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Here, we attempt to reveal how 2-aminofluorene (AF), benzo(α)pyrene (BP) and their major metabolites affect T–cell responses to antigenic and mitogenic stimuli. P-450-related metabolism of these parent compounds to metabolites seems to precede the observed immunosuppression; therefore, we investigated the influence of α-naphthoflavone (P-450 inhibitor) and β-naphthoflavone (P-450 inducer) on BP and AF immunosuppression. We used proliferative responses to concanavalin A and the allogeneic mixed lymphocyte response as correlates of immunosuppression. We also attempted to correlate DNA-adduction to the extent of observed immunosuppression for AF and BP metabolites. These data show that the pathway to the strongest immunosuppressive agents for polycyclic aromatic hydrocarbons and arylamines are divergent and related to metabolism by P450 enzymes. 相似文献
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《Actas dermo-sifiliográficas》2014,105(10):940-946
IntroductionNonmelanoma skin cancer (NMSC) is the most common malignancy in patients who have received a solid organ transplant. Multiple factors are involved in the onset of posttransplant NMSC.ObjectivesTo analyze the relationship between new immunosuppressive drugs and the onset of NMSC in renal transplant recipients.MethodThis was a combined retrospective and prospective observational study in which we studied 289 patients who received a kidney transplant between January 1996 and December 2010 at Hospital Universitario Doctor Peset in Valencia, Spain.ResultsSeventy-three patients (25.2%) developed 162 NMSCs over a median follow-up of 72 months. There were no statistically significant differences in the onset of NMSC on comparing different induction therapy strategies involving monoclonal and polyclonal antibodies. NMSCs occurred less frequently in patients treated with mammalian target of rapamycin (mTOR) inhibitors than in those treated with other immunosuppressive regimens, although the differences were not statistically significant. Three of 5 patients with recurrent NMSC who were switched from calcineurin inhibitors to mTOR inhibitors developed additional NMSCs despite the change.ConclusionsInduction therapy with monoclonal and polyclonal antibodies in renal transplant recipients is not associated with an increased risk of NMSC. While mTOR inhibitors are associated with a lower risk of posttransplant NMSC, it remains to be determined whether a switch to these drugs is useful in the management of patients who develop multiple NMSCs. 相似文献
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《Anais brasileiros de dermatologia》2019,94(1):29-36
Background:Diseases caused by melanized fungi include mycetoma, chromoblastomycosis and phaeohyphomycosis. This broad clinical spectrum depends on the dynamic interactions between etiologic agent and host. The immune status of the host influences on the development of the disease, as, an exemple. phaeohyphomicosis is more frequently observed in immunocompromised patients.Objectives:Examine the histological inflammatory response induced by Fonsecaea pedrosoi in several different strains of mice (BALB/c, C57BL/6, Nude and SCID, and reconstituted Nude).Methods:Fonsecaea pedrosoi was cultivated on agar gel and a fragment of this gel was implanted subcutaneously in the abdominal region of female adult mice. After infection has been obtained, tissue fragment was studied histopathologically.Results:There were significant changes across the strains, with the nodular lesion more persistent in Nude and SCID mice, whereas in immunocompetent mice the lesion progressed to ulceration and healing. The histopathological analysis showed a significant acute inflammatory reaction which consisted mainly of neutrophils in the initial phase that was subsequently followed by a tuberculoid type granuloma in immunocompetent mice.Study limitations:There is no a suitable animal model for chromoblastomycosis.Conclusions:The neutrophilic infiltration had an important role in the containment of infection to prevent fungal spreading, including in immunodeficient mice. The fungal elimination was dependent on T lymphocytes. The re-exposure of C57BL/6 mice to Fonsecaea pedrosoi caused a delay in resolving the infection, and appearance of muriform cells, which may indicate that re-exposure to fungi, might lead to chronicity of infection. 相似文献
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Ellen Strijbos Martijn R. Tannemaat Iris Alleman Robert H.P. de Meel Jaap A. Bakker Ruud van Beek Frank P. Kroon Guus F. Rimmelzwaan Jan J.G.M. Verschuuren 《Vaccine》2019,37(7):919-925