BLOOD COAGULATION & HEMORRHAGIC DISEASE

血液凝固

• 批准号: 3337890
• 负责人: WILLIAM R JR BELL
• 金额: $ 15.16万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-09-30 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3337890
• 关键词: binding proteins; blood proteins; calcium; calmodulin; cellular pathology; chromatography; coagulation factor VIII; cortisone; cyclic nucleoside monophosphate; enzyme linked immunosorbent assay; fibrinogen; gel electrophoresis; gene expression; hemorrhagic disorders; interleukin 1; laboratory rat; liver cells; membrane activity; messenger RNA; nucleic acid probes; peptides; plasminogen activator; prostacyclins; protein C; protein biosynthesis; protein kinase C; protein sequence; radioimmunoassay; radiotracer; spectrometry; tissue /cell culture; vascular endothelium

The overall and long term goals of the proposed research is an increased understanding of the mechanisms involved in fibrinogen biosynthesis. Particular emphasis and interest is directed at the understanding of those mechanisms and components involved in controlling the synthesis of plasma fibrinogen by parenchymal cells of the liver. Our recent studies indicate that rat fibrinogen fragment D90 (FDP-D90) (90,000 daltons) in micro molar concentrations directly and specifically induces the synthesis of fibrinogen by isolated hepatocytes in a chemically-defined, serum-free medium. Particular attention will be directed to identify and define the receptor on the hepatocyte responsible for the binding of FDP-D90. Additional studies will be performed to identify if this peptide is internalized and if the individual genes are stimulated to express increased quantities of mRNA for the Aalpha, B beta and gamma chains respectively by utilization of the appropriate genomic C-DNA probes. We will identify if cyclic nucleotides, cAMP, adenylate cyclase and Interleukin 1, protein kinase c, Ca++, and clamodulin are mediators of this synthetic path. Since it is possible that FDP-D90 may synergistically act with a "cofactor," detailed studies have been proposed to identify, isolate and purify this component and identify its cell of origin. Because we have recently demonstrated that human fibrinogen fragments D94 (94,000 daltons) and D78 (78,000 daltons) induce striking morphologic abnormalities in vascular endothelial cells, we propose continuation of these studies to identify the mechanisms involved. Expansion of the binding studies in progress will include verification of stimulation of cyclic AMP via adenylate cyclase. We will also measure secretion of prostacyclin and tissue plasminogen activator by Factor VIII:Ag and thrombomodulin to learn if these components that modulate thrombogenesis are disturbed by these fragments of fibrinogen. These comprehensive studies will provide new information on how rat fibrinogen FDP-D90 specifically induces the stimulation of the biosynthesis of fibrinogen and how human fibrinogen FDP-D78 and D94 induce damage in vascular endothelial cells.

拟议研究的总体和长期目标是一个

项目成果

Abrupt reversal of gestational autoimmune thrombocytopenia after delivery. A case report.

分娩后妊娠期自身免疫性血小板减少症突然逆转。

• 发表时间: 1989
• 期刊: The Journal of reproductive medicine
• 作者: Bartholomew,JR;Bell,WR;Kickler,TM;Repke,J
• 通讯作者: Repke,J

Heparin requirement for the quantitation of fibrinogen production by primary hepatocyte cultures.

原代肝细胞培养物中纤维蛋白原产生定量所需的肝素。

• DOI: 10.1016/0003-2697(88)90658-6
• 发表时间: 1988
• 期刊: Analytical biochemistry
• 影响因子: 2.9
• 作者: Dang,CV;LaDuca,FM;Bell,WR
• 通讯作者: Bell,WR

Extensive thrombus formation with heparin resistance during extracorporeal circulation. A new presentation of familial antithrombin III deficiency.

体外循环期间出现肝素抗性的广泛血栓形成。

• 发表时间: 1987
• 期刊: Archives of internal medicine
• 作者: Nielsen,LE;Bell,WR;Borkon,AM;Neill,CA
• 通讯作者: Neill,CA

Fibrinogen Seattle II: congenital dysfibrinogenemia with an Arg (A alpha 16)----his substitution.

纤维蛋白原西雅图 II：先天性纤维蛋白原异常血症，带有 Arg（A α 16）----他的替代品。

• DOI: 10.1016/0049-3848(86)90040-x
• 发表时间: 1986
• 期刊: Thrombosis research
• 影响因子: 7.5
• 作者: Ebert,RF;Schreiler,WE;Bell,WR
• 通讯作者: Bell,WR

The fibrinolytic system in man.

人体的纤溶系统。

• DOI: 10.1016/s1040-8428(84)80004-9
• 发表时间: 1984
• 期刊: Critical reviews in oncology/hematology
• 作者: Reiner,AP;Bell,WR
• 通讯作者: Bell,WR