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

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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