Studies on the pathogenesis and pathophysiology of thromboembolisms in the field of surgery. Development of novel techniques for analyzing the regulatory systems of blood coagulation.

外科领域血栓栓塞的发病机制和病理生理学研究。

基本信息

批准号：
63480293
负责人：
MATSUDA Michio
金额：
$ 4.22万
依托单位：
Jichi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

1. Structure analysis of abnormal fibrinogens: We have analyzed 10 abnormal fibrinogens newly referred to us from several institutions an over the country during the term covered by this research grant-in- aid. The mutations identified included two Arg-275 to His; four Arg-275 to Cys; one each of Met-310 to Thr accompanied by N-glycosylated Asn-308; Asp-330 to Tyr and Arg-375 to Gly substitutions. All these mutations could be accounted for by a single base exchange in the codon encoding respective amino acids.This particular region of the gamma chain seems to constitute critical structures required for fibrin polymerization, and their perturbation solely by a single amino acid replacement should have resulted in severely altered fibrin clot formation. Except the gamma Arg-275 to His substitution, all the mutations identified near the carboxy-terminal region of the gamma chain were found to be newly elucidated structural derangements. Gene analysis studies are currently in progress in o … More ur laboratory.In these structure analyses, we successfully applied several monoclonal antibodies recognizing various structures of fibrinogen as will be stated later in item 3.2. Blood coagulation and fibrinolysis which proceed on the cultured human endothelial cells(EC): We have provided lines of evidence that protein C, normally produced by hepatocytes, was also synthesized by the EC's on the basis of identification of protein C molecules as well as messenger RNA for protein C derived from the cultured EC's. This finding has not been reported heretofore, and thus further studies are necessary to more precisely elucidate the EC-mediated regulation of thrombus formation in vivo.3. Monoclonal antibodies raised against substances related to blood coagulation and fibrinolysis: We have prepared and characterized various monoclonal antibodies against fibrinogen, factors IX, X and XIII, plasminogen activator inhibitor and the thrombin-antithrombin complex. An antibody that recognizes the gamma 86-302 residue peptide of fibrinogen and another one that recognizes the NH_2-terminal conformation of plasmic fragment D were successfully utilized for the structure analysis of abnormal fibrinogens. Antibodies raised against other molecules have also been introduced into the analyses of molecular interactions relevant to thrombus formation and its regulation. Less

1。异常纤维蛋白的结构分析：我们已经分析了10个从全国各地的纤维纤维人物新向我们介绍的纤维蛋白，在本研究授予的术语期间，我们已经分析了全国各地。确定的突变包括他的两个Arg-275。四个Arg-275 to Cys; Met-310中的一个通过N-糖基化ASN-308完成； ASP-330送给Tyr和Arg-375的Gly取代。所有这些突变都可以通过编码相关氨基酸的密码子中的单个碱基交换来解释。伽马链的特定区域似乎构建了纤维蛋白聚合所需的关键结构，仅由单个氨基酸替代摄取，应导致严重改变的纤维蛋白粘液膜形成。除了他的替代伽玛Arg-275外，发现在伽马链的羧基末端区域附近发现的所有突变被发现是新阐明的结构演变。基因分析研究目前正在进行o…更多的实验室。在这些结构分析中，我们成功地应用了几种单克隆抗体，识别纤维蛋白原的各种结构，如稍后在项目3.2中所述。血液凝血和纤维蛋白溶解在培养的人内皮细胞（EC）上进行：我们提供了一系列证据，表明通常由肝细胞产生的蛋白C基于蛋白C分子的鉴定以及蛋白质C的蛋白质C的蛋白质RNA，也由EC合成。这一发现尚未得到报道，因此需要进一步的研究才能更精确地阐明体内的EC介导的血栓形成的调节。3。针对与血液凝血和纤维蛋白溶解有关的物质提出的单克隆抗体：我们已经准备并表征了针对纤维蛋白原，IX，X和XIII，纤溶酶原激活剂抑制剂和凝集素 - 抗抗激素蛋白复合物的各种单克隆抗体。一种识别纤维蛋白原的伽玛86-302保留肽的抗体，另一种识别粘液纤维片段D的NH_2-末端构象的抗体成功地用于了异常纤维蛋白原的结构分析。针对其他分子提出的抗体也已引入与血栓形成及其调节有关的分子相互作用的分析。较少的