Complement Activation and Pregnancy Loss

补体激活和妊娠失败

• 批准号: 7676198
• 负责人: ANNE M. LYNCH
• 金额: $ 13.1万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-12 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7676198
• 关键词: Animals; Area; Award; Biological Assay; Classical Complement Pathway; Clinical; Clinical Research; Colorado; Complement; Complement 3 Convertase; Complement Activation; Conceptus; DBA/2 Mouse; Deposition; Development; Discipline of obstetrics; Doctor of Philosophy; Environment; Epidemiology; Fetal Resorption; Frequencies; Gynecology; Habitual Abortion; Health Sciences; Human; Immune; Immunoglobulin G; Immunology; Inflammatory Response; Lead; Logistic Regressions; Mediating; Medical Research; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Modeling; Mus; Natural History; Neutrophil Infiltration; Outcome; Perinatal; Placenta; Plasma; Pregnancy; Pregnancy Complications; Pregnancy loss; Pregnant Women; Preventive; Recording of previous events; Regression Analysis; Research; Research Personnel; Research Project Grants; Resources; Role; Sampling; Study models; Thrombosis; Time; Training; Translating; Universities; Visit; Woman; abortion; career development; cohort; comparison group; design; fetal; follow-up; follower of religion Jewish; human study; in utero; inhibitor/antagonist; mouse crry protein; mouse model; patient oriented research; pregnant; prevent; professor; programs; skills

DESCRIPTION (provided by applicant): Anne Lynch MD, MSPH is an Assistant Professor in the Department of Obstetrics and Gynecology at the University of Colorado at Denver and Health Sciences Center (UCDHSC). Dr Lynch has an established commitment to clinical research. This Mentored Patient-Oriented Research Career Development Award will facilitate the development of Dr. Lynch into a successful independent investigator in patient-oriented research. The proposed training under the mentorship of Michael Holers MD (Immunology) Tim Byers MD, MPH (Epidemiology) and other advisors is designed to increase her skills in the area of perinatal epidmiology and immunology. This award will allow Dr. Lynch to pursue higher level epidemiology and statistical courses from the Epidemiology PhD program at UCDHSC. Classes from the UCDHSC Integrated Department of Immunology Graduate program are also included in the coursework. The objective of her research project is to study the contribution of split products from complement activation to pregnancy loss in a cohort of 1000 women. Recent studies in experimental murine models suggest that complement activation is the final effector mechanism for immunologically-mediated pregnancy loss. The proposal will translate these observations to a human study in the setting of the award. A sample for split products will be obtained from all women in the cohort in early pregnancy (<15 weeks gestation) along with a detailed clinical history. At the conclusion of the study, women with pregnancy loss will be identified from the incident cohort. The plasma samples for these women will be assayed along with those of a randomly selected comparison group of women without pregnancy loss. The levels of split products in cases will be compared to the levels in the controls. A follow-up sample will be obtained on women who suffer a loss, to evaluate for change in levels from baseline. James Muphy PhD at National Jewish Medical and Research Center will guide the univariate and multivariable logistic regression analysis of the study. This project, the mentors, the enthusiastic support from the Dept. of OB/GYN and the research resources available at UCDHSC will provide Dr Lynch with an excellent environment for her career development. The proposed study will provide unique information on the role of complement activation split products among women with pregnancy loss, and may ultimately lead to preventive treatment for this tragic outcome.

描述（由申请人提供）：MSPH的Anne Lynch MD是科罗拉多大学丹佛和健康科学中心（UCDHSC）的妇产科助理教授。林奇博士对临床研究有了既定的承诺。这项受到指导的以患者为导向的研究职业发展奖将促进林奇博士的发展成为一个成功的以患者为导向的独立研究者。 Michael Holers MD（免疫学）Tim Byers MD，MPH（流行病学）和其他顾问的指导下的拟议培训旨在提高她在围产期流行病学和免疫学领域的技能。该奖项将使林奇博士能够在UCDHSC的流行病学博士学位课程中攻读更高级别的流行病学和统计课程。课程中还包括来自UCDHSC综合综合研究生课程课程的课程。她的研究项目的目的是研究1000名女性队列中分裂产品从补体激活到怀孕丧失的贡献。实验鼠模型的最新研究表明，补体激活是免疫学介导的妊娠丧失的最终效应机制。该提案将这些观察结果转化为奖项的人类研究。分裂产品的样本将在怀孕初期（妊娠<15周）以及详细的临床病史的所有女性中获得。在研究结束时，将从事件队列中确定怀孕丧失的妇女。这些女性的血浆样本将与随机选择的没有怀孕丧失的妇女的比较组一起进行测定。在情况下，分裂产品的水平将与对照中的水平进行比较。将对遭受损失的妇女获得后续样本，以评估基线的变化。国家犹太医学和研究中心的詹姆斯·穆普利（James Muphy）博士将指导研究的单变量和多变量逻辑回归分析。这项项目，导师，OB/GYN系的热情支持以及UCDHSC提供的研究资源将为Lynch博士提供极好的环境，以实现其职业发展。拟议的研究将提供有关妊娠丧失的女性补体激活分裂产品作用的独特信息，并最终可能导致预防性治疗这一悲惨结果。