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Study on functinal domains of von Willebrand (vW) factor in patients with vW disease.

Research Project

Project/Area Number 01570744
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionNara Medical University (1991)
The University of Tokyo (1989-1990)

Principal Investigator

TAKAHASHI Yukihiro (1991)  Nara Medical University, Pediatrics, Associate Professor, 医学部, 助教授 (60142379)

跡見 裕  東京大学, 医学部・(病), 助手 (60107654)

Co-Investigator(Kenkyū-buntansha) 杉山 政則  東京大学, 医学部・(病), 助手
黒田 慧  東京大学, 医学部・(病), 助手 (70010270)
寺島 裕夫  東京大学, 医学部(病), 医員
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1990: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1989: ¥700,000 (Direct Cost: ¥700,000)
Keywordsvon Willebrand factor / von Willebrand disease / ヒト膵臓性カリクレイン / トリプシン / プロカリクレイン / アミノ酸分析 / カリクレイン / 組織性カリクレイン / 糖鎖構造
Research Abstract

I. The analysis of functional domains of von Willebrand factor(vWf) and the production and characterization of monoclonal antibodies (MAbs) against vWf.
A. the factorVIII-binding domain: vWf-plasmin or trypsin digested fragment p-34(amino acid residue 1-298(273)) was purified using DEAE and Heparin column. 4 different MAbs against p-34 were produced by D.Meyer, INSERM 143 France, collaborated with me. Now, I'm going to characterize these antibodies
B. Platelet glycoprotein Ib(GPIb)-binding domain: Two different MAbs (NMC/vW4 from our lab. 322 from france) against vWf which inhibit the binding of vWf to GPIb were characterized, and I discovered the different functional site of GPIb-binding of vWf by two inducers, such as antibiotics ristocetin and venom factor botrocetin. and Aurin tricarboxylic acid (ATA) is known to inhibit ristocetin-induced platelet aggregation but not the other platelet aggregaters. Its capacity to abolish human vWf-platelet interaction was further in vestigated and was found that ATA which blocks the vWf/GPIb pathway by interfering with vWf and not with platelet, is a potential tool in prevention the early stages of thrombosis
C. Human collagen-binding domain: One MAb(NMC/vW3) which inhibit the vWf-human typeIII fibrilar collagen binding was discovered and was shown the epitope in vWf subunit. That is, The epitope was localized between the amino acid residue 911 and 1365.
II. The analysis of plasma von Willebrand factor in von Willebrand disease. I studied on the establishment of several vWf function assays and vWf protein analysis of plasma vWf in normal and several types of von Willebrand disease.
A. The vWf-human collagen binding assay, using a minute plasma was established. The abnormality of the collagen- binding in type II vWd was discovered.
B. The analytical method of vWf subunit in plasma vWf using a minute sample was established. Now the plasma vWf in several types of vWd is going to examine.

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] J.P Girma: "Aurin tricarboxylic acid abolishes von Willebrand factor.Mediated platelet adhesion to collagen by acting as a GPIb competitor" Thrombosis and Haemostasis.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y.Takahashi: "Functional domains of von Willebrand factor" The japanese journal of clinical pathology. 92. 47-61 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] J.P Girma: "Ristocetin and botrocetin involve two distinct domains of von Willebrand factor for binding to platelet membrane glycoprotein." Thrombosis and Haemostasis. 64(2). 326-332 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] J. P. Girma: "Aurin tricarboxylic acid abolishes von Willebrand factor. Mediated platelet adhesion to collagen by acting as a GPIb competiter." Thrombosis and Haemostasis.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Takahashi: "Functional domains of von Willebrand factor" The japanese journal of clinical pathology. 92. 47-61 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] J. P. Girma: "Ristocetin and botrocetin involve two distinct domains of von Willebrand factor for binding to platelet membrane glycoprotein." Thrombosis and Haemostasis. 62(2). 326-332 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary

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Published: 1989-04-01   Modified: 2016-04-21  

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