| Project/Area Number |
10044316
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
General surgery
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| Research Institution | Jichi Medical School |
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Principal Investigator |
MATSUDA Michio Division of Hemostasis and Thrombosis Research, Jichi Medical School Professor, 医学部, 教授 (50048980)
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| Co-Investigator(Kenkyū-buntansha) |
MIMURO Jun Division of Hemostasis and Thrombosis Research, Jichi Medical School Instructor, 医学部, 講師 (10221607)
SUGO Teruko Division of Hemostasis and Thrombosis Research, Jichi Medical School Instructor, 医学部, 講師 (60183844)
SAKATA Yoichi Division of Hemostasis and Thrombosis Research, Jichi Medical School Associate Professor, 医学部, 助教授 (40129028)
MOSESSON Michael W. University of Wisconsin Medical School, Professor, 医学部, 教授
WEISEL John w. School of Medicine University of Pennsylvania, Professor, 医学部, 教授
MOSESSON Mic ウィスコンシン大学, 医学部, 教授
WEISEL John ペンシルバニア大学, 医学部, 教授
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| Project Period (FY) |
1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | hereditary dysfibrinogen / fibrin gels / extra oligosaccharide / deep veinthrombosis / pulmonary embolism / intermolecular crosslink / plasmin / electron microscopic analysis of fibrin / XIIIa因子による分子間架橋 |
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| Research Abstract |
Studies on two hereditary dysfibrinogens were conducted in collaboration with Dr. Michael W. Mosesson focusing on electron microscopic analyses. 1) Fbg Niigata was found to have a unique Bβ Asn-160 to Ser substitution with an extra oligosaccharide N-linked to Bβ Asn-150.Although the double-stranded fibrin protofibrils are normally formed, their lateral association is impaired, most probably due to the extra oligosaccharide attached to the coiled-coil region. Indeed, enzymatic deglycosylation resulted in enhancement of fibrin monomer polymerization to a great extent. Scanning electron microscopic analyses of fibrin clots revealed an abnormal architecture, being composed of curvilinear fibrin fibers. After deglycosylation, the fibrin fibers became nearly normal, being straight and appropriately branched. The result together with biochemical and gene analysis data is now under the status of revision in BLOOD. Fibrinogen Marburg from Germany was found in a 20-year-old woman who underwent a Caesarian section on her first delivery at the age of 20.Severe bleeding and successive recurrent thrombo-embolic complications were characteristic. This molecule has a 150-amino acid residue truncation of the Aα-chain, and is partly disulfide-bridged with serum albumin at Aα Cys-442. The Marburg fibrin clots are apparently fragile but totally resistant against plasmin Furthermore, factor XIIIa-crosslinking profiles analyzed by SDS-PAGE manifested several α・β- heteromultimers, not observed in the normal sample. To be noted is that the Aα-chain-linked serum albumin was crosslinked to the g-chain of another fibrin molecules, creating disordered fibrin clots. Scanning electron microscopy showed compact fibrin gels consisting of extremely thin but highly branched fibrin fibers. These findings seem to account for recurrent postoperativethrombo-embolic complications. Part of these results appeared in BLOOD (91 : 3282-3288, 1998) and the remainder is now in preparation for publication.
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