TEMPORAL ANALYSIS OF PLATELETS AS CYTOTOXIC MEDIATORS IN SEPSIS

脓毒症中血小板作为细胞毒性介质的时间分析

• 批准号: 7951117
• 负责人: Robert J Freishtat
• 金额: $ 0.09万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951117
• 关键词: Accounting; Acute Lung Injury; Biological Assay; Blood Platelets; Blood specimen; Categories; Cell Fraction; Cessation of life; Child; Clinical; Clinical Research; Collection; Computer Retrieval of Information on Scientific Projects Database; DNA; Databases; Development; Enrollment; Funding; Genetic; Genomics; Grant; Granzyme; Hour; Immune response; In Vitro; Individual; Infectious Agent; Institution; Lymphocyte; Mediator of activation protein; Molecular; Morbidity - disease rate; Participant; Patients; Pattern; Peripheral; Process; Recruitment Activity; Research; Research Personnel; Resources; Sampling; Sepsis; Sepsis Syndrome; Septic Shock; Source; Testing; United States National Institutes of Health; Whole Blood; base; cytotoxic; cytotoxicity; insight; killings; mortality; peripheral blood; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The body's response to an infectious or non-infectious insult has been termed the systemic inflammatory response syndrome (SIRS). When this process is known to be caused by an infectious agent, the terms sepsis and SIRS are synonymous. SIRS/sepsis and its sequelae, including Acute Lung Injury, remain a leading cause of morbidity and mortality in children. Based on new insights into the molecular processes of SIRS, we hypothesize that in children with SIRS, the progression to septic shock, MODS, and/or death, is associated with the variable expression patterns of platelet granzymes. Specific Aim 1: Development of a genomic database of children with SIRS, septic shock, and/or MODS and healthy controls. In order to test our central hypothesis, it will be necessary to establish a genetic and clinical database of 22 individuals to account for the anticipated diversity of host responses to SIRS. We propose to isolate cell fractions from concurrent collections of peripheral whole blood from 22 children with SIRS recruited from the CNMC PICU. Two samples will be obtained from each SIRS participant; one will be obtained at the onset of SIRS and then the other sample 48 hours after that. DNA will also be isolated from the blood samples. SIRS participants will be recruited from the CNMC PICU. In addition, a single peripheral blood sample will be collected from 20 healthy normal control children enrolled in the CNMC ED. Specific Aim 2: Perform functional in vitro lymphocyte killing assays on platelets from all enrolled patients in Aim 1. We will classify our patients according to the proposed categories: 1) controls, 2) SIRS alone, 3) SIRS progressing to septic shock/MODS, and 4) SIRS progressing to septic shock/MODS and death. Using the in vitro lymphocyte killing assays, we will determine the degree of cytotoxicity of each participant's platelets. Cytotoxicity in each of the proposed categories will be compared in order to test our central hypothesis that the progression from SIRS to septic shock, MODS, and/or death is dependent on the expression patterns of platelet granzymes.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 人体对传染性或非感染侮辱的反应已被称为系统性炎症反应综合征（SIRS）。 当已知该过程是由传染剂引起的，术语败血症和sir是同义词。 SIRS/败血症及其后遗症，包括急性肺损伤，仍然是儿童发病率和死亡率的主要原因。基于对SIRS分子过程的新见解，我们假设在SIRS的儿童中，败血性休克，MOD和/或死亡的进展与血小板颗粒的可变表达模式有关。 特定目的1：开发具有SIRS，化粪池休克和/或MOD和健康对照儿童的基因组数据库。 为了检验我们的中心假设，有必要建立一个22个人的遗传和临床数据库，以说明宿主对SIRS的预期多样性。我们建议将细胞分数与从CNMC PICU招募的22名儿童的周围全血收集中分离出来。将从每个SIRS参与者那里获得两个样本；一个将在SIRS的发作开始，然后将获得另一个样本，然后再获得48小时。 DNA也将从血液样本中分离出来。 SIRS参与者将从CNMC PICU招募。此外，将从CNMC ED中招收的20名健康正常对照儿童中收集单个外周血样本。 具体目标2：对AIM 1中所有入学的患者的血小板进行功能性淋巴细胞杀死测定法。我们将根据提议的类别对患者进行分类：1）对照组，2）单独使用，3）SIRS，3）SIRS逐渐发展为败血性冲击/MOD，以及4）SIRS SIRS sIRS SIRS SICSIC SHOCK/MOD和MODS和MODS和死亡。使用体外淋巴细胞杀伤测定法，我们将确定每个参与者血小板的细胞毒性程度。为了检验我们的中心假设，即从SIRS到败血性休克，mod和/或死亡的进展取决于血小板颗粒酶的表达模式，将比较每个提出类别的细胞毒性。