Trauma Primes Cells

创伤引发细胞

• 批准号: 8069421
• 负责人: ANIRBAN BANERJEE
• 金额: $ 44.97万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-30 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8069421
• 关键词: Anti-Inflammatory Agents; Antibodies; Blood; CD14 Antigen; Cells; Charge; Clinical; Complex; Cytometry; Data; Databases; Drops; Endosomes; Endothelium; Equipment; Funding; Future; Heat shock proteins; Hemorrhagic Shock; Housing; Howard Temin Award; Human; Inflammation; Inflammatory; Injury; Institution; Lead; Lipids; Lung; Lymph; Mesentery; Molecular; Pathway interactions; Patients; Property; Proteins; Resuscitation; Sampling; Seasons; Signal Transduction; Specimen; Testing; Tissues; Toxic effect; Transfusion; Trauma; Trauma Research; cellular imaging; cytokine; cytotoxic; insight; novel; receptor; therapy development; trauma centers

This application is an extension of our funded 2000 Trauma Center application and a resubmission of our competing renewal thaw was awarded bridge funding for 2004-2005. Our global hypothesis is that twoway exchanges between Human Core (housing clinical databases and patient samples) with mechanistic studies of inflammatory signaling will help us devise THERAPY FOR TRAUMA PRIMES CELLS. Since initial funding in 1993, our MOF databases have grown substantially to yield novel insights into fundamental problems inherent to hemorrhagic shock (I), transfusion (II), tissue injury (IV) and mechanisms of antiinflammatory resuscitation (V). The projects remain highly dependent on each other, and invite the Human Core to further test hypotheses. Proj. I focuses on cytotoxic properties of mesenteric lymph that occur after hemorrhagic shock, presumably due to mesenteric hypoperfusion. In this proposal we expand on the potential bioactivity of this lymph, the condition necessary for its toxicity, and attempt to dissect its components. Proj. II undertakes a detailed analysis of analogous lipid metabolites accruing in lymph and stored blood, focusing on lung endothelium. Proj. Ill focused on heat shock proteins but is being dropped form this proposal. Proj. IV focuses on another type of ubiquitous intracellular protein HMGBP that may be the penultimate effector of inflammation, caused by either cytokines or LPS. Curiously, its signaling mechanism could lead to the same LPS receptor pathway. Proj. V challenges other projects that signaling by inflammatory agents depends on large signaling complexes that form as activated receptors are internalized. Therefore, by disrupting assembly of the endosome-scaffolded signaling modules, inflammatory manifestations might be avoided. To validate these ideas, the Human Core is charged with supplying specimens, gather data, and re-annotate the database while remaining in strict regulatory compliance. With young clinicians and bio-statisticians returning to query this powerful database, we reassess the impact of changing therapy and develop new hypotheses for bench-testing in future cycles. A vigorous Cell & Imaging Core will provide each project with commonly used human cells, and equipment and expertise to perform advanced molecular colocalization and cytometry using antibodies. These efforts are supported by a seasoned Administrative Core that seeks to further the prowess of our three institutions to promulgate Trauma Research.

此申请是我们资助的2000年创伤中心申请的扩展，并重新提交我们的 竞争性更新解冻被授予2004 - 2005年的桥梁资金。我们的全球假设是Twoway 与机械的人核（住房临床数据库和患者样本）之间的交流 炎症信号传导的研究将有助于我们为创伤素细胞设计治疗。自从 1993年的最初资金，我们的MOF数据库已大大增长，以产生对基本的新见解 出血性休克（I），输血（II），组织损伤（IV）和抗炎机制固有的问题 复苏（V）。这些项目仍然高度依赖彼此，并邀请人类 进一步检验假设的核心。 Proj。我专注于在此之后发生的肠系膜淋巴的细胞毒性特性 出血性休克，大概是由于肠系膜灌注灌注。在此提案中，我们扩展了 这种淋巴的潜在生物活性，其毒性所需的疾病，并试图剖析 成分。 Proj。 II对淋巴和 储存的血液，专注于肺部内皮。 Proj。专注于热冲击蛋白，但正在掉落 形成此建议。 Proj。 IV专注于另一种无处不在的细胞内蛋白HMGBP 由细胞因子或LPS引起的炎症的倒数效应子。奇怪的是，它的信号 机制可能导致相同的LPS受体途径。 Proj。 V挑战其他信号的项目 炎症剂取决于形成活化受体的大信号传导复合物 内部化。因此，通过破坏内体相关信号模块的组装， 可以避免炎症表现。为了验证这些想法，人核被指控 提供标本，收集数据并重新注释数据库，同时严格监管 遵守。随着年轻的临床医生和生物统计学家返回查询这个功能强大的数据库，我们重新评估 改变治疗并提出新的假设的影响，以在未来的周期中进行基准测试。一个 剧烈的细胞和成像核心将为每个项目提供常用的人类细胞，设备以及 使用抗体进行晚期分子共定位和细胞仪的专业知识。这些努力是 在经验丰富的行政核心的支持下，旨在进一步的实力 颁布创伤研究。