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91.
Critical roles for IL-4, IL-5, and eosinophils in chronic skin allograft rejection 总被引:7,自引:0,他引:7
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Alain Le Moine Véronique Flamand Fran?ois-Xavier Demoor Jean-Christophe No?l Murielle Surquin Robert Kiss Marie-Anne Nahori Marina Pretolani Michel Goldman Daniel Abramowicz 《The Journal of clinical investigation》1999,103(12):1659-1667
C57BL/6 mice injected with the 145-2C11 anti-CD3 mAb and grafted with MHC class II disparate bm12 skin develop a chronic rejection characterized by interstitial dermal fibrosis, a marked eosinophil infiltrate, and an obliterative intimal vasculopathy. Because these changes occur in the absence of alloreactive antibodies, we examined the contribution of cytokines in their pathogenesis. Chronically rejected grafts showed a marked accumulation of both IL-4 and IL-5 mRNA. Mixed lymphocyte reaction experiments established that mice undergoing chronic rejection were primed for IL-4, IL-5, and IL-10 secretion. In vivo administration of anti-IL-4 mAb completely prevented allograft vasculopathy as well as graft eosinophil infiltration and dermal fibrosis. Injection of anti-IL-5 mAb or the use of IL-5-deficient mice as recipients also resulted in the lack of eosinophil infiltration or dermal fibrosis, but these mice did develop allograft vasculopathy. Administration of anti-IL-10 mAb did not influence any histologic parameter of chronic rejection. Thus, in this model, IL-4- and IL-5-mediated tissue allograft eosinophil infiltration is associated with interstitial fibrosis. IL-4, but not eosinophils, is also required for the development of obliterative graft arteriolopathy. 相似文献
92.
S Pillet M H Prevost A Preira P M Girard N Rogine J Hakim M A Gougerot-Pocidalo C Elbim 《Laboratory investigation; a journal of technical methods and pathology》1999,79(7):815-822
We used flow cytometry to study the expression of adhesion molecules at the cell surface and actin polymerization of whole-blood monocytes in 35 HIV-infected patients at different stages of the disease. Monocytes were activated in vivo, as demonstrated by increased expression of the adhesion molecule CD11b/CD18, reduced L-selectin antigen expression, and increased actin polymerization. These abnormalities were present in asymptomatic patients with CD4+ cell counts greater than 500/microl and did not increase with disease progression or viral load. Sialyl-Lewis x and CD31 expression at the monocyte surface was normal in asymptomatic and symptomatic non-AIDS patients. In contrast expression of both molecules was strongly reduced in patients with AIDS. This change, despite normal maximal CD11b/CD18 expression and normal maximal actin polymerization, could contribute to the increased susceptibility to bacterial infections in AIDS. In contrast enhanced monocyte activation may promote their transendothelial migration in non-AIDS patients, possibly explaining the macrophage infiltration that can occur early in the disease. 相似文献
93.
Josse R Dumont J Fautrel A Robin MA Guillouzo A 《Toxicology and applied pharmacology》2012,258(2):176-187
Gene expression profiling has recently emerged as a promising approach to identify early target genes and discriminate genotoxic carcinogens from non-genotoxic carcinogens and non-carcinogens. However, early gene changes induced by genotoxic compounds in human liver remain largely unknown. Primary human hepatocytes and differentiated HepaRG cells were exposed to aflatoxin B1 (AFB1) that induces DNA damage following enzyme-mediated bioactivation. Gene expression profile changes induced by a 24 h exposure of these hepatocyte models to 0.05 and 0.25 μM AFB1 were analyzed by using oligonucleotide pangenomic microarrays. The main altered signaling pathway was the p53 pathway and related functions such as cell cycle, apoptosis and DNA repair. Direct involvement of the p53 protein in response to AFB1 was verified by using siRNA directed against p53. Among the 83 well-annotated genes commonly modulated in two pools of three human hepatocyte populations and HepaRG cells, several genes were identified as altered by AFB1 for the first time. In addition, a subset of 10 AFB1-altered genes, selected upon basis of their function or tumor suppressor role, was tested in four human hepatocyte populations and in response to other chemicals. Although they exhibited large variable inter-donor fold-changes, several of these genes, particularly FHIT, BCAS3 and SMYD3, were found to be altered by various direct and other indirect genotoxic compounds and unaffected by non-genotoxic compounds. Overall, this comprehensive analysis of early gene expression changes induced by AFB1 in human hepatocytes identified a gene subset that included several genes representing potential biomarkers of genotoxic compounds. 相似文献
94.
Mathias Bruyand Marie-Anne Vandenhende Guillaume Marcel Estibaliz Lazaro Marie-Edith Lafon Michel Dupon François Dabis Stéphane Geffard Hervé Fleury Muriel Faure-Della Corte Fabrice Bonnet Rodolphe Thiebaut Isabelle Garrigue 《Journal of clinical virology》2011,50(2):177-180
BackgroundCMV reactivation, which enhances immune senescence, could be associated with a higher risk of cancer.ObjectivesWe compared the prevalence of positive CMV DNAemia in HIV-infected patients with and without cancer.Study designThis case–control study, nested in the ANRS-CO3 Aquitaine Cohort, included patients with a first diagnosis of cancer (2002–2007) as cases. Two controls were matched per case.Cancer risk was estimated using conditional logistic regression models, an Odds Ratio (OR) of 2 could be detected with 80% power. The variables considered were: ≥1 positive CMV DNAemia, CD4+ and CD8+ counts, HIV plasma load. Plasma CMV DNA was retrospectively quantified within the 3-year period preceding the endpoint.ResultsThe 143 cases (93 non-AIDS-related and 50 AIDS-related cancers) and 284 controls had a median age of 47 years (IQR: 41–56). At the time of diagnosis or censorship, for cases and controls, median values were respectively, for CD4+ count: 327 cells/mm3 (IQR: 164–514) and 416 (IQR: 275–582), and for HIV plasma load: 2.6 log10 copies/mL (IQR: 1.7–4.7) and 1.7 log10 copies/mL (IQR: 1.7–3.3). We performed 2056 CMV PCR; 14 cases (9.8% [95% CI: 4.9–14.7]) and 19 controls (6.7% [CI: 3.8–9.6]) presented ≥1 positive PCR. CMV DNAemia was not associated with the risk of cancer (unadjusted and adjusted p-values = 0.19 and 0.54, respectively). HIV load >500 copies/mL was independently associated with a higher risk of cancer (OR = 2.02; p = 0.002; 95% CI: 1.29–3.17).ConclusionThis large case–control study did not show any differential exposure to positive CMV plasma DNAemia between cancer cases and controls. 相似文献
95.
Vanderhasselt MA De Raedt R Baeken C Leyman L D'haenen H 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2006,172(4):561-565
High frequency (HF) repetitive transcranial magnetic stimulation (rTMS) has an excitatory effect on neurons of a specific brain area. The dorsolateral prefrontal cortex (DLPFC) has been associated with executive functions, such as task set switching. One important experimental paradigm for investigating such higher order cognitive control is the task-switching (TS) paradigm. A TS paradigm requires switching between two conditional response tasks with mutually incompatible response–selection rules. In the present study, the influence of HF rTMS over the right DLPFC in healthy female volunteers on a modified TS paradigm was investigated. As expected, reaction time on cued switching trials decreased significant after rTMS, as compared to non-cued switch trials. No changes emerged after the placebo sham condition. Mood remained unchanged after rTMS. These findings demonstrate the role of the right DLPFC in cued intentional set switch initiation. 相似文献
96.
97.
98.
Letellier MA Guillard J Caignard DH Ferry G Boutin JA Viaud-Massuard MC 《European journal of medicinal chemistry》2008,43(8):1730-1736
A new series of substituted 4,4-dimethyl-3,4-dihydro-1H-quinolin-2-one have been prepared via condensation of 3,3-dimethylacryloyl chloride with aniline. Details of synthetic procedures are shown. Our aim was to investigate the potency of our original heterocycle in the inhibition of the Rho-kinase enzyme, known to be of major importance in the cascade reactions leading to arterial hypertension. Biological activity for the seven compounds has been investigated and is presented. 相似文献
99.
Marie-Anne Froment Scarlett L. Gomez Audrey Roux Mindy C. DeRouen Elizabeth A. Kidd 《Gynecologic oncology》2014