SCOR-LUNG BIOLOGY AND DISEASES IN INFANTS AND CHILDREN

这项建议旨在提高我们对因素的理解 与新生儿肺损伤的相关性及其远期临床意义 后果 该组成项目将研究急性肺结核的基础 损伤以及导致长期损伤的序列 气道的结构和功能改变。 该中心将 包括6个主要项目， 中心的规划需求。 具体项目有：1）新生儿 肺基质驱动肺修复。 这项研究将确定的影响 氧化损伤对肺上皮基底膜基质的相互作用; 2） 氧化损伤中肺泡上皮细胞的分化。 本研究将 检测氧化损伤对Na+/K+ ATP酶的影响， 肺内γ-谷氨酰转移酶; 3）应激蛋白之间的关系 和抗氧化剂在高氧。 热休克反应已被证明， 在涉及损伤和修复的各种系统中很重要。 我们 将研究热休克蛋白与内源性抗氧化剂的关系 高氧损伤后的机制; 4）表面活性剂的调节 成人肺损伤和发育中的磷脂代谢。 这 项目将研究表面活性剂磷脂合成在不同的 二氧化硅诱导的肺损伤后的II型细胞群; 5） 丁酸对SP-A基因转录的影响 该项目将 研究肺对特定生化损伤的反应， 基因表达的改变; 6）患有哮喘的婴儿的呼吸能量学 慢性肺疾病。 在这个项目中，我们将研究肺的变化， 工作，呼吸效率和能量消耗的BPD婴儿， 代表急性肺损伤的最终共同途径。 SCOR将 包括两个核心， 教育和监督组成部分以及生物统计支持， 共享仪器设施。 一个共同的形态学和电子显微镜 核心方案将为实验室项目的组成部分提供支助。 的 通过中心提供的互动和共享知识将导致 更好地了解潜在的肺损伤事件， 在制定合理的预防战略之前， 开发和测试。

This proposal is directed toward improving our understanding of factors associated with neonatal lung injury and its long term clinical consequences. The component projects will examine the basis of acute lung injury as well as the sequence of injury that result in long term structural and functional alterations of the airway. The Center will include 6 major projects in addition to defined cores for administrative and programmatic needs of the Center. Specific projects are: 1) Neonatal Lung Matrix Drives Lung Repair. This study will define the influence of oxidant injury on lung epithelial basement membrane matrix interactions; 2) Alveolar Epithelial Differentiation in Oxidant Injury. This study will examine the influence of oxidant injury on Na+/K+ ATPase and gammaglutamyltransferase in lung; 3) Relationship Between Stress Proteins and Antioxidants in Hyperoxia. The heat shock response has been shown to be important in a variety of systems involved in injury and repair. We will examine heat shock proteins in relationship to endogenous antioxidant mechanisms following hyperoxic insult; 4) Regulation of Surfactant Phospholipid Metabolism in Injured Adult and Developing Lungs. This project will examine surfactant phospholipid synthesis in different populations of type II cells following silica induced lung injury; 5) The Influence of Butyrate Acid on SP-A Gene Transcription. This project will study the response of lung to a specific biochemical insult associated with alterations in gene expression; 6) Energetics of Breathing in Infants with Chronic Lung Disease. In this project, we will study alterations in lung work, respiratory efficiency and energy expenditure in infants with BPD who represent the final common pathway of acute lung injury. The SCOR will include 2 Cores which will provide support for the programmatic, educational, and oversight components as well as biostatistical support and a shared instrument facility. A shared morphology and electron microscopy core will provide support for the component laboratory projects. The interactions and shared knowledge provided through the Center will lead to a better understanding of the events underlying lung injury that will be essential before rational strategies for prevention can be rigorously developed and tested.