Trauma Primes Cells

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 2004-2005年间，与之竞争的更新解冻项目获得了过桥资金。我们的全球假设是双向的 人类核心(存储临床数据库和患者样本)与机械学之间的交换 对炎症信号的研究将有助于我们设计创伤原始细胞的治疗方法。自.以来 最初的资金是在1993年，我们的财政部数据库有了很大的增长，产生了对基本面的新见解 失血性休克(I)、输血(II)、组织损伤(IV)的固有问题及抗炎机制 复苏(五)。这些项目仍然高度依赖于彼此，并邀请人类 核心，以进一步检验假设。项目。I侧重于肠系膜淋巴的细胞毒性特性 失血性休克，可能是由于肠系膜低灌流所致。在本提案中，我们将扩展到 这种淋巴的潜在生物活性，其毒性的必要条件，并试图剖析其 组件。项目。Ii对淋巴和血液中积累的类似脂质代谢物进行详细分析 储存血液，重点是肺内皮细胞。项目。不太关注热休克蛋白，但正在放弃 形成这份提案。项目。IV重点研究了另一种普遍存在的细胞内蛋白HMGBP，它可能是 炎症的倒数第二个效应物，由细胞因子或脂多糖引起。奇怪的是，它发出的信号 机制可能导致相同的内毒素受体途径。项目。V挑战其他发出信号的项目 通过炎症介质依赖于大的信号复合体，这些复合体作为激活的受体形成 内化了。因此，通过破坏内体支架信号模块的组装， 炎性表现可以避免。为了验证这些想法，人类核心负责 提供样本，收集数据，重新注释数据库，同时保持严格的监管 合规性。随着年轻的临床医生和生物统计学家回来质疑这个强大的数据库，我们重新评估 改变治疗的影响，并开发新的假说，以便在未来的周期中进行平台测试。一个 活力细胞和成像核心将为每个项目提供常用的人体细胞、设备和 使用抗体执行高级分子共定位和细胞学的专业知识。这些努力是 由经验丰富的行政核心支持，寻求进一步加强我们三个机构的能力 发布创伤研究报告。

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.