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• W2014157265 abstract "Summary. Background and objectives: We have previously reported that recombinant γ275Cys fibrinogen exhibits a marked impairment of functions as well as aberrant fibrin clot and bundle structures, as compared with wild-type, γ275Arg, and plasma fibrinogen from a heterozygous proband. Since γArg275His mutations have also been reported in 10 families, we synthesized recombinant γ275His fibrinogen and γ275Ala fibrinogen (as a control) and analyzed and compared them with γ275Cys and γ275Arg. Methods: A variant γ-chain expression plasmid was transfected into Chinese hamster ovary cells expressing normal human fibrinogen Aα- and Bβ-chains. After purification of the recombinant variant fibrinogens, we performed functional analyzes for thrombin-catalyzed fibrin polymerization and factor XIIIa (FXIIIa)-catalyzed γ-γ dimer formation from fibrin or fibrinogen and also ultrastructural analysis of fibrin clots and bundles. Results: By comparison with both γ275His and γ275Ala fibrinogens, recombinant γ275Cys fibrinogen exhibited a more impaired γ-γ dimer formation from fibrin or fibrinogen, a more aberrant fibrin clot structure, and thicker fibers in fibrin bundles. In 1 : 1 mixtures of γ275Arg and γ275Cys fibrinogens or γ275Arg and γ275His fibrinogens, thrombin-catalyzed fibrin polymerization and both fibrin clot and fiber structures showed some compensation (as compared with γ275Cys or γ275His alone). Conclusion: These results strongly suggest that an amino acid substitution of γ275Arg alone disrupts D:D interactions in thrombin-catalyzed fibrin polymerization and the formation of fibrin bundles and fibrin clots. Moreover, the existence of a subsequent disulfide-linked Cys in γ275C fibrinogen augments the impairment caused by a His or Ala substitution." @default.
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• W2014157265 date "2004-08-01" @default.
• W2014157265 modified "2023-09-30" @default.
• W2014157265 title "Comparison of thrombin‐catalyzed fibrin polymerization and Factor XIIIa‐catalyzed cross‐linking of fibrin among three recombinant variant fibrinogens, γ275C, γ275H, and γ275A" @default.
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• W2014157265 doi "https://doi.org/10.1111/j.1538-7836.2004.00844.x" @default.
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