1991 Fiscal Year Final Research Report Summary
Functional Domains on Human Platelet Glycoprotein IIb/IIIa.
| Project/Area Number |
02671140
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Tokyo Metropolitan Institute of Medical Science. |
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Principal Investigator |
TANOUE Kenjiro Tokyo Metropolitan Institute of Medical Science., Dept. of Cardiovas. Res., Researcher., 循環器病研究部門, 研究員 (30014137)
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| Co-Investigator(Kenkyū-buntansha) |
OHNO Shigeo Yokohama City University, School of Med., Dept. of Biochemistry, Professor., 医学部, 教授 (10142027)
SAKURABA Hitoshi Tokyo Metropolitan Institute of Medical Science., Dept. of Clinical Genetics, Re, 臨床遺伝学研究部門, 研究員 (60114493)
AKAMATU Noriko Tokyo Metropolitan Institute of Medical Science., Dept. of Cardiovas. Res., Rese, 循環器病研究部門, 研究員 (30124431)
YAMAMOTO Naomasa Tokyo Metropolitan Institute of Medical Science., Dept. of Cardiovas. Res., Rese, 循環器病研究部門, 研究員 (50150884)
KATAGIRI Yasuhiro Tokyo Metropolitan Institute of Medical Science., Dept. of Cardiovas. Res., Rese, 循環器病研究部門, 研究員 (60194768)
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| Project Period (FY) |
1990 – 1991
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| Keywords | Platelet GPIIb / IIIa / Integrin alpha_<IIb> beta_3 / Thrombasthenia / Platelet Aggregation / Intra-Platelet Fibrinogen / Plasma Fibrinogen |
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| Research Abstract |
Immunological studies by crossed-immi-inoelectrophoresis of the platelets from 22 Japanese thrombasthenic patients (7 males, 13 females) identified 8 cases of type I with no detectable GPIIb/IIIa complex(Integrin alpha_<IIb> beta_3), 9 cases of type II with a trace amount of GPIIb/IIIa and 3 cases of variant type with normal amount of GPIIb/IIIa. Analysis of PCR-amplified CDNA of GPIIIa from the platelets of a thrombasthenic type II patient revealed mutations of 192-193 amino acid residues from His-Val to Gln-Asn. The mutation of GPIIIa may result in poor complex-formation with GPIIb followed by the decrease in the GPIIb/IIIa complex.
Determination of intra-platelet fibrinogen in the thrombasthenic platelets showed 4.6 <plus-minus> 1.7% of normals, 21.9<plus-minus> 6.1% and 70.6% in type I (4 cases), type II (7 cases) and variant type (1 case) platelets, respectively. There was a positive correlationship between intra platelet fibrinogen and the residual GPIIb/IIIa in the thrombasthenic platelets, suggesting that membrane GPIIb/IIIa on the circulating non-activated platelets may uptake plasma fibrinogen. The GPIIb/IIIa of the variant type thrombasthenic platelets could not support aggregation induced by ADP because of inability of fibrinogen binding, while they could still uptake plasma fibrinogen as much as normal platelets. This suggests that the fibrinogen binding domain of GPIIb/IIIa is different from a domain uptaking plasma fibrino
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