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Development of Molecular Markers for Injured Endothelial Cells and Its Clinical Application

Research Project

Project/Area Number 05557122
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Laboratory medicine
Research InstitutionMie University

Principal Investigator

SUZUKI Koji  Mie University School of Medicine, Professor, 医学部, 教授 (70077808)

Co-Investigator(Kenkyū-buntansha) TAMEI Hironori  Fuji-Yakuhin Kogyo Co., Research Institute Research Member, 主任
IWATA Kazushi  Fuji-Yakuhin Kogyo Co., Research Institute Research Head, 主席
HAYASHI Tatsuya  Mie University School of Medicine, Assistant, 医学部, 助手 (00242959)
TAKEYA Hiroyuki  Mie University School of Medicine, Assistant, 医学部, 助手 (60222105)
IDO Masaru  Mie University School of Medicine, Lecturer, 医学部, 講師 (90167263)
種田 寛  三重大学, 医学部・附属病院, 助手 (00236712)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥15,700,000 (Direct Cost: ¥15,700,000)
Fiscal Year 1995: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1994: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1993: ¥10,700,000 (Direct Cost: ¥10,700,000)
KeywordsEndothelium injury / Molecular marker for injured endothelim / Soluble thrombomodulin / Soluble E-selectin / Activated protein C-protein C inhibitor complex / Enzume-linked immunosorbent assay (ELISA) / Diabetes mellitus / Thrombotic disease / 活性化プロテインC-プロテインCインヒビター複合体 / プロテインS / プロテインC / 血栓形成阻止 / 機能ドメイン / EGFドメイン / 組換え蛋白質 / 分子間相互作用 / プロテインC凝固制御系 / プロテインCインヒビター / α_1アンチトリプシン / APC-PCI複合体 / APC-α_1-AT複合体 / 分子マーカー / 凝固亢進状態 / 血管内凝固
Research Abstract

The blood fluidity in the vessel is maintained by the activation of several anticoagulant and fibrinolytic systems, such as anticoagulant protein C pathway system, antithrombin III-heparan sulfate system, and tissue plasminogen activator (t-PA) -plasminogen system, on the surface of normal vascular endothelial cells. However, when the endothelial cells are injured by some physical, chemical and/or biological stimulants, the ability to maintain the blood fluidity by anticoagulant and fibrinolytic systems on the endothelial cells are broken down, then, resulting in thromboembolic disease in specific or non-specific organs (multi-organs failure). Thus, to diagnose the signals of the injured endothelium as early as possible is critical to prevent the patients from the occurring of thrombotic disease. The present study was aimed to develop the assay kits for determining the molecular markers to detect the early stage of the endothelial injury and to apply the assay kits for several diseases having a tendency to fall in thrombotic disease. We developed ELISA kits to assay soluble thrombomodulin (sTM) , soluble E-selectin (sE-S) and activated protein C-protein C inhibitor complex (CIC) , and found that these assay kits are useful to get information of the injury of endothelium in the hereditary and acquired thrombotic diseases, such as hereditary deficiency of protein C or S,diabetes mellitus and autoimmune disease.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Gabazza EC,Takeya H,Suzuki K,et al.: "Protein C activation in patients with non-insulin-dependent diabetes mellitus." Diabetologia. in press (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Mori T,Takeya H,Suzuki K,et al.: "β2-Glycoprotein I modulates anticoagulant activity of activated protein C on phospholipids." Thromb.Haemostas.75. 49-55 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ohnishi K,Nagata K,Suzuki K,et al.: "Stimulation of Sky receptor tyrosine kinase by the product of growth-arrest-specific gene 6." J.Biol.Chem.270. 22681-22684 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hayashi T,Nishioka J & Suzuki K.: "Molecular mechanism of dysfunctional protein S-Tokushima (Lys^<155>→Glu)in the regulation of blood coagulation." Biochim.Biophys.Acta.1272. 159-167 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Iino M,Takeya H & Suzuki K.: "Characterization of factor Xa binding to fibrinogen/fibrin derivatives. Comparative study with thrombin binding." Eur.J.Biochem.232. 90-97 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nakagawa H,Takahashi N,Suzuki K,et al.: "A structural study of the oligosaccharide moeities of human coagulation factor X activation peptide." Glycoconjugate J.12. 173-181 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suzuki K.: "Molecular Basis of Thrombosis an Hemostasis (protein C)" Marcel Dekker,Inc,New York(eds.Roberts HR & High KA), 688(31) (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suzuki K.: "Molecular Basis of Thrombosis and Hemostasis (protein S)" Marcel Dekker,Inc,New York(eds.Roberts HR & High KA), 688(19) (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Gabazza EC,Takeya H,Suzuki K,et al.: "Protein C activation in patients with non-insulin-dependent diabetes mellitus." Diabetologia. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Mori T.Takeya H,Suzuki K,et al.: "beta2-Glycoprotein I modulates anticoagulant activity of activated protein C on phospholipids." Thromb.Haemostas. 75. 49-55 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ohnishi K,Nagata K,Suzuki K,et al.: "Stimulation of Sky receptor tyrosine kinase by the product of growth-arrest-specific gene 6." J.Biol.Chem.270. 22681-22684 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hayashi T,Nishioka J & Suzuki K.: "Molecular mechanism of dysfunctional protein S-Tokushima (Lys^<155>*Glu) in the regulation of blood coagulation." Biochim.Biophys.Acta.1272. 159-167 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Iino M,Takeya H & Suzuki K.: "Characterization of factor Xa binding to fibrinogen/fibrin derivatives. Comparative study with thrombin binding." Eur.J.Biochem.232. 90-97 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nakagawa H,Takahashi N,Suzuki K,et al.: "A structural study of the oligosaccharide moeities of human coagulation factor X activation peptide." Glycoconjugate J.12. 173-181 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suzuki K.: Protein C. Molecular Basis of Thromobosis and Hemostasis. (eds.Roberts HR & High KA) , Marcel Dekker, Inc, New York, 393-423 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suzuki K.: Protein S. Molecular Basis of Thromobosis and Hemostasis. (eds.Roberts HR & High KA) , Marcel Dekker, Inc, New York, 459-477 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Mori T,Takeya H,Suzuki K,et al.: "β2-Glycoprotein I modulates anticoagulant activity of activated protein C on phospholipids." Thromb. Haemostas.75. 49-55 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ohnishi K,Nagata K,Suzuki K,et al.: "Stimulation of Sky receptor tyrosine Kinase by the product of growth-arrest-specific gene 6." J. Biol. Chem.270. 22681-22684 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hayashi T,Nishioka J & Suzuki K.: "Molecular mechanism of dysfunctional protein S-Tokushima(Lys^<155>→Glu)in the regulation of blood coagulation." Biochim. Biophys. Acta.1272. 159-167 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Iino M,Takeya H & Suzuki K.: "Characterization of factor Xa binding to fibrinogen/fibrin derivatives. Comparative study with thrombin binding." Eur. J. Biochem.232. 90-97 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yasuda H,Hayashi T & Suzuki K.: "Molecular cloning and functional characterization of rat plasma protein S." J. Biochem.117. 374-383 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakagawa H,Takahashi N,Suzuki K,et al.: "A structural study of the oligosaccharide moeities of human coagulation factor X activation peptide." Glycoconjugate J.12. 173-181 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Suzuki K.: "Molecular Basis of Thrombosis and Hemostasis(Protein C)" Marcel Dekker, Inc, New York(eds. Roberts HR & High KA), 688(31) (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Suzuki K.: "Molecular Basis of Thrombosis and Hemostasis(Protein S)" Marcel Dekker, Inc, New York(eds. Roberts HR & High KA), 688(19) (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yasuda,H.,Hayashi,T.,Nishioka,J.and Suzuki,K.: "Molecular cloning and functional characterization of rat plasma protein S." J.Biochem.117. 374-383 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ogawa,H.,Ido,M.and Suzuki,K.: "The thrombin receptor transmits signals through a 33-kDa protein kinase" Biochem.Biophys.Res.Commun.203. 907-913 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Taneda,H.,Andoh,K.,Suzuki,K.,et al.: "Blood coagulation factor Xa interacts with a linear sequence of the kringle 2 domain of prothrombin." J.Biochem.116. 589-597 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Iino,M.,Takeya,H.,Suzuki,K.,et al.: "The role of human factor X activation peptide in activation of factor X by factor IXa." J.Biochem.116. 335-340 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ohiwa,M.,Hayashi,T.,Suzuki,K.,et al.: "Factor VII Mie:homozygous asymptomatic type I deficiency caused by an amino acid substitution of His(CAC)for Arg(247)(CGC)in the catalytic domain." Thromb.Haemostas.71. 773-777 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hayashi,T.,Nishioka,J.,Suzuki,K.,et al.: "Protein S Tokushima:abnormal molecule with a substitution of Glu for Lys-155 in the second epidermal growth factor-like domain of protein S." Blood. 83. 683-690 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Suzuki,K.: "Molecular Bilogy of Thrombosis and Hemostasis.(Protein C.)" Marcel Dekker,Inc,New York(eds.by Roberts,H.R.and High,K.A.), 688(32) (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Suzuki,K.: "Molecular Bilogy of Thrombosis and Hemostasis.(Protein S.)" Marcel Dekker,Inc,New York(eds.by Roberts,H.R.and High,K.A.), 688(20) (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hayashi,T.,Nishioka,J.,Suzuki,K.,et al.: "Protein S Tokushima:abnormal molecule with a substitution of Glu for Lys-155 in the second epidermal growth factor-like domain of protein S." Blood. 83. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shigekiyo,T.,Uno,Y.,Suzuki,K.,et al.: "Protein S Tokushima:an abnormal protein S found in a Japanese family with thrombosis." Thromb.Haemostas.70. 244-246 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hayashi,T. and Suzuki,K.: "Gene organization of human protein C inhibitor,a member of SERPIN family proteins encoded in five exons." Int.J.Hematol.58. 213-224 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ido,M.,Ohiwa,M.,Suzuki,K.,et al.: "A compound heterozygous protein C deficiency with a single nucleotide G deletion encoding gly-381 and an amino acid substitution of Lys for Gla-26." Thromb.Haemostas.70. 636-641 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ito,T.,Hiraiwa,J.,Nishioka,J.,Suzuki,K.: "Characterization of functionally important regions of tissue factor by using monoclonal antibodies." J.Biochem.114. 691-696 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Wada,H.,Mori,Y.,Suzuki,K.,et al.: "Elevated plasma levels of vascular endothelial cell markers in patients with hypercholesterolemia." Am.J.Hematol.44. 112-116 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Suzuki,K.: "Molecular Biology of Thrombosis and Hemostasis.(Protein S.)" Marcel Dekker,New York (eds.by Roberts,H.R.and High,K.A.), (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Suzuki,K.: "Methods in Enzumology.(Protein C inhibitor.)" Academic Press,New York (eds.by Lorand,L and Mann,K.G.), 613(15) (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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