Molecular basis for the fibrinogen structure and functions-Analysis of hereditary dysfibrinogens and their application to the study

在为期三年的国际合作期间，我们能够进行以下研究。在Jichi医学院（JMS）首席研究员（Matsuda）实验室进行的研究：来自新发现的遗传性纤维蛋白原异常家族的10多份血浆和/或DNA样本被运送到JMS，这些样本主要来自日本的机构，一些来自德国、以色列、韩国和委内瑞拉。在其中一些样本中，我们已经能够鉴定出基因决定的突变，即，A α Arg-19转化为Gly ; B β Asn-160转化为Ser，伴有B β Asn-158的糖基化，以及除已知类型外，γ Gly-268转化为Glu。通过仔细分析这些分子，我们能够提供已知类型的新信息。通过仔细分析这些分子，我们能够提供关于人纤维蛋白原的结构-功能关系的新信息。研究结果已在国际期刊上发表或提交发表。 ...更多信息 在其他地方所列的有关国际会议上作口头报告。与国外合作者John Weisel和Michael W.Mosesson合作进行的研究：将在JMS进行结构分析的纤维蛋白原异常转移到John Weisel（美国宾夕法尼亚大学）进行的电子显微镜分析。和Michael W.Mosesson（美国威斯康星州大学）。异常纤维蛋白原包括纤维蛋白原Tokyo II（γ Arg-275至Cys）、Asahi（γ Met-310至Thr，伴有γ Asn-308处的额外糖基化）、Kurashiki I（γ Gly-268至Gly）和加拉加斯II（Aalpha Ser-434至Asn，其上连接有额外的寡糖）。通过这些合作，获得了一系列新的信息，并在其他地方列出的国际期刊和国际会议上进行了报道。在英国曼彻斯特、捷克布拉格、以色列耶路撒冷、德国马尔堡、西班牙巴塞罗那、韩国济州、澳大利亚堪培拉等地召开的相关国际会议上，报告了本实验室的研究进展。除了这些介绍之外，首席研究员Matsuda还访问了费城和密尔沃基（美国）的外国合作者以及马尔莫（瑞典）、马尔堡（德国）、马德里（西班牙）和堪培拉（澳大利亚）的其他专家，以便结合或不结合国际会议进行讨论。Arocha-Pinango的研究员，Lundberg博士和JMS进行了一个月的纤维蛋白原Guarenas的结构分析，我发现在委内瑞拉。他逗留期间的部分费用由这项合作研究的补助金支付。少

During the three-year term of this international collaboration, we were able to conduct follwing studies.1. Studies conducted in the chief investigator's (Matsuda's) laboratory at Jichi Medical School (JMS) :More than 10 plasma and/or DNA samples derived from newly found families with hereditary dysfibrinogens were shipped to JMS mostly from institutions in Japan and some from Germany, Israel, Korea and Venezuela. In some of these samples, we have been able to identify genetically determined mutations, i.e., Aalpha Arg-19 to Gly ; Bbeta Asn-160 to Ser accompanied by extraglycosylation at Bbeta Asn-158, and gamma Gly-268 to Glu besides already known types. By carefully analyzing these molecules, we were able to provide lines of new information on the known types. By carefully analyzying these molecules, we were able to provide lines of new information on the structure-function relationships of human fibrinogen. The results were published or submitted for publication in international jou … More rnals and/or reported orally at the relevant international meetings as listed elsewhere.2. Studies conducted in collaboration with the foreign collaborators, John Weisel and Michael W.Mosesson :Dysfibrinogens, which had been analyzed structurally at JMS,were forwarded to electron microscopic analyzes conducted by John Weisel (Pennsylvania University, U.S.A.) and Michael W.Mosesson (University of Wisconsin, U.S.A.). The dysfibrinogens include fibrinogens Tokyo II (gamma Arg-275 to Cys), Asahi (gamma Met-310 to Thr accompanied by extra glycosylation at gamma Asn-308), Kurashiki I (gamma Gly-268 to Gly) and Caracas II (Aalpha Ser-434 to Asn, to which an extra oligosaccharide had been linked). Be these collaborations, lines of new information were obtained, and reported in international journals and at international meetings, as listed elsewhere.3. Research progresses in our laboratory were reported at relevant international meetings held in several places including Manchester (UK), Prague (Czech), Jerusalem (Israel), Marburg (Germany), Barcelona (Span), Cheju (Korea) and Canberra (Australia). Besides these presentations the chief investigator, Matsuda, visited the foreign collaborators in Philadelphia and Milwaukee (USA), and other experts in Malmo (Sweden), Marburg (Germany), Madrid (Spain) and Canberra (Australia) for discussion in conjunction with or without the international meetings.4. Arocha-Pinango's fellow, Dr.Lundberg visiteid JMS for one month to conduct structure analysis of fibrinogen Guarenas I found in Venezuela. Part of the cost for his stay was covered by the grant-in-aid for this collaborative study. Less