SCOR--LUNG BIOLOGY AND DISEASES IN INFANTS AND CHILDREN

这是专业研究中心(SCOR)的续签申请 用于婴儿和儿童的肺部生物学和疾病。该提案是 由一系列基础研究组成，旨在理解 肺损伤、生长和发育的细胞和分子方面，以及 然后将这些与正在开发的直接临床研究相结合 优化婴儿相关呼吸系统疾病的治疗方法。一个 与肺表面活性物质相关的现象在 拟议的研究，但主要工作也旨在分析和 描述一系列的细胞、生化和生理现象 在肺部疾病、损伤和发育中起重要作用。这些目标是 在本SCOR提案中通过以下补充解决 研究：1)生长因子的细胞和分子生物学研究 巨噬细胞和其他细胞的细胞因子及其对II型的影响 正常肺和损伤肺中的细胞和成纤维细胞；2)分子生物学 涉及特定分子(TIMP、金属硫蛋白等)的研究谁的 基因表达和产物在高氧肺损伤中发生改变， 脂肪酸的管理，以及其他原因，以及调节和作用 这些物质在损伤过程中的作用；3)对 表面活性、组分相互作用和生物物理抑制 天然和合成的肺表面活性物质及其衍生物 肺部疾病和损伤的病理生理和治疗现象； 4)细胞生物学、生物化学和生理学的机理研究 急性肺损伤动物模型(高氧、气压伤和肺表面活性物质 缺乏症，或油酸和胎粪给药)以及这些 条件可以用外源表面活性剂、抗氧化酶、 和类固醇激素；5)一系列临床研究，包括 表面活性物质替代和其他治疗，包括喷射通风治疗 新生儿呼吸窘迫综合征与新生儿肺损伤 继发于肺炎和胎粪吸入。这些相互关联的基本 科学和临床研究继续并扩展我们目前的SCOR研究， 并由一个多学科的调查小组进行， 富有成效的科学合作的历史。

This is a renewal application for a Specialized Center of Research (SCOR) for Lung Biology and Disease in Infants and Children. The proposal is comprised of a series of fundamental studies aimed at understanding the cellular and molecular aspects of lung injury, growth and development, and these are then coupled with direct clinical studies developing and optimizing therapies for related respiratory disorders in infants. a strong emphasis is placed on pulmonary surfactant-related phenomena in the proposed research, but major effort is also aimed at analyzing and describing a range of cellular, biochemical, and physiological phenomena important in lung disease, injury and development. These objectives are addressed in this SCOR proposal through the following complementary studies: 1) cell and molecular biological studies of growth factors and cytokines from macrophages and other cells, and their effects on type II cells and fibroblasts in normal and injured lungs; 2) molecular biological studies involving specific molecules (TIMP, metallothionein, etc.) whose gene expression and production is altered in lung injury from hyperoxia, fatty acid administration, and other causes, and the regulation and roles of these materials in the injury process; 3) physicochemical studies of the surface activity, component interactions, and biophysical inhibition of natural and synthetic lung surfactants, and the ramifications of these phenomena for the pathophysiology and therapy of lung disease and injury; 4) mechanistic studies of the cell biology, biochemistry, and physiology of acute lung injury in animal models (hyperoxia, barotrauma and surfactant- deficiency, or oleic acid and meconium administration) and how these conditions can be treated with exogenous surfactants, anti-oxidant enzymes, and steroid hormones; and 5) a series of clinical studies involving surfactant replacement and other therapies including jet ventilation for the neonatal Respiratory Distress Syndrome and for neonatal lung injury secondary to pneumonia and meconium aspiration. These inter-related basic science and clinical studies continue and extend our current SCOR research, and are carried out by a multi-disciplinary group of investigators with a history of productive scientific collaboration.