MECHANISMS OF MICROVASCULAR THROMBOSIS

微血管血栓形成的机制

基本信息

  • 批准号:
    6096825
  • 负责人:
  • 金额:
    $ 13.85万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1986
  • 资助国家:
    美国
  • 起止时间:
    1986-12-01 至 2000-03-31
  • 项目状态:
    已结题

项目摘要

In studies of the role of C4b binding protein (C4bBP) in the baboon response to E. coli, we observed a microvascular thrombotic (MVT) variant which mimics the hematolytic uremic syndrome (HUS). We identified the key inflammatory and coagulant mediators (ie. tumor necrosis factor, tissue factor, etc.) and anticoagulant regulators (ie. protein C and S, etc.). We established that inflammatory mediators initiated the coagulant response. We did not, however, establish how the inflammatory, coagulant, and anticoagulant systems interacted. In this proposal, we hypothesize that coagulant mediators can amplify inflammatory activity, and that as a consequence, anticoagulants also act as anti-inflammatory regulators. Conversely, we hypothesize that these inflammatory mediators decrease anticoagulant activity. This is a circle in which the regulator systems are influenced by disturbances in the two mediator systems and visa versa. We will ask the following three questions: First, does C4bBP neutralization of anticoagulant protein S affect platelet/coagulant status, and is the stage set for an increased inflammatory (MVT) response to TNF, I1-6, etc.? Second, conversely do these cytokines disable the normal regulatory protein C anticoagulant/fibrinolytic response to factor Xa phospholipid (XaPCPS) and "tip the balance" in favor of MVT? Third, do these or similar events involving these mediator/regulator systems occur in a baboon model of MVT/HUS induced by Shiga-like toxin? The coagulant, anticoagulant, and inflammatory (neutrophil), responses to C4bBP alone will be studied. These studies will include determination of neutrophil opsonin/receptor expression by blood luminescence analysis, and appearance of enzyme/inhibitor complexes composed of components of regulator systems. Platelet receptor, and, neutrophil receptor participation will be assessed using appropriate Fab monoclonal antibodies. Both the C4bBP and XaPCPS models will be perturbed with TNF and I1-6, etc., to determine the effect of the absence of protein C and S on the response to these mediators and their effect on a stressed, but compensated, anticoagulant/fibrinolytic response to XaPCPS. We will determine whether the compensated response to XaPCPS can be converted into a response by these cytokines and/or by coinfusion of antibodies to both protein C and tissue plasminogen activator. The experience and techniques used in the above intervention and reconstitution studies will be applied to mechanistic, diagnostic and treatment studies of the fully expressed Shiga-like toxin model of HUS/MVT.
补体C4b结合蛋白(C4bBP)在狒狒体内作用的研究 对大肠杆菌的反应,我们观察到一种微血管血栓(MVT)变异体 它模仿溶血性尿毒症综合征(HUS)。我们找到了钥匙 炎症和凝血介质(即肿瘤坏死因子,组织 因素等)和抗凝剂调节剂(即蛋白C和S等)。 我们确定是炎症介质启动了凝血剂 回应。然而,我们没有确定炎症性的, 凝血剂和抗凝血剂系统相互作用。 在这个提议中,我们假设凝血剂中介物可以放大 炎症活性,因此,抗凝剂也起作用 作为消炎调节剂。相反,我们假设这些 炎症介质会降低抗凝血活性。这是一个圆圈 其中调节系统受到两个系统中的干扰的影响 调解人系统,反之亦然。 我们将问以下三个问题:第一,C4bBP 中和抗凝蛋白S对血小板/凝血因子的影响 状态,是炎症(MVT)反应增加的阶段 对肿瘤坏死因子、I1-6等?第二,反过来,这些细胞因子是否会使 正常调节蛋白C抗凝/纤溶反应 Xa磷脂(XaPCPS)和“天平”有利于MVT?第三, 这些事件或类似事件是否涉及这些调解人/监管机构系统 发生在志贺样毒素诱导的MVT/HUS的恒河猴模型中? 凝血剂、抗凝剂和炎症(中性粒细胞)的反应 将仅对C4bBP进行研究。这些研究将包括确定 血液发光分析中性粒细胞调理素/受体的表达, 以及由以下组分组成的酶/抑制剂复合体的出现 调节系统。血小板受体和中性粒细胞受体 将使用适当的Fab单抗对参与情况进行评估 抗体。C4bBP和XaPCPS模型都会受到肿瘤坏死因子的干扰 和I1-6等,以确定缺少蛋白C和 S对这些调解人的回应及其效果进行了一次强调,但 对XaPCPS的代偿抗凝/纤溶反应。我们会 确定是否可以转换对XaPCPS的补偿响应 通过这些细胞因子和/或通过共同注射抗体来产生反应 蛋白C和组织型纤溶酶原激活剂。 上述干预和干预中使用的经验和技术 重建研究将应用于机械性、诊断性和 全表达志贺样毒素模型的治疗研究 HUS/MVT。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

FLETCHER B TAYLOR其他文献

FLETCHER B TAYLOR的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('FLETCHER B TAYLOR', 18)}}的其他基金

MECHANISMS OF MICROVASULAR THROMBOSIS IN BABOONS
狒狒微血管血栓形成机制
  • 批准号:
    6385663
  • 财政年份:
    1986
  • 资助金额:
    $ 13.85万
  • 项目类别:
SUPPRESSION OF ANTICOAGULANT FACTORS
抑制抗凝因子
  • 批准号:
    3293272
  • 财政年份:
    1986
  • 资助金额:
    $ 13.85万
  • 项目类别:
PROTECTION FROM ENDOTOXIN SHOCK BY ACTIVATED PROTEIN C
活化蛋白 C 防止内毒素休克
  • 批准号:
    3293267
  • 财政年份:
    1986
  • 资助金额:
    $ 13.85万
  • 项目类别:
PROTEIN S, C4BBP, AND THREE COAGULANT MODELS
PROTEIN S、C4BBP 和三种凝血剂模型
  • 批准号:
    2178913
  • 财政年份:
    1986
  • 资助金额:
    $ 13.85万
  • 项目类别:
PROTEIN S, C4BBP, AND THREE COAGULANT MODELS
PROTEIN S、C4BBP 和三种凝血剂模型
  • 批准号:
    2178912
  • 财政年份:
    1986
  • 资助金额:
    $ 13.85万
  • 项目类别:
PROTECTION FROM ENDOTOXIN SHOCK BY ACTIVATED PROTEIN C
活化蛋白 C 防止内毒素休克
  • 批准号:
    3293271
  • 财政年份:
    1986
  • 资助金额:
    $ 13.85万
  • 项目类别:
MECHANISMS OF MICROVASULAR THROMBOSIS IN BABOONS
狒狒微血管血栓形成机制
  • 批准号:
    6128901
  • 财政年份:
    1986
  • 资助金额:
    $ 13.85万
  • 项目类别:
SUPPRESSION OF ANTICOAGULANT FACTORS
抑制抗凝因子
  • 批准号:
    3293273
  • 财政年份:
    1986
  • 资助金额:
    $ 13.85万
  • 项目类别:
PROTEIN S AND C4BBP IN THREE COAGULANT MODELS
三种凝固剂模型中的蛋白质 S 和 C4BBP
  • 批准号:
    3293269
  • 财政年份:
    1986
  • 资助金额:
    $ 13.85万
  • 项目类别:
MECHANISMS OF MICROVASCULAR THROMBOSIS
微血管血栓形成的机制
  • 批准号:
    2444643
  • 财政年份:
    1986
  • 资助金额:
    $ 13.85万
  • 项目类别:

相似海外基金

EPIphANy (Evaluation of Pharmacological Interactions with Anticoagulants in caNcer patients) program - prostate cancer cohort
EPIPHANy(癌症患者抗凝药理相互作用的评估)计划 - 前列腺癌队列
  • 批准号:
    479295
  • 财政年份:
    2023
  • 资助金额:
    $ 13.85万
  • 项目类别:
    Operating Grants
Inhibitors of Human Factor XIIIa as New Anticoagulants
人类因子 XIIIa 抑制剂作为新型抗凝剂
  • 批准号:
    10629057
  • 财政年份:
    2023
  • 资助金额:
    $ 13.85万
  • 项目类别:
Establishment of comprehensive monitoring of direct oral anticoagulants (DOACs) for clinical application
建立临床应用直接口服抗凝剂(DOAC)综合监测体系
  • 批准号:
    23K06906
  • 财政年份:
    2023
  • 资助金额:
    $ 13.85万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Interactions of Enzyme-Inducing Antiepileptic Drugs with Direct-Acting Oral Anticoagulants: Risk of Thromboembolic Events
酶诱导抗癫痫药物与直接作用口服抗凝剂的相互作用:血栓栓塞事件的风险
  • 批准号:
    10605482
  • 财政年份:
    2023
  • 资助金额:
    $ 13.85万
  • 项目类别:
The Comparative Effectiveness and Safety of Oral Anticoagulants in Patients with Cirrhosis and Atrial Fibrillation
口服抗凝药对肝硬化合并心房颤动患者的有效性和安全性比较
  • 批准号:
    10559071
  • 财政年份:
    2023
  • 资助金额:
    $ 13.85万
  • 项目类别:
Search for indicators of blood levels of directly inhibitory oral anticoagulants in coagulation tests using artificial intelligence
使用人工智能在凝血测试中搜索直接抑制性口服抗凝剂的血液水平指标
  • 批准号:
    22K07388
  • 财政年份:
    2022
  • 资助金额:
    $ 13.85万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Bleeding on Direct Oral Anticoagulants: Identification of Genetic Risk Factors and a Polygenic Predictive Score in Patients with Atrial Fibrillation
直接口服抗凝剂导致的出血:房颤患者遗传风险因素的鉴定和多基因预测评分
  • 批准号:
    10536789
  • 财政年份:
    2022
  • 资助金额:
    $ 13.85万
  • 项目类别:
Study on proper use of oral anticoagulants combined with 5-fluorouracil
口服抗凝药联合5-氟尿嘧啶正确使用研究
  • 批准号:
    22K06743
  • 财政年份:
    2022
  • 资助金额:
    $ 13.85万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Benchmarking a point-of-care test kit for detection of direct-oral anticoagulants
用于检测直接口服抗凝剂的即时检测试剂盒的基准测试
  • 批准号:
    461790
  • 财政年份:
    2022
  • 资助金额:
    $ 13.85万
  • 项目类别:
    Operating Grants
Direct oral anticoagulants and the risk of colorectal and pancreatic cancers: a population-based cohort study.
直接口服抗凝剂与结直肠癌和胰腺癌的风险:一项基于人群的队列研究。
  • 批准号:
    474475
  • 财政年份:
    2022
  • 资助金额:
    $ 13.85万
  • 项目类别:
    Studentship Programs
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了