GENETIC DETERMINATION OF ALLOGRAFT VASCULOPATHY

描述 （改编自申请人摘要）Benza博士将成为助理 1997年4月，心血管疾病科医学教授 (DCD)在亚拉巴马大学（UAB）。 本扎医生的专科培训 是在心脏移植领域的研究兴趣， 血管生物学 他曾获得多项杰出部门奖， 他在内皮细胞介导的纤维蛋白溶解方面的研究，并提出了他的 在多个国家和国际会议上进行研究。 他收到了一 第一年获得美国心脏协会/亚拉巴马附属奖 奖学金，以资助他在内皮细胞介导的纤维蛋白溶解方面的工作， 在同行评审的期刊上发表了几篇文章。 他提出的研究将确定受损的 纤溶活性与心脏移植血管病的发生 (Tx CAD），这是移植后常见且昂贵的问题。 前提 这些研究中的一个结论是，Tx CAD的发展可能与 某些纤溶蛋白（t-PA、PAI-1、u-PA）基因的存在 基因多态性（FPGP）在供体和受体。 具体地说， 这些基因的表达可能以基因型特异性方式受到影响 由于某些因素（高胆固醇血症）的发展， 移植 这种纤溶蛋白（FP）表达的改变将 然后导致纤维蛋白沉积和Tx CAD的发展， 国产CAD的发展。 在这种情况下，用于t-PA、PAI-1、u-PA的FPGA 和纤维蛋白原将通过Southern印迹和PCR技术测定， 150对捐赠者和接受者。 然后，这些患者将接受随访， 为期4年，以确定这些FPGP是否可预测 Tx CAD的开发。 此外，血浆水平（受体）和组织 将通过ELISA测定FP水平（活检标本）， 免疫细胞化学荧光染色，分别，以确定是否 这些蛋白质的表达、纤溶基因型之间存在联系 TX CAD UAB，医学系和DCD将提供研究空间， 设施、资源（秘书支助和办公空间）和适当的 时间承诺（80%），让候选人进行和完成 本申请中提出的研究目标。 他将不再会 在此期间的行政或教学职责。 如果 如果他的教师导师离开该机构，一位新的导师将在 任命和他的持续发展，成为一个独立的 医生科学家支持和鼓励。

DESCRIPTION (Adapted from applicants' abstract) Dr. Benza will become an Assistant Professor of Medicine in April 1997, in the Division Cardiovascular Diseases (DCD) at the University of Alabama (UAB). Dr. Benza's subspecialty training is in the area of Cardiac Transplantation with a research interest in vascular biology. He has won several distinguished departmental awards for his research in endothelial cell-mediated fibrinolysis and has presented his research at several national and international meetings. He received an American Heart Association/Alabama Affiliate Award during his first year of fellowship to fund his work in endothelial cell-mediated fibrinolysis and has several publications in peer reviewed journals. His proposed studies will define the relationship between impaired fibrinolytic activity and the development of cardiac allograft vasculopathy (Tx CAD), a frequent and costly problem post transplantation. The premise of these studies is that the development of Tx CAD may be related to the presence of certain fibrinolytic protein (t-PA, PAI-1, u-PA) gene polymorphisms (FPGP) in both the donor graft and recipient. Specifically, the expression of these genes may be affected in a genotype-specific manner by certain factors (hypertriglyceridemia) which develop as a result of the transplant. This altered expression of fibrinolytic proteins (FPs) will then lead to fibrin deposition and the development of Tx CAD analogous to the development of native CAD. In this context, FPGPs for t-PA, PAI-1, u-PA and fibrinogen will be determined by Southern blot and PCR techniques for 150 donor/recipient pairs. These patients will then be followed for a period of 4 years to determine if these FPGP are predictive for the development of Tx CAD. In addition, plasma levels (recipient) and tissue levels (biopsy specimens) of FPs will be determined by ELISA and immuncytochemical fluorescent staining, respectively, to determine whether a link exists between the expression of these proteins, fibrinolytic genotypes and TX CAD. UAB, Department of Medicine and DCD will provide the research space, facilities, resources (secretarial support and office space) and appropriate time commitment (80%) to allow the candidate to conduct and accomplish the research goals set forth in this application. He will have no administrative or teaching duties during the period of this application. If his faculty mentor were to leave the institution, a new mentor will be appointed and his continued development toward becoming a independent physician scientist supported and encouraged.