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

Research Project

Project/Area Number 06044196
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionJichi Medical School, School of Medicine

Principal Investigator

MATSUDA Michio  Division of Hemostasis and Thrombosis Research, Professor, 医学部, 教授 (50048980)

Co-Investigator(Kenkyū-buntansha) AROCHA Pinan  ベネズエラ科学研究所, 主任研究員
WEISEL John W  University of Pennsylvania, School of Medicine, Professor, 医学部, 教授
ASAKURA Shinji  Division of Hemostasis and Thrombosis Research, Instructor, 医学部, 講師 (70245033)
MIMURO Jun  Division of Hemostasis and Thrombosis Research, Instructor, 医学部, 講師 (10221607)
SUGO Teruko  Division of Hemostasis and Thrombosis Research, Instructor, 医学部, 講師 (60183844)
AROCHA-PINANGO Carmen Lo  Instituto Venezolano de Investigaciones Cientificas, Centro Medicina Experimenta
AROCHAーPINAN ピニャンゴ カルメンルイ  ベネズエラ科学研究所, 主任研究員
CARMEN Louis  ベネズエラ科学研究所, 主任研究員
Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1996: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1995: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsfibrinogen / hereditary dysfibrinogen / fibrin gel / polymerization / electron microscopy of fibrinogen / electron microscopy of fibrin / thrombosis / wound healing insufficiency / フィリン・ゲル / 異常フィブリノゲン / 構造異常 / 電顕学的分析 / 機能障害 / 構造機能関係
Research Abstract

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

Report

(4 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (56 results)

All Other

All Publications (56 results)

  • [Publications] Shosaku Nomura: "β_2-Glycoprotein land anticardiolipin antibody influence factor Xa generation but not factor" Thromb.Haemostas. 71(4). 526-530 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kunihiko Umezawa: "Localization of vitronectin-and fibronectin-receptors on cultured human glioma cells." Brain Res.659. 23-32 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nobuhiko Yoshida: "Effect of calcium on the mobility of γ-chain from fibrinogen Osaka V on sodium dodecyl sulfate-polyacrylamide gel electrophoresis." Thromb.Res.73(1). 79-82 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Teruko Sugo: "Activation of prothrombin by factor Xa bound to the membrane surface of human umbilical vein endothelial cells:Its catalytic efficiency is similar to that of prothrombinase complex on platelets." J.Biochem.177. 244-250 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mikihiro Takebe: "Calcium-dependent monoclonal antibody against human fibrinogen:preparation,characterization,and application to fibrinogen purification." Thromb.Haemost.73(4). 662-667 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Michael W.Mosesson: "The role of fibrinogen D domain inter-molecular association sites in the polymerization of fibrin and fibrinogen Tokyo II(γ275Arg→Cys)." J.Clin.Invest.96. 1053-1058 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Gilbu Soe: "A rapid latex immunoassay for the detection of plasmin-α 2-plasmin inhibitor complesx:Utilization of tswo monoclonal antibodies differentially recognizing respective components of the complex" Blood Coagulation and Fibrinolysis. 6. 249-258 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Koichi Arai: "Effect of staphylokinase concentration on plasminogen activation." Biochim.Biophys.Acta.1245. 69-75 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kazuki Niwa: "A γ Gly-268 to Glu substitution is responsible for impaired fibrin assembly in a homozygous dysfibrinogen Kurashiki I." Blood. 87(11). 4686-4694 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Gilbu Soe: "A monoclonal antibody that recognizes aneoantigen exposed in the E domain of fibrin monomer complexed with fibrinogen or its derivatives.Its application to the measurement of soluble fibrin in plasma." Blood. 88(6). 2109-2117 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Jhon L.Woodhead: "The ultrastructure of fibrinogen Caracas II molecules,fibers and clots." J.Biol.Chem.271(9). 4946-4953 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Michio Matsuda: "The structure-function relationship of hereditary dysfibrinogens." Int.J.Hematol.64. 167-179 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 周紅: "フィブリンの重合とγ鎖架橋形成を阻害する抗フィブリノゲンモノクロナル抗体の性状" 日本血栓止血学会誌. 7(3). 244-250 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 松田道生: "フィブリノゲンの誘導体,とくに可溶性フィブリン(soluble fibrin)とDダイマー(D dimer)について:その生成と存在様式についての考察その1.可溶性フィブリン" 日本血栓止血学会誌. 8. 24-32 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Seiji Madoiwa: "A battery of monoclonal antibodies that induce unique conformations to evolve cryptic but constitutive functions of plasminogen." J.Biochem.121. 278-287 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shinji Asakura: "Fibroblats spread on immobilized fibrin monomer by mobilizing a β1-class integrin,together with a vitronectin receptors,αVβ3 on their surface." J.Biol.Chem.,in press. (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Michio Matsuda: "Glycosylation defects in blood clotting.In:Glycoproteins and Disease.J.Montreuil et al.(Eds.)" Elsevier Science B.V., 439-444 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shosaku Nomura: "beta2-Glycoprotein land anticardiolipin antibody influence factor Xa generation but not factor Xa binding to platelet derived microparticles." Thromb.Haemostas. 71 (4). 526-530 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kunihiko Umezawa: "Localization of vitronectin-and fibronectin-receptors on cultured human glioma cells." Brain Res.659. 23-32 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nobuhiko Yoshida: "Effect of calcium on the mobility of gamma-chain from fibrinogen Osaka V on sodium dodecyl sulfate-polyacrylamide gel electrophoresis." Thromb.Res.73 (1). 79-82 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Teruko Sugo: "Activation of prothrombin by factor Xa bound to the membrane surface of human umbilical vein endothelial cells : Its catalytic efficiency is similar to that of prothrombinase complex on platelets." J.Biochem.117. 244-250 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mikihiro Takebe: "Calcium-dependent monoclonal antibody against human fibrinogen : preparation, characterization, and application to fibrinogen purification." Thromb.Haemost.73 (4). 662-667 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Michael W.Mosesson: "The role of fibrinogen D domain inter-molecular association sites in the polymerization of fibrin and fibrinogen Tokyo II (gamma 275 Arg*Cys)." J.Clin.Invest.96. 1053-1058 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Gilbu Soe: "A rapid latex immunoassay for the detection of plasmin-alpha2-plasmin inhibitor complex : Utilization of two monoclonal antibodies differentially recognizing respective components of the complex." Blood Coagulation and Fibrinolysis. 6. 249-258 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Koichi Arai: "Effect of staphylokinase concentration on plasminogen activation." Biochim.Biophys.Acta.1245. 69-75 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kazuki Niwa: "A gamma Gly-268 to Glu substitution is responsible for impaired fibrin assembly in a homozygous dysfibrinogen Kurashiki I." Blood. 87 (11). 4686-4694 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Gilbu Soe: "A monoclonal antibody that recognizes a neo-antigen exposed in the E domain of fibrin monomer complexed with fibrinogen or its derivatives. Its application to the measurement of soluble fibrin in plasma." Blood. 88 (6). 2109-2117 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] John L.Woodhead: "The ultrastructure of fibrinogen Caracas II molecules, fibers and clots." J.Biol.Chem.271 (9). 4946-4953 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Michio Matsuda: "The structure-function relationship of hereditary dysfibrinogens." Int.J.Hematol.64. 167-179 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hong Zhou: "A monoclonal antibody that inhibits fibrin polymerization and cross-linking of the fibrin gamma-chains" Jpn.J.Thromb.Hemost.7 (3). 244-250 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Michio Matsuda: "The derivatives of human fibrinogen with sepcial reference to soluble fibrin and the D-dimer. Their generation and status in the circulating blood. 1. Soluble fibrin" Jpn.J.Thromb.Hemost.8. 24-32 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Seiji Madoiwa: "A battery of monoclonal antibodies that induce unique conformations to evolve eryptic but constitutive functions of plasminogen." J.Biochem.121. 278-287 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shinji Asakura: "Fibroblats spread on immobilized fibrin monomer by mobilizing a beta1-class integrin, together with a vitronectin receptors, alphaVbeta3 on their surface." J.Biol.Chem.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Michio Matsuda: Elsevier Science B.V.Glycosylation defects in blood clotting. In : Glycoproteins and Disease. J Montreuil et al. (Eds.), 439-444 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kazuki Niwa: "A γ Gly-268 to Glu substitution is responsible for impaired fibrin assembly in a homozygous dysfibrinogen Kurashiki I." Blood. 87(11). 4686-4694 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Gilbu Soe: "A monoclonal antibody that recognized a neo-antigen exposed in the E domain of fibrin monomer complexed with fibrinogen or its derivatives. Its application to the measurement of soluble fibrin in plasma." Blood. 88(6). 2109-2117 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] John L. Woodhead: "The ultrastructure of fibrinogen Caracas II molecules, fibers and clots." J. Biol. Chem.271(9). 4946-4953 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Michio Matsuda: "The structure-function relationship of hereditary dysfibrinogens." Int. J. Hematol.64. 167-179 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 周 紅: "フィブリンの重合とγ鎖架橋形成を阻害する抗フィブリノゲンモノクロナル抗体の性状" 日本血栓止血学会誌. 7(3). 244-250 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 松田道生: "フィブリノゲンの誘導体,とくに可溶性フィブリン(soluble fibrin)とDダイマー(D dimer)について:その生成と存在様式についての考察 その1.可溶性フィブリン" 日本血栓止血学会誌. 8. 24-32 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Seiji Madoiwa: "A battery of monoclonal antibodies that induce unique conformations to evolve cryptic but constitutive functions of plasminogen." J. Biochem.121. 278-287 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shinji Asakura: "Fibroblats spread on immobilized fibrin monomer by mobilizing a β1-class integrin, together with a vitronectin receptors, αVβ3 on their surface." J. Biol. Chem.,. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Michio Matsuda: "Glycosylation defects in blood clotting. In : Glycoproteins and Disease. J. Montreuil et al. (Eds.)" Elsevier Science B. V., 439-444 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Mikihiro Takebe: "Calciumion-dependent monoclonal antibody against human fibrinogen : Preparation,characterization and application to fibrinogen purification." Thromb.Haemost.73(4). 662-667 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Michael W.Mosesson: "The role of fibrinogen D domain inter-molecular association sites in the polymeriza-tion of fibrin and fibrinogen Tokyo II (γ275→Cys)." J.Clin.Invest.96. 1053-1058 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Michio Matsuda: "Hereditary dysfibrinogens with special reference to their structure-function relationship." Int.J.Hematol.,. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] John L.Woodhead: "The ultrastructure of fibrinogen Caracas II Molecules,fibers and clots." J.Biol.Chem.,. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Kazuki Niwa: "A γ Gly-268 to Glu substitution is responsible for impaired fibrin assembly in a homozygous dysfibrinogen Kurashiki I." Blood,. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Gilbu Soe: "A monoclonal antibody that recognizes a neo-antigen exposed in the E domain of fibrin monomer complexed with fibrinogen or its derivatives. Its application to the measurement of soluble fibrin in plasma." Blood,. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Umezawa,Kunihiko: "Localization of vitronectin-and fidronectin-receptors on cultured human glioma cells." Brain Research. 659. 23-32 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sugo,Teruko: "Activation of prothrombin by factor Xa bound to the membrane surface of human umbilical vein endothelial cells:its catalytic efficiency is similar to that of prothrombinase complex on platelets." Journal of Biochemistry. 117. 244-250 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takebe,Mikihiro: "Calcium-dependent monoclonal antibody against human fibrinogen:preparation,characterization,and application to fibrinogen purification." Thrombosis and Haemostasis. (印刷中).

    • Related Report
      1994 Annual Research Report
  • [Publications] Soe,Gilbu: "A rapid latex immunoassay for the detection of plasmin-α2-plasmin inhibitor complex:Utilization of two monoclonal antibodies defferentially recognizing respective components of the complex."

    • Related Report
      1994 Annual Research Report
  • [Publications] Blood Coagulation and Fibrinolysis. (印刷中).

    • Related Report
      1994 Annual Research Report
  • [Publications] Matsuda,Michio: "Fibrinogen Kurashiki I:a homozygous dysfibrinogen with a γ Gly-268 to Glu substitution." Blood. (投稿予定).

    • Related Report
      1994 Annual Research Report
  • [Publications] Zhou,Hong: "A monoclonal antibody that specifically inhibits factor XIIIa-catalyzed crosslinking of the fibrinogen γ-chain." Blood. (投稿予定).

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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