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Résumé Plusieurs dérivés thiol et deux antioxidants inhibent la bronchoconstriction chez le cobaye, une partie de l'hypotension chez le lapin et la libération de «rabbit aorta contracting substance» (RCS) dues à la bradykinine Il est proposé que les effets communs à la bradykinine, à la SRS-A, SRS-C et à l'acide arachidonique, qui sont bloqués par des antiinflammatoires, acides, et par les dérivés thiol, sont dus à la formation de RCS, constituée par des péroxydes cicliques analogues aux précurseurs instables des prostaglandines E 2 et F 2 alpha.
We thank MrsB. Charpentier andC. Bellevrat for technical help, Prof.H. Clauser andJ. R. Vane and DrH. O. J. Collier for comments and DrS. H. Ferreira for advice concerning the superfusion technique and for BPP9. Squibb provided BPP5. This work is part of a thesis leading to the degree of Docteur-ès-Sciences, Orsay (B.B.V.). 相似文献
We thank MrsB. Charpentier andC. Bellevrat for technical help, Prof.H. Clauser andJ. R. Vane and DrH. O. J. Collier for comments and DrS. H. Ferreira for advice concerning the superfusion technique and for BPP9. Squibb provided BPP5. This work is part of a thesis leading to the degree of Docteur-ès-Sciences, Orsay (B.B.V.). 相似文献
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Effect of cyproheptadine on the octopamine-induced responses in the mammalian central nervous system
Summary Extracellular recordings have been made from rat thalamic neurones anaesthetized with urethane, 1.5–2 g/kg i.p. Iontophoretically applied octopamine excited certain thalamic neurones in the ventral basal complex while inhibiting others. Both effects were reversibly antagonized by iontophoretically applied cyproheptadine without affecting responses to noradrenaline and dopamine.Acknowledgment. We are grateful to Merck, Sharp and Dohme for a gift of cyproheptadine HCl. 相似文献
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Stephens PJ Tarpey PS Davies H Van Loo P Greenman C Wedge DC Nik-Zainal S Martin S Varela I Bignell GR Yates LR Papaemmanuil E Beare D Butler A Cheverton A Gamble J Hinton J Jia M Jayakumar A Jones D Latimer C Lau KW McLaren S McBride DJ Menzies A Mudie L Raine K Rad R Chapman MS Teague J Easton D Langerød A;Oslo Breast Cancer Consortium 《Nature》2012,486(7403):400-404
All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease. 相似文献
147.
Wu X Northcott PA Dubuc A Dupuy AJ Shih DJ Witt H Croul S Bouffet E Fults DW Eberhart CG Garzia L Van Meter T Zagzag D Jabado N Schwartzentruber J Majewski J Scheetz TE Pfister SM Korshunov A Li XN Scherer SW Cho YJ Akagi K MacDonald TJ Koster J McCabe MG Sarver AL Collins VP Weiss WA Largaespada DA Collier LS Taylor MD 《Nature》2012,482(7386):529-533
Medulloblastoma, the most common malignant paediatric brain tumour, arises in the cerebellum and disseminates through the cerebrospinal fluid in the leptomeningeal space to coat the brain and spinal cord. Dissemination, a marker of poor prognosis, is found in up to 40% of children at diagnosis and in most children at the time of recurrence. Affected children therefore are treated with radiation to the entire developing brain and spinal cord, followed by high-dose chemotherapy, with the ensuing deleterious effects on the developing nervous system. The mechanisms of dissemination through the cerebrospinal fluid are poorly studied, and medulloblastoma metastases have been assumed to be biologically similar to the primary tumour. Here we show that in both mouse and human medulloblastoma, the metastases from an individual are extremely similar to each other but are divergent from the matched primary tumour. Clonal genetic events in the metastases can be demonstrated in a restricted subclone of the primary tumour, suggesting that only rare cells within the primary tumour have the ability to metastasize. Failure to account for the bicompartmental nature of metastatic medulloblastoma could be a major barrier to the development of effective targeted therapies. 相似文献
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