THE SEARCH FOR THE RANSMISSIBLE AGENT AND PATHOGENESIS OF CREUTZFELDT-JAKOB DISEASE (CJD)

克雅氏病 (CJD) 传播媒介的寻找和发病机制

基本信息

批准号：
62480246
负责人：
TAMAI Yoichi
金额：
$ 2.24万
依托单位：
KITASATO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

1. To elucidate the possible relationship between the CJD infectivity and prion proceins, the CJD mouse brain was fractionated into ten fractions, and the infectivity was examined. The CJD infectivity was found not only in the prion fraction but also to comparable extent in the fractions that were free of prion protein. Thus, we concluded that prion proteins are not necessarily requisits for the CJD infectivity.2. Microsomal fractions which had been found to contain the high CJD titer were solubilized with a detergent to obtain the more CJD agent-enriched fraction. The titration study is in progress.3. The affinity of prion proteins with lipids were examined by the ELISA method. The total ganglioside extracts from rat brain and phosphatidyl ethanolamine were found to react with the synthetic prion peptides in the range of about 80% of the control. These findings may indicate that prion peptides require some lipid species to form their characteristic fibrillar structures.4. To make the simple and convenient conditions for the deactivation of the CJD agent, a variety of procedures were tested. The complete inactivation was obtained by autoclaving at 121 C for 60 min after In NaOH treatment for 60 min and also by autoclaving at 131 C for 60 min.5. Ganglisoside composition from the brain of a human case of subacute sclerosing panencephlitis and from the brain of zitter rat with genetic spongiform encephalopathy were investigated. The findings obtained indicate that the ganglioside composition in these two diseases were different from each other and also from that of CJD brain which had been reported. It was suggested, thus, that ganglioside alterations are specific to the respective diseases and closely related to their pathogenesis.

1。为了阐明CJD感染性与prion蛋白之间的可能关系，将CJD小鼠脑分离为十个部分，并检查了感染性。 CJD感染性不仅在王室部分中发现，而且在不含prion蛋白的馏分中也可比较。因此，我们得出的结论是，prion蛋白不一定是CJD感染性的要求2。已经发现包含高CJD滴度的微粒体馏分用洗涤剂溶解，以获得更富含CJD剂的含量。滴定研究正在进行3。通过ELISA方法检查了prion蛋白与脂质的亲和力。发现来自大鼠脑和磷脂酰乙醇胺的总节神经脂提取物与大约80％对照范围内的合成prion肽反应。这些发现可能表明prion肽需要一些脂质物种形成其特征性的纤维结构。4。为了使CJD代理失活的简单方便条件，测试了各种程序。通过在NaOH处理60分钟后，在121 C下在121 C下进行高压灭菌，并在131 C下进行高压灭菌60分钟，从而获得了完整的失活60分钟。研究了从人类大脑中的神经糖苷组成，该病例是亚急性硬化脑炎和带有遗传海绵状脑病的zitter大鼠大脑的大脑。获得的发现表明，这两种疾病中的神经节苷脂组成彼此不同，并且与已报道的CJD脑部不同。因此，有人建议，神经节苷脂的改变是针对各自疾病的特异性，并且与它们的发病机理密切相关。