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Development of mechanical device to continuously guantitute platelet thrunbus formation under flow conditions.

Research Project

Project/Area Number 07557079
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Hematology
Research InstitutionKeio University School of Medicine

Principal Investigator

IKEDA Yasuo  Keio University School of Medicine Internal Medicine Professor, 医学部, 教授 (00110883)

Co-Investigator(Kenkyū-buntansha) ODA Atsushi  Keio University School of Medicine Internal Medicine, Instructor, 医学部, 助手 (50255436)
MURATA Mitsuru  Keio University School of Medicine Internal Medicine, Assist.Professor, 医学部, 講師 (50174305)
HANDA Makoto  Keio University School of Medicine Internal Medicine, Assist.Professor, 医学部, 講師 (40129614)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 1997: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1995: ¥8,000,000 (Direct Cost: ¥8,000,000)
KeywordsPlatelet adhesion / Wall shear rate / Hematocrit / Platelet membrane glycoproteins / Adhesion molecules / Anti-platelet agents / ずり速度 / 血栓
Research Abstract

Platelet adhesion to subendothelium, one of the earliest steps in primary hemostasis and pathological thrombus formation is followed by subsequent platelet plug formation including platelet-platelet interactions. Therefore, it is difficult to seggregate from the subsequent platelet interactions and analyze the mechanism of platelet adhesion only. We developed a recirculating flow system including a quartz crystal microbalance (QCM) as a sensor which allows continuous monitoring of the surface coverage of firmly adherent platelets only. Using this system, we found that platelet adhesions to collagen (bovine tendon type 1 : CL) and human von Willebrand factor (vWf) were dependent upon wall shear rate (310/s-2,400/s) and hematocrit (20-45%). It was found that there existed two recptor-ligand pairs i.e. platelet glycoprotein (GP) Ib/IX-vWf and GPIa/IIa-CL independently operating in platelet adhesion to CL evenunder higher flow conditions. Interestingly, well-known anti-platelet agents such as aspirin and cilostazol were found to enhance platelet adhesion to CL,although they readily inhibited subsequent platelet-platelet interactions. Thus, our newly-developed QCM system may be useful to study the mechanism of platelet adhesion under flow conditions and to screen the efficacy of new anti-platelet adhesion drugs.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] Kameda H, Morita I, Handa M., Ikeda Yetal: "Re-expression of functional P-selectin molecules on the endothelial cell surface by repeated stimulation with thrombin." Brit J Haematol 97. 97. 348-355 (1997.)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Goto S., Sakai H., Ikeda Y, and Handa S.:"Acute myocardial infarction plasma augments platelet thrombus growth in high shear rates." The Lancet. 349(9051). 543-544 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yokoyama K., Handa M., and Ikeda Y.et al: "Characterization of the novel murine monoclonal anti-von Willebrand factor(vWf)antibody GUR76-23 which inhibits vWf interaction with α IIb β 3 but not αvβ3 integrin." Biochem Biophys Res Commun. 234. 147-152 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Iijima K, Murata M., Handa M., Ikeda Y.et al: "High shear stress attenuates agonist-induced,glycoprotein IIb/IIIa-mediated platelet aggregation when von Willebrand factor binding to glycoprotein Ib/IX is blocked." Biochem Biophys Res Commun. 233(3). 796-800 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miyakawa Y., Oda A., Handa M., Ikeda Y.et al: "Thrombopoietin and thrombin induce tyrosine phosphorylation of vav in human blood platelets." Blood. 89(8). 2789-2798 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ikeda Y., Murata M., and Goto S.: "von Willebrand factor-dependent shear-induced platelet aggregation:basic mechanisms and clinical implications." The Annals of the New York Academy of Sciences. 811. 325-336 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Moriki T., Murata M., Handa M., Ikeda Y.: "Expression and functional characterization of an abnormal platelet membrane glycoprotein Ib α(Met239→Val)reported in patients with platelet-type von Willebrand disease." Blood. 89(10). 3565-3573 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kameda H., Morita I., Handa M., Ikeda Y et al: "Re-expression of functional P-selectin molecules on the endothelial cell surface by repeated stimulation with thrombin." Brit J Haematol. 97. 348-355 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Goto S., Sakai H., Ikeda Y,and Handa S.: "Acute myocardial infarction plasma augments platelet thrombus growth in high shear rates." The Lancet. 349(9051). 543-544 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yokoyama K., Handa M., Oda A.and Ikeda Y.et al: "Characterization of the novel murine monoclonal anti-von Willebrand factor (vWf) antibody GUR76-23 which inhibits vWf interaction with alpha IIb beta 3 but not alpha v beta 3 integrin." Biochem Biophys Res Commun. 234. 147-152 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Iijima K., Murata M., Handa M., Ikeda Y.et al: "High shear stress attenuates agonist-induced, glycoprotein IIb/IIIamediated platelet aggregation when von Willebrand factor binding to glycoprotein Ib/IX is blocked." Biochem Biophys Res Commun. 233(3). 796-800 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miyakawa Y., Oda A., Handa M., Ikeda Y.et al: "Thrombopoietin and thrombin induce tyrosine phosphorylation of vav in human blood platelets." Blood. 89(8). 2789-2798 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ikeda Y., Murata M., and Goto S.: "von Willebrand factor-dependent shear-induced platelet aggregation : basic mechanisms and clinical implications." The Annals of the New York Academy of Sciences. 811. 325-336 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Moriki T., Murata M., Handa M., Ikeda Y.: "Expression and functional characterization of an abnormal platelet membrane glycoprotein Ib alpha (Met239*Val) reported in patients with platelet-type von Willebrand disease." Blood. 89(10). 3565-3573 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kameda H.,Morita I.,Handa M.,Ikeda Y et al: "Re-expression of functional P-selectin molecules on the endothelial cell surface by repeated stimulation with thrombin." Brit J Haematol 97. 97. 348-355 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Goto S.,Sakai H.,Ikeda Y,and Handa S.: "Acute myocardial infarction plasma augments platelet thrombus growth in high shear rates." The Lancet. 349(9051). 543-544 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yokoyama K.,Handa M.,and Ideda Y.et al: "Characterization of the novel murine monoclonal anti-von Willebrand factor (vWf) antibody GUR76-23 which inhibits vWf interaction with α IIb β 3 but not α v β 3 integrin." Biochem Biophys Res Commun. 234. 147-152 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Iijima K,Murata M.,Handa M.,Ikeda Y.et al: "High shear stress attenuates agonist-induced,glycoprotein IIb/IIIa-mediated platelet aggregation when von Willebrand factor binding to glycoprotein Ib/IX is blocked." Biochem Biophys Res Commun. 233(3). 796-800 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miyakawa Y.,Handa M.,Ikeda Y.et al: "Thrombopoietin and thrombin induce tyrosine phosphorylation of vav in human blood platelets." Blood. 89(8). 2789-2798 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ikeda Y.,Murata M.,and Goto S.: "von Willebrand factor-dependent shear-induced platelet aggregation : basic mechanisms and clinical implications." The Annals of the New York Academy of Sciences. 811. 325-336 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Moriki T.,Murata M.,Handa M.,Ikeda Y.: "Expression and functional characterization of an abnormal platelet membrane glycoprotein Ib α (Met239→Val) reported in patients with platelet-type von Willebrand disease." Blood. 89(10). 3565-3573 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kitaguchi T: "Establishment and characterization of transgenic mice expressing human platelet glycoprotein lba" 220. 418-424 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Oda,A: "Thrombopoietin primes human platelet aggregation induced by shear stress and by multiple agonists" Blood. 87. 4664-4670 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Oda,A: "_p120^<c-cbl> is present in human blood platelets and is differenrially involned in signaling by thrombopoietin and thrombin" Blood. 88. 1330-1338 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shiraga,M: "Affinity modulation of the platelet integrin αIIbβ3 by α-chymotrypsin:a possible role for Na^+/Ca^<2+> exchanger" Blood. 88. 2594-2602 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tokuhira M: "A novel regulatory epitope difined by a murine monoclonal antibody to the platelet GPIIB-IIIa complex (αIIbβ3 integrin)" Thromb Haemost. 76. 1038-1046 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Oda,A: "CrKl is constitutively tyrosine phosphorylated in platelets from chronic myelogenous leukemid patients and inducibly phosphorylated in normal platelets stimulated by thrombopoietin" Blood. 88. 4304-4313 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Goto,S: "Synergistic effect of epinephrine and shearing on platelet activation" Throm Res. 84. 351-359 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sakamaki F.: "Plasmasoluble form of P-Selectin is eleuated in acute lung in jury." Am.J.Respirat & Crinical Care Med.151. 1824-1826 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Watanabe K.: "Automated measurement of reticarated plate lets in estimating thrombopoiesis." Eur.J.Haematol.0. 1-9 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takahashi H.: "Substitution of Vol for Met at residue 239 of platelet glycoprotein Ib in Japanese patients with plotelet-type von Willebrand disease." Blood. 85. 727-733 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sakamaki F.: "Soluble form of P-Selectin in Plasma is elevated in acute 1 ung injury." Am.J.Resp.Crit.Care Med.151. 1821-1826 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fujimura Y.: "Isolation and characterization of jararaca GPIb BP, asnake venom antagonist Specific to platelet glycoprotein Ib." Thromb,and Haemost.74. 743-750 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Goto S.: "Cnanacterization of the unigue mechanism mediating the Shear-dependent binding of Soluble von Willebrand factor to platelets." J.Biol.Chem.270. 23352-23361 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Handa.M.: "Platelet unresponsivenes to collagen : involvement of grycopralein Ia-II(α2β1 integlin) difeciencyassociated with a myeloprolefe be rative disorder." Thromb.Haemost.73. 521-528 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Miyakawa Y.: "Recombinant thrompopotelin induces rapiaprotein throsine phosphory latiom of janus kinase 2 and shcin human blood platelet." Blood. 86. 23-27 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Oda,A.: "Pnotin iyhe sine phos phory lation in hum an plate lets during Shear-Stress-induced. Platelet aggregation (SIPA) is reguratea by glycopratein (GP) Ib/Ixas well as GIIb/IIIa and requies intact cytoskeleton and endogenepus A bp." Thromb.Haemost.74. 736-742 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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