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Sample records for vibropac fas irradiation

  1. In vivo UVB irradiation induces clustering of Fas (CD95) on human epidermal cells

    DEFF Research Database (Denmark)

    Bang, Bo; Gniadecki, Robert; Larsen, Jørgen K

    2003-01-01

    In vitro studies with human cell lines have demonstrated that the death receptor Fas plays a role in ultraviolet (UV)-induced apoptosis. The purpose of the present study was to investigate the relation between Fas expression and apoptosis as well as clustering of Fas in human epidermis after...... clustering has a functional significance. Our results ar in accordance with previous findings from in vitro studies, and suggest that Fas is activated in vivo in human epidermis after UVB exposure....

  2. Comparison of apoptosis in wild-type and Fas-resistant cells: chemotherapy-induced apoptosis is not dependent on Fas/Fas ligand interactions.

    Science.gov (United States)

    Eischen, C M; Kottke, T J; Martins, L M; Basi, G S; Tung, J S; Earnshaw, W C; Leibson, P J; Kaufmann, S H

    1997-08-01

    The Fas/Fas ligand (FasL) pathway is widely involved in apoptotic cell death in lymphoid and nonlymphoid cells. It has recently been postulated that many chemotherapeutic agents also induce cell death by activating the Fas/FasL pathway. In the present study we compared apoptotic pathways induced by anti-Fas or chemotherapeutic agents in the Jurkat human T-cell leukemia line. Immunoblotting showed that treatment of wild-type Jurkat cells with anti-Fas or the topoisomerase II-directed agent etoposide resulted in proteolytic cleavage of precursors for the cysteine-dependent aspartate-directed proteases caspase-3 and caspase-7 and degradation of the caspase substrates poly(ADP-ribose) polymerase (PARP) and lamin B1. Likewise, affinity labeling with N-(N(alpha)-benzyloxycarbonylglutamyl-N(epsilon)-biotinyllysyl+ ++)aspartic acid [(2,6-dimethyl-benzoyl)oxy]methyl ketone [Z-EK(bio)D-amok] labeled the same five active caspase species after each treatment, suggesting that the same downstream apoptotic pathways have been activated by anti-Fas and etoposide. Treatment with ZB4, an antibody that inhibits Fas-mediated cell death, failed to block etoposide-induced apoptosis, raising the possibility that etoposide does not initiate apoptosis through Fas/FasL interactions. To further explore the relationship between Fas- and chemotherapy-induced apoptosis, Fas-resistant Jurkat cells were treated with various chemotherapeutic agents. Multiple independently derived Fas-resistant Jurkat lines underwent apoptosis that was indistinguishable from that of the Fas-sensitive parental cells after treatment with etoposide, doxorubicin, topotecan, cisplatin, methotrexate, staurosporine, or gamma-irradiation. These results indicate that antineoplastic treatments induce apoptosis through a Fas-independent pathway even though Fas- and chemotherapy-induced pathways converge on common downstream apoptotic effector molecules.

  3. FAS Ligand Triggers Pulmonary Silicosis

    Science.gov (United States)

    Borges, Valéria M.; Falcão, Haroldo; Leite-Júnior, José H.; Alvim, Luciana; Teixeira, Gerlinde P.; Russo, Momtchilo; Nóbrega, Alberto F.; Lopes, Marcela F.; Rocco, Patricia M.; Davidson, Wendy F.; Linden, Rafael; Yagita, Hideo; Zin, Walter A.; DosReis, George A.

    2001-01-01

    We investigated the role of Fas ligand in murine silicosis. Wild-type mice instilled with silica developed severe pulmonary inflammation, with local production of tumor necrosis factor (TNF)-α, and interstitial neutrophil and macrophage infiltration in the lungs. Strikingly, Fas ligand–deficient generalized lymphoproliferative disease mutant (gld) mice did not develop silicosis. The gld mice had markedly reduced neutrophil extravasation into bronchoalveolar space, and did not show increased TNF-α production, nor pulmonary inflammation. Bone marrow chimeras and local adoptive transfer demonstrated that wild-type, but not Fas ligand–deficient lung macrophages recruit neutrophils and initiate silicosis. Silica induced Fas ligand expression in lung macrophages in vitro and in vivo, and promoted Fas ligand–dependent macrophage apoptosis. Administration of neutralizing anti-Fas ligand antibody in vivo blocked induction of silicosis. Thus, Fas ligand plays a central role in induction of pulmonary silicosis. PMID:11457890

  4. Apoptosis, Fas and Fas-ligand expression in melanocytic tumors.

    Science.gov (United States)

    Sprecher, E; Bergman, R; Meilick, A; Kerner, H; Manov, L; Reiter, I; Shafer, Y; Maor, G; Friedman-Birnbaum, R

    1999-02-01

    Impaired regulation of apoptosis is known to be associated with the development of various forms of cancer. Fas binding to its ligand, Fas ligand (Fas-L), has been shown to trigger apoptosis in various cell types. Fas-L is expressed by melanoma cells and has been suggested to play a role in melanoma escape from immune surveillance. In the present study, we assessed apoptotic activity and examined Fas and Fas-L expression in malignant melanomas, Spitz nevi and ordinary melanocytic nevi. We evaluated apoptotic activity using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling. Apoptotic activity was found to be minimal in melanomas and moderate in Spitz nevi. In contrast, common nevi demonstrated significant levels of apoptosis in the deep parts of the tumor. Fas was found to be expressed by all Spitz nevi, most melanocytic nevi and approximately half of the malignant melanoma specimens. Fas expression was also significantly more pronounced in Spitz nevus cells as compared with the two other tumors. The anti-Fas-L antibody was found to stain all three melanocytic tumors. Staining was shown to be stronger and more frequent in melanoma cells as compared to the nevus cells. Using the Spearman test, no significant correlation between Fas-L expression in melanoma cells and apoptosis in MM-infiltrating mononuclear cells was found, suggesting that Fas-L expression in melanoma cells may not be instrumental in their ability to escape immune mechanisms of defense. In contrast, increased levels of apoptosis in the deep parts of melanocytic nevi may reflect and possibly contribute to their benign nature.

  5. Fas receptor-mediated apoptosis : a clinical application?

    NARCIS (Netherlands)

    Timmer, T; de Vries, EGE; de Jong, S

    Fas is a membrane protein belonging to the death receptor family. Cross-linking of Fas by its ligand, FasL, or agonistic anti-Fas antibodies, induces apoptosis of cells expressing Fas on the membrane by triggering a cascade of caspases. Since many different tumours express Fas on their membrane,

  6. Fas and Fas ligand in cyst fluids, serum and tumors of patients with benign and (borderline) malignant ovarian tumors

    NARCIS (Netherlands)

    Arts, HJG; De Jong, S; Hollema, H; Ten Hoor, KA; De Vries, EGE; Van Der Zee, AGJ

    Drug resistance in ovarian cancer treatment urges the exploration of new targets for drugs against this malignancy. Fas is a cell membrane receptor which, after engagement with Fas ligand (FasL), triggers apoptotic death. In this study Fas and FasL levels in cyst fluids and sera of patients with

  7. Soluble FAS and FAS ligand levels in seminal plasma: association with basic parameters of semen analysis.

    Science.gov (United States)

    Passadaki, Theoktisti; Asimakopoulos, Byron; Zeginiadou, Theodosia; Nikolettos, Nikos

    2013-01-01

    Binding of FAS ligand (FASL) to its physiological receptor FAS, induces the activation of caspase-8, which triggers cell death. The FAS-FASL system regulates germ cell death. In this study, the role of the FAS-FASL system in male infertility was examined. 72 samples were used (age=38.76 ± 9.06 years). Basic semen analysis was performed according to the WHO Laboratory Manual. Soluble (s) forms of FAS and FASL were measured in seminal plasma using commercially available immunoassay kits. Among the examined samples, 24 were normal and 48 abnormal, as evaluated by basic semen analysis. sFAS and sFASL levels in abnormal samples were slightly higher than in the normal ones. In all samples, sFAS correlated negatively with pH. In normal samples, sFAS was positively correlated with sperm concentration. In abnormal samples, sFAS strongly correlated with sFASL. Both factors of the FAS system were detected in seminal plasma. Further studies are necessary to shed light into the possible role of FAS-FASL system in male infertility.

  8. Neurodevelopmental functioning in children with FAS, pFAS, and ARND.

    Science.gov (United States)

    Chasnoff, Ira J; Wells, Anne M; Telford, Erin; Schmidt, Christine; Messer, Gwendolyn

    2010-04-01

    The purpose of this article is to compare the neurodevelopmental profiles of 78 foster and adopted children with fetal alcohol syndrome (FAS), partial FAS (pFAS), or alcohol-related neurodevelopmental disorder (ARND). Seventy-eight foster and adopted children underwent a comprehensive diagnostic evaluation. By using criteria more stringent than those required by current guidelines, the children were placed in 1 of 3 diagnostic categories: FAS, pFAS, or ARND. Each child was evaluated across the domains of neuropsychological functioning most frequently affected by prenatal exposure to alcohol. Multivariate analyses of variance were conducted to examine differences in neuropsychological functioning between the 3 diagnostic groups. Descriptive discriminant analyses were performed in follow-up to the multivariate analyses of variance. The children in the 3 diagnostic categories were similar for descriptive and child welfare variables. Children with FAS had significantly decreased mean weight, height, and head circumference. Children with FAS exhibited the most impaired level of general intelligence, significantly worse language-based memory compared with children with ARND, and significantly poorer functional communication skills than children with pFAS. On executive functioning, the FAS group of children performed significantly worse on sequencing and shift than either the pFAS or ARND groups. Children with pFAS and ARND were similar in all neurodevelopmental domains that were tested. The children who met tightly defined physical criteria for a diagnosis of FAS demonstrated significantly poorer neurodevelopmental functioning than children with pFAS and ARND. Children in these latter 2 groups were similar in all neurodevelopmental domains that were tested.

  9. A new function of the Fas-FasL pathway in macrophage activation.

    Science.gov (United States)

    Chakour, Reza; Allenbach, Cindy; Desgranges, Florian; Charmoy, Mélanie; Mauel, Jacques; Garcia, Irène; Launois, Pascal; Louis, Jacques; Tacchini-Cottier, Fabienne

    2009-07-01

    Upon infection with the protozoan parasite Leishmania major, susceptible BALB/c mice develop unhealing lesions associated with the maturation of CD4(+)Th2 cells secreting IL-4. In contrast, resistant C57BL/6 mice heal their lesions, because of expansion and secretion of IFN-gamma of CD4(+) Th1 cells. The Fas-FasL pathway, although not involved in Th cell differentiation, was reported to be necessary for complete resolution of lesions. We investigate here the role of IFN-gamma and IL-4 on Fas-FasL nonapoptotic signaling events leading to the modulation of macrophage activation. We show that addition of FasL and IFN-gamma to BMMø led to their increased activation, as reflected by enhanced secretion of TNF, IL-6, NO, and the induction of their microbicidal activity, resulting in the killing of intracellular L. major. In contrast, the presence of IL-4 decreased the synergy of IFN-gamma/FasL significantly on macrophage activation and the killing of intracellular L. major. These results show that FasL synergizes with IFN-gamma to activate macrophages and that the tight regulation by IFN-gamma and/or IL-4 of the nonapoptotic signaling events triggered by the Fas-FasL pathway affects significantly the activation of macrophages to a microbicidal state and may thus contribute to the pathogenesis of L. major infection.

  10. Fas/FasL pathway-mediated alveolar macrophage apoptosis involved in human silicosis

    Science.gov (United States)

    Yao, San-qiao; Rojanasakul, Liying Wang; Chen, Zhi-yuan; Xu, Ying-jun; Bai, Yu-ping; Chen, Gang; Zhang, Xi-ying; Zhang, Chun-min; Yu, Yan-qin; Shen, Fu-hai; Yuan, Ju-xiang; Chen, Jie

    2016-01-01

    In vitro and in vivo studies have demonstrated that lung cell apoptosis is associated with lung fibrosis; however the relationship between apoptosis of alveolar macrophages (AMs) and human silicosis has not been addressed. In the present study, AM apoptosis was determined in whole-lung lavage fluid from 48 male silicosis patients, 13 male observers, and 13 male healthy volunteers. The relationships between apoptosis index (AI) and silica exposure history, soluble Fas (sFas)/membrane-bound Fas (mFas), and caspase-3/caspase-8 were analyzed. AI, mFas, and caspase-3 were significantly higher in lung lavage fluids from silicosis patients than those of observers or healthy volunteers, but the level of sFas demonstrated a decreasing trend. AI was related to silica exposure, upregulation of mFas, and activation of caspase-3 and -8, as well as influenced by smoking status after adjusting for confounding factors. These results indicate that AM apoptosis could be used as a potential biomarker for human silicosis, and the Fas/FasL pathway may regulate this process. The present data from human lung lavage samples may help to understand the mechanism of silicosis and in turn lead to strategies for preventing or treating this disease. PMID:21910009

  11. Fas Ligand Expression in Lynch Syndrome-Associated Colorectal Tumours

    NARCIS (Netherlands)

    Koornstra, Jan J.; de Jong, Steven; Boersma-van Eck, Wietske; Zwart, Nynke; Hollema, Harry; de Vries, Elisabeth G. E.; Kleibeuker, Jan H.

    Fas Ligand (FasL) expression by cancer cells may contribute to tumour immune escape via the Fas counterattack against tumour-infiltrating lymphocytes (TILs). Whether this plays a role in colorectal carcinogenesis in Lynch syndrome was examined studying FasL expression, tumour cell apoptosis and

  12. Fas/FasL pathway participates in regulation of antiviral and inflammatory response during mousepox infection of lungs.

    Science.gov (United States)

    Bień, Karolina; Sokołowska, Justyna; Bąska, Piotr; Nowak, Zuzanna; Stankiewicz, Wanda; Krzyzowska, Malgorzata

    2015-01-01

    Fas receptor-Fas ligand (FasL) signalling is involved in apoptosis of immune cells as well as of the virus infected target cells but increasing evidence accumulates on Fas as a mediator of apoptosis-independent processes such as induction of activating and proinflammatory signals. In this study, we examined the role of Fas/FasL pathway in inflammatory and antiviral response in lungs using a mousepox model applied to C57BL6/J, B6. MRL-Faslpr/J, and B6Smn.C3-Faslgld/J mice. Ectromelia virus (ECTV) infection of Fas- and FasL-deficient mice led to increased virus titers in lungs and decreased migration of IFN-γ expressing NK cells, CD4+ T cells, CD8+ T cells, and decreased IL-15 expression. The lungs of ECTV-infected Fas- and FasL-deficient mice showed significant inflammation during later phases of infection accompanied by decreased expression of anti-inflammatory IL-10 and TGF-β1 cytokines and disturbances in CXCL1 and CXCL9 expression. Experiments in vitro demonstrated that ECTV-infected cultures of epithelial cells, but not macrophages, upregulate Fas and FasL and are susceptible to Fas-induced apoptosis. Our study demonstrates that Fas/FasL pathway during ECTV infection of the lungs plays an important role in controlling local inflammatory response and mounting of antiviral response.

  13. Enhanced expression of Fas Ligand (FasL in the lower airways of patients with fibrotic interstitial lung diseases (ILDs

    Directory of Open Access Journals (Sweden)

    Teresa Iwaniec

    2012-01-01

    Full Text Available The exact role of FasL, and particularly its soluble and membrane-bound forms, in the development of chronic ILDs and lung fibrosis has not been extensively explored. We aimed at analyzing membrane-bound FasL expression on alveolar macrophages (AM and lymphocytes (AL as well as soluble FasL (sFasL levels in bronchoalveolar lavage (BAL from ILDs patients, incl. pulmonary sarcoidosis (PS, hypersensitivity pneumonitis (HP, silicosis, asbestosis, idiopathic pulmonary fibrosis (IPF, nonspecific interstitial pneumonia (NSIP, and healthy subjects (n = 89, 12, 7, 8, 23, 6, 17, respectively. In IPF, significantly increased percentage of AM FasL+ and CD8+FasL+ cells as well as sFasL levels in BAL were found. Increased sFasL levels were also observed in HP. NSIP and asbestosis were characterized by higher AM FasL+ relative number; CD8+FasL+ population was expanded in asbestosis only. There was a significant decline in AL FasL+ percentage in PS and HP. Vital capacity was negatively correlated with sFasL levels, AM FasL+ and CD8+FasL+ cell relative count. CD4+FasL+ and CD8+FasL+ percentage strongly correlated with BAL neutrophilia, an unfavorable prognostic factor in lung fibrosis. The concurrent comparative BAL analysis of FasL expression indicates that FasL+ AM and AL (mainly Tc cells comprise an important element of the fibrotic process, mostly in IPF. FasL might play a crucial role in other fibrosis-complicated ILDs, like NSIP and asbestosis. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 636–645

  14. The signaling pathways by which the Fas/FasL system accelerates oocyte aging.

    Science.gov (United States)

    Zhu, Jiang; Lin, Fei-Hu; Zhang, Jie; Lin, Juan; Li, Hong; Li, You-Wei; Tan, Xiu-Wen; Tan, Jing-He

    2016-02-01

    In spite of great efforts, the mechanisms for postovulatory oocyte aging are not fully understood. Although our previous work showed that the FasL/Fas signaling facilitated oocyte aging, the intra-oocyte signaling pathways are unknown. Furthermore, the mechanisms by which oxidative stress facilitates oocyte aging and the causal relationship between Ca2+ rises and caspase-3 activation and between the cell cycle and apoptosis during oocyte aging need detailed investigations. Our aim was to address these issues by studying the intra-oocyte signaling pathways for Fas/FasL to accelerate oocyte aging. The results indicated that sFasL released by cumulus cells activated Fas on the oocyte by increasing reactive oxygen species via activating NADPH oxidase. The activated Fas triggered Ca2+ release from the endoplasmic reticulum by activating phospholipase C-γ pathway and cytochrome c pathway. The cytoplasmic Ca2+ rises activated calcium/calmodulin-dependent protein kinase II (CaMKII) and caspase-3. While activated CaMKII increased oocyte susceptibility to activation by inactivating maturation-promoting factor (MPF) through cyclin B degradation, the activated caspase-3 facilitated further Ca2+releasing that activates more caspase-3 leading to oocyte fragmentation. Furthermore, caspase-3 activation and fragmentation were prevented in oocytes with a high MPF activity, suggesting that an oocyte must be in interphase to undergo apoptosis.

  15. The Contribution of the Fas/FasL Apoptotic Pathway in Ulcer Formation during Leishmania major-Induced Cutaneous Leishmaniasis

    Science.gov (United States)

    Eidsmo, Liv; Nylen, Susanne; Khamesipour, Ali; Hedblad, Mari-Anne; Chiodi, Francesca; Akuffo, Hannah

    2005-01-01

    Cutaneous leishmaniasis (CL), caused by the intracellular protozoan Leishmania major, is characterized by lesion formation and ulceration at the site of infection. The mechanism of ulcer formation during CL is not fully understood. The expression of Fas and FasL and the levels of apoptosis in skin biopsies and in restimulated blood mononuclear cells from patients with 1 to 7 months of L. major-induced CL were analyzed using immunohistochemistry and fluorescence-activated cell sorting analysis. The levels of soluble Fas and FasL were also analyzed by enzyme-linked immunosorbent assay. A substantial number of apoptotic keratinocytes were observed mainly in the superficial epidermis of morphologically active and healing CL skin samples. Fas expression was increased on epidermis in active CL, whereas Fas expression was similar in healing and healthy epidermis. FasL-expressing macrophages and T cells were found in subepidermal infiltrate, mainly in active disease. When CL peripheral blood mononuclear cells were restimulated with L. major, Fas was up-regulated on effector T cells, and high levels of sFasL were secreted. Supernatants from restimulated cultures induced apoptosis in human keratinocytes (HaCaT), possibly through Fas/FasL interactions. Our results indicate that FasL-expressing effector T cells and macrophages may act to induce apoptosis and ulcer formation in Fas-expressing keratinocytes during L. major infection. PMID:15793290

  16. Fas and Fas ligand gene polymorphisms in Turkish patients with Familial Mediterranean Fever.

    Science.gov (United States)

    Ozel, Emine Gulce; Duran, Gulay Gulbol; Celik, Muhammet Murat; Duran, Nizami; Gunesacar, Ramazan

    2017-08-05

    Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder characterized by recurrent fever, serositis, abdominal pain, arthritis, arthralgia and erysipelas like erythema. Fas and Fas ligand molecules play a central role in the apoptosis signaling of various cell types including neutrophils. Neutrophils are the major cell population involved in acute inflammation in patients with FMF and the role of Fas and Fas ligand molecules in this cells of FMF patients may be crucial. Therefore, in the present study, we aimed to investigate whether the Fas cell surface receptor gene (FAS); NM_000043.5: c.-671A>G (rs1800682, MvaI) and Fas ligand gene (FASLG), NM_000639.2: c.-844C>T (rs763110, BsrD1) functional polymorphisms in patients with FMF and their relation to the main clinical features of the disease. The polymorphisms in the promoter regions of FAS c.-671A>G and FASLG c.-844C>T were investigated in 97 non-related FMF patients and 70 non-related healthy controls by using PCR-RFLP technique. The frequencies of FAS c-671AG genotype and G allele were not significantly different between FMF patients and healthy subjects. The frequency of FASLG -844TC genotype was found significantly different between the patients with FMF and healthy controls whereas T or C allele frequency was not significantly different between the groups. Haplotype frequencies of the studied polymorphisms were also not significantly different between FMF patients and controls. There were no correlations between the studied FAS c.-671A>G and FASLG c.-844C>T polymorphisms and the main clinical features of FMF such as fever, arthritis, abdominal and chest pain, arthralgia and erysipelas-like erythema. Our findings suggest that FAS c.-671AG genotype or G allele and FASLG c.-844 allele are not to be a risk factor, whereas FASLG c.-844TC genotype may be protective in the studied Turkish population. According to our results we may suggest that although not statistically significant

  17. Expression of cytotoxic mediators (perforin, granzyme B, FAS, and FAS-l in renal allograft biopsies

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    Therezinha Gauri Leitão

    2006-12-01

    Full Text Available Objectives: To analyze the in situ expression of perforin, granzymeB, FAS-L and FAS in renal allograft biopsies by means ofimmunohistochemistry and correlate these findings with the degreeof histologic rejection and allograft outcome. Methods: Ninety-sixallograft biopsies were divided into three groups: acute rejection (n= 56, chronic rejection (n = 31, and cases with stable renal function(no rejection; n = 9. The expression of perforin, granzyme B, FAS-L,and FAS was evaluated by immunohistochemistry. Results: Asignificantly higher expression of perforin and granzyme B wasobserved in acute rejection biopsies (4.83 ± 0.65 and 30.05 ± 7.93cells/mm2 compared to chronic rejection biopsies (0.71 ± 0.13 and11.4 ± 3.84 cells/mm2; p < 0.001, and p <0.05, respectively, but thiswas not the case for FAS-L (24.44 ± 5.56 in acute rejection versus 18.87± 6.83 in chronic rejection. Perforin, granzyme B, and FAS-L expressionwas significantly higher in the acute rejection group compared to the norejection and control groups. FAS expression was similar in all groups. Amodest correlation between perforin expression and the severity of ARwas observed (r = 0.28, p = 0.05. Perforin was the most reliable markerfor acute rejection diagnosis, with 80% sensitivity and 84.3% specificity.Conclusion: The in situ expression of perforin, granzyme B, and FAS-Lin AR reflects the presence of an active cytotoxic process. Additionalallograft biopsies are necessary in order to evaluate the usefulness ofthese markers for allograft rejection monitoring.

  18. Levels and clinic significance of serum soluble Fas and soluble Fas ligand in coal workers' pneumoconiosis

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, B.J.; Liu, Z.Z.; Ding, X.R.; Zou, J.M. [North China Coal Medical College, Tangshan (China). Department of Clinical Laboratory

    2006-02-15

    Serum levels of sFas and sFasL were determined in 52 patients with silicosis, 57 coal workers' pneumonoconiosis, 46 healthy underground coal workers' (the underground control group) and 40 healthy volunteers working on the ground (the ground control group) with a sandwich ELISA. Compared to the control groups, the serum levels of sFas and sFasL in the patients with silicosis and the coal workers' pneumonoconiosis were significantly higher. Serum levels of sFas and sFasL in the underground control group were higher than those in the ground control group; Serum sFas levels in coal workers' pneumonoconiosis was higher than those in the patients with silicosis. In the patients with silicosis and the coal workers' pneumonoconiosis patients, the serum sFas levels in Phase I patients combined with emphysema and simple Phase II + III patients were higher than those in simple Phase Ipatients. In the patients with silicosis and the coal workers' pneumonoconiosis, serum levels of sFas and sFasL were not significantly altered among different duration of exposure to dusts. There was a slightly positive correlation between sFas and sFasL levels in the coal workers' pneumonoconiosis. In the patients with silicosis and the coal workers' pneumonoconiosis, the serum levelsof sFas and sFasL areassociated with the development of the pneumonoconiosis. The changes of serum sFas levels may indicate the development and progression of the pneumonoconiosis. The detection of the serum sFas level may be used in the differential diagnosis for the silicosis and the coal worker's pneumonoconiosis.

  19. Serum levels of soluble Fas ligand in patients with silicosis

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    Tomokuni, A; Otsuki, T; Isozaki, Y; Kita, S; Ueki, H; Kusaka, M; Kishimoto, T; Ueki, A

    1999-01-01

    Certain patients with silicosis have been reported to exhibit immunological abnormalities such as the appearance of antinuclear antibodies and the occurrence of autoimmune diseases. Fas ligand (FasL) is a type II membrane protein which induces apoptosis by binding to its membrane receptor, Fas. FasL is converted to a soluble form by a metalloproteinase-like enzyme. We have already found serum soluble Fas (sFas) levels in silicosis patients as well as in patients with systemic lupus erythematosus (SLE) to be significantly higher than those in healthy volunteers. To examine further the role of the Fas/FasL system in silica-induced immunological abnormalities, we investigated serum soluble FasL (sFasL) levels in silicosis patients with no clinical symptoms of autoimmune diseases, using ELISA for sFasL. Although the serum sFasL levels in patients with SLE were significantly higher than those in healthy volunteers and showed a slight positive correlation with serum sFas levels, those in silicosis patients exhibited no significant difference from those in healthy volunteers, and there was no correlation with serum sFas levels. However, sFasL levels were elevated in silicosis patients with slight dyspnoea or normal PCO2 among various clinical parameters of silicosis. It may be speculated that the immunological disturbances presented by the abnormalities of apoptosis-related molecules in silicosis patients do not occur with a similar degree of respiratory involvement. Further studies are required to clarify which kinds of factors are involved in silicosis patients who exhibit immunological abnormalities. PMID:10594565

  20. Serum soluble Fas ligand (sFasL in patients with primary squamous cell carcinoma of the esophagus.

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    Lech Chyczewski

    2007-10-01

    Full Text Available Esophageal carcinomas have been shown to express Fas ligand (FasL and down-regulate Fas to escape from host immune surveillance. Circulating soluble FasL (sFasL has been suggested to provide protection from Fas-mediated apoptosis. The aim of this study was to assess serum sFasL levels in esophageal cancer. The pretreatment levels of sFasL in the serum of 100 patients with esophageal squamous cell cancer and 41 healthy volunteers were determined by ELISA. Probability of survival was calculated according to the method of Kaplan-Meier. The prognostic influence of high and low level of sFasL was analyzed with the log-rank test. The mean serum level of sFasL in patients with esophageal cancer was significantly higher than that in healthy donors (1.567+/-1.786 vs 0.261+/-0.435, p<0.0001. The levels of serum sFasL were significantly higher in advanced stages (II vs IV p<0.034; III vs IV p<0.041; except II vs III p=0.281, patients with lymph node (N0 vs N1 p<0.0389 or distant (M0 vs. M1 p<0.0388 metastases and significantly lower in patients with well differentiated tumors (G1 vs G2 p<0.0272. The serum levels of soluble FasL were not related to gender, age, tumor size, T-stage, tobacco smoking and history of chronic alcohol intake. The survival difference between pretreatment high and low level of sFasL in surgery and chemio- and/or radiotherapy group was not statistically significant (p=0.525; p=0.840. Our results indicate that elevated serum sFasL levels might be associated with a disease progression in patients with esophageal squamous cell carcinoma.

  1. FAS: dispensers and complete autogas filling stations; FAS: distributeurs et stations de GPLC

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2004-10-15

    Since 1975 the company FAS Flussiggas-Anlagen GmbH, Salzgitter - Germany, is one of the leading manufacturers of LPG equipment and components according to PED and ATEX with CE-marking for mobile and stationary bulk plants in Europe. The main products are dispensers, Autogas filling stations, vaporizers, loading arms, electronic cylinder filling scales, flanged valves and safety equipment. (authors)

  2. Serum Fas/FasL levels in dependence on clinical presentations of coronary disease and their relationship with risk factors

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    Ristić Tatjana

    2010-01-01

    Full Text Available Background/Aim. Ischemic heart disease is mostly a consequence of atherosclerosis. Besides the inflammation, the Fas/Fas ligand (FasL/caspase death pathway is documented to be activated in atherosclerotic lesions. The aim of this study was to compare the values of soluble forms of Fas and FasL in patients with different presentations of coronary disease and to correlate Fas/FasL with risk factors. Methods. We studied 30 patients with chronic stable angina pectoris (SAP, 27 with non-stable angina pectoris (NSAP, and 39 with acute ST-elevation myocardial infarction (STEMI and 27 age-matched healthy volunteers (the control group. Serum Fas/APO1 and FasL concentrations were determined using a commercially available enzymelinked immunoassays (ELISA. Results. Fas/APO-1 levels in the STEMI patients (6.981 ± 2.689 ng/mL were significantly higher than Fas levels in the controls (5.092 ± 1.252 ng/mL, p < 0.01, but not significantly higher than Fas values in the SAP (5.952 ± 2.069 ng/mL and the USAP patients (5.627±2.270 ng/ml. Levels of FasL did not show any significant difference among the studied groups. In the SAP patients Fas/APO1 showed a significant positive correlation with high sensitivity C-reactive protein (hsCRP (p < 0.05 and a negative correlation with high-density lipoprotein cholesterol (HDL-C (p < 0.05, while FasL showed a significant positive correlation with low-density lipoprotein cholesterol (LDL-C (p < 0.05. Fas levels between the patients having cholesterol within normal range and those whose cholesterol was above the normal range showed a significant difference (p < 0.05 only in the NSAP patients. Fas and FasL levels between the patients with hsCRP lower than 3.0 mg/L and those with hsCRP higher than 3.0 mg/L of the SAP group showed a significant differences (p < 0.001, p < 0.05, respectively. Strong correlation between Fas concentration and diabetes mellitus (p < 0.05 and FasL concentrations and both cholesterol (p < 0.01 and

  3. Fas and FasL expression in placentas complicated with intrauterine growth retardation with and without preeclampsia.

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    Rešić Karara, Jasminka; Zekić Tomas, Sandra; Marušić, Jelena; Roje, Damir; Kuzmić Prusac, Ivana

    2016-01-01

    To compare the level of Fas and FasL immunohistochemical expression in villous trophoblast (VT), extravillous trophoblast (EVT) cells, decidual cells (DC), endothelial cells (EC) of villous blood vessels and spiral arteries between the study groups of intrauterine growth retardation (IUGR) placentas with and without preeclampsia (PE). The study included 17 placentas from pregnancies complicated by IUGR + PE and 17 placentas from pregnancies complicated by idiopathic IUGR (I-IUGR). Seventeen placentas from normal pregnancies served as a control group. CD31 was used to detect endothelial cells (EC). Immunohistochemical expression of Fas and FasL was assessed in all examined parts of placenta using the semi-quantitative HSCORE method. FasL expression was significantly higher in all examined parts of placenta in I-IUGR as compared to IUGR + PE and control group. Placentas with IUGR + PE had the significantly lowest expression of FasL in VT and EC of villi vessels. Expression of Fas did not differ significantly between the study groups. Different expression of FasL in placentas from I-IUGR and IUGR + PE suggests that FasL probably has a different role in the etiology of these two syndromes.

  4. GBV-C coinfection is negatively correlated to Fas expression and Fas-mediated apoptosis in HIV-1 infected patients.

    Science.gov (United States)

    Moenkemeyer, Maren; Schmidt, Reinhold E; Wedemeyer, Heiner; Tillmann, Hans L; Heiken, Hans

    2008-11-01

    Persistent coinfection with the apathogenic GB virus C (GBV-C) is associated with slower disease progression of human immunodeficiency virus (HIV)-1 infection. Aim of this study was to investigate whether Fas plays a role in this beneficial effect. Fas expression and susceptibility to Fas-mediated apoptosis (FMA) was analyzed in peripheral blood mononuclear cells (PBMCs) of HIV-1 patients coinfected and non-coinfected with GBV-C. Fas expression and function was evaluated in 42 GBV-C coinfected and 101 non-coinfected HIV-1 patients. Thirteen healthy and 11 Hepatitis C virus (HCV)-monoinfected individuals were analyzed as controls. Cell surface Fas expression was determined by flow cytometric analysis. Apoptosis was evaluated by staining with Annexin V and Viaprobe followed by multiparameter flow cytometry analysis. In untreated HIV-1 patients GBV-C coinfection was associated with significantly lower percentage of Fas expressing cells as compared to GBV-C non-coinfected individuals. Expression of Fas was directly correlated with sensitivity to Fas-mediated apoptosis. Sensitivity to FMA was unchanged in GBV-C coinfected patients. PBMCs of patients receiving highly active antiretroviral therapy (HAART) did not show such a difference. Untreated HIV-1 patients with GBV-C coinfection have reduced cell surface Fas expression. Lower FMA of T-cells might contribute to prolonged survival of GBV-C coinfected HIV-1 patients. 2008 Wiley-Liss, Inc.

  5. Involvement of the Fas system in liver allograft rejection.

    Science.gov (United States)

    Rivero, M; Crespo, J; Mayorga, M; Fábrega, E; Casafont, F; Pons-Romero, F

    2002-06-01

    Recent studies suggest that apoptosis is an important mechanism of cell death in the rejection of liver allografts and that this process is mediated via Fas. The aim of this study was to analyze the expression of the Fas system during the liver allograft rejection and its evolution after treatment. We evaluated 14 patients with liver allograft rejection before and after treatment. Fas immunostaining was performed by the labeled streptavidin-biotin peroxidase method using a 200-fold dilution of a monoclonal antibody. Assessment of apoptosis was determined by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) technique on deparaffined liver samples. Serum levels of soluble Fas antigen (sFas) were detected by an enzyme immunoassay procedure. Twelve liver transplant patients without allograft rejection were analyzed as a control group. The number of hepatocytes expressing Fas antigen, the percentage of apoptotic hepatocytes, and the sFas levels were higher in patients with liver allograft rejection than in controls (27.9+/-23.1% vs 1.4+/-1.2%, p < 0.001; 2.2+/-0.9% vs 1.0+/-0.1%, p = 0.02; 24.2+/-39.6 vs 2.8+/-4.0 IU/ml, p = 0.03, respectively). There was a correlation between the levels of sFas, AST (r = 0.86, p < 0.001), ALT (r = 0.78, p = 0.02), and gamma-globulin levels (r = 0.86, p < 0.001). After the rejection treatment we found a significant decrease in the Fas antigen expression (18.6+/-13.3%, p < 0.05), TUNEL index (0.2+/-0.4, p < 0.05), and levels of sFas (9.9+/-30.25 IU/ml, p = 0.005). 1) The demonstration of hepatocytes with Fas antigen expression and the labeling of the nuclei by the TUNEL assay suggest that apoptosis mediated by the Fas system plays a role in the pathogenesis of liver allograft rejection. 2) The Fas expression and the sFas levels decreased in patients with treatment response.

  6. Inhibition of tumor growth using salmonella expressing Fas ligand.

    Science.gov (United States)

    Loeffler, Markus; Le'Negrate, Gaelle; Krajewska, Maryla; Reed, John C

    2008-08-06

    Intravenous administration of bacteria leads to their accumulation in tumors and to sporadic tumor regression. We therefore explored the hypothesis that Salmonella typhimurium engineered to express the proapoptotic cytokine Fas ligand (FasL) would exhibit enhanced antitumor activity. Immunocompetent mice carrying tumors derived from syngeneic murine D2F2 breast carcinoma or CT-26 colon carcinoma cells were treated intravenously with FasL-expressing S. typhimurium or with phosphate-buffered saline (PBS; control). Treatment with FasL-expressing S. typhimurium inhibited growth of primary tumors by an average of 59% for D2F2 tumors and 82% for CT-26 tumors (eg, at 25 days after initial treatment, mean volume of PBS-treated CT-26 colon carcinomas = 1385 mm(3) and of S. typhimurium FasL-treated CT-26 tumors = 243 mm(3), difference = 1142 mm(3), 95% confidence interval = 800 mm(3) to 1484 mm(3), P strategy for some cancers.

  7. Apoptosis and expression of Bcl-2, Bax, p53, caspase-3, and Fas, Fas ligand in placentas complicated by preeclampsia.

    Science.gov (United States)

    Mendilcioglu, I; Karaveli, S; Erdogan, G; Simsek, M; Taskin, O; Ozekinci, M

    2011-01-01

    To determine whether preeclampsia is associated with an increase in placental apoptosis and altered expression of mediators of apoptosis such as Fas, Fas ligand, caspase-3, p53, Bcl-2 and Bax. Placental samples obtained from 20 women with preeclampsia and 14 normal women were analyzed using the Klenow, Frag-EL DNA fragmentation detection kit for apoptosis. Expression of Fas, Fas ligand, caspase-3, p53 Bcl-2, and Bax was assessed using immunohistochemistry. The median percentage of apoptotic nuclei in trophoblasts was significantly higher for the preeclampsia group than for the controls (6.9 vs 0.25; p =.001). Fas ligand expression was significantly higher in the decidua among the subjects with preeclampsia compared with controls (1.2 vs 0; p = .023). Otherwise no difference was observed in the expression of Bax , Bcl-2, p53, caspase-3, and Fas between groups. Increased apoptosis in preeclampsia may not be associated with significant alterations in Fas, Fas ligand, caspase-3, p53, Bcl-2 and Bax expression.

  8. Fas signalling promotes intercellular communication in T cells.

    Science.gov (United States)

    Luchetti, Francesca; Canonico, Barbara; Arcangeletti, Marcella; Guescini, Michele; Cesarini, Erica; Stocchi, Vilberto; Degli Esposti, Mauro; Papa, Stefano

    2012-01-01

    Cell-to-cell communication is a fundamental process for development and maintenance of multicellular organisms. Diverse mechanisms for the exchange of molecular information between cells have been documented, such as the exchange of membrane fragments (trogocytosis), formation of tunneling nanotubes (TNTs) and release of microvesicles (MVs). In this study we assign to Fas signalling a pivotal role for intercellular communication in CD4+ T cells. Binding of membrane-bound FasL to Fas expressing target cells triggers a well-characterized pro-apoptotic signalling cascade. However, our results, pairing up flow cytometric studies with confocal microscopy data, highlight a new social dimension for Fas/FasL interactions between CD4+ T cells. Indeed, FasL enhances the formation of cell conjugates (8 fold of increase) in an early time-frame of stimulation (30 min), and this phenomenon appears to be a crucial step to prime intercellular communication. Our findings show that this communication mainly proceeds along a cytosolic material exchange (ratio of exchange >10, calculated as ratio of stimulated cells signal divided by that recorded in control cells) via TNTs and MVs release. In particular, inhibition of TNTs genesis by pharmacological agents (Latruculin A and Nocodazole) markedly reduced this exchange (inhibition percentage: >40% and >50% respectively), suggesting a key role for TNTs in CD4+ T cells communication. Although MVs are present in supernatants from PHA-activated T cells, Fas treatment also leads to a significant increase in the amount of released MVs. In fact, the co-culture performed between MVs and untreated cells highlights a higher presence of MVs in the medium (1.4 fold of increase) and a significant MVs uptake (6 fold of increase) by untreated T lymphocytes. We conclude that Fas signalling induces intercellular communication in CD4+ T cells by different mechanisms that seem to start concomitantly with the main pathway (programmed cell death) promoted

  9. Fas signalling promotes intercellular communication in T cells.

    Directory of Open Access Journals (Sweden)

    Francesca Luchetti

    Full Text Available Cell-to-cell communication is a fundamental process for development and maintenance of multicellular organisms. Diverse mechanisms for the exchange of molecular information between cells have been documented, such as the exchange of membrane fragments (trogocytosis, formation of tunneling nanotubes (TNTs and release of microvesicles (MVs. In this study we assign to Fas signalling a pivotal role for intercellular communication in CD4+ T cells. Binding of membrane-bound FasL to Fas expressing target cells triggers a well-characterized pro-apoptotic signalling cascade. However, our results, pairing up flow cytometric studies with confocal microscopy data, highlight a new social dimension for Fas/FasL interactions between CD4+ T cells. Indeed, FasL enhances the formation of cell conjugates (8 fold of increase in an early time-frame of stimulation (30 min, and this phenomenon appears to be a crucial step to prime intercellular communication. Our findings show that this communication mainly proceeds along a cytosolic material exchange (ratio of exchange >10, calculated as ratio of stimulated cells signal divided by that recorded in control cells via TNTs and MVs release. In particular, inhibition of TNTs genesis by pharmacological agents (Latruculin A and Nocodazole markedly reduced this exchange (inhibition percentage: >40% and >50% respectively, suggesting a key role for TNTs in CD4+ T cells communication. Although MVs are present in supernatants from PHA-activated T cells, Fas treatment also leads to a significant increase in the amount of released MVs. In fact, the co-culture performed between MVs and untreated cells highlights a higher presence of MVs in the medium (1.4 fold of increase and a significant MVs uptake (6 fold of increase by untreated T lymphocytes. We conclude that Fas signalling induces intercellular communication in CD4+ T cells by different mechanisms that seem to start concomitantly with the main pathway (programmed cell death

  10. The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma.

    LENUS (Irish Health Repository)

    Bennett, M W

    2012-02-03

    Various cancer cell lines express Fas ligand (FasL) and can kill lymphoid cells by Fas-mediated apoptosis in vitro. FasL expression has been demonstrated in several human malignancies in vivo. We sought to determine whether human esophageal carcinomas express FasL, and whether FasL expression is associated with increased apoptosis of tumor-infiltrating lymphocytes (TIL) in vivo, thereby contributing to the immune privilege of the tumor. Using in situ hybridization and immunohistochemistry, respectively, FasL mRNA and protein were colocalized to neoplastic esophageal epithelial cells in all esophageal carcinomas (squamous, n = 6; adenocarcinoma, n = 2). The Extent of FasL expression was variable, with both FasL-positive and FasL-negative neoplastic regions occurring within tumors. TIL were detected by immunohistochemical staining for the leukocyte common Ag, CD45. FasL expression was associated with a mean fourfold depletion of TIL when compared with FasL-negative areas within the same tumors (range 1.6- to 12-fold, n = 6,p < 0.05). Cell death of TIL was detected by dual staining of CD45 (immunohistochemistry) and DNA strand breaks (TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling). There was a mean twofold increase in detectable cell death among TIL in FasL-positive areas compared with FasL-negative areas (range 1.6- to 2.4-fold, n = 6, p < 0.05). In conclusion, we demonstrate a statistically significant, quantitative reduction of TIL concomitant with significantly increased TIL apoptosis within FasL-expressing areas of esophageal tumors. Our findings suggest Fas-mediated apoptotic depletion of TIL in response to FasL expression by esophageal cancers, and provide the first direct, quantitative evidence to support the Fas counterattack as a mechanism of immune privilege in vivo in human cancer.

  11. The Relationship of Serum Soluble Fas Ligand (sFasL) Level with the Extent of Coronary Artery Disease.

    Science.gov (United States)

    Sahinarslan, Asife; Boyaci, Bulent; Kocaman, Sinan Altan; Topal, Salih; Ercin, Ugur; Okyay, Kaan; Bukan, Neslihan; Yalçin, Ridvan; Cengel, Atiye

    2012-03-01

    Fas/Fas ligand system contributes to the programmed cell death induced by myocardial ischemia. We investigated whether serum soluble Fas ligand (sFasL) level is independently related with the severity and extent of angiographically assessed coronary artery disease (CAD). We included 169 patients in this study. Two groups were formed based on the existence of a lesion on coronary angiography. First group included patients with normal coronary arteries (NCA; n = 53). Patients with atherosclerotic lesions were included in the second group (n = 116). We used the coronary vessel score (the number of the coronary arteries with a lesion leading to ≥ 50% luminal obstruction) and the Azar score to determine the extent and the severity of CAD. Standard enzyme-linked immunosorbent assay kits were used to measure serum sFasL levels. The serum sFasL level was higher in patients with CAD than in patients with NCA (0.52 ± 0.23 mU/mL vs. 0.45 ± 0.18 mU/mL, p = 0.023). The sFasL level correlated with Azar score (r = 0.231, p = 0.003) and with coronary vessel score (r = 0.269, p < 0.001). In the multivariate analysis, we found that age (beta: 0.188, p = 0.008), gender (beta: 0.317, p < 0.001), diabetes mellitus (DM; beta: 0.195, p = 0.008), and sFasL level (beta: 0.209, p = 0.003) were independently related with Azar score. When we used coronary vessel score as the dependent variable, we found that age (p = 0.020), gender (p < 0.001), DM (p = 0.006), and sFasL level (p = 0.001) were independent predictors. Serum sFasL level is associated with angiographically more severe CAD. Our findings suggest that sFasL level may be a biochemical surrogate of severe coronary atherosclerosis.

  12. Myeloid-derived suppressor cells express the death receptor Fas and apoptose in response to T cell–expressed FasL

    Science.gov (United States)

    Chornoguz, Olesya; Clements, Virginia K.; Artemenko, Konstantin A.; Zubarev, Roman A.

    2011-01-01

    Myeloid-derived suppressor cells (MDSCs) inhibit adaptive and innate immunity and accumulate in the blood of persons with cancer, chronic inflammation, trauma, infection, and stress. Some of the factors inducing their accumulation are known; however, mechanisms regulating their turnover have not been identified. Mass spectrometry showed prominent expression of apoptosis pathway proteins, suggesting that MDSC turnover may be regulated by Fas-FasL–mediated apoptosis. This hypothesis was confirmed by showing that blood MDSCs induced by 3 mouse tumors were Fas+ and apoptosed in response to Fas agonist in vitro and to activated FasL+ T cells in vivo. FasL-deficient mice contained significantly more blood MDSCs than FasL+/+ mice, and after removal of primary tumors MDSCs regressed in STAT6−/− and CD1−/− mice but not in STAT6−/−FasL−/− or CD1−/−FasL−/− mice. Fas+ macrophages and dendritic cells did not apoptose in response to activated T cells, indicating that Fas-FasL regulation of myeloid cells was restricted to MDSCs. These results identify a new mechanism regulating MDSC levels in vivo and show a retaliatory relationship between T cells and MDSCs in that MDSCs suppress T-cell activation; however, once activated, T cells mediate MDSC apoptosis. PMID:21450901

  13. Myeloid-derived suppressor cells express the death receptor Fas and apoptose in response to T cell-expressed FasL.

    Science.gov (United States)

    Sinha, Pratima; Chornoguz, Olesya; Clements, Virginia K; Artemenko, Konstantin A; Zubarev, Roman A; Ostrand-Rosenberg, Suzanne

    2011-05-19

    Myeloid-derived suppressor cells (MDSCs) inhibit adaptive and innate immunity and accumulate in the blood of persons with cancer, chronic inflammation, trauma, infection, and stress. Some of the factors inducing their accumulation are known; however, mechanisms regulating their turnover have not been identified. Mass spectrometry showed prominent expression of apoptosis pathway proteins, suggesting that MDSC turnover may be regulated by Fas-FasL-mediated apoptosis. This hypothesis was confirmed by showing that blood MDSCs induced by 3 mouse tumors were Fas(+) and apoptosed in response to Fas agonist in vitro and to activated FasL(+) T cells in vivo. FasL-deficient mice contained significantly more blood MDSCs than FasL(+/+) mice, and after removal of primary tumors MDSCs regressed in STAT6(-/-) and CD1(-/-) mice but not in STAT6(-/-)FasL(-/-) or CD1(-/-)FasL(-/-) mice. Fas(+) macrophages and dendritic cells did not apoptose in response to activated T cells, indicating that Fas-FasL regulation of myeloid cells was restricted to MDSCs. These results identify a new mechanism regulating MDSC levels in vivo and show a retaliatory relationship between T cells and MDSCs in that MDSCs suppress T-cell activation; however, once activated, T cells mediate MDSC apoptosis.

  14. FAS: Using FPGA to Accelerate and Secure SDN Software Switches

    Directory of Open Access Journals (Sweden)

    Wenwen Fu

    2018-01-01

    Full Text Available Software-Defined Networking (SDN promises the vision of more flexible and manageable networks but requires certain level of programmability in the data plane to accommodate different forwarding abstractions. SDN software switches running on commodity multicore platforms are programmable and are with low deployment cost. However, the performance of SDN software switches is not satisfactory due to the complex forwarding operations on packets. Moreover, this may hinder the performance of real-time security on software switch. In this paper, we analyze the forwarding procedure and identify the performance bottleneck of SDN software switches. An FPGA-based mechanism for accelerating and securing SDN switches, named FAS (FPGA-Accelerated SDN software switch, is proposed to take advantage of the reconfigurability and high-performance advantages of FPGA. FAS improves the performance as well as the capacity against malicious traffic attacks of SDN software switches by offloading some functional modules. We validate FAS on an FPGA-based network processing platform. Experiment results demonstrate that the forwarding rate of FAS can be 44% higher than the original SDN software switch. In addition, FAS provides new opportunity to enhance the security of SDN software switches by allowing the deployment of bump-in-the-wire security modules (such as packet detectors and filters in FPGA.

  15. Association of genetic variants in apoptosis genes FAS and FASL with radiation-induced late toxicity after prostate cancer radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Thurner, E.M.; Krenn-Pilko, S.; Kapp, K.S.; Langsenlehner, T. [Medical University of Graz, Department of Therapeutic Radiology and Oncology, Graz (Austria); Langsenlehner, U. [Division of Internal Medicine, GKK Outpatient Department, Graz (Austria); Renner, W. [Medical University of Graz, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz (Austria); Gerger, A. [Medical University of Graz, Division of Oncology, Department of Internal Medicine, Graz (Austria)

    2014-03-15

    Fas ligand (FASL) triggers apoptotic cell death by cross-linking with its receptor FAS, and after irradiation, expression of FAS and FASL is increased. In the present study, we investigated the association between common polymorphisms in the genes for FAS and FASL and the risk of late side effects after radiotherapy for prostate cancer. The role of FAS (- 1377G > A, rs2234767 and - 670A > G, rs1800682) and FASL (- 844C > T, rs763110) gene polymorphisms in the development of high-grade late rectal and/or urinary toxicity (defined as late toxicity EORTC/RTOG grade ≥ 2) was analyzed in 607 prostate cancer patients treated with radiotherapy. DNA was isolated and the selected polymorphisms were determined by 5'-nuclease (TaqMan) assays. After a median follow-up time of 82 months, high-grade late rectal and/or urinary toxicity was observed in 175 patients (29.7 %). Univariate analysis revealed a significantly decreased risk of high-grade late toxicity in carriers of the FASL - 844T allele. After adjusting for covariates, patients harboring at least one - 844T allele (CT or TT genotype) remained at decreased risk of high-grade late toxicity compared with patients harboring the CC genotype [hazard ratio (HR) 0.585, 95 %CI 0.39-0.878; p = 0.010]. For patients with the - 844TT genotype, the HR was 0.404 (95 %CI 0.171-0.956; p = 0.039) in multivariate analysis. No significant associations were found for the remaining polymorphisms analyzed. These results provide the first evidence that the presence of the FASL - 844T variant allele may have a protective effect against the development of high-grade late rectal and/or urinary side effects after prostate cancer radiotherapy. (orig.) [German] Fas-Ligand (FASL) triggert durch Bindung an seinen Rezeptor FAS den apoptotischen Zelltod, desweiteren konnte nach Bestrahlung eine Ueberexpression von FAS und FASL beobachtet werden. Ziel der vorliegenden prospektiven Studie war die Untersuchung der Zusammenhaenge von

  16. Analysis of apoptotic cell death following irradiation in SCC malignant cell lines derived from the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Uno, Masako [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    2000-07-01

    To explore radiation-resistancy in head and neck squamous cell carcinoma (HNSCC), two HNSCC lines, KB derived from the oral floor and HEp-2 from the larynx, were used to clarify the cellular biological alterations related to apoptotic cell death induced by irradiation. Both cell lines revealed ultrastructual apoptotic morphological changes and showed dose- and time- dependent increase in to the apoptotic fraction examined by the TUNEL method using flow cytometry. The KB cells showed time- and dose-dependent upregulation of membrane Fas (mFas) expression after irradiation. Analysis of alteration in the mRNA expression levels of apoptosis-related genes demonstrated slight upregulation of Fas, Flice, Bax, and TNFRl genes in KB cells and of the Fas ligand gene in HEp-2 cells. In addition, the DcR3 gene, which completes Fas-Fas ligand binding and inhibits Fas-mediated apoptosis, was upregulated in KB cells after irradiation. Based on these results, Fas-mediated apoptotic pathway may be involved in irradiation- induced apoptosis via p53 upregulation. Further investigations are required to resolve questions regarding the radiation-resistancy which often occurs after radiotherapy for head and neck malignancies. (author)

  17. Apoptosis and JNK activation are differentially regulated by Fas expression level in renal tubular epithelial cells.

    Science.gov (United States)

    Khan, S; Koepke, A; Jarad, G; Schlessman, K; Cleveland, R P; Wang, B; Konieczkowski, M; Schelling, J R

    2001-07-01

    In chronic renal disease, renal tubular epithelial cell (RTC) Fas expression is up-regulated, leading to apoptotic RTC deletion and tubular atrophy. In vitro, cytokine- or hypoxia-induced up-regulation of Fas expression is associated with RTC apoptosis. In contrast, constitutively expressed, low level RTC Fas does not mediate apoptosis, suggesting that Fas may be coupled to expression level-dependent RTC signaling pathways. Fas is known to signal through JNK in many systems, but the requirement of JNK activation for apoptosis remains controversial. To determine if RTC Fas regulates JNK activity and apoptosis, human RTC were transfected with graded concentrations of a eukaryotic expression vector for murine Fas. Apoptosis was measured by annexin V, TUNEL and PARP cleavage assays. JNK activity was determined by immune complex kinase assay and/or immunoblots with phospho-specific JNK antibodies, in the presence or absence of co-expressed dominant negative JNK constructs. Fas antibody stimulation of RTC with high Fas expression levels (to model RTC phenotype in renal disease) caused a tenfold increase in apoptosis, while RTC with low level Fas expression (to model normal RTC phenotype) were apoptosis-resistant. Fas ligation activated JNK in RTC expressing low levels of Fas, but not in apoptosis-sensitive RTC with increased Fas expression. Dominant negative JNK co-expression failed to inhibit apoptosis in RTC expressing high levels of Fas, suggesting that JNK is neither necessary, nor sufficient, for Fas-dependent apoptosis. At high levels of expression, RTC Fas promotes apoptosis in a JNK-independent manner. At low basal expression, Fas induces JNK activation, but not apoptosis, consistent with novel roles for RTC Fas as a mediator of cell stress or chronic inflammation.

  18. The role of Fas mediated apoptosis in preeclampsia.

    Science.gov (United States)

    Neale, Donna M; Mor, Gil

    2005-01-01

    It has become clear in recent years that apoptosis is a normal process in trophoblast turnover during pregnancy. Increased trophoblast apoptosis has been observed in the placenta of women with preeclampsia, serum from women with preeclampsia has been found to induce increased trophoblast sensitivity to Fas-mediated apoptosis, and serum from women with preeclampsia has elevated levels of various chemokines, growth factors and cytokines that are involved in the regulation of apoptosis. This review highlights the importance of apoptosis in normal placental development and explores the mechanisms whereby Fas-mediated apoptosis may play a role in conditions related to abnormal placentation, such as preeclampsia.

  19. Mechanical ventilation-induced apoptosis in newborn rat lung is mediated via FasL/Fas pathway.

    Science.gov (United States)

    Kroon, Andreas A; Delriccio, Veronica; Tseu, Irene; Kavanagh, Brian P; Post, Martin

    2013-12-01

    Mechanical ventilation induces pulmonary apoptosis and inhibits alveolar development in preterm infants, but the molecular basis for the apoptotic injury is unknown. The objective was to determine the signaling mechanism(s) of ventilation (stretch)-induced apoptosis in newborn rat lung. Seven-day-old rats were ventilated with room air for 24 h using moderate tidal volumes (8.5 ml/kg). Isolated fetal rat lung epithelial and fibroblast cells were subjected to continuous cyclic stretch (5, 10, or 17% elongation) for up to 12 h. Prolonged ventilation significantly increased the number of apoptotic alveolar type II cells (i.e., terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling and anti-cleaved caspase-3 immunochemistry) and was associated with increased expression of the apoptotic mediator Fas ligand (FasL). Fetal lung epithelial cells, but not fibroblasts, subjected to maximal (i.e., 17%, but not lesser elongation) cyclic stretch exhibited increased apoptosis (i.e., nuclear fragmentation and DNA laddering), which appeared to be mediated via the extrinsic pathway (increased expression of FasL and cleaved caspase-3, -7, and -8). The intrinsic pathway appeared not to be involved [minimal mitochondrial membrane depolarization (JC-1 flow analysis) and no activation of caspase-9]. Universal caspases inhibition and neutralization of FasL abrogated the stretch-induced apoptosis. Prolonged mechanical ventilation induces apoptosis of alveolar type II cells in newborn rats and the mechanism appears to involve activation of the extrinsic death pathway via the FasL/Fas system.

  20. Prostaglandin E2 stimulates Fas ligand expression via the EP1 receptor in colon cancer cells.

    LENUS (Irish Health Repository)

    O'Callaghan, G

    2012-02-03

    Fas ligand (FasL\\/CD95L) is a member of the tumour necrosis factor superfamily that triggers apoptosis following crosslinking of the Fas receptor. Despite studies strongly implicating tumour-expressed FasL as a major inhibitor of the anti-tumour immune response, little is known about the mechanisms that regulate FasL expression in tumours. In this study, we show that the cyclooxygenase (COX) signalling pathway, and in particular prostaglandin E(2) (PGE(2)), plays a role in the upregulation of FasL expression in colon cancer. Suppression of either COX-2 or COX-1 by RNA interference in HCA-7 and HT29 colon tumour cells reduced FasL expression at both the mRNA and protein level. Conversely, stimulation with PGE(2) increased FasL expression and these cells showed increased cytotoxicity against Fas-sensitive Jurkat T cells. Prostaglandin E(2)-induced FasL expression was mediated by signalling via the EP1 receptor. Moreover, immunohistochemical analysis using serial sections of human colon adenocarcinomas revealed a strong positive correlation between COX-2 and FasL (r=0.722; P<0.0001) expression, and between EP1 receptor and FasL (r=0.740; P<0.0001) expression, in the tumour cells. Thus, these findings indicate that PGE(2) positively regulates FasL expression in colon tumour cells, adding another pro-neoplastic activity to PGE(2).

  1. Detección de fibrinógeno, FAS B-10, FAS ZB4 y FAS C-20 durante la placentación porcina (Detection of fibrinogen, FAS B-10, FAS ZB4 and FAS C-20 during porcine placentation)

    OpenAIRE

    Cristofolini, A. ; Merkis, C. ; Barroso, F. ; Vaquer, V. ;Lloret, M. ; Koncurat, M.; E Moschetti

    2008-01-01

    El objetivo del presente trabajo fue determinar el número de vasossanguíneos, la presencia de fibrinógeno y la expresión de los receptores de membrana FAS B-10, FAS ZB4 y FAS C-20 durante la placentación porcina, a fin de detectar una relación entre la presencia de fibrinógeno y la angiogénesis placentaria; determinando además la expresión de receptores de apoptosis involucrados en la remodelación celular. Se utilizaron cortes histológicos de ± 4 μm provenientes de placentas porcinas de difer...

  2. Fas ligand-dependent suppression of autoimmunity via recruitment and subsequent termination of activated T cells.

    Science.gov (United States)

    Modiano, Jaime F; Sun, Juan; Lang, Julie; Vacano, Guido; Patterson, David; Chan, Daniel; Franzusoff, Alex; Gianani, Roberto; Meech, Sandra J; Duke, Richard; Bellgrau, Donald

    2004-07-01

    Signals transmitted by binding of Fas ligand (FasL) to the Fas receptor (CD95/Apo-1) have pleiotropic effects on cellular function that present opportunities for therapeutic applications. For example, depending on the circumstances, overexpression of FasL can enhance, prevent, or reverse growth of spontaneous or transplantable tumors. Furthermore, local administration of FasL into a single paw in susceptible mice protects from or reduces the severity of collagen-induced arthritis (CIA) in all paws. Here, we define mechanisms that mediate systemic protection induced by locally delivered FasL. Protection is not solely dependent on local interactions between Fas and FasL, but rather requires induction of a paradoxical inflammatory response that not only destroys Fas-resistant tumors, but also recruits motile, activated, Fas-bearing T cells that are Fas sensitive. We demonstrate by following the antigen-specific recruitment and subsequent termination of transgenic T cells that activated T cells, including autoreactive cells responsible for CIA, are eliminated within this inflammatory environment through the overexpressed FasL. The nature of the inflammatory response, which depends on the Fas ligand being cell bound and not soluble, and the magnitude of FasL expression within the inflammatory milieu are essential for this effect, as arthritogenic inflammation alone resulting from CIA induction is insufficient to ameliorate the disease or eliminate antigen-specific T cells, even upon systemic delivery of soluble FasL. These data show that gene delivery of membrane-bound FasL can effectively recruit and eliminate autoreactive T cells.

  3. 7 CFR 1484.57 - Will FAS make advance payments to a Cooperator?

    Science.gov (United States)

    2010-01-01

    ... DEVELOP FOREIGN MARKETS FOR AGRICULTURAL COMMODITIES Contributions and Reimbursements § 1484.57 Will FAS make advance payments to a Cooperator? (a) Policy. In general, FAS operates the Cooperator program on a.... The first is a revolving fund operating advance provided by FAS only to Cooperators with foreign...

  4. Identification of the Calmodulin-Binding Domains of Fas Death Receptor.

    Directory of Open Access Journals (Sweden)

    Bliss J Chang

    Full Text Available The extrinsic apoptotic pathway is initiated by binding of a Fas ligand to the ectodomain of the surface death receptor Fas protein. Subsequently, the intracellular death domain of Fas (FasDD and that of the Fas-associated protein (FADD interact to form the core of the death-inducing signaling complex (DISC, a crucial step for activation of caspases that induce cell death. Previous studies have shown that calmodulin (CaM is recruited into the DISC in cholangiocarcinoma cells and specifically interacts with FasDD to regulate the apoptotic/survival signaling pathway. Inhibition of CaM activity in DISC stimulates apoptosis significantly. We have recently shown that CaM forms a ternary complex with FasDD (2:1 CaM:FasDD. However, the molecular mechanism by which CaM binds to two distinct FasDD motifs is not fully understood. Here, we employed mass spectrometry, nuclear magnetic resonance (NMR, biophysical, and biochemical methods to identify the binding regions of FasDD and provide a molecular basis for the role of CaM in Fas-mediated apoptosis. Proteolytic digestion and mass spectrometry data revealed that peptides spanning residues 209-239 (Fas-Pep1 and 251-288 (Fas-Pep2 constitute the two CaM-binding regions of FasDD. To determine the molecular mechanism of interaction, we have characterized the binding of recombinant/synthetic Fas-Pep1 and Fas-Pep2 peptides with CaM. Our data show that both peptides engage the N- and C-terminal lobes of CaM simultaneously. Binding of Fas-Pep1 to CaM is entropically driven while that of Fas-Pep2 to CaM is enthalpically driven, indicating that a combination of electrostatic and hydrophobic forces contribute to the stabilization of the FasDD-CaM complex. Our data suggest that because Fas-Pep1 and Fas-Pep2 are involved in extensive intermolecular contacts with the death domain of FADD, binding of CaM to these regions may hinder its ability to bind to FADD, thus greatly inhibiting the initiation of apoptotic signaling

  5. Blockade of Fas signaling in breast cancer cells suppresses tumor growth and metastasis via disruption of Fas signaling-initiated cancer-related inflammation.

    Science.gov (United States)

    Liu, Qiuyan; Tan, Qinchun; Zheng, Yuanyuan; Chen, Kun; Qian, Cheng; Li, Nan; Wang, Qingqing; Cao, Xuetao

    2014-04-18

    Mechanisms for cancer-related inflammation remain to be fully elucidated. Non-apoptotic functions of Fas signaling have been proposed to play an important role in promoting tumor progression. It has yet to be determined if targeting Fas signaling can control tumor progression through suppression of cancer-related inflammation. In the current study we found that breast cancer cells with constitutive Fas expression were resistant to apoptosis induction by agonistic anti-Fas antibody (Jo2) ligation or Fas ligand cross-linking. Higher expression of Fas in human breast cancer tissue has been significantly correlated with poorer prognosis in breast cancer patients. To determine whether blockade of Fas signaling in breast cancer could suppress tumor progression, we prepared an orthotopic xenograft mouse model with mammary cancer cells 4T1 and found that blockade of Fas signaling in 4T1 cancer cells markedly reduced tumor growth, inhibited tumor metastasis in vivo, and prolonged survival of tumor-bearing mice. Mechanistically, blockade of Fas signaling in cancer cells significantly decreased systemic or local recruitment of myeloid derived suppressor cells (MDSCs) in vivo. Furthermore, blockade of Fas signaling markedly reduced IL-6, prostaglandin E2 production from breast cancer cells by impairing p-p38, and activity of the NFκB pathway. In addition, administration of a COX-2 inhibitor and anti-IL-6 antibody significantly reduced MDSC accumulation in vivo. Therefore, blockade of Fas signaling can suppress breast cancer progression by inhibiting proinflammatory cytokine production and MDSC accumulation, indicating that Fas signaling-initiated cancer-related inflammation in breast cancer cells may be a potential target for treatment of breast cancer.

  6. Levels of soluble Fas/APO-1 in patients with Behçet's disease

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    K. Hamzaoui

    1998-01-01

    Full Text Available The aim of this study was to quantify soluble Fas/APO1 (sFas/APO-1 protein in the serum of patients with Behcet's disease (BD in active and inactive stages, compared with patients with systemic lupus erythematosus (SLE and patients with rheumatoid arthritis (RA. Soluble Fas/APO-1 was quantified using a sandwich enzyme-linked immunosorbent assay. Increased serum sFas/APO-1 levels were observed in active BD, compared with inactive BD, RA patients and SLE patients. Increased serum sFas/APO-1 levels were correlated with the presence of neurologic manifestations or pulmonary involvement in active BD. In conclusion, increased levels of sFas/APO-1 occurred frequently and exclusively in active BD patients. Preliminary evidence suggested that elevated levels of sFas/APO-1 are associated with the clinical stage and clinical manifestations in BD.

  7. Role of thymidine phosphorylase in Fas-induced apoptosis.

    Science.gov (United States)

    Mori, S; Takao, S; Ikeda, R; Noma, H; Mataki, Y; Wang, X; Akiyama, S; Aiko, T

    2001-12-01

    Thymidine phosphorylase (TP) has chemotactic and angiogenic activity in vitro, and it promotes tumor growth and inhibits apoptosis in vivo. It plays a key role in the invasiveness and metastasis of TP-expressing solid tumors. KB/TP cells transfected with a TP cDNA have been shown to be resistant to hypoxia-induced apoptosis, suggesting that TP has effects on tumor growth and cell death independent of its effects on angiogenesis. However, the mechanisms of cell death inhibition by TP are unknown. In the present study, we demonstrate that caspase-8 is cleaved in control transfectant KB cells early on during Fas-induced apoptosis. Caspase-8 activation leads to the loss of mitochondrial membrane potential, followed by the release of cytochrome c, the activation of caspase-3, and apoptosis. In contrast, Fas-induced caspase-8 cleavage is inhibited in KB/TP cells, which lead to inhibition of the downstream apoptotic cascade and inhibition of apoptosis. These findings indicate that TP plays an important role in intracellular apoptotic signal transduction in the Fas-induced apoptotic pathway. Therefore, inhibition of TP may suppress the progression of TP-overexpressing solid tumors by inducing apoptosis.

  8. Human FasL gene is a target of β-catenin/T-cell factor pathway and complex FasL haplotypes alter promoter functions.

    Directory of Open Access Journals (Sweden)

    Jianming Wu

    Full Text Available FasL expression on human immune cells and cancer cells plays important roles in immune homeostasis and in cancer development. Our previous study suggests that polymorphisms in the FasL promoter can significantly affect the gene expression in human cells. In addition to the functional FasL SNP -844C>T (rs763110, three other SNPs (SNP -756A>G or rs2021837, SNP -478A>T or rs41309790, and SNP -205 C>G or rs74124371 exist in the proximal FasL promoter. In the current study, we established three major FasL hyplotypes in humans. Interestingly, a transcription motif search revealed that the FasL promoter possessed two consensus T-cell factor (TCF/LEF1 binding elements (TBEs, which is either polymorphic (SNP -205C>G or close to the functional SNP -844C>T. Subsequently, we demonstrate that both FasL TBEs formed complexes with the TCF-4 and β-catenin transcription factors in vitro and in vivo. Co-transfection of LEF-1 and β-catenin transcription factors significantly increased FasL promoter activities, suggesting that FasL is a target gene of the β-catenin/T-cell factor pathway. More importantly, we found that the rare allele (-205G of the polymorphic FasL TBE (SNP -205C>G failed to bind the TCF-4 transcription factor and that SNP -205 C>G significantly affected the promoter activity. Furthermore, promoter reporter assays revealed that FasL SNP haplotypes influenced promoter activities in human colon cancer cells and in human T cells. Finally, β-catenin knockdown significantly decreased the FasL expression in human SW480 colon cancer cells. Collectively, our data suggest that β-catenin may be involved in FasL gene regulation and that FasL expression is influenced by FasL SNP haplotypes, which may have significant implications in immune response and tumorigenesis.

  9. Involvement of the fas system in hepatitis C virus recurrence after liver transplantation.

    Science.gov (United States)

    Crespo, J; Rivero, M; Mayorga, M; Fabrega, E; Casafont, F; Gomez-Fleitas, M; Pons-Romero, F

    2000-09-01

    To date, there have been no reports of the involvement of the Fas system in recurrent hepatitis C virus (HCV) infection after orthotopic liver transplantation (OLT). In 25 patients who underwent OLT for HCV-related liver cirrhosis, we evaluated the expression of the Fas antigen (FasAg) on hepatocytes, apoptic hepatocytes, and serum levels of soluble Fas (sFas). The level of HCV viremia and HCV genotype were determined by polymerase chain reaction. Serum sFas levels were determined by an enzyme immunoassay procedure. DNA fragmentation was determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) technique on deparaffinized liver samples. FasAg expression was evaluated by an immunoperoxidase method. Sixteen patients had evidence of recurrent HCV disease. The number of hepatocytes expressing FasAg and the percentage of apoptotic hepatocytes was greater among patients who developed recurrent hepatitis than among those who did not (P <.01 and P <.0001, respectively). There was a correlation between hepatic expression of FasAg, intensity of lobular inflammation (P =.007), and TUNEL index (P <.001). The levels of sFas were greater among the patients with recurrent HCV hepatitis than those without recurrent hepatitis (P <.04). We conclude that (1) Fas expression is up-regulated in recurrent HCV after OLT and is related to the grading of liver disease; likewise, levels of sFas were greater in the patients with recurrent HCV hepatitis; and (2) the demonstration of hepatocytes with FasAg expression and the labeling of the nuclei by TUNEL assay suggest that hepatic apoptosis mediated by the Fas system may have a role in the pathogenesis of recurrent HCV hepatitis after OLT.

  10. Fas receptor clustering and involvement of the death receptor pathway in rituximab-mediated apoptosis with concomitant sensitization of lymphoma B cells to Fas-induced apoptosis

    NARCIS (Netherlands)

    Stel, Alia J.; ten Cate, Bram; Jacobs, Susan; Kok, Jan Willem; Spierings, Diana C. J.; Dondorff, Monica; Helfrich, Wijnand; Kluin-Nelemans, Hanneke C.; de Leij, Lou F. A. H.; Withoff, Sebo; Kroesen, Bart Jan

    2007-01-01

    Ab binding to CD20 has been shown to induce apoptosis in B cells. In this study, we demonstrate that rituximab sensitizes lymphoma B cells to Fas-induced apoptosis in a caspase-8-dependent manner. To elucidate the mechanism by which Rituximab affects Fas-mediated cell death, we investigated

  11. Autoimmune lymphoproliferative syndrome caused by a homozygous null FAS ligand (FASLG) mutation

    Science.gov (United States)

    Magerus-Chatinet, Aude; Stolzenberg, Marie-Claude; Lanzarotti, Nina; Neven, Bénédicte; Daussy, Cécile; Picard, Capucine; Neveux, Nathalie; Desai, Mukesh; Rao, Meghana; Ghosh, Kanjaksha; Madkaikar, Manisha; Fischer, Alain; Rieux-Laucat, Frédéric

    2013-01-01

    Background Autoimmune lymphoproliferative syndrome (ALPS) is characterized by chronic nonmalignant lymphoproliferation, accumulation of double-negative T cells, hypergammaglobulinemia G and A, and autoimmune cytopenia. Objectives Although mostly associated with FAS mutations, different genetic defects leading to impaired apoptosis have been described in patients with ALPS, including the FAS ligand gene (FASLG) in rare cases. Here we report on the first case of complete FAS ligand deficiency caused by a homozygous null mutant. Methods Double-negative T-cell counts and plasma IL-10 and FAS ligand concentrations were determined as ALPS markers. The FASLG gene was sequenced, and its expression was analyzed by means of Western blotting. FAS ligand function was assessed based on reactivation-induced cell death. Results We describe a patient born to consanguineous parents who presented with a severe form of ALPS caused by FASLG deficiency. Although the clinical presentation was compatible with a homozygous FAS mutation, FAS-induced apoptosis was normal, and plasma FAS ligand levels were not detectable. This patient carries a homozygous, germline, single-base-pair deletion in FASLG exon 1, leading to a premature stop codon (F87fs x95) and a complete defect in FASLG expression. The healthy parents were each heterozygous for the mutation, confirming its recessive trait. Conclusion FAS ligand deficiency should be screened in patients presenting with ALPS features but lacking the usual markers, including plasma soluble FAS ligand and an in vitro apoptotic defect. An activation-induced cell death test could help in discrimination. PMID:22857792

  12. Functional promoter haplotypes of the human FAS gene are associated with the phenotype of SLE characterized by thrombocytopenia

    DEFF Research Database (Denmark)

    Nolsøe, R L; Kelly, J A; Pociot, F

    2005-01-01

    to SLE or subphenotypes in 126 multiplex American SLE pedigrees and found association of the FAS codon214 AC(C/T) as well as the FAS-670G>A'-codon214 AC(C/T)' haplotype to thrombocytopenia in SLE. Furthermore we have functionally characterized the FAS/FASL promoter polymorphisms associated with SLE...... variant, determines the promoter activity. We conclude that the FAS/FASL promoter haplotypes are functional and that polymorphisms in FAS may contribute to thrombocytopenia in SLE....

  13. Evaluation of sFas in serum and follicular fluid during ovarian stimulation for assisted reproduction

    Directory of Open Access Journals (Sweden)

    Ayman Nady Abdelmeged

    2011-03-01

    Conclusions: A lower level of sFas in serum was associated with a higher pregnancy rates. This may be attributed to the presence of good fertilized oocytes. The above phenomena may suggest that low levels of sFas in serum may be associated with improved implantation of fertilized oocytes or may prevent damage to the embryo. Lower levels of sFas seem to support embryo implantation.

  14. Significant role of Fas ligand-binding but defective Fas receptor (CD95) in lymph node hyperplasia composed of abnormal double-negative T cells

    Science.gov (United States)

    Matsuzawa, Akio; Shimizu, Motomu; Takeda, Yasutaka; Nagase, Hisashi; Sayama, Kazutoshi; Kimura, Mikio

    2002-01-01

    The functional differences between two mutations of the Fas (CD95) locus, Faslpr (lpr) and Faslprcg (lprcg), were investigated using bone marrow (BM) transplantation on the C3H mouse background. Both lpr/lpr and lprcg/lprcg BM transferred caused lymph node (LN) hyperplasia in lpr/+ and lprcg/+ recipients, although it was clearly smaller than that in lpr/lpr and lprcg/lprcg recipients of lpr/lpr and lprcg/lprcg BM. In addition, both BM induced significantly larger LN hyperplasia in lprcg/+ than lpr/+ recipients. Appearance of CD4− CD8−[double negative (DN)] T cells in the periphery is the most consistent phenotype of Fas mutations. Importantly, the proportion of DN T cells was higher in larger LN hyperplasia in the order of lpr/+, lprcg/+ and lpr/lpr or lprcg/lprcg recipients. On the other hand, both lpr/lpr and lprcg/lprcg BM transferred into wild-type (+/+) mice caused marked LN atrophy. The former, but not the latter, induced wasting syndrome. Faslg1d (gld)-homozygous lpr/lpr BM transferred into +/+ mice elicited LN hyperplasia of the same extent as that in lpr/lpr mice transferred with lpr/lpr BM, but not wasting syndrome. Taken together with the fact that DN T cells massively express Fas ligand (FasL), this study implied that FasL overexpressed on DN cells may be involved in the accumulation of DN T cells in LN, LN atrophy and wasting syndrome, and that lprcg Fas, which can bind to Fas ligand but not transduce apoptosis signal into cells, may modulate these pathological conditions by interfering with the binding of FasL to Fas. PMID:12153509

  15. Calreticulin Binds to Fas Ligand and Inhibits Neuronal Cell Apoptosis Induced by Ischemia-Reperfusion Injury

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    Beilei Chen

    2015-01-01

    Full Text Available Background. Calreticulin (CRT can bind to Fas ligand (FasL and inhibit Fas/FasL-mediated apoptosis of Jurkat T cells. However, its effect on neuronal cell apoptosis has not been investigated. Purpose. We aimed to evaluate the neuroprotective effect of CRT following ischemia-reperfusion injury (IRI. Methods. Mice underwent middle cerebral artery occlusion (MCAO and SH-SY5Y cells subjected to oxygen glucose deprivation (OGD were used as models for IRI. The CRT protein level was detected by Western blotting, and mRNA expression of CRT, caspase-3, and caspase-8 was measured by real-time PCR. Immunofluorescence was used to assess the localization of CRT and FasL. The interaction of CRT with FasL was verified by coimmunoprecipitation. SH-SY5Y cell viability was determined by MTT assay, and cell apoptosis was assessed by flow cytometry. The measurement of caspase-8 and caspase-3 activity was carried out using caspase activity assay kits. Results. After IRI, CRT was upregulated on the neuron surface and bound to FasL, leading to increased viability of OGD-exposed SH-SY5Y cells and decreased activity of caspase-8 and caspase-3. Conclusions. This study for the first time revealed that increased CRT inhibited Fas/FasL-mediated neuronal cell apoptosis during the early stage of ischemic stroke, suggesting it to be a potential protector activated soon after IRI.

  16. Decitabine immunosensitizes human gliomas to NY-ESO-1 specific T lymphocyte targeting through the Fas/Fas Ligand pathway

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    Konkankit Veerauo V

    2011-11-01

    Full Text Available Abstract Background The lack of effective treatments for gliomas makes them a significant health problem and highlights the need for the development of novel and innovative treatment approaches. Immunotherapy is an appealing strategy because of the potential ability for immune cells to traffic to and destroy infiltrating tumor cells. However, the absence of well-characterized, highly immunogenic tumor-rejection antigens (TRA in gliomas has limited the implementation of targeted immune-based therapies. Methods We hypothesized that treatment with the demethylating agent, decitabine, would upregulate the expression of TRA on tumor cells, thereby facilitating enhanced surveillance by TRA-specific T cells. Results and Discussion Treatment of human glioma cells with decitabine increased the expression of NY-ESO-1 and other well characterized cancer testes antigens. The upregulation of NY-ESO-1 made these tumors susceptible to NY-ESO-1-specific T-cell recognition and lysis. Interestingly, decitabine treatment of T98 glioma cells also sensitized them to Fas-dependent apoptosis with an agonistic antibody, while a Fas blocking antibody could largely prevent the enhanced functional recognition by NY-ESO-1 specific T cells. Thus, decitabine treatment transformed a non-immunogenic glioma cell into an immunogenic target that was efficiently recognized by NY-ESO-1--specific T cells. Conclusions Such data supports the hypothesis that agents which alter epigenetic cellular processes may "immunosensitize" tumor cells to tumor-specific T cell-mediated lysis.

  17. Decitabine immunosensitizes human gliomas to NY-ESO-1 specific T lymphocyte targeting through the Fas/Fas Ligand pathway

    Science.gov (United States)

    2011-01-01

    Background The lack of effective treatments for gliomas makes them a significant health problem and highlights the need for the development of novel and innovative treatment approaches. Immunotherapy is an appealing strategy because of the potential ability for immune cells to traffic to and destroy infiltrating tumor cells. However, the absence of well-characterized, highly immunogenic tumor-rejection antigens (TRA) in gliomas has limited the implementation of targeted immune-based therapies. Methods We hypothesized that treatment with the demethylating agent, decitabine, would upregulate the expression of TRA on tumor cells, thereby facilitating enhanced surveillance by TRA-specific T cells. Results and Discussion Treatment of human glioma cells with decitabine increased the expression of NY-ESO-1 and other well characterized cancer testes antigens. The upregulation of NY-ESO-1 made these tumors susceptible to NY-ESO-1-specific T-cell recognition and lysis. Interestingly, decitabine treatment of T98 glioma cells also sensitized them to Fas-dependent apoptosis with an agonistic antibody, while a Fas blocking antibody could largely prevent the enhanced functional recognition by NY-ESO-1 specific T cells. Thus, decitabine treatment transformed a non-immunogenic glioma cell into an immunogenic target that was efficiently recognized by NY-ESO-1--specific T cells. Conclusions Such data supports the hypothesis that agents which alter epigenetic cellular processes may "immunosensitize" tumor cells to tumor-specific T cell-mediated lysis. PMID:22060015

  18. Primary and malignant cholangiocytes undergo CD40 mediated Fas dependent apoptosis, but are insensitive to direct activation with exogenous Fas ligand.

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    Elizabeth H Humphreys

    2010-11-01

    Full Text Available Cholangiocarcinoma is a rare malignancy of the biliary tract, the incidence of which is rising, but the pathogenesis of which remains uncertain. No common genetic defects have been described but it is accepted that chronic inflammation is an important contributing factor. We have shown that primary human cholangiocyte and hepatocyte survival is tightly regulated via co-operative interactions between two tumour necrosis family (TNF receptor family members; CD40 and Fas (CD95. Functional deficiency of CD154, the ligand for CD40, leads to a failure of clearance of biliary tract infections and a predisposition to cholangiocarcinoma implying a direct link between TNF receptor-mediated apoptosis and the development of cholangiocarcinoma.To determine whether malignant cholangiocytes display defects in CD40 mediated apoptosis. By comparing CD40 and Fas-mediated apoptosis and intracellular signalling in primary human cholangiocytes and three cholangiocyte cell lines.Primary cholangiocytes and cholangiocyte cell lines were relatively insensitive to direct Fas-mediated killing with exogenous FasL when compared with Jurkat cells, which readily underwent Fas-mediated apoptosis, but were extremely sensitive to CD154 stimulation. The sensitivity of cells to CD40 activation was similar in magnitude in both primary and malignant cells and was STAT-3 and AP-1 dependent in both.1 Both primary and malignant cholangiocytes are relatively resistant to Fas-mediated killing but show exquisite sensitivity to CD154, suggesting that the CD40 pathway is intact and fully functional in both primary and malignant cholangiocytes 2 The relative insensitivity of cholangiocytes to Fas activation demonstrates the importance of CD40 augmentation of Fas dependent death in these cells. Agonistic therapies which target CD40 and associated intracellular signalling pathways may be effective in promoting apoptosis of malignant cholangiocytes.

  19. Effect of iodide on Fas, Fas-ligand and Bcl-w mRNA expression in thyroid of NOD mice pretreated with methimazole

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    L.H.B. Boechat

    2002-03-01

    Full Text Available Nonobese diabetic (NOD mice and a derived strain, NOD.H.2h4, have been used as a model for experimental spontaneous thyroiditis and thyroiditis induced by iodide excess after a goiter-inducing period. Some authors have proposed that iodide, given after methimazole or propylthiouracil, is capable of inducing apoptosis in thyroid cells and that anti-thyroid drugs can modulate the expression of apoptosis components such as Fas and its ligand (Fas-L. Here we evaluated the effect of potassium iodide (20 µg/animal for 4 days, ip given to NOD mice at the 10th week of life after exposure to methimazole (1 mg/ml in drinking water from the 4th to the 10th week of life. Fas, Fas-L and Bcl-w expression were analyzed semiquantitatively by RT-PCR immediately after potassium iodide administration (group MI44D or at week 32 (MI32S. Control groups were added at 10 (C10 and 32 weeks (C32, as well as a group that received only methimazole (CM10. An increase in the expression of Fas-L and Bcl-w (P<0.01, ANOVA was observed in animals of group MI44D, while Fas was expressed at higher levels (P = 0.02 in group C32 (72.89 ± 47.09 arbitrary units when compared to group C10 (10.8 ± 8.55 arbitrary units. Thus, the analysis of Fas-L and Bcl-w expression in the MI44D group and Fas in group C32 allowed us to detect two different patterns of expression of these apoptosis components in thyroid tissue of NOD mice.

  20. Attenuated apoptosis response to Fas-ligand in active ulcerative colitis

    DEFF Research Database (Denmark)

    Seidelin, Jakob B; Nielsen, Ole H

    2008-01-01

    BACKGROUND: From mainly carcinoma cell line studies, apoptosis has been thought to play a major role in the pathogenesis of ulcerative colitis (UC). Apoptosis has been suggested to be due to a Fas ligand / Fas receptor interaction, but has never been studied in cells from patients with active UC...

  1. Association of FAS (TNFRSF6)-670 gene polymorphism with villous atrophy in coeliac disease.

    NARCIS (Netherlands)

    Wu, J; Alizadeh, BZ; Veen, TV; Meijer, JW; Mulder, C.J.J.; Pena, A.S.

    2004-01-01

    AIM: To investigate the association of FAS gene polymorphism with coeliac disease (CD) development. METHODS: FAS-G670A gene polymorphism, located in a gamma interferon activation site, was studied in 146 unrelated CD patients and 203 healthy ethnically matched controls. The restriction fragment

  2. Effects of deoxycycline induced lentivirus encoding FasL gene on ...

    African Journals Online (AJOL)

    Spleen lymphocytes of rats were transfected with the lentiviral vector system encoding FasL gene and 5 days later were induced by doxycycline for 24 h, followed by detection of FasL mRNA. The apoptosis index of Th1 cells was measured through both Annexin V-FITC flow cytometry and TUNEL. Additionally flow cytometry ...

  3. Lack of FasL expression in cultured human retinal pigment epithelial cells

    DEFF Research Database (Denmark)

    Kaestel, C G; Madsen, H O; Prause, J U

    2001-01-01

    Retinal pigment epithelial (RPE) cells have been proposed to play a part in maintaining the eye as an immune privileged organ. However, our knowledge of the implicated mechanism is still sparse. Fas ligand (FasL) expression of RPE cells is generally recognized to be essential for the immune...

  4. Effects of deoxycycline induced lentivirus encoding FasL gene on ...

    African Journals Online (AJOL)

    Yomi

    2011-02-14

    Feb 14, 2011 ... Viral vector-mediated gene transfer of neurotrophins to promote regeneration of the injured spinal cord. Prog. Brain. Res. 146: 451-. 476. Ji J, Chen JJ, Braciale VL, Cloyd MW (2007). Apoptosis induced in. HIV-1-exposed, resting CD4+ T cells subsequent to signaling through homing receptors is Fas/Fas ...

  5. Foxo3a induces motoneuron death through the Fas pathway in cooperation with JNK

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    Pettmann Brigitte

    2004-11-01

    Full Text Available Abstract Background Programmed cell death of motoneurons in the developing spinal cord is thought to be regulated through the availability of target-derived neurotrophic factors. When deprived of trophic support, embryonic spinal motoneurons in vitro over-express FasL, a ligand activating a Fas-mediated death pathway. How trophic factors regulate the expression of FasL is presently unclear, but two regulators of FasL, FOXO3a (FKHRL1 and JNK have been described to play a role in other cell types. Thus, their potential function in motoneurons was investigated in this study. Results We show here that as a result of removal of neurotrophic factors and the consequent reduction in signalling through the PI3K/Akt pathway, Foxo3a translocates from the cytoplasm to the nucleus where it triggers cell death. Death is reduced in Fas and FasL mutant motoneurons and in the presence of JNK inhibitors indicating that a significant part of it requires activation of the Fas/FasL pathway through JNK. Conclusions Therefore, in motoneurons as in other cell types, FOXO transcriptional regulators provide an important link between other signalling pathways and the cell death machinery.

  6. 75 FR 13329 - Implications of Financial Accounting System (FAS) 166 on SBA Guaranteed Loan Programs

    Science.gov (United States)

    2010-03-19

    ... ADMINISTRATION Implications of Financial Accounting System (FAS) 166 on SBA Guaranteed Loan Programs AGENCY... Administration (SBA) is soliciting information and views from the public on: (1) The effect that the accounting changes mandated by the Financial Accounting Standards Board (FASB) in Financial Accounting Standard (FAS...

  7. Expression of FAS/APO 1/CD 95 in thyroid tumors.

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    Waldemar Balcerzak

    2007-06-01

    Full Text Available Using immunohistochemistry, Fas/Apo-1 protein expression was investigated in thyroid cancers of 67 patients. Thyroid biopsies from twenty eight patients with benign thyroid diseases were also examined. The patients with thyroid cancer manifested a variable histology of the cancer, including 14 patients with follicular carcinoma, 48 with papillary carcinoma, 5 patients with medullary carcinoma. The benign thyroid disease involved nodular goitre in 11 patients and follicular adenoma in other 17 patients. The study aimed at examining immunohistochemical expression of Fas protein in order to determine whether the level of its expression correlated with histological diagnosis. In individual patients Fas expression was more prevalent in thyroid carcinomas as compared to benign tumors (p=0.001. A marked increase in Fas expression was found in papillary carcinoma, as compared to follicular and medullary carcinomas (p=0.02. In conclusion, Fas was significantly more frequently overexpressed in thyroid cancer, indicating its role in thyroid tumorigenesis.

  8. The extracellular matrix, p53 and estrogen compete to regulate cell-surface Fas/Apo-1 suicide receptor expression in proliferating embryonic cerebral cortical precursors, and reciprocally, Fas-ligand modifies estrogen control of cell-cycle proteins

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    Newman Joseph M

    2004-03-01

    Full Text Available Abstract Background Apoptosis is important for normal cerebral cortical development. We previously showed that the Fas suicide receptor was expressed within the developing cerebral cortex, and that in vitro Fas activation resulted in caspase-dependent death. Alterations in cell-surface Fas expression may significantly influence cortical development. Therefore, in the following studies, we sought to identify developmentally relevant cell biological processes that regulate cell-surface Fas expression and reciprocal consequences of Fas receptor activation. Results Flow-cytometric analyses identified two distinct neural sub-populations that expressed Fas on their cell surface at high (FasHi or moderate (FasMod levels. The anti-apoptotic protein FLIP further delineated a subset of Fas-expressing cells with potential apoptosis-resistance. FasMod precursors were mainly in G0, while FasHi precursors were largely apoptotic. However, birth-date analysis indicated that neuroblasts express the highest levels of cell-surface Fas at the end of S-phase, or after their final round of mitosis, suggesting that Fas expression is induced at cell cycle checkpoints or during interkinetic nuclear movements. FasHi expression was associated with loss of cell-matrix adhesion and anoikis. Activation of the transcription factor p53 was associated with induction of Fas expression, while the gonadal hormone estrogen antagonistically suppressed cell-surface Fas expression. Estrogen also induced entry into S-phase and decreased the number of Fas-expressing neuroblasts that were apoptotic. Concurrent exposure to estrogen and to soluble Fas-ligand (sFasL suppressed p21/waf-1 and PCNA. In contrast, estrogen and sFasL, individually and together, induced cyclin-A expression, suggesting activation of compensatory survival mechanisms. Conclusions Embryonic cortical neuronal precursors are intrinsically heterogeneous with respect to Fas suicide-sensitivity. Competing intrinsic (p53

  9. Systemic FasL and TRAIL neutralisation reduce leishmaniasis induced skin ulceration.

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    Geremew Tasew

    Full Text Available Cutaneous leishmaniasis (CL is caused by Leishmania infection of dermal macrophages and is associated with chronic inflammation of the skin. L. aethiopica infection displays two clinical manifestations, firstly ulcerative disease, correlated to a relatively low parasite load in the skin, and secondly non-ulcerative disease in which massive parasite infiltration of the dermis occurs in the absence of ulceration of epidermis. Skin ulceration is linked to a vigorous local inflammatory response within the skin towards infected macrophages. Fas ligand (FasL and Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL expressing cells are present in dermis in ulcerative CL and both death ligands cause apoptosis of keratinocytes in the context of Leishmania infection. In the present report we show a differential expression of FasL and TRAIL in ulcerative and non-ulcerative disease caused by L. aethiopica. In vitro experiments confirmed direct FasL- and TRAIL-induced killing of human keratinocytes in the context of Leishmania-induced inflammatory microenvironment. Systemic neutralisation of FasL and TRAIL reduced ulceration in a model of murine Leishmania infection with no effect on parasitic loads or dissemination. Interestingly, FasL neutralisation reduced neutrophil infiltration into the skin during established infection, suggesting an additional proinflammatory role of FasL in addition to direct keratinocyte killing in the context of parasite-induced skin inflammation. FasL signalling resulting in recruitment of activated neutrophils into dermis may lead to destruction of the basal membrane and thus allow direct FasL mediated killing of exposed keratinocytes in vivo. Based on our results we suggest that therapeutic inhibition of FasL and TRAIL could limit skin pathology during CL.

  10. Functional polymorphisms in FAS/FASL system increase the risk of neuroblastoma in Chinese population.

    Directory of Open Access Journals (Sweden)

    Wei Han

    Full Text Available The FAS and FASL system plays a substantial role in apoptosis and immune escape of cells. Three polymorphisms located in the promoter regions of FAS (-1377G/A and -670A/G and FASL (-844T/C have been shown to alter the transcriptional activity of the genes, respectively. This study was conducted to evaluate the effects of these polymorphisms on the susceptibility of neuroblastoma in the Chinese population. A total of 203 patients with neuroblastoma and 411 controls were recruited in this case-control study. Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP was applied for genotyping. Unconditional logistic regression was used to estimate cancer risk by calculating odds ratios (ORs and their 95% confidence intervals (95% CIs. It was observed that significantly increased risks of neuroblastoma associated with FAS -1377G/A and FASL -844T/C polymorphisms, with ORs equal to 1.55 (95% CI, 1.10-2.20 for FAS -1377 A allele and 2.90 (95% CI, 2.04-4.12 for FASL -844CC genotype carriers compared with non-carriers, respectively. However, no association was found between the polymorphisms of FAS -670A/G and risk of neuroblastoma. In addition, the cumulative effect of FAS and FASL polymorphisms on risk of neuroblastoma was observed (P for trend = 2.502×10(-10, with OR for the carriers of both FAS -1377A allele and FASL -844CC genotypes equaled to 3.95 (95% CI, 2.40-6.51. This work reveals that polymorphisms of FAS -1377G/A and FASL -844T/C but not FAS -670A/G are associated with risk of neuroblastoma in Chinese. These findings support the hypothesis that genetic polymorphism in FAS/FASL death system may influence individual susceptibility to neuroblastoma.

  11. Autoimmune lymphoproliferative syndrome caused by a homozygous null FAS ligand (FASLG) mutation.

    Science.gov (United States)

    Magerus-Chatinet, Aude; Stolzenberg, Marie-Claude; Lanzarotti, Nina; Neven, Bénédicte; Daussy, Cécile; Picard, Capucine; Neveux, Nathalie; Desai, Mukesh; Rao, Meghana; Ghosh, Kanjaksha; Madkaikar, Manisha; Fischer, Alain; Rieux-Laucat, Frédéric

    2013-02-01

    Autoimmune lymphoproliferative syndrome (ALPS) is characterized by chronic nonmalignant lymphoproliferation, accumulation of double-negative T cells, hypergammaglobulinemia G and A, and autoimmune cytopenia. Although mostly associated with FAS mutations, different genetic defects leading to impaired apoptosis have been described in patients with ALPS, including the FAS ligand gene (FASLG) in rare cases. Here we report on the first case of complete FAS ligand deficiency caused by a homozygous null mutant. Double-negative T-cell counts and plasma IL-10 and FAS ligand concentrations were determined as ALPS markers. The FASLG gene was sequenced, and its expression was analyzed by means of Western blotting. FAS ligand function was assessed based on reactivation-induced cell death. We describe a patient born to consanguineous parents who presented with a severe form of ALPS caused by FASLG deficiency. Although the clinical presentation was compatible with a homozygous FAS mutation, FAS-induced apoptosis was normal, and plasma FAS ligand levels were not detectable. This patient carries a homozygous, germline, single-base-pair deletion in FASLG exon 1, leading to a premature stop codon (F87fs x95) and a complete defect in FASLG expression. The healthy parents were each heterozygous for the mutation, confirming its recessive trait. FAS ligand deficiency should be screened in patients presenting with ALPS features but lacking the usual markers, including plasma soluble FAS ligand and an in vitro apoptotic defect. An activation-induced cell death test could help in discrimination. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  12. Expression of Fas (CD95/APO-1) ligand by human breast cancers: significance for tumor immune privilege.

    LENUS (Irish Health Repository)

    O'Connell, J

    2012-02-03

    Breast cancers have been shown to elicit tumor-specific immune responses. As in other types of cancer, the antitumor immune response fails to contain breast tumor growth, and a reduction in both the quantity and cytotoxic effectiveness of tumor-infiltrating lymphocytes (TILs) is associated with a poorer prognosis. Fas ligand (FasL) induces apoptotic death of activated lymphocytes that express its cell surface receptor, FasR (CD95\\/APO-1). FasL-mediated apoptosis of activated lymphocytes contributes to normal immune downregulation through its roles in tolerance acquisition, immune response termination, and maintenance of immune privilege in the eye, testis, and fetus. In this report, we demonstrate that breast carcinomas express FasL. Using in situ hybridization and immunohistochemistry, we show that breast tumors constitutively express FasL at both the mRNA and protein levels, respectively. FasL expression is prevalent in breast cancer: 100% of breast tumors (17 of 17) were found to express FasL, and expression occurred over more than 50% of the tumor area in all cases. By immunohistochemistry, FasR was found to be coexpressed with FasL throughout large areas of all the breast tumors. This suggests that the tumor cells had acquired intracellular defects in FasL-mediated apoptotic signaling. FasL and FasR expression were independent of tumor type or infiltrative capacity. FasL expressed by tumor cells has previously been shown to kill Fas-sensitive lymphoid cells in vitro and has been associated with apoptosis of TILs in vivo. We conclude that mammary carcinomas express FasL in vivo as a potential inhibitor of the antitumor immune response.

  13. Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer.

    LENUS (Irish Health Repository)

    Bennett, M W

    2012-02-03

    BACKGROUND: Despite being immunogenic, gastric cancers overcome antitumour immune responses by mechanisms that have yet to be fully elucidated. Fas ligand (FasL) is a molecule that induces Fas receptor mediated apoptosis of activated immunocytes, thereby mediating normal immune downregulatory roles including immune response termination, tolerance acquisition, and immune privilege. Colon cancer cell lines have previously been shown to express FasL and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tumours have since been found to express FasL suggesting that a "Fas counterattack" against antitumour immune effector cells may contribute to tumour immune escape. AIM: To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer. SPECIMENS: Thirty paraffin wax embedded human gastric adenocarcinomas. METHODS: FasL protein was detected in gastric tumours using immunohistochemistry; FasL mRNA was detected in the tumours using in situ hybridisation. Cell death was detected in situ in tumour infiltrating lymphocytes using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). RESULTS: Prevalent expression of FasL was detected in all 30 resected gastric adenocarcinomas examined. In the tumours, FasL protein and mRNA were co-localised to neoplastic gastric epithelial cells, confirming expression by the tumour cells. FasL expression was independent of tumour stage, suggesting that it may be expressed throughout gastric cancer progression. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumour. CONCLUSIONS: Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer.

  14. Progesterone augments epirubicin-induced apoptosis in HA22T/VGH cells by increasing oxidative stress and upregulating Fas/FasL.

    Science.gov (United States)

    Chang, Wen-Tsan; Hsieh, Bau-Shan; Cheng, Hsiao-Ling; Lee, King-Teh; Chang, Kee-Lung

    2014-05-15

    Although epirubicin, an anthracycline drug, is widely used to treat hepatocellular carcinoma, its therapeutic efficacy is disappointing. Thus, the efficacy of epirubicin may be improved when combined with other drugs. This study investigated the therapeutic potential of combination of progesterone and epirubicin in the treatment of the human hepatoma cell line HA22T/VGH and the possible mechanisms through which this combination might induce apoptosis. HA22T/VGH cells were treated without or with 25 μM progesterone and/or 0.5 μM epirubicin and analyzed for oxidative stress, redox status, Fas/FasL expression, caspase activity, and apoptosis. HA22T/VGH cells treated with epirubicin increased the production of reactive oxygen species and nitric oxide, the expression of Fas, FasL, and Fas-associated death domain, and the activities of caspase-8 and caspase-3. Epirubicin treatment also decreased glutathione resulting in the induction of apoptosis. Treatment with progesterone alone increased nitric oxide production, but it did not affect the other parameters. However, when HA22T/VGH cells were treated with progesterone and epirubicin, the effects of epirubicin were enhanced. Our observations suggest that progesterone enhances the efficacy of epirubicin. The increased efficacy is potentially attributed to progesterone's enhancement of epirubicin-induced oxidative stress, thereby reducing redox status. In addition, progesterone sequentially upregulates Fas/FasL to induce the caspase-8 and caspase-3 pathways, thereby resulting in increased apoptosis. The combination had a greater effect on the induction of HA22T/VGH cell apoptosis and could potentially serve as a more effective treatment for hepatocellular carcinoma than epirubicin alone. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. An Examination of the Validity of the Family Affluence Scale II (FAS II) in a General Adolescent Population of Canada

    Science.gov (United States)

    Boudreau, Brock; Poulin, Christiane

    2009-01-01

    This study examined the performance of the FAS II in a general population of 17,545 students in grades 7, 9, 10 and 12 in the Atlantic provinces of Canada. The FAS II was assessed against two other measures of socioeconomic status: mother's highest level of education and family structure. Our study found that the FAS II reduces the likelihood of…

  16. Apoptosis mediated by the Fas system in the fulminant hepatitis by hepatitis B virus.

    Science.gov (United States)

    Rivero, Montserrat; Crespo, J; Fábrega, E; Casafont, F; Mayorga, M; Gomez-Fleitas, M; Pons-Romero, F

    2002-03-01

    The pathogenesis of the fulminant hepatitis B is poorly understood and both viral factors and the hosts immune response play a role. Previous studies in liver tissues of patients with chronic hepatitis B showed overexpression of Fas antigen and this was correlated with the activity of the hepatitis. The present study was done to determine the role of Fas in fulminant hepatitis B and the virological characteristics of hepatitis B infection. We studied three patients with fulminant hepatitis B. HBV-DNA was detected by dot-blot hybridization and polymerase chain reaction. The S and C gene were sequenced. Levels of serum soluble Fas antigen were detected by enzymoimmunoassays procedure. Apoptosis was determined by the TUNEL technique. Fas antigen expression was evaluated by a immunoperoxidase method. Ten healthy subjects acted as controls. The three patients showed a high expression of Fas antigen particularly among infiltrating lymphocytes; in these areas we also found many cells with in situ DNA nick labelling signals in the nuclei of most viable hepatocytes. Serum levels of soluble Fas antigen were higher in patients with fulminant hepatitis B than in controls. No specific genome mutations of hepatitis B virus were found. These data suggest that the Fas system involved in the liver injury of patients with fulminant hepatitis B.

  17. Fas-mediated apoptosis is suppressed by calf serum in cultured bovine luteal cells.

    Science.gov (United States)

    Skarzynski, Dariusz J; Shibaya, Masami; Tasaki, Yukari; Korzekwa, Anna; Murakami, Shuko; Woclawek-Potocka, Izabela; Majewska, Magdalena; Okuda, Kiyoshi

    2007-03-01

    Calf serum (CS) is a common supplement used in cell culture. It has been suggested that CS contains substances protecting cells against apoptosis. To examine whether a culture system including CS is appropriate for studying apoptosis in bovine luteal cells, we examined the influence of CS on the expression of Fas, bcl-2 and bax gene. Since progesterone (P(4)) is known to be an anti-apoptotic factor in bovine luteal cells, the present study was carried out to examine the P(4) effect on apoptosis. Bovine mid-luteal cells were exposed to Fas ligand (Fas L) in the presence or in the absence of P(4) antagonist (onapristone, OP) in a basal medium (BM) containing 5% CS (BM-CS) or BM containing 0.1% BSA (BM-BSA). Although Fas L alone, OP alone or Fas L plus OP did not show any cytotoxic effect on the cells cultured in BM-CS, administration of OP or OP in combination with Fas L resulted in the killing of 30% and 55% of the cells cultured in BM-BSA medium, respectively (pbovine luteal cells by promoting the ratio of bcl-2 to bax expression and by inhibiting Fas expression. Therefore, it may be suggested that CS contains such anti-apoptotic substances (growth factors) amplifying the cell survival pathways in the bovine corpus luteum (CL) in vitro.

  18. Killer B Lymphocytes and their Fas Ligand Positive Exosomes as Inducers of Immune Tolerance

    Directory of Open Access Journals (Sweden)

    Steven Karl Lundy

    2015-03-01

    Full Text Available Induction of immune tolerance is a key process by which the immune system is educated to modulate reactions against benign stimuli such as self-antigens and commensal microbes. Understanding and harnessing the natural mechanisms of immune tolerance may become an increasingly useful strategy for treating many types of allergic and autoimmune diseases, as well as for improving the acceptance of solid organ transplants. Our laboratory and others have been interested in the natural ability of some B lymphocytes to express the death-inducing molecule Fas ligand (FasL, and their ability to kill T helper (TH lymphocytes. We have recently shown that experimental transformation of human B cells by a non-replicative variant of Epstein-Barr virus (EBV consistently resulted in high expression of functional FasL protein. The production and release of FasL+ exosomes that co-expressed MHC Class II molecules and had the capacity to kill antigen-specific TH cells was also observed. Several lines of evidence indicate that FasL+ B cells and FasL+MHCII+ exosomes have important roles in natural immune tolerance and have a great deal of therapeutic potential. Taken together, these findings suggest that EBV-immortalized human B lymphoblastoid cell lines could be used as cellular factories for FasL+ exosomes, which would be employed to therapeutically establish and/or regain immune tolerance toward specific antigens. The goals of this review are to summarize current knowledge of the roles of FasL+ B cells and exosomes in immune regulation, and to suggest methods of manipulating killer B cells and FasL+ exosomes for clinical purposes.

  19. XIAP acts as a switch between type I and type II FAS-induced apoptosis signalling

    OpenAIRE

    Jost, Philipp J.; Grabow, Stephanie; Gray, Daniel; McKenzie, Mark D.; Nachbur, Ueli; Huang, David C.S; Bouillet, Philippe; Thomas, Helen E.; Borner, Christoph; Silke, John; Strasser, Andreas; Kaufmann, Thomas

    2009-01-01

    FAS (APO-1/CD95) and its physiological ligand, FASL, regulate apoptotic death of unwanted or dangerous cells in many tissues, functioning as a guardian against autoimmunity and cancer development1-4. Distinct cell types differ in the mechanisms by which the ‘death receptor’ FAS triggers their apoptosis1-4. In type I cells, such as lymphocytes, activation of ‘effector caspases’ by FAS-induced activation of caspase-8 suffices for cell killing whereas in type II cells, including hepatocytes and ...

  20. Lipopolysaccharides induced increases in Fas ligand expression by Kupffer cells via mechanisms dependent on reactive oxygen species.

    Science.gov (United States)

    Uchikura, Keiichiro; Wada, Tatehiko; Hoshino, Sumito; Nagakawa, Yuichi; Aiko, Takashi; Bulkley, Gregory B; Klein, Andrew S; Sun, Zhaoli

    2004-09-01

    Fas-Fas ligand (FasL)-dependent pathways exert a suppressive effect on inflammatory responses in immune-privileged organs. FasL expression in hepatic Kupffer cells (KC) has been implicated in hepatic immunoregulation. In this study, modulation of FasL expression of KC by endogenous gut-derived bacterial LPS and the role of reactive oxygen species (ROS) as potential mediators of FasL expression in KC were investigated. LPS stimulation of KC resulted in upstream ROS generation and, subsequently, increased FasL expression and consequent Jurkat cell (Fas-positive) apoptosis. The NADPH oxidase and xanthine oxidase enzymatic pathways appear to be major sources of this upstream ROS generation. Increased FasL expression was blocked by antioxidants and by enzymatic blocking of ROS generation. Exogenous administration of H2O2 stimulated KC FasL expression and subsequent Jurkat cell apoptosis. Intracellular endogenous ROS generation may therefore represent an important signal transduction pathway for FasL expression in KC.

  1. An examination of the Apo-1/Fas promoter Mva I polymorphism in Japanese patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Yabe Ichiro

    2002-08-01

    Full Text Available Abstract Background The Apo-1/Fas (CD95 molecule is an apoptosis-signaling cell surface receptor belonging to the tumor necrosis factor (TNF receptor family. Both Fas and Fas ligand (FasL are expressed in activated mature T cells, and prolonged cell activation induces susceptibility to Fas-mediated apoptosis. The Apo-1/Fas gene is located in a chromosomal region that shows linkage in multiple sclerosis (MS genome screens, and studies indicate that there is aberrant expression of the Apo-1/Fas molecule in MS. Methods Mva I polymorphism on the Apo-1/Fas promoter gene was detected by PCR-RFLP from the DNA of 114 Japanese patients with conventional MS and 121 healthy controls. We investigated the association of the Mva I polymorphism in Japanese MS patients using a case-control association study design. Results We found no evidence that the polymorphism contributes to susceptibility to MS. Furthermore, there was no association between Apo-1/Fas gene polymorphisms and clinical course (relapsing-remitting course or secondary-progressive course. No significant association was observed between Apo-1/Fas gene polymorphisms and the age at disease onset. Conclusions Overall, our findings suggest that Apo-1/Fas promoter gene polymorphisms are not conclusively related to susceptibility to MS or the clinical characteristics of Japanese patients with MS.

  2. Food irradiation

    Energy Technology Data Exchange (ETDEWEB)

    1987-02-28

    A brief article examines the controversy over food irradiation regarding the wholesomeness of irradiated food, its microbiological safety, loss of vitamins and changes in flavour. The benefits of food irradiation are also outlined including the destruction of certain food-borne pathogens and the prolongation of the shelf-life of food by killing pests and delaying the deterioration process.

  3. Increased FasL expression correlates with apoptotic changes in granulocytes cultured with oxidized clozapine.

    Science.gov (United States)

    Husain, Zaheed; Almeciga, Ingrid; Delgado, Julio C; Clavijo, Olga P; Castro, Januario E; Belalcazar, Viviana; Pinto, Clara; Zuñiga, Joaquin; Romero, Viviana; Yunis, Edmond J

    2006-08-01

    Clozapine has been associated with a 1% incidence of agranulocytosis. The formation of an oxidized intermediate clozapine metabolite has been implicated in direct polymorphonuclear (PMN) toxicity. We utilized two separate systems to analyze the role of oxidized clozapine in inducing apoptosis in treated cells. Human PMN cells incubated with clozapine (0-10 microM) in the presence of 0.1 mM H2O2 demonstrated a progressive decrease of surface CD16 expression along with increased apoptosis. RT-PCR analysis showed decreased CD16 but increased FasL gene expression in clozapine-treated PMN cells. No change in constitutive Fas expression was observed in treated cells. In HL-60 cells induced to differentiate with retinoic acid (RA), a similar increase in FasL expression, but no associated changes in CD16 gene expression, was observed following clozapine treatments. Our results demonstrate increased FasL gene expression in oxidized clozapine-induced apoptotic neutrophils suggesting that apoptosis in granulocytes treated with clozapine involves Fas/FasL interaction that initiates a cascade of events leading to clozapine-induced agranulocytosis.

  4. Attenuated Disease in SIV-Infected Macaques Treated with a Monoclonal Antibody against FasL

    Directory of Open Access Journals (Sweden)

    Maria S. Salvato

    2007-01-01

    Full Text Available Acute SIVmac infection in macaques is accompanied by high levels of plasma viremia that decline with the appearance of viral immunity and is a model for acute HIV disease in man. Despite specific immune responses, the virus establishes a chronic, persistent infection. The destruction of CD4+ and CD4- lymphocyte subsets in macaques contributes to viral persistence and suggests the importance of mechanisms for depleting both infected and uninfected (bystander cells. Bystander cell killing can occur when FasL binds the Fas receptor on activated lymphocytes, which include T and B cell subpopulations that are responding to the infection. Destruction of specific immune cells could be an important mechanism for blunting viral immunity and establishing persistent infection with chronic disease. We inhibited the Fas pathway in vivo with a monoclonal antibody against FasL (RNOK203. Here we show that treatment with anti-FasL reduced cell death in circulating T and B cells, increased CTL and antibody responses to viral proteins, and lowered the setpoint viremia. By blocking FasL during only the first few weeks after infection, we attenuated SIVmac disease and increased the life span for infected and treated macaques.

  5. Hyperoxia accelerates Fas-mediated signaling and apoptosis in the lungs of Legionella pneumophila pneumonia

    Directory of Open Access Journals (Sweden)

    Tanabe Yoshinari

    2011-04-01

    Full Text Available Abstract Background Oxygen supplementation is commonly given to the patients with severe pneumonia including Legionella disease. Recent data suggested that apoptosis may play an important role, not only in the pathogenesis of Legionella pneumonia, but also in oxygen-induced tissue damage. In the present study, the lethal sensitivity to Legionella pneumonia were compared in the setting of hyperoxia between wild-type and Fas-deficient mice. Findings C57BL/6 mice and B6.MRL-Faslpr mice characterized with Fas-deficiency were used in this study. After intratracheal administration of L. pneumophila, mice were kept in hyperoxic conditions (85-90% O2 conc. in an airtight chamber for 3 days. Bone-marrow derived macrophages infected with L. pneumophila were also kept in hyperoxic conditions. Caspase activity and cytokine production were determined by using commercially available kits. Smaller increases of several apoptosis markers, such as caspase-3 and -8, were demonstrated in Fas-deficient mice, even though the bacterial burdens in Fas-deficient and wild type mice were similar. Bone-marrow derived macrophages from Fas-deficient mice were shown to be more resistant to Legionella-induced cytotoxicity than those from wild-type mice under hyperoxia. Conclusions These results demonstrated that Fas-mediated signaling and apoptosis may be a crucial factor in the pathogenesis of Legionella pneumonia in the setting of hyperoxia.

  6. Interferon-gamma and tumor necrosis factor-alpha sensitize primarily resistant human endometrial stromal cells to Fas-mediated apoptosis

    DEFF Research Database (Denmark)

    Fluhr, Herbert; Krenzer, Stefanie; Stein, Gerburg M

    2007-01-01

    The subtle interaction between the implanting embryo and the maternal endometrium plays a pivotal role during the process of implantation. Human endometrial stromal cells (ESCs) express Fas and the implanting trophoblast cells secrete Fas ligand (FASLG, FasL), suggesting a possible role for Fas...

  7. Epstein-Barr virus induces Fas (CD95) in T cells and Fas ligand in B cells leading to T-cell apoptosis.

    Science.gov (United States)

    Tanner, J E; Alfieri, C

    1999-11-15

    Epstein-Barr virus (EBV) acute infectious mononucleosis (AIM) is characterized by transient immunosuppression in vivo and increased T-cell apoptosis after ex vivo culture of AIM peripheral blood mononuclear cells. We undertook experiments to test whether EBV or purified virion envelope glycoprotein gp350 could contribute to Fas-mediated T-cell apoptosis. Our in vitro results indicate that EBV increased Fas expression in CD4(+) T cells and Fas ligand (FasL) expression in B cells and macrophages. Purified gp350 was also shown to significantly increase CD95 expression in CD4(+) T cells. When T-cell CD95 was cross-linked, EBV-stimulated T cells underwent apoptosis. The induction of T-cell CD95 by EBV followed by CD95 cross-linking with anti-CD95 monoclonal antibody resulted in a loss in the number of T cells responding to the T-cell mitogens, anti-CD3 antibody, and interleukin-2. These results indicate that, in addition to serving as a principal ligand for the attachment of virus to target cells, gp350 may also act as an immunomodulatory molecule that promotes T-cell apoptosis.

  8. FAS: equipment with PED and ATEX EC-Certificates; FAS: equipements CE au titre de la DESP et de l'ATEX

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2004-04-15

    Since 1975 the company FAS Flussiggas-Anlagen GmbH, Salzgitter Germany, is one of the leading manufacturers of LPG equipment and components for mobile and stationary bulk plants in Europe. The main products are dispensers, Autogas filling stations, vaporizers, loading arms, electronic cylinder filling scales, flanged valves and safety equipment. (authors)

  9. JAK2 inhibitor combined with DC-activated AFP-specific T-cells enhances antitumor function in a Fas/FasL signal-independent pathway.

    Science.gov (United States)

    Liu, Yang; Wang, Yue-Ru; Ding, Guang-Hui; Yang, Ting-Song; Yao, Le; Hua, Jie; He, Zhi-Gang; Qian, Ming-Ping

    2016-01-01

    Combination therapy for cancer is more effective than using only standard chemo- or radiotherapy. Our previous results showed that dendritic cell-activated α-fetoprotein (AFP)-specific T-cells inhibit tumor in vitro and in vivo. In this study, we focused on antitumor function of CD8(+) T-cells combined with or without JAK2 inhibitor. Proliferation and cell cycle were analyzed by CCK-8 and flow cytometry. Western blot was used to analyze the expression level of related protein and signaling pathway. We demonstrated reduced viability and induction of apoptosis of tumor cells with combination treatment. Intriguingly, cell cycle was blocked at the G1 phase by using AFP-specific CD8(+) T-cells combined with JAK2 inhibitor (AG490). Furthermore, an enhanced expression of BAX but no influence on Fas/FasL was detected from the tumor cells. These results indicate a Fas/FasL-independent pathway for cellular apoptosis in cancer therapies with the treatment of AFP-specific CD8(+) T-cells combined with JAK2 inhibitor.

  10. Examining the psychometric properties of the Hindi version of Family Accommodation Scale-Self-Report (FAS-SR).

    Science.gov (United States)

    Mahapatra, Ananya; Gupta, Rishi; Patnaik, Kuppili Pooja; Pattanaik, Raman Deep; Khandelwal, Sudhir Kumar

    2017-10-01

    Family accommodation (FA) is the phenomenon whereby caregivers assist or facilitate rituals or behaviours related to obsessive compulsive disorder (OCD). There is a need for a self-rated instrument to assess this construct in resource-strained clinical settings of India. To explore the factor structure of Hindi version of Family Accommodation Scale-Self Rated version (FAS-SR) and compare its validity with the gold standard Family Accommodation Scale-Interviewer Rated (FAS-IR) scale. The Hindi version of FAS-SR scale and FAS-IR scale was applied on 105 caregivers of patients with OCD. The initial factor analysis yielded three-factor models with an eigenvalue of >1 and the total variance explained by these factors was 72.017%. The internal consistency of the 19-item scale was 0.93 indicating good inter-item correlation. There was a significant positive correlation between FAS-IR scale total score and all the factors of the FAS-SR Scale. The average measure ICC was 0.889 with a 95% confidence interval from 0.783 to 0.981 (F (62,84)=37.547, pHindi version of FAS-SR and the FAS-IR scale. FAS-SR is a practical alternative to FAS-IR and has the potential to be used widely in an Indian setting. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Fas activation induces renal tubular epithelial cell beta 8 integrin expression and function in the absence of apoptosis.

    Science.gov (United States)

    Jarad, George; Wang, Bingcheng; Khan, Shenaz; DeVore, Jay; Miao, Hui; Wu, Karen; Nishimura, Stephen L; Wible, Barbara A; Konieczkowski, Martha; Sedor, John R; Schelling, Jeffrey R

    2002-12-06

    Cell fate following Fas (CD95) ligand or agonistic anti-Fas antibody stimulation is determined by multiple factors, including Fas expression level, microdomain localization, and modulating cytokines. Highly expressed Fas clusters and activates a canonical apoptosis signaling pathway. In less susceptible cells, Fas transduces apoptosis-independent signals, which are not well defined, but have been linked to inflammation, angiogenesis, and fibrosis. To identify apoptosis-independent Fas pathways, cultured renal tubular epithelial cells were stimulated with agonistic anti-Fas antibodies under conditions that did not cause cell death. Analysis of filter cDNA microarrays revealed beta(8) integrin subunit mRNA induction in Fas-stimulated cells. beta(8) integrin mRNA expression increased within 3-6 h of Fas ligation due to enhanced mRNA stabilization, and mRNA increases were sustained for 48-72 h. Expression of plasma membrane beta(8) integrin, as well as its heterodimer partner alpha(v), was increased by Fas activation with a similar kinetic pattern. Fas-induced alpha(v)beta(8) expression correlated with increased migration to vitronectin, the ligand for alpha(v)beta(8). Results from studies with function-blocking antibodies against other alpha(v)beta integrins or suppression of beta(8) integrin expression by RNA interference demonstrated that induced beta(8) integrin expression mediated Fas-stimulated migration. We conclude that alpha(v)beta(8) integrin induction defines an unexpected role for Fas in cell migration, rather than as a cell death receptor.

  12. P2X7 signaling promotes microsphere embolism-triggered microglia activation by maintaining elevation of Fas ligand

    OpenAIRE

    Lu Ying-mei; Tao Rong-rong; Huang Ji-yun; Li Li-tao; Liao Mei-hua; Li Xiao-ming; Fukunaga Kohji; Hong Ze-Hui; Han Feng

    2012-01-01

    Abstract Background The cerebral microvascular occlusion elicits microvascular injury which mimics the different degrees of stroke severity observed in patients, but the mechanisms underlying these embolic injuries are far from understood. The Fas ligand (FasL)-Fas system has been implicated in a number of pathogenic states. Here, we examined the contribution of microglia-derived FasL to brain inflammatory injury, with a focus on the potential to suppress the FasL increase by inhibition of th...

  13. Upregulation of Fas-Fas-L (CD95/CD95L)-mediated epithelial apoptosis--a putative role in pouchitis?

    LENUS (Irish Health Repository)

    Coffey, J C

    2012-02-03

    INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) remains the gold standard for patients with refractory ulcerative colitis. Pouchitis causes considerable morbidity in 40% of patients with IPAA. This study examined the role of increased epithelial apoptosis in the etiology of pouchitis. METHODS: Following ethical approval pouch biopsies taken from patients with a history of pouchitis were compared with age-matched controls from patients who were pouchitis free. Apoptosis was detected immunohistochemically using a monoclonal antibody (M30) and terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin end labeling (TUNEL). Villous atrophy was assessed histologically and correlated with levels of apoptosis. Epithelial Fas-ligand (L) was also assessed immunohistochemically. RESULTS: A significant increase in TUNEL staining was seen at the epithelial but not at the lamina propria level for known pouchitis patients versus controls (0.091 vs 0.035; P < 0.01). Similarly, epithelial M30 immunoreactivity (0.225 vs 0.082; P < 0.05) and villous atrophy (0.035 vs 0.10; P < 0.05) were significantly increased in pouches with previous pouchitis when compared with normal pouches. Upregulation of Fas-L expression was characteristic of this epithelium. Mononuclear cells were strongly positive for Fas-L. Increased epithelial levels of apoptosis correlated with increased levels of villous atrophy. CONCLUSIONS: Our data suggest a role for elevated Fas-Fas-L (CD95-CD95L)-mediated epithelial apoptosis in the etiology of pouchitis. Increased levels of villous atrophy may result from increased apoptosis and thereby predispose to infection by otherwise apathogenic organisms.

  14. FAS-L, IL-10, and double-negative CD4- CD8- TCR alpha/beta+ T cells are reliable markers of autoimmune lymphoproliferative syndrome (ALPS) associated with FAS loss of function.

    Science.gov (United States)

    Magerus-Chatinet, Aude; Stolzenberg, Marie-Claude; Loffredo, Maria S; Neven, Bénédicte; Schaffner, Catherine; Ducrot, Nicolas; Arkwright, Peter D; Bader-Meunier, Brigitte; Barbot, José; Blanche, Stéphane; Casanova, Jean-Laurent; Debré, Marianne; Ferster, Alina; Fieschi, Claire; Florkin, Benoit; Galambrun, Claire; Hermine, Olivier; Lambotte, Olivier; Solary, Eric; Thomas, Caroline; Le Deist, Francoise; Picard, Capucine; Fischer, Alain; Rieux-Laucat, Frédéric

    2009-03-26

    Autoimmune lymphoproliferative syndrome (ALPS) is characterized by splenomegaly, lymphadenopathy, hypergammaglobulinemia, accumulation of double-negative TCRalphabeta(+) CD4(-)CD8(-) T cells (DNT cells), and autoimmunity. Previously, DNT cell detection and a functional defect of T cells in a FAS-induced apoptosis test in vitro had been used for ALPS diagnosis. However, a functional defect can also be detected in mutation-positive relatives (MPRs) who remain free of any ALPS-related disease. In contrast, lymphocytes from patients carrying a somatic mutation of FAS exhibit normal sensitivity to FAS-induced apoptosis in vitro. We assessed the soluble FAS-L concentration in the plasma of ALPS patients carrying FAS mutations. Overall, we showed that determination of the FAS-L represents, together with the IL-10 concentration and the DNT cell percentage, a reliable tool for the diagnosis of ALPS.

  15. The FAS fluency test in Brazilian children and teenagers: executive demands and the effects of age and gender

    Directory of Open Access Journals (Sweden)

    Natália Martins Dias

    2014-01-01

    Full Text Available The FAS Verbal Fluency Test is widely used in neuropsychological clinical services and research. This study investigated the contributions of different executive functions, age and gender to FAS test performance in a sample of children and teenagers divided into two groups: G1 comprised 263 children aged 6-10 years, and G2 comprised 150 teenagers aged 10-14 years. All participants were assessed using the Cancellation Attention Test, the Auditory Working Memory Test, the Visual Working Memory Test, the Semantic Generation Test, and the Trail Making Test, in addition to the FAS test. For G1, age, auditory working memory and shifting were predictors of FAS performance. For G2, gender, auditory working memory, shifting and inhibition comprised the FAS explanatory model. The study contributed to our understanding of which are the best predictor variables for the FAS test in a Brazilian sample and how executive demands change with age.

  16. FAS -670A>G genetic polymorphism Is associated with Treatment Resistant Depression.

    Science.gov (United States)

    Santos, Marlene; Carvalho, Serafim; Lima, Luís; Mota-Pereira, Jorge; Pimentel, Paulo; Maia, Dulce; Correia, Diana; Gomes, Sofia; Cruz, Agostinho; Medeiros, Rui

    2015-10-01

    Hippocampal neurogenesis has been suggested as a downstream event of antidepressants (AD) mechanism of action and might explain the lag time between AD administration and the therapeutic effect. Despite the widespread use of AD in the context of Major Depressive Disorder (MDD) there are no reliable biomarkers of treatment response phenotypes, and a significant proportion of patients display Treatment Resistant Depression (TRD). Fas/FasL system is one of the best-known death-receptor mediated cell signaling systems and is recognized to regulate cell proliferation and tumor cell growth. Recently this pathway has been described to be involved in neurogenesis and neuroplasticity. Since FAS -670A>G and FASL -844T>C functional polymorphisms never been evaluated in the context of depression and antidepressant therapy, we genotyped FAS -670A>G and FASL -844T>C in a subset of 80 MDD patients to evaluate their role in antidepressant treatment response phenotypes. We found that the presence of FAS -670G allele was associated with antidepressant bad prognosis (relapse or TRD: OR=6.200; 95% CI: [1.875-20.499]; p=0.001), and we observed that patients carrying this allele have a higher risk to develop TRD (OR=10.895; 95% CI: [1.362-87.135]; p=0.008). Moreover, multivariate analysis adjusted to potentials confounders showed that patients carrying G allele have higher risk of early relapse (HR=3.827; 95% CI: [1.072-13.659]; p=0.039). FAS mRNA levels were down-regulated among G carriers, whose genotypes were more common in TRD patients. No association was found between FASL-844T>C genetic polymorphism and any treatment phenotypes. Small sample size. Patients used antidepressants with different mechanisms of action. To the best of our knowledge this is the first study to evaluate the role of FAS functional polymorphism in the outcome of antidepressant therapy. This preliminary report associates FAS -670A>G genetic polymorphism with Treatment Resistant Depression and with time to

  17. Psychometric properties of the Fatigue Assessment Scale (FAS in women with breast problems

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    Jolanda De Vries

    2010-01-01

    Full Text Available Se examina la utilidad de la Escala de Evaluación de la Fatiga (FAS en mujeres con problemas benignos de mama (BBP y en mujeres con cáncer precoz de mama (BC. Las mujeres con un nódulo palpable en la mama o una anomalía en unamamografía de cribado (N = 560 completaron la FAS (en cuatro momentos y medidas de ansiedad, síntomas depresivos, neuroticismo, y fatiga. La FAS tuvo un buen ajuste en la población total (CFI = 0,96; ×2 (29 = 104,5, p < 0,001; NNFI = 0,95; RMSEA = 0,091, en el grupo de BC (CFI = 0,95; X2 (32 = 69,6, p < 0,001; NNFI = 0,91; RMSEA = 0,090 y en el grupo BBP (CFI = 0,95; ×2 (34 = 99,9, p < 0,001; NNFI = 0,92; RMSEA = 0,105. La consistencia interna (0,89 para el grupo total y la fiabilidad test-retest (grupo BBP, r = 0,88 intervalo de tres meses fueron buenas. La FAS diferenció síntomas depresivos, neuroticismo, estado de ansiedad. En conclusión, la FAS tiene una buena fiabilidad y validez en mujeres con problemas de mama y mide fatiga sin superponerse de forma importante con síntomas depresivos, estado de ansiedad y neuroticismo.

  18. Inflammation, apoptosis, and necrosis induced by neoadjuvant fas ligand gene therapy improves survival of dogs with spontaneous bone cancer.

    Science.gov (United States)

    Modiano, Jaime F; Bellgrau, Donald; Cutter, Gary R; Lana, Susan E; Ehrhart, Nicole P; Ehrhart, Ej; Wilke, Vicki L; Charles, J Brad; Munson, Sibyl; Scott, Milcah C; Pozniak, John; Carlson, Cathy S; Schaack, Jerome; Duke, Richard C

    2012-12-01

    Fas ligand (FasL) gene therapy for cancer has shown promise in rodents; however, its efficacy in higher mammals remains unknown. Here, we used intratumoral FasL gene therapy delivered in an adenovirus vector (Ad-FasL) as neoadjuvant to standard of care in 56 dogs with osteosarcoma. Tumors from treated dogs had greater inflammation, necrosis, apoptosis, and fibrosis at day 10 (amputation) compared to pretreatment biopsies or to tumors from dogs that did not receive Ad-FasL. Survival improvement was apparent in dogs with inflammation or lymphocyte-infiltration scores >1 (in a 3-point scale), as well as in dogs that had apoptosis scores in the top 50th percentile (determined by cleaved caspase-3). Survival was no different than that expected from standard of care alone in dogs with inflammation scores ≤1 or apoptosis scores in the bottom 50th percentile. Reduced Fas expression by tumor cells was associated with prognostically advantageous inflammation, and this was seen only in dogs that received Ad-FasL. Together, the data suggest that Ad-FasL gene therapy improves survival in a subset of large animals with naturally occurring tumors, and that at least in some tumor types like osteosarcoma, it is most effective when tumor cells fail to express Fas.

  19. Transplanted Human Umbilical Cord Mesenchymal Stem Cells Facilitate Lesion Repair in B6.Fas Mice

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    Guang-ping Ruan

    2014-01-01

    Full Text Available Background. Systemic lupus erythematosus (SLE is a multisystem disease that is characterized by the appearance of serum autoantibodies. No effective treatment for SLE currently exists. Methods. We used human umbilical cord mesenchymal stem cell (H-UC-MSC transplantation to treat B6.Fas mice. Results. After four rounds of cell transplantation, we observed a statistically significant decrease in the levels of mouse anti-nuclear, anti-histone, and anti-double-stranded DNA antibodies in transplanted mice compared with controls. The percentage of CD4+CD25+Foxp3+ T cells in mouse peripheral blood significantly increased after H-UC-MSC transplantation. Conclusions. The results showed that H-UC-MSCs could repair lesions in B6.Fas mice such that all of the relevant disease indicators in B6.Fas mice were restored to the levels observed in normal C57BL/6 mice.

  20. Irradiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Howe, L.M

    2000-07-01

    There is considerable interest in irradiation effects in intermetallic compounds from both the applied and fundamental aspects. Initially, this interest was associated mainly with nuclear reactor programs but it now extends to the fields of ion-beam modification of metals, behaviour of amorphous materials, ion-beam processing of electronic materials, and ion-beam simulations of various kinds. The field of irradiation damage in intermetallic compounds is rapidly expanding, and no attempt will be made in this chapter to cover all of the various aspects. Instead, attention will be focused on some specific areas and, hopefully, through these, some insight will be given into the physical processes involved, the present state of our knowledge, and the challenge of obtaining more comprehensive understanding in the future. The specific areas that will be covered are: point defects in intermetallic compounds; irradiation-enhanced ordering and irradiation-induced disordering of ordered alloys; irradiation-induced amorphization.

  1. Anti-Fas conjugated hyaluronic acid microsphere gels for neural stem cell delivery.

    Science.gov (United States)

    Shendi, Dalia; Albrecht, Dirk R; Jain, Anjana

    2017-02-01

    Central nervous system (CNS) injuries and diseases result in neuronal damage and loss of function. Transplantation of neural stem cells (NSCs) has been shown to improve locomotor function after transplantation. However, due to the immune and inflammatory response at the injury site, the survival rate of the engrafted cells is low. Engrafted cell viability has been shown to increase when transplanted within a hydrogel. Hyaluronic acid (HA) hydrogels have natural anti-inflammatory properties and the backbone can be modified to introduce bioactive agents, such as anti-Fas, which we have previously shown to promote NSC survival while suppressing immune cell activity in bulk hydrogels in vitro. Although bulk HA hydrogels have shown to promote stem cell survival, microsphere gels for NSC encapsulation and delivery may have additional advantages. In this study, a flow-focusing microfluidic device was used to fabricate either vinyl sulfone-modified HA (VS-HA) or anti-Fas-conjugated HA (anti-Fas HA) microsphere gels encapsulated with NSCs. The majority of encapsulated NSCs remained viable for at least 24 h in the VS-HA and anti-Fas HA microsphere gels. Moreover, T-cells cultured in suspension with the anti-Fas HA microsphere gels had reduced viability after contact with the microsphere gels compared to the media control and soluble anti-Fas conditions. This approach can be adapted to encapsulate various cell types for therapeutic strategies in other physiological systems in order to increase survival by reducing the immune response. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 608-618, 2017. © 2016 Wiley Periodicals, Inc.

  2. 4-Nonylphenol induces disruption of spermatogenesis associated with oxidative stress-related apoptosis by targeting p53-Bcl-2/Bax-Fas/FasL signaling.

    Science.gov (United States)

    Duan, Peng; Hu, Chunhui; Butler, Holly J; Quan, Chao; Chen, Wei; Huang, Wenting; Tang, Sha; Zhou, Wei; Yuan, Meng; Shi, Yuqin; Martin, Francis L; Yang, Kedi

    2017-03-01

    4-Nonylphenol (NP) is a ubiquitous environmental chemical with estrogenic activity. Our aim was to test the hypothesis that pubertal exposure to NP leads to testicular dysfunction. Herein, 24 7-week-old rats were randomly divided into four groups and treated with NP (0, 25, 50, or 100 mg/kg body weight every 2 days for 20 consecutive days) by intraperitoneal injection. Compared to untreated controls, the parameters of sperm activation rate, curvilinear velocity, average path velocity, and swimming velocity were significantly lower at doses of 100 mg/kg, while sperm morphological abnormalities were higher, indicating functional disruption and reduced fertilization potential. High exposure to NP (100 mg/kg) resulted in disordered arrangement of spermatoblasts and reduction of spermatocytes in seminiferous tubules, while tissues exhibited a marked decline in testicular fructose content and serum FSH, LH, and testosterone levels. Oxidative stress was induced by NP (50 or 100 mg/kg) as evidenced by elevated MDA, decreased SOD and GSH-Px, and inhibited antioxidant gene expression (CAT, GPx, SOD1, and CYP1B1). In addition, NP treatment decreased proportions of Ki-67-positive cells and increased apoptosis in a dose-dependent manner. Rats treated with 100 mg/kg NP exhibited significantly increased mRNA expression of caspase-1, -2, -9, and -11, decreased caspase-8 and PCNA1 mRNA expression, downregulation of Bcl-2/Bax ratios and upregulation of Fas, FasL, and p53 at the protein and mRNA levels. Taken together, NP-induced apoptosis, hormonal deficiencies, and depletion of fructose potentially impairs spermatogenesis and sperm function. p53-independent Fas/FasL-Bax/Bcl-2 pathways may be involved in NP-induced oxidative stress-related apoptosis. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 739-753, 2017. © 2016 Wiley Periodicals, Inc.

  3. Clinical significance of soluble Fas plasma levels in patients with sepsis

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    Mikić Dragan

    2015-01-01

    Full Text Available Background/Aim. The goal of modern clinical and experimental researches in the field of sepsis is to find one or more sensitive parameters that could predict the severity of sepsis and its outcome. In this study we investigated and compared the relationship of initial soluble Fas (sFas plasma levels as well as Acute Physiology, Age and Chronic Health Evaluation II (APACHE II score in 58 septic patients with severity and outcome of sepsis. Methods. The diagnosis and assessment of disease severity was performed on the same day, based on clinical and laboratory parameters. The blood samples were used for monitoring of laboratory standard parameters necessary for the diagnosis of sepsis, organ dysfunction and assessment of disease severity, as well as for determination of levels of sFas. According to consensus criteria, patients were divided into those with sepsis (n = 16, severe sepsis (n = 30 or septic shock (n = 12, those with (n = 26 and without (n = 32 multiple organ dysfunction syndrome (MODS, and survivors (n = 45 and non-survivors (n = 13. Results. Plasma sFas level (9.7 ± 10.1; 0-44.2 U/mL was elevated in 54.4% of patients. All the patients with septic shock, 76.9% of the patients with MODS and 84.6% patients who died had elevated sFas level. We observed a strong positive correlation between sFas and APACHE II score (p < 0.001. The level of sFas was significantly higher in patients with septic shock compared to normotensive patients (p < 0.001, patients with MODS compared to those without MODS (p < 0.001 and survivors compared to nonsurvivors (p < 0.01. Conclusions. Our results suggest that initial sFas plasma levels in patients with sepsis correlated with the values of APACHE II score and separated very well the patients with septic shock versus the normotensive patients, the patients with and without MODS, and survivors versus non-survivors.

  4. Adaphostin promotes caffeine-evoked autocrine Fas-mediated death pathway activation in Bcr/Abl-positive leukaemia cells.

    Science.gov (United States)

    Liu, Wen-Hsin; Chang, Long-Sen

    2011-11-01

    The present study was conducted to verify whether caffeine is beneficial for improving leukaemia therapy. Co-treatment with adaphostin (a Bcr/Abl inhibitor) was found to potentiate caffeine-induced Fas/FasL up-regulation. Although adaphostin did not elicit ASK1 (apoptosis signal-regulating kinase 1)-mediated phosphorylation of p38 MAPK (mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase), co-treatment with adaphostin notably increased p38 MAPK/JNK activation in caffeine-treated cells. Suppression of p38 MAPK and JNK abrogated Fas/FasL up-regulation in caffeine- and caffeine/adaphostin-treated cells. Compared with caffeine, adaphostin markedly suppressed Akt/ERK (extracellular-signal-regulated kinase)-mediated MKP-1 (MAPK phosphatase 1) protein expression in K562 cells. MKP-1 down-regulation eventually elucidated the enhanced effect of adaphostin on p38 MAPK/JNK activation and subsequent Fas/FasL up-regulation in caffeine-treated cells. Knockdown of p38α MAPK and JNK1, ATF-2 (activating transcription factor 2) and c-Jun by siRNA (small interfering RNA) proved that p38α MAPK/ATF-2 and JNK1/c-Jun pathways were responsible for caffeine-evoked Fas/FasL up-regulation. Moreover, Ca2+ and ROS (reactive oxygen species) were demonstrated to be responsible for ASK1 activation and Akt/ERK inactivation respectively in caffeine- and caffeine/adaphostin-treated cells. Likewise, adaphostin functionally enhanced caffeine-induced Fas/FasL up-regulation in leukaemia cells that expressed Bcr/Abl. Taken together, the results of the present study suggest a therapeutic strategy in improving the efficacy of adaphostin via Fas-mediated death pathway activation in Bcr/Abl-positive leukaemia.

  5. CD47 deficiency ameliorates autoimmune nephritis in Fas(lpr) mice by suppressing IgG autoantibody production.

    Science.gov (United States)

    Shi, Lei; Bian, Zhen; Chen, Celia X J; Guo, Ya-Nan; Lv, Zhiyuan; Zeng, Caihong; Liu, Zhihong; Zen, Ke; Liu, Yuan

    2015-11-01

    CD47, a self-recognition marker, plays an important role in both innate and adaptive immune responses. To explore the potential role of CD47 in activation of autoreactive T and B cells and the production of autoantibodies in autoimmune disease, especially systemic lupus erythematosus (SLE), we have generated CD47 knockout Fas(lpr) (CD47(-/-) -Fas(lpr) ) mice and examined histopathological changes in the kidneys, cumulative survival rates, proteinuria, extent of splenomegaly and autoantibodies, serum chemistry and immunological parameters. In comparison with Fas(lpr) mice, CD47(-/-) -Fas(lpr) mice exhibit a prolonged lifespan and delayed autoimmune nephritis, including glomerular cell proliferation, basement membrane thickening, acute tubular atrophy and vacuolization. CD47(-/-) -Fas(lpr) mice have lower levels of proteinuria, associated with reduced deposition of complement C3 and C1q, and IgG but not IgM in the glomeruli, compared to age-matched Fas(lpr) mice. Serum levels of antinuclear antibodies and anti-double-stranded DNA antibodies are significantly lower in CD47(-/-) -Fas(lpr) than in Fas(lpr) mice. CD47(-/-) -Fas(lpr) mice also display less pronounced splenomegaly than Fas(lpr) mice. The mechanistic studies further suggest that CD47 deficiency impairs the antigenic challenge-induced production of IgG but not IgM, and that this effect is associated with reduction of T follicular cells and impairment of germinal centre development in lymphoid tissues. In conclusion, our results demonstrate that CD47 deficiency ameliorates lupus nephritis in Fas(lpr) mice via suppression of IgG autoantibody production. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  6. Fas Ligand Has a Greater Impact than TNF-α on Apoptosis and Inflammation in Ischemic Acute Kidney Injury

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    Kengo Furuichi

    2012-02-01

    Full Text Available Background/Aim: Fas ligand (FasL and tumor necrosis factor (TNF-α are major pro-apoptotic molecules and also induce inflammation through cytokine and chemokine production. Although precise intracellular mechanisms of action have been reported for each molecule, the differential impact of these molecules on kidney injury in vivo still requires clarification. Methods: We explored the differential impact of FasL and TNF-α upon apoptosis and inflammation in ischemic acute kidney injury using neutralizing anti-FasL antibodies and TNF-α receptor 1 (TNFR1-deficient mice. Results: TNFR1 deficiency was associated with a lesser anti-inflammatory effect upon leukocyte infiltration and tubular necrosis than treatment with anti-FasL antibody. Furthermore, the number of TUNEL-positive cells was significantly reduced in anti-FasL antibody-treated mice, whereas it was only partially diminished in TNFR1-deficient mice. In vitro studies confirmed these findings. FasL administration induced both apoptosis and cytokine/chemokine production from cultured tubular epithelial cells. However, TNF-α had a limited effect upon tubular epithelial cells. Conclusion: In ischemic acute kidney injury, FasL has a greater impact than TNF-α on the apoptosis and inflammatory reaction through cytokine/chemokine production from tubular epithelial cells.

  7. Perforin-dependent apoptosis functionally compensates Fas deficiency in activation-induced cell death of human T lymphocytes.

    Science.gov (United States)

    Mateo, Véronique; Ménager, Michael; de Saint-Basile, Geneviève; Stolzenberg, Marie-Claude; Roquelaure, Bertrand; André, Nicolas; Florkin, Benoit; le Deist, Françoise; Picard, Capucine; Fischer, Alain; Rieux-Laucat, Frédéric

    2007-12-15

    Activation-induced cell death (AICD) is involved in peripheral tolerance by controlling the expansion of repeatedly stimulated T cells via an apoptotic Fas (CD95; APO-1)-dependent pathway. The TNFRSF-6 gene encoding Fas is mutated in children suffering from autoimmune lymphoproliferative syndrome (ALPS), which is characterized by lymphoproliferation and autoimmunity. We examined AICD in Fas-deficient T cells from ALPS patients. We showed that primary activated Fas-deficient T cells die by apoptosis after repeated T cell antigen receptor (TCR) stimulation despite resistance to Fas-mediated cell death. This Fas-independent AICD was found to be mediated through a cytotoxic granules-dependent pathway. Cytotoxic granules-mediated AICD was also detected in normal T lymphocytes though to a lesser extent. As expected, the cytotoxic granules-dependent AICD was abolished in T cells from Rab27a- or perforin-deficient patients who exhibited defective granules-dependent cytotoxicity. Supporting an in vivo relevance of the cytotoxic granules-dependent AICD in ALPS patients, we detected an increased number of circulating T lymphocytes expressing granzymes A and B. Altogether, these data indicated that the cytotoxic granules-dependent cell death in ALPS may compensate for Fas deficiency in T lymphocytes. Furthermore, they identified a novel AICD pathway as a unique alternative to Fas apoptosis in human peripheral T lymphocytes.

  8. Fas-ligand (CD178) and TRAIL synergistically induce apoptosis of CD40-activated chronic lymphocytic leukemia B cells

    NARCIS (Netherlands)

    Dicker, Frank; Kater, Arnon P.; Fukuda, Tetsuya; Kipps, Thomas J.

    2005-01-01

    Chronic lymphocytic leukemia (CLL) B cells become sensitive to Fas (CD95)-mediated apoptosis 3 to 5 days after CD40 ligation. However, CD4+ cytotoxic T lymphocytes (CTLs) can kill CLL B cells via a Fas-ligand (CD178)-dependent process within 24 hours after CD40 cross-linking, when ligation of CD95

  9. Cells bearing mutations causing Leber's hereditary optic neuropathy are sensitized to Fas-Induced apoptosis.

    Science.gov (United States)

    Danielson, Steven R; Wong, Alice; Carelli, Valerio; Martinuzzi, Andrea; Schapira, Anthony H V; Cortopassi, Gino A

    2002-02-22

    Three prevalent mitochondrial DNA pathogenic mutations at positions 11778, 3460, and 14484, which affect different subunits of Complex I, cause retinal ganglion cell death and optic nerve atrophy in Leber's hereditary optic neuropathy (LHON). The cell death is painless and without inflammation, consistent with an apoptotic mechanism. We have investigated the possibility that the LHON mutation confers a pro-apoptotic stimulus and have tested the sensitivity of osteosarcoma-derived cybrid cells carrying the most common and severe mutations (11778 and 3460) to cell death induced by Fas. We observed that LHON cybrids were sensitized to Fas-dependent death. Control cells that bear the same mitochondrial genetic background (the J haplogroup) without the pathogenic 11778 mutation are no more sensitive than other controls, indicating that increased Fas-dependent death in LHON cybrids was induced by the LHON pathogenic mutations. The type of death was apoptotic by several criteria, including induction by Fas, inhibition by the caspase inhibitor zVAD-fmk (zVal-Ala-Asp-fluoro-methyl ketone), activation of DEVDase activity (Asp-Glu-Val-Asp protease), specific cleavage of caspase-3, DNA fragmentation, and increased Annexin-V labeling. These data indicate that the most common and severe LHON pathogenic mutations 11778 and 3460 predispose cells to apoptosis, which may be relevant for the pathophysiology of cell death in LHON, and potential therapy.

  10. Prevalence and clinical significance of resistance to perforin- and FAS-mediated cell death in leukemia

    NARCIS (Netherlands)

    Otten, H. G.; van Ginkel, W. G. J.; Hagenbeek, A.; Petersen, E. J.

    2004-01-01

    Killer lymphocytes play a central therapeutic role in graft-versus-leukemia following allogeneic hematopoietic stem cell transplantation (HSCT). The Perforin/Granzyme and FAS/CD95 pathways are of crucial importance in tumor cell elimination by killer cells. In this study, we have examined whether

  11. Myocardial overexpression of Mecr, a gene of mitochondrial FAS II leads to cardiac dysfunction in mouse.

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    Zhijun Chen

    Full Text Available It has been recently recognized that mammalian mitochondria contain most, if not all, of the components of fatty acid synthesis type II (FAS II. Among the components identified is 2-enoyl thioester reductase/mitochondrial enoyl-CoA reductase (Etr1/Mecr, which catalyzes the NADPH-dependent reduction of trans-2-enoyl thioesters, generating saturated acyl-groups. Although the FAS type II pathway is highly conserved, its physiological role in fatty acid synthesis, which apparently occurs simultaneously with breakdown of fatty acids in the same subcellular compartment in mammals, has remained an enigma. To study the in vivo function of the mitochondrial FAS in mammals, with special reference to Mecr, we generated mice overexpressing Mecr under control of the mouse metallothionein-1 promoter. These Mecr transgenic mice developed cardiac abnormalities as demonstrated by echocardiography in vivo, heart perfusion ex vivo, and electron microscopy in situ. Moreover, the Mecr transgenic mice showed decreased performance in endurance exercise testing. Our results showed a ventricular dilatation behind impaired heart function upon Mecr overexpression, concurrent with appearance of dysmorphic mitochondria. Furthermore, the data suggested that inappropriate expression of genes of FAS II can result in the development of hereditary cardiomyopathy.

  12. Association of FAS (TNFRSF6)-670 gene polymorphism with villous atrophy in coeliac disease.

    Science.gov (United States)

    Wu, Jing; Alizadeh, B Z; Veen, T V; Meijer, J W R; Mulder, C J J; Pena, A S

    2004-03-01

    To investigate the association of FAS gene polymorphism with coeliac disease (CD) development. FAS-G670A gene polymorphism, located in a gamma interferon activation site, was studied in 146 unrelated CD patients and 203 healthy ethnically matched controls. The restriction fragment length polymorphism (RFLP) method was used to identify FAS-G670A gene polymorphism. No significant difference was found in genotype frequency between CD cases and controls. In controls, however, the frequency of the GG genotype was significantly higher in women (26.5%) than in men (12.8%) (OR= 2.44, 95% CI 1.15-5.20, P=0.020) and it was also higher in men with CD than controls (OR=2.60, 95% CI 0.96-7.05, P=0.061). The GG genotype frequency was significantly higher in patients with most severe villous atrophy (Marsh IIIc lesions) (OR=3.74, 95% CI 1.19-11.82, P=0.025). A significantly less proportion of men suffered from Marsh IIIc lesions than women (OR=0.20, 95% CI 0.06-0.68, P=0.01). The risk of having severe villous atrophy increased with the additive effect of the G allele in women (P=0.027 for trend, age and gender adjusted). FAS-G670A gene polymorphism is associated with the severity of villous atrophy in CD. Female gender is also associated with the severity of villous atrophy.

  13. Relationship between Fas rs1800682 Gene Polymorphism and Susceptibility to Polycystic Ovary Syndrome

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    Samira Heidarpanah

    2017-01-01

    Full Text Available Abstract Background: Polycystic ovary syndrome(PCOS is the most common endocrine aberration in women. PCOS is characterized by ovarian hyperandrogenism and anovulation resulted from a disorder of follicular maturation. Apoptosis is a regulatory mechanism for oocyte maturation and survival. Several studies have shown a possible role of Fas in ovarian apoptosis. The present study is the first investigation to examine the possible association of Fas rs1800682gene polymorphism with PCOS risk in Iranian women. Materials and Methods: This case-control study was conducted on 251 patients with PCOS and 213 healthy control women. The Fas rs1800682 gene polymorphism genotypes were analyzed using the Tetra-ARMS-PCR method. Also, logistic regression analysis was used to investigate the association between genotypes and PCOS risk. Results: There was a significant association between A allele and susceptibility to PCOS(OR =1.4, %95CI=1.08-1.83, p=0.011. Moreover, in the recessive genetic model for A allele, the AA genotype increased the risk of PCOS after adjusting age and body mass index(OR=1.6, %95CI=1.02-2.51, p=0.041. Conclusion: For the first time, this study showed that Fas rs1800682 polymorphism is associated with PCOS risk in Iranian women and the A allele may act as a recessive allele for increasing the risk of PCOS.

  14. Effects of smoking on activation markers, Fas expression and apoptosis of peripheral blood lymphocytes

    NARCIS (Netherlands)

    Bijl, Marc; Limburg, Piet; Kallenberg, Cees; Horst, G.

    Background Smoking influences numbers and function of peripheral blood lymphocytes (PBL) by a process that is badly understood. We conducted this study to evaluate whether the immune impairment of smoking might be related to changes in the expression or functionality of Fas, a cell surface molecule

  15. FAS on tarneklausel, mis sobib ainult laevaga kaupa vedades / Jürgen Valter

    Index Scriptorium Estoniae

    Valter, Jürgen

    2008-01-01

    Rahvuvahelise Kaubanduskoja (ICC) koostatud rahvusvaheliste kaubandusreeglite tarneklauslite süsteemi teisest klauslist FAS, mis on suhteliselt müüjasõbralik, kuid seab samas müüjale mõnevõrra rohkem kohustusi kui esimene, EXW-klausel. Tabel: klauslitel on erinev vastutusmäär

  16. The Fas pathway is involved in pancreatic beta cell secretory function

    DEFF Research Database (Denmark)

    Schumann, Desiree M; Maedler, Kathrin; Franklin, Isobel

    2007-01-01

    Pancreatic beta cell mass and function increase in conditions of enhanced insulin demand such as obesity. Failure to adapt leads to diabetes. The molecular mechanisms controlling this adaptive process are unclear. Fas is a death receptor involved in beta cell apoptosis or proliferation, depending...

  17. The Effectiveness of Peer-Led FAS/FAE Prevention Presentations in Middle and High Schools

    Science.gov (United States)

    Boulter, Lyn

    2007-01-01

    Pregnant women and women who might become pregnant, including middle school- and high school-age adolescents, continue to consume alcohol, placing themselves at risk of having a child with the effects of prenatal alcohol exposure. However, most prevention programs that attempt to increase public awareness and knowledge of FAS and related disorders…

  18. Germline FAS gene mutation in a case of ALPS and NLP Hodgkin lymphoma

    NARCIS (Netherlands)

    van den Berg, Anke; Maggio, Ewerton; Diepstra, A; de Jong, Doetje; van Krieken, J; Poppema, S

    2002-01-01

    FAS germline mutations have been associated with the development of autoimmune lymphoproliferative syndrome (ALPS). Occurrence of Hodgkin lymphoma (HL) has been reported in 2 families with ALPS. In both families an uncle of the index patient developed HL. A 15-year-old boy with autoommune

  19. XIAP discriminates between type I and type II FAS-induced apoptosis.

    Science.gov (United States)

    Jost, Philipp J; Grabow, Stephanie; Gray, Daniel; McKenzie, Mark D; Nachbur, Ueli; Huang, David C S; Bouillet, Philippe; Thomas, Helen E; Borner, Christoph; Silke, John; Strasser, Andreas; Kaufmann, Thomas

    2009-08-20

    FAS (also called APO-1 and CD95) and its physiological ligand, FASL, regulate apoptosis of unwanted or dangerous cells, functioning as a guardian against autoimmunity and cancer development. Distinct cell types differ in the mechanisms by which the 'death receptor' FAS triggers their apoptosis. In type I cells, such as lymphocytes, activation of 'effector caspases' by FAS-induced activation of caspase-8 suffices for cell killing, whereas in type II cells, including hepatocytes and pancreatic beta-cells, caspase cascade amplification through caspase-8-mediated activation of the pro-apoptotic BCL-2 family member BID (BH3 interacting domain death agonist) is essential. Here we show that loss of XIAP (X-chromosome linked inhibitor of apoptosis protein) function by gene targeting or treatment with a second mitochondria-derived activator of caspases (SMAC, also called DIABLO; direct IAP-binding protein with low pI) mimetic drug in mice rendered hepatocytes and beta-cells independent of BID for FAS-induced apoptosis. These results show that XIAP is the critical discriminator between type I and type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions.

  20. XIAP acts as a switch between type I and type II FAS-induced apoptosis signalling

    Science.gov (United States)

    Jost, Philipp J.; Grabow, Stephanie; Gray, Daniel; McKenzie, Mark D.; Nachbur, Ueli; Huang, David C.S.; Bouillet, Philippe; Thomas, Helen E.; Borner, Christoph; Silke, John; Strasser, Andreas; Kaufmann, Thomas

    2010-01-01

    FAS (APO-1/CD95) and its physiological ligand, FASL, regulate apoptotic death of unwanted or dangerous cells in many tissues, functioning as a guardian against autoimmunity and cancer development1-4. Distinct cell types differ in the mechanisms by which the ‘death receptor’ FAS triggers their apoptosis1-4. In type I cells, such as lymphocytes, activation of ‘effector caspases’ by FAS-induced activation of caspase-8 suffices for cell killing whereas in type II cells, including hepatocytes and pancreatic β-cells, amplification of the caspase cascade through caspase-8 mediated activation of the pro-apoptotic BCL-2 family member BID5 is essential6-8. Here we show, that loss of X-chromosome linked inhibitor of apoptosis (XIAP)9,10 function by gene-targeting or treatment with a second mitochondria-derived activator of caspases (SMAC11, also called DIABLO12: direct IAP binding protein with low pI) mimetic drug rendered hepatocytes independent of BID for FAS-induced apoptosis signalling. These results show that XIAP is the critical discriminator between type I versus type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions. PMID:19626005

  1. Interaction of calreticulin with CD40 ligand, TRAIL and Fas ligand

    DEFF Research Database (Denmark)

    Duus, K; Pagh, R T; Holmskov, U

    2007-01-01

    found to bind calreticulin strongly. A low level or no binding was observed for adiponectin, tumour necrosis factor-alpha (TNF-alpha), CD30L, surfactant protein-A and -D and collagen VIII. The interaction with calreticulin required a conformational change in CD40L, TRAIL and FasL and showed the same...

  2. An Evolution-Guided Analysis Reveals a Multi-Signaling Regulation of Fas by Tyrosine Phosphorylation and its Implication in Human Cancers.

    Directory of Open Access Journals (Sweden)

    Krittalak Chakrabandhu

    2016-03-01

    Full Text Available Demonstrations of both pro-apoptotic and pro-survival abilities of Fas (TNFRSF6/CD95/APO-1 have led to a shift from the exclusive "Fas apoptosis" to "Fas multisignals" paradigm and the acceptance that Fas-related therapies face a major challenge, as it remains unclear what determines the mode of Fas signaling. Through protein evolution analysis, which reveals unconventional substitutions of Fas tyrosine during divergent evolution, evolution-guided tyrosine-phosphorylated Fas proxy, and site-specific phosphorylation detection, we show that the Fas signaling outcome is determined by the tyrosine phosphorylation status of its death domain. The phosphorylation dominantly turns off the Fas-mediated apoptotic signal, while turning on the pro-survival signal. We show that while phosphorylations at Y232 and Y291 share some common functions, their contributions to Fas signaling differ at several levels. The findings that Fas tyrosine phosphorylation is regulated by Src family kinases (SFKs and the phosphatase SHP-1 and that Y291 phosphorylation primes clathrin-dependent Fas endocytosis, which contributes to Fas pro-survival signaling, reveals for the first time the mechanistic link between SFK/SHP-1-dependent Fas tyrosine phosphorylation, internalization route, and signaling choice. We also demonstrate that levels of phosphorylated Y232 and Y291 differ among human cancer types and differentially respond to anticancer therapy, suggesting context-dependent involvement of Fas phosphorylation in cancer. This report provides a new insight into the control of TNF receptor multisignaling by receptor phosphorylation and its implication in cancer biology, which brings us a step closer to overcoming the challenge in handling Fas signaling in treatments of cancer as well as other pathologies such as autoimmune and degenerative diseases.

  3. The construction and application of diploid sake yeast with a homozygous mutation in the FAS2 gene.

    Science.gov (United States)

    Kotaka, Atsushi; Sahara, Hiroshi; Hata, Yoji

    2010-12-01

    In Japanese sake brewing, cerulenin-resistant sake yeasts produce elevated levels of ethyl caproate, an important flavor component. The FAS2 mutation FAS2-1250S of Saccharomyces cerevisiae generates a cerulenin-resistant phenotype. This mutation is dominant, and, in general, cerulenin-resistant diploid sake yeast strains carry this mutation heterozygously. Here we constructed diploid sake yeast with a homozygous mutation of FAS2 using the high-efficiency loss of heterozygosity method. The homozygous mutants grew more slowly in YPD medium than did the wild-type and heterozygous mutants, and they produced more ethyl caproate during sake brewing. In addition, although both the wild-type and heterozygous mutant were sensitive to 4 mg/l cerulenin, the homozygous mutant was resistant to more than 4 mg/l cerulenin. Next, we obtained a homozygous mutant of FAS2 without inducing genetic modification. After cultivating the heterozygous FAS2 mutant K-1801 in YPD, homozygous mutants were selected on medium containing high concentrations of cerulenin. Non-genetically modified yeast with a homozygous mutation of FAS2 produced 2.2-fold more ethyl caproate than did heterozygous yeast. Moreover, high-quality Japanese sake with a very rich flavor could be brewed using yeast containing a homozygous mutation in the FAS2 gene. Copyright © 2010. Published by Elsevier B.V.

  4. Irradiation subassembly

    Science.gov (United States)

    Seim, O.S.; Filewicz, E.C.; Hutter, E.

    1973-10-23

    An irradiation subassembly for use in a nuclear reactor is described which includes a bundle of slender elongated irradiation -capsules or fuel elements enclosed by a coolant tube and having yieldable retaining liner between the irradiation capsules and the coolant tube. For a hexagonal bundle surrounded by a hexagonal tube the yieldable retaining liner may consist either of six segments corresponding to the six sides of the tube or three angular segments each corresponding in two adjacent sides of the tube. The sides of adjacent segments abut and are so cut that metal-tometal contact is retained when the volume enclosed by the retaining liner is varied and Springs are provided for urging the segments toward the center of the tube to hold the capsules in a closely packed configuration. (Official Gazette)

  5. Fas ligand expression in human and mouse cancer cell lines; a caveat on over-reliance on mRNA data

    Directory of Open Access Journals (Sweden)

    Ryan Aideen E

    2006-02-01

    Full Text Available Abstract Background During carcinogenesis, tumors develop multiple mechanisms for evading the immune response, including upregulation of Fas ligand (FasL/CD95L expression. Expression of FasL may help to maintain tumor cells in a state of immune privilege by inducing apoptosis of anti-tumor immune effector cells. Recently this idea has been challenged by studies reporting that tumor cells of varying origin do not express FasL. In the present study, we aimed to comprehensively characterize FasL expression in tumors of both murine and human origin over a 72 hour time period. Methods RNA and protein was extracted from six human (SW620, HT29, SW480, KM12SM, HCT116, Jurkat and three mouse (CMT93, CT26, B16F10 cancer cell lines at regular time intervals over a 72 hour time period. FasL expression was detected at the mRNA level by RT-PCR, using intron spanning primers, and at the protein level by Western Blotting and immunofluorescence, using a polyclonal FasL- specific antibody. Results Expression of FasL mRNA and protein was observed in all cell lines analysed. However, expression of FasL mRNA varied dramatically over time, with cells negative for FasL mRNA at many time points. In contrast, 8 of the 9 cell lines constitutively expressed FasL protein. Thus, cells can abundantly express FasL protein at times when FasL mRNA is absent. Conclusion These findings demonstrate the importance of complete analysis of FasL expression by tumor cells in order to fully characterize its biological function and may help to resolve the discrepancies present in the literature regarding FasL expression and tumor immune privilege.

  6. MSP-4, an Antimicrobial Peptide, Induces Apoptosis via Activation of Extrinsic Fas/FasL- and Intrinsic Mitochondria-Mediated Pathways in One Osteosarcoma Cell Line.

    Science.gov (United States)

    Kuo, Hsiao-Mei; Tseng, Chung-Chih; Chen, Nan-Fu; Tai, Ming-Hong; Hung, Han-Chun; Feng, Chien-Wei; Cheng, Shu-Yu; Huang, Shi-Ying; Jean, Yen-Hsuan; Wen, Zhi-Hong

    2018-01-02

    Osteosarcoma (OS) is a common malignant bone cancer. The relatively high density of a person's bone structure means low permeability for drugs, and so finding drugs that can be more effective is important and should not be delayed. MSPs are marine antimicrobial peptides (AMP) and natural compounds extracted from Nile tilapia ( Oreochromis niloticus ). MSP-4 is a part of the AMPs series, with the advantage of having a molecular weight of about 2.7-kDa and anticancer effects, although the responsible anticancer mechanism is not very clear. The goal of this study is to determine the workings of the mechanism associated with apoptosis resulting from MSP-4 in osteosarcoma MG63 cells. The study showed that MSP-4 significantly induced apoptosis in MG63 cells, with Western blot indicating that MSP-4 induced this apoptosis through an intrinsic pathway and an extrinsic pathway. Thus, a pretreatment system with a particular inhibitor of Z-IETD-FMK (caspase-8 inhibitor) and Z-LEHD-FMK (caspase-9 inhibitor) significantly attenuated the cleavage of caspase-3 and prevented apoptosis. These observations indicate that low concentrations of MSP-4 can help induce the apoptosis of MG63 through a Fas/FasL- and mitochondria-mediated pathway and suggest a potentially innovative alternative to the treatment of human osteosarcoma.

  7. The role of TNF-α, Fas/Fas ligand system and NT-proBNP in the early detection of asymptomatic left ventricular dysfunction in cancer patients treated with anthracyclines

    Directory of Open Access Journals (Sweden)

    Alexandros Kouloubinis

    2015-03-01

    Conclusion: SFas, sFas-L and NT-proBNP correlate with reductions in LVEF and could be used as sensitive biochemical indices for the detection of asymptomatic left ventricular dysfunction in cancer patients under cardiotoxic chemotherapy.

  8. Dominant inhibition of Fas ligand-mediated apoptosis due to a heterozygous mutation associated with autoimmune lymphoproliferative syndrome (ALPS Type Ib

    Directory of Open Access Journals (Sweden)

    McDonald Jay M

    2007-07-01

    Full Text Available Abstract Background: Autoimmune lymphoproliferative syndrome (ALPS is a disorder of lymphocyte homeostasis and immunological tolerance due primarily to genetic defects in Fas (CD95/APO-1; TNFRSF6, a cell surface receptor that regulates apoptosis and its signaling apparatus. Methods: Fas ligand gene mutations from ALPS patients were identified through cDNA and genomic DNA sequencing. Molecular and biochemical assessment of these mutant Fas ligand proteins were carried out by expressing the mutant FasL cDNA in mammalian cells and analysis its effects on Fas-mediated programmed cell death. Results: We found an ALPS patient that harbored a heterozygous A530G mutation in the FasL gene that replaced Arg with Gly at position 156 in the protein's extracellular Fas-binding region. This produced a dominant-interfering FasL protein that bound to the wild-type FasL protein and prevented it from effectively inducing apoptosis. Conclusion: Our data explain how a naturally occurring heterozygous human FasL mutation can dominantly interfere with normal FasL apoptotic function and lead to an ALPS phenotype, designated Type Ib.

  9. Fas ligand based immunotherapy: A potent and effective neoadjuvant with checkpoint inhibitor properties, or a systemically toxic promoter of tumor growth?

    Science.gov (United States)

    Modiano, Jaime F; Bellgrau, Donald

    2016-02-01

    Fas ligand (FasL, CD95L) is a 40-kDa type II transmembrane protein that binds to Fas (CD95) receptors and promotes programmed cell death. Fas receptors are expressed at higher levels in many tumors than in normal cells; however, systemic administration of FasL or agonistic anti-Fas antibodies to mice with tumors caused lethal hepatitis. Somewhat paradoxically, elimination of Fas or FasL from tumors also leads to death induced by CD95 receptor/ligand elimination (DICE). At face value, this suggests that Fas signaling not only kills normal cells, but that it also is essential for tumor cell survival. Targeting this pathway may not only fail to kill tumors, but instead may even enhance their growth, leading some to report the demise of Fas ligand in cancer immunotherapy. But, to paraphrase Mark Twain, is this death an exaggeration? Here, we provide a careful examination of the literature exploring the merits of FasL as a novel form of cancer immunotherapy. With local administration using delivery vectors that achieve high levels of expression in the tumor environment, our results indicate that the potential for systemic toxicity is eliminated in higher mammals, and that a systemic anti-tumor response ensues, which delays or prevents progression and simultaneously attacks distant metastases.

  10. Fas-associated factor 1 interacts with protein kinase CK2 in vivo upon apoptosis induction

    DEFF Research Database (Denmark)

    Guerra, B; Boldyreff, B; Issinger, O G

    2001-01-01

    We show here that in several different cell lines protein kinase CK2 and Fas-associated factor 1 (FAF1) exist together in a complex which is stable to high monovalent salt concentration. The CK2/FAF1 complex formation is significantly increased after induction of apoptosis with various DNA damaging...... the view that protein kinase CK2 plays an important role in certain steps of apoptosis....

  11. FasT-Fix versus inside-out suture meniscal repair in the goat model.

    Science.gov (United States)

    Hospodar, Steven J; Schmitz, Matthew R; Golish, S Raymond; Ruder, Craig R; Miller, Mark D

    2009-02-01

    Recent all-inside meniscal repair devices are available, but in vivo studies with these devices are sparse. The FasT-Fix has inferior meniscal healing compared with the inside-out suture technique in the goat model. Controlled laboratory study. After Institutional Review Board approval, 73 male castrated goats (Capra hircus) underwent a 2-cm meniscal incision and subsequent repair with the FasT-Fix device on one knee and inside-out meniscal repair on the contralateral knee. Both repairs used a vertical mattress suture technique. Access to the menisci was via an open technique with an extra-articular osteotomy of the medial collateral ligament origin on the femur. The animals were then allowed to ambulate unrestricted in a pasture after a 7-day stay in cages. Necropsy was carried out 6 months postoperatively, and the menisci and articular cartilage were studied with gross and microscopic inspection. Nine of the 73 animals were excluded before necropsy. A total of 64 animals underwent necropsy, gross measurement of residual lesions, gross evaluation for chondral damage, histologic evaluation of meniscal repair, histologic evaluation of any adjacent inflammatory reaction to implants, and data analysis. Compared with the inside-out group, the FasT-Fix group had longer residual full-thickness defects (1.2 +/- 2.9 mm vs 0.2 +/- 1.1 mm; P = .011) and longer residual partial-thickness defects (8.4 +/- 6.3 mm vs 3.6 +/- 5.5 mm; P inside-out meniscal repair technique in the goat model. The clinical significance of this finding is not known. Further clinical study of the FasT-Fix implant is warranted.

  12. A survey of physicians knowledge regarding awareness of maternal alcohol use and the diagnosis of FAS.

    Directory of Open Access Journals (Sweden)

    Koren Gideon

    2002-02-01

    Full Text Available Abstract Background Alcohol is the most widely used drug in the world that is a human teratogen whose use among women of childbearing age has been steadily increasing. It is also probable that Fetal Alcohol Syndrome is under diagnosed by physicians. The objectives of this study were twofold: 1 to evaluate the experience, knowledge and confidence of family physicians with respect to the diagnosis of FAS and 2 to evaluate physicians awareness of maternal drinking patterns. Methods and Participants A multiple choice anonymous questionnaire was sent to a randomly selected group of family physicians in the Metropolitan Toronto area. Results There was a 73% (75/103 total response rate; Overall, 6/75 (8% of family physicians reported that they had actually diagnosed a child with FAS. 17.9% had suspicions but did not make a diagnosis and 12.7% reported making a referral to confirm the diagnosis. Physician rated confidence in the ability to diagnosis FAS was low, with 49% feeling they had very little confidence. 75% reported counselling pregnant women and 60.8% reported counselling childbearing women in general on the use of alcohol. When asked what screening test they used to detect the use of alcohol, 75% described frequency/quantity. Not a single respondent identified using the current accepted screening method for alcohol use (TWEAK which is recommended by The Centre for Addiction and Mental Health. Conclusions Family physicians do not feel confident about diagnosing FAS. None of the physicians were aware of the current screening methods to accurately gage alcohol use in pregnant and childbearing women

  13. The microbiota regulates susceptibility to Fas-mediated acute hepatic injury

    Science.gov (United States)

    Celaj, Stela; Gleeson, Michael W.; Deng, Jie; O'Toole, George A.; Hampton, Thomas H.; Toft, Martin F.; Morrison, Hilary G.; Sogin, Mitchell L.; Putra, Juan; Suriawinata, Arief A.; Gorham, James D.

    2014-01-01

    Whereas a significant role for intestinal microbiota in affecting the pathogenesis and progression of chronic hepatic diseases is well documented, the contribution of the intestinal flora to acute liver injury has not been extensively addressed. Elucidating the influence of the intestinal microbiota on acute liver inflammation would be important for better understanding the transition from acute injury to chronic liver disease. Using the Concanavalin A (ConA)-induced liver injury model in laboratory mice, we show that the severity of acute hepatic damage varies greatly among genetically identical mice raised in different environments and harboring distinct microbiota. Through reconstitution of germ-free (GF) mice, and the co-housing of conventional mice, we provide direct evidence that manipulation of the intestinal flora alters susceptibility to ConA-induced liver injury. Through deep sequencing of the fecal microbiome, we observe that the relative abundance of Ruminococcaceae, a Gram(+) family within the class Clostridia, but distinct from segmented filamentous bacteria, is positively associated with the degree of liver damage. Searching for the underlying mechanism(s) that regulate susceptibility to ConA, we provide evidence that the extent of liver injury following triggering of the death receptor Fas varies greatly as a function of the microbiota. We demonstrate that the extent of Fas induced liver injury increases in GF mice after microbiota reconstitution, and decreases in conventionally raised mice following reduction of intestinal bacterial load, by antibiotic treatment. We also show that the regulation of sensitivity to Fas induced liver injury is dependent upon the Toll-Like Receptor signaling molecule MyD88. Conclusion The status and composition of the intestinal microbiota determine the susceptibility to ConA-induced acute liver injury. The microbiota acts as a rheostat, actively modulating the extent of liver damage in response to Fas triggering. PMID

  14. Dental follicle cells and cementoblasts induce apoptosis of ameloblast-lineage and Hertwig's epithelial root sheath/epithelial rests of Malassez cells through the Fas-Fas ligand pathway.

    Science.gov (United States)

    Lee, Ji-Hyun; Lee, Dong-Seol; Nam, Hyun; Lee, Gene; Seo, Byoung-Moo; Cho, Young-Sik; Bae, Hyun-Sook; Park, Joo-Cheol

    2012-02-01

    Hertwig's epithelial root sheath (HERS), epithelial rests of Malassez (ERM) cells, and reduced ameloblasts undergo apoptosis during tooth development. This study examined the effects of dental follicle cells and cementoblasts on the apoptosis of ameloblast-lineage and HERS/ERM cells derived from the enamel organ. We also elucidated the induction pathways and identified the apoptotic pathway involved in this process. Here, we showed terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling (TUNEL)-positive HERS cells and reduced ameloblasts near dental follicle cells during tooth development. Co-culturing ameloblast-lineage cell line (ALC) ameloblasts and HERS/ERM cells with either dental follicle cells or OCCM-30 cementoblasts markedly enhanced the apoptosis of ameloblasts and HERS/ERM cells compared with cells cultured alone. However, dental follicle cells and cementoblasts did not modulate the apoptotic responses of co-cultured non-odontogenic MCF10A or KB cells. When ameloblasts + HERS and cementoblasts + dental follicle cells were co-cultured, the expression of Fas ligand (FasL) increased in cementoblasts + dental follicle cells, while the expression of Fas increased in ameloblasts + HERS. Interestingly, recombinant FasL induced ameloblast apoptosis while the cementoblast-induced ameloblast apoptosis was suppressed by the Fas/FasL antagonist Kp7-6. These results suggest that during tooth development, dental follicle cells and cementoblasts induce apoptosis of ameloblast-lineage and HERS/ERM cells through the Fas-FasL pathway, but do not induce the apoptosis of non-odontogenic epithelial cells. © 2011 Eur J Oral Sci.

  15. Norsolorinic acid inhibits proliferation of T24 human bladder cancer cells by arresting the cell cycle at the G0/G1 phase and inducing a Fas/membrane-bound Fas ligand-mediated apoptotic pathway.

    Science.gov (United States)

    Wang, Clay C C; Chiang, Yi-Ming; Kuo, Po-Lin; Chang, Jiunn-Kae; Hsu, Ya-Ling

    2008-11-01

    1. Norsolorinic acid, isolated from Aspergillus nidulans, has been shown to have antiproliferative activity in T24 human bladder cancer cells by arresting the cell cycle at the G(0)/G(1) phase and inducing apoptosis. The aim of the present study was to investigate the antiproliferative activity of norsolorinic acid in T24 human bladder cancer cells. 2. The effects of norsolorinic acid (1, 5, 10 and 20 micromol/L) on the proliferation of T24 cells and on the distribution of cells within different phases of the cell cycle were investigated indirectly using an XTT assay and a flow cytometer, respectively. Factors affecting the cell cycle and apoptosis, including p53, p21, Fas receptor, Fas ligand (FasL) and caspase 8 activity, were examined using ELISA. 3. The results showed that norsolorinic acid inhibited proliferation of T24 cells in a dose-dependent manner, with an IC(50) of 10.5 micromol/L. The effect involved the induction of cell cycle arrest at the G(0)/G(1) phase and apoptosis. 4. These results demonstrate that G(0)/G(1) phase arrest is due to increased expression of p21 in cells treated with norsolorinic acid (10 and 20 micromol/L) for 24 h. Moreover, enhanced Fas and membrane-bound Fas ligand (mFasL) may be responsible for the apoptotic effect of norsolorinic acid. Thus, the present study reports, for the first time, that induction of p21 and the Fas/mFas ligand apoptotic system may participate in the antiproliferative action of norsolorinic acid in T24 human bladder cancer cells.

  16. Motoneuron death triggered by a specific pathway downstream of Fas. potentiation by ALS-linked SOD1 mutations

    National Research Council Canada - National Science Library

    Raoul, Cédric; Estévez, Alvaro G; Nishimune, Hiroshi; Cleveland, Don W; deLapeyrière, Odile; Henderson, Christopher E; Haase, Georg; Pettmann, Brigitte

    2002-01-01

    .... We show that Fas-triggered death of normal embryonic motoneurons requires transcriptional upregulation of neuronal NOS and involves Daxx, ASK1, and p38 together with the classical FADD/caspase-8 cascade...

  17. Decoy receptor 3 suppresses FasL-induced apoptosis via ERK1/2 activation in pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yi; Li, Dechun; Zhao, Xin; Song, Shiduo; Zhang, Lifeng; Zhu, Dongming [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006 (China); Wang, Zhenxin [Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006 (China); Chen, Xiaochen [Department of Pathology, The Obstetrics & Gynecology Hospital of Fudan University, Shanghai 200090 (China); Zhou, Jian, E-mail: zhoujian20150602@126.com [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006 (China)

    2015-08-07

    Resistance to Fas Ligand (FasL) mediated apoptosis plays an important role in tumorigenesis. Decoy receptor 3 (DcR3) is reported to interact with FasL and is overexpressed in some malignant tumors. We sought to investigate the role of DcR3 in resistance to FasL in pancreatic cancer. We compared expression of apoptosis related genes between FasL-resistant SW1990 and FasL-sensitive Patu8988 pancreatic cell lines by microarray analysis. We explored the impact of siRNA knockdown of, or exogenous supplementation with, DcR3 on FasL-induced cell growth inhibition in pancreatic cancer cell lines and expression of proteins involved in apoptotic signaling. We assessed the level of DcR3 protein and ERK1/2 phosphorylation in tumor and non-tumor tissue samples of 66 patients with pancreatic carcinoma. RNAi knockdown of DcR3 expression in SW1990 cells reduced resistance to FasL-induced apoptosis, and supplementation of Patu8988 with rDcR3 had the opposite effect. RNAi knockdown of DcR3 in SW1990 cells elevated expression of caspase 3, 8 and 9, and reduced ERK1/2 phosphorylation (P < 0.05), but did not alter phosphorylated-Akt expression. 47 tumor tissue specimens, but only 15 matched non-tumor specimens stained for DcR3 (χ{sup 2} = 31.1447, P < 0.001). The proliferation index of DcR3 positive specimens (14.26  ±  2.67%) was significantly higher than that of DcR3 negative specimens (43.58  ±  7.88%, P < 0.01). DcR3 expression positively correlated with p-ERK1/2 expression in pancreatic cancer tissues (r = 0.607, P < 0.001). DcR3 enhances ERK1/2 phosphorylation and opposes FasL signaling in pancreatic cancer cells. - Highlights: • We investigated the role of DcR3 in FasL resistance in pancreatic cancer. • Knockdown of DcR3 in SW1990 cells reduced resistance to FasL-induced apoptosis. • DcR3 knockdown also elevated caspase expression, and reduced ERK1/2 phosphorylation. • Tumor and non-tumor tissues were collected from 66 pancreatic carcinoma patients

  18. High-fluoride acitivates the FasL signalling pathway and leads to damage of ameloblast ultrastructure.

    Science.gov (United States)

    Wang, Lin; Zhu, Yong; Wang, Danyang

    2016-11-01

    High fluoride can induce stress-mediated apoptosis and degradation of ameloblasts. Fas ligand (FasL) has been regarded as a key regulator in intracellular responses for stress-induced apoptosis in reproductive or cancerous cell lineages. The objective of this study is to explore the role of FasL in the regulation of ameloblast ultrastructure damage. Primary ameloblasts were isolated from the molar tooth germ of 4-day-old SD rats. The ameloblasts were incubated with 3.2mM NaF or nothing. After incubation for different time arranging from 12h to 72h, ELISA was used to detected the secretion levels of FasL in the medium. Then at 48h post treatment, the ameloblast ultrastructure was detected with Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM), and expression of apoptotic proteins and peroxidative enzymes/products were examined. Finally, a specific FasL inhibitor was applied to co-treat the ameloblasts with NaF, and the ameloblast ultrastructure was detected with TEM and SEM. The secretion of FasL was notably increased by 3.2mM NaF treatment, and the increase reached to the peak after incubation for 48h. High fluoride incubation damaged the ameloblast untrastructure manifesting a series of intracelluar stress responsing cell organelle destruction, and a marked increase in expression of apoptotic genes and oxidative stress. The FasL inhibitor treatment partially mitigated the untrastructure damage caused by high dose NaF. High-fluoride leads to damage of the ameloblast ultrastructure through paritially acitivating the FasL signalling pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Analysis of sFas IL-6 levels in thyroid-associated ophthalmopathy: Pre- or poststeroid pulse treatment

    Directory of Open Access Journals (Sweden)

    Kimihito Maeda

    2008-10-01

    Full Text Available Kimihito Maeda, Yuichiro Ohara, Masato Hashimoto, Hiroshi OhguroDepartment of Ophthalmology, Sapporo Medical University, School of Medicine, Sapporo, JapanPurpose: To investigate whether serum levels of soluble Fas (sFas and interleukin-6 (IL-6 could function as an index of the efficacy of steroid pulse treatment, we examined the serum level of these proteins before and after steroid pulse treatment in thyroid-associated ophthalmopathy patients.Methods: We gathered the blood of thyroid-associated ophthalmopathy patients before or after steroid pulse treatment, obtained serum with a centrifuge, and measured the serum levels of sFas and IL-6 by enzyme-linked immunosorbent assay (ELISA.Results: There was no difference in serum IL-6 value between pre- and poststeroid pulse treatment. Serum sFas value was significantly decreased in both pre- and poststeroid pulse treatment. Furthermore, there was a recognizable improvement in the degree of the extraocular muscle thickening after treatment in cases in whom the serum sFas value was lower than 3 ng/ml prior to the beginning of the therapy. In patients who had a serum sFas value of more than 3 ng/ml, there was no improvement in the degree of thickening of the extraocular muscle.Conclusions: Serum level of sFas is an accurate index of the outcome of steroid pulse treatment in thyroid-associated ophthalmopathy and may become a useful index to gauge the status of convalescence.Keywords: sFas, IL-6, ELISA, thyroid associated ophthalmopathy, steroid pulse treatment

  20. The FAS-670 AA genotype is associated with high proviral load in peruvian HAM/TSP patients.

    Science.gov (United States)

    Rosado, Jason; Morales, Sandra; López, Giovanni; Clark, Daniel; Verdonck, Kristien; Gotuzzo, Eduardo; Van Camp, Guy; Talledo, Michael

    2017-04-01

    Human T-lymphotropic virus 1 (HTLV-1) is the etiologic agent of the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Apoptosis is a mechanism of defense elicited by many triggers, including cross-linking of the FAS receptor expressed in viruses-infected cells, and the ligand FASL presented by T-cytotoxic cells. As HAM/TSP has been associated with high levels of proviral load (PVL), we hypothesized that certain genotypes of single-nucleotide polymorphisms (SNPs) associated with a decreased protein expression of FAS and FASL could be risk factors for this disease. Three SNPs: FAS-670A/G (rs1800682), FAS-1377G/A (rs2234767), and FASL-844C/T (rs763110) were analyzed in 73 HAM/TSP patients and 143 HTLV-1 asymptomatic carriers. Ancestry informative markers were used to adjust for ethnicity through a principal component analysis. Gender, age, PVL, and the first three principal components were used as covariates. The FAS/FASL genotype distribution was not associated with HAM/TSP presence (P-> 0.05). The FAS-670 AA genotype was associated with high PVL in comparison to FAS-670 GG in HAM/TSP patients (P = 0.015), while in asymptomatic carriers low levels of PVL were observed (P > 0.05). Our findings suggest that rs1800682, rs2234767, and rs763110 genotypes are not associated with the presence of HAM/TSP, but that the FAS-670 AA genotype can promote higher PVL values in HAM/TSP patients. J. Med. Virol. 89:726-731, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Association between lymphocyte expression of the apoptotic receptor Fas and pain in critically ill patients

    Directory of Open Access Journals (Sweden)

    Papathanassoglou EDE

    2017-01-01

    Full Text Available Elizabeth DE Papathanassoglou,1,* Meropi DA Mpouzika,2,* Margarita Giannakopoulou,3 Evangelos Bozas,3 Nicos Middleton,2 George Tsiaousis,2 Andreas Karabinis4,5 1Faculty of Nursing, University of Alberta, Edmonton, AB, Canada; 2Department of Nursing, Cyprus University of Technology, Limassol, Cyprus; 3Department of Nursing, School of Health Sciences, National and Kapodistrian University of Athens, 4Surgical Care Unit, The Onassis Cardiac Surgery Center, Kallithea, 5School of Medicine, National and Kapodistrian University of Athens, Athens, Greece *These authors contributed equally to this work Objective: Lymphocyte apoptosis in critical illness is associated with immunosuppression. We explored for the first time the associations between pain ratings and expression of the apoptotic receptor Fas on B and T cells in critically ill patients and the potential mediating effects of adrenocorticotropic hormone (ACTH, cortisol, and substance P (SP.Design: This is an exploratory correlational study with repeated measurements (14 days follow-up and cross-sectional comparisons.Setting: This study was conducted in a state hospital in the metropolitan area of Athens, Greece.Participants: The participants were 36 consecutive critically ill patients and 36 matched controls.Outcome measures: Pain measured by the self-reported numeric rating scale [NRS], the behavioral pain scale, and the pain assessment scale was the primary outcome measure. Flow cytometry (Fas, electrochemiluminescence (ACTH and cortisol and enzyme-linked immunosorbent assay (SP were used. Mixed linear models for repeated measurements and bivariable associations at discrete time points were employed.Results: Significant pain at rest was noted. Pain ratings associated with Fas expression on cytotoxic T cells (P=0.041 and B cells (P=0.005, even after adjustment for a number of clinical treatment factors (P=0.006 and P=0.052, respectively. On the day that more patients were able to communicate, Fas

  2. Comparison of the expression levels of Fas and Apaf-1 genes in systemic sclerosis dermal fibroblasts

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    Majid Abed Khojasteh

    2016-07-01

    Full Text Available Background: Systemic sclerosis (SSc is an autoimmune rheumatic connective tissue disease. In normal wound healing process, fibroblasts are activated, proliferated and involved in tissue repair, and then removed by apoptosis. In systemic sclerosis, patient’s fibrosis occurs when fibroblasts become resistant to apoptosis and secrete a large amount of collagen and other extracellular matrixes. As the primary causes the disease are very complex and often unknown, it is necessary to consider or target the secondary causes of disease, such as the unresponsiveness of activated fibroblasts to apoptosis as the major factor in the creation and deployment of illness. In this study, we examined the expression levels of two key pro-apoptotic genes, Fas and Apaf-1, which are respectively involved in external and internal pathway of apoptosis. Methods: In a case-control study skin biopsy samples were obtained from 19 patients with diffuse SSc, and 16 healthy controls. Dermal fibroblasts were cultured and total RNA was isolated from cell populations using High Pure RNA Isolation Kit (Roche Applied Science, Mannheim, Germany, followed by cDNA synthesis using RevertAid First Strand cDNA Synthesis Kit (Thermo Fisher Scientific Inc., Massachusetts, USA. Real-time PCR was performed using SYBRGreen gene expression master mix (Takara Shuzo, Co., Ltd, Shiga, Japan and specific primers for Fas and Apaf-1. Real-time data were analyzed using the (2-ΔCT×1000 method. Statistical analysis was accomplished by using the SPSS software, v22 (IBM, Armonk, NY, USA. The P value less than 0.05 were recognized as a significant threshold. All data are represented as the mean ± SEM. Results: Our results showed no significant difference in Fas (P=0.8 and Apaf-1 (P=0.17 mRNA expression levels between skin fibroblasts of systemic sclerosis patients and healthy controls. Conclusion: In this study we observed no significant change in Apaf-1 and Fas mRNA levels in systemic sclerosis

  3. Involvement of FOXO transcription factors, TRAIL-FasL/Fas, and sirtuin proteins family in canine coronavirus type II-induced apoptosis.

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    Gabriella Marfè

    Full Text Available n our previous study, we have shown that canine coronavirus type II (CCoV-II activates both extrinsic and intrinsic apoptotic pathway in a canine fibrosarcoma cell line (A-72 cells. Herein we investigated the role of Sirtuin and Forkhead box O (FOXO families in this experimental model using Nortern Blot and Western Blot analysis. Our results demonstrated that mitochondrial SIRT3 and SIRT4 protein expression increased from 12 and 24 h post infection (p.i. onwards, respectively, whereas the nuclear SIRT1 expression increased during the first 12 h p.i. followed by a decrease after 36 h p.i., reaching the same level of control at 48 h p.i. Sirtuins interact with/and regulate the activity of FOXO family proteins, and we herein observed that FOXO3A and FOXO1 expression increased significantly and stably from 12 h p.i. onwards. In addition, CCoV-II induces a remarkable increase in the expression of TNF-related apoptosis-inducing ligand (TRAIL, while we observed a slight up-regulation of FasL/Fas at 36 p.i. with a decrease of both proteins at the end of infection. Furthermore, we found that virus infection increased both bax translocation into mitochondria and decreased bcl-2 expression in cytosol in a time-dependent manner.These data suggest that FOXO transcription factors mediate pro-apoptotic effects of CCoV-II, in part due to activation of extrinsic apoptosis pathway, while some Sirtuin family members (such as SIRT3 and SIRT4 may be involved in intrinsic apoptotic pathway. Moreover, these results propose that TRAIL is an important mediator of cell death induced by CCoV-II during in vitro infection.

  4. Estrous cycle-dependent changes of Fas expression in the bovine corpus luteum: influence of keratin 8/18 intermediate filaments and cytokines

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    Duncan Alice

    2012-10-01

    Full Text Available Abstract Background Fas expression and Fas-induced apoptosis are mechanisms attributed to the selective destruction of cells of the corpus luteum (CL during luteal regression. In certain cell-types, sensitivity to these death-inducing mechanisms is due to the loss or cleavage of keratin-containing intermediate filaments. Specifically, keratin 8/18 (K8/K18 filaments are hypothesized to influence cell death in part by regulating Fas expression at the cell surface. Methods Here, Fas expression on bovine luteal cells was quantified by flow cytometry during the early (Day 5, postovulation and late stages (Days 16–18, postovulation of CL function, and the relationship between Fas expression, K8/K18 filament expression and cytokine-induced cell death in vitro was evaluated. Results Both total and cell surface expression of Fas on luteal cells was greater for early versus late stage bovine CL (89% vs. 44% of cells for total Fas; 65% vs.18% of cells for cell surface Fas; respectively, P0.05, n=4 CL/stage, despite evidence these conditions increased Fas expression on HepG2 cells (P0.05 or stage of CL (P>0.05, n= 4 CL/stage on this outcome. Conclusion In conclusion, we rejected our null hypothesis that the cell surface expression of Fas does not differ between luteal cells of early and late stage CL. The results also did not support the idea that K8/K18 filaments influence the expression of Fas on the surface of bovine luteal cells. Potential downstream effects of these filaments on death signaling, however, remain a possibility. Importantly, the elevated expression of Fas observed on cells of early stage bovine CL compared to late stage bovine CL raises a provocative question concerning the physiological role(s of Fas in the corpus luteum, particularly during early luteal development.

  5. Spontaneous down-regulation of Fas-associated phosphatase-1 may contribute to excessive apoptosis in myelodysplastic marrows.

    Science.gov (United States)

    Mundle, S D; Mativi, B Y; Bagai, K; Feldman, G; Cheema, P; Gautam, U; Reza, S; Cartlidge, J D; Venugopal, P; Shetty, V; Gregory, S A; Robin, E; Rifkin, S; Shah, R; Raza, A

    1999-08-01

    In this study, we examined the role of Fas-signaling in the apoptotic pathway in myelodysplastic syndromes (MDS). Ficoll-separated mononuclear cells from 18 bone marrow aspirate specimens obtained from 17 MDS patients, 4 normal healthy donors, and 3 acute myeloid leukemia patients transformed from MDS (t-AML) were studied for mRNA expression of Fas-L, Fas, and the effectors of their signaling, Caspase 1 and Caspase 3, using reverse transcriptase polymerase chain reaction. Fas-L, Fas, and Caspase 1 were detectable in all of the samples in the three groups. Caspase 3 was detectable both in MDS and t-AML specimens but was negligible in normal cells. The apoptotic index (AI%) determined by in situ end labeling of fragmented DNA in 4-hour cultures of mononuclear cells was significantly higher in MDS cells compared to normal or t-AML cells (mean +/- SEM: 2.3% +/- 0.4% in MDS, n = 10 vs. 0.6% +/- 0.2%, n = 4, P = 0.014 in normal cells, and 0.2% +/- 0.2%, n = 3, P = 0.007 in t-AML cells). Treatment of MDS cells with anti-Fas-L antibody suppressed apoptosis (AI%: 2.1% +/- 0.6% in untreated vs. 1.37% +/- 0.5% in treated, n = 6, P = 0.02), indicating functional participation of Fas-signaling in MDS. Further, it was found that Fas-L, Fas, and Caspase 1 mRNA expression remained unchanged in 4 hours. Caspase 3 expression appeared in normal cells after 4 hours and was present at both 0 and 4 hours in MDS and t-AML cells. In contrast to persistent expression in normal and t-AML cells, cells from the 5 MDS patients studied consistently showed significantly lowered or undetectable expression of a negative regulator of Fas, called Fas-associated phosphatase-1 (Fap-1) after 4 hours. Thus, the high AI% in MDS corresponds to a rapid decline in Fap-1. Furthermore, in tumor necrosis factor alpha (TNF-alpha) treated HL60 promyelocytic cells, a definite periodicity in the expression of different mRNAs was observed with upregulation of TNF-alpha itself at 30 minutes, increased expression of

  6. Anti-Fas mAb-induced apoptosis and cytolysis of airway tissue eosinophils aggravates rather than resolves established inflammation

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    Persson Carl GA

    2005-08-01

    Full Text Available Abstract Background Fas receptor-mediated eosinophil apoptosis is currently forwarded as a mechanism resolving asthma-like inflammation. This view is based on observations in vitro and in airway lumen with unknown translatability to airway tissues in vivo. In fact, apoptotic eosinophils have not been detected in human diseased airway tissues whereas cytolytic eosinophils abound and constitute a major mode of degranulation of these cells. Also, Fas receptor stimulation may bypass the apoptotic pathway and directly evoke cytolysis of non-apoptotic cells. We thus hypothesized that effects of anti-Fas mAb in vivo may include both apoptosis and cytolysis of eosinophils and, hence, that established eosinophilic inflammation may not resolve by this treatment. Methods Weeklong daily allergen challenges of sensitized mice were followed by airway administration of anti-Fas mAb. BAL was performed and airway-pulmonary tissues were examined using light and electron microscopy. Lung tissue analysis for CC-chemokines, apoptosis, mucus production and plasma exudation (fibrinogen were performed. Results Anti-Fas mAb evoked apoptosis of 28% and cytolysis of 4% of eosinophils present in allergen-challenged airway tissues. Furthermore, a majority of the apoptotic eosinophils remained unengulfed and eventually exhibited secondary necrosis. A striking histopathology far beyond the allergic inflammation developed and included degranulated eosinophils, neutrophilia, epithelial derangement, plasma exudation, mucus-plasma plugs, and inducement of 6 CC-chemokines. In animals without eosinophilia anti-Fas evoked no inflammatory response. Conclusion An efficient inducer of eosinophil apoptosis in airway tissues in vivo, anti-Fas mAb evoked unprecedented asthma-like inflammation in mouse allergic airways. This outcome may partly reflect the ability of anti-Fas to evoke direct cytolysis of non-apoptotic eosinophils in airway tissues. Additionally, since most apoptotic tissue

  7. Stimulation of Fas agonistic antibody–mediated apoptosis by heparin-like agents suppresses Hsp27 but not Bcl-2 protective activity

    OpenAIRE

    Manero, Florence; Ljubic-Thibal, Vesna; Moulin, Maryline; Goutagny, Nadège; Yvin, Jean-Claude; Arrigo, André-Patrick

    2004-01-01

    We report that in Jurkat T cells or freshly isolated T lymphocytes, physiological concentrations of high– molecular weight sulfated polysaccharides such as heparin, heparan sulfate, and dextran sulfate significantly increased the percentage of cell death induced by Fas IgM agonistic antibody. The phenomenon was caspase dependent and P53 independent and correlated with an increased accessibility of cell surface Fas receptors. We also observed that the Fas IgM agonistic antibody–dependent forma...

  8. Data in support of transcriptional regulation and function of Fas-antisense long noncoding RNA during human erythropoiesis

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    Olga Villamizar

    2016-06-01

    Full Text Available This paper describes data related to a research article titled, “Fas-antisense long noncoding RNA is differentially expressed during maturation of human erythrocytes and confers resistance to Fas-mediated cell death” [1]. Long noncoding RNAs (lncRNAs are increasingly appreciated for their capacity to regulate many steps of gene expression. While recent studies suggest that many lncRNAs are functional, the scope of their actions throughout human biology is largely undefined including human red blood cell development (erythropoiesis. Here we include expression data for 82 lncRNAs during early, intermediate and late stages of human erythropoiesis using a commercial qPCR Array. From these data, we identified lncRNA Fas-antisense 1 (Fas-AS1 or Saf described in the research article. Also included are 5′ untranslated sequences (UTR for lncRNA Saf with transcription factor target sequences identified. Quantitative RT-PCR data demonstrate relative levels of critical erythroid transcription factors, GATA-1 and KLF1, in K562 human erythroleukemia cells and maturing erythroblasts derived from human CD34+ cells. End point and quantitative RT-PCR data for cDNA prepared using random hexamers versus oligo(dT18 revealed that lncRNA Saf is not effectively polyadenylated. Finally, we include flow cytometry histograms demonstrating Fas levels on maturing erythroblasts derived from human CD34+ cells transduced using mock conditions or with lentivirus particles encoding for Saf.

  9. Phytosanitary Irradiation

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    Guy J. Hallman

    2016-01-01

    Full Text Available Phytosanitary treatments disinfest traded commodities of potential quarantine pests. Phytosanitary irradiation (PI treatments use ionizing radiation to accomplish this, and, since their international commercial debut in 2004, the use of this technology has increased by ~10% annually. Generic PI treatments (one dose is used for a group of pests and/or commodities, although not all have been tested for efficacy are used in virtually all commercial PI treatments, and new generic PI doses are proposed, such as 300 Gy, for all insects except pupae and adult Lepidoptera (moths. Fresh fruits and vegetables tolerate PI better than any other broadly used treatment. Advances that would help facilitate the use of PI include streamlining the approval process, making the technology more accessible to potential users, lowering doses and broadening their coverage, and solving potential issues related to factors that might affect efficacy.

  10. The role of Fas ligand protein in the oxidative stress induced by azoxymethane on crypt colon of rats O papel da proteína ligante Fas no estresse oxidativo induzido pelo azoximetano em criptas do colo de ratos

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    Luiz Antonio Maksoud Bussuan

    2010-12-01

    Full Text Available PURPOSE: To study the protein Fas ligand (FasL on the expression of apoptosis, using a model of oxidative stress induced by azoxymethane (AOM, in the crypt of colon in rats. METHODS: Wistar rats (n=14 were assigned into two groups: control (n=7 and AOM (n=7. A single subcutaneous administration of AOM (5mg/kg or saline solution was performed at the beginning of third week and after three hours samples of proximal colon were collected. The expression of FasL was quantified (Software ImageLab in percentage of areas in the top, base and all crypt. Results were expressed as mean ± sd (Shapiro-Wilks test and t Student test (p OBJETIVO: Avaliar o marcador de apoptose Fas ligante (FasL em um modelo de estresse oxidativo induzido pelo azoximetano (AOM na cripta de cólon em ratos. MÉTODOS: 14 ratos Wistar foram distribuídos em dois grupos: controle (n=7 e AOM (n=7. A AOM (5mg/kg ou solução salina foi aplicada via subcutânea e a coleta de amostras de colo proximal ocorreu 3 horas após. A FasL foi quantificada pelo percentual de áreas no topo, base e toda a cripta. Os resultados foram submetidos aos testes de Shapiro-Wilks e t de Student (p < 0,05. RESULTADOS: No grupo GC, não houve diferença significativa entre a expressão da FasL no topo (10,75 ± 3,33 e base (11,14 ± 3,53 da cripta (p=0,34293740. No grupo AOM não houve diferença significativa entre a expressão da FasL no topo (8,86 ± 4,19 e base (8,99 ± 4,08 e cripta (p=0,78486003. No grupo GC (10,95 ± 3,43 e AOM (8,92 ± 4,13, houve uma diferença significativa da expressão da FasL (p=0,026466821. Redução significativa na expressão da FasL ocorreu nos em GC (10,75 ± 3,33 e AOM (8,86 ± 4,19 no topo da cripta (p = 0,00003755*. Foi observada diminuição significativa em GC (11,14 ± 3,53 e AOM (8,99 ± 4,08 na base da cripta (p=0,00000381**. CONCLUSÃO: Azoximetano induziu o estresse oxidativo identificado pela diminuição significativa da expressão da FasL, embora não haja

  11. The strength of the Fas ligand signal determines whether hepatocytes act as type-1 or type-2 cells in murine livers

    OpenAIRE

    Schüngel, Sven; Buitrago-Molina, Laura Elisa; Nalapareddy, Padmavathi; Lebofsky, Margitta; Manns, Michael P.; Jaeschke, Hartmut; Gross, Atan; Vogel, Arndt

    2009-01-01

    The BH3-interacting domain death agonist Bid has been shown to be critical for Fas-induced hepatocellular apoptosis. Furthermore, some studies have suggested that phosphorylation of Bid may determine the apoptotic function of Bid and may act as a switch to non-apoptotic functions. The aim of this study was to evaluate the role of Bid and phosphorylated Bid for FasL-induced apoptosis in murine livers. The monoclonal antibody Jo2 and a hexameric form of sFasL (MegaFasL) were used to induce apop...

  12. Ethanol induces mouse spermatogenic cell apoptosis in vivo through over-expression of Fas/Fas-L, p53, and caspase-3 along with cytochrome c translocation and glutathione depletion.

    Science.gov (United States)

    Jana, Kuladip; Jana, Narayan; De, Dipak Kumar; Guha, Sujoy Kumar

    2010-09-01

    Although it has been well established that spermatogenic cells undergo apoptosis when treated with ethanol, the molecular mechanisms behind it remain to be investigated. Adult male mice were given intra-peritoneal injection (IP) of ethanol at a dose of 3 g (15%, v/v) per kg body weight per day during the period of 14 days. Testicular androgenesis and apoptotic germ cell death, along with different interrelated proteins expression, were evaluated. Ethanol treatment induced apoptotic spermatogenic cell death with a decrease in the plasma and intra-testicular testosterone concentration. Western blot analysis revealed that repeated ethanol treatment decreased the expression of steroidogenic acute regulatory protein (StAR), 3 beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17 beta-hydroxysteroid dehydrogenase (17beta-HSD); increased the expression of active caspase-3, p53, Fas and Fas-L; and led to up-regulation of Bax/Bcl-2 ratio and translocation of cytochrome c from mitochondria to cytosol in testis. It has also been shown in our study that repeated ethanol treatment led to up-regulation of caspase-3, p53, Fas, Fas-L transcripts; increase in caspase-3 and caspase-8 activities; diminution of 3beta-HSD, 17beta-HSD, and GPx activities; decrease in the mitochondrial membrane potential along with ROS generation and depletion of glutathione pool in the testicular tissue. The present study has indicated that the ethanol treatment induced apoptosis in the mouse testis through the increased expression of Fas/Fas-L and p53, up-regulation of Bax/Bcl-2 ratio, cytosolic translocation of cytochrome c along with caspase-3 activation and glutathione depletion. (c) 2010 Wiley-Liss, Inc.

  13. GloFAS – global ensemble streamflow forecasting and flood early warning

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    L. Alfieri

    2013-03-01

    Full Text Available Anticipation and preparedness for large-scale flood events have a key role in mitigating their impact and optimizing the strategic planning of water resources. Although several developed countries have well-established systems for river monitoring and flood early warning, figures of populations affected every year by floods in developing countries are unsettling. This paper presents the Global Flood Awareness System (GloFAS, which has been set up to provide an overview on upcoming floods in large world river basins. GloFAS is based on distributed hydrological simulation of numerical ensemble weather predictions with global coverage. Streamflow forecasts are compared statistically to climatological simulations to detect probabilistic exceedance of warning thresholds. In this article, the system setup is described, together with an evaluation of its performance over a two-year test period and a qualitative analysis of a case study for the Pakistan flood, in summer 2010. It is shown that hazardous events in large river basins can be skilfully detected with a forecast horizon of up to 1 month. In addition, results suggest that an accurate simulation of initial model conditions and an improved parameterization of the hydrological model are key components to reproduce accurately the streamflow variability in the many different runoff regimes of the earth.

  14. A novel inhibitor of glucose uptake sensitizes cells to FAS-induced cell death.

    Science.gov (United States)

    Wood, Tabitha E; Dalili, Shadi; Simpson, Craig D; Hurren, Rose; Mao, Xinliang; Saiz, Fernando Suarez; Gronda, Marcela; Eberhard, Yanina; Minden, Mark D; Bilan, Philip J; Klip, Amira; Batey, Robert A; Schimmer, Aaron D

    2008-11-01

    Evasion of death receptor ligand-induced apoptosis is an important contributor to cancer development and progression. Therefore, molecules that restore sensitivity to death receptor stimuli would be important tools to better understand this biological pathway and potential leads for therapeutic adjuncts. Previously, the small-molecule N-[4-chloro-3-(trifluoromethyl)phenyl]-3-oxobutanamide (fasentin) was identified as a chemical sensitizer to the death receptor stimuli FAS and tumor necrosis factor apoptosis-inducing ligand, but its mechanism of action was unknown. Here, we determined that fasentin alters expression of genes associated with nutrient and glucose deprivation. Consistent with this finding, culturing cells in low-glucose medium recapitulated the effects of fasentin and sensitized cells to FAS. Moreover, we showed that fasentin inhibited glucose uptake. Using virtual docking studies with a homology model of the glucose transport protein GLUT1, fasentin interacted with a unique site in the intracellular channel of this protein. Additional chemical studies with other GLUT inhibitors and analogues of fasentin supported a role for partial inhibition of glucose transport as a mechanism to sensitize cells to death receptor stimuli. Thus, fasentin is a novel inhibitor of glucose transport that blocks glucose uptake and highlights a new mechanism to sensitize cells to death ligands.

  15. Interleukin-10 overexpression promotes Fas-ligand-dependent chronic macrophage-mediated demyelinating polyneuropathy.

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    Dru S Dace

    Full Text Available BACKGROUND: Demyelinating polyneuropathy is a debilitating, poorly understood disease that can exist in acute (Guillain-Barré syndrome or chronic forms. Interleukin-10 (IL-10, although traditionally considered an anti-inflammatory cytokine, has also been implicated in promoting abnormal angiogenesis in the eye and in the pathobiology of autoimmune diseases such as lupus and encephalomyelitis. PRINCIPAL FINDINGS: Overexpression of IL-10 in a transgenic mouse model leads to macrophage-mediated demyelinating polyneuropathy. IL-10 upregulates ICAM-1 within neural tissues, promoting massive macrophage influx, inflammation-induced demyelination, and subsequent loss of neural tissue resulting in muscle weakness and paralysis. The primary insult is to perineural myelin followed by secondary axonal loss. Infiltrating macrophages within the peripheral nerves demonstrate a highly pro-inflammatory signature. Macrophages are central players in the pathophysiology, as in vivo depletion of macrophages using clodronate liposomes reverses the phenotype, including progressive nerve loss and paralysis. Macrophage-mediate demyelination is dependent on Fas-ligand (FasL-mediated Schwann cell death. SIGNIFICANCE: These findings mimic the human disease chronic idiopathic demyelinating polyneuropathy (CIDP and may also promote further understanding of the pathobiology of related conditions such as acute idiopathic demyelinating polyneuropathy (AIDP or Guillain-Barré syndrome.

  16. Functional analysis of miR-181a and Fas involved in hepatitis B virus-related hepatocellular carcinoma pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Chengcheng; Chen, Juan; Chen, Ke; Wang, Sen; Cao, Yiyi; Zhang, Jinnan; Sheng, Yanrui; Huang, Ailong; Tang, Hua, E-mail: tanghua86162003@aliyun.com

    2015-02-15

    The hepatitis B virus (HBV) is responsible for most of hepatocellular carcinoma (HCC). However, whether HBV plays an important role during hepatocarcinogenesis through effecting miRNAs remains unknown. Here, we reported that HBV up-regulated microRNA-181a (miR-181a) by enhancing its promoter activity. Simultaneously, we found that miR-181a inhibited apoptosis in vitro and promoted tumor cell growth in vivo. TNF receptor superfamily member 6 (Fas) was further identified as a target of miR-181a. We also found that Fas could reverse the apoptosis-inhibition effect induced by miR-181a. Moreover, HBV could inhibit cell apoptosis by down-regulating Fas expression, which could be reversed by miR-181a inhibitor. Our data demonstrated that HBV suppressed apoptosis of hepatoma cells by up-regulating miR-181a expression and down-regulating Fas expression, which may provide a new understanding of the mechanism in HBV-related HCC pathogenesis. - Highlights: • HBV could up-regulate miR-181a expression by interacting with nt−800 to +240 in its promoter region in HCC cell lines. • HBV could down-regulate Fas expression and suppress apoptosis of hepatoma cells, which could be reversed by miR-181a inhibitor. • Up-regulation of miR-181a promoted proliferation of hepatoma cells and repressed apoptosis, which could be reversed by Fas. • Our study provides a new understanding of the mechanism in HBV-related HCC pathogenesis.

  17. Fas-independent T-cell apoptosis by dendritic cells controls autoimmune arthritis in MRL/lpr mice.

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    Takashi Izawa

    Full Text Available BACKGROUND: Although autoimmunity in MRL/lpr mice occurs due to a defect in Fas-mediated cell death of T cells, the role of Fas-independent apoptosis in pathogenesis has rarely been investigated. We have recently reported that receptor activator of nuclear factor (NF-κB ligand (RANKL-activated dendritic cells (DCs play a key role in the pathogenesis of rheumatoid arthritis (RA in MRL/lpr mice. We here attempted to establish a new therapeutic strategy with RANKL-activated DCs in RA by controlling apoptosis of peripheral T cells. Repeated transfer of RANKL-activated DCs into MRL/lpr mice was tested to determine whether this had a therapeutic effect on autoimmunity. METHODS AND FINDING: Cellular and molecular mechanisms of Fas-independent apoptosis of T cells induced by the DCs were investigated by in vitro and in vivo analyses. We demonstrated that repeated transfers of RANKL-activated DCs into MRL/lpr mice resulted in therapeutic effects on RA lesions and lymphoproliferation due to declines of CD4(+ T, B, and CD4(-CD8(- double negative (DN T cells. We also found that the Fas-independent T-cell apoptosis was induced by a direct interaction between tumor necrosis factor (TNF-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2 on T cells and TRAIL on Fas-deficient DCs in MRL/lpr mice. CONCLUSION: These results strongly suggest that a novel Fas-independent apoptosis pathway in T cells maintains peripheral tolerance and thus controls autoimmunity in MRL/lpr mice.

  18. FasL Mediates T-Cell Eradication of Tumor Cells Presenting Low Levels of Antigens | Center for Cancer Research

    Science.gov (United States)

    One approach to cancer immunotherapy, as opposed to therapeutic vaccination, is the transfusion of large numbers of tumor-specific killer T cells (cytotoxic T cells or CTLs) into patients. The body’s own defense killer T cells are a subgroup of T lymphocytes (a type of white blood cells) that are capable of inducing death in tumor cells. CTLs can cause the death of target cells either by releasing granules containing toxic molecules including perforin, or by producing a membrane protein called Fas ligand (FasL) which on interaction with the tumor cell results in cell death.

  19. Overexpression of Telomerase Protects Human and Murine Lung Epithelial Cells from Fas- and Bleomycin-Induced Apoptosis via FLIP Upregulation.

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    Nissim Arish

    Full Text Available High doses of bleomycin administered to patients with lymphomas and other tumors lead to significant lung toxicity in general, and to apoptosis of epithelial cells, in particular. Apoptosis of alveolar epithelium is an important step in the pathogenesis of bleomycin-induced pulmonary fibrosis. The Fas-FasL pathway is one of the main apoptotic pathways involved. Telomerase is a ribonucleoprotein RNA-dependent DNA polymerase complex consisting of an RNA template and a catalytic protein, telomerase reverse transcriptase (TERT. Telomerase also possess extra-telomeric roles, including modulation of transcription of anti-apoptotic genes, differentiation signals, and more. We hypothesized that telomerase overexpression affects Fas-induced epithelial cell apoptosis by an extra-telomeric role such as regulation of anti-apoptotic genes, specifically FLICE-like inhibitory protein (FLIP. Telomerase in mouse (MLE and human (A549 lung epithelial cell lines was upregulated by transient transfection using cDNA hTERT expression vector. Telomerase activity was detected using a real-time PCR-based system. Bleomycin, and bleomycin-induced Fas-mediated apoptosis following treatment with anti-Fas activating mAb or control IgG, were assessed by Annexin V staining, FACS analysis, and confocal microscopy; caspase cleavage by Western blot; FLIP or Fas molecule detection by Western blot and flow cytometry. hTERT transfection of lung epithelial cells resulted in a 100% increase in their telomerase activity. Fas-induced lung epithelial cell apoptosis was significantly reduced in hTERT-transfected cells compared to controls in all experiments. Lung epithelial cells with increased telomerase activity had higher levels of FLIP expression but membrane Fas expression was unchanged. Upregulation of hTERT+ in human lung epithelial cells and subsequent downregulation of FLIP by shFLIP-RNA annulled hTERT-mediated resistance to apoptosis. Telomerase-mediated FLIP overexpression may

  20. Irradiation Facilities at CERN

    CERN Document Server

    Gkotse, Blerina; Carbonez, Pierre; Danzeca, Salvatore; Fabich, Adrian; Garcia, Alia, Ruben; Glaser, Maurice; Gorine, Georgi; Jaekel, Martin, Richard; Mateu,Suau, Isidre; Pezzullo, Giuseppe; Pozzi, Fabio; Ravotti, Federico; Silari, Marco; Tali, Maris

    2017-01-01

    CERN provides unique irradiation facilities for applications in many scientific fields. This paper summarizes the facilities currently operating for proton, gamma, mixed-field and electron irradiations, including their main usage, characteristics and information about their operation. The new CERN irradiation facilities database is also presented. This includes not only CERN facilities but also irradiation facilities available worldwide.

  1. Stimulation of Fas agonistic antibody-mediated apoptosis by heparin-like agents suppresses Hsp27 but not Bcl-2 protective activity.

    Science.gov (United States)

    Manero, Florence; Ljubic-Thibal, Vesna; Moulin, Maryline; Goutagny, Nadège; Yvin, Jean-Claude; Arrigo, André-Patrick

    2004-01-01

    We report that in Jurkat T cells or freshly isolated T lymphocytes, physiological concentrations of high-molecular weight sulfated polysaccharides such as heparin, heparan sulfate, and dextran sulfate significantly increased the percentage of cell death induced by Fas IgM agonistic antibody. The phenomenon was caspase dependent and P53 independent and correlated with an increased accessibility of cell surface Fas receptors. We also observed that the Fas IgM agonistic antibody-dependent formation of sodium dodecyl sulfate (SDS)-resistant large structures containing Fas receptor was decreased in the presence of heparin-like agents. In contrast, the different agents had no effect when cell death was triggered by FasL, the natural ligand of Fas that does not generate SDS-resistant forms of Fas. Interestingly, the synergistic effect of heparin-like agents toward Fas IgM agonistic antibody-mediated cell death abolished Hsp27 antiapoptotic activity but did not alter much the protection generated by Bcl-2 expression.

  2. Stimulation of Fas agonistic antibody–mediated apoptosis by heparin-like agents suppresses Hsp27 but not Bcl-2 protective activity

    Science.gov (United States)

    Manero, Florence; Ljubic-Thibal, Vesna; Moulin, Maryline; Goutagny, Nadège; Yvin, Jean-Claude; Arrigo, André-Patrick

    2004-01-01

    We report that in Jurkat T cells or freshly isolated T lymphocytes, physiological concentrations of high– molecular weight sulfated polysaccharides such as heparin, heparan sulfate, and dextran sulfate significantly increased the percentage of cell death induced by Fas IgM agonistic antibody. The phenomenon was caspase dependent and P53 independent and correlated with an increased accessibility of cell surface Fas receptors. We also observed that the Fas IgM agonistic antibody–dependent formation of sodium dodecyl sulfate (SDS)–resistant large structures containing Fas receptor was decreased in the presence of heparin-like agents. In contrast, the different agents had no effect when cell death was triggered by FasL, the natural ligand of Fas that does not generate SDS-resistant forms of Fas. Interestingly, the synergistic effect of heparin-like agents toward Fas IgM agonistic antibody–mediated cell death abolished Hsp27 antiapoptotic activity but did not alter much the protection generated by Bcl-2 expression. PMID:15497502

  3. IFN-gamma receptor signaling is essential for the initiation, acceleration, and destruction of autoimmune kidney disease in MRL-Fas(lpr) mice

    National Research Council Canada - National Science Library

    Schwarting, A; Wada, T; Kinoshita, K; Tesch, G; Kelley, V R

    1998-01-01

    CSF-1 and TNF-alpha in the kidney of MRL-Fas(lpr) mice are proximal events that precede and promote autoimmune lupus nephritis, while apoptosis of renal parenchymal cells is a feature of advanced human lupus nephritis. In the MRL-Fas(lpr...

  4. The expression of Fas ligand on normal and stabbed-disc cells in a rabbit model of intervertebral disc degeneration: a possible pathogenesis.

    Science.gov (United States)

    Wang, Jing; Tang, Tiansi; Yang, Huilin; Yao, Xiaoshen; Chen, Liang; Liu, Wei; Li, Tao

    2007-05-01

    The nucleus pulposus has been reported to be an immunologically privileged site. The expression of Fas ligand (FasL) on normal and herniated lumbar disc cells has been reported. The relationship between a physiological barrier and the role of FasL has not yet been addressed. To clarify this relationship and to investigate a possible pathogenesis of intervertebral disc degeneration (IDD), the expression of Fas and FasL (a mean apoptosis index) on normal and stabbed-disc cells was examined in a rabbit model of IDD. Using defined needle gauges and depths, the anular puncture model of IDD was established in rabbits. The normal and stabbed discs were harvested at 3, 6, and 10 weeks after surgery. Immunohistochemical staining of these discs for Fas and FasL was performed using standard procedures. The mean apoptosis indices of the disc cells were determined using flow cytometry analysis. The nucleus pulposus cells from the normal discs exhibited relatively weak immunopositivity, whereas the nucleus pulposus cells from the stabbed discs exhibited strong immunopositivity. There was a significant difference (p < 0.001) in the percentage of FasL-positive nucleus pulposus cells between the normal discs and the stabbed discs. The mean apoptosis indices of the stabbed-disc cells at 3, 6, and 10 weeks poststab were significantly higher than those in normal disc cells (p < 0.001, 0.002, and 0.006, respectively). There was a significant correlation between the degree of FasL-positive expression and the degree of Fas-positive expression of the nucleus pulposus cells poststab (r = 0.571, p = 0.0036). These observations indicate that the nucleus pulposus is an immunologically privileged site. This immunological privilege is maintained by FasL and the physiological barrier together. When the physiological barrier was damaged (by stabbing the disc), the role of FasL changed, and FasL was coexpressed with Fas to induce apoptosis of disc cells. These results indicate that an autoimmune

  5. Mechanism of nuclear factor of activated T-cells mediated FasL expression in corticosterone -treated mouse Leydig tumor cells

    Directory of Open Access Journals (Sweden)

    Wang Qian

    2008-06-01

    Full Text Available Abstract Background Fas and FasL is important mediators of apoptosis. We have previously reported that the stress levels of corticosterone (CORT, glucocorticoid in rat increase expression of Fas/FasL and activate Fas/FasL signal pathway in rat Leydig cells, which consequently leads to apoptosis. Moreover, our another study showed that nuclear factor of activated T-cells (NFAT may play a potential role in up-regulation of FasL during CORT-treated rat Leydig cell. It is not clear yet how NFAT is involved in CORT-induced up-regulation of FasL. The aim of the present study is to investigate the molecular mechanisms of NFAT-mediated FasL expression in CORT-treated Leydig cells. Results Western blot analysis showed that NFAT2 expression is present in mouse Leydig tumor cell (mLTC-1. CORT-induced increase in FasL expression in mLTC-1 was ascertained by Western Blot analysis and CORT-induced increase in apoptotic frequency of mLTC-1 cells was detected by FACS with annexin-V labeling. Confocal imaging of NFAT2-GFP in mLTC-1 showed that high level of CORT stimulated NFAT translocation from the cytoplasm to the nucleus. RNA interference-mediated knockdown of NFAT2 significantly attenuated CORT-induced up-regulation of FasL expression in mLTC. These results corroborated our previous finding that NFAT2 is involved in CORT-induced FasL expression in rat Leydig cells and showed that mLTC-1 is a suitable model for investigating the mechanism of CORT-induced FasL expression. The analysis of reporter constructs revealed that the sequence between -201 and +71 of mouse FasL gene is essential for CORT-induced FasL expression. The mutation analysis demonstrated that CORT-induced FasL expression is mediated via an NFAT binding element located in the -201 to +71 region. Co-transfection studies with an NFAT2 expression vector and reporter construct containing -201 to +71 region of FasL gene showed that NFAT2 confer a strong inducible activity to the FasL promoter at its

  6. IL-1beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells

    DEFF Research Database (Denmark)

    Jacobsen, M L B; Rønn, S G; Bruun, C

    2008-01-01

    AIMS/HYPOTHESIS: Chemokines recruit activated immune cells to sites of inflammation and are important mediators of insulitis. Activation of the pro-apoptotic receptor Fas leads to apoptosis-mediated death of the Fas-expressing cell. The pro-inflammatory cytokines IL-1beta and IFN-gamma regulate...... the transcription of genes encoding the Fas receptor and several chemokines. We have previously shown that suppressor of cytokine signalling (SOCS)-3 inhibits IL-1beta- and IFN-gamma-induced nitric oxide production in a beta cell line. The aim of this study was to investigate whether SOCS-3 can influence cytokine......-induced Fas and chemokine expression in beta cells. METHODS: Using a beta cell line with inducible Socs3 expression or primary neonatal rat islet cells transduced with a Socs3-encoding adenovirus, we employed real-time RT-PCR analysis to investigate whether SOCS-3 affects cytokine-induced chemokine and Fas m...

  7. A novel cisplatin mediated apoptosis pathway is associated with acid sphingomyelinase and FAS proapoptotic protein activation in ovarian cancer.

    Science.gov (United States)

    Maurmann, L; Belkacemi, L; Adams, N R; Majmudar, P M; Moghaddas, S; Bose, R N

    2015-07-01

    Platinum-based anticancer drugs, including cisplatin and carboplatin, have been cornerstones in the treatment of solid tumors. We report here that these DNA-damaging agents, particularly cisplatin, induce apoptosis through plasma membrane disruption, triggering FAS death receptor via mitochondrial (intrinsic) pathways. Our objectives were to: quantify the composition of membrane metabolites; and determine the potential involvement of acid sphingomyelinase (ASMase) in the FAS-mediated apoptosis in ovarian cancer after cisplatin treatment. The resulting analysis revealed enhanced apoptosis as measured by: increased phosphocholine, and glycerophosphocholine; elevated cellular energetics; and phosphocreatine and nucleoside triphosphate concentrations. The plasma membrane alterations were accompanied by increased ASMase activity, leading to the upregulation of FAS, FASL and related pro-apoptotic BAX and PUMA genes. Moreover FAS, FASL, BAX, PUMA, CASPASE-3 and -9 proteins were upregulated. Our findings implicate ASMase activity and the intrinsic pathways in cisplatin-mediated membrane demise, and contribute to our understanding of the mechanisms by which ovarian tumors may become resistant to cisplatin.

  8. HIV-1 Nef-induced FasL induction and bystander killing requires p38 MAPK activation

    Science.gov (United States)

    Muthumani, Karuppiah; Choo, Andrew Y.; Hwang, Daniel S.; Premkumar, Arumugam; Dayes, Nathanael S.; Harris, Crafford; Green, Douglas R.; Wadsworth, Scott A.; Siekierka, John J.; Weiner, David B.

    2005-01-01

    The human immunodeficiency virus (HIV) has been reported to target noninfected CD4 and CD8 cells for destruction. This effect is manifested in part through up-regulation of the death receptor Fas ligand (FasL) by HIV-1 negative factor (Nef), leading to bystander damage. However, the signal transduction and transcriptional regulation of this process remains elusive. Here, we provide evidence that p38 mitogen-activated protein kinase (MAPK) is required for this process. Loss-of-function experiments through dominant-negative p38 isoform, p38 siRNA, and chemical inhibitors of p38 activation suggest that p38 is necessary for Nef-induced activator protein-1 (AP-1) activation, as inhibition leads to an attenuation of AP-1-dependent transcription. Furthermore, mutagenesis of the FasL promoter reveals that its AP-1 enhancer element is required for Nef-mediated transcriptional activation. Therefore, a linear pathway for Nef-induced FasL expression that encompasses p38 and AP-1 has been elucidated. Furthermore, chemical inhibition of the p38 pathway attenuates HIV-1-mediated bystander killing of CD8 cells in vitro. (Blood. 2005;106:2059-2068) PMID:15928037

  9. Human phenotypically distinct TGFBI corneal dystrophies are linked to the stability of the fourth FAS1 domain of TGFBIp

    DEFF Research Database (Denmark)

    Runager, Kasper; Basaiawmoit, Rajiv Vaid; Deva, Taru

    2011-01-01

    the overall stability of intact TGFBIp revealing the following stability ranking R555W>WT>R555Q>A546T. Significantly, the stability ranking of the isolated FAS1-4 domains mirrored the behavior of the intact protein. In addition, it was linked to the aggregation propensity as the least stable mutant (A546T...

  10. Literacy-Based Supports for Young Adults with FAS/FAE [Fetal Alcohol Syndrome/Fetal Alcohol Effects].

    Science.gov (United States)

    Raymond, Margaret; Belanger, Joe

    During a 1-year period, a study investigated the contributions made by 3 literacy-based supports (support circles, cognitive compensatory tools, and cognitive enhancement tools) to the lives of 5 young adults, aged 16-34, with FAS/FAE (Fetal Alcohol Syndrome/Fetal Alcohol Effects). Four of the five subjects had IQs (intelligence quotients) above…

  11. CD95 (Fas) ligand expression of Epstein-Barr virus (EBV)-infected lymphocytes: a possible mechanism of immune evasion in chronic active EBV infection.

    Science.gov (United States)

    Ohshima, K; Suzumiya, J; Sugihara, M; Nagafuchi, S; Ohga, S; Kikuchi, M

    1999-01-01

    The Epstein-Barr virus (EBV) induces infectious mononucleosis (IM) and can be associated with chronic active EBV infection (CAEBV). Cytotoxic T lymphocytes (CTL) play an important role in excluding EBV-infected cells. Two cytotoxic mechanisms of CTL have been demonstrated: one perforin/granzyme-based and the other Fas (CD95)/Fas ligand (FasL)-based. To clarify these two pathways in CAEBV, we analyzed six patients with CAEBV and four patients with IM using immunohistochemical staining of the lymph nodes. In both CAEBV and IM, CD8+ T-cells increased in number, but CD56+ natural killer cells were rare. In four of six cases with CAEBV, approximately half the lymphocytes were positive for T cell-restricted intracellular antigens (TIA-1), which were recognized by the cytolytic granules of CTL. In IM, the number of TIA-1 positive cells was smaller than that in CAEBV. Fas-positive lymphocytes were frequently encountered in both CAEBV and IM. However, FasL-positive lymphocytes increased in three of six patients with CAEBV, but not in patients with IM. Except for one case with CAEBV, the number of perforin- and/or granzyme-positive cells was small in number in both CAEBV and IM cases. In double-staining FasL and EBV in situ hybridization, FasL-positive EBV-infected lymphocytes were detected in CAEBV but not in IM. In CAEBV, the Fas/FasL pathway and not perforin pathways appears to play an important role in the pathogenesis. The data suggest that EBV-infected lymphocytes may evade immune attack through the expression of FasL.

  12. Fas-deficient mice have impaired alveolar neutrophil recruitment and decreased expression of anti-KC autoantibody:KC complexes in a model of acute lung injury

    Directory of Open Access Journals (Sweden)

    Gil Sucheol

    2012-10-01

    Full Text Available Abstract Background Exposure to mechanical ventilation enhances lung injury in response to various stimuli, such as bacterial endotoxin (LPS. The Fas/FasL system is a receptor ligand system that has dual pro-apoptotic and pro-inflammatory functions and has been implicated in the pathogenesis of lung injury. In this study we test the hypothesis that a functioning Fas/FasL system is required for the development of lung injury in mechanically ventilated mice. Methods C57BL/6 (B6 and Fas-deficient lpr mice were exposed to either intra-tracheal PBS followed by spontaneous breathing or intra-tracheal LPS followed by four hours mechanical ventilation with tidal volumes of 10 mL/kg, respiratory rate of 150 breaths per minute, inspired oxygen 0.21 and positive end expiratory pressure (PEEP of 3 cm of water. Results Compared with the B6 mice, the lpr mice showed attenuation of the neutrophilic response as measured by decreased numbers of BAL neutrophils and lung myeloperoxidase activity. Interestingly, the B6 and lpr mice had similar concentrations of pro-inflammatory cytokines, including CXCL1 (KC, and similar measurements of permeability and apoptosis. However, the B6 mice showed greater deposition of anti-KC:KC immune complexes in the lungs, as compared with the lpr mice. Conclusions We conclude that a functioning Fas/FasL system is required for full neutrophilic response to LPS in mechanically ventilated mice.

  13. The "Fas counterattack" is not an active mode of tumor immune evasion in colorectal cancer with high-level microsatellite instability.

    LENUS (Irish Health Repository)

    Houston, Aileen M

    2012-02-03

    Microsatellite instability (MSI) is an alternative pathway of colorectal carcinogenesis. It is found in 10% to 15% of sporadic colorectal neoplasms and is characterized by failure of the DNA mismatch-repair system. High-level MSI (MSI-H) is associated with tumor-infiltrating lymphocytes (TILs) and a favorable prognosis. Expression of Fas ligand (FasL\\/CD95L) by cancer cells may mediate tumor immune privilege by inducing apoptosis of antitumor immune cells. The aim of this study was to investigate the relationship between FasL expression and MSI status in primary colon tumors. Using immunohistochemistry, we detected FasL expression in 91 colorectal carcinoma specimens, previously classified according to the level of MSI as MSI-H (n = 26), MSI-low (MSI-L) (n = 29), and microsatellite stable (n = 36). Tumor-infiltrating lymphocyte density was quantified by immunohistochemical staining for CD3. MSI-H tumors were significantly associated with reduced frequency (P = .04) and intensity (P = .066) of FasL expression relative to non-MSI-H (ie, microsatellite stable and MSI-L) tumors. Higher FasL staining intensity correlated with reduced TIL density (P = .059). Together, these findings suggest that the abundance of TILs found in MSI-H tumors may be due to the failure of these tumor cells to up-regulate FasL and may explain, in part, the improved prognosis associated with these tumors.

  14. Serum soluble Fas ligand and nitric oxide in long-term pulmonary complications induced by sulfur mustard: Sardasht-Iran Cohort Study.

    Science.gov (United States)

    Ghazanfari, Tooba; Sharifnia, Zarin; Yaraee, Roya; Pourfarzam, Shahryar; Kariminia, Amina; Mahlojirad, Maryam; Faghihzadeh, Soghrat; Jalali-Nodoushan, Mohammad Reza; Ardestani, Sussan K; Soroush, Mohammad R; Amiri, Sara; Hassan, Zuhair M; Ghavami, Saeid; Ghanei, Mostafa

    2009-12-01

    Sulfur mustard (SM) has short- and long-term toxicity against various organs including the respiratory system. However, the basic and molecular mechanisms of SM long-term toxicity have not clearly been defined. Thus, the aim of this study was to evaluate the association of soluble Fas ligand (sFasL) as well as nitric oxide (NO) serum levels with long-term pulmonary complications in a SM exposed population 20 years after SM exposure. In this historical cohort study 372 male SM exposed subjects and 128 age-matched unexposed controls were studied. Clinical evaluation and pulmonary function tests were carried out for all participants and serum concentrations of sFasL and NO measured. According to our results, the serum levels of sFasL and NO were not significantly different between the exposed and control groups. However, the serum levels of sFasL in the exposed group with pulmonary problems were significantly higher than their corresponding in the control group (116.711+/-81.166 vs 86.027+/-30.199 and p=0.028). Furthermore a significant elevation in sFasL levels was found in the exposed subjects with pulmonary problems compared to those exposed participants without pulmonary problems (116.711+/-81.166 vs 90.692+/-57.853 and p=0.004). Based on Global Initiative for chronic Obstructive Lung Disease (GOLD) classification analysis a positive correlation was observed between sFasL levels and pulmonary problems. There was also a significant negative correlation between sFasL and the white blood cell (WBC) count in the SM exposed cohort, but not in the control group. No significant association was shown between NO and pulmonary impairment in the SM exposed subjects. Thus, our results indicate that elevated serum levels of sFasL may be associated with progression of pulmonary diseases in the SM exposed subjects.

  15. Molecular manipulation of keratin 8/18 intermediate filaments: modulators of FAS-mediated death signaling in human ovarian granulosa tumor cells.

    Science.gov (United States)

    Trisdale, Sarah K; Schwab, Nicolette M; Hou, Xiaoying; Davis, John S; Townson, David H

    2016-02-24

    Granulosa cell tumors (GCT) are a rare ovarian neoplasm but prognosis is poor following recurrence. Keratin intermediate filaments expressed in these tumors are a diagnostic marker, yet paradoxically, may also constitute a target for therapeutic intervention. In the current study, we evaluated keratin 8/18 (K8/18) filament expression as a mechanism of resistance to apoptosis in GCT, specifically focusing on regulation of the cell surface death receptor, Fas (FAS). The GCT cell line, KGN, was transiently transfected with siRNA to KRT8 and KRT18 to reduce K8/18 filament expression. Expression of K8/18, FAS, and apoptotic proteins (PARP, cleaved PARP) were evaluated by fluorescence microscopy, flow cytometric analysis, and immunoblotting, respectively. The incidence of FAS-mediated apoptosis in KGN cells was measured by caspase 3/7 activity. All experiments were performed independently three to six times, using a fresh aliquot of KGN cells for each experiment. Quantitative data were analyzed by one- or two-way analysis of variance (ANOVA), followed by a Tukey's post-test for multiple comparisons; differences among means were considered statistically significant at P cells exhibited abundant K8/18 filament expression (~90 % of cells), and minimal expression of FAS (cells). These cells were resistant to FAS-activating antibody (FasAb)-induced apoptosis, as determined by detection of cleaved PARP and measurement of caspase 3/7 activity. Conversely, siRNA-mediated knock-down of K8/18 filament expression enhanced FAS expression (> 70 % of cells) and facilitated FasAb-induced apoptosis, evident by increased caspase 3/7 activity (P cells and their role in apoptotic resistance provides a greater mechanistic understanding of ovarian tumorgenicity, specifically GCT, as well as a clinically-relevant target for potential therapeutic intervention.

  16. Tumor necrosis factor α sensitizes primary murine hepatocytes to Fas/CD95-induced apoptosis in a Bim- and Bid-dependent manner.

    Science.gov (United States)

    Schmich, Kathrin; Schlatter, Rebekka; Corazza, Nadia; Sá Ferreira, Karine; Ederer, Michael; Brunner, Thomas; Borner, Christoph; Merfort, Irmgard

    2011-01-01

    Fas/CD95 is a critical mediator of cell death in many chronic and acute liver diseases and induces apoptosis in primary hepatocytes in vitro. In contrast, the proinflammatory cytokine tumor necrosis factor α (TNFα) fails to provoke cell death in isolated hepatocytes but has been implicated in hepatocyte apoptosis during liver diseases associated with chronic inflammation. Here we report that TNFα sensitizes primary murine hepatocytes cultured on collagen to Fas ligand (FasL)-induced apoptosis. This synergism is time-dependent and is specifically mediated by TNFα. Fas itself is essential for the sensitization, but neither Fas up-regulation nor endogenous FasL is responsible for this effect. Although FasL is shown to induce Bid-independent apoptosis in hepatocytes cultured on collagen, the sensitizing effect of TNFα is clearly dependent on Bid. Moreover, both c-Jun N-terminal kinase activation and Bim, another B cell lymphoma 2 homology domain 3 (BH3)-only protein, are crucial mediators of TNFα-induced apoptosis sensitization. Bim and Bid activate the mitochondrial amplification loop and induce cytochrome c release, a hallmark of type II apoptosis. The mechanism of TNFα-induced sensitization is supported by a mathematical model that correctly reproduces the biological findings. Finally, our results are physiologically relevant because TNFα also induces sensitivity to agonistic anti-Fas-induced liver damage. Our data suggest that TNFα can cooperate with FasL to induce hepatocyte apoptosis by activating the BH3-only proteins Bim and Bid. Copyright © 2010 American Association for the Study of Liver Diseases.

  17. L-carnitine protects against testicular dysfunction caused by gamma irradiation in mice.

    Science.gov (United States)

    Ahmed, Mohamed Mohamed; Ibrahim, Zein Shaban; Alkafafy, Mohamed; El-Shazly, Samir Ahmed

    2014-07-01

    This study was conducted on mice to evaluate the radioprotective role of L-carnitine against γ-ray irradiation-induced testicular damage. Adult male mice were exposed to whole body irradiation at a total dose of 1 Gy. Radiation exposure was continued 24 h a day (0.1 Gy/day) throughout the 10 days exposure period either in the absence and/or presence of L-carnitine at an i.p. dose of 10 mg/kg body weight/day. Results revealed that γ-rays irradiation suppressed the expression of ABP and CYP450SCC mRNA, whereas treatment with L-carnitine prior and throughout γ-rays irradiation exposure inhibited this suppression. Treatment with γ-ray irradiation or L-carnitine down-regulated expression of aromatase mRNA. With combined treatment, L-carnitine significantly normalized aromatase expression. γ-Ray irradiation up-regulated expression of FasL and Cyclin D2 mRNA, while L-carnitine inhibited these up-regulations. Results also showed that γ-ray-irradiation up-regulated TNF-α, IL1-β and IFN-γ mRNA expressions compared to either controls or the L-carnitine treated group. Moreover, γ-irradiation greatly reduced serum testosterone levels, while L-carnitine, either alone or in combination with irradiation, significantly increased serum testosterone levels compared to controls. In addition, γ-irradiation induced high levels of sperm abnormalities (43%) which were decreased to 12% in the presence of L-carnitine. In parallel with these findings, histological examination showed that γ-irradiation induced severe tubular degenerative changes, which were reduced by L-carnitine pre-treatment. These results clarified the immunostimulatory effects of L-carnitine and its radioprotective role against testicular injury. Copyright © 2014 Elsevier GmbH. All rights reserved.

  18. Effect of light irradiation by light emitting diode on colon cancer cells.

    Science.gov (United States)

    Matsumoto, Noriko; Yoshikawa, Kozo; Shimada, Mitsuo; Kurita, Nobuhiro; Sato, Hirohiko; Iwata, Takashi; Higashijima, Jun; Chikakiyo, Motoya; Nishi, Masaaki; Kashihara, Hideya; Takasu, Chie; Eto, Shohei; Takahashi, Akira; Akutagawa, Masatake; Emoto, Takahiro

    2014-09-01

    Recent studies have demonstrated the efficacy of irradiation from light emitting diodes (LED) for wound healing, anti-inflammation and anticancer therapies. However, little is known about the effects of visible light in colon cancer cells. The purpose of this study was to evaluate the biological response (including gene expression changes) of human colon cancer cells to different wavelengths of LED irradiation. Human colon cancer cells (HT29 or HCT116) were seeded onto laboratory dishes that were then put on LED irradiation equipment with a 465 nm-, 525 nm-, or 635 nm-LED. Irradiation at 15 or 30 mW was performed 10 min/day, each day for 5 days. The cell counting kit8 was then used to measure cell viability. Apoptosis and expression of several mRNAs (caspase, MAPK and autophagy pathway) in HT29 cultures irradiated with 465 nm LED were evaluated via AnnexinV/PI and RT-PCR, respectively. Viability of HT29 and HCT116 cells was lower in 465 nm-LED irradiated cultures than in control cultures, but viability of HT29 cells did not differ between control cultures and 525 nm-LED or 635 nm-LED irradiated cultures. Moreover, the expression of FAS, caspase-3, capase-8, and JUK were significantly higher in 465 nm-LED irradiated cultures than in control cultures, and expression of ERK1/2 and LC3 was lower in blue-irradiated cells. LED irradiation at 465 nm inhibited the proliferation of HT29 cells and of HCT116 cells. Notably, LED irradiation at 465 nm promoted apoptosis inHT29 cultures via the extrinsic apoptosis pathway and the MAPK pathway. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  19. Children and adolescents with fetal alcohol syndrome (FAS): better social and emotional integration after early diagnosis.

    Science.gov (United States)

    Alex, K; Feldmann, R

    2012-03-01

    Alcoholism during pregnancy is one of the most common factors in western societies causing persisting congenital and multiple physical as well as neurological impairments. Finding the diagnosis at first sight puts medical professionals into a demanding situation. Therefore the objective of this study was to detect patients' developmental characteristics with the main focus on the necessity of the diagnosis itself. 125 young patients, whose diagnosis of fetal alcohol syndrome (FAS) was made at the Muenster University Hospital, were followed up. Biographic details such as living conditions, health, developmental problems and educational career were gathered using a structured interview. The diagnosis itself and the impact of this on the patients were also explored. Patients displayed characteristics of a less mature trait of character. The majority were looked after by foster parents. High rates of social and developmental problems could be found. The diagnosis was identified as a protective factor, with significantly better outcomes for patients being diagnosed in early childhood. A diagnosis established later in life was particularly helpful for the families and caregivers. Feelings of failure and self-blame could be diminished. The early detection of affected children has to be improved as receiving the correct diagnosis, despite the persistent impairments, is of major benefit for both patients and their families. © Georg Thieme Verlag KG Stuttgart · New York.

  20. The chemokine fractalkine inhibits Fas-mediated cell death of brain microglia.

    Science.gov (United States)

    Boehme, S A; Lio, F M; Maciejewski-Lenoir, D; Bacon, K B; Conlon, P J

    2000-07-01

    Fractalkine is a CX3C-family chemokine, highly and constitutively expressed on the neuronal cell surface, for which a clear CNS physiological function has yet to be determined. Its cognate receptor, CX3CR-1, is constitutively expressed on microglia, the brain-resident macrophages; however, these cells do not express fractalkine. We now show that treatment of microglia with fractalkine maintains cell survival and inhibits Fas ligand-induced cell death in vitro. Biochemical characterization indicates that this occurs via mechanisms that may include 1) activation of the phosphatidylinositol-3 kinase/protein kinase B pathway, resulting in phosphorylation and blockade of the proapoptotic functions of BAD; 2) up-regulation of the antiapoptotic protein Bcl-xL; and 3) inhibition of the cleavage of BH3-interacting domain death agonist (BID). The observation that fractalkine serves as a survival factor for primary microglia in part by modulating the protein levels and the phosphorylation status of Bcl-2 family proteins reveals a novel physiological role for chemokines. These results, therefore, suggest that the interaction between fractalkine and CX3CR-1 may play an important role in promoting and preserving microglial cell survival in the CNS.

  1. Psychometric properties of the Fibromyalgia Assessment Status (FAS) index: a national web-based study of fibromyalgia.

    Science.gov (United States)

    Iannuccelli, C; Sarzi-Puttini, P; Atzeni, F; Cazzola, M; di Franco, M; Guzzo, M P; Bazzichi, L; Cassisi, G A; Marsico, A; Stisi, S; Salaffi, F

    2011-01-01

    Fibromyalgia (FM) is a generalized chronic pain condition that is often accompanied by symptoms such as fatigue, sleep disturbances, psychological and cognitive alterations, headache, migraine, variable bowel habits, diffuse abdominal pain, and urinary frequency. Its key assessment domains include pain, fatigue, disturbed sleep, physical and emotional functioning, and patient global satisfaction and health-related quality of life (HRQL). A number of evaluation measures have been adapted from the fields of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, and others such as the Fibromyalgia Assessment Status (FAS) index and the Fibromyalgia Impact Questionnaire (FIQ) have been specifically developed. The aim of this study was to assess the impact of FM on HRQL by comparing the performance of the FAS index, the FIQ and the Health Assessment Questionnaire [HAQ] in 541 female and 31 male FM patients (mean age 50 years; mean disease duration 7.7 years) entered in the database of a web-based survey registry developed by the Italian Fibromyalgia Network (IFINET). Tests of convergent validity showed that the FAS index and FIQ significantly correlated with each other (rho=0.608, pindex and other clinical measures of disability, including the HAQ (rho=0.423, pindex revealed a statistically significant difference between males and females (p=0.048), analysed using the Mann-Whitney U-test for all pair wise comparisons. The FAS index is a valid three-item instrument (pain, fatigue and sleep disturbances) that performs at least as well as the FIQ in FM patients, and is simpler to administer and score. Both questionnaires may be useful when screening FM patients, with the choice of the most appropriate instrument depending on the setting.

  2. The retinal pigment epithelium (RPE) induces FasL and reduces iNOS and Cox2 in primary monocytes.

    Science.gov (United States)

    Hettich, Christin; Wilker, Sebastian; Mentlein, Rolf; Lucius, Ralph; Roider, Johann; Klettner, Alexa

    2014-11-01

    Retinal pigment epithelium (RPE) cells may alter the phenotype of monocytes by soluble factors that may be influenced by stimulation of the RPE. Since RPE cells carry the toll-like receptor-3 (TLR3) that detects and reacts to viral infection through binding of dsRNA we investigated the effects of RPE cells with or without TLR3 stimulation on blood-derived monocytes with respect to regulation of pro-/anti-inflammatory cytokines, anti-angiogenic factors and migratory properties. Primary RPE cells were prepared from porcine eyes; monocytes were prepared from porcine blood. TLR3 activation was induced by polyinosinic:polycytidylic acid (Poly I:C). RPE cells were stimulated with Poly I:C in different concentrations for 24 hours and a cell culture supernatant was applied to the monocytes. Expression of CD14 and Fas ligand (FasL) was determined via flow cytometry. The expression of IL-6, IL-1ß, TNFα, Cox2, iNOS and IL-10 was determined via quantitative RT-PCR. Migration was determined using Boyden chamber experiments. The supernatant of RPE cells, irrespective of TLR3 activation, induced FasL expression in the monocytes. Expression of iNOS and Cox2 was reduced by RPE cells and the reduction of Cox2 but not if iNOS was lost under TLR3 activation. No induction of IL-6, IL-1ß, IL-10 or TNFα by the RPE was seen. TLR3-activated RPE cells induced monocyte migration. RPE cells induce an upregulation of FasL and a downregulation of iNOS and Cox2 without upregulating inflammatory cytokines, possibly inducing an anti-angiogenic phenotype in the monocytes. This phenotype is still upheld after challenging RPE cells with dsRNA, mimicking a viral infection.

  3. Crystal structure of FAS thioesterase domain with polyunsaturated fatty acyl adduct and inhibition by dihomo-[gamma]-linolenic acid

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wei; Chakravarty, Bornali; Zheng, Fei; Gu, Ziwei; Wu, Hongmei; Mao, Jianqiang; Wakil, Salih J.; Quiocho, Florante A. (Baylor)

    2012-05-29

    Human fatty acid synthase (hFAS) is a homodimeric multidomain enzyme that catalyzes a series of reactions leading to the de novo biosynthesis of long-chain fatty acids, mainly palmitate. The carboxy-terminal thioesterase (TE) domain determines the length of the fatty acyl chain and its ultimate release by hydrolysis. Because of the upregulation of hFAS in a variety of cancers, it is a target for antiproliferative agent development. Dietary long-chain polyunsaturated fatty acids (PUFAs) have been known to confer beneficial effects on many diseases and health conditions, including cancers, inflammations, diabetes, and heart diseases, but the precise molecular mechanisms involved have not been elucidated. We report the crystal structure of the hFAS TE domain covalently modified and inactivated by methyl {gamma}-linolenylfluorophosphonate. Whereas the structure confirmed the phosphorylation by the phosphonate head group of the active site serine, it also unexpectedly revealed the binding of the 18-carbon polyunsaturated {gamma}-linolenyl tail in a long groove-tunnel site, which itself is formed mainly by the emergence of an {alpha} helix (the 'helix flap'). We then found inhibition of the TE domain activity by the PUFA dihomo-{gamma}-linolenic acid; {gamma}- and {alpha}-linolenic acids, two popular dietary PUFAs, were less effective. Dihomo-{gamma}-linolenic acid also inhibited fatty acid biosynthesis in 3T3-L1 preadipocytes and selective human breast cancer cell lines, including SKBR3 and MDAMB231. In addition to revealing a novel mechanism for the molecular recognition of a polyunsaturated fatty acyl chain, our results offer a new framework for developing potent FAS inhibitors as therapeutics against cancers and other diseases.

  4. Altered circadian rhythms of the stress hormone and melatonin response in lupus-prone MRL/MP-fas(Ipr) mice.

    Science.gov (United States)

    Lechner, O; Dietrich, H; Oliveira dos Santos, A; Wiegers, G J; Schwarz, S; Harbutz, M; Herold, M; Wick, G

    2000-06-01

    The immune system interacts with the hypothalamo-pituitary-adrenal axis via so-called glucocorticoid increasing factors, which are produced by the immune system during immune reactions, causing an elevation of systemic glucocorticoid levels that contribute to preservation of the immune reactions specificities. Previous results from our laboratory had already shown an altered immuno-neuroendocrine dialogue via the hypothalamo-pituitary-adrenal axis in autoimmune disease-prone chicken and mouse strains. In the present study, we further investigated the altered glucocorticoid response via the hypothalamo-pituitary-adrenal axis in murine lupus. We established the circadian rhythms of corticosterone, dehydroepiandrosterone-sulfate, adrenocorticotropic hormone and melatonin, as well as the time response curves after injection of interleukin-1 of the first three parameters in normal SWISS and lupus-prone MRL/MP-fas(Ipr) mice. The results show that lupus-prone MRL/ MP-fas(Ipr) mice do not react appropriately to changes of the light/dark cycle, circadian melatonin rhythms seem to uncouple from the light/dark cycle, and plasma corticosterone levels are elevated during the resting phase. Diurnal changes of dehydroepiandrosterone-sulfate and adrenocorticotropic hormone were normal compared to healthy controls. These data indicate that MRL/ MP-fas(Ipr) mice not only show an altered glucocorticoid response mediated via the hypothalamo pituitary adrenal axis to IL-1, but are also affected by disturbances of corticosterone and melatonin circadian rhythms. Our findings may have implications for intrathymic T cell development and the emergence of autoimmune disease.

  5. Caspase-6 Induces 7A6 Antigen Localization to Mitochondria During FAS-induced Apoptosis of Jurkat Cells.

    Science.gov (United States)

    Suita, Hiroaki; Shinomiya, Takahisa; Nagahara, Yukitoshi

    2017-04-01

    Mitochondria are central to apoptosis. However, apoptosis progression involving mitochondria is not fully understood. A factor involved in mitochondria-mediated apoptosis is 7A6 antigen. 7A6 localizes to mitochondria from the cytosol during apoptosis, which seems to involve 'effector' caspases. In this study, we investigated the precise role of effector caspases in 7A6 localization to mitochondria during apoptosis. Human T-cell lymphoma Jurkat cells were treated with an antibody against FAS. 7A6 localization was analyzed by confocal laser scanning microscopy and flow cytometry. Caspases activation was determined by western blot analysis. 7A6 localization to mitochondria during anti-FAS-induced apoptosis was significantly reduced by the caspase-6 inhibitor, N-acetyl-Val-Glu-Ile-Asp-aldehyde, but not by the caspase-3 inhibitor, N-acetyl-Asp-Asn-Leu-Asp-aldehyde, nor caspase-7/3 inhibitor, N-acetyl-Asp-Gln-Thr-Asp-aldehyde. Moreover, caspase-6 down-regulation suppressed 7A6 localization to mitochondria. Caspase-6 regulates 7A6 localization to mitochondria during anti-FAS-induced apoptosis of Jurkat cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  6. Exacerbated autoimmunity in the absence of TLR9 in MRL.Fas(lpr) mice depends on Ifnar1.

    Science.gov (United States)

    Nickerson, Kevin M; Cullen, Jaime L; Kashgarian, Michael; Shlomchik, Mark J

    2013-04-15

    TLR9 suppresses TLR7-driven pathogenesis in the MRL.Fas(lpr) murine model of systemic lupus erythematosus, but the mechanisms by which TLR7 promotes and TLR9 prevents disease in this and other lupus models remain unclear. Type I IFNs (IFN-I) have also been implicated in the pathogenesis of lupus both in patients and in several murine models of disease, but their role in MRL.Fas(lpr) mice is controversial. Using MRL.Fas(lpr) mice genetically deficient in a subunit of the receptor for IFN-I, Ifnar1, we show that IFN-I contribute significantly to renal disease in this model. Ifnar1 had no effect on anti-nucleosome or anti-Sm autoantibody titers, but instead regulated anticytoplasmic and anti-RNA specificities. Moreover, Ifnar1 deficiency prevented the exacerbation of clinical disease observed in Tlr9-deficient animals in this lupus model. Thus, IFN-I signaling is an important mediator of lupus pathogenesis and anti-RNA Ab production that is dysregulated in the absence of Tlr9.

  7. Expression of Apoptosis Inducing-Ligands, TRAIL and Fas-L in Hydatid Cyst Germinal Layer and Normal Tissue

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    Adel Spotin

    2012-04-01

    Full Text Available Background & objectives: Hydaticosis is a zoonotic helminthic disease of human and other intermediated hosts in which larval stages of the tapeworm Echinococcus granulosu transfect human. The liver and lung are the host tissues for the hydatid cyst . It is unknown which mechanisms are involved in infertility of the cyst and suppression of the fertile cyst. This study was aimed to evaluate the expression of the apoptosis inducing-ligands such as TRAIL and Fas-L in germinal layer of the cyst and human normal tissue surrounding the cyst that is one of the unknown host innate immunity mechanisms against the hydatid cyst.   Methods: In this study, four isolated hydatid cysts were used which had been diagnosed in patients by radiography and parasitological examination in Mashhad Ghaem hospital. Furthermore, the germinal layer of the cyst and accompanied normal peripheral tissues were separated by scalpel in sterile conditions. After homogenization, expression of TRAIL and Fas-L genes were studied by semi-quantitive RT-PCR method.   Results: The TRAIL and Fas-L showed significant higher level expression in germinal layer of infertile cyst than the fertile cyst and host normal tissues.   Conclusion: The host tissue-induced apoptosis of germinal layer of the fertile cysts is probably one of the infertility mechanism in patients with hydaticosis

  8. Palpebral fissure length measurement: accuracy of the FAS facial photographic analysis software and inaccuracy of the ruler.

    Science.gov (United States)

    Astley, Susan J

    2015-01-01

    Accurate fetal alcohol spectrum disorder diagnoses require accurate facial measurement. The Fetal Alcohol Syndrome (FAS) Facial Photographic Analysis Software was developed to overcome measurement error known to occur with ruler measurement of the PFL. Recent publications have queried the Software's accuracy. 1) Demonstrate the Software's ability to accurately measure a PFL from a 2-dimensional digital facial photograph. 2) Demonstrate the frequency and magnitude of error when the PFL is measured directly by clinicians using a ruler. Objective 1: PFLs of mannequins were measured using the Software and a sliding digital caliper, with the latter serving as the gold-standard accurate measure. Mannequins allowed the caliper prongs to be placed directly on the landmarks that define the PFL. Objective 2: PFLs of 1,027 patients evaluated at the University of Washington FAS Diagnostic & Prevention Network were measured with the Software and directly by one or two clinicians using a ruler. Objective 1: The Software derived PFLs that were identical to or within 0.2 mm of the caliper measures. Objective 2: There was tremendous inter-rater variability in PFLs measured by clinicians using a hand held ruler. Seventy-seven percent of patients had their PFLs measured incorrectly (greater than 1 mm error) by at least one of the two clinicians using a ruler. The FAS Facial Photographic Analysis Software measures the PFL with the same accuracy as a sliding digital caliper, as it was programmed to do. Direct measurement of the PFL with a ruler is very prone to error.

  9. The Fas/CD95 receptor regulates the death of autoreactive B cells and the selection of antigen-specific B cells

    Directory of Open Access Journals (Sweden)

    Anne-Odile eHUEBER

    2012-07-01

    Full Text Available Cell death receptors have crucial roles in the regulation of immune responses. Here we review recent in vivo data confirming that the Fas death receptor (TNFSR6 on B cells is important for the regulation of autoimmunity since the impairment of only Fas function on B cells results in uncontrolled autoantibody production and autoimmunity. Fas plays a role in the elimination of the non-specific and auto-reactive B cells in germinal center, while during the selection of antigen specific B cells different escape signals ensure the resistance to Fas-mediated apoptosis. Antigen specific survival such as BCR or MHCII signal or coreceptors (CD19 cooperating with BCR inhibits the formation of death inducing signaling complex. Antigen-specific survival can be reinforced by antigen-independent signals of IL4 or CD40 overproducing the anti-apoptotic members of the Bcl-2 family proteins.

  10. Evaluation of diabetic polyneuropathy in Type 2 diabetes mellitus by nerve conduction study and association of severity of neuropathy with serum sFasL level

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    Avijit Mondal

    2012-01-01

    Full Text Available Introduction: Diabetes mellitus (DM, a growing health problem globally, has reached epidemic proportions in India. Recently, Fas-mediated apoptosis has been proposed as a causative factor responsible for neuronal degeneration in diabetic polyneuropathy (DPN, but there are very few studies to show association of serum soluble Fas ligand (sFasL level with severity of neuropathy. Aim and Objective: The aim of this study was to investigate whether serum sFasL, a transmembrane glycoprotein involved in apoptosis, has any association with severity of peripheral neuropathy in Type 2 DM. Materials and Methods: The study was conducted in Department of Physiology in collaboration with Department of Endocrinology, IPGME&R. sFasL levels in serum were assessed using ELISA method in healthy individuals (n = 16, newly diagnosed diabetic controls (n = 16 without any complications, and in DPN cases (n = 33 with predominant neuropathy only. All subjects underwent both electrodiagnostic procedures and vibration perception threshold (VPT for quantitative assessment of the severity of neuropathy. Using nerve conduction studies, amplitudes, velocities, and latencies of both sensory and motor nerves were recorded. Results: In DPN patients, concentration of sFasL levels (87.53 ± 3.49 was significantly decreased (P < 0.0001 not only when compared with normal controls (225.30 ± 2.97 but also when compared with diabetic patients without any complication (161 ± 3.63. Moreover, the concentration of sFasL is significantly (P < 0.0001 associated with the severity of neuropathy both by VPT and nerve conduction velocity (NCV. Conclusion: Fas-mediated apoptosis is involved in Type 2 DM and might be associated with the severity of polyneuropathy.

  11. Development of the SoFAS (solid fats and added sugars) concept: the 2010 Dietary Guidelines for Americans.

    Science.gov (United States)

    Nicklas, Theresa A; O'Neil, Carol E

    2015-05-01

    The diets of most US children and adults are poor, as reflected by low diet quality scores, when compared with the recommendations of the Dietary Guidelines for Americans (DGAs). Contributing to these low scores is that most Americans overconsume solid fats, which may contain saturated fatty acids and added sugars; although alcohol consumption was generally modest, it provided few nutrients. Thus, the 2005 DGAs generated a new recommendation: to reduce intakes of solid fats, alcohol, and added sugars (SoFAAS). What precipitated the emergence of the new SoFAAS terminology was the concept of discretionary calories (a "calorie" is defined as the amount of energy needed to increase the temperature of 1 kg of water by 1°C), which were defined as calories consumed after an individual had met his or her recommended nutrient intakes while consuming fewer calories than the daily recommendation. A limitation with this concept was that additional amounts of nutrient-dense foods consumed beyond the recommended amount were also considered discretionary calories. The rationale for this was that if nutrient-dense foods were consumed beyond recommended amounts, after total energy intake was met then this constituted excess energy intake. In the 2010 DGAs, the terminology was changed to solid fats and added sugars (SoFAS); thus, alcohol was excluded because it made a minor contribution to overall intake and did not apply to children. The SoFAS terminology also negated nutrient-dense foods that were consumed in amounts above the recommendations for the specific food groups in the food patterns. The ambiguous SoFAS terminology was later changed to "empty calories" to reflect only those calories from solid fats and added sugars (and alcohol if consumed beyond moderate amounts). The purpose of this review is to provide an historical perspective on how the dietary recommendations went from SoFAAS to SoFAS and how discretionary calories went to empty calories between the 2005 and 2010

  12. The majority of lamina propria CD4(+) T-cells from scid mice with colitis undergo Fas-mediated apoptosis in vivo

    DEFF Research Database (Denmark)

    Bregenholt, S; Petersen, T R; Claesson, Mogens Helweg

    2001-01-01

    We have previously shown that adoptively transferred CD4(+) T-cells mediate an chronic colitis in severe combined immune deficient (scid) mice. Colitis is accompanied by activation and apoptosis of Fas ligand and TNF-alpha expressing CD4(+) T-cells in the diseased colonic lamina propria (Eur. J....... Immunol. 28:3655 (1998)). Here we investigate the apoptosis-inducing mechanism in these lamina propria infiltrating CD4(+) T-cells. We observe that freshly isolated lamina propria CD4(+) T-cells can kill Fas transfected P815 mastocytoma cells in a TCR/CD3 redirected chromium-release assay, but do...... not express TNF-alpha mediated cytotoxicity. Pre-incubation of the isolated lamina propria CD4(+) T-cells with an anti-FasL antiserum partially blocked killing of the Fas transfected target cells, indicating a role for the Fas-FasL system in the killing process. Treatment of scid mice with colitis with anti...

  13. Combined adenovirus-mediated artificial microRNAs targeting mfgl2, mFas, and mTNFR1 protect against fulminant hepatic failure in mice.

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    Dong Xi

    Full Text Available Hepatitis B virus (HBV-related acute-on-chronic liver failure (ACLF has a poor prognosis with high in-hospital mortality. Hepatic and circulating inflammatory cytokines, such as fibrinogen like protein 2 (fgl2, FasL/Fas, and TNFα/TNFR1, play a significant role in the pathophysiology of ACLF. This study aimed to investigate the therapeutic effect of recombinant adenoviral vectors carrying constructed DNA code for non-native microRNA (miRNA targeting mouse fgl2 (mfgl2 or both mFas and mTNFR1 on murine hepatitis virus (MHV-3-induced fulminant hepatitis in BALB/cJ mice. Artificial miRNA eukaryotic expression plasmids against mfgl2, mFas, and mTNFR1 were constructed, and their inhibitory effects on the target genes were confirmed in vitro. pcDNA6.2-mFas-mTNFR1- miRNA,which expresses miRNA against both mFas and mTNFR1 simultaneously,was constructed. To construct a miRNA adenovirus expression vector against mfgl2, pcDNA6.2-mfgl2-miRNA was cloned using Gateway technology. Ad-mFas-mTNFR1- miRNA was also constructed by the same procedure. Adenovirus vectors were delivered by tail-vein injection into MHV-3-infected BALB/cJ mice to evaluate the therapeutic effect. 8 of 18 (44.4% mice recovered from fulminant viral hepatitis in the combined interference group treated with Ad-mfgl2-miRNA and Ad-mFas-mTNFR1-miRNA. But only 4 of 18 (22.2% mice receiving Ad-mfgl2-miRNA and 3 of 18 (16.7% mice receiving Ad-mFas-mTNFR1- miRNA survived. These adenovirus vectors significantly ameliorated inflammatory infiltration, fibrin deposition, hepatocyte necrosis and apoptosis, and prolonged survival time. Our data illustrated that combined interference using adenovirus-mediated artificial miRNAs targeting mfgl2, mFas, and mTNFR1 might have significant therapeutic potential for the treatment of fulminant hepatitis.

  14. Modelling property changes in graphite irradiated at changing irradiation temperature

    CSIR Research Space (South Africa)

    Kok, S

    2011-01-01

    Full Text Available A new method is proposed to predict the irradiation induced property changes in nuclear; graphite, including the effect of a change in irradiation temperature. The currently used method; to account for changes in irradiation temperature, the scaled...

  15. A survey of Italian and Spanish neonatologists and paediatricians regarding awareness of the diagnosis of FAS and FASD and maternal ethanol use during pregnancy

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    Tarani L

    2011-06-01

    Full Text Available Abstract Background Ethanol is the most widely used drug in the world and a human teratogen whose consumption among women of childbearing age has been steadily increasing. There are no Italian or Spanish statistics on ethanol consumption during pregnancy nor any information regarding prevalence of fetal alcohol syndrome (FAS and fetal alcohol spectrum disorders (FASD. There is also a reasonable suspicion that these two diseases are underdiagnosed by professionals from the above-reported countries. The objectives of this study were: 1 to evaluate the experience, knowledge and confidence of Italian and Spanish neonatologists and paediatricians with respect to the diagnosis of FAS and FASD, and 2 to evaluate professionals awareness of maternal drinking patterns during pregnancy. Methods A multiple-choice anonymous questionnaire was e-mailed to Italian neonatologists registered in the mailing list of the corresponding Society and administered to Italian and Spanish paediatricians during their National Congress. Results The response rate was 16% (63/400 for the Italian neonatologists of the National Society while a total of 152 Spanish and 41 Italian paediatricians agreed to complete the questionnaire during National Congress. Over 90% of the surveyed physicians declared that FAS is an identifiable syndrome and over 60% of them identified at least one of the most important features of FAS. Although over 60% Italian responders and around 80% Spanish responders were aware that ethanol use in pregnancy is dangerous, approximately 50% Italian responders and 40% Spanish ones allowed women to drink sometimes a glass of wine or beer during pregnancy. Neonatologists and paediatricians rated confidence in the ability to diagnosis FAS and FASD as low, with over 50% responders feeling they needed more information regarding FAS and FASD identification in newborn and child. Conclusions Italian and Spanish neonatologists and paediatricians do not feel confident

  16. Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand

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    Venu Venkatarame Gowda Saralamma

    2015-09-01

    Full Text Available Poncirin, a natural bitter flavanone glycoside abundantly present in many species of citrus fruits, has various biological benefits such as anti-oxidant, anti-microbial, anti-inflammatory and anti-cancer activities. The anti-cancer mechanism of Poncirin remains elusive to date. In this study, we investigated the anti-cancer effects of Poncirin in AGS human gastric cancer cells (gastric adenocarcinoma. The results revealed that Poncirin could inhibit the proliferation of AGS cells in a dose-dependent manner. It was observed Poncirin induced accumulation of sub-G1 DNA content, apoptotic cell population, apoptotic bodies, chromatin condensation, and DNA fragmentation in a dose-dependent manner in AGS cells. The expression of Fas Ligand (FasL protein was up-regulated dose dependently in Poncirin-treated AGS cells Moreover, Poncirin in AGS cells induced activation of Caspase-8 and -3, and subsequent cleavage of poly(ADP-ribose polymerase (PARP. Inhibitor studies’ results confirm that the induction of caspase-dependent apoptotic cell death in Poncirin-treated AGS cells was led by the Fas death receptor. Interestingly, Poncirin did not show any effect on mitochondrial membrane potential (ΔΨm, pro-apoptotic proteins (Bax and Bak and anti-apoptotic protein (Bcl-xL in AGS-treated cells followed by no activation in the mitochondrial apoptotic protein caspase-9. This result suggests that the mitochondrial-mediated pathway is not involved in Poncirin-induced cell death in gastric cancer. These findings suggest that Poncirin has a potential anti-cancer effect via extrinsic pathway-mediated apoptosis, possibly making it a strong therapeutic agent for human gastric cancer.

  17. Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand.

    Science.gov (United States)

    Saralamma, Venu Venkatarame Gowda; Nagappan, Arulkumar; Hong, Gyeong Eun; Lee, Ho Jeong; Yumnam, Silvia; Raha, Suchismita; Heo, Jeong Doo; Lee, Sang Joon; Lee, Won Sup; Kim, Eun Hee; Kim, Gon Sup

    2015-09-18

    Poncirin, a natural bitter flavanone glycoside abundantly present in many species of citrus fruits, has various biological benefits such as anti-oxidant, anti-microbial, anti-inflammatory and anti-cancer activities. The anti-cancer mechanism of Poncirin remains elusive to date. In this study, we investigated the anti-cancer effects of Poncirin in AGS human gastric cancer cells (gastric adenocarcinoma). The results revealed that Poncirin could inhibit the proliferation of AGS cells in a dose-dependent manner. It was observed Poncirin induced accumulation of sub-G1 DNA content, apoptotic cell population, apoptotic bodies, chromatin condensation, and DNA fragmentation in a dose-dependent manner in AGS cells. The expression of Fas Ligand (FasL) protein was up-regulated dose dependently in Poncirin-treated AGS cells Moreover, Poncirin in AGS cells induced activation of Caspase-8 and -3, and subsequent cleavage of poly(ADP-ribose) polymerase (PARP). Inhibitor studies' results confirm that the induction of caspase-dependent apoptotic cell death in Poncirin-treated AGS cells was led by the Fas death receptor. Interestingly, Poncirin did not show any effect on mitochondrial membrane potential (ΔΨm), pro-apoptotic proteins (Bax and Bak) and anti-apoptotic protein (Bcl-xL) in AGS-treated cells followed by no activation in the mitochondrial apoptotic protein caspase-9. This result suggests that the mitochondrial-mediated pathway is not involved in Poncirin-induced cell death in gastric cancer. These findings suggest that Poncirin has a potential anti-cancer effect via extrinsic pathway-mediated apoptosis, possibly making it a strong therapeutic agent for human gastric cancer.

  18. Irradiation Creep in Graphite

    Energy Technology Data Exchange (ETDEWEB)

    Ubic, Rick; Butt, Darryl; Windes, William

    2014-03-13

    An understanding of the underlying mechanisms of irradiation creep in graphite material is required to correctly interpret experimental data, explain micromechanical modeling results, and predict whole-core behavior. This project will focus on experimental microscopic data to demonstrate the mechanism of irradiation creep. High-resolution transmission electron microscopy should be able to image both the dislocations in graphite and the irradiation-induced interstitial clusters that pin those dislocations. The team will first prepare and characterize nanoscale samples of virgin nuclear graphite in a transmission electron microscope. Additional samples will be irradiated to varying degrees at the Advanced Test Reactor (ATR) facility and similarly characterized. Researchers will record microstructures and crystal defects and suggest a mechanism for irradiation creep based on the results. In addition, the purchase of a tensile holder for a transmission electron microscope will allow, for the first time, in situ observation of creep behavior on the microstructure and crystallographic defects.

  19. Differential Effects of Alpha-Particle Radiation and X-Irradiation on Genes Associated with Apoptosis

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    Vinita Chauhan

    2011-01-01

    Full Text Available This study examined differential effects of alpha-(α- particle radiation and X-rays on apoptosis and associated changes in gene expression. Human monocytic cells were exposed to α-particle radiation and X-rays from 0 to 1.5 Gy. Four days postexposure, cell death was measured by flow cytometry and 84 genes related to apoptosis were analyzed using real-time PCR. On average, 33% of the cells were apoptotic at 1.5 Gy of α-particle radiation. Transcript profiling showed statistical expression of 15 genes at all three doses tested. Cells exposed to X-rays were <5% apoptotic at ~1.5 Gy and induced less than a 2-fold expression in 6 apoptotic genes at the higher doses of radiation. Among these 6 genes, Fas and TNF-α were common to the α-irradiated cells. This data suggests that α-particle radiation initiates cell death by TNF-α and Fas activation and through intermediate signalling mediators that are distinct from X-irradiated cells.

  20. Family Aggregation of HTLV-1 Infection Associated with FAS -670A/G Polymorphism: A Case Report

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    Antonio C. R. Vallinoto

    2018-01-01

    Full Text Available Human T-lymphotropic virus 1 (HTLV-1 infection has been associated with ATL and inflammatory diseases but remains a neglected health problem. HTLV-1 associated diseases were originally described as sporadic entities, but family aggregations have been reported. Viral, genetic, immunological and behavioral factors were used to explain family clusters, but until now a clear explanation remains uncertain. In the present study we report, for the first time, a family cluster of diseased persons presenting the infection across three generations associated with FAS -670A/G polymorphism.

  1. A biomechanical comparison of the FasT-Fix meniscal repair suture system and the RapidLoc device in cadaver meniscus.

    Science.gov (United States)

    Kocabey, Yavuz; Chang, Haw Chong; Brand, Jeff C; Nawab, Akbar; Nyland, John; Caborn, David N M

    2006-04-01

    This biomechanical study compared the fixation characteristics of horizontally or vertically implanted FasT-Fix devices (Smith & Nephew, Endoscopy Division, Andover, MA) consisting of two 5-mm PLLA suture T-bar anchors with a pretied self-sliding knot (No. 0 nonabsorbable, USP, braided polyester suture material) and the RapidLoc device (Mitek Surgical Products, Westwood, MA) consisting of a PLLA T-bar anchor or "backstop," a connecting suture (No. 2 nonbiodegradable Ethibond; Ethicon, Somerville, NJ), and a PLLA grommet, for repairing posterior third lesions in human menisci. Controlled laboratory biomechanical study. After repair of a vertical longitudinal meniscus lesion with either vertically or horizontally implanted FasT-Fix devices or RapidLoc devices, 3 groups of 6 specimens underwent cyclic loading (5 mm/minute, cycling between 5 and 50 N at 1 Hz for 500 cycles) before load to failure testing on a servo hydraulic device. One-way analysis of variance and Tukey HSD post hoc tests were used to evaluate group differences (P biomechanical characteristics for meniscal fixation during cyclic and load to failure testing compared with horizontal FasT-Fix or RapidLoc devices. Although the RapidLoc devices provided fixation characteristics comparable to horizontally implanted FasT-Fix devices, vertically implanted FasT-Fix devices may provide superior all-inside fixation.

  2. FAS and FASL Gene Polymorphisms Are Not Associated with Hepatitis B Virus Infection Based on a Case-Control Study in a Brazilian Population

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    Bárbara B. Santana

    2013-01-01

    Full Text Available Objective. This study investigated the association of the single nucleotide polymorphisms (SNPs in the FAS and FASL genes with the outcome of hepatitis B virus (HBV infection. Methods. Blood samples were collected from 116 HBV-infected patients at the Hospital of the Santa Casa de Misericordia Foundation (Belém, PA, Brazil. Seronegative individuals were used as controls. DNA samples were extracted from the leukocytes and assayed using the polymerase chain reaction (PCR followed by RFLP analysis with restriction endonucleases. Results. The frequencies of the mutant genotypes for -670FAS (GG, Ivs2nt-124FASL (GG, Ivs3nt-169FASL (ΔT/ΔT, and -844FASL (TT were higher in the HBV patients, and the FAS-1377AA genotype was more frequent in the control group; however, the differences between the allele and genotype frequencies were not statistically significant. When the HBV patient population was divided into two groups (inactive carriers and active chronic hepatitis patients, the mutant genotypes were found to be more prevalent in the active chronic hepatitis group with respect to the FAS gene polymorphisms; however, this difference was not statistically significant. Conclusions. The results suggest that the polymorphisms in FAS and FASL genes are not associated with HBV infection or even with the natural history of the infection in the Brazilian Amazon region.

  3. FAS inhibitor cerulenin reduces food intake and melanocortin receptor gene expression without modulating the other (an)orexigenic neuropeptides in chickens.

    Science.gov (United States)

    Dridi, Sami; Ververken, Cedric; Hillgartner, F Bradley; Arckens, Lutgarde; Lutgarde, Arckens; Van der Gucht, Estel; Cnops, Lieselotte; Decuypere, Eddy; Buyse, Johan

    2006-07-01

    Cerulenin, a natural fatty acid synthase (FAS) inhibitor, and its synthetic analog C75 are hypothesized to alter the metabolism of neurons in the hypothalamus that regulate ingestive behavior to cause a profound decrease of food intake and an increase in metabolic rate, leading to body weight loss. The bulk of data exclusively originates from mammals (rodents); however, such effects are currently lacking in nonmammalian species. We have, therefore, addressed this issue in broiler chickens because this species is selected for high growth rate and high food intake and is prone to obesity. First, we demonstrate that FAS messenger and protein are expressed in the hypothalamus of chickens. FAS immunoreactivity was detected in a number of brain regions, including the nucleus paraventricularis magnocellularis and the nucleus infundibuli hypothalami, the avian equivalent of the mammalian arcuate nucleus, suggesting that FAS may be involved in the regulation of food intake. Second, we show that hypothalamic FAS gene expression was significantly (P inhibition of fatty acid synthesis on food intake, we administered cerulenin by intravenous injections (15 mg/kg) to 2-wk-old broiler chickens. Cerulenin administration significantly reduced food intake by 23 to 34% (P agouti gene-related peptide, orexin, and orexin receptor) and anorexigenic (pro-opiomelanocortin and corticotropin-releasing hormone) neuropeptide mRNA levels remained unchanged after cerulenin treatment. These results suggest that the catabolic effect of cerulenin in chickens may be mediated through the melanocortin system rather than the other neuropeptides known to be involved in food intake regulation.

  4. Family Accommodation Scale for Obsessive-Compulsive Disorder-Interviewer-Rated (FAS-IR), Brazilian Portuguese version: internal consistency, reliability, and exploratory factor analysis.

    Science.gov (United States)

    Gomes, Juliana Braga; Cordioli, Aristides; Van Noppen, Barbara; Pato, Michele; Wolitzky-Taylor, Kate; Gonçalves, Francine; Heldt, Elizeth

    2015-02-01

    To examine the psychometric properties of the Brazilian Portuguese version of the Family Accommodation Scale for Obsessive-Compulsive Disorder-Interviewer-Rated (FAS-IR). A total of 114 family members of patients with obsessive-compulsive disorder (OCD) were assessed. The following analyses of the FAS-IR were carried out: internal consistency, inter-rater and test-retest reliability, and exploratory factor analysis. The Brazilian Portuguese version of the FAS-IR showed excellent inter-rater reliability (intraclass correlation coefficient [ICC]=0.94) and acceptable test-retest reliability (ICC=0.77), with no significant differences in FAS-IR scores. Factor analysis produced three factors for the scale. However, factor loadings were not well defined within each factor, and the factors did not have distinct constructs. Thus, a global analysis approach was chosen, revealing good internal consistency of the scale as a whole (Cronbach's α=0.805). The Brazilian Portuguese FAS-IR showed sound psychometric properties for the evaluation of family accommodation, and is, therefore, a reliable instrument for use in research and clinical practice. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. p,p′-DDE Induces Apoptosis of Rat Sertoli Cells via a FasL-Dependent Pathway

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    Yuqin Shi

    2009-01-01

    Full Text Available One,1-dichloro-2,2 bis(p-chlorophenyl ethylene (p,p′-DDE, the major metabolite of 2,2-bis(4-Chlorophenyl-1,1,1-trichloroethane (DDT, is a known persistent organic pollutant and male reproductive toxicant. It has antiandrogenic effect. However, the mechanism by which p,p′-DDE exposure causes male reproductive toxicity remains unknown. In the present study, rat Sertoli cells were used to investigate the molecular mechanism involved in p,p′-DDE-induced toxicity in male reproductive system. The results indicated that p,p′-DDE exposure at over 30 μM showed the induction of apoptotic cell death. p,p′-DDE could induce increases in FasL mRNA and protein, which could be blocked by an antioxidant agent, N-acetyl-l-cysteine (NAC. In addition, caspase-3 and -8 were activated by p,p′-DDE treatment in these cells. The activation of NF-κB was enhanced with the increase of p,p′-DDE dose. Taken together, these results suggested that exposure to p,p′-DDE might induce apoptosis of rat Sertoli cells through a FasL-dependent pathway.

  6. 4SC-101, a novel small molecule dihydroorotate dehydrogenase inhibitor, suppresses systemic lupus erythematosus in MRL-(Fas)lpr mice.

    Science.gov (United States)

    Kulkarni, Onkar P; Sayyed, Sufyan G; Kantner, Claudia; Ryu, Mi; Schnurr, Max; Sárdy, Miklós; Leban, Johann; Jankowsky, Ruediger; Ammendola, Aldo; Doblhofer, Robert; Anders, Hans-Joachim

    2010-06-01

    Immunosuppressive treatments of systemic lupus (SLE) remain associated with significant toxicities; hence, compounds with better toxicity profiles are needed. Dihydroorotate dehydrogenase (DHODH) inhibition with leflunomide has proven to be effective in autoimmune diseases including SLE, but leflunomide can cause a variety of side effects. We hypothesized that 4SC-101, a novel DHODH inhibitor with a more favorable toxicity profile, would be as effective as high-dose cyclophosphamide (CYC) in controlling experimental SLE of female MRL(Fas)lpr mice. Daily oral gavage of 30, 100, and 300 mg/kg 4SC-101 from 12 to 22 weeks of age was compared with either vehicle or CYC treatment (30 mg/kg/week, i.p.) in terms of efficacy and toxicity. Three hundred milligrams per kilogram 4SC-101 was as effective as CYC in depleting spleen autoreactive T cells, B cells, and plasma cells as well as the respective DNA and RNA serum autoantibodies. This was associated with a comparable amelioration of the renal, dermal, and pulmonary SLE manifestations of MRL(Fas)lpr mice. However, even the highest dose of 4SC-101 had no effect on bone marrow neutrophil counts, which were significantly reduced in CYC-treated mice. Together, the novel DHODH inhibitor 4SC-101 is as effective as high dose CYC in controlling SLE without causing myelosuppression. Hence, DHODH inhibition with 4SC-101 might be suitable to treat active SLE with fewer side effects than CYC.

  7. AGC-2 Irradiation Report

    Energy Technology Data Exchange (ETDEWEB)

    Rohrbaugh, David Thomas [Idaho National Lab. (INL), Idaho Falls, ID (United States); Windes, William [Idaho National Lab. (INL), Idaho Falls, ID (United States); Swank, W. David [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-06-01

    The Next Generation Nuclear Plant (NGNP) will be a helium-cooled, very high temperature reactor (VHTR) with a large graphite core. In past applications, graphite has been used effectively as a structural and moderator material in both research and commercial high temperature gas cooled reactor (HTGR) designs.[ , ] Nuclear graphite H 451, used previously in the United States for nuclear reactor graphite components, is no longer available. New nuclear graphites have been developed and are considered suitable candidates for the new NGNP reactor design. To support the design and licensing of NGNP core components within a commercial reactor, a complete properties database must be developed for these current grades of graphite. Quantitative data on in service material performance are required for the physical, mechanical, and thermal properties of each graphite grade with a specific emphasis on data related to the life limiting effects of irradiation creep on key physical properties of the NGNP candidate graphites. Based on experience with previous graphite core components, the phenomenon of irradiation induced creep within the graphite has been shown to be critical to the total useful lifetime of graphite components. Irradiation induced creep occurs under the simultaneous application of high temperatures, neutron irradiation, and applied stresses within the graphite components. Significant internal stresses within the graphite components can result from a second phenomenon—irradiation induced dimensional change. In this case, the graphite physically changes i.e., first shrinking and then expanding with increasing neutron dose. This disparity in material volume change can induce significant internal stresses within graphite components. Irradiation induced creep relaxes these large internal stresses, thus reducing the risk of crack formation and component failure. Obviously, higher irradiation creep levels tend to relieve more internal stress, thus allowing the

  8. Inactivation of caspase-8 on mitochondria of Bcl-xL-expressing MCF7-Fas cells: role for the bifunctional apoptosis regulator protein.

    Science.gov (United States)

    Stegh, Alexander H; Barnhart, Bryan C; Volkland, Jorg; Algeciras-Schimnich, Alicia; Ke, Ning; Reed, John C; Peter, Marcus E

    2002-02-08

    Apoptosis induction through CD95 (APO-1/Fas) critically depends on generation of active caspase-8 at the death-inducing signaling complex (DISC). Depending on the cell type, active caspase-8 either directly activates caspase-3 (type I cells) or relies on mitochondrial signal amplification (type II cells). In MCF7-Fas cells that are deficient for pro-caspase-3, even high amounts of caspase-8 produced at the DISC cannot directly activate downstream effector caspases without mitochondrial help. Overexpression of Bcl-x(L) in these cells renders them resistant to CD95-mediated apoptosis. However, activation of caspase-8 in control (vector) and Bcl-x(L) transfectants of MCF7-Fas cells proceeds with similar kinetics, resulting in a complete processing of cellular caspase-8. Most of the cytosolic caspase-8 substrates are not cleaved in the Bcl-x(L) protected cells, raising the question of how Bcl-x(L)-expressing MCF7-Fas cells survive large amounts of potentially cytotoxic caspase-8. We now demonstrate that active caspase-8 is initially generated at the DISC of both MCF7-Fas-Vec and MCF7-Fas-Bcl-x(L) cells and that the early steps of CD95 signaling such as caspase-8-dependent cleavage of DISC bound c-FLIP(L), caspase-8-dependent clustering, and internalization of CD95, as well as processing of pro-caspase-8 bound to mitochondria are very similar in both transfectants. However, events downstream of mitochondria, such as release of cytochrome c, only occur in the vector-transfected MCF7-Fas cells, and no in vivo caspase-8 activity can be detected in the Bcl-x(L)-expressing cells. Our data suggest that, in Bcl-x(L)-expressing MCF7-Fas cells, active caspase-8 is sequestered on the outer mitochondrial surface presumably by association with the protein "bifunctional apoptosis regulator" in a way that does not allow substrates to be cleaved, identifying a novel mechanism of regulation of apoptosis sensitivity by mitochondrial Bcl-x(L).

  9. Ligation of major histocompatibility complex class I antigens (MHC-I) prevents apoptosis induced by Fas or SAPK/JNK activation in T-lymphoma cells

    DEFF Research Database (Denmark)

    Lamberth, K; Claesson, M H

    2001-01-01

    Early apoptosis in Jurkat T-lymphoma cells was induced by agonistic anti-Fas Ab or by anisomycin which activates the stress kinases SAPK/JNK. Apoptosis was inhibited by ligation of major histocompatibility complex class I antigens (MHC-I). MHC-I ligation induced upregulation of the anti......-apoptotic Bcl-2 protein and stabilized the mitochondrial membrane potential (Deltapsim). MHC-I ligation also prevented downregulation of Bcl-2 and destabilization of Deltapsim induced by anti-Fas Ab treatment or anisomycin exposure. Studies on three different Jurkat cell mutants deficient for src p56(lck), ZAP...

  10. The Interaction of CD154 with the α5β1 Integrin Inhibits Fas-Induced T Cell Death.

    Directory of Open Access Journals (Sweden)

    Meriem Bachsais

    Full Text Available CD154, a critical regulator of the immune response, is usually associated with chronic inflammatory, autoimmune diseases as well as malignant disorders. In addition to its classical receptor CD40, CD154 is capable of binding other receptors, members of the integrin family, the αIIbβ3, αMβ2 and α5β1. Given the role attributed to integrins and particularly the β1 integrins in inhibiting apoptotic events in normal as well as malignant T cells, we were highly interested in investigating the role of the CD154/α5β1 interaction in promoting survival of malignant T cells contributing as such to tumor development and/or propagation. To support our hypothesis, we first show that soluble CD154 binds to the T-cell acute lymphoblastic leukemia cell line, Jurkat E6.1 in a α5β1-dependent manner. Binding of soluble CD154 to α5β1 integrin of Jurkat cells leads to the activation of key survival proteins, including the p38 and ERK1/2 mitogen-activated protein kinases (MAPKs, phosphoinositide 3 kinase (PI-3K, and Akt. Interestingly, soluble CD154 significantly inhibits Fas-mediated apoptosis in T cell leukemia-lymphoma cell lines, Jurkat E6.1 and HUT78 cells, an important hallmark of T cell survival during malignancy progression. These anti-apoptotic effects were mainly mediated by the activation of the PI-3K/Akt pathway but also involved the p38 and the ERK1/2 MAPKs cascades. Our data also demonstrated that the CD154-triggered inhibition of the Fas-mediated cell death response was dependent on a suppression of caspase-8 cleavage, but independent of de novo protein synthesis or alterations in Fas expression on cell surface. Together, our results highlight the impact of the CD154/α5β1 interaction in T cell function/survival and identify novel targets for the treatment of malignant disorders, particularly of T cell origin.

  11. Robust Therapeutic Efficacy of Matrix Metalloproteinase-2-Cleavable Fas-1-RGD Peptide Complex in Chronic Inflammatory Arthritis.

    Science.gov (United States)

    Nam, Eon Jeong; Kang, Jin Hee; Sa, Keum Hee; Sung, Shijin; Park, Jae Yong; Jo, Dong-Gyu; Park, Jae Hyung; Kim, In San; Kang, Young Mo

    2016-01-01

    Therapeutic agents that are transformable via introducing cleavable linkage by locally enriched MMP-2 within inflamed synovium would enhance therapeutic efficacy on chronic inflammatory arthritis. Transforming growth factor-β-inducible gene-h3 (βig-h3), which consists of four fas-1 domains and an Arg-Gly-Asp (RGD) motif, intensifies inflammatory processes by facilitating adhesion and migration of fibroblast-like synoviocyte in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to investigate whether a MMP-2-cleavable peptide complex consisting of a fas-1 domain and an RGD peptide blocks the interaction between βig-h3 and resident cells and leads to the amelioration of inflammatory arthritis. We designed βig-h3-derivatives, including the fourth fas-1 domain truncated for H1 and H2 sequences of mouse (MFK00) and MMP-2-cleavable peptide complex (MFK902). MMP-2 selectivity was examined by treatment with a series of proteases. MFK902 efficacy was determined by the adhesion and migration assay with NIH3T3 cells in vitro and collagen-induced arthritis (CIA) model using male DBA/1J mice in vivo. The mice were treated intraperitoneally with MFK902 at different dosages. MFK902 was specifically cleaved by active MMP-2 in a concentration-dependent manner, and βig-h3-mediated adhesion and migration were more effectively inhibited by MFK902, compared with RGD or MFK00 peptides. The arthritis activity of murine CIA, measured by clinical arthritis index and incidence of arthritic paws, was significantly ameliorated after treatment with all dosages of MFK902 (1, 10, and 30 mg/kg). MFK902 ameliorated histopathologic deterioration and reduced the expression of inflammatory mediators simultaneously with improvement of clinical features. In addition, a favorable safety profile of MFK902 was demonstrated in vivo. The present study revealed that MMP-2-cleavable peptide complex based on βig-h3 structure is a potent and safe therapeutic agent for chronic

  12. Robust Therapeutic Efficacy of Matrix Metalloproteinase-2-Cleavable Fas-1-RGD Peptide Complex in Chronic Inflammatory Arthritis.

    Directory of Open Access Journals (Sweden)

    Eon Jeong Nam

    Full Text Available Therapeutic agents that are transformable via introducing cleavable linkage by locally enriched MMP-2 within inflamed synovium would enhance therapeutic efficacy on chronic inflammatory arthritis. Transforming growth factor-β-inducible gene-h3 (βig-h3, which consists of four fas-1 domains and an Arg-Gly-Asp (RGD motif, intensifies inflammatory processes by facilitating adhesion and migration of fibroblast-like synoviocyte in the pathogenesis of rheumatoid arthritis (RA. The aim of this study was to investigate whether a MMP-2-cleavable peptide complex consisting of a fas-1 domain and an RGD peptide blocks the interaction between βig-h3 and resident cells and leads to the amelioration of inflammatory arthritis.We designed βig-h3-derivatives, including the fourth fas-1 domain truncated for H1 and H2 sequences of mouse (MFK00 and MMP-2-cleavable peptide complex (MFK902. MMP-2 selectivity was examined by treatment with a series of proteases. MFK902 efficacy was determined by the adhesion and migration assay with NIH3T3 cells in vitro and collagen-induced arthritis (CIA model using male DBA/1J mice in vivo. The mice were treated intraperitoneally with MFK902 at different dosages.MFK902 was specifically cleaved by active MMP-2 in a concentration-dependent manner, and βig-h3-mediated adhesion and migration were more effectively inhibited by MFK902, compared with RGD or MFK00 peptides. The arthritis activity of murine CIA, measured by clinical arthritis index and incidence of arthritic paws, was significantly ameliorated after treatment with all dosages of MFK902 (1, 10, and 30 mg/kg. MFK902 ameliorated histopathologic deterioration and reduced the expression of inflammatory mediators simultaneously with improvement of clinical features. In addition, a favorable safety profile of MFK902 was demonstrated in vivo.The present study revealed that MMP-2-cleavable peptide complex based on βig-h3 structure is a potent and safe therapeutic agent for

  13. Credit Crisis with focus on level three valuations anFAS157: Analysis and Recommendations for Change

    Directory of Open Access Journals (Sweden)

    Ph.D. candidate Arber H. Hoti

    2012-05-01

    Full Text Available The paper examines the effect of level three valuations and FAS 157 implications on investors, auditors’ work, valuation disclosures and gives recommendations for improvements based on best practices. The aim of this research is to demonstrate that the fair value measurements should not be suspended. The standards provide for measurement of fair value in all market conditions. Therefore, level 3 measurements or mark-to-model is an answer for many issuers that are not sure how to measure their assets and liabilities at the fair value. The paper concludes that fair value measurement has not caused the current crisis and has no pro-cyclical effect and suggests several recommendations for policy makers and regulators.

  14. LMNA E82K mutation activates FAS and mitochondrial pathways of apoptosis in heart tissue specific transgenic mice.

    Directory of Open Access Journals (Sweden)

    Dan Lu

    Full Text Available The lamin A/C (LMNA, nuclear intermediate filament proteins, is a basic component of the nuclear lamina. Mutations in LMNA are associated with a broad range of laminopathies, congenital diseases affecting tissue regeneration and homeostasis. Heart tissue specific transgenic mice of human LMNA E82K, a mutation causing dilated cardiomyopathy, were generated. Lmna(E82K transgenic mouse lines exhibited thin-walled, dilated left and right ventricles, a progressive decrease of contractile function assessed by echocardiography. Abnormalities of the conduction system, myocytes disarray, collagen accumulation and increased levels of B-type natriuretic peptide (BNP, procollagen type III α1 (Col3α1 and skeletal muscle actin α1 (Actα1 were detected in the hearts of Lmna(E82K transgenic mice. The LMNA E82K mutation caused mislocation of LMNA in the nucleus and swollen mitochondria with loss of critae, together with the loss of nuclear envelope integrity. Most interestingly, we found that the level of apoptosis was 8.5-fold higher in the Lmna(E82K transgenic mice than that of non-transgenic (NTG mice. In the presence of the LMNA E82K, both of FAS and mitochondrial pathways of apoptosis were activated consistent with the increase of FAS expression, the release of cytochrome c from mitochondria to cytosol and activation of caspase-8, -9 and -3. Our results suggested that the apoptosis, at least for the LMNA E82K or the mutations in the rod region of Lamin A/C, might be an important mechanism causing continuous loss of myocytes and lead to myocardial dysfunction. It could be a potential therapeutic means to suppress and/or prevent inappropriate cardiac cell death in patients carrying LMNA mutation.

  15. The Birmingham Irradiation Facility

    CERN Document Server

    Dervan, P; Hodgson, P; Marin-Reyes, H; Wilson, J

    2013-01-01

    At the end of 2012 the proton irradiation facility at the CERN PS [1] will shut down for two years. With this in mind, we have been developing a new ATLAS scanning facility at the University of Birmingham Medical Physics cyclotron. With proton beams of energy approximately 30 MeV, fluences corresponding to those of the upgraded Large Hadron Collider (HL-LHC) can be reached conveniently. The facility can be used to irradiate silicon sensors, optical components and mechanical structures (e.g. carbon fibre sandwiches) for the LHC upgrade programme. Irradiations of silicon sensors can be carried out in a temperature controlled cold box that can be scanned through the beam. The facility is described in detail along with the first tests carried out with mini (1 x 1 cm^2 ) silicon sensors.

  16. Vero cells infected with the Lederle strain of canine distemper virus have increased Fas receptor signaling expression at 15 h post-infection.

    Science.gov (United States)

    Del Puerto, H L; Martins, A S; Braz, G F; Alves, F; Heinemann, M B; Rajão, D S; Araújo, F C; Martins, S F; Nascimento, D R; Leite, R C; Vasconcelos, A C

    2011-10-18

    We evaluated the expression of the Fas receptor gene in Vero cells infected with the Lederle vaccine strain of canine distemper virus using RT-PCR. Vero cells were plated, and after being grown for 24 h in MEM with 5% FBS, 80-90% confluent monolayer cultures were infected with the virus. The cells were harvested at 3, 6, 9, and 15 h post-infection. Uninfected Vero cells were used as a control. Total RNA was isolated from Vero cells using 1 mL Trizol(®) LS, and RT was performed using 2 μg total RNA. Primer pairs for RT-PCR amplification for the canine distemper virus nucleocapsid gene, the S26 reference gene, and the Vero rFas gene were used to analyze expression in Vero cells. RT-PCR results revealed virus activity at 3, 6, 9, and 15 h in the virus-infected Vero cells. The S26 housekeeping gene was amplified in virus infected and control samples. However, expression of the cell death receptor Fas was detected in Vero cells only at 15 h post-infection. We suggest that the Lederle vaccine induces apoptosis by Fas receptor signaling, possibly through caspase-8 signaling rather than through mitochondrial signaling in the infected cells.

  17. Decidual Macrophages Are Significantly Increased in Spontaneous Miscarriages and Over-Express FasL: A Potential Role for Macrophages in Trophoblast Apoptosis

    Directory of Open Access Journals (Sweden)

    Antonis Makrigiannakis

    2012-07-01

    Full Text Available Decidual macrophages (DM are the second most abundant population in the fetal-maternal interface. Their role has been so far identified as being local immuno-modulators favoring the maternal tolerance to the fetus. Herein we investigated tissue samples from 11 cases of spontaneous miscarriages and from 9 cases of elective terminations of pregnancy. Using immunohistochemistry and dual immunofluorescence we have demonstrated that in spontaneous miscarriages the DM are significantly increased. Additionally, we noted a significant up-regulation of macrophage FasL expression. Our results further support a dual role for DM during pregnancy and miscarriages. We hypothesize that the baseline DM population in normal pregnancy is in line with an M2 phenotype supporting the ongoing gestation. In contrast, during spontaneous miscarriages, the increased FasL-expressing population could be a part of an M1 phenotype participating in Fas/FasL-related apoptosis. Our results highlight a new aspect of macrophage biology in pregnancy physiology and pathophysiology. Further studies with larger samples are needed to verify the current results and evaluate their clinical impact.

  18. BIP induces mice CD19(hi) regulatory B cells producing IL-10 and highly expressing PD-L1, FasL.

    Science.gov (United States)

    Tang, Youfa; Jiang, Qing; Ou, Yanghui; Zhang, Fan; Qing, Kai; Sun, Yuanli; Lu, Wenjie; Zhu, Huifen; Gong, Feili; Lei, Ping; Shen, Guanxin

    2016-01-01

    Many studies have shown that B cells possess a regulatory function in mouse models of autoimmune diseases. Regulatory B cells can modulate immune response through many types of molecular mechanisms, including the production of IL-10 and the expression of PD-1 Ligand and Fas Ligand, but the microenvironmental factors and mechanisms that induce regulatory B cells have not been fully identified. BIP (binding immunoglobulin protein), a member of the heat shock protein 70 family, is a type of evolutionarily highly conserved protein. In this article, we have found that IL-10(+), PD-L1(hi) and FasL(hi) B cells are discrete cell populations, but enriched in CD19(hi) cells. BIP can induce IL-10-producing splenic B cells, IL-10 secretion and B cells highly expressing PD-L1 and FasL. CD40 signaling acts in synergy with BIP to induce regulatory B cells. BIP increased surface CD19 molecule expression intensity and IL-10(+), PD-L1(hi) and FasL(hi) B cells induced by BIP share the CD19(hi) phenotype. Furthermore, B cells treated with BIP and anti-CD40 can lead to suppression of T cell proliferation and the effect is partially IL-10-dependent and mainly BIP-induced. Taken together, our findings identify a novel function of BIP in the induction of regulatory B cells and add a new reason for the therapy of autoimmune disorders or other inflammatory conditions. Copyright © 2015. Published by Elsevier Ltd.

  19. Fas-Mediated Apoptosis Regulates the Composition of Peripheral αβ T Cell Repertoire by Constitutively Purging Out Double Negative T Cells

    Science.gov (United States)

    Mohamood, Abdiaziz S.; Bargatze, Dylan; Xiao, Zuoxiang; Jie, Chunfa; Yagita, Hideo; Ruben, Dawn; Watson, Julie; Chakravarti, Shukti; Schneck, Jonathan P.; Hamad, Abdel Rahim A.

    2008-01-01

    Background The Fas pathway is a major regulator of T cell homeostasis, however, the T cell population that is controlled by the Fas pathway in vivo is poorly defined. Although CD4 and CD8 single positive (SP) T cells are the two major T cell subsets in the periphery of wild type mice, the repertoire of mice bearing loss-of-function mutation in either Fas (lpr mice) or Fas ligand (gld mice) is predominated by CD4−CD8− double negative αβ T cells that also express B220 and generally referred to as B220+DN T cells. Despite extensive analysis, the basis of B220+DN T cell lymphoproliferation remains poorly understood. In this study we re-examined the issue of why T cell lymphoproliferation caused by gld mutation is predominated by B220+DN T cells. Methodology and Principal Findings We combined the following approaches to study this question: Gene transcript profiling, BrdU labeling, and apoptosis assays. Our results show that B220+DN T cells are proliferating and dying at exceptionally high rates than SP T cells in the steady state. The high proliferation rate is restricted to B220+DN T cells found in the gut epithelium whereas the high apoptosis rate occurred both in the gut epithelium and periphery. However, only in the periphery, apoptosis of B220+DN T cell is Fas-dependent. When the Fas pathway is genetically impaired, apoptosis of peripheral B220+DN T cells was reduced to a baseline level similar to that of SP T cells. Under these conditions of normalized apoptosis, B220+DN T cells progressively accumulate in the periphery, eventually resulting in B220+DN T cell lymphoproliferation. Conclusions/Significance The Fas pathway plays a critical role in regulating the tissue distribution of DN T cells through targeting and elimination of DN T cells from the periphery in the steady state. The results provide new insight into pathogenesis of DN T cell lymphoproliferation. PMID:18941614

  20. Fas-mediated apoptosis regulates the composition of peripheral alphabeta T cell repertoire by constitutively purging out double negative T cells.

    Directory of Open Access Journals (Sweden)

    Abdiaziz S Mohamood

    Full Text Available BACKGROUND: The Fas pathway is a major regulator of T cell homeostasis, however, the T cell population that is controlled by the Fas pathway in vivo is poorly defined. Although CD4 and CD8 single positive (SP T cells are the two major T cell subsets in the periphery of wild type mice, the repertoire of mice bearing loss-of-function mutation in either Fas (lpr mice or Fas ligand (gld mice is predominated by CD4(-CD8(- double negative alphabeta T cells that also express B220 and generally referred to as B220+DN T cells. Despite extensive analysis, the basis of B220+DN T cell lymphoproliferation remains poorly understood. In this study we re-examined the issue of why T cell lymphoproliferation caused by gld mutation is predominated by B220+DN T cells. METHODOLOGY AND PRINCIPAL FINDINGS: We combined the following approaches to study this question: Gene transcript profiling, BrdU labeling, and apoptosis assays. Our results show that B220+DN T cells are proliferating and dying at exceptionally high rates than SP T cells in the steady state. The high proliferation rate is restricted to B220+DN T cells found in the gut epithelium whereas the high apoptosis rate occurred both in the gut epithelium and periphery. However, only in the periphery, apoptosis of B220+DN T cell is Fas-dependent. When the Fas pathway is genetically impaired, apoptosis of peripheral B220+DN T cells was reduced to a baseline level similar to that of SP T cells. Under these conditions of normalized apoptosis, B220+DN T cells progressively accumulate in the periphery, eventually resulting in B220+DN T cell lymphoproliferation. CONCLUSIONS/SIGNIFICANCE: The Fas pathway plays a critical role in regulating the tissue distribution of DN T cells through targeting and elimination of DN T cells from the periphery in the steady state. The results provide new insight into pathogenesis of DN T cell lymphoproliferation.

  1. Correlation of the expression of YY1 and Fas cell surface death receptor with apoptosis of peripheral blood mononuclear cells, and the development of multiple organ dysfunction in children with sepsis

    Science.gov (United States)

    Reséndiz-Martínez, Judith; Asbun-Bojalil, Juan; Huerta-Yepez, Sara; Vega, Mario

    2017-01-01

    Multiple organ dysfunction (MOD) is a lethal complication in children with sepsis. Apoptosis of several cell types is involved in this process, and it is associated with increased Fas cell surface death receptor (Fas) expression. As YY1 transcription factor (YY1) negatively regulates the expression of Fas in cancer models, and is associated with the clinical outcome, it may be important in MOD. The present study aimed to determine the association between the expression of Fas, YY1 and apoptosis in children with sepsis, and its association with MOD, these factors were analyzed in 30 pediatric patients that had been diagnosed with sepsis. Peripheral blood mononuclear cells were purified from patients, and YY1 and Fas protein expression was assessed by immunocytochemistry. Apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling. Sepsis was monitored using clinical parameters, pediatric logistic organ dysfunction (PELOD) score and the pediatric mortality index. The results demonstrated that Fas expression was directly correlated with apoptosis levels and the expression of YY1 was inversely correlated with apoptosis levels. Patients with high levels of apoptosis exhibited increased disease severity and poor clinical outcome. Notably, the findings of the present study demonstrated that there were higher survival rates in patients with high YY1 expression, compared with those with low YY1 expression. Additionally, patients with MOD exhibited lower proportions of apoptotic cells compared with sepsis patients without MOD. Furthermore, the PELOD score was positively correlated with Fas and inversely correlated with YY1 expression. Finally, high apoptosis and low YY1 expression were prognostic factors associated with poor survival rates. These data suggested that YY1 may be important for apoptosis induction via the regulation of Fas during sepsis. Therefore, Fas may be a potential therapeutic target to prevent MOD through regulation of YY1

  2. Fuel or irradiation subassembly

    Science.gov (United States)

    Seim, O.S.; Hutter, E.

    1975-12-23

    A subassembly for use in a nuclear reactor is described which incorporates a loose bundle of fuel or irradiation pins enclosed within an inner tube which in turn is enclosed within an outer coolant tube and includes a locking comb consisting of a head extending through one side of the inner sleeve and a plurality of teeth which extend through the other side of the inner sleeve while engaging annular undercut portions in the bottom portion of the fuel or irradiation pins to prevent movement of the pins.

  3. Declining Physical Performance Associates with Serum FasL, miR-21, and miR-146a in Aging Sprinters

    Directory of Open Access Journals (Sweden)

    Reeta Kangas

    2017-01-01

    Full Text Available Aging is associated with systemic inflammation and cellular apoptosis accelerating physiological dysfunctions. Whether physically active way of life affects these associations is unclear. This study measured the levels of serum inflammatory and apoptotic molecules, their change over 10 years, and their associations with physical performance in sprint-trained male athletes. HsCRP, cell counts, HGB, FasL, miR-21, and miR-146a were measured cross-sectionally (n=67, 18–90 yrs and serum FasL, miR-21, and miR-146a and their aging-related associations with physical performance were assessed over a 10-year follow-up (n=49, 50–90 yrs. The cross-sectional study showed positive age correlations for neutrophils and negative for lymphocytes, red blood cells, HGB, FasL, and miR-146a. During the 10-year follow-up, FasL decreased (P=0.017 and miR-21 (P<0.001 and miR-146a (P=0.005 levels increased. When combining the molecule levels, aging, and physical performance, FasL associated with countermovement jump and bench press (P<0.001, miR-21 and miR-146a with knee flexion (P=0.023; P<0.001, and bench press (P=0.004; P<0.001 and miR-146a with sprint performance (P<0.001. The studied serum molecules changed in an age-dependent manner and were associated with declining physical performance. They have potential as biomarkers of aging-related processes influencing the development of physiological dysfunctions. Further research is needed focusing on the origins and targets of circulating microRNAs to clarify their function in various tissues with aging.

  4. Declining Physical Performance Associates with Serum FasL, miR-21, and miR-146a in Aging Sprinters

    Science.gov (United States)

    Alen, Markku; Suominen, Harri; Kovanen, Vuokko; Korhonen, Marko T.

    2017-01-01

    Aging is associated with systemic inflammation and cellular apoptosis accelerating physiological dysfunctions. Whether physically active way of life affects these associations is unclear. This study measured the levels of serum inflammatory and apoptotic molecules, their change over 10 years, and their associations with physical performance in sprint-trained male athletes. HsCRP, cell counts, HGB, FasL, miR-21, and miR-146a were measured cross-sectionally (n = 67, 18–90 yrs) and serum FasL, miR-21, and miR-146a and their aging-related associations with physical performance were assessed over a 10-year follow-up (n = 49, 50–90 yrs). The cross-sectional study showed positive age correlations for neutrophils and negative for lymphocytes, red blood cells, HGB, FasL, and miR-146a. During the 10-year follow-up, FasL decreased (P = 0.017) and miR-21 (P < 0.001) and miR-146a (P = 0.005) levels increased. When combining the molecule levels, aging, and physical performance, FasL associated with countermovement jump and bench press (P < 0.001), miR-21 and miR-146a with knee flexion (P = 0.023; P < 0.001), and bench press (P = 0.004; P < 0.001) and miR-146a with sprint performance (P < 0.001). The studied serum molecules changed in an age-dependent manner and were associated with declining physical performance. They have potential as biomarkers of aging-related processes influencing the development of physiological dysfunctions. Further research is needed focusing on the origins and targets of circulating microRNAs to clarify their function in various tissues with aging. PMID:28127562

  5. NSUF Irradiated Materials Library

    Energy Technology Data Exchange (ETDEWEB)

    Cole, James Irvin [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-09-01

    The Nuclear Science User Facilities has been in the process of establishing an innovative Irradiated Materials Library concept for maximizing the value of previous and on-going materials and nuclear fuels irradiation test campaigns, including utilization of real-world components retrieved from current and decommissioned reactors. When the ATR national scientific user facility was established in 2007 one of the goals of the program was to establish a library of irradiated samples for users to access and conduct research through competitively reviewed proposal process. As part of the initial effort, staff at the user facility identified legacy materials from previous programs that are still being stored in laboratories and hot-cell facilities at the INL. In addition other materials of interest were identified that are being stored outside the INL that the current owners have volunteered to enter into the library. Finally, over the course of the last several years, the ATR NSUF has irradiated more than 3500 specimens as part of NSUF competitively awarded research projects. The Logistics of managing this large inventory of highly radioactive poses unique challenges. This document will describe materials in the library, outline the policy for accessing these materials and put forth a strategy for making new additions to the library as well as establishing guidelines for minimum pedigree needed to be included in the library to limit the amount of material stored indefinitely without identified value.

  6. Childhood Head and Neck Irradiation

    Science.gov (United States)

    ... Thyroid Association ® www.thyroid.org Childhood Head & Neck Irradiation What is the thyroid gland? The thyroid gland ... Thyroid Association ® www.thyroid.org Childhood Head & Neck Irradiation Thyroid nodules (see Thyroid Nodule brochure) • Thyroid nodules ...

  7. Involvement of a chromatin modifier in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury: Probably an indirect action via the regulation of NFκB/FasL circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shiwei [Department of Urology, 174th Hospital of PLA, Fujian 361001 (China); Dong, Yushu [Department of Neurosurgery, 463rd Hospital of PLA, Shenyang 110042 (China); Xu, Chun; Jiang, Liming; Chen, Yongjie; Jiang, Cheng [Department of Urology, 174th Hospital of PLA, Fujian 361001 (China); Hou, Wugang, E-mail: gangwuhou@163.com [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032 (China); Li, Wei, E-mail: liweipepeyato@163.com [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi’an 710032 (China)

    2013-11-01

    Highlights: •MTA1 expression is upregulated in SCs upon MEHP treatment. •Knockdown of MTA1 in SCs impairs the MEHP-induced NFκB signaling activation. •Knockdown of MTA1 inhibits recruitment of NFκB onto FasL promoter in MEHP-treated SCs. -- Abstract: The Fas/FasL signaling pathway, controlled by nuclear factor-κB (NFκB) at the transcriptional level, is critical for triggering germ cell apoptosis in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC) injury, but the exact regulation mechanism remain unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), a component of the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs during the early recovery after MEHP exposure. This expression change was in line with the dynamic changes in germ cell apoptosis in response to MEHP treatment. Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP-induced early activation of NFκB pathway and abolish the recruitment of NFκB onto FasL promoter, which consequently diminished the MEHP-triggered FasL induction. Considering that Fas/FasL is a well characterized apoptosis initiating signaling during SCs injury, our results point to a potential “switch on” effect of MTA1, which may govern the activation of NFκB/FasL cascade in MEHP-insulted SCs. Overall, the MTA1/NFκB/FasL circuit may serve as an important defensive/repairing mechanism to help to control the germ cell quality after SCs injury.

  8. Safety of irradiated foods

    Energy Technology Data Exchange (ETDEWEB)

    Iwahara, Shigeo (Foods Medicines Safety Center (Japan)); Kobayashi, Kazuo

    1983-01-01

    The safety of 7 irradiated foods (potato, onion, rice, wheat, vienna sausage, fish paste and mandarine orange), in terms of 2-year long-term toxic effect, reproductive physiology and possible teratogenesis, was studied using 3 generations of rats, mice and monkeys. The genetic toxicity was studied by means of various mutagenicity tests. The details of the studies conducted by the authors to date and some overseas data were reported. The available data showed no toxic effect.

  9. Thymoquinone inhibits the CXCL12-induced chemotaxis of multiple myeloma cells and increases their susceptibility to Fas-mediated apoptosis.

    Directory of Open Access Journals (Sweden)

    Gamal Badr

    Full Text Available In multiple myeloma (MM, malignant plasma cells reside in the bone marrow, where they accumulate in close contact with stromal cells. The mechanisms responsible for the chemotaxis of malignant plasma cells are still poorly understood. Thus, we investigated the mechanisms involved in the chemotaxis of MDN and XG2 MM cell lines. Both cell lines strongly expressed CCR9, CXCR3 and CXCR4 chemokine receptors but only migrated toward CXCL12. Activation of CXCR4 by CXCL12 resulted in the association of CXCR4 with CD45 and activation of PLCβ3, AKT, RhoA, IκBα and ERK1/2. Using siRNA-silencing techniques, we showed CD45/CXCR4 association is essential for CXCL12-induced migration of MM cells. Thymoquinone (TQ, the major active component of the medicinal herb Nigella sativa Linn, has been described as a chemopreventive and chemotherapeutic compound. TQ treatment strongly inhibited CXCL12-mediated chemotaxis in MM cell lines as well as primary cells isolated from MM patients, but not normal PBMCs. Moreover, TQ significantly down-regulated CXCR4 expression and CXCL12-mediated CXCR4/CD45 association in MM cells. Finally, TQ also induced the relocalization of cytoplasmic Fas/CD95 to the membrane of MM cells and increased CD95-mediated apoptosis by 80%. In conclusion, we demonstrate the potent anti-myeloma activity of TQ, providing a rationale for further clinical evaluation.

  10. Association of a microsatellite in FASL to type II diabetes and of the FAS-670G>A genotype to insulin resistance

    DEFF Research Database (Denmark)

    Nolsøe, R L; Hamid, Y H; Pociot, F

    2006-01-01

    Type II diabetes is caused by a failure of the pancreatic beta-cells to compensate for insulin resistance leading to hyperglycaemia. There is evidence for an essential role of an increased beta-cell apoptosis in type II diabetes. High glucose concentrations induce IL-1beta production in human beta...... in the 3' UTR of FASL for association to type II diabetes in 549 type II diabetic patients and 525 normal-glucose-tolerant (NGT) control subjects. Furthermore, we have tested these polymorphisms for association to estimates of beta-cell function and insulin resistance in NGT subjects. We found significant...... association to type II diabetes for the allele distribution of the FASL microsatellite (P-value 0.02, Bonferroni corrected). The FAS-670G>A was associated with homeostasis model assessment insulin resistance index and body mass index (P-values 0.02 and 0.02). We conclude that polymorphisms of FASL and FAS...

  11. ATF Neutron Irradiation Program Irradiation Vehicle Design Concepts

    Energy Technology Data Exchange (ETDEWEB)

    Geringer, J. W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Materials Science and Technology Division; Katoh, Yutai [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Materials Science and Technology Division; Howard, Richard H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Materials Science and Technology Division; Cetiner, N. O. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Materials Science and Technology Division; Petrie, Christian M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Materials Science and Technology Division; Smith, Kurt R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Materials Science and Technology Division; McDuffee, J. M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Materials Science and Technology Division

    2016-03-01

    The Japan Atomic Energy Agency (JAEA) under the Civil Nuclear Energy Working Group (CNWG) is engaged in a cooperative research effort with the U.S. Department of Energy (DOE) to explore issues related to nuclear energy, including research on accident-tolerant fuels and materials for use in light water reactors. This work develops a draft technical plan for a neutron irradiation program on the candidate accident-tolerant fuel cladding materials and elements using the High Flux Isotope Reactor (HFIR). The research program requires the design of a detailed experiment, development of test vehicles, irradiation of test specimens, possible post irradiation examination and characterization of irradiated materials and the shipment of irradiated materials to Japan. This report discusses the conceptual design, the development and irradiation of the test vehicles.

  12. FLASH knockdown sensitizes cells to Fas-mediated apoptosis via down-regulation of the anti-apoptotic proteins, MCL-1 and Cflip short.

    Directory of Open Access Journals (Sweden)

    Song Chen

    Full Text Available FLASH (FLICE-associated huge protein or CASP8AP2 is a large multifunctional protein that is involved in many cellular processes associated with cell death and survival. It has been reported to promote apoptosis, but we show here that depletion of FLASH in HT1080 cells by siRNA interference can also accelerate the process. As shown previously, depletion of FLASH halts growth by down-regulating histone biosynthesis and arrests the cell cycle in S-phase. FLASH knockdown followed by stimulating the cells with Fas ligand or anti-Fas antibodies was found to be associated with a more rapid cleavage of PARP, accelerated activation of caspase-8 and the executioner caspase-3 and rapid progression to cellular disintegration. As is the case for most anti-apoptotic proteins, FLASH was degraded soon after the onset of apoptosis. Depletion of FLASH also resulted in the reduced intracellular levels of the anti-apoptotic proteins, MCL-1 and the short isoform of cFLIP. FLASH knockdown in HT1080 mutant cells defective in p53 did not significantly accelerate Fas mediated apoptosis indicating that the effect was dependent on functional p53. Collectively, these results suggest that under some circumstances, FLASH suppresses apoptosis.

  13. Exopolysaccharides from Lactobacillus plantarum NCU116 induce c-Jun dependent Fas/Fasl-mediated apoptosis via TLR2 in mouse intestinal epithelial cancer cells.

    Science.gov (United States)

    Zhou, Xingtao; Hong, Tao; Yu, Qiang; Nie, Shaoping; Gong, Deming; Xiong, Tao; Xie, Mingyong

    2017-10-27

    Exopolysaccharides (EPS) from lactic acid bacteria (LAB) have been reported to play vital parts in the modulation of cell-cycle and apoptosis in cancer cells. However, the mechanisms by which EPS regulate the proliferation and apoptosis of cancer cells remain incompletely understood. We thus used different cancer cells to evaluate the anticancer ability and to investigate the underlying molecular mechanism of EPS from Lactobacillus plantarum NCU116 (EPS116). Our studies showed that EPS116 inhibited the proliferation of cancer cells in a cell type manner, and remarkably repressed the growth and survival of CT26 through induction of apoptosis. Moreover, EPS116 increased the expression of pro-apoptotic genes, including Fas, Fasl and c-Jun, induced the phosphorylation of c-Jun in CT26 cells. Furthermore, TLR2 (Toll like receptor 2) was upregulated by EPS116, and the CT26 cells with TLR2 knockdown were found to be insensitive to EPS116, suggesting that the anti-cancer activity of EPS116 may be TLR2-dependent. Taken together, the suppressive efficacy of EPS116 on the proliferation of CT26 cells may be mediated via TLR2 and the activation of c-Jun dependent Fas/Fasl-mediated apoptotic pathway. Our study has, for the first time, shown that EPS from LAB induced c-Jun dependent Fas/Fasl-mediated apoptosis via TLR2 in CT26 cells.

  14. A mass-conservative adaptive FAS multigrid solver for cell-centered finite difference methods on block-structured, locally-cartesian grids

    Science.gov (United States)

    Feng, Wenqiang; Guo, Zhenlin; Lowengrub, John S.; Wise, Steven M.

    2018-01-01

    We present a mass-conservative full approximation storage (FAS) multigrid solver for cell-centered finite difference methods on block-structured, locally cartesian grids. The algorithm is essentially a standard adaptive FAS (AFAS) scheme, but with a simple modification that comes in the form of a mass-conservative correction to the coarse-level force. This correction is facilitated by the creation of a zombie variable, analogous to a ghost variable, but defined on the coarse grid and lying under the fine grid refinement patch. We show that a number of different types of fine-level ghost cell interpolation strategies could be used in our framework, including low-order linear interpolation. In our approach, the smoother, prolongation, and restriction operations need never be aware of the mass conservation conditions at the coarse-fine interface. To maintain global mass conservation, we need only modify the usual FAS algorithm by correcting the coarse-level force function at points adjacent to the coarse-fine interface. We demonstrate through simulations that the solver converges geometrically, at a rate that is h-independent, and we show the generality of the solver, applying it to several nonlinear, time-dependent, and multi-dimensional problems. In several tests, we show that second-order asymptotic (h → 0) convergence is observed for the discretizations, provided that (1) at least linear interpolation of the ghost variables is employed, and (2) the mass conservation corrections are applied to the coarse-level force term.

  15. Smac mimetic enables the anticancer action of BCG-stimulated neutrophils through TNF-α but not through TRAIL and FasL.

    Science.gov (United States)

    Jinesh G, Goodwin; Chunduru, Srinivas; Kamat, Ashish M

    2012-07-01

    BCG, the current gold standard immunotherapy for bladder cancer, exerts its activity via recruitment of neutrophils to the tumor microenvironment. Many patients do not respond to BCG therapy, indicating the need to understand the mechanism of action of BCG-stimulated neutrophils and to identify ways to overcome resistance to BCG therapy. Using isolated human neutrophils stimulated with BCG, we found that TNF-α is the key mediator secreted by BCG-stimulated neutrophils. RT4v6 human bladder cancer cells, which express TNFR1, CD95/Fas, CD95 ligand/FasL, DR4, and DR5, were resistant to BCG-stimulated neutrophil conditioned medium but effectively killed by the combination of conditioned medium and Smac mimetic. rhTNF-α and rhFasL, but not rhTRAIL, in combination with Smac mimetic, generated signature molecular events similar to those produced by BCG-stimulated neutrophils in combination with Smac mimetic. However, experiments using neutralizing antibodies to these death ligands showed that TNF-α secreted from BCG-stimulated neutrophils was the key mediator of anticancer action. These findings explain the mechanism of action of BCG and identified Smac mimetics as potential combination therapeutic agents for bladder cancer.

  16. Craniospinal irradiation techniques

    Energy Technology Data Exchange (ETDEWEB)

    Scarlatescu, Ioana, E-mail: scarlatescuioana@gmail.com; Avram, Calin N. [Faculty of Physics, West University of Timisoara, Bd. V. Parvan 4, 300223 Timisoara (Romania); Virag, Vasile [County Hospital “Gavril Curteanu” - Oradea (Romania)

    2015-12-07

    In this paper we present one treatment plan for irradiation cases which involve a complex technique with multiple beams, using the 3D conformational technique. As the main purpose of radiotherapy is to administrate a precise dose into the tumor volume and protect as much as possible all the healthy tissues around it, for a case diagnosed with a primitive neuro ectoderm tumor, we have developed a new treatment plan, by controlling one of the two adjacent fields used at spinal field, in a way that avoids the fields superposition. Therefore, the risk of overdose is reduced by eliminating the field divergence.

  17. Increased Fas and Bcl-2 Expression on Peripheral Blood T and B Lymphocytes from Juvenile-Onset Systemic Lupus Erythematosus, but not from Juvenile Rheumatoid Arthritis and Juvenile Dermatomyositis

    Directory of Open Access Journals (Sweden)

    Bernadete L. Liphaus

    2006-01-01

    Full Text Available Defective regulation of apoptosis may play a role in the development of autoimmune diseases. Fas and Bcl-2 proteins are involved in the control of apoptosis. The aims of this study were to determine the expression of Fas antigen and Bcl-2 protein on peripheral blood T and B lymphocytes from patients with juvenile-onset systemic lupus erythematosus (JSLE, juvenile rheumatoid arthritis (JRA and juvenile dermatomyositis (JDM. Thirty-eight patients with JSLE, 19 patients with JRA, 10 patients with JDM and 25 healthy controls entered the study. Freshly isolated peripheral blood mononuclear cells (PBMC were stained for lymphocyte markers CD3, CD4, CD8, CD19 and for Fas and Bcl-2 molecules. Expressions were measured by three-color flow cytometry. Statistical analysis was performed using Kruskal–Wallis test. Percentages of freshly isolated T lymphocytes positively stained for Fas protein from JSLE patients were significantly increased compared to healthy controls, patients with JRA and patients with JDM. Percentages of B lymphocytes positive for Fas from JSLE patients were higher than healthy controls and JRA patients. In addition, Fas expression on T cells from patients with JRA was increased compared to JDM patients. Otherwise, Fas expression on T and B cells from JRA and JDM patients were similar to healthy controls. MFI of Bcl-2 positive T lymphocytes from JSLE patients were significantly increased compared to healthy controls and JRA patients. MFI of Bcl-2 protein on B lymphocytes from JSLE patients was similar to healthy controls and patients with JRA and JDM. Bcl-2 expression did not differ between JRA and JDM patients and healthy controls. In conclusion, increased expression of Fas and Bcl-2 proteins observed in circulating T and B lymphocytes from patients with JSLE, but not from patients with JRA and JDM, suggests that abnormalities of apoptosis may be related to the pathogenesis of JSLE and probably are not a result of chronic inflammation.

  18. Sustained activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase pathways by hepatitis B virus X protein mediates apoptosis via induction of Fas/FasL and tumor necrosis factor (TNF) receptor 1/TNF-alpha expression.

    Science.gov (United States)

    Wang, Wen-Horng; Grégori, Gérald; Hullinger, Ronald L; Andrisani, Ourania M

    2004-12-01

    Activation of the cellular stress pathways (c-Jun N-terminal kinase [JNK] and p38 mitogen-activated protein [MAP] kinase) is linked to apoptosis. However, whether both pathways are required for apoptosis remains unresolved. Hepatitis B virus X protein (pX) activates p38 MAP kinase and JNK pathways and, in response to weak apoptotic signals, sensitizes hepatocytes to apoptosis. Employing hepatocyte cell lines expressing pX, which was regulated by tetracycline, we investigated the mechanism of apoptosis by p38 MAP kinase and JNK pathway activation. Inhibition of the p38 MAP kinase pathway rescues by 80% the initiation of pX-mediated apoptosis, whereas subsequent apoptotic events involve both pathways. pX-mediated activation of p38 MAP kinase and JNK pathways is sustained, inducing the transcription of the death receptor family genes encoding Fas/FasL and tumor necrosis factor receptor 1 (TNFR1)/TNF-alpha and the p53-regulated Bax and Noxa genes. The pX-dependent expression of Fas/FasL and TNFR1/TNF-alpha mediates caspase 8 activation, resulting in Bid cleavage. In turn, activated Bid, acting with pX-induced Bax and Noxa, mediates the mitochondrial release of cytochrome c, resulting in the activation of caspase 9 and apoptosis. Combined antibody neutralization of FasL and TNF-alpha reduces by 70% the initiation of pX-mediated apoptosis. These results support the importance of the pX-dependent activation of both the p38 MAP kinase and JNK pathways in pX-mediated apoptosis and suggest that this mechanism of apoptosis occurs in vivo in response to weak apoptotic signals.

  19. International Developments of Food Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Loaharanu, P. [Head, Food Preservation Section, Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, Wagramerstr. 5, A-1400, Vienna (Austria)

    1997-12-31

    Food irradiation is increasingly accepted and applied in many countries in the past decade. Through its use, food losses and food-borne diseases can be reduced significantly, and wider trade in many food items can be facilitated. The past five decades have witnessed a positive evolution on food irradiation according to the following: 1940`s: discovery of principles of food irradiation; 1950`s: initiation of research in advanced countries; 1960`s: research and development were intensified in some advanced and developing countries; 1970`s: proof of wholesomeness of irradiated foods; 1980`s: establishment of national regulations; 1990`s: commercialization and international trade. (Author)

  20. Food irradiation and the consumer

    Science.gov (United States)

    A Thomas, P.

    The poster presents a review of research work undertaken on the perception and understanding that consumers have of food irradiation. Food irradiation is not a revolutionary new food processing technique, in fact it is probably one of the most investigated methods presently available. Many countries such as Belgium, France, Denmark, Italy, Spain, the Netherlands and the United States of America permit food irradiation. In Britain it is presently banned although this is currently under review. Awareness of food irradiation by the general public in Britain, although not extensively researched would appear to be increasing, especially in the light of recent media coverage. New quantitative and qualitative work indicates that the general public are concerned about the safety and effectiveness of food irradiation. Research has shown that a large proportion of consumers in Britain, if given the opportunity to purchase irradiated food, would not do so. Further exploration into this response revealed the fact that consumers are confused over what food irradiation is. In addition, there is concern over the detection of irradiated food. The views presented in this paper, of the consumer reaction to irradiated food are of great importance to those involved in the food industry and industries allied to it, which are ultimately dependent on the consumer for their commercial survival.

  1. Silencing of Pokemon enhances caspase-dependent apoptosis via fas- and mitochondria-mediated pathways in hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Yu-Qin Zhang

    Full Text Available The role of Pokemon (POK erythroid myeloid ontogenic actor, a recently identified POK transcription factor with proto-oncogenic activity, in hepatocellular carcinogenesis has only been assessed by a few studies. Our previous study revealed that Pokemon is overexpressed in hepatocellular carcinomas (HCC and promotes HCC cell proliferation and migration via an AKT- and ERK- dependent manner. In the present study, we used the TUNEL assay and FACS analysis to demonstrate that oxaliplatin induced apoptosis was significantly increased in cells with silenced Pokemon. Western blots showed that p53 expression and phosphorylation were significantly increased in Pokemon defective cells, thereby initiating the mitochondria-mediated and death receptor-mediated apoptotic pathways. In the mitochondria-mediated pathway, expression of pro-apoptotic Bcl-2 family members (including Bad, Bid, Bim and Puma as well as AIF was increased and decreasing the mitochondrial membrane potential resulted in cytochrome C released from mitochondrial in HepG2 si-Pokemon cells. In addition, upon oxaliplatin treatment of Pokemon-silenced cells, the FAS receptor, FADD and their downstream targets caspase-10 and caspase-8 were activated, causing increased release of caspase-8 active fragments p18 and p10. Increased activated caspase-8-mediated cleavage and activation of downstream effector caspases such as caspase-9 and caspase-3 was observed in HepG2 si-Pokemon cells as compared to control. Therefore, Pokemon might serve as an important mediator of crosstalk between intrinsic and extrinsic apoptotic pathways in HCC cells. Moreover, our findings suggest that Pokemon could be an attractive therapeutic target gene for human cancer therapy.

  2. Silencing of Pokemon enhances caspase-dependent apoptosis via fas- and mitochondria-mediated pathways in hepatocellular carcinoma cells.

    Science.gov (United States)

    Zhang, Yu-Qin; Xiao, Chuan-Xing; Lin, Bi-Yun; Shi, Ying; Liu, Yun-Peng; Liu, Jing-Jing; Guleng, Bayasi; Ren, Jian-Lin

    2013-01-01

    The role of Pokemon (POK erythroid myeloid ontogenic actor), a recently identified POK transcription factor with proto-oncogenic activity, in hepatocellular carcinogenesis has only been assessed by a few studies. Our previous study revealed that Pokemon is overexpressed in hepatocellular carcinomas (HCC) and promotes HCC cell proliferation and migration via an AKT- and ERK- dependent manner. In the present study, we used the TUNEL assay and FACS analysis to demonstrate that oxaliplatin induced apoptosis was significantly increased in cells with silenced Pokemon. Western blots showed that p53 expression and phosphorylation were significantly increased in Pokemon defective cells, thereby initiating the mitochondria-mediated and death receptor-mediated apoptotic pathways. In the mitochondria-mediated pathway, expression of pro-apoptotic Bcl-2 family members (including Bad, Bid, Bim and Puma) as well as AIF was increased and decreasing the mitochondrial membrane potential resulted in cytochrome C released from mitochondrial in HepG2 si-Pokemon cells. In addition, upon oxaliplatin treatment of Pokemon-silenced cells, the FAS receptor, FADD and their downstream targets caspase-10 and caspase-8 were activated, causing increased release of caspase-8 active fragments p18 and p10. Increased activated caspase-8-mediated cleavage and activation of downstream effector caspases such as caspase-9 and caspase-3 was observed in HepG2 si-Pokemon cells as compared to control. Therefore, Pokemon might serve as an important mediator of crosstalk between intrinsic and extrinsic apoptotic pathways in HCC cells. Moreover, our findings suggest that Pokemon could be an attractive therapeutic target gene for human cancer therapy.

  3. Hepatitis C virus protects human B lymphocytes from Fas-mediated apoptosis via E2-CD81 engagement.

    Directory of Open Access Journals (Sweden)

    Zhihui Chen

    2011-04-01

    Full Text Available HCV infection is often associated with B-cell regulatory control disturbance and delayed appearance of neutralizing antibodies. CD81 is a cellular receptor for HCV and can bind to HCV envelope protein 2 (E2. CD81 also participates to form a B cell costimulatory complex. To investigate whether HCV influences B cell activation and immune function through E2 -CD81 engagement, here, human Burkitt's lymphoma cell line Raji cells and primary human B lymphocytes (PHB were treated with HCV E2 protein and cell culture produced HCV particles (HCVcc, and then the related cell phenotypes were assayed. The results showed that both E2 and HCVcc triggered phosphorylation of IκBα, enhanced the expression of anti-apoptosis Bcl-2 family proteins, and protected Raji cells and PHB cells from Fas-mediated death. In addition, both E2 protein and HCVcc increased the expression of costimulatory molecules CD80, CD86 and CD81 itself, and decreased the expression of complement receptor CD21. The effects were dependent on E2-CD81 interaction on the cell surface, since CD81-silenced Raji cells did not respond to both treatments; and an E2 mutant that lose the CD81 binding activity, could not trigger the responses of both Raji cells and PHB cells. The effects were not associated with HCV replication in cells, for HCV pseudoparticle (HCVpp and HCVcc failed to infect Raji cells. Hence, E2-CD81 engagement may contribute to HCV-associated B cell lymphoproliferative disorders and insufficient neutralizing antibody production.

  4. RIPK3/Fas-Associated Death Domain Axis Regulates Pulmonary Immunopathology to Cryptococcal Infection Independent of Necroptosis

    Directory of Open Access Journals (Sweden)

    Zhenzong Fa

    2017-09-01

    Full Text Available Fas-associated death domain (FADD and receptor interacting protein kinase 3 (RIPK3 are multifunctional regulators of cell death and immune response. Using a mouse model of cryptococcal infection, the roles of FADD and RIPK3 in anti-cryptococcal defense were investigated. Deletion of RIPK3 alone led to increased inflammatory cytokine production in the Cryptococcus neoformans-infected lungs, but in combination with FADD deletion, it led to a robust Th1-biased response with M1-biased macrophage activation. Rather than being protective, these responses led to paradoxical C. neoformans expansion and rapid clinical deterioration in Ripk3−/− and Ripk3−/−Fadd−/− mice. The increased mortality of Ripk3−/− and even more accelerated mortality in Ripk3−/−Fadd−/− mice was attributed to profound pulmonary damage due to neutrophil-dominant infiltration with prominent upregulation of pro-inflammatory cytokines. This phenomenon was partially associated with selective alterations in the apoptotic frequency of some leukocyte subsets, such as eosinophils and neutrophils, in infected Ripk3−/−Fadd−/− mice. In conclusion, our study shows that RIPK3 in concert with FADD serve as physiological “brakes,” preventing the development of excessive inflammation and Th1 bias, which in turn contributes to pulmonary damage and defective fungal clearance. This novel link between the protective effect of FADD and RIPK3 in antifungal defense and sustenance of immune homeostasis may be important for the development of novel immunomodulatory therapies against invasive fungal infections.

  5. Food irradiation and sterilization

    Science.gov (United States)

    Josephson, Edward S.

    Radiation sterilization of food (radappertization) requires exposing food in sealed containers to ionizing radiation at absorbed doses high enough (25-70 kGy) to kill all organisms of food spoilage and public health significance. Radappertization is analogous to thermal canning is achieving shelf stability (long term storage without refrigeration). Except for dry products in which autolysis is negligible, the radappertization process also requires that the food be heated to an internal temperature of 70-80°C (bacon to 53°C) to inactivate autolytic enzymes which catalyze spoilage during storage without refrigeration. To minimize the occurence of irradiation induced off-flavors and odors, undesirable color changes, and textural and nutritional losses from exposure to the high doses required for radappertization, the foods are vacuum sealed and irradiated frozen (-40°C to -20°C). Radappertozed foods have the characteristic of fresh foods prepared for eating. Radappertization can substitute in whole or in part for some chemical food additives such as ethylene oxide and nitrites which are either toxic, carcinogenic, mutagenic, or teratogenic. After 27 years of testing for "wholesomeness" (safety for consumption) of radappertized foods, no confirmed evidence has been obtained of any adverse effecys of radappertization on the "wholesomeness" characteristics of these foods.

  6. Color and COD degradation in photocatalytic process of procion red by using TiO2 catalyst under solar irradiation

    Science.gov (United States)

    Sari, Melati Ireng; Agustina, Tuty Emilia; Melwita, Elda; Aprianti, Tine

    2017-11-01

    Increasing textile industries in Indonesia resulted in increasing the utilization of dyes. The use of synthetic dyes are still dominating because they have many advantages. But, synthetic dyes are difficult to decompose in nature so they can cause potential pollution if discharged directly into the environment. In this study, Procion Red was used as a model of synthetic dye wastewater. The objective of this research is to study the effect of TiO2 catalyst concentration and irradiation time on the degradation of Procion Red under solar irradiation. Photo degradation takes place by using TiO2 catalyst powder in the various concentration of Procion Red of 150-300 ppm. The various concentrations of TiO2 catalyst of 0.5-8 g/l were used. The color and COD degradation of Procion Red for 12 hours of solar irradiation were investigated. Color degradation was measured by using a spectrophotometer. While COD degradation was measured by using Ferrous Ammonium Sulfate (FAS) analysis method. The result showed when using Procion Red of 150 ppm, the highest color degradation of 100% was achieved by using TiO2 catalyst of 6 g/l and the highest COD degradation of 62% was obtained by using TiO2 catalyst of 8 g/l, under 12 hours of solar irradiation

  7. Sensorial evaluation of irradiated mangoes

    Energy Technology Data Exchange (ETDEWEB)

    Broisler, Paula Olhe; Cruz, Juliana Nunes da; Sabato, Susy Frey [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mails: paulabroisler@hotmail.com; juliananc@ig.com.br; sfsabato@ipen.br

    2007-07-01

    Mango (Mangifera indica L.) is a tropical fruit of great economical relevance in the world, mainly for tropical countries like Brazil. It consists in the second tropical fruit more important grown in the world. On the other hand it is a very perishable fruit and its delivery to distant points is restricted due to short shelf life at environmental temperature. Food irradiation process is applied to fruits for their preservation, once it promotes disinfestation and even maturation retard, among other mechanisms. The Brazilian legislation permits the food irradiation and does not restrict the doses to be delivered. In order to verify eventual changes, sensorial evaluation is very important to study how irradiation affects the quality of the fruit and its acceptability. Mangoes were irradiated in a Cobalto-60 source, from the Radiation Technology Center, CTR, of IPEN/CNEN-SP at doses 0,5 kGy e 0,75 kGy. The sensorial evaluation was measured through Acceptance Test where irradiated samples were offered together with control sample to the tasters who answered their perception through hedonic scale. The parameters Color, Odor, Flavor and Texture were analyzed. Statistical analysis showed that only Odor parameter was different from control (sample irradiated at 0.5 kGy). Few tasters indicated that irradiated mangoes had fewer odors in relation to non-irradiated samples. (author)

  8. Consumer acceptance of irradiated food

    Energy Technology Data Exchange (ETDEWEB)

    Loaharanu, P. [Head, Food Preservation Section, Joint FAO/ IAEA Division of Nuclear Techniques in Food and Agriculture, Wagramerstr. 5, A-1400, Vienna (Austria)

    1997-12-31

    There was a widely held opinion during the 1970`s and 1980`s that consumers would be reluctant to purchase irradiated food, as it was perceived that consumers would confuse irradiated food with food contaminated by radionuclides. Indeed, a number of consumer attitude surveys conducted in several western countries during these two decades demonstrated that the concerns of consumers on irradiated food varied from very concerned to seriously concerned.This paper attempts to review parameters conducting in measuring consumer acceptance of irradiated food during the past three decades and to project the trends on this subject. It is believed that important lessons learned from past studies will guide further efforts to market irradiated food with wide consumer acceptance in the future. (Author)

  9. Irradiation of fresh fish

    Science.gov (United States)

    Yueh-jen, Yen; Jin-lai, Zhou; Shao-chun, Lai

    Occasionally, in China, marine products can not be provided for the markets in good quality, for during the time when they are being transported from the sea port to inland towns or even at the time when they are unloaded from the ship, they are beginning to spoil. Obviously, it is very important that appropiate measures should be taken to prevent them from decay. Our study has proved that the shelf life of fresh Flatfish (Cynoglossue robustus) and Silvery pomfret (stromateoides argenteus), which, packed in sealed containers, are irradiated by 1.5 kGy, 2.2 kGy and 3.0 kGy, can be stored for about 13-26 days at 3° - 5° C.

  10. Irradiation for xenogeneic transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Halperin, E.C.; Knechtle, S.J.; Harland, R.C.; Yamaguchi, Yasua; Sontag, M.; Bollinger, R.R. (Duke Univ., Durham, NC (USA). Dept. of Radiology Duke Univ., Durham, NC (USA). Dept. of Microbiology and Immunology)

    1990-05-01

    Xenogeneic transplantation (XT) is the transplantation of organs or tissues from a member of one species to a member of another. Mammalian species frequently have circulating antibody which is directed against the foreign organ irrespective of known prior antigen exposure. This antibody may lead to hyperacute rejection once it ensues so efforts must be directed towards eliminating the pre-existing antibody. In those species in which hyperacute rejection of xenografts does not occur, cell-mediated refection, similar to allograft rejection, may occur. It is in the prevention of this latter form of refection that radiation is most likely to be beneficial in XT. Both total lymphoid irradiation (TLI) and selective lyphoid irradiation (LSI) have been investigated for use in conjunction with XT. TLI has contributed to the prolongation of pancreatic islet-cell xenografts from hamsters to rats. TLI has also markedly prolonged the survival of cardiac transplants from hamsters to rats. A more modest prolongation of graft survival has been seen with the use of TLI in rabbit-to-rat exchanges. Therapy with TLI, cyclosporine, and splenectomy has markedly prolonged the survival of liver transplants from hamsters to rats, and preliminary data suggest that TLI may contribute to the prolongation of graft survival in the transplantation of hearts from monkeys to baboons. SLI appears to have prolonged graft survival, when used in conjunction with anti-lymphocyte globulin, in hamster-to-rat cardiac graft exchanges. The current state of knowledge of the use of irradiaiton in experimental XT is reviewed. (author). 38 refs.; 1 fig.; 5 tabs.

  11. Granzyme B- and Fas ligand-mediated cytotoxic function induced by mitogenic CD28 stimulation of human memory CD4+ T cells.

    Science.gov (United States)

    Medina, Miguel A; Couturier, Jacob; Feske, Marsha L; Mahne, Ashley E; Turner, Mary; Yu, Xiaoyong; Kozinetz, Claudia A; Orozco, Aaron F; Hutchison, Alexander T; Savidge, Tor C; Rodgers, John R; Lewis, Dorothy E

    2012-05-01

    Some human memory CD4(+) T cells have cytotoxic functions best understood in the context of viral infections; however, their possible role in pathologic processes is understudied. The novel discovery that mitogenic CD28 antibodies induced proliferation and expansion of Tregs offered therapeutic promise for autoimmune disorders. However, the failed TGN1412 trial forced reassessment of this concept. As memory CD4(+) T cells are known to produce toxic molecules, including granzyme B (GrzB) and FasL, we wondered whether mitogenic CD28 was able to induce these cytotoxic molecules. A commercially available mitogenic human CD28 mAb (clone ANC28.1) was used to determine whether mitogenic CD28 induces cytotoxic function from human memory CD4(+) T cells. We found that stimulation of memory CD4(+) T cells by ANC28.1, as well as by conventional costimulation (CD3/CD28 mAb), robustly induced enzymatically active GrzB, along with increased surface expression of FasL. These functional phenotypes were induced in association with increased expression of T cell activation markers CD69 and CD25, and elimination of target cells by ANC28.1-activated memory CD4(+) T cells involved both GrzB and FasL. Additionally, ANC28.1-activated memory CD4(+) T cells caused disruption of epithelial cell monolayer integrity, which was partially mediated by GrzB. These findings reveal functions of memory CD4(+) T cells previously unknown to be induced by mitogenic CD28, and suggest that these pathogenic mechanisms may have been responsible for some of the widespread tissue destruction that occurred in the TGN1412 trial recipients.

  12. FasL and FADD delivery by a glioma-specific and cell cycle-dependent HSV-1 amplicon virus enhanced apoptosis in primary human brain tumors

    Directory of Open Access Journals (Sweden)

    Lam Paula Y

    2010-10-01

    Full Text Available Abstract Background Glioblastoma multiforme is the most malignant cancer of the brain and is notoriously difficult to treat due to the highly proliferative and infiltrative nature of the cells. Herein, we explored the combination treatment of pre-established human glioma xenograft using multiple therapeutic genes whereby the gene expression is regulated by both cell-type and cell cycle-dependent transcriptional regulatory mechanism conferred by recombinant HSV-1 amplicon vectors. Results We demonstrated for the first time that Ki67-positive proliferating primary human glioma cells cultured from biopsy samples were effectively induced into cell death by the dual-specific function of the pG8-FasL amplicon vectors. These vectors were relatively stable and exhibited minimal cytotoxicity in vivo. Intracranial implantation of pre-transduced glioma cells resulted in better survival outcome when compared with viral vectors inoculated one week post-implantation of tumor cells, indicating that therapeutic efficacy is dependent on the viral spread and mode of viral vectors administration. We further showed that pG8-FasL amplicon vectors are functional in the presence of commonly used treatment regimens for human brain cancer. In fact, the combined therapies of pG8-FasL and pG8-FADD in the presence of temozolomide significantly improved the survival of mice bearing intracranial high-grade gliomas. Conclusion Taken together, our results showed that the glioma-specific and cell cycle-dependent HSV-1 amplicon vector is potentially useful as an adjuvant therapy to complement the current gene therapy strategy for gliomas.

  13. Producción de tanasa de Aspergillus niger mediante un sistema de fermentación por adhesión a superficie (FAS)

    OpenAIRE

    Cortés Avendaño, Paola Marlene

    2015-01-01

    Universidad Nacional Agraria La Molina. Escuela de Posgrado. Maestría en Tecnología de Alimentos El presente trabajo de investigación tuvo como objetivo la producción de enzima tanasa a partir de Aspergillus niger ATCC 10864 mediante un sistema de Fermentación por Adhesión a Superfie (FAS), con las siguientes condiciones de cultivo: 40 ml de medio de cultivo; temperatura 28 °C; tiempo de incubación 96 horas; pH inicial 5.5; velocidad de agitación 175rpm. Se estudió tres concentraciones...

  14. Bifidobacterial recombinant thymidine kinase-ganciclovir gene therapy system induces FasL and TNFR2 mediated antitumor apoptosis in solid tumors.

    Science.gov (United States)

    Wang, Changdong; Ma, Yongping; Hu, Qiongwen; Xie, Tingting; Wu, Jiayan; Zeng, Fan; Song, Fangzhou

    2016-07-27

    Directly targeting therapeutic suicide gene to a solid tumor is a hopeful approach for cancer gene therapy. Treatment of a solid tumor by an effective vector for a suicide gene remains a challenge. Given the lack of effective treatments, we constructed a bifidobacterial recombinant thymidine kinase (BF-rTK) -ganciclovir (GCV) targeting system (BKV) to meet this requirement and to explore antitumor mechanisms. Bifidobacterium (BF) or BF-rTK was injected intratumorally with or without ganciclovir in a human colo320 intestinal xenograft tumor model. The tumor tissues were analyzed using apoptosis antibody arrays, real time PCR and western blot. The colo320 cell was analyzed by the gene silencing method. Autophagy and necroptosis were also detected in colo320 cell. Meanwhile, three human digestive system xenograft tumor models (colorectal cancer colo320, gastric cancer MKN-45 and liver cancer SSMC-7721) and a breast cancer (MDA-MB-231) model were employed to validate the universality of BF-rTK + GCV in solid tumor gene therapy. The survival rate was evaluated in three human cancer models after the BF-rTK + GCV intratumor treatment. The analysis of inflammatory markers (TNF-α) in tumor indicated that BF-rTK + GCV significantly inhibited TNF-α expression. The results suggested that BF-rTK + GCV induced tumor apoptosis without autophagy and necroptosis occurrence. The apoptosis was transduced by multiple signaling pathways mediated by FasL and TNFR2 and mainly activated the mitochondrial control of apoptosis via Bid and Bim, which was rescued by silencing Bid or/and Bim. However, BF + GCV only induced apoptosis via Fas/FasL signal pathway accompanied with increased P53 expression. We further found that BF-rTK + GCV inhibited the expression of the inflammatory maker of TNF-α. However, BF-rTK + GCV did not result in necroptosis and autophagy. BF-rTK + GCV induced tumor apoptosis mediated by FasL and TNFR2 through the mitochondrial control

  15. AFIP-4 Irradiation Summary Report

    Energy Technology Data Exchange (ETDEWEB)

    Danielle M Perez; Misti A Lillo; Gray S. Chang; Glenn A Roth; Nicolas Woolstenhulme; Daniel M Wachs

    2011-09-01

    The Advanced Test Reactor (ATR) Full size plate In center flux trap Position (AFIP) experiment AFIP-4 was designed to evaluate the performance of monolithic uranium-molybdenum (U-Mo) fuels at a scale prototypic of research reactor fuel plates. The AFIP-4 test further examine the fuel/clad interface and its behavior under extreme conditions. After irradiation, fission gas retention measurements will be performed during post irradiation (PIE). The following report summarizes the life of the AFIP-4 experiment through end of irradiation, including a brief description of the safety analysis, as-run neutronic analysis results, hydraulic testing results, and thermal analysis results.

  16. AFIP-4 Irradiation Summary Report

    Energy Technology Data Exchange (ETDEWEB)

    Danielle M Perez; Misti A Lillo; Gray S. Chang; Glenn A Roth; Nicolas Woolstenhulme; Daniel M Wachs

    2012-01-01

    The Advanced Test Reactor (ATR) Full size plate In center flux trap Position (AFIP) experiment AFIP-4 was designed to evaluate the performance of monolithic uranium-molybdenum (U-Mo) fuels at a scale prototypic of research reactor fuel plates. The AFIP-4 test further examine the fuel/clad interface and its behavior under extreme conditions. After irradiation, fission gas retention measurements will be performed during post irradiation (PIE)1,2. The following report summarizes the life of the AFIP-4 experiment through end of irradiation, including a brief description of the safety analysis, as-run neutronic analysis results, hydraulic testing results, and thermal analysis results.

  17. Craniospinal Irradiation for Trilateral Retinoblastoma Following Ocular Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Marks, Lawrence B.; Bentel, Gunilla; Sherouse, George W.; Spencer, David P.; Light, Kim

    2015-01-15

    A case study is presented. Craniospinal radiotherapy and a three-field pineal boost for trilateral retinoblastoma were delivered to a patient previously irradiated for ocular retinoblastoma. The availability of CT-based three-dimensional treatment planning provided the capability of identifying the previously irradiated volume as a three-dimensional anatomic structure and of designing a highly customized set of treatment beams that minimized reirradiation of that volume.

  18. (Irradiation creep of graphite)

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, C.R.

    1990-12-21

    The traveler attended the Conference, International Symposium on Carbon, to present an invited paper, Irradiation Creep of Graphite,'' and chair one of the technical sessions. There were many papers of particular interest to ORNL and HTGR technology presented by the Japanese since they do not have a particular technology embargo and are quite open in describing their work and results. In particular, a paper describing the failure of Minor's law to predict the fatigue life of graphite was presented. Although the conference had an international flavor, it was dominated by the Japanese. This was primarily a result of geography; however, the work presented by the Japanese illustrated an internal program that is very comprehensive. This conference, a result of this program, was better than all other carbon conferences attended by the traveler. This conference emphasizes the need for US participation in international conferences in order to stay abreast of the rapidly expanding HTGR and graphite technology throughout the world. The United States is no longer a leader in some emerging technologies. The traveler was surprised by the Japanese position in their HTGR development. Their reactor is licensed and the major problem in their graphite program is how to eliminate it with the least perturbation now that most of the work has been done.

  19. Stillbirths and male irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Boice, John D. Jr. [International Epidemiology Institute, Rockville, MD (United States)]. E-mail: boicej@compuserve.com; Robison, Leslie L. [University of Minnesota, Minneapolis, MN (United States); Mertens, Ann [University of Texas M D Anderson Cancer Center, Houston, TX (United States); Stovall, Marilyn; Green, Daniel M.; Mulvihill, John J.; ); Roswell Park Cancer Institute, Buffalo, NY (United States); University of Oklahoma, Oklahoma City, OK (US))

    2000-09-01

    Little (1999) recently reviewed the evidence that paternal preconception irradiation in the Sellafield workforce (Parker et al 1999) and among Japanese atomic bomb survivors (Otake et al 1990) might be associated with an increased risk of stillbirth. He concluded that the association reported for radiation workers was statistically incompatible with the absence of an association seen among the exposed Japanese parents. These studies and analyses illustrate the considerable difficulty in assessing stillbirths conceived by men exposed to ionising radiation at work. For example, occupational doses may not be sufficiently large to result in a detectable effect and maternal factors that are associated with stillbirths and important to adjust for may not be available. These papers also bring to focus a relevant but not well-studied public health issue, namely, what are the reproductive risks for men and women exposed to potential mutagens? We wish to emphasise here the theoretical and practical advantages of addressing this issue in persons not with low dose occupational or acute atomic bomb exposures, but with higher dose medical experiences; in particular, in survivors of cancers of childhood, adolescents, and young adulthood (Blatt 1999, Bryne et al 1998, Sankila et al 1998, Green et al 1997, Hawkins and Stevens 1996). Letter-to-the-editor.

  20. Irradiation pretreatment for coal desulfurization

    Science.gov (United States)

    Hsu, G. C.

    1979-01-01

    Process using highly-penetrating nuclear radiation (Beta and Gamma radiation) from nuclear power plant radioactive waste to irradiate coal prior to conventional desulfurization procedures increases total extraction of sulfur.

  1. UV irradiance radiometers calibration procedure

    OpenAIRE

    Doctorovich I. V.; Butenko V. K.; Hodovaniouk V. N.; Fodchuk I. M.; Yuriev V. G.

    2008-01-01

    The paper deals with the problems arising at calibration of narrow-band spectral-sensitive radiometers. The procedure of irradiance unit transfer to UV radiometers — UV radiometers calibration procedure — is presented.

  2. URAM-2 Cryogenic Irradiation Facility

    CERN Document Server

    Shabalin, E P; Kulikov, S A; Kulagin, E N; Melihov, V V; Belyakov, A A; Golovanov, L B; Borzunov, Yu T; Konstantinov, V I; Androsov, A V

    2002-01-01

    The URAM-2 irradiation facility has been built and mounted at the channel No. 3 of the IBR-2 reactor. It was constructed for study of radiolysis effects by fast neutron irradiation in some suitable for effective cold neutron production materials (namely: solid methane, methane hydrate, water ice, etc.). The facility cooling system is based on using liquid helium as a coolant material. The original charging block of the rig allows the samples to be loaded by condensing gas into irradiation cavity or by charging beads of ice prepared before. Preliminary tests for each facility block and assembling them at the working position were carried out. Use of the facility for study accumulation of chemical energy under irradiation at low temperature in materials mentioned above and its spontaneous release was started.

  3. FAS-ligand regulates differential activation-induced cell death of human T-helper 1 and 17 cells in healthy donors and multiple sclerosis patients.

    Science.gov (United States)

    Cencioni, M T; Santini, S; Ruocco, G; Borsellino, G; De Bardi, M; Grasso, M G; Ruggieri, S; Gasperini, C; Centonze, D; Barilá, D; Battistini, L; Volpe, E

    2015-05-07

    Functionally distinct T-helper (Th) subsets orchestrate immune responses. Maintenance of homeostasis through the tight control of inflammatory Th cells is crucial to avoid autoimmune inflammation. Activation-Induced Cell Death (AICD) regulates homeostasis of T cells, and it has never been investigated in human Th cells. We generated stable clones of inflammatory Th subsets involved in autoimmune diseases, such as Th1, Th17 and Th1/17 cells, from healthy donors (HD) and multiple sclerosis (MS) patients and we measured AICD. We find that human Th1 cells are sensitive, whereas Th17 and Th1/17 are resistant, to AICD. In particular, Th1 cells express high level of FAS-ligand (FASL), which interacts with FAS and leads to caspases' cleavage and ultimately to cell death. In contrast, low FASL expression in Th17 and Th1/17 cells blunts caspase 8 activation and thus reduces cell death. Interestingly, Th cells obtained from healthy individuals and MS patients behave similarly, suggesting that this mechanism could explain the persistence of inflammatory IL-17-producing cells in autoimmune diseases, such as MS, where their generation is particularly substantial.

  4. Fas-Induced Apoptosis of Renal Cell Carcinoma is Mediated by Apoptosis Signal-Regulating Kinase 1 via Mitochondrial Damage-Dependent Caspase-8 Activation

    Directory of Open Access Journals (Sweden)

    Mohamed Hassan

    2009-01-01

    Full Text Available Renal cell carcinoma (RCC is a prototype of a chemo refractory tumour. It remains the most lethal of the common urologic cancers and is highly resistant to conventional therapy. Here, we confirmed the efficiency of anti-Fas monoclonal antibody (CH11 as alternative therapeutic approach for the treatment of RCC and investigated the molecular mechanism(s, whereby CH11 induces apoptosis of RCC cells. The present study shows an essential role for apoptosis signal-regulating kinase 1 (ASK1, together with both c-jun-N-terminal kinase (JNK and p38 pathways, and caspase-8 in this process. Furthermore, CH11-dependent induction of the ASK1–JNK/p38 pathways was found to activate the transcription factors AP-1 and ATF-2, and FADD-caspase-8-Bid signalling, resulting in the translocation of both Bax and Bak proteins, and subsequently mitochondrial dysregulation that is characterized by the loss of mitochondrial membrane potential (ΔΨm, cytochrome c release and cleavage of caspase-9, caspase-3 and PARP. Thus, the described molecular mechanisms of CH11-induced apoptosis suggest the reliability of Fas activation as an alternative therapeutic approach for the treatment of patients with advanced renal cell carcinoma.

  5. Exploring Prostate Cancer Genome Reveals Simultaneous Losses of PTEN, FAS and PAPSS2 in Patients with PSA Recurrence after Radical Prostatectomy

    Science.gov (United States)

    Ibeawuchi, Chinyere; Schmidt, Hartmut; Voss, Reinhard; Titze, Ulf; Abbas, Mahmoud; Neumann, Joerg; Eltze, Elke; Hoogland, Agnes Marije; Jenster, Guido; Brandt, Burkhard; Semjonow, Axel

    2015-01-01

    The multifocal nature of prostate cancer (PCa) creates a challenge to patients’ outcome prediction and their clinical management. An approach that scrutinizes every cancer focus is needed in order to generate a comprehensive evaluation of the disease, and by correlating to patients’ clinico-pathological information, specific prognostic biomarker can be identified. Our study utilized the Affymetrix SNP 6.0 Genome-wide assay to investigate forty-three fresh frozen PCa tissue foci from twenty-three patients. With a long clinical follow-up period that ranged from 2.0–9.7 (mean 5.4) years, copy number variation (CNV) data was evaluated for association with patients’ PSA status during follow-up. From our results, the loss of unique genes on 10q23.31 and 10q23.2–10q23.31 were identified to be significantly associated to PSA recurrence (p < 0.05). The implication of PTEN and FAS loss (10q23.31) support previous reports due to their critical roles in prostate carcinogenesis. Furthermore, we hypothesize that the PAPSS2 gene (10q23.2–10q23.31) may be functionally relevant in post-operative PSA recurrence because of its reported role in androgen biosynthesis. It is suggestive that the loss of the susceptible region on chromosome 10q, which implicates PTEN, FAS and PAPSS2 may serve as genetic predictors of PSA recurrence after radical prostatectomy. PMID:25679447

  6. Exploring Prostate Cancer Genome Reveals Simultaneous Losses of PTEN, FAS and PAPSS2 in Patients with PSA Recurrence after Radical Prostatectomy

    Directory of Open Access Journals (Sweden)

    Chinyere Ibeawuchi

    2015-02-01

    Full Text Available The multifocal nature of prostate cancer (PCa creates a challenge to patients’ outcome prediction and their clinical management. An approach that scrutinizes every cancer focus is needed in order to generate a comprehensive evaluation of the disease, and by correlating to patients’ clinico-pathological information, specific prognostic biomarker can be identified. Our study utilized the Affymetrix SNP 6.0 Genome-wide assay to investigate forty-three fresh frozen PCa tissue foci from twenty-three patients. With a long clinical follow-up period that ranged from 2.0–9.7 (mean 5.4 years, copy number variation (CNV data was evaluated for association with patients’ PSA status during follow-up. From our results, the loss of unique genes on 10q23.31 and 10q23.2–10q23.31 were identified to be significantly associated to PSA recurrence (p < 0.05. The implication of PTEN and FAS loss (10q23.31 support previous reports due to their critical roles in prostate carcinogenesis. Furthermore, we hypothesize that the PAPSS2 gene (10q23.2–10q23.31 may be functionally relevant in post-operative PSA recurrence because of its reported role in androgen biosynthesis. It is suggestive that the loss of the susceptible region on chromosome 10q, which implicates PTEN, FAS and PAPSS2 may serve as genetic predictors of PSA recurrence after radical prostatectomy.

  7. Fas-associated Phosphatase 1 (Fap1) Influences βCatenin Activity in Myeloid Progenitor Cells Expressing the Bcr-abl Oncogene

    Science.gov (United States)

    Huang, Weiqi; Bei, Ling; Eklund, Elizabeth A.

    2013-01-01

    Increased βcatenin activity correlates with leukemia stem cell expansion and disease progression in chronic myeloid leukemia (CML). We found previously that expression of the CML-related Bcr-abl oncoprotein in myeloid progenitor cells increases expression of Fas-associated phosphatase 1 (Fap1). This resulted in Fap1-dependent resistance to Fas-induced apoptosis in these cells. Fap1 also interacts with the adenomatous polyposis coli (Apc) protein, but the functional significance of this interaction is unknown. Apc participates in a complex that includes glycogen synthase kinase β (Gsk3β) and βcatenin. Assembly of this complex results in phosphorylation of βcatenin by Gsk3β, which facilitates βcatenin ubiquitination and degradation by the proteasome. In this study, we found increased association of Fap1 with the Apc complex in Bcr-abl+ myeloid progenitor cells. We also found Fap1-dependent inactivation of Gsk3β and consequent stabilization of βcatenin in these cells. Consistent with this, Bcr-abl+ cells exhibited a Fap1-dependent increase in βcatenin activity. Our studies identified Fap1-dependent Gsk3β inactivation as a molecular mechanism for increased βcatenin activity in CML. PMID:23519466

  8. DHEA and non-alcoholic fat liver disease: increased gene expression of peroxisome proliferation-activated receptor γ (PPARγ and fatty acid synthase (FAS

    Directory of Open Access Journals (Sweden)

    Felipe Natali Almeida

    2014-05-01

    Full Text Available Dehydroespiandrosterone (DHEA is associated with improvements in chronic degenerative diseases, including obesity, insulin resistance, and cardiovascular diseases. Nevertheless, it is observed an increase in its concentration in individuals with liver lipid infiltration, but it is not precise if this condition emerges as a cause or a consequence. In this way, we aimed to identify gene expression alterations in lipid and glucose liver metabolism markers, as well as oxidative stress markers. For this purpose, male Wistar rats, 12-14 months old were treated with subcutaneous injections of DHEA (only dose of 10 mg kg-1; and after 7 days, hepatic gene expression by PCR real time were performed for the following genes:  G6Pase, PEPCK, FAS, PPARγ, malic enzyme, ChREBP, LXR, catalase, GPx, iNOS, NADPH oxidase subunits and PCNA. We observed a tendency of reduction in G6Pase gene expression in treated group (p = 0.08. In addition, it was identified an increase in liver PPARγ and FAS gene expressions, two markers of increased activity of lipogenic pathway. We also observed an increase in iNOS gene expression, a known inductor of systemic and hepatic insulin resistance. In conclusion, our data indicates that the treatment with DHEA can be associated with the development of liver lipid infiltration and hepatic insulin resistance.

  9. Both the Fas ligand and inducible nitric oxide synthase are needed for control of parasite replication within lesions in mice infected with Leishmania major whereas the contribution of tumor necrosis factor is minimal.

    Science.gov (United States)

    Chakour, Reza; Guler, Reto; Bugnon, Mélanie; Allenbach, Cindy; Garcia, Irène; Mauël, Jacques; Louis, Jacques; Tacchini-Cottier, Fabienne

    2003-09-01

    Following infection with the protozoan parasite Leishmania major, C57BL/6 mice develop a small lesion that heals spontaneously. Resistance to infection is associated with the development of CD4(+) Th1 cells producing gamma interferon (IFN-gamma) and tumor necrosis factor (TNF), which synergize in activating macrophages to their microbicidal state. We show here that C57BL/6 mice lacking both TNF and Fas ligand (FasL) (gld TNF(-/-) mice) infected with L. major neither resolved their lesions nor controlled Leishmania replication despite the development of a strong Th1 response. Comparable inducible nitric oxide synthase (iNOS) activities were detected in lesions of TNF(-/-), gld TNF(-/-), and gld mice, but only gld and gld TNF(-/-) mice failed to control parasite replication. Parasite numbers were high in gld mice and even more elevated in gld TNF(-/-) mice, suggesting that, in addition to iNOS, the Fas/FasL pathway is required for successful control of parasite replication and that TNF contributes only a small part to this process. Furthermore, FasL was shown to synergize with IFN-gamma for the induction of leishmanicidal activity within macrophages infected with L. major in vitro. Interestingly, TNF(-/-) mice maintained large lesion size throughout infection, despite being able to largely control parasite numbers. Thus, IFN-gamma, FasL, and iNOS appear to be essential for the complete control of parasite replication, while the contribution of TNF is more important in controlling inflammation at the site of parasite inoculation.

  10. Food irradiation: Gamma processing facilities

    Energy Technology Data Exchange (ETDEWEB)

    Kunstadt, P. [MDS Nordion International, 447 March Road. Kanata, Ontario, K2K148 (Canada)

    1997-12-31

    The number of products being radiation processed is constantly increasing and today include such diverse items as medical disposable, fruits and vegetables, bulk spices, meats, sea foods and waste effluents. Not only do the products differ but also many products, even those within the same groupings, require different minimum and maximum radiation doses. These variations create many different requirements in the irradiator design. The design of Cobalt-60 radiation processing facilities is well established for a number of commercial applications. Installations in over 40 countries, with some in operation since the early 1960s, are testimony to the fact that irradiator design, manufacture, installation and operation is a well established technology. However, in order to design gamma irradiators for the preservation of foods one must recognize those parameters typical to the food irradiation process as well as those systems and methods already well established in the food industry. This paper discusses the basic design concepts for gamma food irradiators. They are most efficient when designed to handle a limited product density range at an established dose. Safety of Cobalt-60 transport, safe facility operation principles and the effect of various processing parameters on economics, will also be discussed. (Author)

  11. Proton irradiation for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Matsuzaki, Yasushi; Chiba, Shunya [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine; Tanaka, Naomi

    1999-02-01

    A curative effect of high dose proton irradiation for hepatoma was investigated. In cases of single nodular type HCC, radiation field was limited to tumor, and in cases of multi nodular type HCC, irradiation was also fractionated. An average dose of radiation was 4 Gy/time, average times were 16, and an average total dose was 72 Gy. Tumor size reduction rate at 6 months after proton irradiation (123 cases) was CR (17.9%), PR (52.0%), NC (29.3%) and PD (0.8%). And the reduction rate of tumor size in monotherapy cases was 100% (after 3 weeks), 96% (after 1 year) and 88% (after 2 years). The local control rate was 99.1% (after 1 year) and 91.4% (after 3-5 years). AFP value significantly decreased from 571.0{+-}1266.6 ng/ml before radiation to 145.4{+-}346.3 ng/ml after radiation (p<0.0005). The recurrence after radiation occurred more at outside of radiation field, significantly. Indication basis of proton irradiation was showed in this article. Because selective radiation is possible, the proton irradiation should be optimum therapy in specific carcinomas of deep organ. (K.H.)

  12. Elective ilioingunial lymph node irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, R.H.; Parsons, J.T.; Morgan, L.; Million, R.R.

    1984-06-01

    Most radiologists accept that modest doses of irradiation (4500-5000 rad/4 1/2-5 weeks) can control subclinical regional lymph node metastases from squamous cell carcinomas of the head and neck and adenocarcinomas of the breast. There have been few reports concerning elective irradiation of the ilioinguinal region. Between October 1964 and March 1980, 91 patients whose primary cancers placed the ilioinguinal lymph nodes at risk received elective irradiation at the University of Florida. Included are patients with cancers of the vulva, penis, urethra, anus and lower anal canal, and cervix or vaginal cancers that involved the distal one-third of the vagina. In 81 patients, both inguinal areas were clinically negative; in 10 patients, one inguinal area was positive and the other negative by clinical examination. The single significant complication was a bilateral femoral neck fracture. The inguinal areas of four patients developed mild to moderate fibrosis. One patient with moderate fibrosis had bilateral mild leg edema that was questionably related to irradiation. Complications were dose-related. The advantages and dis-advantages of elective ilioinguinal node irradiation versus elective inguinal lymph node dissection or no elective treatment are discussed.

  13. Currently developing opportunities in food irradiation and modern irradiation facilities

    Energy Technology Data Exchange (ETDEWEB)

    Wanke, R. [Director Business Development. SteriGenics International Inc. 17901 East Warren Avenue No. 4, Detroit, Michigan 48224-1333 (United States)

    1997-12-31

    I. Factor currently influencing advancing opportunities for food irradiation include: heightened incidence and awareness of food borne illnesses and causes. Concerns about ensuring food safety in international as well as domestic trade. Regulatory actions regarding commonly used fumigants/pesticides e.g. Me Br. II. Modern irradiator design: the SteriGenics {sup M}ini Cell{sup .} A new design for new opportunities. Faster installation of facility. Operationally and space efficient. Provides local {sup o}nsite control{sup .} Red meat: a currently developing opportunity. (Author)

  14. Acclimation to a dynamic irradiance regime changes excessive irradiance sensitivity of Emiliania huxleyi and Thalassiosira weissflogii

    OpenAIRE

    van De Poll, Willem H.; Visser, Ronald J. W.; Buma, Anita G. J.

    2007-01-01

    Effects of fluctuating irradiance regimes on excessive photosynthetically active radiation (PAR) and ultraviolet (UV) radiation sensitivity were assessed for Emiliania huxleyi (Lohman) and Thalassiosira weissflogii (Grunow) Fryxell and Hasle. Cultures acclimated to low irradiance were subjected to two irradiance regimes of equal daily dose: dynamic irradiance simulating vertical mixing within the water column and constant irradiance. For each regime two irradiance levels were studied. Growth ...

  15. Materials irradiation research in neutron science

    Energy Technology Data Exchange (ETDEWEB)

    Noda, Kenji; Oyama, Yukio [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1997-11-01

    Materials irradiation researches are planned in Neutron Science Research Program. A materials irradiation facility has been conceived as one of facilities in the concept of Neutron Science Research Center at JAERI. The neutron irradiation field of the facility is characterized by high flux of spallation neutrons with very wide energy range up to several hundred MeV, good accessibility to the irradiation field, good controllability of irradiation conditions, etc. Extensive use of such a materials irradiation facility is expected for fundamental materials irradiation researches and R and D of nuclear energy systems such as accelerator-driven incineration plant for long-lifetime nuclear waste. In this paper, outline concept of the materials irradiation facility, characteristics of the irradiation field, preliminary technical evaluation of target to generate spallation neutrons, and materials researches expected for Neutron Science Research program are described. (author)

  16. Directional irradiances and fractional clouds

    Science.gov (United States)

    Pagh Nielsen, Kristian; Andersen, Elsa; Dragsted, Janne; Furbo, Simon

    2017-04-01

    For large scale implementation of solar energy, better understanding of the directional and temporal variations in the solar resource is needed. This includes understanding the shading within a multiple row field of solar panels and how this affects the electricity or heat production. We have studied directional irradiances measured simultaneously from 16 downward directions at 1 minute temporal resolution. Also, we have performed measurements of the variations in the field of view across individual solar heating panels in the operational solar district heating plant in Hedehusene in Denmark. By combining a model of directional diffuse irradiances with the field of view variation across a solar panel in a solar panel field we can quantify the effect of shading of diffuse irradiances on the heat flow from the panel.

  17. Endodontics and the irradiated patient

    Energy Technology Data Exchange (ETDEWEB)

    Cox, F.L.

    1976-11-01

    With increasingly larger numbers of irradiated patients in our population, it seems likely that all dentists will eventually be called upon to manage the difficult problems that these patients present. Of utmost concern should be the patient's home care program and the avoidance of osteroradionecrosis. Endodontics and periodontics are the primary areas for preventing or eliminating the infection that threatens osteoradionecrosis. Endodontic treatment must be accomplished with the utmost care and maximum regard for the fragility of the periapical tissues. Pulpally involved teeth should never be left open in an irradiated patient, and extreme care must be taken with the between-visits seal. If one is called upon for preradiation evaluation, routine removal of all molar as well as other compromised teeth should be considered. Attention should be directed to the literature for further advances in the management of irradiated patients.

  18. Irradiation test of high density Si material

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Man Soon; Choo, Kee Nam; Lee, Chul Yong; Yang, Seong Woo; Shim, Kyue Taek; Park, Sang Jun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2012-10-15

    The feasibility of irradiation test for the high-density Si material entrusted by Guju Inc. was reviewed. The high density Si material is used for a sealing of the penetration holes of piping at the nuclear power plants. The irradiation test was performed and the density changes between before and after irradiation test were measured. The irradiation tests were performed 2 times for 1 day and 20 days at IP 4 hole of HANARO. The 3 Si specimens irradiated were without flaws and the density changes after irradiation were successfully measured. The result satisfies the requirement of the design specification.

  19. Notes on irradiation of neodymium

    Energy Technology Data Exchange (ETDEWEB)

    Woods, W.K.

    1966-06-07

    The fission product, promethium-147, would be much more desirable as a heat-producing radioisotope if it were not in such short supply. C.A. Rohrmann`s chart ``Characteristics of Radioisotopic Heat Sources`` lists the annual availability of Pm-147 as 5-5 kw, corresponding to about 17 kg. Hence, consideration has been given to irradiation of neodymium-146 in order to augment the supply of Pm-147, A method for separating Nd-146 from other neodymium isotopes does not exist today. This memorandum presents the results of a brief look at the irradiation of mixed neodymium isotopes which are available without isotopic separation.

  20. Significance of irradiation of blood

    Energy Technology Data Exchange (ETDEWEB)

    Sekine, Hiroshi; Gotoh, Eisuke; Mochizuki, Sachio (Jikei Univ., Tokyo (Japan). School of Medicine)

    1992-10-01

    Many reports of fatal GVHD occurring in non-immunocompromised patients after blood transfusion have been published in Japan. One explantation is that transfused lymphocytes were simulated and attack the recipient organs recognized as HLA incompatible. That is so called 'one-way matching'. To reduce the risk of post-transfusion GVHD, one of the most convenient methods is to irradiate the donated blood at an appropriate dose for inactivation of lymphocytes. Because no one knows about the late effect of irradiated blood, it is necessary to make the prospective safety control. (author).

  1. Prostaglandin F2alpha- and FAS-activating antibody-induced regression of the corpus luteum involves caspase-8 and is defective in caspase-3 deficient mice

    Directory of Open Access Journals (Sweden)

    Flavell Richard A

    2003-02-01

    Full Text Available Abstract We recently demonstrated that caspase-3 is important for apoptosis during spontaneous involution of the corpus luteum (CL. These studies tested if prostaglandin F2α (PGF2α or FAS regulated luteal regression, utilize a caspase-3 dependent pathway to execute luteal cell apoptosis, and if the two receptors work via independent or potentially shared intracellular signaling components/pathways to activate caspase-3. Wild-type (WT or caspase-3 deficient female mice, 25–26 days old, were given 10 IU equine chorionic gonadotropin (eCG intraperitoneally (IP followed by 10 IU human chorionic gonadotropin (hCG IP 46 h later to synchronize ovulation. The animals were then injected with IgG (2 micrograms, i.v., the FAS-activating antibody Jo2 (2 micrograms, i.v., or PGF2α (10 micrograms, i.p. at 24 or 48 h post-ovulation. Ovaries from each group were collected 8 h later for assessment of active caspase-3 enzyme and apoptosis (measured by the TUNEL assay in the CL. Regardless of genotype or treatment, CL in ovaries collected from mice injected 24 h after ovulation showed no evidence of active caspase-3 or apoptosis. However, PGF2α or Jo2 at 48 h post-ovulation and collected 8 h later induced caspase-3 activation in 13.2 ± 1.8% and 13.7 ± 2.2 % of the cells, respectively and resulted in 16.35 ± 0.7% (PGF2α and 14.3 ± 2.5% TUNEL-positive cells when compared to 1.48 ± 0.8% of cells CL in IgG treated controls. In contrast, CL in ovaries collected from caspase-3 deficient mice whether treated with PGF2α , Jo2, or control IgG at 48 h post-ovulation showed little evidence of active caspase-3 or apoptosis. CL of WT mice treated with Jo2 at 48 h post-ovulation had an 8-fold increase in the activity of caspase-8, an activator of caspase-3 that is coupled to the FAS death receptor. Somewhat unexpectedly, however, treatment of WT mice with PGF2α at 48 h post-ovulation resulted in a 22-fold increase in caspase-8 activity in the CL, despite the fact

  2. {sup 99m}Tc-HYNIC-annexin V SPECT imaging of acute stroke and its response to neuroprotective therapy with anti-Fas ligand antibody

    Energy Technology Data Exchange (ETDEWEB)

    Blankenberg, Francis G.; Kalinyak, Judy; Cheng, Danye; Goris, Michael L. [Stanford University Hospital, Division of Pediatric Radiology/Department of Radiology, Palo Alto, CA (United States); Liu, Liping; Koike, Maya; Yenari, Midori Anne [University of California San Francisco and San Francisco Veterans Affairs Medical Center, Department of Neurology, San Francisco, CA (United States); Green, Allan; Vanderheyden, Jean-Luc [Theseus Imaging Corporation, Boston, MA (United States); Tong, David C. [Stanford University Hospital, Neurology and Neurological Sciences, Stanford, CA (United States)

    2006-05-15

    The first aim of the study was to determine whether {sup 99m}Tc-HYNIC-annexin V, a marker of cellular stress and apoptosis, can detect ischemic injury in patients with acute stroke. Secondly, we wished to test radiolabeled annexin's ability to monitor therapy in a rodent model of focal ischemic injury. SPECT imaging of patients was performed between 1 and 2 h after intravenous injection of 30 mCi (1,110 MBq) of tracer. Eight MFL4 (anti-FasL) antibody-treated (400 {mu}g i.p. days 0 and 3) and 21 control adult male Sprague-Dawley rats underwent small animal SPECT imaging with 5-10 mCi (185-370 MBq) of tracer, 1 and 6 days after a 2-h intraluminal thread occlusion of the left middle cerebral artery. Two patients with acute stroke had regions of multifocal annexin uptake that correlated with sites of restricted diffusion on MRI. Anti-FasL antibody treatment significantly reduced annexin uptake by 92% with a 60% decrease in the number of caspase-8 staining (apoptotic) neurons on day 1. On day 6, treated animals had an 80% reduction in tracer uptake with a 75% decrease in infarct size as compared with controls. Annexin uptake in controls and treated animals (day 6) linearly correlated with infarct size (r {sup 2}=0.603, p=0.0036) and the number of TUNEL-positive (apoptotic) nuclei (r {sup 2}=0.728, p=0.00084). Annexin imaging shows foci of increased uptake at sites of ischemic injury in patients with acute stroke. Annexin imaging can assess the effects of therapy for ischemic cerebral injury in rats, suggesting its potential as a non-invasive indicator of drug efficacy in future clinical trials. (orig.)

  3. The Drosophila transcription factor Adf-1 (nalyot) regulates dendrite growth by controlling FasII and Staufen expression downstream of CaMKII and neural activity.

    Science.gov (United States)

    Timmerman, Christina; Suppiah, Somu; Gurudatta, Baraka V; Yang, Jingping; Banerjee, Christopher; Sandstrom, David J; Corces, Victor G; Sanyal, Subhabrata

    2013-07-17

    Memory deficits in Drosophila nalyot mutants suggest that the Myb family transcription factor Adf-1 is an important regulator of developmental plasticity in the brain. However, the cellular functions for this transcription factor in neurons or molecular mechanisms by which it regulates plasticity remain unknown. Here, we use in vivo 3D reconstruction of identifiable larval motor neuron dendrites to show that Adf-1 is required cell autonomously for dendritic development and activity-dependent plasticity of motor neurons downstream of CaMKII. Adf-1 inhibition reduces dendrite growth and neuronal excitability, and results in motor deficits and altered transcriptional profiles. Surprisingly, analysis by comparative chromatin immunoprecipitation followed by sequencing (ChIP-Seq) of Adf-1, RNA Polymerase II (Pol II), and histone modifications in Kc cells shows that Adf-1 binding correlates positively with high Pol II-pausing indices and negatively with active chromatin marks such as H3K4me3 and H3K27ac. Consistently, the expression of Adf-1 targets Staufen and Fasciclin II (FasII), identified through larval brain ChIP-Seq for Adf-1, is negatively regulated by Adf-1, and manipulations of these genes predictably modify dendrite growth. Our results imply mechanistic interactions between transcriptional and local translational machinery in neurons as well as conserved neuronal growth mechanisms mediated by cell adhesion molecules, and suggest that CaMKII, Adf-1, FasII, and Staufen influence crucial aspects of dendrite development and plasticity with potential implications for memory formation. Further, our experiments reveal molecular details underlying transcriptional regulation by Adf-1, and indicate active interaction between Adf-1 and epigenetic regulators of gene expression during activity-dependent neuronal plasticity.

  4. Aloe-emodin Induces Apoptosis in Human Liver HL-7702 Cells through Fas Death Pathway and the Mitochondrial Pathway by Generating Reactive Oxygen Species.

    Science.gov (United States)

    Dong, Xiaoxv; Fu, Jing; Yin, Xingbin; Yang, Chunjing; Ni, Jian

    2017-06-01

    Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone) is one of the primary active compounds in total rhubarb anthraquinones isolated from some traditional medicinal plants such as Rheum palmatum L. and Cassia occidentalis, which induce hepatotoxicity in rats. Thus, the aim of this study was to determine the potential cytotoxic effects and the underlying mechanism of aloe-emodin on human normal liver HL-7702 cells. The CCK-8 assays demonstrated that aloe-emodin decreased the viability of HL-7702 cells in a dose-dependent and time-dependent manner. Aloe-emodin induced S and G2/M phase cell cycle arrest in HL-7702 cells. This apoptosis was further investigated by flow cytometry and nuclear morphological changes by DAPI staining, respectively. Moreover, aloe-emodin provoked the production of intracellular reactive oxygen species and the depolarization of mitochondrial membrane potential (MMP). Further studies by western blot indicated that aloe-emodin dose-dependently up-regulated the levels of Fas, p53, p21, Bax/Bcl-2 ratio, and cleaved caspase-3, -8, -9, and subsequent cleavage of poly(ADP-ribose)polymerase (PARP). Taken together, these results suggest that aloe-emodin inhibits cell proliferation of HL-7702 cells and induces cell cycle arrest and caspase-dependent apoptosis via both Fas death pathway and the mitochondrial pathway by generating reactive oxygen species, indicating that aloe-emodin should be taken into account in the risk assessment for human exposure. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Repair of the Posterior Third of the Meniscus During Meniscus Allograft Transplantation: Conventional Inside-Out Repair Versus FasT-Fix All-Inside Repair.

    Science.gov (United States)

    Ahn, Ji Hyun; Kim, Chang Hee; Lee, Sung Hyun

    2016-02-01

    To compare conventional inside-out (IO) repair and all-inside (AI) repair for the posterior third of the meniscus during meniscus allograft transplantation (MAT). Among the 64 enrolled patients, 31 patients underwent MAT with conventional IO repair, and 33 patients underwent MAT with AI repair using the FasT-Fix instrument for the posterior third of the meniscus allograft. All of the patients were retrospectively evaluated through clinical assessment at the last follow-up (54.3 months in the IO group and 55.4 months in the AI group) and through magnetic resonance imaging assessment for meniscal extrusion at 1 year postoperatively. Thirty patients (15 in each group) were evaluated through second-look arthroscopy at 1 year postoperatively. There was no significant difference in the mean Lysholm score (91.3 in the IO group and 92.3 in the AI group; P = .358) or the mean Tegner activity scale (7.1 in each group; P = .885) between the 2 groups. There was no significant difference in the mean meniscal extrusion (2.6 mm in the IO group and 2.8 mm in the AI group; P = .454), relative percentage of extrusion value (25.6% in the IO group and 24.7% in the AI group; P = .721), or meniscal healing on second-look arthroscopy (P = .796) between the 2 groups. The difference in operative time between the 2 groups was found to be statistically significant (169.9 minutes in the IO group and 123.3 minutes in the AI group; P < .001). Our comparative study on the different techniques for posterior repair of meniscus allograft suggested that AI posterior repair using FasT-Fix could be an alternative method to conventional IO repair as it gives a similar postoperative result and requires a shorter operative time. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  6. Microstructural processes in irradiated materials

    Science.gov (United States)

    Byun, Thak Sang; Morgan, Dane; Jiao, Zhijie; Almer, Jonathan; Brown, Donald

    2016-04-01

    These proceedings contain the papers presented at two symposia, the Microstructural Processes in Irradiated Materials (MPIM) and Characterization of Nuclear Reactor Materials and Components with Neutron and Synchrotron Radiation, held in the TMS 2015, 144th Annual Meeting & Exhibition at Walt Disney World, Orlando, Florida, USA on March 15-19, 2015.

  7. Progress in food irradiation: Germany

    Energy Technology Data Exchange (ETDEWEB)

    Diehl, J.F.

    1982-11-01

    The report by the FRG deals with irradiation of foodstuffs, such as potatoes, onions, fish and meats, with gamma and X-rays and with radiochemical changes. Radioresistence is tested for in Salmonella. Wholesomeness studies and mutagenicity tests were carried out showing high losses in vitamins whereas long-lived, free radicals could be measured obtaining to dried material only.

  8. Inhomogeneous microstructural growth by irradiation

    DEFF Research Database (Denmark)

    Krishan, K.; Singh, Bachu Narain; Leffers, Torben

    1985-01-01

    In the present paper we discuss the development of heterogeneous microstructure for uniform irradiation conditions. It is shown that microstructural inhomogeneities on a scale of 0.1 μm can develop purely from kinematic considerations because of the basic structure of the rate equations used...

  9. Solar Spectral Irradiance and Climate

    Science.gov (United States)

    Pilewskie, P.; Woods, T.; Cahalan, R.

    2012-01-01

    Spectrally resolved solar irradiance is recognized as being increasingly important to improving our understanding of the manner in which the Sun influences climate. There is strong empirical evidence linking total solar irradiance to surface temperature trends - even though the Sun has likely made only a small contribution to the last half-century's global temperature anomaly - but the amplitudes cannot be explained by direct solar heating alone. The wavelength and height dependence of solar radiation deposition, for example, ozone absorption in the stratosphere, absorption in the ocean mixed layer, and water vapor absorption in the lower troposphere, contribute to the "top-down" and "bottom-up" mechanisms that have been proposed as possible amplifiers of the solar signal. New observations and models of solar spectral irradiance are needed to study these processes and to quantify their impacts on climate. Some of the most recent observations of solar spectral variability from the mid-ultraviolet to the near-infrared have revealed some unexpected behavior that was not anticipated prior to their measurement, based on an understanding from model reconstructions. The atmospheric response to the observed spectral variability, as quantified in climate model simulations, have revealed similarly surprising and in some cases, conflicting results. This talk will provide an overview on the state of our understanding of the spectrally resolved solar irradiance, its variability over many time scales, potential climate impacts, and finally, a discussion on what is required for improving our understanding of Sun-climate connections, including a look forward to future observations.

  10. Status of irradiation technology development in JMTR

    Energy Technology Data Exchange (ETDEWEB)

    Inaba, Y.; Inoue, S.; Izumo, H.; Kitagishi, S.; Tsuchiya, K.; Saito, T.; Ishitsuka, E. [Japan Atomic Energy Agency (JAEA), Ibaraki (Japan)

    2008-11-15

    Irradiation Engineering Section of the Neutron Irradiation and Testing Reactor Centre was organised to development the new irradiation technology for the application at JMTR re-operation. The new irradiation engineering building was remoulded from the old RI development building, and was started to use from the end of September, 2008. Advanced in-situ instrumentation technology(high temperature multi-paired thermocouple, ceramic sensor,application of optical measurement), {sup 99}Mo production technology by new Mo solution irradiation method,recycling technology on used beryllium reflector, and so on are planned as the development of new irradiation technologies. The development will be also important for the education and training programs through the development of young generation in not only Japan but also Asian countries. In this report, as the status of the development the new irradiation technology, new irradiation engineering building, high temperature multi-paired thermocouple, experiences of optical measurement, recycling technology on used beryllium reflector are introduced.

  11. Status of Irradiation technology development in JMTR

    Energy Technology Data Exchange (ETDEWEB)

    Inaba, Y.; Inoue, S.; Izumo, H.; Kitagishi, S.; Tsuchiya, K.; Saito, T.; Ishitsuka, E. [Japan Atomic Energy Agency, Ibaraki Ken (Japan)

    2008-11-15

    Irradiation Engineering Section of the Neutron Irradiation and Testing Reactor Center was organized to development the new irradiation technology for the application at JMTR re operation. The new irradiation engineering building was remodeled from the old RI development building, and was started to use from the end of September, 2008. Advanced in situ instrumentation technology (high temperature multi paired thermocouple, ceramic sensor, application of optical measurement), {sup 99M}o production technology by new Mo solution irradiation method, recycling technology on used beryllium reflector, and so on are planned as the development of new irradiation technologies. The development will be also important for the education and training programs through the development of young generation in not only Japan but also Asian counties. In this report, as the status of the development the new irradiation technology, new irradiation engineering building, high temperature multi paired thermocouple, experiences of optical measurement, recycling technology on used beryllium reflector are introduced.

  12. The transition of mouse pluripotent stem cells from the naïve to the primed state requires Fas signaling through 3-O sulfated heparan sulfate structures recognized by the HS4C3 antibody

    Energy Technology Data Exchange (ETDEWEB)

    Hirano, Kazumi [Laboratory of Cell Biology, Department of Bioinformatics, Faculty of Engineering, Soka University, 1-236 Tangi-cho, Hachioji, Tokyo 192-8577 (Japan); Van Kuppevelt, Toin H. [Department of Biochemistry, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, 280 P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Nishihara, Shoko, E-mail: shoko@soka.ac.jp [Laboratory of Cell Biology, Department of Bioinformatics, Faculty of Engineering, Soka University, 1-236 Tangi-cho, Hachioji, Tokyo 192-8577 (Japan)

    2013-01-18

    Highlights: ► Fas transcript increases during the transition from the naïve to the primed state. ► 3OST-5 transcript, the HS4C3 epitope synthesis gene, increases during the transition. ► Fas signaling regulates the transition from the naïve to the primed state. ► HS4C3-binding epitope regulates the transition from the naïve to the primed state. ► Fas signaling is regulated by the HS4C3 epitope during the transition. -- Abstract: The characteristics of pluripotent embryonic stem cells of human and mouse are different. The properties of human embryonic stem cells (hESCs) are similar to those of mouse epiblast stem cells (mEpiSCs), which are in a later developmental pluripotency state, the so-called “primed state” compared to mouse embryonic stem cells (mESCs) which are in a naïve state. As a result of the properties of the primed state, hESCs proliferate slowly, cannot survive as single cells, and can only be transfected with genes at low efficiency. Generating hESCs in the naïve state is necessary to overcome these problems and allow their application in regenerative medicine. Therefore, clarifying the mechanism of the transition between the naïve and primed states in pluripotent stem cells is important for the establishment of stable methods of generating naïve state hESCs. However, the signaling pathways which contribute to the transition between the naïve and primed states are still unclear. In this study, we carried out induction from mESCs to mEpiSC-like cells (mEpiSCLCs), and observed an increase in the activation of Fas signaling during the induction. The expression of Fgf5, an epiblast marker, was diminished by inhibition of Fas signaling using the caspase-8 and -3 blocking peptides, IETD and DEVD, respectively. Furthermore, during the induction, we observed increased expression of 3-O sulfated heparan sulfate (HS) structures synthesized by HS 3-O-sulfotransferase (3OST), which are recognized by the HS4C3 antibody (HS4C3-binding epitope

  13. Ultrasonic Transducer Irradiation Test Results

    Energy Technology Data Exchange (ETDEWEB)

    Daw, Joshua [Idaho National Lab. (INL), Idaho Falls, ID (United States); Palmer, Joe [Idaho National Lab. (INL), Idaho Falls, ID (United States); Ramuhalli, Pradeep [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Keller, Paul [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Montgomery, Robert [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Chien, Hual-Te [Argonne National Lab. (ANL), Argonne, IL (United States); Kohse, Gordon [MIT (Massachusetts Inst. of Technology), Cambridge, MA (United States); Tittmann, Bernhard [Pennsylvania State Univ., University Park, PA (United States); Reinhardt, Brian [Pennsylvania State Univ., University Park, PA (United States); Rempe, Joy [Rempe and Associates, Idaho Falls, ID (United States)

    2015-02-01

    Ultrasonic technologies offer the potential for high-accuracy and -resolution in-pile measurement of a range of parameters, including geometry changes, temperature, crack initiation and growth, gas pressure and composition, and microstructural changes. Many Department of Energy-Office of Nuclear Energy (DOE-NE) programs are exploring the use of ultrasonic technologies to provide enhanced sensors for in-pile instrumentation during irradiation testing. For example, the ability of small diameter ultrasonic thermometers (UTs) to provide a temperature profile in candidate metallic and oxide fuel would provide much needed data for validating new fuel performance models. Other ongoing efforts include an ultrasonic technique to detect morphology changes (such as crack initiation and growth) and acoustic techniques to evaluate fission gas composition and pressure. These efforts are limited by the lack of identified ultrasonic transducer materials capable of long term performance under irradiation test conditions. For this reason, the Pennsylvania State University (PSU) was awarded an ATR NSUF project to evaluate the performance of promising magnetostrictive and piezoelectric transducers in the Massachusetts Institute of Technology Research Reactor (MITR) up to a fast fluence of at least 1021 n/cm2. The goal of this research is to characterize and demonstrate magnetostrictive and piezoelectric transducer operation during irradiation, enabling the development of novel radiation-tolerant ultrasonic sensors for use in Material Testing Reactors (MTRs). As such, this test is an instrumented lead test and real-time transducer performance data is collected along with temperature and neutron and gamma flux data. The current work bridges the gap between proven out-of-pile ultrasonic techniques and in-pile deployment of ultrasonic sensors by acquiring the data necessary to demonstrate the performance of ultrasonic transducers. To date, one piezoelectric

  14. Neutron irradiation effects on plasma facing materials

    Science.gov (United States)

    Barabash, V.; Federici, G.; Rödig, M.; Snead, L. L.; Wu, C. H.

    2000-12-01

    This paper reviews the effects of neutron irradiation on thermal and mechanical properties and bulk tritium retention of armour materials (beryllium, tungsten and carbon). For each material, the main properties affected by neutron irradiation are described and the specific tests of neutron irradiated armour materials under thermal shock and disruption conditions are summarized. Based on current knowledge, the expected thermal and structural performance of neutron irradiated armour materials in the ITER plasma facing components are analysed.

  15. Food irradiation for phytosanitary and quarantine treatment

    Science.gov (United States)

    Irradiation at doses less than 1 kGy is an effective phytosanitary measure with minimal adverse effects on the quality of most fresh produce. There are internationally recognized guidelines for the use of irradiation as a phytosanitary measure and for the conduct of trade in irradiated fresh produce...

  16. Enhancing utilization of cowpeas through gamma irradiation ...

    African Journals Online (AJOL)

    Several techniques including the use of gamma irradiation are available to Food Scientists in this respect. Gamma irradiation has the potential to modify the functional properties of cowpeas mainly through its effects on inherent protein and starch components. The effects of γ-irradiation on the functional properties of cowpea ...

  17. CORRELATION BETWEEN PROTEIN-WITH-MOLECULAR-WEIGHT-53 (P53, BURKIT CELL LYMPHOMA 2 (BCL2, AND FAS LIGAND (FASL AND VASCULAR-CELL-ADHESION-MOLECULE-1 (VCAM-1 MRNA EXPRESSION LEVELS IN A PATHOGENESIS STUDY OF PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    Mintareja Teguh

    2014-06-01

    Full Text Available Objective: To determine the role of protein-with-molecular-weight-53 (p53, burkit cell lymphoma 2 (Bcl2, Fas ligand (FasL mRNA, and vascular cell adhesion molecule 1 (VCAM-1, known as the apoptosis-related molecular pathway, in preeclamptic patients. Methods: Observation on the correlation between the mRNA levels of p53, Bcl2 and FasL and VCAM-1 in 31 subjects at 28-42 weeks gestational age was performed in this study using the real time reverse transcriptase-polymerase chain reaction (RT-PCR. Results: The results showed that p53 mRNA increased (>1.2350 ng/μL in the preeclampsia group compared to the normal pregnancy group (p=0.010, Bcl2 mRNA was lower (≤0.9271 ng/μL in the preeclampsia group than the control group (p=0.041. There was also a tendency of increased FasL mRNA expression (>0.5509 ng/μL in the preeclampsia group compared to the normal pregnancy group (p=0.300. The level of VCAM-1 elevated (>890.08 ng/mL in the preeclampsia group compared to the normal pregnancy group (p=0.001. In preeclampsia, the correlation between the Bcl2/p53 ratio and VCAM-1 was r=0.541 (p=0.002, whereas the correlation in normal pregnancy was r=0.099 (p=0.595. Conclusions: There are correlations between the mRNA expression levels of p53 and Bcl2 as an intrinsic pathway of apoptosis along with the VCAM-1 levels in the incidence of preeclampsia. However, no correlation is found between FasL mRNA expression and the incidence of preeclampsia.

  18. Irradiation-induced hardening and softening of CLAM steel under Fe ion irradiation

    Science.gov (United States)

    Li, Qingshan; Shen, Yinzhong; Huang, Xi; Xu, Zhiqiang; Zhu, Jun

    2017-11-01

    The irradiation-induced hardening and softening of CLAM steel irradiated with 3.5 MeV Fe13+ ions at temperatures of 300 °C and 550 °C were investigated by nanoindentation tests in combination with microstructures. Irradiation- induced hardening occurred in the steel irradiated at 300 °C to doses of 0.46 dpa, 0.94 dpa, and 2.79 dpa. The hardening occurred at 300 °C is mainly attributed to the formation of irradiation-produced dislocation loops and a network of tangled dislocations in the irradiated steel samples. Significant hardening was found in the steel irradiated at 550 °C to 0.38 dpa. On the contrary, irradiation-induced softening occurred in the steel irradiated at 550 °C to both 0.76 dpa and 2.75 dpa. Irradiation-produced dislocation loops are not dominant effect on the irradiation hardening of the steel samples irradiated at 550 °C. The hardening and softening of the irradiated steel were explained in terms of the irradiation-produced defects and recovery process occurred during the irradiation.

  19. Development of data base on food irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Hitoshi; Kume, Tamikazu; Hashimoto, Shoji [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment; Izumi, Fumio

    1995-12-01

    For the exact understanding on food irradiation in Japan, it is important to provide information of food irradiation to consumers, industries and government offices. However, many of information on food irradiation are only restricted in a few experts or institutes relating to this field. For this reason, data base of food irradiation has been completed together with the systems necessary for input the data using computer. In this data base, about 630 data with full reports were inputted in computer in the field of wholesomeness studies, irradiation effects on food, radiation engineering, detection methods of irradiated food and Q and A of food irradiation for easy understanding. Many of these data are inputted by Japanese language. Some English reports on wholesomeness studies are also included which were mainly obtained from international projects of food irradiation. Many of data on food irradiation are responsible in the fields of food science, dietetics, microbiology, radiation biology, molecular biology, medical science, agricultural science, radiation chemistry, radiation engineering and so on. Data base of food irradiation contains many useful data which can apply to many other fields of radiation processing not only on food irradiation but also on sterilization of medical equipments, upgrading of agricultural wastes and others. (author).

  20. Food irradiation development in Pakistan

    Science.gov (United States)

    Khan, I.

    The large scale trials were held to extend the storage life of potatoes, onions and dry fruits by gamma radiation. It was concluded that radiation preservation of potatoes and onions was much cheaper as compared to conventional methods. A dose of 1 kGy can control the insects in dry fruits and nuts. The consumers' acceptability and market testing performed during the last four years are also conducive to the commercialization of the technology in this country. The Government of Pakistan has accorded clearance for the irradiation of some food items like potatoes, onions, garlic and spices for human consumption. The Pakistan Radiation Services (PARAS), the commercial irradiator (200 Kci) at Lahore, has already started functioning in April, 1987. It is planned to start large scale sterilization of spices by gamma radiation in PARAS shortly.

  1. [The intraoperative irradiation of tumors].

    Science.gov (United States)

    Zyrianov, B N; Chakhlov, V L; Khodkevich, B S; Anisenia, I I

    1992-01-01

    Intraoperative irradiation of tumor was performed in 40 patients with cancer of the lung, stomach, breast, bone and soft tissues. It included irradiation of the bed of tumor removed. Fast electron beam was produced by a small betatron (collimator size--5 x 6 cm and 8 x 12 cm) installed in the operating room. Radiation was given to a single or to multiple fields in a single dose of 10-20 Gy to each field. Location of the radioactive source in the operating room proved technically, economically and medically advantageous since it was cheaper, assured a shorter period of the treatment and delivered from patient transportation to a radiotherapy department and ensuing complications. The procedure did not interfere with postoperative period. The efficacy of the treatment modality will be evaluated as soon as sufficient end results have been obtained.

  2. Spectrophotometric analysis of irradiated spices

    Energy Technology Data Exchange (ETDEWEB)

    Josimovic, L.; Cudina, I.

    1987-01-01

    Seven different spices (thyme, cinnamon, coriander, caraway, pimento, paprika, black pepper) were treated by gamma radiation at an absorbed dose of 10 kGy, and the effect on chemical quality was determined. The effects of this dose were assessed by spectrophotometric analysis of some water-soluble constituents of spices (carbohydrates; carbonyl compounds) and on the content of water-insoluble steam-volatile oils. The colour of paprika and the content of piperine in pepper held in different packaging materials were measured in unirradiated and irradiated samples as a function of storage time. In all cases irradiation does not bring about any distinct qualitative or quantitative chemical changes based on spectrophotometric analysis of spice extracts.

  3. Study of rice. gamma. -irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lien, J.J.; Chau, R.S.; Chen, S.C.; Chu, S.L.; Fu, Y.K.; Fang, C.K.; Fu, Y.H.

    1981-03-01

    The purpose of this experiment was to investigate whether the /sup 60/Co gamma-irradiated milled rice packed in economic and practical sealed bags could be preserved in common granaries in Taiwan for more than one year rather than slightly over one month without quality deterioration. As a result of this experiment we found that during the preservation of over a period of 18 months, the contents, such as moisture, ash, protein and fiber, of Tainan-5 Bon-Lai (Japonica Type) rice irradiated with 20 and 40 krad doses were quite stable, whereas reducing sugar showed slight fluctuations but did not vary significantly either. The fat, vitamin B/sub 1/ and niacin contents were found being reduced, while the increase in fatty acid content was an inevitable phenomenon along with the proceeding of the preservation.

  4. Future Satellite Observations of Solar Irradiance

    Science.gov (United States)

    Cahalan, R. F.; Rottman, G.; Woods, T.; Lawrence, G.; Harder, J.; McClintock, W.; Kopp, G.

    2003-01-01

    Required solar irradiance measurements for climate studies include those now being made by the Total Irradiance Monitor (TIM) and the Spectral Irradiance Monitor (SIM) onboard the SORCE satellite, part of the Earth Observing System fleet of NASA satellites. Equivalent or better measures of Total Solar Irradiance (TSI) and Spectral Solar Irradiance (SSI, 200 to 2000 nm) are planned for the post-2010 satellites of the National Polar-orbiting Operational Environmental Satellite System ("OESS). The design life of SORCE is 5 years, so a "Solar Irradiance Gap Filler" EOS mission is being planned for launch in the 2007 time frame, to include the same TSI and SSI measurements. Besides avoiding any gap, overlap of the data sources is also necessary for determination of possible multi-decadal trends in solar irradiance. We discuss these requirements and the impacts of data gaps, and data overlaps, that may occur in the monitoring of the critical solar radiative forcing.

  5. Microstructural processes in irradiated materials

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Thak Sang; Morgan, Dane; Jiao, Zhijie; Almer, Jonathan; Brown, Donald

    2016-04-01

    This is an editorial article (preface) for the publication of symposium papers in the Journal of Nuclear materials: These proceedings contain the papers presented at two symposia, the Microstructural Processes in Irradiated Materials (MPIM) and Characterization of Nuclear Reactor Materials and Components with Neutron and Synchrotron Radiation, held in the TMS 2015, 144th Annual Meeting & Exhibition at Walt Disney World, Orlando, Florida, USA on March 15–19, 2015.

  6. Spectroscopic analysis of irradiated erythrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Selim, Nabila S. [Biophysics Lab, Radiation Physics Department, National Center for Radiation Research and Technology (NCRRT), AEA, P.O. Box 29, Madinat Nasr, Cairo (Egypt); Desouky, Omar S., E-mail: omardesouky@yahoo.com [Biophysics Lab, Radiation Physics Department, National Center for Radiation Research and Technology (NCRRT), AEA, P.O. Box 29, Madinat Nasr, Cairo (Egypt); Ismail, Nagla M.; Dakrory, Amira Z. [Physics Department, Faculty of Girls for Arts, Sciences and Education, Ain Shams University, Cairo (Egypt)

    2011-12-15

    The aim of the present work is to study the effect of gamma radiation on the lipid part of the erythrocyte membrane, and to test the efficiency of lipoic acid as a radioprotector. This effect was evaluated using electron paramagnetic resonance (EPR), and Fourier transform infrared (FT-IR) spectroscopy. The results showed an increase in the number of spin density by 14%, 22% and 65% after exposure to 25, 50 and 100 Gy respectively; whereas there was a decline in the obtained density after incubation with lipoic acid by a factor of approximately 32%. The FT-IR spectra of the irradiated erythrocytes samples showed a marked decrease in the intensity of all characteristic peaks, which increased as the irradiation dose increased. The second-derivative of these spectra, allow the conformationally sensitive membrane acyl chain methylene stretching modes to be separated from the protein (mostly hemoglobin) vibrations that dominate the spectra of intact cells. The 2850 cm{sup -1} band showed changes in the band shape and position after exposure to 50 and 100 Gy. Therefore it can be concluded that the band at 2850 cm{sup -1} only is useful in monitoring the radiation effect of the lipids cell membrane intact cells. - Highlights: > Effect of {gamma} radiation on erythrocyte membrane was studied using EPR and FT-IR. > Efficiency of {alpha}-lipoic acid as radioprotector was tested. > Lipoic acid diminished the free radicals number after gamma irradiation by 32%. > FT-IR spectra of the irradiated erythrocyte showed a decrease in their intensity. > Lipoic acid enhances the membrane to resist the action of gamma radiation.

  7. Food Preservation by Irradiation (Rev.)

    Energy Technology Data Exchange (ETDEWEB)

    Urrows, Grace M.

    1968-01-01

    Up to 30% of food harvests are lost in some parts of the world because of animal pests and microorganisms. Nuclear techniques can help reduce and extend the shelf life of these foods. Around 55 countries now have food irradiation programs. The use of radiation is the most recent step in man's attempts to preserve some of his harvest for the lean part of the year.

  8. Triple ion beam irradiation facility

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, M.B.; Allen, W.R.; Buhl, R.A.; Packan, N.H.; Cook, S.W.; Mansur, L.K.

    1988-12-01

    A unique ion irradiation facility consisting of three accelerators is described. The accelerators can be operated simultaneously to deliver three ion beams on one target sample. The energy ranges of the ions are 50 to 400 keV, 200 keV to 2.5 MeV, and 1.0 to 5.0 MeV. Three different ions in the appropriate mass range can be simultaneously implanted to the same depth in a target specimen as large as 100 mm/sup 2/ in area. Typical depth ranges are 0.1 to 1.0 ..mu..m. The X-Y profiles of all three ion beams are measured by a system of miniature Faraday cups. The low-voltage accelerator can periodically ramp the ion beam energy during the implantation. Three different types of target chambers are in use at this facility. The triple-beam high-vacuum chamber can hold nine transmission electron microscopy specimens at elevated temperature during a irradiation by the three simultaneous beams. A second high-vacuum chamber on the medium-voltage accelerator beamline houses a low- and high-temperature translator and a two-axis goniometer for ion channeling measurements. The third chamber on the high-energy beamline can be gas-filled for special stressed specimen irradiations. Special applications for the surface modification of materials with this facility are described. Appendixes containing operating procedures are also included. 18 refs., 27 figs., 1 tab.

  9. Implant therapy in irradiated patients.

    Science.gov (United States)

    Sammartino, Gilberto; Marenzi, Gaetano; Cioffi, Iacopo; Teté, Stefano; Mortellaro, Carmen

    2011-03-01

    In this multicenter study, submerged implants were prospectively followed to evaluate their long-term prognosis in irradiated patients. In a total of 77 patients treated for oral or neck cancer, 188 implants were consecutively placed. After a healing period, the successfully integrated implants were restored with 69 removable and 38 fixed restorations. The implants cumulative survival and success rates were evaluated over a period of at least 36 months. In addition, cumulative success rates were calculated for implant subgroups divided per implant site (mandible or maxilla), radiation dosage, and the time interval between the last irradiation and implant placement. During the healing period, 20 implants did not successfully integrate, whereas 168 implants were classified as success (including both survival and success rates). The analysis of implant subgroups showed slightly more favorable cumulative success rate for mandibular implants (98.4%) compared with maxillary implants (57.1%) and clearly better success rate for a radiation dosage minor of 50-Gy doses. A time greater than 12 months as interval between last irradiation and implant placement seems not to promote better clinical results.

  10. Status of Post Irradiation Examination of FCAB and FCAT Irradiation Capsules

    Energy Technology Data Exchange (ETDEWEB)

    Field, Kevin G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Fuel Cycle Research and Development (FCRD); Yamamoto, Yukinori [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Fuel Cycle Research and Development (FCRD); Howard, Richard H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Fuel Cycle Research and Development (FCRD)

    2016-09-29

    A series of irradiation programs are ongoing to address the need for determining the radiation tolerance of FeCrAl alloys. These irradiation programs, deemed the FCAT and FCAB irradiation programs, use the High Flux Isotope Reactor (HFIR) to irradiate second generation wrought FeCrAl alloys and early-generation powder-metallurgy (PM) oxide dispersion-strengthened (ODS) FeCrAl alloys. Irradiations have been or are being performed at temperatures of 200°C, 330°C, and 550°C from doses of 1.8 dpa up to 16 dpa. Preliminary post-irradiation examination (PIE) on low dose (<2 dpa) irradiation capsules of tensile specimens has been performed. Analysis of co-irradiated SiC thermometry have shown reasonable matching between the nominal irradiation temperatures and the target irradiation temperatures. Room temperature tensile tests have shown typical radiation-induced hardening and embrittlement at irradiations of 200°C and 330°C, but a propensity for softening when irradiated to 550°C for the wrought alloys. The PM-ODS FeCrAl specimens showed less hardening compared to the wrought alloys. Future PIE includes high temperature tensile tests on the low dose irradiation capsules as well as the determination of reference fracture toughness transition temperature, To, in alloys irradiated to 7 dpa and higher.

  11. Effect of irradiation on the Porphyromonas gingivalis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chang Hee; Kim, Gyu Tae; Choi, Yong Suk; Hwang, Eui Hwan [School of Dentistry, Kyung Hee University, Seoul (Korea, Republic of)

    2008-03-15

    The aim of this study was to observe a direct effect of irradiation on the periodontopathic Porphyromonas gingivalis (P. gingivalis). P. gingivalis 2561 was exposed to irradiation with a single absorbed dose of 10, 20, 30, and 40 Gy. Changes in viability and antibiotic sensitivity, morphology, transcription, and protein profile of the bacterium after irradiation were examined by pour plating method, disc diffusion method, transmission electron microscopy, RT-PCR, and immunoblot, respectively. Viability of irradiated P. gingivalis drastically reduced as irradiation dose was increased. Irradiated P. gingivalis was found to have become more sensitive to antibiotics as radiation dose was increased. With observation under the transmission electron microscope, the number of morphologically abnormal cells was increased with increasing of irradiation dose. In RT-PCR, decrease in the expression of fim A and sod was observed in irradiated P. gingivalis. In immunoblot, change of profile in irradiated P. gingivalis was found in a number of proteins including 43-kDa fimbrillin. These results suggest that irradiation may affect the cell integrity of P. gingivalis, which is manifested by the change in cell morphology and antibiotic sensitivity, affecting viability of the bacterium.

  12. Development of detection methods for irradiated foods

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jae Seung; Kim, Chong Ki; Lee, Hae Jung [Korea Atomic Energy Research Insitiute, Taejon (Korea, Republic of); Kim, Kyong Su [Chosun University, Kwangju (Korea, Republic of)

    1999-04-01

    To identify irradiated foods, studies have been carried out with electron spin resonance (ESR) spectroscopy on bone containing foods, such as chicken, pork, and beef. The intensity of the signal induced in bones increased linearly with irradiation doses in the range of 1.0 kGy to 5.0 kGy, and it was possible to distinguish between samples given low and high doses of irradiation. The signal stability for 6 weeks made them ideal for the quick and easy identification of irradiated meats. The analysis of DNA damage made on single cells by agarose gel electrophoresis (DNA 'comet assay') can be used to detect irradiated food. All the samples irradiated with over 0.3 kGy were identified to detect post-irradiation by the tail length of their comets. Irradiated samples showed comets with long tails, and the tail length of the comets increased with the dose, while unirradiated samples showed no or very short tails. As a result of the above experiment, the DNA 'comet assay' might be applied to the detection of irradiated grains as a simple, low-cost and rapid screening test. When fats are irradiated, hydrocarbons contained one or two fewer carbon atoms are formed from the parent fatty acids. The major hydrocarbons in irradiated beef, pork and chicken were 1,7-hexadecadiene and 8-heptadecene originating from leic acid. 1,7 hexadecadiene was the highest amount in irradiated beef, pork and chicken. Eight kinds of hydrocarbons were identified from irradiated chicken, among which 1,7-hexadecadiene and 8-heptadecen were detected as major compounds. The concentration of radiation-induced hydrocarbons was relatively constant during 16 weeks.

  13. Effect of irradiation on the streptococcus mutans

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Ki Dong; Kim, Gyu Tae; Choi, Yong Suk; Hwang, Eui Hwan [Kyung Hee Univ., Seoul (Korea, Republic of)

    2007-03-15

    To observe direct effect of irradiation on cariogenic Streptococcus mutans. S. mutans GS5 was exposed to irradiation with a single absorbed dose of 10, 20, 30, and 40 Gy. Viability and changes in antibiotic sensitivity, morphology, transcription of virulence factors, and protein profile of bacterium after irradiation were examined by pour plate, disc diffusion method, Transmission electron microscopy. RT-PCR, and SDS-PAGE, respectively. After irradiation with 10 and 20 Gy, viability of S. mutans was reduced. Further increase in irradiation dose, however, did not affect the viability of the remaining cells of S. mutans. Irradiated S. mutans was found to have become sensitive to antibiotics. In particular, the bacterium irradiated with 40 Gy increased its susceptibility to cefotaxime, penicillin, and tetracycline. Under the transmission electron microscope, number of morphologically abnormal cells was increased as the irradiation dose was increased. S. mutans irradiated with 10 Gy revealed a change in the cell wall and cell membrane. As irradiation dose was increased. a higher number of cells showed thickened cell wall and cell membrane and lysis, and appearance of ghost cells was noticeable. In RT-PCR, no difference was detected in expression of gtfB and spaP between cells with and without irradiation of 40 Gy. In SDS-PAGE, proteins with higher molecular masses were gradually diminished as irradiation dose was increased. These results suggest that irradiation affects the cell integrity of S. mutans, as observed by SDS-PAGE, and as manifested by the change in cell morphology, antibiotic sensitivity, and eventually viability of the bacterium.

  14. Tratamiento contable de las transacciones separadas en las combinaciones de negocios. Proceso armonizador de la normativa contable internacional (IFRS y americana (FAS

    Directory of Open Access Journals (Sweden)

    Montserrat Manzaneque Lizano

    2013-01-01

    Full Text Available Los cambios introducidos en la FAS 141(R (2007 americana y en la IFRS 3 (R (2008, con el fin de armonizar los aspectos contables de las operaciones referentes a la combinación de negocios, han puesto de manifiesto la existencia de determinadas transacciones que no forman parte de la propia combinación y a las que se denomina transacciones separadas, cuya delimitación de la combinación de negocios queda dispersa en ambas normas, por lo que en ocasiones resulta poco clarificador. Así, este trabajo pretende facilitar al lector la comprensión de su tratamiento contable abordando la problemática de identificar las transacciones que se producen, y las que no, como consecuencia de la combinación de negocios, el tratamiento contable de esta disyuntiva y su efecto sobre el reconocimiento y valoración del fondo de comercio (cuenta de crédito mercantil.

  15. Essential complicity of perforin-granzyme and FAS-L mechanisms to achieve tumor rejection following treatment with anti-CD137 mAb.

    Science.gov (United States)

    Morales-Kastresana, Aizea; Catalán, Elena; Hervás-Stubbs, Sandra; Palazón, Asis; Azpilikueta, Arantza; Bolaños, Elixabet; Anel, Alberto; Pardo, Julián; Melero, Ignacio

    2013-01-01

    Treatment with agonist anti-CD137 (4-1BB) immunostimulatory monoclonal antibodies elicits complete tumor regressions in a number of transplanted hematological and solid malignancies in mice. Rejection is mainly dependent on cytotoxic T lymphocytes (CTL) and IFNγ, although a role for NK cells and dendritic cells has been observed in some tumor models. Rejection of EG7-derived thymomas has been shown to be CTL-dependent but not NK-dependent. In this therapeutic setting, we show that both the perforin-granzyme and FasL effector systems are readily expressed by CD8(+) T lymphocytes infiltrating the EG7 lymphomas which are undergoing rejection. Using knock-out mice, we demonstrate that both effector cytolytic systems are involved in the execution of complete immune rejections against EG7 established tumors. In accordance, EG7 tumor cells were susceptible in vitro to both killing mechanisms acting in a synergistic fashion. CD137-elicited rejection of EG7-derived tumors involves the interplay of at least two final effector cytolytic mechanisms that act in cooperation.

  16. Interferon-β therapy specifically reduces pathogenic memory B cells in multiple sclerosis patients by inducing a FAS-mediated apoptosis.

    Science.gov (United States)

    Rizzo, Fabiana; Giacomini, Elena; Mechelli, Rosella; Buscarinu, Maria Chiara; Salvetti, Marco; Severa, Martina; Coccia, Eliana Marina

    2016-10-01

    Growing evidences put B lymphocytes on a central stage in multiple sclerosis (MS) immunopathology. While investigating the effects of interferon-β (IFN-β) therapy, one of the most used first-line disease-modifying drugs for the treatment of relapsing-remitting MS, in circulating B-cell sub-populations, we found a specific and marked decrease of CD27+ memory B cells. Interestingly, memory B cells are considered a population with a great disease-driving relevance in MS and resulted to be also target of B-cell depleting therapies. In addition, Epstein-Barr virus (EBV), associated with MS etiopathogenesis, harbors in this cell type and an IFN-β-induced reduction of the memory B-cell compartment, in turn, resulted in a decreased expression of the EBV gene latent membrane protein 2A in treated patients. We found that in vivo IFN-β therapy specifically and highly induced apoptosis in memory B cells, in accordance with a strong increase of the apoptotic markers Annexin-V and active caspase-3, via a mechanism requiring the FAS-receptor/TACI (transmembrane activator and CAML interactor) signaling. Thus, efficacy of IFN-β therapy in MS may rely not only on its recognized anti-inflammatory activities but also on the specific depletion of memory B cells, considered to be a pathogenic cell subset, reducing their inflammatory impact in target organs.

  17. Charge Transport in Non-Irradiated and Irradiated Silicon Diodes

    CERN Document Server

    Leroy, C; Casse, G L; Glaser, M; Grigoriev, E; Lemeilleur, F

    1999-01-01

    A model describing the transport of charge carriers generated in silicon detectors (standard planar float zone and MESA diodes) by ionizing particles is presented. The current pulse response induced by $\\alpha$ and $\\beta$ particles in non-irradiated detectors and detectors irradiated up to fluences $\\Phi \\approx 3 \\cdot 10^{14}$ particles/cm$^2$ is reproduced through this model: i) by adding a small n-type region 15 $\\mu$m deep on the $p^+$ side for the standard planar float zone detectors at fluences beyond the n to p-type inversion and ii) for the MESA detectors, by considering one dead layer 14 $\\mu$m deep (observed experimentally) on each side, and introducing a second (delayed) component. For both types of detectors, the model gives mobilities decreasing linearily up to fluences of about $5 \\cdot 10^{13}$ particles/cm$^2$ and converging, beyond, to saturation values of about 1000 cm$^2$/Vs and 455 cm$^2$/Vs for electrons and holes, respectively. At a fluence $\\Phi \\approx 10^{14}$ particles/cm$^2$, char...

  18. Thermal analysis applied to irradiated propolis

    Science.gov (United States)

    Matsuda, Andrea Harumi; Machado, Luci Brocardo; del Mastro, Nélida Lucia

    2002-03-01

    Propolis is a resinous hive product, collected by bees. Raw propolis requires a decontamination procedure and irradiation appears as a promising technique for this purpose. The valuable properties of propolis for food and pharmaceutical industries have led to increasing interest in its technological behavior. Thermal analysis is a chemical analysis that gives information about changes on heating of great importance for technological applications. Ground propolis samples were 60Co gamma irradiated with 0 and 10 kGy. Thermogravimetry curves shown a similar multi-stage decomposition pattern for both irradiated and unirradiated samples up to 600°C. Similarly, through differential scanning calorimetry , a coincidence of melting point of irradiated and unirradiated samples was found. The results suggest that the irradiation process do not interfere on the thermal properties of propolis when irradiated up to 10 kGy.

  19. Thermal analysis applied to irradiated propolis

    Energy Technology Data Exchange (ETDEWEB)

    Matsuda, Andrea Harumi; Machado, Luci Brocardo; Mastro, N.L. del E-mail: nelida@usp.br

    2002-03-01

    Propolis is a resinous hive product, collected by bees. Raw propolis requires a decontamination procedure and irradiation appears as a promising technique for this purpose. The valuable properties of propolis for food and pharmaceutical industries have led to increasing interest in its technological behavior. Thermal analysis is a chemical analysis that gives information about changes on heating of great importance for technological applications. Ground propolis samples were {sup 60}Co gamma irradiated with 0 and 10 kGy. Thermogravimetry curves shown a similar multi-stage decomposition pattern for both irradiated and unirradiated samples up to 600 deg. C. Similarly, through differential scanning calorimetry , a coincidence of melting point of irradiated and unirradiated samples was found. The results suggest that the irradiation process do not interfere on the thermal properties of propolis when irradiated up to 10 kGy.

  20. Irradiation preservation of seafood: Literature review

    Energy Technology Data Exchange (ETDEWEB)

    Molton, P.M.

    1987-10-01

    The application of gamma-irradiation for extending the shelf life of seafood has been of interest for many years. This report reviews a number of studies on seafood irradiation conducted over the past several years. Topics covered include seafood irradiation techniques and dosages, species applicability and differences, the effects of packaging on seafood preservation, and changes in organoleptic acceptability as a result of irradiation. Particular attention is given to radiation effects (likely and unlikely) of concern to the public. These include the potential for generation of toxic chemical products, botulinum toxin production, and other health concerns. No scientifically defensible evidence of any kind was found for any harmful effect of irradiation of seafoods at the doses being considered (less than 300 krad), and all indications are that irradiation is an acceptable and needed additional tool for seafood preservation. 49 refs., 14 figs., 14 tabs.

  1. Lymphangioma secondary to irradiation after mastectomy

    OpenAIRE

    Oliveti,Aline; Biasi, Tatiana Basso; Funchal, Gabriella Di Giunta

    2017-01-01

    Abstract Lymphangioma is a rare benign disease of the lymphatic vessels. Typically, they are primary conditions but may be acquired secondarily, such as those caused by irradiation during radiotherapy for the treatment of breast cancer. The local lymphatic obstruction provoked by irradiation causes the appearance of asymptomatic hyaline vesicles on the irradiated skin. The present report describes a 78-year-old female patient, who initially presented hyaline vesicles that progressed into mult...

  2. Food Irradiation Update and Cost Analysis

    Science.gov (United States)

    1991-11-01

    spices in the United States. In Japan, 10,000 tons of potatoes are irradiated each year to prevent sprouting (chemical treatments to inhibit potato... irradiation can extend the shelf life of refrigerated products, which reduces losses due to spoilage. It can also greatly reduce the pathogens in foods...AD-A273 506 ýil il lit i i1 ii , TECHNICAL REPORT AD NATICK /TR-92 / 002 FOOD IRRADIATION UPDATE-,. .•0 , AND COST ANALYSIS f. .• By Robert T

  3. Resistance of acrylic vessel to gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Carneiro, Andre Cavalcanti; Menezes, Maria Angela de B.C.; Pereira, Marcio Tadeu; Rocha, Nirlando Antonio; Vilela, Jefferson Jose, E-mail: andreccarneiro@gmail.com, E-mail: menezes@cdtn.br, E-mail: mtp@cdtn.br, E-mail: nar@cdtn.br, E-mail: jjv@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Braga, Mario Roberto Martins S.S., E-mail: mariomartins@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Programa de Pos-Graduacao em Ciencias e Tecnicas Nucleares

    2013-07-01

    This paper describes the preliminary studies made in acrylic material in order to verify the effects of radiolysis in acrylic recipients in which the uranium ore standards are conditioned and check if the material is able to keep the {sup 222}Rn inside the vessel. The preliminary results after gamma irradiation of two kinds of recipients indicate no differences between the vessels irradiated and the ones no irradiated, related to color changes and tension resistance. (author)

  4. Squamous cell carcinoma in situ after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kambara, Takeshi; Nishiyama, Takafumi; Yamada, Rie; Nagatani, Tetsuo; Nakajima, Hiroshi [Yokohama City Univ. (Japan). School of Medicine; Sugiyama, Asami

    1997-12-31

    We report two cases with Squamous Cell Carcinoma (SCC) in situ caused by irradiation to hand eczemas, resistant to any topical therapies. Both of our cases clinically show palmer sclerosis and flexor restriction of the fingers, compatible to chronic radiation dermatitis. Although SCC arising in chronic radiation dermatitis is usually developed ten to twenty years after irradiation, in our cases SCC were found more than forty years after irradiation. (author)

  5. Association of genetic polymorphism -670A>G in the Fas gene and serum markers AST platelet ratio index, AST/ALT with significant fibrosis and cirrhosis in chronic hepatitis C.

    Science.gov (United States)

    Deghady, Akram; Abdou, Alaa; El-Neanaey, Wafaa Ahmed; Diab, Iman

    2012-06-01

    This study was carried out to evaluate the association of genetic polymorphism -670A>G in the promoter of Fas gene as well as serum biomarkers aspartate aminotransferase (AST) platelet ratio index (APRI) and AST/alanine aminotransferase (ALT) with significant fibrosis and cirrhosis in chronic hepatitis C patients. Seventy-nine patients with chronic hepatitis C in addition to 80 age- and sex-matched healthy controls were evaluated for genetic polymorphism -670A>G of Fas gene by polymerase chain reaction-restriction fragment length polymorphism and serum biomarkers APRI and AST/ALT in relation to significant fibrosis and cirrhosis diagnosed by liver biopsy. Genetic polymorphism -670A>G in Fas gene was associated with significant liver fibrosis and cirrhosis. Heterozygous mutation was found in 11.4% of patients and 10% of controls, while homozygous mutation was found only in 7.6% of patients. Odds ratio (OR) was statistically not significant (OR=1.93, 95% confidence interval=0.76-4.92). Mean values of APRI and AST/ALT were significantly higher in patients with (F3-F4) compared with those with (F0-F2). (p-value polymorphism -670A>G of Fas gene was associated with significant fibrosis and cirrhosis in chronic hepatitis C patients. APRI and AST/ALT are independent predictors for significant fibrosis. APRI showed a better sensitivity than AST/ALT for prediction of significant fibrosis. Moreover, APRI can be used as an index to exclude liver cirrhosis without performing liver biopsy.

  6. Acclimation to a dynamic irradiance regime changes excessive irradiance sensitivity of Emiliania huxleyi and Thalassiosira weissflogii

    NARCIS (Netherlands)

    van de Poll, Willem H.; Visser, Ronald J. W.; Buma, Anita G. J.

    Effects of fluctuating irradiance regimes on excessive photosynthetically active radiation (PAR) and ultraviolet (UV) radiation sensitivity were assessed for Emiliania huxleyi (Lohman) and Thalassiosira weissflogii (Grunow) Fryxell and Hasle. Cultures acclimated to low irradiance were subjected to

  7. Tolerance of edible flowers to gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Koike, Amanda C.R.; Araujo, Michel M.; Costa, Helbert S.F.; Almeida, Mariana C.; Villavicencio, Anna Lucia C.H., E-mail: ackoike@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP) Sao Paulo, SP (Brazil)

    2011-07-01

    People have been eating flowers and using them in culinary creations for hundreds of years. Edible flowers are increasingly being used in meals as an ingredient in salads or garnish, entrees, drinks and desserts. The irradiation process is an alternative method that can be used in disinfestation of food and flowers, using doses that do not damage the product. The sensitivity of flowers to irradiation varies from species to species. In the present research was irradiated with doses up to 1 kGy some edible flowers to examine their physical tolerance to gamma-rays. Furthermore, high doses gamma irradiation causes petal withering, browning process and injury in edible flowers. (author)

  8. Detection of hydrocarbons in irradiated foods

    Energy Technology Data Exchange (ETDEWEB)

    Miyahara, Makoto; Maitani, Tamio [National Inst. of Health Sciences, Tokyo (Japan); Saito, Akiko; Kamimura, Tomomi; Nagasawa, Taeko [Kitasato Univ., Sagamihara, Kanagawa (Japan). School of Allied Health Sciences; Kobayashi, Yasuo; Ito, Hitoshi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Establishment

    2003-06-01

    The hydrocarbon method for the detection of irradiated foods is now recognized as the international technique. This method is based on radiolysis of fatty acids in food to give hydrocarbons. In order to expand this technique's application, ten foods (butter, cheese, chicken, pork, beef, tuna, dry shrimp, avocado, papaya, and mango) were irradiated in the range from 0.5 to 10 kGy and the hydrocarbons in them were detected. Recoveries of the hydrocarbons from most foods were acceptable (38-128%). Some hydrocarbons were found in non-irradiated foods, particularly, in butter, cheese, tuna, and shrimp. Seven irradiated foods, butter, cheese, chicken, beef, pork, tuna, dry shrimp, and avocado were detectable at their practical doses by measuring the appropriate marker hydrocarbons. In most case, marker hydrocarbon will be 1,7-hexadecadiene. However, the marker hydrocarbons produced only in irradiated foods varied from food to food; therefore, it is necessary to check a specific irradiated food for marker hydrocarbons. On the other hand, two irradiated foods (papaya and mango which were irradiated at their practical doses) were difficult to distinguish from non-irradiated foods using this method. (author)

  9. Free radical kinetics on irradiated fennel

    Science.gov (United States)

    Yamaoki, Rumi; Kimura, Shojiro; Ohta, Masatoshi

    2008-09-01

    Herein, an electron spin resonance study on the behavior of organic radicals in fennel before and after irradiation is reported. The spectrum of irradiated fennel composed of the spectrum component derived from the un-irradiated sample (near g=2.005) and the spectra components derived from carbohydrates. The time decay of intensity spectral components was well explained by first-order kinetics with a variety of rate constants. Especially, the signal at near g=2.02 ascribed to stable cellulose-derivative components is expected to be a good indicator in the identification of irradiated plant samples.

  10. Využití solární energie pro vytápění a větrání – solární fasády

    OpenAIRE

    Mazáč, Ondřej

    2008-01-01

    Cílem bakalářské práce „Využití solární energie pro vytápění a větrání – solární fasády“ je popis v současnosti používaných typů solárních fasád, posouzení jejich technických parametrů a zhodnocení teoretického popisu na vybrané budově. První část je zaměřena na popis slunečního záření, možnosti využití v solárním systému a vysvětlení jeho principu. V druhé části je popsáno rozdělení solárních fasád z hlediska jejich základních kritérií. Třetí část obsahuje konkrétní zhodnocení budov, na kter...

  11. Correlation of inducible nitric oxide synthase (iNOS) inhibition with TNF-α, caspase-1, FasL and TLR-3 in pathogenesis of rabies in mouse model.

    Science.gov (United States)

    Madhu, B P; Singh, K P; Saminathan, M; Singh, R; Tiwari, A K; Manjunatha, V; Harish, C; Manjunathareddy, G B

    2016-02-01

    The role of inflammatory cytokines such as interleukin-1α/β (IL-1α/β), IL-6, IL-10, tumour necrosis factor-alpha (TNF-α), interferons, nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in pathogenesis of rabies is being actively pursued. Presently, levels of certain immune molecules in pathogenesis of rabies in mice have been investigated. CVS strain of rabies infection resulted in early increase in iNOS, TNF-α, caspase-1, Fas ligand (FasL) and toll-like receptor-3 (TLR-3) mRNA levels in brain, and nitric oxide levels in serum. The severity of clinical signs and microscopic lesions largely correlated with NO levels. Aminoguanidine (AG; iNOS inhibitor) decreased NO production with delay in development of clinical signs and increase in survival time. Prolonged survival time correlated with reduced viral load evident by real-time PCR, reduced fluorescent signals of rabies antigen in brain and reduced immunohistochemistry signals in neuronal cytoplasm. These parameters suggested that nitric oxide did influence the rabies virus replication. Inhibition of iNOS by AG administration led to decreased expression of TNF-α, caspase-1, FasL and TLR-3 mRNA levels suggesting that increase in NO levels in rabies virus infection possibly contributed to development of disease through inflammation, apoptosis and immune-evasive mechanisms.

  12. Irradiation gamma on chitosan films

    Energy Technology Data Exchange (ETDEWEB)

    Mello, Luana Miranda Lopes de; Souza, Adriana Regia Marques de; Arthur, Valter, E-mail: lumilopes@hotmail.com, E-mail: drilavras@yahoo.com.br, E-mail: arthur@cena.usp.br [Universidade Federal do Tocantins (UFT), Palmas,TO (Brazil). Departmento de Ciencia e Tecnologia de Alimentos; Universidade Federal de Goias (UFGO), Goiania (Brazil). Departmento de Ciencia e Tecnologia de Alimentos; Centro de Energia Nuclear na Agricultura (CENA/USP), Piracicaba, SP (Brazil)

    2017-11-01

    Films are preformed structures, independent, that are used to wrap food after processing, increasing their shelf life and enhancing its bright and attractive appearance. They are prepared from biological materials as an alternative to the plastic synthetic containers to improve the quality of the environment. Chitosan is a biodegradable polymer composed of β-(1-4) linked D-glucosamine (deacetylated unit) and N-acetyl-D- glucosamine (acetylated unit). It is produced commercially by deacetylation of chitin, which is a structural component of the exoskeleton of crustaceans. She is able to form films and edible and/or biodegradable coatings. With the objective to evaluate the effect of different doses of gamma radiation (0, 5, 10 and 15 kGy) and chitosan concentrations (1 and 2%) in film properties, it was evaluated its optical, mechanical and morphological properties. The films were produced by casting. Irradiation did not affect the thickness of the films, but influenced its colors, increasing the tone of the film for a stronger yellowish color. This fact can be attributed to the increased concentration of C = O bonds of chitosan due to the breakdown of the chain reaction and the Maillard reaction. Irradiated films showed smoother surface and less rough, due to the degradation of the chitosan molecule and poor mechanical properties, not showing good flexibility and stretching. (author)

  13. Uranium briquettes for irradiation target

    Energy Technology Data Exchange (ETDEWEB)

    Saliba-Silva, Adonis Marcelo; Garcia, Rafael Henrique Lazzari; Martins, Ilson Carlos; Carvalho, Elita Fontenele Urano de; Durazzo, Michelangelo, E-mail: saliba@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Direct irradiation on targets inside nuclear research or multiple purpose reactors is a common route to produce {sup 99}Mo-{sup 99m}Tc radioisotopes. Nevertheless, since the imposed limits to use LEU uranium to prevent nuclear armament production, the amount of uranium loaded in target meats has physically increased and new processes have been proposed for production. Routes using metallic uranium thin film and UAl{sub x} dispersion have been used for this purpose. Both routes have their own issues, either by bringing difficulties to disassemble the aluminum case inside hot cells or by generating great amount of alkaline radioactive liquid rejects. A potential route might be the dispersion of powders of LEU metallic uranium and nickel, which are pressed as a blend inside a die and followed by pulse electroplating of nickel. The electroplating provides more strength to the briquettes and creates a barrier for gas evolution during neutronic disintegration of {sup 235}U. A target briquette platted with nickel encapsulated in an aluminum case to be irradiated may be an alternative possibility to replace other proposed targets. This work uses pulse Ni-electroplating over iron powder briquette to simulate the covering of uranium by nickel. The following parameters were applied 10 times for each sample: 900Hz, -0.84A/square centimeters with duty cycle of 0.1 in Watts Bath. It also presented the optical microscopy analysis of plated microstructure section. (author)

  14. Infectivity of irradiated and non-irradiated metacestodes of Taenia saginata

    Energy Technology Data Exchange (ETDEWEB)

    Geerts, S.; Borchgrave, J. de; Brandt, J.R.A.; Kumar, V.; Deken, R. de; Falla, N.; Brabant, R. van (Institute of Tropical Medicine, Antwerp (Belgium). Veterinary Dept.)

    No data are available on the fate of irradiated cysticerci of T. saginata in the human intestine. Since there is no definitive host of T. saginata other than man, this experiment was set up to study the infectivity of irradiated cysticerci of T. saginata in human volunteers in order to determine the minimal effective irradiation dose to inhibit their development. (Author).

  15. Effects of ion beam irradiation on semiconductor devices

    Energy Technology Data Exchange (ETDEWEB)

    Nashiyama, Isamu; Hirao, Toshio; Itoh, Hisayoshi; Ohshima, Takeshi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    1997-03-01

    Energetic heavy-ion irradiation apparatus has been developed for single-event effects (SEE) testing. We have applied three irradiation methods such as a scattered-ion irradiation method, a recoiled-atom irradiation method, and a direct-beam irradiation method to perform SEE testing efficiently. (author)

  16. Cherry Irradiation Studies. 1984 annual report

    Energy Technology Data Exchange (ETDEWEB)

    Eakin, D.E.; Hungate, F.P.; Tingey, G.L.; Olsen, K.L.; Fountain, J.B.; Burditt, A.K. Jr.; Moffit, H.R.; Johnson, D.A.; Lunden, J.D.

    1985-04-01

    Fresh cherries, cherry fruit fly larvae, and codling moth larvae were irradiated using the PNL cobalt-60 facility to determine the efficacy of irradiation treatment for insect disinfestation and potential shelf life extension. Irradiation is an effective disinfestation treatment with no significant degradation of fruit at doses well above those required for quarantine treatment. Sufficient codling moth control was achieved at projected doses of less than 25 krad; cherry fruit fly control, at projected doses of less than 15 krad. Dose levels up to 60 krad did not adversely affect cherry quality factors tested. Irradiation above 60 krad reduced the firmness of cherries but had no significant impact on other quality factors tested. Irradiation of cherries below 80 krad did not result in any significant differences in sensory evaluations (appearance, flavor, and firmness) in tests conducted at OSU. Irradiation up to 200 krad at a temperature of about 25/sup 0/C (77/sup 0/F) did not measurably extend shelf life. Irradiation at 500 krad at 25/sup 0/C (77/sup 0/F) increased mold and rotting of cherries tested. There is no apparent advantage of irradiation over low-temperature fumigation.

  17. Improving bambara groundnut productivity using gamma irradiation ...

    African Journals Online (AJOL)

    In recent times efforts are being made to improve the productivity of bambara groundnut. Studies were initiated (i) to characterise and evaluate landraces and to select superior ones for irradiation, (ii) to induce genetic variation through gamma irradiation and (iii) to use biotechnological approaches to shorten the generation ...

  18. Mechanical response of proton beam irradiated nitinol

    Energy Technology Data Exchange (ETDEWEB)

    Afzal, Naveed [Centre for Advanced Studies in Physics, GC University, Lahore (Pakistan); Ghauri, I.M., E-mail: ijaz.phys@gmail.co [Centre for Advanced Studies in Physics, GC University, Lahore (Pakistan); Mubarik, F.E.; Amin, F. [Centre for Advanced Studies in Physics, GC University, Lahore (Pakistan)

    2011-01-01

    The present investigation deals with the study of mechanical behavior of proton beam irradiated nitinol at room temperature. The specimens in austenitic phase were irradiated over periods of 15, 30, 45 and 60 min at room temperature using 2 MeV proton beam obtained from Pelletron accelerator. The stress-strain curves of both unirradiated and irradiated specimens were obtained using a universal testing machine at room temperature. The results of the experiment show that an intermediate rhombohedral (R) phase has been introduced between austenite and martensite phase, which resulted in the suppression of direct transformation from austenite to martensite (A-M). Stresses required to start R-phase ({sigma}{sub RS}) and martensitic phase ({sigma}{sub MS}) were observed to decrease with increase in exposure time. The hardness tests of samples before and after irradiation were also carried out using Vickers hardness tester. The comparison reveals that the hardness is higher in irradiated specimens than that of the unirradiated one. The increase in hardness is quite sharp in specimens irradiated for 15 min, which then increases linearly as the exposure time is increased up to 60 min. The generation of R-phase, variations in the transformation stresses {sigma}{sub RS} and {sigma}{sub MS} and increase in hardness of irradiated nitinol may be attributed to lattice disorder and associated changes in crystal structure induced by proton beam irradiation.

  19. Food irradiation; Global aspects and future prospects

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Akira (Tokyo Univ. of Agriculture (Japan). Nodai Research Institute)

    1990-07-01

    This paper reviews researches, commentaries, and conference and public records of food irradiation, published mainly during the period 1987-1989, focusing on the current conditions of food irradiation that may pose not only scientific or technologic problems but also political issues or consumerism. Approximately 50 kinds of food, although not enough to fill economic benefit, are now permitted for food irradiation in the world. Consumerism is pointed out as the major factor that precludes the feasibility of food irradiation in the world. In the United States, irradiation is feasible only for spices. Food irradiation has already been feasible in France, Hollands, Belgium, and the Soviet Union; has under consideration in the Great Britain, and has been rejected in the West Germany. Although the feasibility of food irradiation is projected to increase gradually in the future, commercial success or failure depends on the final selection of consumers. In this respect, the role of education and public information are stressed. Meat radicidation and recent progress in the method for detecting irradiated food are referred to. (N.K.) 128 refs.

  20. Status of food irradiation in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Kikuchi, O.K. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil)

    1996-12-31

    Research on food irradiation in Brazil started in 1968 at the Center of Nuclear Energy for Agriculture (CENA), Piracicaba, Sao Paulo. At the Institute of Nuclear and Energy Research (IPEN-CNEN/SP), Sao Paulo, Sao Paulo, research on detection of irradiated foods is in progress. In 1973, the Brazilian government established a regulation about food irradiation. Nowadays, the products authorized to be irradiated are: rice, poultry, fish and fish products, potatoes, onions, avocados, persimmons, pineapples, wheat flour, maize, beans, spices, tomatoes, guavas, oranges, lemons, strawberries, mangoes, melons and papayas. The other recommended products to be approved in the future are: acerolas, apples, beans (dose > 1 kGy), beef, blueberries, cherries, cheeses, coffee, figs, fresh guaranas, garlics, grapefruits, grapes, mushrooms, nuts and pork. Today, there is only one commercial facility for irradiation services in the country, the Empresa Brasileira de Radiacoes Ltda. (EMBRARAD). This company operates a Nordion JS-7500 irradiator, with a present activity of about 1,000 kCi, designed for sterilizing medical devices. It also irradiates spices, dried foods, gemstones, cosmetics, wood and raw materials for pharmaceuticals. The plant operates 24 hours a day and the spices and dried foods represent 15% of the business. Powder of guarana seeds is irradiated also for exportation. There are two other commercial facilities for radiation sterilization in Brazil, operating exclusively for their own production. (J.P.N.)

  1. Brazilian Consumer views on food irradiation

    NARCIS (Netherlands)

    Behrens, J.H.; Barcellos, M.N.; Frewer, L.J.; Nunes, T.P.; Landgraf, M.

    2009-01-01

    This study investigated the consumer attitude to food irradiation in São Paulo, Brazil, through a qualitative research perspective. Three focus groups were conducted with 30 consumers, responsible for food choices and purchases. Both irradiated and nonirradiated food samples were served in the

  2. Models of Solar Irradiance Variations: Current Status

    Indian Academy of Sciences (India)

    2016-01-27

    Jan 27, 2016 ... Regular monitoring of solar irradiance has been carried out since 1978 to show that solar total and spectral irradiance varies at different time scales. Whereas variations on time scales of minutes to hours are due to solar oscillations and granulation, variations on longer time scales are driven by the ...

  3. Splenic irradiation for hairy cell leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Al-Moundhri, A.; Graham, P.H. [St George Hospital, Kogarah, NSW, (Australia). Department of Radiation Oncology

    1997-11-01

    Splenic irradiation in the management of hairy cell leukaemia is previously unreported. A case is presented here to illustrate that splenic irradiation may be a useful addition to systemic therapies. It achieved local splenic and blood picture response and remission similar to splenectomy without any significant toxicity. (authors). 7 refs., 2 figs.

  4. Schedule and status of irradiation experiments

    Energy Technology Data Exchange (ETDEWEB)

    Rowcliffe, A.F.; Grossbeck, M.L.; Robertson, J.P. [Oak Ridge National Lab., TN (United States)

    1998-09-01

    The current status of reactor irradiation experiments is presented in tables summarizing the experimental objectives, conditions, and schedule. Currently, the program has one irradiation experiment in reactor and five experiments in the design or construction stages. Postirradiation examination and testing is in progress on ten experiments.

  5. Advances in SEM beam micro-irradiation

    Science.gov (United States)

    Thomson, I.; Mackay, G.; Haythornthwaite, R.

    1991-03-01

    An instrument designed to measure the dose deposited by the beam under routine irradiation conditions using Metal Oxide Semiconductor Field Effect Transistor (MOSFET) dosimeter cells is described. The dosimeter response is calibrated against various types of radiation sources to enable intercomparisons with Co-60, electrons and protons. The technique enables Scanning Electron Microscope (SEM) users to carry out micro-irradiations of operating devices.

  6. Conditional Macrophage Depletion Increases Inflammation and Does Not Inhibit the Development of Osteoarthritis in Obese Macrophage Fas-Induced Apoptosis-Transgenic Mice.

    Science.gov (United States)

    Wu, Chia-Lung; McNeill, Jenna; Goon, Kelsey; Little, Dianne; Kimmerling, Kelly; Huebner, Janet; Kraus, Virginia; Guilak, Farshid

    2017-09-01

    To investigate whether short-term, systemic depletion of macrophages can mitigate osteoarthritis (OA) following injury in the setting of obesity. CSF-1R-GFP+ macrophage Fas-induced apoptosis (MaFIA)-transgenic mice that allow conditional depletion of macrophages were placed on a high-fat diet and underwent surgery to induce knee OA. A small molecule (AP20187) was administrated to deplete macrophages in MaFIA mice. The effects of macrophage depletion on acute joint inflammation, OA severity, and arthritic bone changes were evaluated using histology and micro-computed tomography. Immunohistochemical analysis was performed to identify various immune cells. The levels of serum and synovial fluid cytokines were also measured. Macrophage-depleted mice had significantly fewer M1 and M2 macrophages in the surgically operated joints relative to controls and exhibited decreased osteophyte formation immediately following depletion. Surprisingly, macrophage depletion did not attenuate the severity of OA in obese mice; instead, it induced systemic inflammation and led to a massive infiltration of CD3+ T cells and particularly neutrophils, but not B cells, into the injured joints. Macrophage-depleted mice also demonstrated a markedly increased number of proinflammatory cytokines including granulocyte colony-stimulating factor, interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor in both serum and joint synovial fluid, although the mice showed a trend toward decreased levels of insulin and leptin in serum after macrophage depletion. Our findings indicate that macrophages are vital for modulating homeostasis of immune cells in the setting of obesity and suggest that more targeted approaches of depleting specific macrophage subtypes may be necessary to mitigate inflammation and OA in the setting of obesity. © 2017, American College of Rheumatology.

  7. Crosstalk Influence between P38MAPK and Autophagy on Mitochondria-Mediated Apoptosis Induced by Anti-Fas Antibody/Actinomycin D in Human Hepatoma Bel-7402 Cells

    Directory of Open Access Journals (Sweden)

    Yu Wang

    2017-10-01

    Full Text Available Our previous study indicated that anti-Fas antibody/actinomycin D (AF/AD induced apoptosis of human hepatocellular carcinoma Bel-7402 cells; however, crosstalk influence between P38MAPK and autophagy on mitochondria-mediated apoptosis induced by AF/AD in Bel-7402 cells remains unclear. Therefore, effect of AF/AD on apoptosis, autophagy, phosphorylated-P38MAPK (p-P38MAPK, and membrane potential (ΔΨm with or without the P38MAPK inhibitor SB203580 or the autophagy inhibitor 3-methyladenine (3-MA in Bel-7402 cells was investigated in the present study. The results showed that AF/AD resulted in induction of apoptosis concomitant with autophagy, upregulation of p-P38MAPK and autophagy-associated gene proteins (Atg5-Atg12 protein complex, Atg7, Atg10, Beclin-1, LC3 I, and LC3 II, and downregulation of ΔΨm in Bel-7402 cells. In contrast, SB203580 attenuated the effects of AF/AD in Bel-7402 cells. Furthermore, the findings also demonstrated that 3-MA inhibited the impact of AF/AD on autophagy, Atg5-Atg12 protein complex, Atg7, Atg10, Beclin-1, LC3 I, LC3 II, and ΔΨm, and promoted the influence of AF/AD on apoptosis and p-P38MAPK in Bel-7402 cells. Taken together, we conclude that crosstalk between P38MAPK and autophagy regulates mitochondria-mediated apoptosis induced by AF/AD in Bel-7402 cells.

  8. Complementary roles of Fas-associated death domain (FADD) and receptor interacting protein kinase-3 (RIPK3) in T-cell homeostasis and antiviral immunity

    Science.gov (United States)

    Lu, Jennifer V.; Weist, Brian M.; van Raam, Bram J.; Marro, Brett S.; Nguyen, Long V.; Srinivas, Prathna; Bell, Bryan D.; Luhrs, Keith A.; Lane, Thomas E.; Salvesen, Guy S.; Walsh, Craig M.

    2011-01-01

    Caspase-8 (casp8) is required for extrinsic apoptosis, and mice deficient in casp8 fail to develop and die in utero while ultimately failing to maintain the proliferation of T cells, B cells, and a host of other cell types. Paradoxically, these failures are not caused by a defect in apoptosis, but by a presumed proliferative function of this protease. Indeed, following mitogenic stimulation, T cells lacking casp8 or its adaptor protein FADD (Fas-associated death domain protein) develop a hyperautophagic morphology, and die a programmed necrosis-like death process termed necroptosis. Recent studies have demonstrated that receptor-interacting protein kinases (RIPKs) RIPK1 and RIPK3 together facilitate TNF-induced necroptosis, but the precise role of RIPKs in the demise of T cells lacking FADD or casp8 activity is unknown. Here we demonstrate that RIPK3 and FADD have opposing and complementary roles in promoting T-cell clonal expansion and homeostasis. We show that the defective proliferation of T cells bearing an interfering form of FADD (FADDdd) is rescued by crossing with RIPK3−/− mice, although such rescue ultimately leads to lymphadenopathy. Enhanced recovery of these double-mutant T cells following stimulation demonstrates that FADD, casp8, and RIPK3 are all essential for clonal expansion, contraction, and antiviral responses. Finally, we demonstrate that caspase-mediated cleavage of RIPK1-containing necrosis inducing complexes (necrosomes) is sufficient to prevent necroptosis in the face of death receptor signaling. These studies highlight the “two-faced” nature of casp8 activity, promoting clonal expansion in some situations and apoptotic demise in others. PMID:21876153

  9. AGR-1 Post Irradiation Examination Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Demkowicz, Paul Andrew [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-08-01

    The post-irradiation examination (PIE) of the Advanced Gas Reactor (AGR)-1 experiment was a multi-year, collaborative effort between Idaho National Laboratory (INL) and Oak Ridge National Laboratory (ORNL) to study the performance of UCO (uranium carbide, uranium oxide) tristructural isotropic (TRISO) coated particle fuel fabricated in the U.S. and irradiated at the Advanced Test Reactor at INL to a peak burnup of 19.6% fissions per initial metal atom. This work involved a broad array of experiments and analyses to evaluate the level of fission product retention by the fuel particles and compacts (both during irradiation and during post-irradiation heating tests to simulate reactor accident conditions), investigate the kernel and coating layer morphology evolution and the causes of coating failure, and explore the migration of fission products through the coating layers. The results have generally confirmed the excellent performance of the AGR-1 fuel, first indicated during the irradiation by the observation of zero TRISO coated particle failures out of 298,000 particles in the experiment. Overall release of fission products was determined by PIE to have been relatively low during the irradiation. A significant finding was the extremely low levels of cesium released through intact coatings. This was true both during the irradiation and during post-irradiation heating tests to temperatures as high as 1800°C. Post-irradiation safety test fuel performance was generally excellent. Silver release from the particles and compacts during irradiation was often very high. Extensive microanalysis of fuel particles was performed after irradiation and after high-temperature safety testing. The results of particle microanalysis indicate that the UCO fuel is effective at controlling the oxygen partial pressure within the particle and limiting kernel migration. Post-irradiation examination has provided the final body of data that speaks to the quality of the AGR-1 fuel, building

  10. Identification of irradiated pepper with comet assay

    Energy Technology Data Exchange (ETDEWEB)

    Prieto Miranda, Enrique Fco.; Moreno Alvarez, Damaris L.; Carro Palacio, Sandra [Centro de Aplicaciones Tecnologicas y Desarrollo Nuclear. (CEADEN), Ciudad de La Habana (Cuba)]. E-mail: efprieto@ceaden.edu.cu; damaris@ceaden.edu.cu; Iglesia Enriquez, Isora [Instituto de Investigacion para la Industria Alimenticia (IIIA), Ciudad de La Habana (Cuba)

    2007-07-01

    The treatment of foods with ionizing radiations is a technological process utilized in order to increase the hygienic quality and the storage time of the foods. Several methods of detection of irradiated foods have been recommended. The comet assay of DNA is one fast and economical technique for the qualitative identification of irradiated foods. The objective of the present paper was to identify with the comet assay technique the modifications of the DNA molecule of irradiated pepper storage at environment and refrigeration temperatures and different post-irradiation times for different absorbed dose values, (0.1, 0.3 and 0.5 kGy). It was demonstrated that for the high absorbed dose values was observed a greater break into fragments of the DNA molecule, which shows the application of this technique for the identification of irradiated foods. (author)

  11. Anti-fungal activity of irradiated chitosan

    Energy Technology Data Exchange (ETDEWEB)

    Pham ThiLe Ha; Tran Thi Thuy; Nguyen Quoc Hien [Nuclear Research Inst., No.1 Nguyen Tu Luc, Dalat (Viet Nam); Nagasawa, Naotsugu; Kume, Tamikazu [Takasaki Radiation Chemistry Research Establishment, Japan Atomic Energy Research Institute, Gunma (Japan)

    1999-09-01

    Anti-fungal activity of chitosan induced by irradiation has been investigated. Commercial chitosan samples of 8B (80% deacetylation) and l0B (99% deacetylation) were irradiated by {gamma}-ray in dry condition. Highly deacethylated chitosan (10B) at low dose irradiation (75 kGy) was effective for inhibition of fungal growth. The sensitivities of Exobasidium vexans, Septoria chrysanthemum and Gibberella fujikuroi for the irradiated chitosan were different and the necessary concentrations of chitosan were 550, 350 and 250 {mu}g/ml, respectively. For the plant growth, low deacethylation (chitosan 8B) and high dose (500 kGy) was effective and the growth of chrysanthemum was promoted by spraying the irradiated chitosan. (author)

  12. ATF Neutron Irradiation Program Technical Plan

    Energy Technology Data Exchange (ETDEWEB)

    Geringer, J. W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Materials Science and Technology Division; Katoh, Yutai [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Materials Science and Technology Division

    2016-03-01

    The Japan Atomic Energy Agency (JAEA) under the Civil Nuclear Energy Working Group (CNWG) is engaged in a cooperative research effort with the U.S. Department of Energy (DOE) to explore issues related to nuclear energy, including research on accident-tolerant fuels and materials for use in light water reactors. This work develops a draft technical plan for a neutron irradiation program on the candidate accident-tolerant fuel cladding materials and elements using the High Flux Isotope Reactor (HFIR). The research program requires the design of a detailed experiment, development of test vehicles, irradiation of test specimens, possible post-irradiation examination and characterization of irradiated materials and the shipment of irradiated materials to JAEA in Japan. This report discusses the technical plan of the experimental study.

  13. AFIP-3 Irradiation Summary Report

    Energy Technology Data Exchange (ETDEWEB)

    Danielle M Perez; M. A. Lillo; G. S. Chang; G. A. Roth; N. E. Woolstenhulme; D. M. Wachs

    2012-03-01

    The Advanced Test Reactor (ATR) Full size plate In center flux trap Position (AFIP) experiment AFIP-3 was designed to evaluate the performance of monolithic fuels at a prototypic scale of 2.25 inches x 21.5 inches x 0.050 inches (5.75 cm x 54.6 cm x 0.13cm). The AFIP-3 experiment was fabricated by hot isostatic pressing (HIP) and consists of two plates, one with a zirconium (Zr) diffusion barrier and one with a silicon (Si) enhanced fuel/clad interface1,2. The following report summarizes the life of the AFIP-3 experiment through end of irradiation, including a brief description of the safety analysis, as-run neutronic analysis results, hydraulic testing results, and thermal analysis results.

  14. AFIP-3 Irradiation Summary Report

    Energy Technology Data Exchange (ETDEWEB)

    Danielle M Perez; M. A. Lillo; G. S. Chang; G. A. Roth; N. E. Woolstenhulme; D. M. Wachs

    2011-05-01

    The Advanced Test Reactor (ATR) Full size plate In center flux trap Position (AFIP) experiment AFIP-3 was designed to evaluate the performance of monolithic fuels at a prototypic scale of 2.25 inches x 21.5 inches x 0.050 inches (5.75 cm x 54.6 cm x 0.13cm). The AFIP-3 experiment was fabricated by hot isostatic pressing (HIP) and consists of two plates, one with a zirconium (Zr) diffusion barrier and one with a silicon (Si) enhanced fuel/clad interface1,2. The following report summarizes the life of the AFIP-3 experiment through end of irradiation, including a brief description of the safety analysis, as-run neutronic analysis results, hydraulic testing results, and thermal analysis results.

  15. AFIP-1 Irradiation Summary Report

    Energy Technology Data Exchange (ETDEWEB)

    D. M. Perez; M. A. Lillo; G. S. Chang; G. A. Roth; N. E. Woolstenhulme; D. M. Wachs

    2011-05-01

    The Advanced Test Reactor (ATR) Full size plate In center flux trap Position (AFIP) experiment AFIP-1 was designed to demonstrate the performance of second-generation dispersion fuels at a prototypic scale with a length of 21.5 inches (54.6 cm), width of 2.25 inches (5.75 cm) and a thickness of 0.050 inch (0.13 cm). The experiment was fabricated using commercially standard practices at BWX Technology, Inc. (BWXT). The U-7Mo fuel particles were supplied by the Korean Atomic Energy Research Institute (KAERI) using equipment intended for commercial supply. Two fuel plates were tested that incorporated two different matrix compositions, Al-2Si and Al-4043.1 The following report summarizes the life of the AFIP-1 experiment through end of irradiation, including a brief description of the safety analysis, as-run neutronic analysis results, hydraulic testing results, and thermal analysis results

  16. AFIP-2 Irradiation Summary Report

    Energy Technology Data Exchange (ETDEWEB)

    Danielle M Perez; M. A. Lillo; G. S. Chang; G. A. Roth; N. E. Woolstenhulme; D. M. Wachs

    2011-05-01

    The Advanced Test Reactor (ATR) Full size plate In center flux trap Position (AFIP) experiment AFIP-2 was designed to evaluate the performance of monolithic fuels at a prototypic scale of 2.25 inches x 21.5 inches x 0.050 inches (5.75 cm x 54.6 cm x 0.13cm). The AFIP-2 experiment was fabricated by friction bond (FB) and consists of two plates, one with a zirconium (Zr) diffusion barrier and one with a silicon (Si) enhanced fuel/clad interface1,2. The following report summarizes the life of the AFIP-2 experiment through end of irradiation, including a brief description of the safety analysis, as-run neutronic analysis results, hydraulic testing results, and thermal analysis results. The safety analyses performed for AFIP-2 are summarized in Table 5 of the following report.

  17. AFIP-2 Irradiation Summary Report

    Energy Technology Data Exchange (ETDEWEB)

    Danielle M Perez

    2011-04-01

    The Advanced Test Reactor (ATR) Full size plate In center flux trap Position (AFIP) experiment AFIP-2 was designed to evaluate the performance of monolithic fuels at a prototypic scale of 2.25 inches x 21.5 inches x 0.050 inches (5.75 cm x 54.6 cm x 0.13cm). The AFIP-2 experiment was fabricated by friction bond (FB) and consists of two plates, one with a zirconium (Zr) diffusion barrier and one with a silicon (Si) enhanced fuel/clad interface1,2. The following report summarizes the life of the AFIP-2 experiment through end of irradiation, including a brief description of the safety analysis, as-run neutronic analysis results, hydraulic testing results, and thermal analysis results. The safety analyses performed for AFIP-2 are summarized in Table 5 of the following report.

  18. Osteonecrosis of acetabulum after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ishihara, Gintaro; Matuda, Tatsuo; Takeuchi, Norihiro; Itoh, Haruo [Tokyo Koseinenkin Hospital (Japan)

    1996-11-01

    A case of osteonecrosis 8 years post irradiation was reported. The 70 years old female patient who, 8 years ago, received abdominal hysterectomy due to cervical cancer and then radiotherapy of 92.1 Gy within about 1.5 mo, had a pain at the left hip joint with a slight elevation of ALP. The roentgenography showed the fracture and callus of the left acetabulum; bone scintigraphy, a high accumulation of {sup 99m}Tc at the site; CT, abnormal fracture; MRI, low bright T1-weighted image and equi-bright T2-image; and MRI with Gd-DTPA, enhanced image. The hip joint was surgically reconstructed with cement (THR). Surgical and histopathological findings confirmed osteonecrosis without tumoral finding and the lesion was considered radiogenic. (K.H.)

  19. High dose irradiation with hyperfractionation

    Energy Technology Data Exchange (ETDEWEB)

    Asakura, Hideo; Kurashima, Shoji; Hasegawa, Maki; Akiyama, Kazuo (Sagamihara National Hospital, Kanagawa (Japan))

    1990-10-01

    From March 1988 to January 1990, 12 patients including 7 primary lung cancers, 2 lung metastases of colorectal cancer, and each 1 gall bladder cancer, ovarian cancer, and spinal cord metastasis of prostatic cancer, received {sup 60}Co-irradiation with high dose by hyperfractionation. This hyperfractionation consisted of 1.2 Gy per fraction, twice a day with 6 hour interval, and 5 days (10 fractions) a week. The total dose administered was 81.6{approx}100 Gy. The acute reaction of skin, lung, and intestines was tolerable, and it seemed that the late damage of normal tissues was slighter and the treatment result was favorable in comparison with the conventional fractionation, but this estimation was not definite because of short observation period. It was discussed that further reduction of dose per fraction (1 Gy or below) and more increased total dose (100 Gy or more) would be promising in hyperfractionation. (author).

  20. IRRADIATION DEVICE FOR IRRADIATION TESTING OF COATED PARTICLE FUEL AT HANARO

    Directory of Open Access Journals (Sweden)

    BONG GOO KIM

    2013-12-01

    Full Text Available The Korean Nuclear-Hydrogen Technology Development (NHTD Plan will be performing irradiation testing of coated particle fuel at HANARO to support the development of VHTR in Korea. This testing will be carried out to demonstrate and qualify TRISO-coated particle fuel for use in VHTR. The testing will be irradiated in an inert gas atmosphere without on-line temperature monitoring and control combined with on-line fission product monitoring of the sweep gas. The irradiation device contains two test rods, one has nine fuel compacts and the other five compacts and eight graphite specimens. Each compact contains about 260 TRISO-coated particles. The irradiation device is being loaded and irradiated into the OR5 hole of the in HANARO core from August 2013. The device will be operated for about 150 effective full-power days at a peak temperature of about 1030°C in BOC (Beginning of Cycle during irradiation testing. After a peak burn-up of about 4 atomic percentage and a peak fast neutron fluence of about 1.7×1021 n/cm2, PIE (Post-Irradiation Examination of the irradiated coated particle fuel will be performed at IMEF (Irradiated Material Examination Facility. This paper reviews the design of test rod and irradiation device for coated particle fuel, and discusses the technical results for irradiation testing at HANARO.

  1. SORCE Level 3 Total Solar Irradiance Daily Means V017

    Data.gov (United States)

    National Aeronautics and Space Administration — The Total Solar Irradiance (TSI) data set SOR3TSID contains the total solar irradiance (a.k.a solar constant) data collected by the Total Irradiance Monitor (TIM)...

  2. HRB-22 capsule irradiation test for HTGR fuel. JAERI/USDOE collaborative irradiation test

    Energy Technology Data Exchange (ETDEWEB)

    Minato, Kazuo; Sawa, Kazuhiro; Fukuda, Kousaku [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment] [and others

    1998-03-01

    As a JAERI/USDOE collaborative irradiation test for high-temperature gas-cooled reactor fuel, JAERI fuel compacts were irradiated in the HRB-22 irradiation capsule in the High Flux Isotope Reactor at the Oak Ridge National Laboratory (ORNL). Postirradiation examinations also were performed at ORNL. This report describes 1) the preirradiation characterization of the irradiation samples of annular-shaped fuel compacts containing the Triso-coated fuel particles, 2) the irradiation conditions and fission gas releases during the irradiation to measure the performance of the coated particle fuel, 3) the postirradiation examinations of the disassembled capsule involving visual inspection, metrology, ceramography and gamma-ray spectrometry of the samples, and 4) the accident condition tests on the irradiated fuels at 1600 to 1800degC to obtain information about fuel performance and fission product release behavior under accident conditions. (author)

  3. Metabolic profiling by (1)H NMR of ground beef irradiated at different irradiation doses.

    Science.gov (United States)

    Zanardi, Emanuela; Caligiani, Augusta; Palla, Luigi; Mariani, Mario; Ghidini, Sergio; Di Ciccio, Pierluigi Aldo; Palla, Gerardo; Ianieri, Adriana

    2015-05-01

    This work describes a metabolic profiling study of non-irradiated and irradiated beef (at 2.5, 4.5 and 8 kGy) using (1)H NMR and chemometrics. The assignment of all major NMR signals of the aqueous/methanolic extracts was performed. A comprehensive multivariate data analysis proved the ability to distinguish between the irradiated and non-irradiated beef. Classification trees revealed that three metabolites (glycerol, lactic acid esters and tyramine or a p-substituted phenolic compound) are important biomarkers for classification of the irradiated and non-irradiated beef samples. Overall, the achieved metabolomic results show that the changes in the metabolic profile of meat provide a valuable insight to be used in detecting irradiated beef. The use of the NMR-based approach simplifies sample preparation and decrease the time required for analysis, compared to available official analytical procedures. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Saturation behavior of irradiation hardening in F82H irradiated in the HFIR

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, T. [Blanket Engineering Group, Japan Atomic Energy Agency, Naka, Ibaraki (Japan); Shiba, K.; Tanigawa, H.; Ando, M. [Japan Atomic Energy Agency, Tokai-mura, Naga-gun, Ibaraki-ken (Japan); Klueh, R.L. [Oak Ridge National Laboratory, TN (United States); Stoller, R. [ORNL - Oak Ridge National Laboratory, Materials Science and Technology Div., Oak Ridge, AK TN (United States)

    2007-07-01

    Full text of publication follows: Post irradiation tensile tests on reduced activation ferritic/martensitic steel, F82H have been conducted over the past two decades using Japan Materials Testing Reactor (JMTR) of JAEA, and Fast Flux Testing Facility (FFTF) of PNNL and High Flux Isotope Reactor (HFIR) of ORNL, USA, under Japan/US collaboration programs. According to these results, F82H does not demonstrate irradiation hardening above 673 K up to 60 dpa. The current study has been concentrated on hardening behavior at temperature around 573 K. A series of low temperature irradiation experiment has been conducted at the HFIR under the international collaborative research between JAEA/US-DOE. In this collaboration, the irradiation condition is precisely controlled by the well matured capsule designing and instrumentation. This paper summarizes recent results of the irradiation experiments focused on F82H and its modified steels compared with the irradiation properties database on F82H. Post irradiation tensile tests have been conducted on the F82H and its modified steels irradiated at 573 K and the dose level was up to 25 dpa. According to these results, irradiation hardening of F82H is saturated by 9 dpa and the as-irradiated 0.2 % proof stress is less than 1 GPa at ambient temperature. The deterioration of total elongation was also saturated by 9 dpa irradiation. The ductility of some modified steels which showed larger total elongation than that of F82H before irradiation become the same level as that of standard F82H steel after irradiation, even though its magnitude of irradiation hardening is smaller than that of F82H. This suggests that the more ductile steel demonstrates the more ductility loss at this temperature, regardless to the hardening level. The difference in ductility loss behavior between various tensile specimens will be discussed as the ductility could depend on the specimen dimension. (authors)

  5. AGC-1 Post Irradiation Examination Status

    Energy Technology Data Exchange (ETDEWEB)

    David Swank

    2011-09-01

    The Next Generation Nuclear Plant (NGNP) Graphite R&D program is currently measuring irradiated material property changes in several grades of nuclear graphite for predicting their behavior and operating performance within the core of new Very High Temperature Reactor (VHTR) designs. The Advanced Graphite Creep (AGC) experiment consisting of six irradiation capsules will generate this irradiated graphite performance data for NGNP reactor operating conditions. All six AGC capsules in the experiment will be irradiated in the Advanced Test Reactor (ATR), disassembled in the Hot Fuel Examination Facility (HFEF), and examined at the INL Research Center (IRC) or Oak Ridge National Laboratory (ORNL). This is the first in a series of status reports on the progress of the AGC experiment. As the first capsule, AGC1 was irradiated from September 2009 to January 2011 to a maximum dose level of 6-7 dpa. The capsule was removed from ATR and transferred to the HFEF in April 2011 where the capsule was disassembled and test specimens extracted from the capsules. The first irradiated samples from AGC1 were shipped to the IRC in July 2011and initial post irradiation examination (PIE) activities were begun on the first 37 samples received. PIE activities continue for the remainder of the AGC1 specimen as they are received at the IRC.

  6. [Near infrared light irradiator using halogen lamp].

    Science.gov (United States)

    Ide, Yasuo

    2012-07-01

    The practical electric light bulb was invented by Thomas Alva Edison in 1879. Halogen lamp is the toughest and brightest electric light bulb. With light filter, it is used as a source of near infrared light. Super Lizer and Alphabeam are made as near infrared light irradiator using halogen lamp. The light emmited by Super Lizer is linear polarized near infrared light. The wave length is from 600 to 1,600 nm and strongest at about 1,000 nm. Concerning Super Lizer, there is evidence of analgesic effects and normalization of the sympathetic nervous system. Super Lizer has four types of probes. SG type is used for stellate ganglion irradiation. B type is used for narrow area irradiation. C and D types are for broad area irradiation. The output of Alphabeam is not polarized. The wave length is from 700 to 1,600 nm and the strongest length is about 1,000nm. Standard attachment is used for spot irradiation. Small attachment is used for stellate ganglion irradiation. Wide attachment is used for broad area irradiation. The effects of Alphabeam are thought to be similar to that of Super Lizer.

  7. Steam-chemical reactivity for irradiated beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Anderl, R.A.; McCarthy, K.A.; Oates, M.A.; Petti, D.A.; Pawelko, R.J.; Smolik, G.R. [Idaho National Engineering and Environmental Lab., Idaho Falls, ID (United States)

    1998-01-01

    This paper reports the results of an experimental investigation to determine the influence of neutron irradiation effects and annealing on the chemical reactivity of beryllium exposed to steam. The work entailed measurements of the H{sub 2} generation rates for unirradiated and irradiated Be and for irradiated Be that had been previously annealed at different temperatures ranging from 450degC to 1200degC. H{sub 2} generation rates were similar for irradiated and unirradiated Be in steam-chemical reactivity experiments at temperatures between 450degC and 600degC. For irradiated Be exposed to steam at 700degC, the chemical reactivity accelerated rapidly and the specimen experienced a temperature excursion. Enhanced chemical reactivity at temperatures between 400degC and 600degC was observed for irradiated Be annealed at temperatures of 700degC and higher. This reactivity enhancement could be accounted for by the increased specific surface area resulting from development of a surface-connected porosity in the irradiated-annealed Be. (author)

  8. ESR identification of irradiated foodstuffs: LARQUA research

    Energy Technology Data Exchange (ETDEWEB)

    Raffi, J. [Laboratoire de Recherche sur la Qualite des Aliments, Marseille (France)

    1996-12-31

    As electron spin resonance (ESR) spectroscopy is the leading method for identification of irradiated foodstuffs, meat and fish bones, fruit and relative products (of vegetable origin), sea-food etc. were studied. In order to prepare a large co-trial on ESR identification of irradiation of irradiated foodstuffs, experiments were carried out at LARQUA, especially on fruits and vegetables. The radicals induced in the fruit pulp are not stable because the water content of fruit is generally high, but ESR can be used with dried fruit or dry components such as achenes, pips or stones. Different responses are observed, depending on the fruit. In ``sugatype`` fruits (papaya, dried grapes), an ESR multicomponent signal is radio-induced, but the non-irradiated fruit presents no ESR signal or a single-line, while in ``cellulose type`` fruits (pistachio nut, berries), a triplet is induced. But a six line signal due to Mn{sup 2+} and a central single line may also be present both in irradiated and non-irradiated samples. In the case of aromatic herbs, the proposed official CEN protocol for irradiated food containing cellulose was used. (author).

  9. Analysis of gamma irradiated pepper constituents, 5

    Energy Technology Data Exchange (ETDEWEB)

    Takagi, Kazuko; Okuyama, Tsuneo; Ishikawa, Toshihiro.

    1988-11-01

    Gamma irradiated peppers (10 krad, 100 krad, 1 Mrad) were analyzed by HPLC. The extraction method and HPLC conditions were same as the first report, that is, the extraction from pepper was performed by Automatic Air Hammer and the extracted samples were separated on a reversed phase C/sub 8/ column with a concave gradient from 0.1% trifluoroaceticacid (TFA) in water to 75% acetonitrile-0.1% TFA in water for 60 minutes and detected at 210 nm, 280 nm. It is difficult to compare with irradiated and unirradiated pepper constituents by their peak height or area. And the method of multivariant statistically analysis was introduced. The 'peak n area/peak n + 1 area' ratio was calculated by computer. Each peak area was accounted by integrator. The value of these ratio were called 'parameter'. Each chromatogram has 741 parameters calculated with 39 chromatographic peaks. And these parameters were abopted to the multivariant statiscally analysis. Comparison of constituents between irradiated pepper and unirradiated pepper was done by 741 parameters. The correlation of parameters between irradiated and unirradiated was investigated by use of computer. Some parameters of irradiated case were selected as which had no correlation with unirradiated case. That is to say these parameters were thought to be changed with gamma spectrum irradiation. By this method, Coumarin was identified as a changed component with gamma irradiation.

  10. Neutron irradiation creep in stainless steel alloys

    Energy Technology Data Exchange (ETDEWEB)

    Schuele, Wolfgang (Commission of the European Union, Institute for Advanced Materials, I-21020 Ispra (Vatican City State, Holy See) (Italy)); Hausen, Hermann (Commission of the European Union, Institute for Advanced Materials, I-21020 Ispra (Vatican City State, Holy See) (Italy))

    1994-09-01

    Irradiation creep elongations were measured in the HFR at Petten on AMCR steels, on 316 CE-reference steels, and on US-316 and US-PCA steels varying the irradiation temperature between 300 C and 500 C and the stress between 25 and 300 MPa. At the beginning of an irradiation a type of primary'' creep stage is observed for doses up to 3-5 dpa after which dose the secondary'' creep stage begins. The primary'' creep strain decreases in cold-worked steel materials with decreasing stress and decreasing irradiation temperature achieving also negative creep strains depending also on the pre-treatment of the materials. These primary'' creep strains are mainly attributed to volume changes due to the formation of radiation-induced phases, e.g. to the formation of [alpha]-ferrite below about 400 C and of carbides below about 700 C, and not to irradiation creep. The secondary'' creep stage is found for doses larger than 3 to 5 dpa and is attributed mainly to irradiation creep. The irradiation creep rate is almost independent of the irradiation temperature (Q[sub irr]=0.132 eV) and linearly dependent on the stress. The total creep elongations normalized to about 8 dpa are equal for almost every type of steel irradiated in the HFR at Petten or in ORR or in EBR II. The negative creep elongations are more pronounced in PCA- and in AMCR-steels and for this reason the total creep elongation is slightly smaller at 8 dpa for these two steels than for the other steels. ((orig.))

  11. Identification of irradiated crab using EPR

    Energy Technology Data Exchange (ETDEWEB)

    Maghraby, A. [Radiation Dosimetry Department, National Institute for Standards (NIS), Ministry of Scientific Research, Haram, 12211- Giza, P.O. Box: 136 (Egypt)]. E-mail: maghrabism@yahoo.com

    2007-02-15

    EPR spectroscopy is a fast and powerful technique for the identification of irradiated food. Crab exoskeleton was divided into six parts: dactyl, cheliped, carapace, apron, swimming legs, and walking legs. Samples of the exoskeleton were prepared and irradiated to Cs-137 gamma radiation in the range (1.156-5.365 kGy). EPR spectra of unirradiated as well as irradiated samples were recorded and analyzed. Response to gamma radiation was plotted for each part of the exoskeleton, dactyl was found to be the most sensitive part, followed by the apron (38%), cheliped (37%), walking legs (30%), swimming legs (24%), and carapace (21%) relative to the dactyl response.

  12. Lymphangioma secondary to irradiation after mastectomy*

    Science.gov (United States)

    Oliveti, Aline; Biasi, Tatiana Basso; Funchal, Gabriella Di Giunta

    2017-01-01

    Lymphangioma is a rare benign disease of the lymphatic vessels. Typically, they are primary conditions but may be acquired secondarily, such as those caused by irradiation during radiotherapy for the treatment of breast cancer. The local lymphatic obstruction provoked by irradiation causes the appearance of asymptomatic hyaline vesicles on the irradiated skin. The present report describes a 78-year-old female patient, who initially presented hyaline vesicles that progressed into multiple papules with serous exudation of a yellowish and odorless secretion on the area of chronic radiodermitis in right breast. Despite the rarity of the case, we emphasize the importance of knowledge regarding dermatological disease for early diagnosis and proper medical conduct.

  13. Pathogenesis of irradiation-induced cognitive dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Abayomi, O.K. [Howard Univ. Hospital, Washington, DC (United States). Dept. of Radiation Oncology

    1996-12-31

    Neurocognitive dysfunction is a common sequela of cranial irradiation that is especially severe in young children. The underlying mechanisms of this disorder have not been described. The present review describes the role of the hippocampus and the anatomically related cortex in memory function and its marked susceptibility to ischemic and hypoxic injury. Based on studies of animal models of human amnesia and histopathological findings in the irradiated brain, the neurocognitive sequela of cranial irradiation can be seen to be mediated through vascular injury, resulting in ischemia and hypoxia in the hippocampal region. Recognition of the site and mechanisms of this injury may lead to the development of techniques to minimize the risks. (orig.).

  14. Food irradiation - pros and cons

    Energy Technology Data Exchange (ETDEWEB)

    1983-01-01

    The use of ionising radiation for food preservation is a much-disputed topic, both among experts and among consumers. Pros and cons of this issue were discussed in detail at the consumers' forum. Professor Dr. Johannes Friedrich Diehl, Director of the Institute for Biochemistry of the Food Research Centre, Karlsruhe, is a well-known supporter of the new method of food preservation; he sees advantages in the radiopreservation of food because, for example, losses due to inedibility are reduced, the danger of salmonellosis is decreased, just as the use of chemicals. He thinks this method to be without danger to health, shown by many years of experience. Opponents to food irradiation like Prof. Dr. Konrad Pfeilsticker, Professor for food science and food chemistry at the Bonn University deem the method to be unnecessary and raise the problem of qualitative changes caused in the food. In the course of the discussions, the pros and cons seemed to balance each other out.

  15. Frequency of a FAS ligand gene variant associated with inherited feline autoimmune lymphoproliferative syndrome in British shorthair cats in New Zealand.

    Science.gov (United States)

    Aberdein, D; Munday, J S; Dittmer, K E; Heathcott, R W; Lyons, L A

    2017-11-01

    AIMS To determine the frequency of the FAS-ligand gene (FASLG) variant associated with feline autoimmune lymphoproliferative syndrome (FALPS) and the proportion of carriers of the variant in three British shorthair (BSH) breeding catteries in New Zealand. METHODS Buccal swabs were collected from all cats in two BSH breeding catteries from the South Island and one from the North Island of New Zealand. DNA was extracted and was tested for the presence of the FASLG variant using PCR. Cats with the FASLG variant were identified and the frequency of the FASLG variant allele calculated. Pedigree analysis was performed and inbreeding coefficients were calculated for cats with the FASLG variant. RESULTS Of 32 BSH cats successfully tested for the presence of the FASLG variant, one kitten (3%) was homozygous (FALPS-affected), and seven (22%) cats were heterozygous (carriers) for the FASLG variant allele, and 24 (75%) cats were homozygous for the wild type allele. The overall frequency of the FASLG variant allele in these 32 cats was 0.14. Cats carrying the FASLG variant were from all three breeding catteries sampled, including two catteries that had not previously reported cases of FALPS. Pedigree analysis revealed common ancestry of FALPS-affected and carrier cats within six generations, as well as frequent inbreeding, with inbreeding coefficients >0.12 for five cats with the FASLG variant. CONCLUSIONS AND CLINICAL RELEVANCE There was a high frequency of the FASLG variant allele (0.14) in this small sample of BSH cats, with 22% of healthy cats identified as carriers of the FASLG variant. For an inherited disease, lethal at a young age, in a small population in which inbreeding is common, these results are significant. To prevent future cases of disease and stop further spread of the FASLG variant allele within the BSH population in New Zealand, it is recommended that all BSH and BSH-cross cats be tested for the presence of the FASLG variant before mating. Cats identified as

  16. Protective efficacy of vitamins C and E on p,p'-DDT-induced cytotoxicity via the ROS-mediated mitochondrial pathway and NF-κB/FasL pathway.

    Science.gov (United States)

    Jin, Xiaoting; Song, Li; Liu, Xiangyuan; Chen, Meilan; Li, Zhuoyu; Cheng, Long; Ren, Hua

    2014-01-01

    Dichlorodiphenoxytrichloroethane (DDT) is a known persistent organic pollutant and liver damage toxicant. However, there has been little emphasis on the mechanism underlying liver damage toxicity of DDT and the relevant effective inhibitors. Hence, the present study was conducted to explore the protective effects of vitamin C (VC) and vitamin E (VE) on the cytotoxicity of DDT in HL-7702 cells and elaborate the specific molecular mechanisms. The results demonstrated that p,p'-DDT exposure at over 10 µM depleted cell viability of HL-7702 cells and led to cell apoptotic. p,p'-DDT treatment elevated the level of reactive oxygen species (ROS) generation, induced mitochondrial membrane potential, and released cytochrome c into the cytosol, with subsequent elevations of Bax and p53, along with suppression of Bcl-2. In addition, the activations of caspase-3 and -8 were triggered. Furthermore, p,p'-DDT promoted the expressions of NF-κB and FasL. When the cells were exposed to the NF-κB inhibitor (PDTC), the up-regulated expression of FasL was attenuated. Strikingly, these alterations caused by DDT treatment were prevented or reversed by the addition of VC or VE, and the protective effects of co-treatment with VC and VE were higher than the single supplement with p,p'-DDT. Taken together, these findings provide novel experimental evidences supporting that VC or/and VE could reduce p,p'-DDT-induced cytotoxicity of HL-7702 cells via the ROS-mediated mitochondrial pathway and NF-κB/FasL pathway.

  17. Protective efficacy of vitamins C and E on p,p'-DDT-induced cytotoxicity via the ROS-mediated mitochondrial pathway and NF-κB/FasL pathway.

    Directory of Open Access Journals (Sweden)

    Xiaoting Jin

    Full Text Available Dichlorodiphenoxytrichloroethane (DDT is a known persistent organic pollutant and liver damage toxicant. However, there has been little emphasis on the mechanism underlying liver damage toxicity of DDT and the relevant effective inhibitors. Hence, the present study was conducted to explore the protective effects of vitamin C (VC and vitamin E (VE on the cytotoxicity of DDT in HL-7702 cells and elaborate the specific molecular mechanisms. The results demonstrated that p,p'-DDT exposure at over 10 µM depleted cell viability of HL-7702 cells and led to cell apoptotic. p,p'-DDT treatment elevated the level of reactive oxygen species (ROS generation, induced mitochondrial membrane potential, and released cytochrome c into the cytosol, with subsequent elevations of Bax and p53, along with suppression of Bcl-2. In addition, the activations of caspase-3 and -8 were triggered. Furthermore, p,p'-DDT promoted the expressions of NF-κB and FasL. When the cells were exposed to the NF-κB inhibitor (PDTC, the up-regulated expression of FasL was attenuated. Strikingly, these alterations caused by DDT treatment were prevented or reversed by the addition of VC or VE, and the protective effects of co-treatment with VC and VE were higher than the single supplement with p,p'-DDT. Taken together, these findings provide novel experimental evidences supporting that VC or/and VE could reduce p,p'-DDT-induced cytotoxicity of HL-7702 cells via the ROS-mediated mitochondrial pathway and NF-κB/FasL pathway.

  18. Protective Efficacy of Vitamins C and E on p,p′-DDT-Induced Cytotoxicity via the ROS-Mediated Mitochondrial Pathway and NF-κB/FasL Pathway

    Science.gov (United States)

    Jin, Xiaoting; Song, Li; Liu, Xiangyuan; Chen, Meilan; Li, Zhuoyu; Cheng, Long; Ren, Hua

    2014-01-01

    Dichlorodiphenoxytrichloroethane (DDT) is a known persistent organic pollutant and liver damage toxicant. However, there has been little emphasis on the mechanism underlying liver damage toxicity of DDT and the relevant effective inhibitors. Hence, the present study was conducted to explore the protective effects of vitamin C (VC) and vitamin E (VE) on the cytotoxicity of DDT in HL-7702 cells and elaborate the specific molecular mechanisms. The results demonstrated that p,p′-DDT exposure at over 10 µM depleted cell viability of HL-7702 cells and led to cell apoptotic. p,p′-DDT treatment elevated the level of reactive oxygen species (ROS) generation, induced mitochondrial membrane potential, and released cytochrome c into the cytosol, with subsequent elevations of Bax and p53, along with suppression of Bcl-2. In addition, the activations of caspase-3 and -8 were triggered. Furthermore, p,p′-DDT promoted the expressions of NF-κB and FasL. When the cells were exposed to the NF-κB inhibitor (PDTC), the up-regulated expression of FasL was attenuated. Strikingly, these alterations caused by DDT treatment were prevented or reversed by the addition of VC or VE, and the protective effects of co-treatment with VC and VE were higher than the single supplement with p,p′-DDT. Taken together, these findings provide novel experimental evidences supporting that VC or/and VE could reduce p,p′-DDT-induced cytotoxicity of HL-7702 cells via the ROS-mediated mitochondrial pathway and NF-κB/FasL pathway. PMID:25464339

  19. Tetrandrine has anti-adipogenic effect on 3T3-L1 preadipocytes through the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Byeong-Churl, E-mail: jangbc123@gw.kmu.ac.kr

    2016-08-05

    Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from the roots of Stephania tetrandra S. Moore and has been shown to possess anti-inflammatory and anti-cancerous activities. In this study, the effect of tetrandrine on adipogenesis in 3T3-L1 preadipocytes was investigated. Tetrandrine at 10 μM concentration strongly inhibited lipid accumulation and triglyceride (TG) synthesis during the differentiation of 3T3-L1 preadipocytes into adipocytes. On mechanistic levels, tetrandrine reduced not only the expressions of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A but also the phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) during 3T3-L1 adipocyte differentiation. Tetrandrine also reduced the mRNA expression of leptin, but not adiponectin, during 3T3-L1 adipocyte differentiation. Collectively, these findings show that tetrandrine has strong anti-adipogenic effect on 3T3-L1 preadipocytes and the effect is largely attributable to the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3. - Highlights: • Tetrandrine, a bisbenzylisoquinoline alkaloid, inhibits adipogenesis. • Tetrandrine inhibits C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3 in 3T3-L1 adipocytes. • Tetrandrine reduces leptin, but not adiponectin, expression in 3T3-L1 adipocytes. • Tetrandrine may thus have therapeutic potential against obesity.

  20. Artesunate inhibits adipogeneis in 3T3-L1 preadipocytes by reducing the expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Byeong-Churl, E-mail: jangbc123@gw.kmu.ac.kr

    2016-05-20

    Differentiation of preadipocyte, also called adipogenesis, leads to the phenotype of mature adipocyte. However, excessive adipogenesis is closely linked to the development of obesity. Artesunate, one of artemisinin-type sesquiterpene lactones from Artemisia annua L., is known for anti-malarial and anti-cancerous activities. In this study, we investigated the effect of artesunate on adipogenesis in 3T3-L1 preadipocytes. Artesunate strongly inhibited lipid accumulation and triglyceride (TG) synthesis during the differentiation of 3T3-L1 preadipocytes into adipocytes at 5 μM concentration. Artesunate at 5 μM also reduced not only the expressions of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A but also the phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) during adipocyte differentiation. Moreover, artesunate at 5 μM reduced leptin, but not adiponectin, mRNA expression during adipocyte differentiation. Taken together, these findings demonstrate that artesunate inhibits adipogenesis in 3T3-L1 preadipoytes through the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3. -- Highlights: •Artesunate, an artemisinin derivative, inhibits adipogenesis. •Artesunate inhibits C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3 in 3T3-L1 adipocytes. •Artesunate reduces leptin, but not adiponectin, expression in 3T3-L1 adipocytes. •Artesunate thus may have therapeutic potential against obesity.

  1. Epigallocatechin-3-gallate inhibits adipogenesis through down-regulation of PPARγ and FAS expression mediated by PI3K-AKT signaling in 3T3-L1 cells.

    Science.gov (United States)

    Wu, Mengqing; Liu, Dan; Zeng, Rong; Xian, Tao; Lu, Yi; Zeng, Guohua; Sun, Zhangzetian; Huang, Bowei; Huang, Qiren

    2017-01-15

    Epigallocatechin-3-gallate (EGCG), a major component in green tea, functions as extensive bioactivities including anti-inflammation, anti-oxidation, and anti-cancer. However, little is known about its anti-adipogenesis and underlying mechanisms. The purport of this study sought to investigate effects of EGCG on 3T3-L1 preadipocyte differentiation and to explore its possible mechanisms. The 3T3-L1 cells were induced to differentiate under the condition of pro-adipogenic cocktail with or without indicated EGCG concentrations (10, 50, 100, 200µM) for 2, 4, 6 and 8 days, respectively. Also, another batch of 3T3-L1 cells was induced under the optimal EGCG concentration (100µM) with or without SC3036 (PI3K activator, 10µM) or SC79 (AKT activator, 0.5µM) for 8 days. Subsequently, the cell viability was examined by MTT assay and the cell morphology was visualized by Oil red O staining. Finally, the mRNA levels including peroxisome proliferator activated receptor γ (PPARγ) and fatty acid synthase (FAS) were detected by quantitative real time PCR, while the protein levels of PPARγ, FAS, phosphatidylinositol 3 kinase (PI3K), insulin receptor substrate1(IRS1), AKT, and p-AKT were measured by immunoblotting analysis. Our results showed that EGCG inhibited adipogenesis of 3T3-L1 preadipocyte in a concentration-dependent manner. Moreover, the inhibitory effects were reversed by SC3036 or SC79, suggesting that the inhibitory effects of EGCG are mediated by PI3K-AKT signaling to down-regulate PPARγ and FAS expression levels. The findings shed light on EGCG anti-adipogenic effects and its underlying mechanism and provide a novel preventive-therapeutic potential for obesity subjects as a compound from Chinese green tea. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Vaporization of perfluorocarbon droplets using optical irradiation

    National Research Council Canada - National Science Library

    Strohm, Eric; Rui, Min; Gorelikov, Ivan; Matsuura, Naomi; Kolios, Michael

    2011-01-01

    .... Droplet vaporization has been previously demonstrated using acoustic methods. We propose using laser irradiation as a means to induce PFC droplet vaporization using a method we term optical droplet vaporization (ODV...

  3. Endoscopic appearance of irradiated gastric mucosa

    Energy Technology Data Exchange (ETDEWEB)

    De Sagher, L.I.; Van den Heule, B.; Van Houtte, P.; Engelholm, L.; Balikdjan, D.; Bleiberg, H.

    1979-09-01

    Irradiation of the epigastric area for gastric cancer may induce actinic lesions of the stomach characterized on endoscopic examination by ulcerations, haemorrhagic gastritis, fragility of the mucosa, thickening and congestion of the gastric folds.

  4. Total lymphoid irradiation in alloimmunity and autoimmunity

    Energy Technology Data Exchange (ETDEWEB)

    Strober, S.

    1987-12-01

    Total lymphoid irradiation has been used as an immunosuppressive regimen in autoimmune disease and organ transplantation. The rationale for its use originated from studies of patients with Hodgkin disease, in whom this radiotherapy regimen was noted to induce profound and long-lasting immune suppression and yet was well tolerated, with few long-term side effects. Total lymphoid irradiation is a unique immunosuppressive regimen that produces a selective (and long-lasting) reduction in the number and function of helper T cells and certain subsets of B cells. Conventional immunosuppressive drugs show little selectivity, and their effects are short-lived. The most important aspect of total lymphoid irradiation is the potential for achieving transplantation tolerance and permanent remissions in autoimmune disease in laboratory animals. Attempts are being made to achieve similar goals in humans given total lymphoid irradiation, so that immunosuppressive drugs can be ultimately withdrawn from transplant recipients and patients with lupus nephritis. 28 references.

  5. Neoplasia in fast neutron-irradiated beagles

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, E.W.; Zook, B.C.; Casarett, G.W.; Deye, J.A.; Adoff, L.M.; Rogers, C.C.

    1981-09-01

    One hundred fifty-one beagle dogs were irradiated with either photons or fast neutrons (15 MeV) to one of three dose-limiting normal tissues--spinal cord, lung, or brain. The radiation was given in four fractions per week for 5 weeks (spinal cord), 6 weeks (lung), or 7 weeks (brain) to total doses encompassing those given clinically for cancer management. To date, no nonirradiated dogs or photon-irradiated dogs have developed any neoplasms. Seven dogs receiving fast neutrons have developed 9 neoplasms within the irradiated field. Of the neutron-irradiated dogs at risk, the incidence of neoplasia was 15%. The latent period for radiation-induced cancers has varied from 1 to 4 1/2 years at this time in the study.

  6. Neoplasia in fast neutron-irradiated beagles

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, E.W. (George Washington Univ. Medical Center, Washington, DC); Zook; B.C.; Casarett, G.W.

    1981-09-01

    One hundred fifty-one beagle dogs were irradiated with either photons or fast neutrons (15 MeV) to one of three dose-limiting normal tissues - spinal cord, lung, or brain. The radiation was given in four fractions per week for 5 weeks (spinal cord), 6 weeks (lung), 7 weeks (brain) to total doses encompassing those given clinically for cancer management. To date, no nonirradiated dogs or photon-irradiated dogs have developed neoplasms within the irradiated field. Of the neutron-irradiated dogs at risk, the incidence of neoplasia was 15%. The latent period for radiation-induced cancers has varied from 1 to 4 1/2 years at this time in the study.

  7. Downscaling of global solar irradiation in R

    CERN Document Server

    Antonanzas-Torres, F; Antonanzas, J; Perpiñán, O

    2013-01-01

    A methodology for downscaling solar irradiation from satellite-derived databases is described using R software. Different packages such as raster, parallel, solaR, gstat, sp and rasterVis are considered in this study for improving solar resource estimation in areas with complex topography, in which downscaling is a very useful tool for reducing inherent deviations in satellite-derived irradiation databases, which lack of high global spatial resolution. A topographical analysis of horizon blocking and sky-view is developed with a digital elevation model to determine what fraction of hourly solar irradiation reaches the Earth's surface. Eventually, kriging with external drift is applied for a better estimation of solar irradiation throughout the region analyzed. This methodology has been implemented as an example within the region of La Rioja in northern Spain, and the mean absolute error found is a striking 25.5% lower than with the original database.

  8. Argon laser irradiation of the otolithic organ

    Energy Technology Data Exchange (ETDEWEB)

    Okuno, T.; Nomura, Y.; Young, Y.H.; Hara, M. (Univ. of Tokyo (Japan))

    1990-12-01

    An argon laser was used to irradiate the otolithic organs of guinea pigs and cynomolgus monkeys. After stapedectomy, the argon laser (1.5 W x 0.5 sec/shot) irradiated the utricle or saccule without touching the sensory organs. The stapes was replaced over the oval window after irradiation. The animals used for acute observation were killed immediately for morphologic studies; those used for long-term observation were kept alive for 2, 4, or 10 weeks. Acute observation revealed that sensory and supporting cells were elevated from the basement membrane only in the irradiated area. No rupture of the membranous labyrinth was observed. Long-term observation revealed that the otolith of the macula utriculi had disappeared in 2-week specimens. The entire macula utricili had disappeared in 10-week specimens. No morphologic changes were observed in cochlea, semicircular canals, or membranous labyrinth. The saccule showed similar changes.

  9. Food Irradiation: What You Need to Know

    Science.gov (United States)

    ... shelf life of foods by reducing or eliminating microorganisms and insects. Like pasteurizing milk and canning fruits ... and delay ripening of fruit to increase longevity. Sterilization – irradiation can be used to sterilize foods, which ...

  10. Van de Graaff Irradiation of Materials

    Energy Technology Data Exchange (ETDEWEB)

    Quigley, Kevin [Argonne National Lab. (ANL), Argonne, IL (United States); Chemerisov, Sergey [Argonne National Lab. (ANL), Argonne, IL (United States); Tkac, Peter [Argonne National Lab. (ANL), Argonne, IL (United States); Vandegrift, George F. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2016-10-01

    Through irradiations using our 3 MeV Van de Graaf accelerator, Argonne is testing the radiation stability of components of equipment that are being used to dispense molybdenum solutions for use as feeds to 99mTc generators and in the 99mTc generators themselves. Components have been irradiated by both a direct electron beam and photons generated from a tungsten convertor.

  11. Molecular dynamics for irradiation driven chemistry

    DEFF Research Database (Denmark)

    Sushko, Gennady B.; Solov'yov, Ilia A.; Solov'yov, Andrey V.

    2016-01-01

    involving small molecules or molecular fragments. We advocate that the quantum transformations, such as molecular bond breaks, creation and annihilation of dangling bonds, electronic charge redistributions, changes in molecular topologies, etc., could be incorporated locally into the molecular force fields......A new molecular dynamics (MD) approach for computer simulations of irradiation driven chemical transformations of complex molecular systems is suggested. The approach is based on the fact that irradiation induced quantum transformations can often be treated as random, fast and local processes...

  12. BNCT irradiation facility at the JRR-4

    Energy Technology Data Exchange (ETDEWEB)

    Torii, Y.; Kishi, T.; Kumada, H.; Yamamoto, K.; Sakurai, F.; Takayanagi, M. [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2000-10-01

    The JRR--4 was modified for fuel enrichment reducing and reactor equipment renewal. And also a medical irradiation facility for the Boron Neutron Capture Therapy (BNCT) was installed at the JRR--4 in that time. The medical irradiation facility has been composed of a heavy water tank, a collimator and an irradiation room. The heavy water tank has four layers of heavy water for spectrum shifter and 75cm-thickness aluminum for the shield of fast neutron. The collimator is for collimating thermal neutron and epithermal neutron using polyethylene with lithium-fluoride and shielding gamma ray by bismuth. The irradiation room has sufficient space at exit side of the beam, to accommodate a large working area for setting the patient. Both of the medical treatment room and the patient-monitoring area were prepared adjacent to the irradiation room. The medical irradiation facility in the JRR-4 is designed to permit selection of neutron energies from thermal neutron to epithermal neutron by changing the thickness of heavy water layers. Therefore it is available to continue the same kind of BNCT with thermal neutron used to perform in the JRR-2, as well as to commence the research and development of BNCT with epithermal neutron, which will make the brain tumor treatment possible at a deep part of brain. The full power operation of the JRR-4 was resumed with LEU fuel in October 1998 and currently performing some experiments to measure the neutron fluxes and physical doses for determinate characterization of the medical irradiation facility. The first medical irradiation for BNCT was carried out on 25th October 1999. The patient was treated by Tsukuba University group using thermal neutron beam included epi-thermal neutrons. (author)

  13. Radiation Biology Irradiator Dose Verification Survey.

    Science.gov (United States)

    Pedersen, Kurt H; Kunugi, Keith A; Hammer, Clifford G; Culberson, Wesley S; DeWerd, Larry A

    2016-02-01

    Interest in standardized dosimetry for radiobiological irradiators has expanded over the last decade. At a symposium held at NIST, "The Importance of Standardization of Dosimetry in Radiobiology", a set of 12 criteria necessary for adequate irradiation was developed by the authors. Here we report on our review of dosimetry methods from various peer-reviewed publications and found that none of them satisfied all 12 criteria set forth by the authors of the NIAD/NCI/NIST proceedings. The inadequate reporting of dosimetry methods in the literature raises questions regarding the accuracy of the dose delivered to animal test subjects and the resulting experimental results. For this reason, we investigated the level of accuracy of dose delivery in radiation biology studies. We performed an irradiator output verification study of 12 radiation biology laboratories (7 gamma and 5 X-ray units) using polymethyl methacrylate (PMMA) mouse phantoms and thermoluminescent dosimeters (TLDs) readouts at the University of Wisconsin Medical Radiation Research Center (UWMRRC). The laboratories housing each of these irradiators were asked to deliver specific doses to individual mouse phantoms. Simultaneously, mouse phantoms at the UWMRRC were irradiated with NIST-traceable reference beams representative of the subject laboratories' beam energies. The irradiated mouse phantoms were returned from the various institutions to the UWMRRC and the TLDs were processed, with their measured dose response compared to the known dose response of the calibration phantom TLDs. Of the five facilities using X-ray irradiators, only one delivered an output within 5% of the target dose. The dose differences for the other four X-ray irradiators ranged from 12 to 42%. These results indicate the potential need for standardization of dose determination and additional oversight of radiobiology investigations.

  14. Development of detection methods for irradiated foods

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jae Seung; Nam, Hye Seon; Oh, Kyong Nam; Woo, Si Ho; Kim, Kyeung Eun; Yi, Sang Duk; Park, Jun Young; Kim, Kyong Su; Hwang, Keum Taek

    2000-04-01

    In 1999, we have been studied (1) on the detection of irradiated foods by ESR spectroscopy, by thermoluminescence, and by viscometry for physical measurements, (2) on the detection of hydrocarbons and 2-alkylcyclobutanones derived from fatty foods by GC/MS for chemical measurements, (3) on the screening and detection of irradiated foods by Comet assay and immunochemical (ELISA) technique for biological or biochemical measurements.

  15. Embrittlement of irradiated ferritic/martensitic steels in the absence of irradiation hardening

    Energy Technology Data Exchange (ETDEWEB)

    Klueh, R.L. [Oak Ridge Noational Laboratory, TN (United States); Shiba, K. [Japan Atomic Energy Agency, Tokai-mura, Naga-gun, Ibaraki-ken (Japan); Sokolov, M. [Oak Ridge National Laboratory, Materials Science and Technology Div., TN (United States)

    2007-07-01

    Full text of publication follows: Neutron irradiation of 9-12% Cr ferritic/martensitic steels below 425-450 deg. C produces microstructural defects that cause an increase in yield stress and ultimate tensile strength. This irradiation hardening causes embrittlement, which is observed in Charpy impact and toughness tests as an increase in ductile-brittle transition temperature (DBTT). Based on observations that show little change in strength in these steels irradiated above 425-450 deg. C, the general conclusion has been that no embrittlement occurs above this irradiation-hardening temperature regime. In a recent study of F82H steel irradiated at 300, 380, and 500 deg. C, irradiation hardening-an increase in yield stress-was observed in tensile specimens irradiated at the two lower temperatures, but no change was observed for the specimens irradiated at 500 deg. C. As expected, an increase in DBTT occurred for the Charpy specimens irradiated at 300 and 380 deg. C. However, there was an unexpected increase in the DBTT of the specimens irradiated at 500 deg. C. The observed embrittlement was attributed to the irradiation-accelerated precipitation of Laves phase. This conclusion was based on results from a detailed thermal aging study of F82H, in which tensile and Charpy specimens were aged at 500, 550, 600, and 650 deg. C to 30,000 h. These studies indicated that there was a decrease in yield stress at the two highest temperatures and essentially no change at the two lowest temperatures. Despite the strength decrease or no change, the DBTT increased for Charpy specimens irradiated at all four temperatures. Precipitates were extracted from thermally aged specimens, and the amount of precipitate was correlated with the increase in transition temperature. Laves phase was identified in the extracted precipitates by X-ray diffraction. Earlier studies on conventional elevated-temperature steels also showed embrittlement effects above the irradiation-hardening temperature

  16. Development of detection methods for irradiated foods; development of immunological identification of irradiated foods

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyong Ae; Lee, Yoon Jin; Choi, Yoon Jung; Han, Su Kyong [Soonchunhyang University, Asan (Korea)

    2002-04-01

    Enzyme-linked Immunosorbent assay systems for the identification of irradiated egg, pork and chicken was developed. Eggs were irradiated in their shells to 0.5{approx}7kGy. Pork was irradiated to 0.5{approx}3kGy and chicken irradiated to 0.5kGy{approx}5kGy. The most sensitive proteins to irradiation were screened by SDS-PAGE and purified. Ovalbumin from egg, salt soluble protein(p) from pork, and salt soluble protein(c) from chicken showed the most sensitivity to irradiation. To investigate for a practical use in identifying of irradiated egg, pork and chicken, competitive ELISA was performed. The binding activity of ovalbumin to anti-ovalbumin IgG was reduced in a dose-dependent manner by irradiating up to 7kGy, and considerably lowered after irradiating at 7kGy. The concentration of 50% inhibition of ovalbumin to IgG was increased to 1.5(0.5kGy){approx}3.7(7kGy) times in an dose-dependent relationship. The binding activity of salt soluble protein(p) to anti-salt soluble protein IgG (anti-SSPp IgG)was also reduced in a dose-dependent manner by irradiating up to 3kGy, and considerably lowered after irradiating at 3kGy. The concentration of 50% inhibition of salt soluble protein to IgG was increased to 1.1(0.5kGy){approx}5.2(3kGy) times in a dose-dependent relationship. On the other hand, the binding activity of salt soluble protein(c) to anti-salt soluble protein IgG(anti-SSPc IgG) was reduced in a dose-dependent manner by irradiating up to 5kGy, too, and considerably lowered after irradiating at 5kGy. The concentration of 50% inhibition of salt soluble protein to IgG was increased to 1.1{approx}2.3 times in a dose-dependent relationship. SDS-PAGE of the irradiation sensitive proteins showed the partial breakdown of it was induced by irradiation. So, the lowering of binding activity was probably due to the partial breakdown of ovalbumin by irradiation. 25 refs., 12 figs., 5 tabs. (Author)

  17. Feasibility of protein-sparing modified fast by tube (ProMoFasT) in obesity treatment: a phase II pilot trial on clinical safety and efficacy (appetite control, body composition, muscular strength, metabolic pattern, pulmonary function test)

    OpenAIRE

    Sukkar, S. G.; Signori, A.; Borrini, C.; Barisione, G.; Ivaldi, C.; Romeo, C; Gradaschi, R.; Machello, N.; Nanetti, E.; Vaccaro, A. L.

    2013-01-01

    Anecdotal data in the last few years suggest that protein-sparing modified diet (PSMF) delivered by naso-gastric tube enteral (with continuous feeding) could attain an significant weight loss and control of appetite oral feeding, but no phase II studies on safety and efficacy have been done up to now. To verify the safety and efficacy of a protein-sparing modified fast administered by naso-gastric tube (ProMoFasT) for 10?days followed by 20?days of a low-calorie diet, in patients with morbid ...

  18. Fluid shear stress suppresses TNF-α-induced apoptosis in MC3T3-E1 cells: Involvement of ERK5-AKT-FoxO3a-Bim/FasL signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Bin, Geng; Bo, Zhang; Jing, Wang; Jin, Jiang; Xiaoyi, Tan; Cong, Chen; Liping, An; Jinglin, Ma; Cuifang, Wang; Yonggang, Chen [The Second Hospital of Lanzhou University, #82 Cuiyingmen, Lanzhou, 730000 Gansu (China); Orthopaedics Key Laboratory of Gansu Province, Lanzhou, 730000 Gansu (China); Yayi, Xia, E-mail: xiayayildey@163.com [The Second Hospital of Lanzhou University, #82 Cuiyingmen, Lanzhou, 730000 Gansu (China); Orthopaedics Key Laboratory of Gansu Province, Lanzhou, 730000 Gansu (China)

    2016-05-01

    TNF-α is known to induce osteoblasts apoptosis, whereas mechanical stimulation has been shown to enhance osteoblast survival. In the present study, we found that mechanical stimulation in the form of fluid shear stress (FSS) suppresses TNF-α induced apoptosis in MC3T3-E1 cells. Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family that has been implicated in cell survival. We also demonstrated that FSS imposed by flow chamber in vitro leads to a markedly activation of ERK5, which was shown to be protective against TNF-α-induced apoptosis, whereas the transfection of siRNA against ERK5 (ERK5-siRNA) reversed the FSS-medicated anti-apoptotic effects. An initial FSS-mediated activation of ERK5 that phosphorylates AKT to increase its activity, and a following forkhead box O 3a (FoxO3a) was phosphorylated by activated AKT. Phosphorylated FoxO3a is sequestered in the cytoplasm, and prevents it from translocating to nucleus where it can increase the expression of FasL and Bim. The inhibition of AKT-FoxO3a signalings by a PI3K (PI3-kinase)/AKT inhibitor (LY294002) or the transfection of ERK5-siRNA led to the nuclear translocation of non-phosphorylated FoxO3a, and increased the protein expression of FasL and Bim. In addition, the activation of caspase-3 by TNF-α was significantly inhibited by aforementioned FSS-medicated mechanisms. In brief, the activation of ERK5-AKT-FoxO3a signaling pathways by FSS resulted in a decreased expression of FasL and Bim and an inhibition of caspase-3 activation, which exerts a protective effect that prevents osteoblasts from apoptosis. - Highlights: • Fluid shear stress inhibits osteoblast apoptosis induced by TNF-α. • Inhibition of ERK5 activity by transfection of ERK5 siRNA blocks FSS-mediated anti-apoptotic effect in osteoblast. • Activated ERK5-AKT-FoxO3a-Bim/FasL signaling pathways by FSS is required to protect osteoblast from apoptosis.

  19. Food Irradiation | RadTown USA | US EPA

    Science.gov (United States)

    2017-08-07

    Using radiation to kill bacteria and other pathogens in food is called food irradiation. Irradiating food kills bacteria and molds that can make people sick. Irradiation does not remove toxins that are already in food. The high energy of the radiation breaks chemical bonds to stop bacteria and other pathogens from multiplying. Irradiation does not make food radioactive.

  20. Total lymphoid irradiation and discordant cardiac xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, E.; Dresdale, A.R.; Diehl, J.T.; Katzen, N.A.; Aronovitz, M.J.; Konstam, M.A.; Payne, D.D.; Cleveland, R.J. (Tufts Univ. School of Medicine, Boston, MA (USA))

    1990-01-01

    Total lymphoid irradiation can prolong concordant cardiac xenografts. The effects of total lymphoid irradiation in a discordant xenograft model (guinea pig to rat) were studied with and without adjuvant pharmacologic immunosuppression. Inbred Lewis rats were randomly allocated to one of four groups. Group 1 (n = 6) served as a control group and rats received no immunosuppression. Group 2 (n = 5) received triple-drug therapy that consisted of intraperitoneal azathioprine (2 mg/kg), cyclosporine (20 mg/kg), and methylprednisolone (1 mg/kg) for 1 week before transplantation. Group 3 animals (n = 5) received 15 Gy of total lymphoid irradiation in 12 divided doses over a 3-week period. Group 4 (n = 6) received both triple-drug therapy and total lymphoid irradiation as described for groups 2 and 3. Complement-dependent cytotoxicity assay was performed to determine if a correlation between complement-dependent cytotoxicity and rejection-free interval existed. Rejection was defined as cessation of graft pulsation and was confirmed by histologic test results. Only groups 1 and 2 showed a difference in survival (group 1, 6.9 +/- 1.0 minutes; group 2, 14.2 +/- 2.7 minutes, p = 0.02). Although total lymphoid irradiation did decrease complement-dependent cytotoxicity, linear regression revealed no correlation between complement-dependent cytotoxicity and graft survival (coefficient of correlation, 0.30). Unlike concordant cardiac xenografts, total lymphoid irradiation with or without triple-drug therapy does not prolong graft survival.

  1. Thermal conductivity of electron-irradiated graphene

    Science.gov (United States)

    Weerasinghe, Asanka; Ramasubramaniam, Ashwin; Maroudas, Dimitrios

    2017-10-01

    We report results of a systematic analysis of thermal transport in electron-irradiated, including irradiation-induced amorphous, graphene sheets based on nonequilibrium molecular-dynamics simulations. We focus on the dependence of the thermal conductivity, k, of the irradiated graphene sheets on the inserted irradiation defect density, c, as well as the extent of defect passivation with hydrogen atoms. While the thermal conductivity of irradiated graphene decreases precipitously from that of pristine graphene, k0, upon introducing a low vacancy concentration, c graphene lattice, further reduction of the thermal conductivity with the increasing vacancy concentration exhibits a weaker dependence on c until the amorphization threshold. Beyond the onset of amorphization, the dependence of thermal conductivity on the vacancy concentration becomes significantly weaker, and k practically reaches a plateau value. Throughout the range of c and at all hydrogenation levels examined, the correlation k = k0(1 + αc)-1 gives an excellent description of the simulation results. The value of the coefficient α captures the overall strength of the numerous phonon scattering centers in the irradiated graphene sheets, which include monovacancies, vacancy clusters, carbon ring reconstructions, disorder, and a rough nonplanar sheet morphology. Hydrogen passivation increases the value of α, but the effect becomes very minor beyond the amorphization threshold.

  2. Helium irradiation induced hardening in MNHS steels

    Science.gov (United States)

    Cui, Minghuan; Wang, Ji; Wang, Zhiguang; Shen, Tielong; Wei, Kongfang; Yao, Cunfeng; Sun, Jianrong; Gao, Ning; Zhu, Yabin; Pang, Lilong; Wang, Dong; Zhu, Huiping; Han, Yi; Fang, Xuesong

    2017-09-01

    A recently developed reduced activation martensitic MNHS steel was irradiated with 200 keV helium (He) ions to a fluence of 1.0 × 1020 ions/m2 at 300 °C and 1.0 × 1021 ions/m2 at 300 °C and 450 °C. After irradiation, transmission electron microscopy (TEM) and nano-indentation measurements were used to investigate the hardness change and defects induced by He irradiation. Two kinds of defects including He bubbles and dislocation loops are observed by TEM. Irradiation induces hardening of MNHS steels and peak hardness values occur in all irradiated samples. Hardness increments induced by He bubbles and dislocation loops are predicted and fitted with the experimental peak hardness increment, based on the dispersed barrier-hardening (DBH) model and the size and number density of the two defects. A good agreement is got between the predicted and experimental hardness increment and the obstacle strength factor of He bubbles is a little stronger than the obstacle strength of dislocation loops. Other possible contributions to irradiation induced hardening are also discussed.

  3. Thermoluminescence method for detection of irradiated food

    Energy Technology Data Exchange (ETDEWEB)

    Pinnioja, S

    1998-12-31

    A method of thermoluminescence (TL) analysis was developed for the detection of irradiated foods. The TL method is based on the determination of thermoluminescence of adhering or contaminating minerals separated from foods by wet sieving and treatment with high density liquid. Carbon tetrachloride provided a suitable alternative for foods that form gels with water. Thermoluminescence response of minerals in a first TL measurement is normalised with a second TL measurement of the same mineral sample after calibration irradiation to a dose of 5 kGy. The decision about irradiation is made on the basis of a comparison of the two TL spectra: if the two TL glow curves match in shape and intensity the sample has been irradiated, and if they are clearly different it has not been irradiated. An attractive feature of TL analysis is that the mineral material itself is used for calibration; no reference material is required. Foods of interest in the investigation were herbs, spices, berries and seafood. The presence of minerals in samples is a criterion for application of the method, and appropriate minerals were found in all herbs, spices and berries. The most common minerals in terrestrial food were tecto-silicates - quartz and feldspars - which with their intense and stable thermoluminescence were well suited for the analysis. Mica proved to be useless for detection purposes, whereas carbonate in the form of calcite separated from intestines of seafood was acceptable. Fading of the TL signal is considerable in the low temperature part of the glow curve during a storage of several months after irradiation. However, spices and herbs could easily be identified as irradiated even after two years storage. Conditions for seafood, which is stored in a freezer, are different, and only slight fading was observed after one year. The effect of mineral composition and structure on TL was studied for feldspars. Feldspars originating from subtropical and tropical regions exhibit lower TL

  4. A Solar Irradiance Climate Data Record

    Science.gov (United States)

    Coddington, O.; Lean, J. L.; Pilewskie, P.; Snow, M.; Lindholm, D.

    2016-08-01

    We present a new climate data record for total solar irradiance and solar spectral irradiance between 1610 and the present day with associated wavelength and time-dependent uncertainties and quarterly updates. The data record, which is part of the National Oceanic and Atmospheric Administration’s (NOAA) Climate Data Record (CDR) program, provides a robust, sustainable, and scientifically defensible record of solar irradiance that is of sufficient length, consistency, and continuity for use in studies of climate variability and climate change on multiple time scales and for user groups spanning climate modeling, remote sensing, and natural resource and renewable energy industries. The data record, jointly developed by the University of Colorado’s Laboratory for Atmospheric and Space Physics (LASP) and the Naval Research Laboratory (NRL), is constructed from solar irradiance models that determine the changes with respect to quiet sun conditions when facular brightening and sunspot darkening features are present on the solar disk where the magnitude of the changes in irradiance are determined from the linear regression of a proxy magnesium (Mg) II index and sunspot area indices against the approximately decade-long solar irradiance measurements of the Solar Radiation and Climate Experiment (SORCE). To promote long-term data usage and sharing for a broad range of users, the source code, the dataset itself, and supporting documentation are archived at NOAA's National Centers for Environmental Information (NCEI). In the future, the dataset will also be available through the LASP Interactive Solar Irradiance Data Center (LISIRD) for user-specified time periods and spectral ranges of interest.

  5. Irradiation test plan of DUPIC fuel

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Ki Kwang; Song, K. C.; Park, H. S. and others

    2000-04-01

    The objective of the irradiation test of DUPIC fuel at HANARO is to obtain the data of in-core behavior and evaluate the nuclear, thermal and mechanical performance of DUPIC fuel. The irradiation of DUPIC fuel will start at April 25, 2000 for about 2 months, and the burnup of 2,000 MWD/MTU will be attained for this period. The pre-irradiation examinations for DUPIC fuel, such as visual inspection, dimension measurement, He leak test and microstructure observation, was carried out. The post-irradiation examination items for the irradiated DUPIC fuel are planned to be the NDA test, visual inspection and dimension measurement, as well as the analyses for the fission gas release, the microstructure of pellets and the distribution and shape of imbedded nuclides. The DUPIC mini-elements were fabricated in the DFDF (IMEF M6 cell) using the G23-G2 rod. For the HANARO core calculation, the initial composition of DUPIC fuel was estimated using ORIGEN-2 code based on the burnup history of the G23-G2 rod. The design features of DUPIC pellets, the mini-element and the irradiation capsule, were supplemented considering the characteristics of DUPIC fuel and the results from the irradiation test of the simulated DUPIC fuel performed in 1999. The nuclear, thermohydraulic and mechanical characteristics of DUPIC fuel under the normal operation condition were evaluated for the safety analysis on the HANARO. Using these results, potential accidents initiated by DUPIC fuel were estimated, and Safety analyses on the locked rotor and RIA accidents were carried out in order to assess the integrity of DUPIC fuel under the accident condition initiated by the HANARO. Based on the results of these safety analyses, the supplemental countermeasures for securing the sufficient thermal margins were set up, as well. At the last, similar overseas and domestic cases were introduced.

  6. Quality of gamma ray-irradiated iceberg lettuce and treatments to minimize irradiation-induced disorders

    Science.gov (United States)

    Irradiation of Iceberg lettuce was recently approved by the FDA to enhance microbial safety and to extend shelf-life at doses up to 4 kGy. However, the radiation tolerance of whole head lettuce is unclear. The present study was conducted to investigate the effects of irradiation on the quality of he...

  7. Path dependent models to predict property changes in graphite irradiated at changing irradiation temperatures

    CSIR Research Space (South Africa)

    Kok, S

    2010-10-01

    Full Text Available .co.za ] Path dependent models to predict property changes in graphite irradiated at changing irradiation temperatures S KOK CSIR Advanced Mathematical Modelling, Modelling and Digital Science, PO Box 395, Pretoria, 0001, South Africa E-mail: skok...

  8. Detection of low amount of irradiated ingredients in non-irradiated precooked meals

    NARCIS (Netherlands)

    Marchioni, E; Horvatovich, P; Ndiaye, B; Miesch, M; Hasselmann, C

    The application of the European Standards for the detection of irradiated food by thermo luminescence of silicates, electron-spin resonance spectroscopy of bones or gas chromatography-mass spectrometry of 2-alkylcyclobutanones does not allow the detection of irradiated ingredients included in small

  9. Biological Effects after Prenatal Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Streffer, C.

    2004-07-01

    A Task Group of the International Commission on Radiological Protection (ICRP) has finished a report Biological Effects after Prenatal Irradiation (Embryo and Fetus) which has been approved by the Main Commission and Will be Published. Some new important scientific data shall be discussed in this contribution. During the preimplantation period lethality of the mammalian embryo is the dominating radiation effect. However, in mouse strains with genetic predispositions it has been shown that also malformations can be caused. This effect is genetically determined and its mechanisms is different from the induction of malformations during major organogenesis. Radiation exposures during this prenatal period leads ato an increase of genomic instability of cells in the normal appearing fetuses. These radiation effects can be transmitted to the next generation. A renewed analysis of individuals with severe mental retardation after exposures during the 8th to 15th week post conception in Hiroshima and Nagasaki gives evidence that a threshold dose exists for this effect around 300 mGy. This is supported by a number of experimental animal data which have been obtained from cellular and molecular investigations during the brain development. The data show the high radiosensitivity of the developing brain but also the various compensatory mechanisms and the enormous plasticity of these processes. The radiosensitivity varies strongly during the prenatal development. The highest sensitivity is found during the early and mid fetal period which is coinciding with weeks 8-15 post conception in humans. The lowest doses causing persistent damage are in the range of 100 to 300 mGy. For intelligence quotient scores a linear dose response model provides a satisfactory fit. From the experimental data it can be concluded that the fetal stage is most sensitive to the carcinogenic effect in comparison to the other prenatal stages. Such as clear situation cannot be obtained from the

  10. Activations of Both Extrinsic and Intrinsic Pathways in HCT 116 Human Colorectal Cancer Cells Contribute to Apoptosis through p53-Mediated ATM/Fas Signaling by Emilia sonchifolia Extract, a Folklore Medicinal Plant.

    Science.gov (United States)

    Lan, Yu-Hsuan; Chiang, Jo-Hua; Huang, Wen-Wen; Lu, Chi-Cheng; Chung, Jing-Gung; Wu, Tian-Shung; Jhan, Jia-Hua; Lin, Kuei-Li; Pai, Shu-Jen; Chiu, Yu-Jen; Tsuzuki, Minoru; Yang, Jai-Sing

    2012-01-01

    Emilia sonchifolia (L.) DC (Compositae), an herbaceous plant found in Taiwan and India, is used as folk medicine. The clinical applications include inflammation, rheumatism, cough, cuts fever, dysentery, analgesic, and antibacteria. The activities of Emilia sonchifolia extract (ESE) on colorectal cancer cell death have not been fully investigated. The purpose of this study explored the induction of apoptosis and its molecular mechanisms in ESE-treated HCT 116 human colorectal cancer cells in vitro. The methanolic ESE was characterized, and γ-humulene was formed as the major constituent (63.86%). ESE induced cell growth inhibition in a concentration- and time-dependent response by MTT assay. Apoptotic cells (DNA fragmentation, an apoptotic catachrestic) were found after ESE treatment by TUNEL assay and DNA gel electrophoresis. Alternatively, ESE stimulated the activities of caspase-3, -8, and -9 and their specific caspase inhibitors protected against ESE-induced cytotoxicity. ESE promoted the mitochondria-dependent and death-receptor-associated protein levels. Also, ESE increased ROS production and upregulated the levels of ATM, p53, and Fas in HCT 116 cells. Strikingly, p53 siRNA reversed ESE-reduced viability involved in p53-mediated ATM/Fas signaling in HCT 116 cells. In summary, our result is the first report suggesting that ESE may be potentially efficacious in the treatment of colorectal cancer.

  11. Activations of Both Extrinsic and Intrinsic Pathways in HCT 116 Human Colorectal Cancer Cells Contribute to Apoptosis through p53-Mediated ATM/Fas Signaling by Emilia sonchifolia Extract, a Folklore Medicinal Plant

    Directory of Open Access Journals (Sweden)

    Yu-Hsuan Lan

    2012-01-01

    Full Text Available Emilia sonchifolia (L. DC (Compositae, an herbaceous plant found in Taiwan and India, is used as folk medicine. The clinical applications include inflammation, rheumatism, cough, cuts fever, dysentery, analgesic, and antibacteria. The activities of Emilia sonchifolia extract (ESE on colorectal cancer cell death have not been fully investigated. The purpose of this study explored the induction of apoptosis and its molecular mechanisms in ESE-treated HCT 116 human colorectal cancer cells in vitro. The methanolic ESE was characterized, and γ-humulene was formed as the major constituent (63.86%. ESE induced cell growth inhibition in a concentration- and time-dependent response by MTT assay. Apoptotic cells (DNA fragmentation, an apoptotic catachrestic were found after ESE treatment by TUNEL assay and DNA gel electrophoresis. Alternatively, ESE stimulated the activities of caspase-3, -8, and -9 and their specific caspase inhibitors protected against ESE-induced cytotoxicity. ESE promoted the mitochondria-dependent and death-receptor-associated protein levels. Also, ESE increased ROS production and upregulated the levels of ATM, p53, and Fas in HCT 116 cells. Strikingly, p53 siRNA reversed ESE-reduced viability involved in p53-mediated ATM/Fas signaling in HCT 116 cells. In summary, our result is the first report suggesting that ESE may be potentially efficacious in the treatment of colorectal cancer.

  12. Extracorporeal immune therapy with immobilized agonistic anti-Fas antibodies leads to transient reduction of circulating neutrophil numbers and limits tissue damage after hemorrhagic shock/resuscitation in a porcine model.

    Science.gov (United States)

    Lögters, Tim T; Altrichter, Jens; Paunel-Görgülü, Adnana; Sager, Martin; Witte, Ingo; Ott, Annina; Sadek, Sarah; Baltes, Jessica; Bitu-Moreno, José; Schek, Alberto; Müller, Wolfram; Jeri, Teresa; Windolf, Joachim; Scholz, Martin

    2010-04-20

    Hemorrhagic shock/resuscitation is associated with aberrant neutrophil activation and organ failure. This experimental porcine study was done to evaluate the effects of Fas-directed extracorporeal immune therapy with a leukocyte inhibition module (LIM) on hemodynamics, neutrophil tissue infiltration, and tissue damage after hemorrhagic shock/resuscitation. In a prospective controlled double-armed animal trial 24 Munich Mini Pigs (30.3 +/- 3.3 kg) were rapidly haemorrhaged to reach a mean arterial pressure (MAP) of 35 +/- 5 mmHg, maintained hypotensive for 45 minutes, and then were resuscitated with Ringer' solution to baseline MAP. With beginning of resuscitation 12 pigs underwent extracorporeal immune therapy for 3 hours (LIM group) and 12 pigs were resuscitated according to standard medical care (SMC). Haemodynamics, haematologic, metabolic, and organ specific damage parameters were monitored. Neutrophil infiltration was analyzed histologically after 48 and 72 hours. Lipid peroxidation and apoptosis were specifically determined in lung, bowel, and liver. In the LIM group, neutrophil counts were reduced versus SMC during extracorporeal immune therapy. After 72 hours, the haemodynamic parameters MAP and cardiac output (CO) were significantly better in the LIM group. Histological analyses showed reduction of shock-related neutrophil tissue infiltration in the LIM group, especially in the lungs. Lower amounts of apoptotic cells and lipid peroxidation were found in organs after LIM treatment. Transient Fas-directed extracorporeal immune therapy may protect from posthemorrhagic neutrophil tissue infiltration and tissue damage.

  13. Quinacrine Inhibits ICAM-1 Transcription by Blocking DNA Binding of the NF-κB Subunit p65 and Sensitizes Human Lung Adenocarcinoma A549 Cells to TNF-α and the Fas Ligand.

    Science.gov (United States)

    Harada, Misuzu; Morimoto, Kyoko; Kondo, Tetsuya; Hiramatsu, Reiko; Okina, Yuji; Muko, Ryo; Matsuda, Iyo; Kataoka, Takao

    2017-12-02

    Quinacrine has been used for therapeutic drugs in some clinical settings. In the present study, we demonstrated that quinacrine decreased the expression of intercellular adhesion molecule-1 (ICAM-1) induced by tumor necrosis factor (TNF)-α and interleukin-1 (IL-1) α in human lung adenocarcinoma A549 cells. Quinacrine inhibited ICAM-1 mRNA expression and nuclear factor κB (NF-κB)-responsive luciferase reporter activity following a treatment with TNF-α and IL-1α. In the NF-κB signaling pathway, quinacrine did not markedly affect the TNF-α-induced degradation of the inhibitor of NF-κB or the TNF-α-induced phosphorylation of the NF-κB subunit, p65, at Ser-536 and its subsequent translocation to the nucleus. In contrast, a chromatin immunoprecipitation assay showed that quinacrine prevented the binding of p65 to the ICAM-1 promoter following TNF-α stimulation. Moreover, TNF-α and the Fas ligand effectively reduced the viability of A549 cells in the presence of quinacrine only. Quinacrine down-regulated the constitutive and TNF-α-induced expression of c-FLIP and Mcl-1 in A549 cells. These results revealed that quinacrine inhibits ICAM-1 transcription by blocking the DNA binding of p65 and sensitizes A549 cells to TNF-α and the Fas ligand.

  14. KEY RESULTS FROM IRRADIATION AND POST-IRRADIATION EXAMINATION OF AGR-1 UCO TRISO FUEL

    Energy Technology Data Exchange (ETDEWEB)

    Demkowicz, Paul A.; Hunn, John D.; Petti, David A.; Morris, Robert N.

    2016-11-01

    The AGR-1 irradiation experiment was performed as the first test of tristructural isotropic (TRISO) fuel in the US Advanced Gas Reactor Fuel Development and Qualification Program. The experiment consisted of 72 right cylinder fuel compacts containing approximately 3×105 coated fuel particles with uranium oxide/uranium carbide (UCO) fuel kernels. The fuel was irradiated in the Advanced Test Reactor for a total of 620 effective full power days. Fuel burnup ranged from 11.3 to 19.6% fissions per initial metal atom and time average, volume average irradiation temperatures of the individual compacts ranged from 955 to 1136°C. This paper focuses on key results from the irradiation and post-irradiation examination, which revealed a robust fuel with excellent performance characteristics under the conditions tested and have significantly improved the understanding of UCO coated particle fuel irradiation behavior within the US program. The fuel exhibited a very low incidence of TRISO coating failure during irradiation and post-irradiation safety testing at temperatures up to 1800°C. Advanced PIE methods have allowed particles with SiC coating failure to be isolated and meticulously examined, which has elucidated the specific causes of SiC failure in these specimens. The level of fission product release from the fuel during irradiation and post-irradiation safety testing has been studied in detail. Results indicated very low release of krypton and cesium through intact SiC and modest release of europium and strontium, while also confirming the potential for significant silver release through the coatings depending on irradiation conditions. Focused study of fission products within the coating layers of irradiated particles down to nanometer length scales has provided new insights into fission product transport through the coating layers and the role various fission products may have on coating integrity. The broader implications of these results and the application of

  15. The influence of Gamma Irradiation on flavonoïds content during storage of irradiated clementina

    Science.gov (United States)

    Oufedjikh, H.; Mahrouz, M.; Lacroix, M.; Amiot, M. J.; Taccini, M.

    1998-06-01

    The influence of Gamma irradiation on content of some important flavonoïds (flavonones glycosides and polymethoxylated flavones) was evaluated during storage of Moroccan clementina treated at a mean dose of 0.3 kGy and stored three months at 3'C. Results shows that at day one, gamma irradiation induced degradation of small quantities of these flavonoïds, however after 14 days of storage, the content of these compounds was significantly higher (p≤0.05) in irradiated samples. Irradiation stimulated biosynthesis of flavonoïds after 14 days of storage. Hesperidin was the major flavanones compounds in clementines. Nobiletin and Heptamethoxyflavone were the major polymethoxylated flavones in clementines. Our study demonstrated that the content of these compounds was significantly higher (p≤0.05) in irradiated samples.

  16. The influence of Gamma Irradiation on flavonoieds content during storage of irradiated clementina

    Energy Technology Data Exchange (ETDEWEB)

    Oufedjikh, H.; Mahrouz, M.; Lacroix, M.; Amiot, M.J.; Taccini, M

    1998-06-01

    The influence of Gamma irradiation on content of some important flavonoieds (flavonones glycosides and polymethoxylated flavones) was evaluated during storage of Moroccan clementina treated at a mean dose of 0.3 kGy and stored three months at 3 deg. C. Results shows that at day one, gamma irradiation induced degradation of small quantities of these flavonoieds, however after 14 days of storage, the content of these compounds was significantly higher (p{<=}0.05) in irradiated samples. Irradiation stimulated biosynthesis of flavonoieds after 14 days of storage. Hesperidin was the major flavanones compounds in clementines. Nobiletin and Heptamethoxyflavone were the major polymethoxylated flavones in clementines. Our study demonstrated that the content of these compounds was significantly higher (p{<=}0.05) in irradiated samples.

  17. Assessing Nutrients Availability of Irradiated and Non-Irradiated Biosolids for the Agriculture Re-use

    Energy Technology Data Exchange (ETDEWEB)

    Magnavacca, Cecilia; Sanchez, Monica

    2003-07-01

    Irradiation provides a fast and reliable means to disinfect biosolids generated by municipal wastewater treatment processes. The chemical integrity of some substances may be altered thus change the availability of plant nutrients. Chemical analyses on the biosolids showed a release of mineral forms of Nitrogen while Phosphorus chemical forms were not altered. Higher amounts of mineralized N were indirectly demonstrated in soils with irradiated biosolids by a respiration experiment, and higher nitrate concentrations were measured in the irradiated biosolids amended soils at field experiments. Crop field experiments (lettuce and sugarcane) confirmed that irradiated biosolids have higher fertilizing capability than equal amounts of non-irradiated biosolids. Maximum dose rate had no additive effect but a depleted result, thus marking the importance of the use of moderate biosolids rates. (author)

  18. Low irradiance losses of photovoltaic modules

    Energy Technology Data Exchange (ETDEWEB)

    Mavromatakis, F.; Vignola, F.; Marion, B.

    2017-11-01

    The efficiency of a photovoltaic cell/module changes, as the intensity of incident irradiance decreases, in a non linear way and these changes are referred to as low irradiance losses. In this study data from field experiments, developed and organized by the National Renewable Energy Laboratory, are used to evaluate the low irradiance losses for a variety of module technologies. The results demonstrate that the ratio of the normalized power divided by the normalized short circuit current provide a good measure of the module's low light efficiency losses after both the maximum power and the short circuit current are adjusted for temperature effects. The normalized efficiencies determined through the field data, spanning for several months, are in good agreement with those determined under controlled conditions in a solar simulator. An analytical relation for the normalized efficiency is proposed based on existing formulation for the fill factor. Despite the approximate nature of the fill factor relation, this approach produces reliable results. It will be shown that a normalized efficiency curve can be used to extract information on the series and shunt resistances of the PV module and that the shunt resistance as a function of solar irradiance can be studied. Alternately, this formulation can be used to study the low irradiance losses of a module when the internal resistances are known.

  19. RESTORATION INDUCED BY CATALASE IN IRRADIATED MICROORGANISMS

    Science.gov (United States)

    Latarjet, Raymond; Caldas, Luis Renato

    1952-01-01

    1. E. coli, strain K-12, and B. megatherium 899, irradiated in strict but still undefined physiological conditions with certain heavy doses of ultraviolet light, are efficiently restored by catalase, which acts on or fixes itself upon the bacteria in a few minutes. This restoration (C. R.), different from photorestoration, is aided by a little visible light. 2. At 37° the restorability lasts for about 2 hours after UV irradiation; the restored cells begin to divide at the same time as the normal survivors. 3. C. R. is not produced after x-irradiation. 4. B. megatherium Mox and E. coli, strain B/r show little C. R.; E. coli strain B shows none. None of these three strains is lysogenic, whereas the two preceding catalase-restorable strains are. 5. Phage production in the system "K-12 infected with T2 phage" is restored by catalase after UV irradiation, whereas phage production in the system "infected B" is not. 6. With K-12, catalase does not prevent the growth of phage and the lysis induced by UV irradiation (Lwoff's phenomenon). 7. Hypotheses are discussed concerning: (a) the chemical nature of this action of catalase; (b) a possible relation between C. R. and lysogenicity of the sensitive bacteria; (c) the consequences of such chemical restorations on the general problem of cell radiosensitivity. PMID:14898028

  20. Mechanical performance of irradiated beryllium pebbles

    Energy Technology Data Exchange (ETDEWEB)

    Scaffidi-Argentina, F.; Dalle-Donne, M.; Werle, H. [Forschungszentrum Karlsruhe GmbH Technik und Umwelt (Germany). Inst. fuer Neutronenphysik und Reaktortechnik

    1998-01-01

    For the Helium Cooled Pebble Bed (HCPB) Blanket, which is one of the two reference concepts studied within the European Fusion Technology Programme, the neutron multiplier consists of a mixed bed of about 2 and 0.1-0.2 mm diameter beryllium pebbles. Beryllium has no structural function in the blanket, however microstructural and mechanical properties are important, as they might influence the material behavior under neutron irradiation. The EXOTIC-7 as well as the `Beryllium` experiments carried out in the HFR reactor in Petten are considered as the most detailed and significant tests for investigating it. This paper reviews the present status of beryllium post-irradiation examinations performed at the Forschungszentrum Karlsruhe with samples from these irradiation experiments, emphasizing the effects of irradiation of essential material properties and trying to elucidate the processes controlling the property changes. The microstructure, the porosity distribution, the impurity content, the behavior under compression loads and the compatibility of the beryllium pebbles with lithium orthosilicate (Li{sub 4}SiO{sub 4}) during the in-pile irradiation are presented and critically discussed. Qualitative information on ductility and creep obtained by hardness-type measurements are also supplied. (author)

  1. Infrared Irradiation: Toward Green Chemistry, a Review

    Directory of Open Access Journals (Sweden)

    René Escobedo

    2016-03-01

    Full Text Available This review provides a comprehensive overview of where infrared irradiation has been employed, mainly as regards activating green mode for natural products extractions, as well as to favor a reaction, highlighting its actual importance. It is also underlined that infrared irradiation heating has been around for a long time; however, only in the last eighteen years have many of its advantages been applied to satisfy a wide range of chemical processes, natural products extractions, and for the promotion of many kinds of reactions. In addition, it is brought to light that near infrared irradiation is more efficient than middle and far infrared irradiations, being easily controllable and with the quality of a fast responding heat source. Thus, the main objective of this review is to offer infrared irradiation as an alternative clean energy source to activate reactions, in addition to favor the selective extraction of natural products, all of which is within the Green Chemistry protocol. Some recent results from our laboratory are also included.

  2. Infrared Irradiation: Toward Green Chemistry, a Review.

    Science.gov (United States)

    Escobedo, René; Miranda, René; Martínez, Joel

    2016-03-26

    This review provides a comprehensive overview of where infrared irradiation has been employed, mainly as regards activating green mode for natural products extractions, as well as to favor a reaction, highlighting its actual importance. It is also underlined that infrared irradiation heating has been around for a long time; however, only in the last eighteen years have many of its advantages been applied to satisfy a wide range of chemical processes, natural products extractions, and for the promotion of many kinds of reactions. In addition, it is brought to light that near infrared irradiation is more efficient than middle and far infrared irradiations, being easily controllable and with the quality of a fast responding heat source. Thus, the main objective of this review is to offer infrared irradiation as an alternative clean energy source to activate reactions, in addition to favor the selective extraction of natural products, all of which is within the Green Chemistry protocol. Some recent results from our laboratory are also included.

  3. ESR spectroscopic properties of irradiated gum Arabic.

    Science.gov (United States)

    Leonor, S J; Gómez, J A; Kinoshita, A; Calandreli, I; Tfouni, E; Baffa, O

    2013-12-01

    Electron spin resonance (ESR) spectra of irradiated gum Arabic with doses between 0.5 and 5 kGy were studied. A linear relationship between the absorbed dose and the intensities of the ESR spectra was observed. ESR spectra of irradiated gum Arabic showed a decay of relative concentrations of free radicals originated by radiation and the production of at least two species of free radicals with half-times: 3.3 and 125.4 h. The results of spectral simulations for these radical groups were giso=2.0046; A=1.2 mT and gx=gy=2.0062, gz=2.0025. Hydration and dehydration of irradiated gum Arabic returns the ESR spectrum to its initial state before irradiation. The results show that ESR can be used as simple and reliable method to detect irradiated gum Arabic up to 60 days after initial radiation with doses on the order of 5 kGy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Mutation induced with ion beam irradiation in rose

    Science.gov (United States)

    Yamaguchi, H.; Nagatomi, S.; Morishita, T.; Degi, K.; Tanaka, A.; Shikazono, N.; Hase, Y.

    2003-05-01

    The effects of mutation induction by ion beam irradiation on axillary buds in rose were investigated. Axillary buds were irradiated with carbon and helium ion beams, and the solid mutants emerged after irradiation by repeated cutting back. In helium ion irradiation, mutations were observed in plants derived from 9 buds among 56 irradiated buds in 'Orange Rosamini' and in plants derived from 10 buds among 61 irradiated buds in 'Red Minimo'. In carbon ion, mutations were observed in plants derived from 12 buds among 88 irradiated buds in 'Orange Rosamini'. Mutations were induced not only in higher doses but also in lower doses, with which physiological effect by irradiation was hardly observed. Irradiation with both ion beams induced mutants in the number of petals, in flower size, in flower shape and in flower color in each cultivar.

  5. Mutation induced with ion beam irradiation in rose

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, H. E-mail: yhiroya@nias.affrc.go.jp; Nagatomi, S.; Morishita, T.; Degi, K.; Tanaka, A.; Shikazono, N.; Hase, Y

    2003-05-01

    The effects of mutation induction by ion beam irradiation on axillary buds in rose were investigated. Axillary buds were irradiated with carbon and helium ion beams, and the solid mutants emerged after irradiation by repeated cutting back. In helium ion irradiation, mutations were observed in plants derived from 9 buds among 56 irradiated buds in 'Orange Rosamini' and in plants derived from 10 buds among 61 irradiated buds in 'Red Minimo'. In carbon ion, mutations were observed in plants derived from 12 buds among 88 irradiated buds in 'Orange Rosamini'. Mutations were induced not only in higher doses but also in lower doses, with which physiological effect by irradiation was hardly observed. Irradiation with both ion beams induced mutants in the number of petals, in flower size, in flower shape and in flower color in each cultivar.

  6. Interleukin-1β Converting Enzyme–like Protease Involvement in Fas-induced and Activation-induced Peripheral Blood T Cell Apoptosis in HIV Infection. TNF-related Apoptosis-inducing Ligand Can Mediate Activation-induced T Cell Death in HIV Infection

    Science.gov (United States)

    Katsikis, Peter D.; Garcia-Ojeda, Marcos E.; Torres-Roca, Javier F.; Tijoe, Iwan M.; Smith, Craig A.; Herzenberg, Leonore A.; Herzenberg, Leonard A.

    1997-01-01

    Apoptosis of peripheral blood T cells has been suggested to play an important role in the pathogenesis of human immunodeficiency virus (HIV) infection. Spontaneous, Fas (CD95)–induced and activation-induced T cell apoptosis have all been described in peripheral blood mononuclear cell cultures of HIV-infected individuals. We have previously shown that activation-induced T cell apoptosis is Fas independent in peripheral blood T cells from HIV+ individuals. In this study, we extend and confirm these observations by using an inhibitor of interleukin-1β converting enzyme (ICE) homologues. We show that z-VAD-fmk, a tripeptide inhibitor of ICE homologues, can inhibit Fas-induced apoptosis of peripheral blood CD4+ and CD8+ T cells from asymptomatic HIV+ individuals. z-VAD-fmk also inhibited activation (anti-CD3)– induced CD4+ and CD8+ T cell apoptosis (AICD) in some but not all asymptomatic HIV+ individuals. Apoptosis was measured by multiparameter flow cytometry. The z-VAD-fmk inhibitor also enhanced survival of T cells in anti-Fas or anti-CD3 antibody-treated cultures and inhibited DNA fragmentation. AICD that could be inhibited by z-VAD-fmk was Fas independent and could be inhibited with a blocking monoclonal antibody to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), a recently described member of the TNF/nerve growth factor ligand family. The above findings show that Fas-induced T cell apoptosis is ICE dependent in HIV infection. AICD can be blocked by ICE inhibitors in some patients, and this AICD is mediated by TRAIL. These results show that TRAIL can be a mediator of AICD in T cells. These different mechanisms of peripheral blood T cell apoptosis may play different roles in the pathogenesis of HIV infection. PMID:9334376

  7. Public health aspects of food irradiation.

    Science.gov (United States)

    Käferstein, F K; Moy, G G

    1993-01-01

    In view of the enormous health and economic consequences of foodborne diseases, the World Health Organization (WHO) encourages its Member States to consider all measures to eliminate or reduce foodborne pathogens in food and improve their supplies of safe and nutritious food. With the wholesomeness of irradiated food clearly established by extensive scientific studies, food irradiation has important roles to play in both ensuring food safety and reducing food losses. Food irradiation may be one of the most significant contributions to public health to be made by food science and technology since the introduction of pasteurization. Because the promotion of a safe, nutritious and adequate food supply is an essential component of its primary health care strategy, WHO is concerned that the unwarranted rejection of this process may endanger public health and deprive consumers of the choice of food processed for safety.

  8. Proton irradiation effects in silicon devices

    Energy Technology Data Exchange (ETDEWEB)

    Simoen, E.; Vanhellemont, J.; Alaerts, A. [IMEC, Leuven (Belgium)] [and others

    1997-03-01

    Proton irradiation effects in silicon devices are studied for components fabricated in various substrates in order to reveal possible hardening effects. The degradation of p-n junction diodes increases in first order proportionally with the fluence, when submitted to 10 MeV proton irradiations in the range 5x10{sup 9} cm{sup -2} to 5x10{sup 11} cm{sup -2}. The damage coefficients for both p- and n-type Czochralski, Float-Zone and epitaxial wafers are reported. Charge-Coupled Devices fabricated in a 1.2 {mu}m CCD-CMOS technology are shown to be quite resistant to 59 MeV H{sup +} irradiations, irrespective of the substrate type. (author)

  9. Degradation of insulating ceramics due to irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Tomohiro; Terai, Takayuki; Yoneoka, Toshiaki; Tanaka, Satoru [Tokyo Univ. (Japan). Faculty of Engineering

    1996-10-01

    Radiation-induced electrical degradation was investigated on single crystal alumina under 2.2 MeV electron irradiation with a dose rate of 5.7 x 10{sup 5} Gy/s and an electrical field of 1.6 x 10{sup 5} V/m at 773 K. After irradiation, electrical resistivity both on the surface and in the bulk decreased in the temperature range of 300 to 773 K. Substantial resistivity decreased from the initial value due to the irradiation, the degradation ratio was much smaller than the case of poly-crystalline specimens. On the other hands, surface resistivity decreased with increasing temperature for measurement with an abrupt change by 4 orders of magnitude around 600 K, and it showed thermal hysteresis. (author)

  10. Signal development in irradiated silicon detectors

    CERN Document Server

    Kramberger, Gregor; Mikuz, Marko

    2001-01-01

    This work provides a detailed study of signal formation in silicon detectors, with the emphasis on detectors with high concentration of irradiation induced defects in the lattice. These defects give rise to deep energy levels in the band gap. As a consequence, the current induced by charge motion in silicon detectors is signifcantly altered. Within the framework of the study a new experimental method, Charge correction method, based on transient current technique (TCT) was proposed for determination of effective electron and hole trapping times in irradiated silicon detectors. Effective carrier trapping times were determined in numerous silicon pad detectors irradiated with neutrons, pions and protons. Studied detectors were fabricated on oxygenated and non-oxygenated silicon wafers with different bulk resistivities. Measured effective carrier trapping times were found to be inversely proportional to fuence and increase with temperature. No dependence on silicon resistivity and oxygen concentration was observ...

  11. Irradiation creep of vanadium-base alloys

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, H.; Billone, M.C.; Strain, R.V.; Smith, D.L. [Argonne National Lab., IL (United States); Matsui, H. [Tohoku Univ. (Japan)

    1998-03-01

    A study of irradiation creep in vanadium-base alloys is underway with experiments in the Advanced Test Reactor (ATR) and the High Flux Isotope Reactor (HFIR) in the United States. Test specimens are thin-wall sealed tubes with internal pressure loading. The results from the initial ATR irradiation at low temperature (200--300 C) to a neutron damage level of 4.7 dpa show creep rates ranging from {approx}0 to 1.2 {times} 10{sup {minus}5}/dpa/MPa for a 500-kg heat of V-4Cr-4Ti alloy. These rates were generally lower than reported from a previous experiment in BR-10. Because both the attained neutron damage levels and the creep strains were low in the present study, however, these creep rates should be regarded as only preliminary. Substantially more testing is required before a data base on irradiation creep of vanadium alloys can be developed and used with confidence.

  12. Horizontal modular dry irradiated fuel storage system

    Science.gov (United States)

    Fischer, Larry E.; McInnes, Ian D.; Massey, John V.

    1988-01-01

    A horizontal, modular, dry, irradiated fuel storage system (10) includes a thin-walled canister (12) for containing irradiated fuel assemblies (20), which canister (12) can be positioned in a transfer cask (14) and transported in a horizontal manner from a fuel storage pool (18), to an intermediate-term storage facility. The storage system (10) includes a plurality of dry storage modules (26) which accept the canister (12) from the transfer cask (14) and provide for appropriate shielding about the canister (12). Each module (26) also provides for air cooling of the canister (12) to remove the decay heat of the irradiated fuel assemblies (20). The modules (26) can be interlocked so that each module (26) gains additional shielding from the next adjacent module (26). Hydraulic rams (30) are provided for inserting and removing the canisters (12) from the modules (26).

  13. Status of food irradiation in the world

    Energy Technology Data Exchange (ETDEWEB)

    Kume, Tamikazu [Takasaki Advanced Radiation Research Institute, Japan Atomic Energy Agency (JAEA), Quantum Beam Science Directorate, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan); Furuta, Masakazu [Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Sakai, Osaka 599-8531 (Japan); Todoriki, Setsuko [National Food Research Institute, 2-1-12 Kannonndai, Tsukuba, Ibaraki 305-8642 (Japan); Uenoyama, Naoki [Department of International Cooperation and Industrial Infrastructure Development, Japan Atomic Industrial Forum, Inc., Shimbashi Fuji Bld., 2-1-3, Shimbashi, Minato-ku, Tokyo 105-8605 Japan (Japan); Kobayashi, Yasuhiko [Quantum Beam Science Directorate, Japan Atomic Energy Agency (JAEA), 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan)], E-mail: kobayashi.yasuhiko@jaea.go.jp

    2009-03-15

    The status of food irradiation in the world in 2005 was investigated using published data, a questionnaire survey and direct visits. The results showed that the quantity of irradiated foods in the world in 2005 was 405,000 ton and comprised 1,86,000 ton (46%) for disinfection of spices and dry vegetables, 82,000 ton (20%) for disinfestation of grains and fruits, 32,000 ton (8%) for disinfection of meat and fish, 88,000 ton (22%) for sprout inhibition of garlic and potato, and 17,000 ton (4%) of other food items that included health foods, mushroom, honey, etc. Commercial food irradiation is increasing significantly in Asia, but decreasing in EU.

  14. POSTHARVEST OF IRRADIATED TAHITI LIME FRUITS

    Directory of Open Access Journals (Sweden)

    SIMONE RODRIGUES DA SILVA

    Full Text Available ABSTRACT This study aimed to evaluate the postharvest quality evolution of gamma-irradiated ‘Tahiti’ limes. Shiny, olivegreen fruits with coarse skin (56 cm equatorial diameter harvested in commercial orchars and processed in commercial packing house line were used. In a preliminary assay, fruits harvested in April 2011 were exposed to a gamma radiation range from 0 to 750 Gy. The 250 and 750 Gy doses negatively affected skin quality and pulp of exposed fruits. For this reason, new assays were carried out using lower doses to irradiate fruits harvested in July 2011 (off-season and January 2012 (regular harvest period. Fruit harvested in both periods were selected and exposed to radiation doses of 0, 50, 100, 150, and 200 Gy. All irradiations occurred at a rate of 0.46 Gy/h. After fruit irradiation, physical and chemical analyses were performed along a 20-day storage period at room temperature (24 ± 1ºC and 80 ± 5% RH. Irradiation of fruits harvested in July 2011 and January 2012 and treated with doses of up to 200 Gy did not affect the ascorbic acid content, but doses > 100 Gy caused skin yellowing of fruits harvested on both periods. Gamma radiation at doses = 50 Gy reduced the total soluble solids content in off-season fruits. Exposure of fruits harvested in the main harvest period to radiation doses = 150 Gy increased weight loss. Irradiation of ‘Tahiti’ limes at doses between 50 Gy and 700 Gy did not preserve postharvest quality during storage at room temperature.

  15. Agglomeration defects on irradiated carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Steini Moura, Cassio [Faculty of Physics, Pontificia Universidade Catolica do Rio Grande do Sul, 90619-900, Porto Alegre, RS (Brazil); Balzaretti, Naira Maria; Amaral, Livio [Institute of Physics, Universidade Federal do Rio Grande do Sul, C.P.: 15051, 91501-070, Porto Alegre, RS (Brazil); Gribel Lacerda, Rodrigo; Pimenta, Marcos A. [Universidade Federal de Minas Gerais, C.P.: 702, 31270-901, Belo Horizonte, MG (Brazil)

    2012-03-15

    Aligned carbon nanotubes (CNT) were irradiated in the longitudinal and perpendicular directions, with low energy carbon and helium ions in order to observe the formation of defects in the atomic structure. Analysis through Raman spectroscopy and scanning electron microscopy indicated bundle rupture and ion track formation on nanotube bundles. Aligned CNT presented a kind of defect comprising ravine formation and tube agglomeration on top of the substrate. The latter structure is possibly caused by static charge accumulation induced by the incoming ions. Fluence plays a role on the short range order. Higher fluence irradiation transforms CNT into amorphous carbon nanowires.

  16. Electric field distribution in irradiated silicon detectors

    CERN Document Server

    Castaldini, A; Polenta, L; Nava, F; Canali, C

    2002-01-01

    Particle irradiation causes dramatic changes in bulk properties of p sup + -n-n sup + silicon structures operating as particle detectors. Several attempts to model and justify such variations have been proposed in the last few years. The main unsolved problem remains in the determination of the electric field and depletion layer distributions as key-parameters to estimate the collection efficiency of the detector. By using optical beam induced current (OBIC) and surface potential (SP) measurements we determined the behavior of the electric field and confirmed the existence of a double-junction structure appearing after irradiation.

  17. Electric field distribution in irradiated silicon detectors

    Energy Technology Data Exchange (ETDEWEB)

    Castaldini, A.; Cavallini, A. E-mail: anna.cavallini@bo.infn.it; Polenta, L.; Nava, F.; Canali, C

    2002-01-11

    Particle irradiation causes dramatic changes in bulk properties of p{sup +}-n-n{sup +} silicon structures operating as particle detectors. Several attempts to model and justify such variations have been proposed in the last few years. The main unsolved problem remains in the determination of the electric field and depletion layer distributions as key-parameters to estimate the collection efficiency of the detector. By using optical beam induced current (OBIC) and surface potential (SP) measurements we determined the behavior of the electric field and confirmed the existence of a double-junction structure appearing after irradiation.

  18. Heavy-Section Steel Irradiation Program

    Energy Technology Data Exchange (ETDEWEB)

    Rosseel, T.M.

    2000-04-01

    Maintaining the integrity of the reactor pressure vessel (RPV) in a light-water-cooled nuclear power plant is crucial in preventing and controlling severe accidents that have the potential for major contamination release. Because the RPV is the only key safety-related component of the plant for which a redundant backup system does not exist, it is imperative to fully understand the degree of irradiation-induced degradation of the RPV's fracture resistance that occurs during service. For this reason, the Heavy-Section Steel Irradiation (HSSI) Program has been established.

  19. Agglomeration defects on irradiated carbon nanotubes

    Directory of Open Access Journals (Sweden)

    Cássio Stein Moura

    2012-03-01

    Full Text Available Aligned carbon nanotubes (CNT were irradiated in the longitudinal and perpendicular directions, with low energy carbon and helium ions in order to observe the formation of defects in the atomic structure. Analysis through Raman spectroscopy and scanning electron microscopy indicated bundle rupture and ion track formation on nanotube bundles. Aligned CNT presented a kind of defect comprising ravine formation and tube agglomeration on top of the substrate. The latter structure is possibly caused by static charge accumulation induced by the incoming ions. Fluence plays a role on the short range order. Higher fluence irradiation transforms CNT into amorphous carbon nanowires.

  20. Evaluation of CERES surface irradiance products

    Science.gov (United States)

    Kato, S.; Loeb, N. G.; Rose, F. G.; Rutan, D. A.; Doelling, D.; Radkevich, A.; Ham, S. H.

    2014-12-01

    Understanding the surface radiation budget is important for several reasons. At the global and large temporal scales, it should balance with the sum of surface latent and sensible heat fluxes and ocean heating. At regional scales, it is an indispensable boundary condition for ocean or snow models or any other models that need energy input to the surface. NASA's Clouds and the Earth's Radiant Energy System (CERES) project provides surface irradiance data products for a range of temporal and spatial scales computed using a radiative transfer model initialized using satellite-derived cloud and aerosol properties. Other inputs to the radiative transfer model include temperature and humidity profiles from NASA Global Modeling and Assimilation Office's (GMAO) reanalysis. The CERES team uses more than 80 surface observation sites located over land and ocean to evaluate computed irradiances. When computed monthly 1° by 1° gridded mean downward irradiances are compared with 10 years of observed irradiances, the bias averaged over all land and ocean sites are, respectively, -1.7 Wm-2 and 4.7 Wm-2 for shortwave and -1.0 Wm-2 and -2.0 Wm-2 for longwave. The shortwave agreement is significantly better than other satellite-based surface irradiance products. One of reasons for the better agreement is careful treatment of diurnal cycle of clouds by merging 3-hourly geostationary satellite-derived cloud properties. In addition, computed surface irradiance variability shows a remarkable agreement with observed variability. However, these data sets have their shortcomings. The uncertainty in nighttime surface longwave irradiance over polar regions is larger than that of other regions primarily due to the difficulty of cloud detection and large uncertainties in skin temperature and near-surface temperature and humidity. The large uncertainty in polar region surface irradiances hampers, for example, investigation of surface radiation budget changes in response to changes in sea ice

  1. Effects of gamma irradiation on deteriorated paper

    Science.gov (United States)

    Bicchieri, Marina; Monti, Michela; Piantanida, Giovanna; Sodo, Armida

    2016-08-01

    Even though gamma radiation application, also at the minimum dosage required for disinfection, causes depolymerization and degradation of the paper substrate, recently published papers seemed, instead, to suggest that γ-rays application could be envisaged in some conditions for Cultural Heritage original documents and books. In some of the published papers, the possible application of γ-rays was evaluated mainly by using mechanical tests that scarcely reflect the chemical modifications induced in the cellulosic support. In the present article the effect of low dosage γ-irradiation on cellulosic substrates was studied and monitored applying different techniques: colorimetry, spectroscopic measurements, carbonyl content and average viscometric degree of polymerization. Two different papers were investigated, a non-sized, non-filled cotton paper, and a commercial permanent paper. To simulate a real deteriorated document, which could need γ-rays irradiation, some samples were submitted to a hydrolysis treatment. We developed a treatment based on the exposition of paper to hydrochloric acid vapors, avoiding any contact of the samples with water. This method induces a degradation similar to that observed on original documents. The samples were then irradiated with 3 kGy γ-rays at a 5258 Gy/h rate. The aforementioned analyses were performed on the samples just irradiated and after artificial ageing. All tests showed negative effects of gamma irradiation on paper. Non-irradiated paper preserves better its appearance and chemical properties both in the short term and after ageing, while the irradiated samples show appreciable color change and higher oxidation extent. Since the Istituto centrale restauro e conservazione patrimonio archivistico e librario is responsible for the choice of all restoration treatments that could be applied on library and archival materials under the protection of the Italian State (http://www.icpal.beniculturali.it/allegati/DM-7

  2. Oxygen interstitial trapping in electron irradiated sapphire

    CERN Document Server

    Morono, A

    2002-01-01

    An existing model for first stage anion vacancy stabilization in irradiated alkali halides has been applied to sapphire. To monitor the F centre concentration growth during irradiation, radioluminescence instead of optical absorption measurements has been employed. The results indicate that the model is valid for sapphire and suggest that the F centre stabilization process depends on oxygen interstitial trapping. This implies that the resistance to radiation damage at low doses should depend on the impurity and dislocation content of the material. One presumes the model may be extended to other oxides.

  3. Evaluation of irradiated coating material specimens

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yong Jin; Nam, Seok Woo; Cho, Lee Moon [RCS Korea Co., Ltd., Seoul (Korea, Republic of)

    2007-12-15

    Evaluation result of irradiated coating material specimens - Coating material specimens radiated Gamma Energy(Co 60) in air condition. - Evaluation conditions was above 1 X 10{sup 4} Gy/hr, and radiated TID 2.0 X 10{sup 6} Gy. - The radiated coating material specimens, No Checking, Cracking, Flaking, Delamination, Peeling and Blistering. - Coating system at the Kori no. 1 and APR 1400 Nuclear power plant, evaluation of irradiated coating materials is in accordance with owner's requirement(2.0 X 10{sup 6} Gy)

  4. Effect of UV irradiation on cutaneous cicatrices

    DEFF Research Database (Denmark)

    Due, Eva; Rossen, Kristian; Sorensen, Lars Tue

    2007-01-01

    The aim of this study was to examine the effect of ultraviolet (UV) irradiation on human cutaneous cicatrices. In this randomized, controlled study, dermal punch biopsy wounds served as a wound healing model. Wounds healed by primary or second intention and were randomized to postoperative solar UV...... postoperatively, UV-irradiated cicatrices healing by second intention: (i) were significantly pointed out as the most disfiguring; (ii) obtained significantly higher scores of colour, infiltration and cicatrix area; and (iii) showed significantly higher increase in skin-reflectance measurements of skin-pigmentation...

  5. Neutron Spectrum Measurements from Irradiations at NCERC

    Energy Technology Data Exchange (ETDEWEB)

    Jackman, Kevin Richard [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mosby, Michelle A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Bredeweg, Todd Allen [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hutchens, Gregory Joe [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); White, Morgan Curtis [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-04-15

    Several irradiations have been conducted on assemblies (COMET/ZEUS and Flattop) at the National Criticality Experiments Research Center (NCERC) located at the Nevada National Security Site (NNSS). Configurations of the assemblies and irradiated materials changed between experiments. Different metallic foils were analyzed using the radioactivation method by gamma-ray spectrometry to understand/characterize the neutron spectra. Results of MCNP calculations are shown. It was concluded that MCNP simulated spectra agree with experimental measurements, with the caveats that some data are limited by statistics at low-energies and some activation foils have low activities.

  6. Microprobe investigations of irradiated uranium carbide

    Energy Technology Data Exchange (ETDEWEB)

    Kleykamp, H.

    1973-12-01

    A shielded Cameca microprobe, MS 46, was used to examine a UC sample canned in SAP and irradiated to a burnup of 0.7%. An annular zone at about 40% of the outer sample radius was seen to contain precipitates loaded with fission products; microprobe analysis showed the precipitates to be U/sub 2/ (Tc, Ru, Rh)C/sub 2/. Small amounts of palladium can be stabilized in this phase. Zirconium and molybdenum were verified in homogeneous distribution in the fuel. The Vickers hardness of the irradiated UC is 1000 to 1200 kg/mm/sup 2/. No signs of incompatibility with the canning material were detected. (auth)

  7. Understanding the Irradiation Behavior of Zirconium Carbide

    Energy Technology Data Exchange (ETDEWEB)

    Motta, Arthur [Pennsylvania State Univ., University Park, PA (United States); Sridharan, Kumar [Univ. of Wisconsin, Madison, WI (United States); Morgan, Dane [Univ. of Wisconsin, Madison, WI (United States); Szlufarska, Izabela [Univ. of Wisconsin, Madison, WI (United States)

    2013-10-11

    Zirconium carbide (ZrC) is being considered for utilization in high-temperature gas-cooled reactor fuels in deep-burn TRISO fuel. Zirconium carbide possesses a cubic B1-type crystal structure with a high melting point, exceptional hardness, and good thermal and electrical conductivities. The use of ZrC as part of the TRISO fuel requires a thorough understanding of its irradiation response. However, the radiation effects on ZrC are still poorly understood. The majority of the existing research is focused on the radiation damage phenomena at higher temperatures (>450{degree}C) where many fundamental aspects of defect production and kinetics cannot be easily distinguished. Little is known about basic defect formation, clustering, and evolution of ZrC under irradiation, although some atomistic simulation and phenomenological studies have been performed. Such detailed information is needed to construct a model describing the microstructural evolution in fast-neutron irradiated materials that will be of great technological importance for the development of ZrC-based fuel. The goal of the proposed project is to gain fundamental understanding of the radiation-induced defect formation in zirconium carbide and irradiation response by using a combination of state-of-the-art experimental methods and atomistic modeling. This project will combine (1) in situ ion irradiation at a specialized facility at a national laboratory, (2) controlled temperature proton irradiation on bulk samples, and (3) atomistic modeling to gain a fundamental understanding of defect formation in ZrC. The proposed project will cover the irradiation temperatures from cryogenic temperature to as high as 800{degree}C, and dose ranges from 0.1 to 100 dpa. The examination of this wide range of temperatures and doses allows us to obtain an experimental data set that can be effectively used to exercise and benchmark the computer calculations of defect properties. Combining the examination of radiation

  8. Post irradiation tensile and fatigue behavior of austenitic PCA stainless steels irradiated in HFIR

    Science.gov (United States)

    Tanaka, M. P.; Hamada, S.; Hishinuma, A.; Grossbeck, M. L.

    1988-07-01

    Mechanical properties were determined on solution annealed (SA) and cold worked (CW) JPCA (Ti-modified austenitic stainless steel) irradiated in the High Flux Isotope Reactor (HFIR) at temperatures ranging from 300 to 600°C. The irradiation produced damage levels from 16 to 56 dpa and helium concentration from 1020 to 4100 appm. The improved stability of MC precipitates which formed in the matrix during irradiation prevent loss of ductility at 500°C and below. Application of solution annealed JPCA is recommended for structural components of fusion reactors to be operated at 500°C and below.

  9. Lactoferrin inhibits dexamethasone-induced chondrocyte impairment from osteoarthritic cartilage through up-regulation of extracellular signal-regulated kinase 1/2 and suppression of FASL, FAS, and Caspase 3

    Energy Technology Data Exchange (ETDEWEB)

    Tu, Yihui [Department of Orthopaedics, Yangpu District Central Hospital Affiliated to Tongji University School of Medicine, 450 Tengyue Road, Shanghai (China); Xue, Huaming [Department of Orthopaedics, Yangpu District Central Hospital Affiliated to Tongji University School of Medicine, 450 Tengyue Road, Shanghai (China); Institute of Life Science, College of Medicine, Swansea University, Singleton Park (United Kingdom); Francis, Wendy [Institute of Life Science, College of Medicine, Swansea University, Singleton Park (United Kingdom); Davies, Andrew P. [Department of Orthopaedics and Trauma, Moriston Hospital, Swansea (United Kingdom); Pallister, Ian; Kanamarlapudi, Venkateswarlu [Institute of Life Science, College of Medicine, Swansea University, Singleton Park (United Kingdom); Xia, Zhidao, E-mail: zhidao.xia@gmail.com [Institute of Life Science, College of Medicine, Swansea University, Singleton Park (United Kingdom)

    2013-11-08

    Highlights: •Dex exerts dose-dependant inhibition of HACs viability and induction of apoptosis. •Dex-induced impairment of chondrocytes was attenuated by rhLF. •ERK and FASL/FAS signaling are involved in the effects of rhLF. •OA patients with glucocorticoid-induced cartilage damage may benefit from treatment with rhLF. -- Abstract: Dexamethasone (Dex) is commonly used for osteoarthritis (OA) with excellent anti-inflammatory and analgesic effect. However, Dex also has many side effects following repeated use over prolonged periods mainly through increasing apoptosis and inhibiting proliferation. Lactoferrin (LF) exerts significantly anabolic effect on many cells and little is known about its effect on OA chondrocytes. Therefore, the aim of this study is to investigate whether LF can inhibit Dex-induced OA chondrocytes apoptosis and explore its possible molecular mechanism involved in. MTT assay was used to determine the optimal concentration of Dex and recombinant human LF (rhLF) on chondrocytes at different time and dose points. Chondrocytes were then stimulated with Dex in the absence or presence of optimal concentration of rhLF. Cell proliferation and viability were evaluated using MTT and LIVE/DEAD assay, respectively. Cell apoptosis was evaluated by multi-parameter apoptosis assay kit using both confocal microscopy and flow cytometry, respectively. The expression of extracellular signal-regulated kinase (ERK), FAS, FASL, and Caspase-3 (CASP3) at the mRNA and protein levels were examined by real-time polymerase chain reaction (PCR) and immunocytochemistry, respectively. The optimal concentration of Dex (25 μg/ml) and rhLF (200 μg/ml) were chosen for the following experiments. rhLF significantly reversed the detrimental effect of Dex on chondrocytes proliferation, viability, and apoptosis. In addition, rhLF significantly prevented Dex-induced down-regulation of ERK and up-regulation of FAS, FASL, and CASP3. These findings demonstrated that rhLF acts as

  10. The validity of socioeconomic status measures among adolescents based on self-reported information about parents occupations, FAS and perceived SES; implication for health related quality of life studies

    Directory of Open Access Journals (Sweden)

    P. Svedberg

    2016-04-01

    Full Text Available Abstract Background Research has shown inconsistencies in results and difficulties in conceptualization of assessment of socioeconomic status (SES among adolescents. The aim of this study was thus to test the validity of self-reported information on SES in two age-groups (11–13 and 14–16 years old in an adolescent population and to evaluate its relationship to self-reported health related quality of life (HRQOL. Different measures of SES commonly used in research in relation to HRQOL were tested in this study; parent’s occupations status, family material affluence status (FAS and perceived SES. Method A cross-sectional study, with a sample of 948 respondents (n = 467, 11–13 years old and n = 481, 14–16 years old completed questionnaires about SES and HRQOL. The adolescents’ completion rates were used, with chi2-test, to investigate differences between gender and age-group. Correlation was used for convergent validity and ANOVA for concurrent validity. Results We found a low completion rate for both fathers’ (41.7 % and mothers' (37.5 % occupation status, and a difference in completion rate between gender and age-groups. FAS had the highest completion rate (100 % compared to parent's occupations status and perceived SES. The convergent validity between the SES-indicators was weak (Spearman correlation coefficient below 0.3, suggesting that the indicators measured different dimensions of SES. Both FAS and perceived SES showed a gradient in mean HRQOL between low and high SES in relation to HRQOL, this was significant only for perceived SES (p < 0.01, both age-groups. Conclusion This study indicates the need for considering different approaches to measures of SES among adolescences and when evaluating SES in relation to HRQOL. Further research is needed to investigate sustainable ways to measure SES, delineating the relevance of tangible measures of education, occupation and income in relation to the perceived

  11. Fas2-ELISA y la técnica de sedimentación rápida modificada por lumbreras en el diagnóstico de la infección por Fasciola hepática

    Directory of Open Access Journals (Sweden)

    Vicente Maco Flores

    2002-04-01

    Full Text Available La fasciolosis humana es un problema de salud pública debido a la mayor incidencia de casos reportados en los últimos años alrededor del mundo. La necesidad de contar con técnicas o métodos de diagnóstico para Fasciola hepatica de mayor sensibilidad y especificidad es importante tanto para la práctica clínica como para determinar zonas endémicas. Objetivo: Evaluar las técnicas coprológicas y serológicas para el diagnóstico de la infección por Fasciola hepatica en humanos. Material y métodos: La población de estudio comprendió a niños en edad escolar entre 1-16 años de edad, pertenecientes a una zona de alta endemicidad (Junin, Perú. Se obtuvieron un total de 194 muestras de heces y 158 muestras de suero. Se evaluaron tres métodos coproparasitológicos: Método de Concentración éter-formol (MCEF, Técnica de Sedimentación Espontánea (TSE y la Técnica de Sedimentación Rápida (TSR modificada por Lumbreras, y tres métodos serológicos: Arco 2, Western blot para F. hepatica y Fas2-ELISA. Resultados: La TSR modificada por Lumbreras fue la de mayor rendimiento (20.61% en comparación con la TSE (13.40% y MCEF (7.72%. La sensibilidad de Fas2-ELISA fue de 96.77% superior a la del Western blot y Arco 2, con sensibilidades de 71.87% y 35.48%, respectivamente. Conclusiones: La TSR es superior a TSE y MCEF para el diagnóstico de la fasciolosis humana en la fase crónica. Fas2-ELISA, es una prueba de inmunodiagnóstico altamente sensible y que se propone debe ser usada como la prueba de diagnóstico de fasciolosis humana y de tamizaje de la infección en poblaciones humanas que habitan en regiones de alta endemicidad para esta parasitosis.

  12. Localized comedo formation after cobalt irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Myskowski, P.L.; Safai, B.

    1981-10-01

    Following Cobalt-60 irradiation for a left frontotemporal tumor, a 61-year-old woman developed comedones on the forehead. These changes responded to conventional acne therapy with retinoic acid. Multiple acneigenic factors were implicated in the pathogenesis of her lesions.

  13. Irradiation Processing Department monthly report, October 1963

    Energy Technology Data Exchange (ETDEWEB)

    1963-11-15

    This document details activities of the irradiation processing department during the month of October, 1963. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; and Financial Operation.

  14. Irradiation Processing Department monthly report, April 1963

    Energy Technology Data Exchange (ETDEWEB)

    1963-05-13

    This document details activities of the Irradiation Processing Department during the month of August, 1958. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; Employee Relations Operation; and Financial Operation.

  15. Effects of hadron irradiation on scintillating fibers

    Energy Technology Data Exchange (ETDEWEB)

    Atac, M. (Univ. of California, Los Angeles, CA (United States) Fermi National Accelerator Lab., Batavia, IL (United States)); Buchanan, C.; Chrisman, D.; Cline, D.; Kolonko, J.; Kubic, J.; Park, J. (Univ. of California, Los Angeles, CA (United States)); Baumbaugh, A.; Binkley, M.; Bross, A.D.; Finley, D.; Elias, J.; Foster, G.W.; Kephart, R.; Kephart, R.; Kim, C.; Park, H.; Pla-Dalmau, A.; Rivetta, C.; Tkaczyk, S.; Wagner, R. (Fermi National Accelerator Lab., Batavia, IL (United States)); Chung, M.; Goldberg, H.; Jeskik, R.; Margulies, S.; Mendez, H.; Solomon, J.; Vaca, F. (Univ. of Illinois, Chicago, IL (United States)); Kelley, C. (Massachusetts College of Pharmacy and Allied Health Sciences, Boston, MA (United States)); Baumbaugh, B.; Bishop, J.; Biswas, N.; Cason, N.; Jacques, J.; Kehoe, R.; Kelly, M.; Kenney, V.; LoSecco, J.; Ruchti, R.; Shephard, W.; Warchol, J.; Wayne, M.; Marchant, J.; Mountain, R.J. (Univ. of Notre Dame, IN (United States)); Davis, D.; Vandergriff, D. (O

    1993-08-01

    Trackers based on scintillating-fiber technology are being considered by the Solenoidal Detector Collaboration at SSC and the D[phi] collaboration at Fermilab. An important issue is the effect of the radiation existing in the detector cores on fiber properties. Most studies of radiation damage in scintillators have irradiated small bulk samples rather than fibers, and have used X-rays, [sup 60]Co gammas, or electron beams, often at accelerated rates. The authors have irradiated some 600 fibers in the Fermilab Tevatron C[phi] area, thereby obtaining a hadronic irradiation at realistic rates. Four-meter-long samples of ten Bicron polystyrene-based fiber types, maintained in air, dry nitrogen, argon, and vacuum atmospheres within stainless-steel tubes, were irradiated for seven weeks at various distances from the accelerator beam pipes. Maximum doses, measured by thermoluminescence detectors, were about 80 Krad. Fiber properties, particularly light yield and attenuation length, have been measured over a one-year period. A description of the work together with the results is presented. At the doses achieved, corresponding to a few years of actual fiber-tracking detector operation, little degradation is observed. In addition, recovery after several days' exposure to air has been noted. Properties of unirradiated samples kept in darkness show no changes after one year.

  16. Irradiation Processing Department monthly report, January 1964

    Energy Technology Data Exchange (ETDEWEB)

    1964-02-14

    This document details activities of the Irradiation Processing Department during the month of August, 1958. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; Employee Relations Operation; and Financial Operation.

  17. Irradiation Processing Department monthly report, February 1963

    Energy Technology Data Exchange (ETDEWEB)

    Greninger, A. B.

    1963-03-14

    This document details activities of the Irradiation Processing Department during the month of August, 1958. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; Employee Relations Operation; and Financial Operation.

  18. New pallet irradiation for Gammaster International

    Science.gov (United States)

    Möhlmann, Mr. J. H. F.

    1993-07-01

    State of the art technology offers many opportunities to improve production process with ionizing radiation. Also the requirements to this process become more and more stringent; who was aware of the ISO-9000 Standards? Now it is a necessary concept? Internal and external audits, in particular by Regulatory Bodies such as the FDA and DHSS/MCA, are necessary and commonplace requirements when operating in the Healthcare and Pharmaceutical sectors. Efficiency is a major requirement for industry and also for our radiation business. With all the above mentioned items in mind, Gammaster International B.V. in close cooperation with Nordion International Inc. has developed and built a new type Pallet Irradiator. In this new concept, our 22 years experience in gamma processing and the expertise gained in 10 years of operation of pallet irradiators was incorporated. For this irradiator Gammaster International designed and built a new process control console, incorporating state of the art technology such as: - A well-balanced safety system - A control panel, with status indication for all essential operating and safety parameters - Advances warning for necessary maintenance work - Automatic timer-setting control in addition to an automatic timer setting modification - Clear indication of the position of the product inside the unit and its status - Fully automatic product information generated when the product leaves the irradiation unit - Visual process control with the help of a color monitor - Incremental dose-control - Fault identification

  19. Irradiation Processing Department monthly report, October 1961

    Energy Technology Data Exchange (ETDEWEB)

    1961-11-17

    This document details activities of the irradiation processing department during the month of October, 1961. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; Employee Relations Operation; and Financial Operation.

  20. Irradiation Processing Department monthly report, March 1961

    Energy Technology Data Exchange (ETDEWEB)

    1961-04-14

    This document details activities of the irradiation processing department during the month of March, 1961. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; Employee Relations Operation; Financial Operation; and NPR project.

  1. Irradiation Processing Department monthly report, December 1961

    Energy Technology Data Exchange (ETDEWEB)

    1962-01-15

    This document details activities of the irradiation processing department during the month of December, 1961. Al general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations: Production and reactor Operations; Facilities Engineering Operation; and NPR project.

  2. Irradiation Processing Department monthly report, August 1960

    Energy Technology Data Exchange (ETDEWEB)

    1960-09-12

    This document details activities of the irradiation processing department during the month of August, 1960. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor operations; Facilities Engineering operation; Employee Relations Operation; and Financial Operation.

  3. Evaluation of gamma irradiation effect and Pseudomonas ...

    African Journals Online (AJOL)

    Antagonistic effect of Pseudomonas fluorescens and influence of gamma irradiation on the development of Penicillium expansum, the causal agent of postharvest disease on apple fruit was studied. P. fluorescens was originally isolated from rhizosphere of the apple trees. Suspension of P. fluorescens and P. expansum ...

  4. Tritium release from neutron irradiated beryllium pebbles

    Energy Technology Data Exchange (ETDEWEB)

    Scaffidi-Argentina, F.; Werle, H. [Forschungszentrum Karlsruhe GmbH Technik und Umwelt (Germany). Inst. fuer Neutronenphysik und Reactortechnik

    1998-01-01

    One of the most important open issues related to beryllium for fusion applications refers to the kinetics of the tritium release as a function of neutron fluence and temperature. The EXOTIC-7 as well as the `Beryllium` experiments carried out in the HFR reactor in Petten are considered as the most detailed and significant tests for investigating the beryllium response under neutron irradiation. This paper reviews the present status of beryllium post-irradiation examinations performed at the Forschungszentrum Karlsruhe with samples from the above mentioned irradiation experiments, trying to elucidate the tritium release controlling processes. In agreement with previous studies it has been found that release starts at about 500-550degC and achieves a maximum at about 700-750degC. The observed release at about 500-550degC is probably due to tritium escaping from chemical traps, while the maximum release at about 700-750degC is due to tritium escaping from physical traps. The consequences of a direct contact between beryllium and ceramics during irradiation, causing tritium implanting in a surface layer of beryllium up to a depth of about 40 mm and leading to an additional inventory which is usually several times larger than the neutron-produced one, are also presented and the effects on the tritium release are discussed. (author)

  5. Structural investigation on gamma-irradiated polyacrylamide ...

    Indian Academy of Sciences (India)

    Small-angle neutron scattering (SANS) and ultraviolet (UV)–visible spectroscopictechniques are used to investigate the microstructural changes in polyacrylamide (PAAm) hydrogels on gamma irradiation. SANS measurements have revealed the presence of inhomogeneities in nanometre scale and reduction of their size ...

  6. Determinants of skin sensitivity to solar irradiation

    NARCIS (Netherlands)

    Broekmans, W.M.R.; Vink, A.A.; Boelsma, E.; Klöpping-Ketelaars, W.A.A.; Tijburg, L.B.M.; Veer, P. van 't; Poppel, G. van; Kardinaal, A.F.M.

    2003-01-01

    Background: Acute effects of UV irradiation include UV-induced erythema. Sunlight plays an important role in the development of skin cancer. Several predictive factors of UV-induced erythema could also be predictive for skin cancer. Objective: Our objective was to quantitatively assess phenotypical

  7. Irradiation Processing Department monthly report, August 1962

    Energy Technology Data Exchange (ETDEWEB)

    1962-09-14

    This document details activities of the Irradiation Processing Department during the month of August, 1962. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; and NPR Project.

  8. Heat Generation by Irradiated Complex Composite Nanostructures

    DEFF Research Database (Denmark)

    Ma, Haiyan; Tian, Pengfei; Pello, Josselin

    2014-01-01

    Heating of irradiated metallic e-beam generated nanostructures was quantified through direct measurements paralleled by novel model-based numerical calculations. By comparing discs, triangles, and stars we showed how particle shape and composition determines the heating. Importantly, our results...

  9. Methods for identification of irradiated food

    Science.gov (United States)

    Bögl, K. W.

    The current position regarding identification of irradiated food is described. Attempts have been made to apply physical, chemical and biological forms of measurement. Up to know, the most appropriate methods, very close to practical routine application, seem to be: the electron spin resonance technique, the luminescence techniques and the analysis of volatiles (originated mainly from the lipid fraction) and o-tyrosine.

  10. Irradiation Processing Department monthly report, April 1960

    Energy Technology Data Exchange (ETDEWEB)

    1960-05-19

    This document details activities of the irradiation processing department during the month of April, 1960. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; Employee Relations Operation; and Financial Operation.

  11. Irradiation Processing Department monthly report, December 1958

    Energy Technology Data Exchange (ETDEWEB)

    1959-01-21

    This document details activities of the irradiation processing department during the month of December 1958. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering operation; Employee Relations Operation; and Financial Operation.

  12. Irradiation Processing Department monthly report, May 1960

    Energy Technology Data Exchange (ETDEWEB)

    Greninger, A.B.

    1960-06-20

    This document details activities of the irradiation processing department during the month of May, 1960. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; Employee Relations Operation; and Financial Operation.

  13. Irradiation Processing Department monthly report, January 1961

    Energy Technology Data Exchange (ETDEWEB)

    1961-02-15

    This document details activities of the irradiation processing department during the month of January, 1961. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; Employee Relations Operation; Financial Operation; and NPR Project.

  14. Thermal annealing in neutron-irradiated tribromobenzenes

    DEFF Research Database (Denmark)

    Siekierska, K.E.; Halpern, A.; Maddock, A. G.

    1968-01-01

    The distribution of 82Br among various products in neutron-irradiated isomers of tribromobenzene has been investigated, and the effect of thermal annealing examined. Reversed-phase partition chromatography was employed for the determination of radioactive organic products, and atomic bromine...

  15. Spatially Resolved Images and Solar Irradiance Variability

    Indian Academy of Sciences (India)

    Variations in UV irradiances seen at earth are the sum of global (solar dynamo) to regional (active region, plage, network, bright points and background) solar magnetic activities that can be identified through spatially resolved photospheric, chromospheric and coronal features. In this research, the images of CaII K-line ...

  16. Studies of Solar EUV Irradiance from SOHO

    Science.gov (United States)

    Floyd, Linton

    2002-01-01

    The Extreme Ultraviolet (EUV) irradiance central and first order channel time series (COC and FOC) from the Solar EUV Monitor aboard the Solar and Heliospheric observatory (SOHO) issued in early 2002 covering the time period 1/1/96-31/1201 were analyzed in terms of other solar measurements and indices. A significant solar proton effect in the first order irradiance was found and characterized. When this effect is removed, the two irradiance time series are almost perfectly correlated. Earlier studies have shown good correlation between the FOC and the Hall core-to-wing ratio and likewise, it was the strongest component of the COC. Analysis of the FOC showed dependence on the F10.7 radio flux. Analysis of the CDC signals showed additional dependences on F10.7 and the GOES x-ray fluxes. The SEM FOC was also well correlated with thein 30.4 nm channel of the SOHO EUV Imaging Telescope (EIT). The irradiance derived from all four EIT channels (30.4 nm, 17.1 nm, 28.4 nm, and 19.5 nm) showed better correlation with MgII than F10.7.

  17. X-ray irradiation of yeast cells

    Science.gov (United States)

    Masini, Alessandra; Batani, Dimitri; Previdi, Fabio; Conti, Aldo; Pisani, Francesca; Botto, Cesare; Bortolotto, Fulvia; Torsiello, Flavia; Turcu, I. C. Edmond; Allott, Ric M.; Lisi, Nicola; Milani, Marziale; Costato, Michele; Pozzi, Achille; Koenig, Michel

    1997-10-01

    Saccharomyces Cerevisiae yeast cells were irradiated using the soft X-ray laser-plasma source at Rutherford Laboratory. The aim was to produce a selective damage of enzyme metabolic activity at the wall and membrane level (responsible for fermentation) without interfering with respiration (taking place in mitochondria) and with nuclear and DNA activity. The source was calibrated by PIN diodes and X-ray spectrometers. Teflon stripes were chosen as targets for the UV laser, emitting X-rays at about 0.9 keV, characterized by a very large decay exponent in biological matter. X-ray doses to the different cell compartments were calculated following a Lambert-Bouguet-Beer law. After irradiation, the selective damage to metabolic activity at the membrane level was measured by monitoring CO2 production with pressure silicon detectors. Preliminary results gave evidence of pressure reduction for irradiated samples and non-linear response to doses. Also metabolic oscillations were evidenced in cell suspensions and it was shown that X-ray irradiation changed the oscillation frequency.

  18. HANARO fuel irradiation test(I)

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Dong Sung; Jeon, Byung Jin; Kim, Hak No; Kang, Byung Wee; Lee, Jong Tak; Kim, Bong Ku; Lim, In Chul; Chae, Hee Taek; Park, Cheol; Lee, Byung Cheol; Oh, Yeon Wo; Ahn, Sang Bok [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1996-07-01

    Various types of test fuel has been reviewed and a 36 element hexagonal bundle design, with only 6 fuel elements at the corners of the peripheral positions and with A1 dummy rods or hollow elements at the remained 30 positions, was selected. The design enables the assembly to get local power boosting and to achieve higher power and faster burnup accumulation than other driver fuel in the core. For the three central positions (CT, IR 1 and IR 2) with maximum neutron flux, three different target burnup levels of {approx} 40, {approx} 65 and 85 {approx} 90 a/o have been chosen for the three test assemblies. One test assembly will be instrumented with thermocouples, neutron and gamma detectors to verify the irradiation condition. The instrumented test assembly has been fabricated in KAERI and other two test assemblies without any instruments were supplied by AECL. Two un-instrumented assemblies was inserted into HANARO at the end of December 1995 and has been under irradiation at IR 1 and IR 2 core positions without any problem. The measured data in the first cycle was conformed well to the predicted results. In the first cycle irradiation, the best estimated maximum power was 100.5 kw/m (MCNP) and the conservative maximum power was 117.7 kw/m. The instrumented test assembly will be irradiated from the second cycle. 5 tabs., 11 figs., 8 refs. (Author).

  19. Characterization of gamma irradiated plasticized carboxymethyl ...

    Indian Academy of Sciences (India)

    Polymer blends based on carboxymethylcellulose (CMC) and gum arabic (GA) were prepared by solution casting method. Glycerol was added to the polymer blend solution as a plasticizer with different ratios (2.5, 5, 10 and 20%). Then, the plasticized blends were exposed to gamma irradiation at different doses (5, 10 and ...

  20. Irradiation Processing Department monthly report, February 1959

    Energy Technology Data Exchange (ETDEWEB)

    1959-03-20

    This document details activities of the irradiation processing department during the month of February 1959. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; Employee Relations Operation; and Financial Operation.

  1. Irradiation Processing Department monthly report, April 1961

    Energy Technology Data Exchange (ETDEWEB)

    1961-05-15

    This document details activities of the irradiation processing department during the month of April, 1961. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; Employee Relations Operation; Financial Operation; and NPR project.

  2. Irradiation Processing Department monthly report, May 1961

    Energy Technology Data Exchange (ETDEWEB)

    1961-06-15

    This document details activities of the irradiation processing department during the month of May, 1961. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; production and Reactor Operations; Facilities Engineering Operation; Employee Relations Operation; and NPR Reactor.

  3. Irradiation Processing Department monthly report, November 1960

    Energy Technology Data Exchange (ETDEWEB)

    1960-12-14

    This document details activities of the irradiation processing department during the month of November, 1960. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operation; Production and Reactor Operations; Facilities Engineering Operation; Employee Relations Operation; Financial Operation; and NPR Project.

  4. Irradiation Processing Department monthly report, July 1960

    Energy Technology Data Exchange (ETDEWEB)

    1960-08-12

    This document details activities of the irradiation processing department during the month of July, 1960. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; Employee Relations Operation; and Financial Operation.

  5. Irradiation Processing Department monthly report, September 1961

    Energy Technology Data Exchange (ETDEWEB)

    1961-10-16

    This document details activities of the irradiation processing department during the month of September, 1961. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; and NPR Project.

  6. Irradiation Processing Department monthly report, July 1961

    Energy Technology Data Exchange (ETDEWEB)

    1961-08-14

    This document details activities of the irradiation processing department during the month of July 1961. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; Employee Relations Operation; Financial Operation; and NPR Project.

  7. Behavior of beryllium pebbles under irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Dalle-Donne, M.; Scaffidi-Argentina, F. [Forschungszentrum Karlsruhe GmbH Technik und Umwelt (Germany). Inst. fuer Neutronenphysik und Reactortechnik; Baldwin, D.L.; Gelles, D.S.; Greenwood, L.R.; Kawamura, H.; Oliver, B.M.

    1998-01-01

    Beryllium pebbles are being considered in fusion reactor blanket designs as neutron multiplier. An example is the European `Helium Cooled Pebble Bed Blanket.` Several forms of beryllium pebbles are commercially available but little is known about these forms in response to fast neutron irradiation. Commercially available beryllium pebbles have been irradiated to approximately 1.3 x 10{sup 22} n/cm{sup 2} (E>1 MeV) at 390degC. Pebbles 1-mm in diameter manufactured by Brush Wellman, USA and by Nippon Gaishi Company, Japan, and 3-mm pebbles manufactured by Brush Wellman were included. All were irradiated in the below-core area of the Experimental Breeder Reactor-II in Idaho Falls, USA, in molybdenum alloy capsules containing helium. Post-irradiation results are presented on density change measurements, tritium release by assay, stepped-temperature anneal, and thermal ramp desorption tests, and helium release by assay and stepped-temperature anneal measurements, for Be pebbles from two manufacturing methods, and with two specimen diameters. The experimental results on density change and tritium and helium release are compared with the predictions of the code ANFIBE. (author)

  8. Irradiation Processing Department monthly report, June 1964

    Energy Technology Data Exchange (ETDEWEB)

    1964-07-15

    This document details activities of the Irradiation Processing Department during the month of June, 1964. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; Employee Relations Operation; and Financial Operation.

  9. Strain engineering in graphene by laser irradiation

    Science.gov (United States)

    Papasimakis, N.; Mailis, S.; Huang, C. C.; Al-Saab, F.; Hewak, D. W.; Luo, Z.; Shen, Z. X.

    2015-02-01

    We demonstrate that the Raman spectrum of graphene on lithium niobate can be controlled locally by continuous exposure to laser irradiation. We interpret our results in terms of changes to doping and mechanical strain and show that our observations are consistent with light-induced gradual strain relaxation in the graphene layer.

  10. Spectral irradiance measurements using a novel spectroradiometer

    Digital Repository Service at National Institute of Oceanography (India)

    Desa, E.S.; Desa, B.A.E.; DeSa, E.J.; Desai, R.G.P.

    aluminium alloy casing. The spectrographs employ 512 element photodiode arrays to measure downward (Ed) and upward (Eu) spectral irradiance in the wavelength region 350-750 mm at minimum practical resolution of 2 nm using 50 mu entrance slits. Apart from...

  11. dielectric constants of irradiated and carbonated polymers

    African Journals Online (AJOL)

    user

    1985-09-01

    Sep 1, 1985 ... irradiated and carbonated polymers as a function of carbon concentration are investigated. Both low and high density polymers are used. Results predict a quadratic increase in the dielectric constant of specimen as the percentage concentration of carbon is increased. This may be due to the formation of ...

  12. Amphytrion: Example of a high capacity irradiator

    Science.gov (United States)

    Keraron(SGN-France), Y.; Santos(Amphytrion-France), P. L.

    SGN recently built a pallet irradiator for the AMPHYTRION Company which incorporates new technological features. After a short review of the design criteria, the major mechanical equipment is described (source-holder, conveyor, automatic warehouse system), together with the ventilation/air conditioning system and the control/management architecture. Information is given on the new technical aspects and the performance of the facility.

  13. Irradiation Processing Department monthly report, January 1962

    Energy Technology Data Exchange (ETDEWEB)

    1962-02-15

    This document details activities of the Irradiation Processing Department during the month of January, 1962. A general summary is included at the start of the report, after which the report is divided into the following sections: Research and Engineering Operations; Production and Reactor Operations; Facilities Engineering Operation; and NPR Project.

  14. Significance of primary irradiation creep in graphite

    CSIR Research Space (South Africa)

    Erasmus, C

    2013-05-01

    Full Text Available of Nuclear Materials, vol. 436(1-3), pp 167-174 Significance of primary irradiation creep in graphite Christiaan Erasmus a,⇑, Schalk Kok b, Michael P. Hindley a a Pebble Bed Modular Reactor (Proprietary) Limited, PO Box 9396, Centurion 0046, South...

  15. Pregnancy complicating irradiation-induced constrictive pericarditis

    Energy Technology Data Exchange (ETDEWEB)

    Bakri, Younes N.; Martan, Ahmed; Amri, Aladin (King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia). Dept. of Obstetrics and Gynecology); Amri, M. (King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia). Dept. of Cardiovascular Diseases)

    1992-01-01

    A case is reported of a 24 year-old primigravida who had severe effusive constrictive pericarditis secondary to mediastinal irradiation following chemotherapy for Hodgkins disease. Pregnancy was threatened by serious maternal cardiovascular complications and a non-viable fetus was born spontaneously and prematurely. Patient was completely asymptomatic before pregnancy. (au).

  16. Renal effects of renal x irradiation and induced autoallergic glomerulonephritis

    Energy Technology Data Exchange (ETDEWEB)

    Rappaport, D.S.; Casarett, G.W.

    1979-09-01

    This study was conducted to determine what influence a single large x-ray exposure of kidney has on the development and course of an experimental autoallergic glomerulonephritis (EAG) in rats. EAG was induced in female Sprague-Dawley rats by immunization with Bordetella pertussis vaccine and homogenate of homologous kidney tissue and Freund's complete adjuvant. Progressive arteriolonephrosclerosis (ANS) was observed in right (irradiated) kidneys following unilateral renal irradiation (1500 rad). Rats were either immunized, sham-immunized, irradiated, sham-irradiated, or both immunized and irradiated. Light and immunofluorescent microscopic observation, urine protein content, and kidney weights were evaluated. In immunized-irradiated animals the effects of irradiation and immunization were largely additive. Immunization did not considerably influence the development and course of ANS and irradiation did not considerably influence the development and course of EAG.

  17. Food irradiation: Standards, regulations and world-wide trade

    Science.gov (United States)

    Roberts, Peter B.

    2016-12-01

    There is an established framework of international standards for food irradiation covering human health, plant protection, labelling, dose delivery, quality assurance and facility management. Approximately 60 countries permit irradiation of one or more food or food classes. National regulations are briefly reviewed. Decontamination of spices, herbs and condiments remains the single largest application of irradiation. However, in recent years the market for irradiated fresh and processed meat has become firmly established in several countries including China and the USA. At least 10 countries have recently established bi-lateral agreements for trade in irradiated fresh fruits and vegetables using phytosanitary irradiation. Irradiated fresh produce volumes now exceed 20,000 t per year. Rationalization and greater consistency in labelling regulations would be advantageous to the future growth of applications of food irradiation.

  18. Study of properties of tungsten irradiated in hydrogen atmosphere

    Science.gov (United States)

    Tazhibayeva, I.; Skakov, M.; Baklanov, V.; Koyanbayev, E.; Miniyazov, A.; Kulsartov, T.; Ponkratov, Yu.; Gordienko, Yu.; Zaurbekova, Zh.; Kukushkin, I.; Nesterov, E.

    2017-12-01

    The paper presents the results of the experiments with DF (double forged) tungsten samples irradiated at the WWR-K research reactor in hydrogen and helium atmospheres. The irradiation time was 3255 h (135.6 d). After reactor irradiation, W samples have been subjected to investigations of their activity level, hardness, and microstructure, as well as x-ray and texture observations. The hydrogen yield released from irradiated tungsten samples have been measured using TDS-method. The hydrogen concentration in the tungsten samples irradiated in hydrogen was higher than that in the samples irradiated in helium atmosphere. It is shown that the surface microstructure of tungsten samples irradiated in hydrogen is characterized by micro-pits, inclusions and blisters in the form of bubbles, which were not observed earlier for tungsten irradiated in hydrogen.

  19. TCTE Level 3 Total Solar Irradiance Daily Means V002

    Data.gov (United States)

    National Aeronautics and Space Administration — The Total Solar Irradiance (TSI) Calibration Transfer Experiment (TCTE) data set TCTE3TSID contains daily averaged total solar irradiance (a.k.a solar constant) data...

  20. How to improve the irradiation conditions for the International Fusion Materials Irradiation Facility

    CERN Document Server

    Daum, E

    2000-01-01

    The accelerator-based intense D-Li neutron source International Fusion Materials Irradiation Facility (IFMIF) provides very suitable irradiation conditions for fusion materials development with the attractive option of accelerated irradiations. Investigations show that a neutron moderator made of tungsten and placed in the IFMIF test cell can further improve the irradiation conditions. The moderator softens the IFMIF neutron spectrum by enhancing the fraction of low energy neutrons. For displacement damage, the ratio of point defects to cascades is more DEMO relevant and for tritium production in Li-based breeding ceramic materials it leads to a preferred production via the sup 6 Li(n,t) sup 4 He channel as it occurs in a DEMO breeding blanket.