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Studies on the Interaction Between Blood and Vascular Wall During Thrombus Formation and Thrombolysis with Special References to Clinical Diagnosis, Treatment and Prophylaxis of Thrombosis.

血栓形成和溶栓过程中血液与血管壁相互作用的研究，特别是血栓形成的临床诊断、治疗和预防。

基本信息

批准号：
63304045
负责人：
SUEISHI Katsuo
金额：
$ 16.9万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Co-operative Research (A)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1990
项目状态：
已结题

项目摘要

This project was co-operatively performed to elucidate the recent topics as the important factors participating in the thrombosis, namely molecular characteristics of coagulation and fibrinolysis factors, genetical expression and regulation of these factors, physiological and pathological properties of endothelial cells, risk factors of endothelial injuries, the interaction between endothelial cells, blood cells and smooth muscle cells, the molecular mechanism of platelet adherence and aggregation, biochemical and immunohistochemical studies of initiating and regulating factors of coagulation-fibrinolysis system. In addition, on these basic researches clinical or preclinical alterations of coagulatory and fibrinolytic functions were enzymologically and immunochemically analyzed for platelets and several factors of coagulation-fibrinolysis system. We established the immunoenzymatic and specific enzymatic assay methods for several serine-proteases and inhibitors.1. Studies on the mechani … More sm of thrombus-formation and thrombolysis :The clearance mechanism of endotoxin in vivo, in the relation to the thrombogenesis, was immunohistochemically and ultrastructurally investigated by the novel histochemical method using crab-shoe horse Factor C as a specific ligand to endotoxin. Angiogenesis was regulated by the endothelial expression of protease activities in an autocrine manner, and also modulated by cytokines such as TGF beta released from smooth muscle cells and macrophages. The several factors of coagulation-fibrinolysis system were analyzed for immunochemical properties using monoclonal antibodies, and for cDNA sequences. The functional domains of thrombomodulin (TM), Factors VII and IX and others were clarified at the molecular bases partly using recombinant peptides.2. Studies on the pathogenesis, diagnosis and treatment of clinical thrombosis :The several parameters in plasma such as TAT, TM and others were clinically estimated for the diagnosis of thrombotic and prethrombotic states. The antiplatelet therapy was clinically standardized to establish the therapeutical plans for thrombotic diseases. Congenital coagulopathies and their heterogeneity were genetically and enzymologically clarified. Less

本项目旨在阐明近年来血栓形成的重要因素，即凝血和纤溶因子的分子特征，这些因子的基因表达和调控，内皮细胞的生理和病理特性，内皮损伤的危险因素，内皮细胞、血细胞和平滑肌细胞之间的相互作用，血小板粘附和聚集的分子机制，凝血纤溶系统启动和调节因子的生化和免疫组化研究。此外，在这些基础研究的临床或临床前的凝血和纤溶功能的变化进行了酶学和免疫化学分析的血小板和凝血-纤溶系统的几个因素。建立了几种丝氨酸蛋白酶和丝氨酸蛋白酶的免疫酶法和特异性酶法.机理研究 ...更多信息血栓形成和溶栓的机制：以蟹靴马C因子为内毒素的特异性配体，用组织化学方法和超微结构观察了内毒素在体内的清除机制与血栓形成的关系。血管生成由自分泌方式的蛋白酶活性的内皮表达调节，并且还由细胞因子如从平滑肌细胞和巨噬细胞释放的TGF β调节。凝血-纤溶系统的几个因素进行了分析，使用单克隆抗体的免疫化学性质，并为cDNA序列。利用重组肽部分阐明了血栓调节蛋白（TM）、因子VII和因子IX等的功能结构域.临床血栓形成的发病机制、诊断和治疗研究：临床上测定了血浆中的几个参数，如达特、TM等，用于诊断血栓形成和血栓前状态。规范抗血小板治疗，制定血栓性疾病的治疗方案。先天性凝血病及其异质性在遗传学和酶学上得到了阐明。少