations in all tissues including fruit flesh and peel. Pear leaf Cd concentrations were 2.0 mg kg{sup {minus}1} from the 10 mg kg{sup {minus}1} soil Cd application after 5 yr. Pear fruit peel and flesh showed elevated, although nonsignificant, Cd concentrations with increased Cd applied. There was little difference between bark and wood tissue Cd concentrations independent of tree type. Root Cd concentrations were highest for pear followed by peach and plum, and lowest in apple.« less

Data-Driven prioritisation of antibody-drug conjugate targets in head and neck squamous cell carcinoma.

PubMed

Hanemaaijer, Saskia H; van Gijn, Stephanie E; Oosting, Sjoukje F; Plaat, Boudewijn E C; Moek, Kirsten L; Schuuring, Ed M; van der Laan, Bernard F A M; Roodenburg, Jan L N; van Vugt, Marcel A T M; van der Vegt, Bert; Fehrmann, Rudolf S N

2018-05-01

For patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) palliative treatment options that improve overall survival are limited. The prognosis in this group remains poor and there is an unmet need for new therapeutic options. An emerging class of therapeutics, targeting tumor-specific antigens, are antibodies bound to a cytotoxic agent, known as antibody-drug conjugates (ADCs). The aim of this study was to prioritize ADC targets in HNSCC. With a systematic search, we identified 55 different ADC targets currently targeted by registered ADCs and ADCs under clinical evaluation. For these 55 ADC targets, protein overexpression was predicted in a dataset containing 344 HNSCC mRNA expression profiles by using a method called functional genomic mRNA profiling. The ADC target with the highest predicted overexpression was validated by performing immunohistochemistry (IHC) on an independent tissue microarray containing 414 HNSCC tumors. The predicted top 5 overexpressed ADC targets in HNSCC were: glycoprotein nmb (GPNMB), SLIT and NTRK-like family member 6, epidermal growth factor receptor, CD74 and CD44. IHC validation showed combined cytoplasmic and membranous GPNMB protein expression in 92.0% of the cases. Strong expression was seen in 65.9% of the cases. In addition, 86.5% and 67.7% of cases showed ≥5% and >25% GPNMB positive tumor cells, respectively. This study provides a data-driven prioritization of ADCs targets that will facilitate clinicians and drug developers in deciding which ADC should be taken for further clinical evaluation in HNSCC. This might help to improve disease outcome of HNSCC patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Corona discharge ion mobility spectrometry with orthogonal acceleration time of flight mass spectrometry for monitoring of volatile organic compounds.

PubMed

Sabo, Martin; Matejčík, Štefan

2012-06-19

We demonstrate the application of corona discharge ion mobility spectrometry with orthogonal acceleration time of flight mass spectrometry (CD IMS-oaTOF) for volatile organic compounds (VOCs) monitoring. Two-dimensional (2D) IMS-oaTOF spectra of VOCs were recorded in nearly real time. The corona discharge atmospheric pressure chemical ionization (APCI) source was operated in positive mode in nitrogen and air. The CD ion source generates in air H(3)O(+)(H(2)O)(n) and NO(+). The NO(+) offers additional possibility for selective ionization and for an increase of the sensitivity of monoaromatic compounds. In addition to H(3)O(+)(H(2)O)(n) and NO(+), we have carried out ionization of VOCs using acetone as dopant gas ((CH(3))(2)COH(+)). Sixteen model VOCs (tetrahydrofuran, butanol, n-propanol, iso-propano, acetone, methanol, ethanol, toluene, benzene, amomnia, dioxan, triethylamine, acetonitrile, formaldehyde, m-xylene, 2,2,2-trifluoroethylamine) were tested using these ionization techniques.

Comparison of electrokinetic soil remediation methods using one fixed anode and approaching anodes.

PubMed

Shen, Zhemin; Chen, Xuejun; Jia, Jinping; Qu, Liya; Wang, Wenhua

2007-11-01

During the cation exchange membrane (CEM) enhanced electrokinetic (EK) soil remediation, the nearer to the anode, the higher are the H+ concentrations and the redox potentials. As both low pH and high redox potential are helpful to speed-up Cd electro-migration, soils near the anode can be quickly remedied. Usually EK process is operated with one fixed anode (FA). A novel CEM enhanced EK method with approaching anodes (AAs) is proposed to accelerate electro-migration effect. Several mesh Ti/Ru anodes were inserted as AAs in the treated soil. They were switched in turn from the anode towards the cathode. Thus high H+ ions concentrations and high redox potentials quickly migrate to the cathode. Consequently, soil remediation is accelerated and nearly 44% of energy and 40% of time can be saved. The mechanism of Cd electro-migration behavior in soils during CEM enhanced EK is described as the elution in an electrokinetically driven chromatogram.