Imaging Endocarditis

心内膜炎影像学检查

基本信息

批准号：
7693804
负责人：
Peter Rolf Panizzi
金额：
$ 0.23万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2009-09-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7693804
关键词：
Accounting Active Sites Acute Address Adult Age Animals Antibiotic Therapy Antigens Area Argatroban Bacteremia Bacteria Bacterial Endocarditis Bacterial Infections Binding Blood Blood Platelets C-terminal C57BL/6 Mouse Catheters Cause of Death Cell surface Cells Chronic Cleaved cell Clinical Coagulase Coagulation Process Complex Development Diagnosis Echocardiography Endocarditis Endothelial Cells Endothelium Environment Enzyme Precursors Fibrin Fibrinogen Flow Cytometry Generations Goals Heart Heart Valves ITGAM gene Image Immune In Vitro Incidence Infection Injury Label Lesion Mechanics Mediating Mediator of activation protein Modeling Molecular Monitor Monocytosis Mus N-terminal Neonatal Outcome Pathogenesis Pathology Patients Property Prothrombin Publishing Recruitment Activity Repetitive Sequence Research Roentgen Rays Role Rolfing Staphylocoagulase Staphylococcus aureus Structure Surface Tandem Repeat Sequences Testing Thrombin Thromboplastin Tissues Virulence Factors Wound Healing analog base human disease imaging modality improved in vivo inhibitor/antagonist insight macrophage molecular imaging monocyte mortality novel resistant strain response small molecule success

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of this proposed research is to define the molecular mechanism of vegetation formation during acute bacterial endocarditis (ABE), a potentially deadly human disease caused by bacterial infection of the valves of the heart. The leading cause of deaths from ABE is associated with coagulase-positive Staphylococcus aureus infections which account for 40-50% of neonatal endocarditis and 30-40% of endocarditis in adults between the ages of 16-60 years, with a mortality rate of 25-47%, even with antibiotic therapy. It is our hypothesis that S. aureus bacteremia induces expression of Ly6CHi monocytes leading to increased bacterial attachment to the heart valve surface. S. aureus expresses staphylocoagulase, a bifunctional molecule that activates prothrombin by N-terminal domains and mediates staphylocoagulaseprothrombin complex tethering to the growing vegetations by C-terminal tandem repeats that bind multiple fibrinogen molecules. Novel prothrombin analogs developed in this proposal are hypothesized to localize to the surface of the growing vegetations during ABE and provide new specific probes to monitor S. aureus ABE development, through powerful in vivo molecular imaging methods. Clinical imaging of endocarditis is performed by transesophageal echocardiogram, which is often difficult to interpret due to poor images and variable bacterial attachment. It is our contention that the use of these novel-imaging agents will be directly translatable to the clinical environment and ultimately, led to improved patient outcomes. The hypotheses proposed above will be tested by the following specific aims: Aim 1. To characterize monocyte response to S. aureus-mediate ABE and to define the role of these cells in vegetation formation, Aim 2. To determine the localization of active site labeled prothrombin in vivo during S. aureus endocarditis, and Aim 3. To characterize the effect of argatroban on the development of fibrin-bacteria-platelet vegetations during ABE.

描述（由申请人提供）：这项拟议研究的长期目标是定义急性细菌性心内膜炎（ABE）期间植被形成的分子机制，这是由心脏瓣膜细菌感染引起的潜在致命的人类疾病。 abe死亡的主要原因与金黄色葡萄球菌感染有关，占新生儿心脏心炎的40-50％，年龄在16-60岁之间的成年人的心内膜炎占30-40％，死亡率为25-47％，即使是25-47％，甚至接受抗生素治疗。我们的假设是，金黄色葡萄球菌菌血症诱导Ly6chi单核细胞的表达，从而导致细菌附着在心脏瓣膜表面上。金黄色葡萄球菌表达葡萄球菌，这是一种双功能分子，通过N末端结构域激活凝血酶蛋白，并介导葡萄球菌eprothrosprothrompin复合蛋白复合蛋白通过C-末端的植被将C-末端串联链球菌束缚在生长的植被中，从而结合多个纤维蛋白原分子。假设在本提案中开发的新型凝血酶原类似物在安倍晋三期间的植被表面定位，并通过强大的体内分子成像方法提供了新的特定探针来监测AUREUS ABE的发育。心内膜炎的临床成像是通过经食管超声心动图进行的，这通常由于图像差和可变的细菌附着而难以解释。我们的论点是，这些新颖成像剂的使用将直接转换为临床环境，并最终导致患者的预后改善。上面提出的假设将通过以下具体目的进行测试：目的1。表征对金黄色葡萄球菌米型abe的单核反应，并定义这些细胞在植被形成中的作用，目的2。确定活跃位点的定位，以确定活跃的现场标记为体内的实质性凝集素在体内的蛋白链球菌在aureus s. aureus s. aureus s. aureus to的炎症中，并在aureus s. aureus of the themeart of the gribriia theart。安倍期间的植被。