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CD95 engagement induces disseminated endothelial cell apoptosis in vivo: immunopathologic implications 总被引:6,自引:3,他引:6
Janin A Deschaumes C Daneshpouy M Estaquier J Micic-Polianski J Rajagopalan-Levasseur P Akarid K Mounier N Gluckman E Socié G Ameisen JC 《Blood》2002,99(8):2940-2947
Fas (CD95) is a death receptor involved in apoptosis induction on engagement by Fas ligand (CD95L). Although CD95L-mediated apoptosis has been proposed as a pathogenic mechanism in a wide range of diseases, including graft-versus-host disease, systemic CD95 engagement in mice by agonistic CD95-specific antibodies or by soluble multimeric CD95L (smCD95L), though lethal, has been reported to cause apoptosis only in a limited range of cell types, that is, hepatocytes, hepatic sinusoidal endothelial cells, and lymphocytes. Another member of the tumor necrosis factor (TNF)/CD95L family, TNF-alpha, induces disseminated vascular endothelial cell apoptosis, which precedes apoptosis of other cell types and lethal multiorgan failure. Here we show that systemic CD95 engagement in vivo by agonistic CD95-specific antibody or smCD95L causes rapid, extensive, and disseminated endothelial cell apoptosis throughout the body, by a mechanism that does not depend on TNF-alpha. Disseminated endothelial cell apoptosis was also the first detectable lesion in a murine model of acute tissue damage induced by systemic transfer of allogeneic lymphocytes and did not occur when allogeneic lymphocytes were from CD95L-defective mice. Both vascular and additional tissue lesions induced by agonistic CD95-specific antibody, smCD95L, or allogeneic lymphocytes were prevented by treatment with an inhibitor of caspase-8, the upstream caspase coupled to CD95 death signaling. Vascular lesions are likely to play an important role in the pathogenesis of allogeneic immune responses and of other diseases involving circulating CD95L-expressing cells or smCD95L, and the prevention of CD95-mediated death signaling in endothelial cells may have therapeutic implications in these diseases. 相似文献
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Sokic-Milutinovic A Todorovic V Milosavljevic T Micev M Drndarevic N Mitrovic O 《World journal of gastroenterology : WJG》2005,11(27):4140-4147
ABM: To assess long-term effects of Helicobacter pylori (H pylori) eradication on antral G cell morphology and function in patients with and without duodenal ulcer (DU). METHODS: Consecutive dyspeptic patients referred to the endoscopy entered the study. Out of 39 H pylori positive patients, 8 had DU (Hpylori+DU) and 31 gastritis (Hpylori +G). Control groups consisted of 11 uninfected dyspeptic patients (CG1) and 7 healthy volunteers (CG2). Basal plasma gastrin (PGL), antral tissue gastrin concentrations (ATGC), immunohistochemical and electron microscopic characteristics of G cells were determined, prior to and 6 mo after therapy. RESULTS: We demonstrated elevated PGL in infected patients compared to uninfected controls prior to therapy. Elevated PGL were registered in all H pylori+patients (H pylori +DU: 106.78±22.72 pg/mL, H pylori+G: 74.95±15.63, CG1: 68.59±17.97, CG2: 39.24±5.59 pg/mL, P<0.01). Successful eradication (e) therapy in H pylori+patients lead to significant decrease in PGL (H pylori+DU:59.93±9.40 and H pylori+Ge: 42.36±10.28 pg/mL, P<0.001). ATGC at the beginning of the study were similar in infected and uninfected patients and eradication therapy lead to significant decrease in ATGC in H pylori+gastritis, but not in DU patients. In the H pylori+DU patients, the mean number of antral G cells was significantly lower in comparison with all other groups (P<0.01), but after successful eradication was close to normal values found in controls. By contrast, G cell number and volume density were significantly decreased (P<0.01) in H pylori+Ge group after successful eradication therapy (294±32 and 0.31±0.02, respectively), in comparison to values before eradication (416±40 and 0.48±0.09). No significant change of the G cell/total endocrine cell ratio was observed during the 6 mo of follow up in any of the groups. A reversible increase in G cell secretory function was seen in all infected individuals, demonstrated by a more prominent secretory apparatus. However, differences between DU and gastritis group were identified. CONCLUSION: H pylori infection induces antral G cell hyperfunction resulting in increased gastrin synthesis and secretion. After eradication therapy complete morphological and functional recovery is observed in patients with gastritis. In the DU patients some other factors unrelated to the H pylori infection influence antral G cell morphology and function. 相似文献
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Benefits and Burdens of Using a SNP Array in Pregnancies at Increased Risk for the Common Aneuploidies
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Diane Van Opstal Femke de Vries Lutgarde Govaerts Marjan Boter Debora Lont Stefanie van Veen Marieke Joosten Karin Diderich Robert‐Jan Galjaard Malgorzata I. Srebniak 《Human mutation》2015,36(3):319-326
We present the nature of pathogenic SNP array findings in pregnancies without ultrasound (US) abnormalities and show the additional diagnostic value of SNP array as compared with rapid aneuploidy detection and karyotyping. 1,330 prenatal samples were investigated with a 0.5‐Mb SNP array after the exclusion of the most common aneuploidies. In 2.7% (36/1,330) of the cases, pathogenic chromosome aberrations were found; a microscopically detectable abnormality in 0.7% and a submicroscopic aberration in 2%. Our results show that in addition to the age‐ or screening‐related aneuploidy risk, in pregnancies without US abnormalities, there is a risk of 1:148 (9/1,330) for a (sub)microscopic abnormality associated with an early‐onset often severe disease, 1:222 (6/1,330) for a submicroscopic aberration causing an early‐onset disease, 1:74 (18/1,330) for carrying a susceptibility locus for a neurodevelopmental disorder, and 1:443 (3/1,330) for a late‐onset disorder (hereditary neuropathy with liability to pressure palsies in all three cases). These risk figures are important for adequate pretest counseling so that prospective parents can make informed individualized choices between targeted prenatal testing and broad testing with SNP array. Based on our results, we believe if invasive testing is performed, SNP array should be the preferred cytogenetic technique irrespective of the indication. 相似文献
25.
Dimitra Micha Dong‐chuan Guo Yvonne Hilhorst‐Hofstee Fop van Kooten Dian Atmaja Eline Overwater Ferdy K. Cayami Ellen S. Regalado René van Uffelen Hanka Venselaar Sultana M.H. Faradz Gerrit Vriend Marjan M. Weiss Erik A. Sistermans Alessandra Maugeri Dianna M. Milewicz Gerard Pals Fleur S. van Dijk 《Human mutation》2015,36(12):1145-1149
We report three families with arterial aneurysms and dissections in which variants predicted to be pathogenic were identified in SMAD2. Moreover, one variant occurred de novo in a proband with unaffected parents. SMAD2 is a strong candidate gene for arterial aneurysms and dissections given its role in the TGF‐β signaling pathway. Furthermore, although SMAD2 and SMAD3 probably have functionally distinct roles in cell signaling, they are structurally very similar. Our findings indicate that SMAD2 mutations are associated with arterial aneurysms and dissections and are in accordance with the observation that patients with pathogenic variants in genes encoding proteins involved in the TGF‐β signaling pathway exhibit arterial aneurysms and dissections as key features 相似文献
26.
Annelies Suetens Marjan Moreels Roel Quintens Els Soors Jasmine Buset Sabina Chiriotti Kevin Tabury Vincent Gregoire Sarah Baatout 《Journal of radiation research》2015,56(1):11-21
Hadrontherapy is an advanced form of radiotherapy that uses beams of charged particles (such as protons and carbon ions). Compared with conventional radiotherapy, the main advantages of carbon ion therapy are the precise absorbed dose localization, along with an increased relative biological effectiveness (RBE). This high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited. Currently, hadrontherapy is being used for the treatment of specific types of cancer. Previous in vitro studies have shown that, under certain circumstances, exposure to charged particles may inhibit cell motility and migration. In the present study, we investigated the expression of four motility-related genes in prostate (PC3) and colon (Caco-2) cancer cell lines after exposure to different radiation types. Cells were irradiated with various absorbed doses (0, 0.5 and 2 Gy) of accelerated 13C-ions at the GANIL facility (Caen, France) or with X-rays. Clonogenic assays were performed to determine the RBE. RT-qPCR analysis showed dose- and time-dependent changes in the expression of CCDC88A, FN1, MYH9 and ROCK1 in both cell lines. However, whereas in PC3 cells the response to carbon ion irradiation was enhanced compared with X-irradiation, the effect was the opposite in Caco-2 cells, indicating cell-type–specific responses to the different radiation types. 相似文献
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Evelien Platje Lucres M.C. Jansen Adrian Raine Susan J.T. Branje Theo A.H. Doreleijers Marjan de Vries-Bouw Arne Popma Pol A.C. van Lier Hans M. Koot Wim H.J. Meeus Robert R.J.M. Vermeiren 《Biological psychology》2013
Although several studies have associated antisocial behavior with decreased cortisol awakening responses (CAR), studies in adolescent samples yielded inconsistent results. In adolescence however, the CAR develops and antisocial behavior is heterogeneous in type and persistence. Therefore this longitudinal study compared persistent aggressive and rule-breaking adolescents to low aggressive and rule-breaking adolescents on the development of the CAR from ages 15 to 17 (N = 390). Persistently high aggressive adolescents showed decreased cortisol levels at awakening consistently over the years (Δχ2(1) = 6.655, p = .01) as compared to low aggressive adolescents. No differences between adolescents showing persistent high rule-breaking and low rule-breaking were found. This longitudinal study is the first to show that persistent aggression, but not rule-breaking behavior, is related to neurobiological alterations. Moreover, despite development of the CAR over adolescence, the decrease in cortisol is consistent over time in persistent high aggressive adolescents, which is an important prerequisite for the prediction of persistent aggression. 相似文献
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Liu Gengbo Mitra Debasis Jones Ella F. Franc Benjamin L. Behr Spencer C. Nguyen Alex Bolouri Marjan S. Wisner Dorota J. Joe Bonnie N. Esserman Laura J. Hylton Nola M. Seo Youngho 《Journal of digital imaging》2021,34(3):630-636
Journal of Digital Imaging - In this proof-of-concept work, we have developed a 3D-CNN architecture that is guided by the tumor mask for classifying several patient-outcomes in breast cancer from... 相似文献