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Basic research for pathogenesis of type 1 von Willebrand disease

Research Project

Project/Area Number 12671011
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionFujita Health University

Principal Investigator

MATSUI Taei  Fujita Health University, Inst. Comprehensive Med. Sci., Assistant Professor, 総合医科学研究所, 講師 (90183946)

Co-Investigator(Kenkyū-buntansha) HAMAKO Jiharu  Fujita Health University, Coll., Associate Professor, 短期大学・医療情報技術科, 助教授 (80180933)
TITANI Koiti  Fujita Health University, Inst. Comprehensive Med. Sci., Research Associate, 総合医科学研究所, 研究員 (60179942)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsvon Willebrand disease / von Willebrand factor / ABO blood group / lectin / bitiscetin / platelet aggregation / Upshaw-Schulman syndrome / kaouthiagin / フォン・ビルブランド因子 / Upshaw-Schulman症候群 / VWF切断プロテアーゼ / ELISA / フォン・ビルブランド病 / 一次構造 / メタロプロテアーゼ / ジスインテグリン / ヘビ毒
Research Abstract

We have screened lectins that can recognize the difference in the carbohydrate structures on von Willebrand factor (VWF) from normal individuals with each ABO blood group and patients with type 1 von Willebrand disease (VWD). Furthermore, we have studied the structure and function of snake venom proteins affecting human hemostasis by interacting with VWF and platelet.
1) Among blood group-reconizing lectins examined, HPA and UEA-I were useful for detection and fractionation of blood group A and O(H) sugar chains on VWF, respectively (BBA, 1525: 50-57, 2001). We have found that the sialic acid-recognizing lectins (SSA and SNA) and the H structure-recognizing lectins (TJA-I and UEA-I) preferentially bound to VWF from group O and type 1 VWD plasmas, suggesting that these VWFs contain terminal sialic acid residues and the H structure in a higher amount.
2) We have determined the amino acid sequence of kaouthiagin which specifically cleaves VWF, and found that its Cys-rich domain has the functional disintegrin-like activity (Biochemistry 40: 4503-4511, 2001). We have determined the crystal structure of bitiscetin which modulates VWF to induce platelet aggregation, and found that it has a central conecave structure rich in negatively charged residues, implying that it might be the VWF-binding site (Biochemistry 40: 13592-13597, 2001).
3) We have found that the deficiency of physiological VWF-cleaving metalloproteinase in plasma causes the presence of ultra-high molecular mass multimers of VWF subunits resulting in the Upshaw-Schulman syndrome (USS), the congenital thrombotic thrombocytopenic purpura (TTP). (Int. J. Hematol, 74: 101-108, 2001, Int. J. Hematol., 75: 25-34, 2002).

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] Y.Fujimura, et al.: "von Willebrand factor-cleaving protease and Upshaw-Schulman syndrome"Int.J.Hematol.. 75(review). 25-34 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S.Hirotsu, et al.: "Crystal structure of bitiscetin, a von Willebrand factor-dependent platelet aggregation inducer"Biochemistry. 40. 13592-13597 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H.Yagi, et al.: "Plasma of patients with Upshaw-Schulman syndrome enhances the aggregation of normal platelets under high shear stress"Br.J.Haematol.. 115. 991-997 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y.Sakurai, et al.: "Inhibition of human platelet aggregation by L-aminoacidoxidase purified from Naja naja kaouthia venom"Toxicon. 39. 1827-1833 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 松井太衛, 他: "フォン・ビルブランド因子のモジュレータータンパク質であるボトロセチンの立体構造と機能"日本血栓止血学会誌. 12(6). 240-245 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M.Ito, et al.: "Complete amino acid sequence of kaouthiagin, a novel cobra venom metalloproteinase with two disintegrin-like sequences"Biochemistry. 40. 4503-4511 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S.Kinoshita, et al.: "Upshaw-Schulman syndrome revisited : a congenital deficiency of von Willebrand factor-cleaving protease, and its correction with fresh frozen plasma"Int.J.Hematol.. 74. 101-108 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H.Takatsuka, et al.: "Molecular characterization of L-amino acid oxidase from Agkistrodon halys blomhoffii with special reference to platelet"Biochim.Biophys.Acta. 1544. 267-277 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Matsui, et al.: "Comparative study of blood group-recognizing lectins toward ABO blood group antigens on neoglycoproteins, glycoproteins and complex-type oligosaccharides"Biochim.Biophys.Acta. 1525. 50-57 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 松井太衛, 他: "立体構造からみたフォン・ビルブランド因子(VWF)の機能ドメイン"日本血栓止血学会誌. 11(3). 268-275 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Matsui, et al.: "Snake venom proteases affecting hemostasis and thrombosis"Biochim.Biophys.Acta. 1477(review). 146-156 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 松井太衛(共著): "関西血栓フォーラム2002・血小板血栓形成の分子機構"関西血栓フォーラム編、アイプリコム出版. 89-95,181-188,195-201,395-397 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 松井太衛(共著): "第7回血液アゴラ"メディカル・ジャーナル社. 85-91 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Fujimura, et al.: "von Willebrand factor-cleaving protease and Upshaw-Schulman syndrome (review)."Int. J. Hematol.. 75. 25-34 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Hirotsu, et al.: "Crystal structure of bitiscetin, a von Willebrand factor-dependent platelet aggregation inducer."Biochemistry. 40. 13592-13597 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Yagi, et al.: "Plasma of patients with Upshaw-Schulman syndrome enhances the aggregation of normal platelets under high shear stress."Br. J. Haematol.. 115. 991-997 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Sakurai, et al.: "Inhibition of human platelet aggregation by L-aminoacid oxidase purified from Naja naja kaouthia venom."Toxicon. 39. 1827-1833 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Ito, et al.: "Complete amino acid sequence of kaouthiagin, a novel cobra venom metalloproteinase with two disintegrin-like sequences."Biochemistry. 40. 4503-4511 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Kinoshita, et al.: "Upshaw-Schulman syndrome revisited: a congenital deficiency of von Willebrand factor-cleaving protease, and its correction with fresh frozen plasma."Int. J. Hematol.. 74. 101-108 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Matsui, et al.: "Comparative study of blood group-recognizing lectins toward ABO blood group antigens on neoglycoproteins, glycoproteins and complex-type oligosaccharides."Biochim. Biophys. Acta. 1525. 50-57 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Takatsuka, et al.: "Molecular characterization of L-amino acid oxidase from Agkistrodon halys blomhoffii with special reference to platelet aggregation."Biochim. Biophys. Acta. 1544. 267-277 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Matsui, et al.: "Snake venom proteases affecting hemostasis and thrombosis (review)."Biochim. Biophys. Acta. 1477. 146-156 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujiyama, Y., et al.: "von Willebrand factor-cleaving protease and Upshaw-Schulman Syndrome"Int.J.Hematol. 75(1). 25-34 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yagi, H., et al.: "Plasma of patients with Upshaw-Schulman syndrome enhances the aggregation of normal platelets under high shear stress"Br.J.Haematol.. 115(4). 991-997 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirotsu, S., et al.: "Crystal structure of bitiscetin, a von Willebrand factor-dependent platelet aggregation inducer"Biochemistry. 40(45). 13592-13597 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kinoshita, S., et al.: "Upshaw-Schulman syndrome revisited : a congenital deficiency of von Willebrand factor-cleaving protease, and its correction with fresh frozen plasma"Int.J.Hematol.. 74(1). 101-108 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ito, M., et al.: "Complete amino acid sequence of kaouthiagin, a novel cobra venon metalloproteinase with two disintegrin-like sequences"Biochemistry. 40(14). 4503-4511 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 松井 太衛: "フォン・ビルブランド因子のモジュレータータンパク質であるボトロセチンの立体構造と機能"日本血栓止血学会誌. 12(6). 240-245 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sakurai, Y., et al.: "Inhibition of human platelet aggregation by L-amino acid oxidase purified from Naja naja kaouthia venom"Toxicon. 39(12). 1827-1833 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 松井太衛(共著): "血小板血栓形成の分子機構(関西血栓フォーラム2002)"アイプリコム. 407 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ito,M., et al.: "Complete amino acid sequence of kaouthiagin, a novel cobra venom metalloproteinase with two disinteqrin-like sequence."Biochemistry. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kinoshita,S., et al.: "Upshaw-Schulman syndrome revisited : a congenital deficiency of von Willebrand factor-cleaving protease, and its correction with fresh frozen plasma."Int.J Hematol.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takatsuka,H., et al.: "Molecular characterization of L-amino acid oxidase from Agkistrodon halys blomhoffi with special reference to platelet aggregation."Biochim.Biophys.Acta. 1544. 207-277 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsui,T., et al.: "Comparative study of blood group-recognizing lectins toward ABO blood group antigens on neoglycoproteins, glycoproteins and complex-type oligosaccharides."Biochim.Biophys.Acta. 1525. 50-57 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsui,T., et al.: "Snake venom proteases affecting hemostasis and thrombosis (Review)."Biochim.Biophys.Acta. 1477. 146-156 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 松井太衛 他: "立体構造から見たフォン・ビルブランド因子(VWF)の機能ドメイン.(総説)"日本血栓止血学会誌. 11(3). 268-275 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 松井太衛 他: "第7回血液アゴラ"メディカル・ジャーナル社. 7 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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