Modern Studies of the Human Temporal Bone

人类颞骨的现代研究

• 批准号: 7192955
• 负责人: Akira Ishiyama
• 金额: $ 40.87万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-20 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7192955
• 关键词: clinical research; human; temporal bone

DESCRIPTION (provided by applicant): Human temporal bone studies have contributed significantly to our understanding of the pathophysiology of hearing and balance disorders. However, despite previous efforts to elucidate the underlying mechanisms of involved in the pathogenesis of temporal bone disorders, there is a tremendous need to create and study temporal bone specimens from patients with well-defined clincial auditory and vestibular disorders who have undergone quantitative auditory and vestibular function testing, and examination by experienced neurotologists. We propose that the advancement of temporal bone science to elucidate the molecular and cellular pathophysiology behind audiovestibular diseases requires a systematic, prospective clinicopathological correlative approach, coupled with rapid fixation and tissue-processing protocols aimed at antigenic and morphological preservation, and the application of the most modern accurate and reliable methodology for quantification and identification of pathological changes in protein and mRNA gene expression. To accomplish this, we propose in aim 1 to expand the National Temporal Bone Hearing and Balance Resource Registry by recruiting donors and obtaining detailed clinical histories and testing on all those pledging temporal bones, in aim 2 to further develop novel human temporal bone processing techniques to maximize morphologic and antigenic and nucleic acie preservation, in aim 3 to apply the modern techniques of immunohistochemistry, unbiased stereology, in situ hybridization and extraction of RNA on microdissected human temporal bone specimens. Additionally, traditional histopathological correlations will be made. DNA will be analyzed for susceptibility genes and correlations between DMA and RNA expression. In aim 4, we plan to train clinician-scientists and postdoctoral students in temporal bone science and neurotology. In aim 5, we plan to systematically categorize and digitalize images to allow data sharing, and plan to cooperate fully with the Temporal Bone Research Consortium and to collaborate with other temporal bone research laboratories. We will collaborate with Dr. Kumar Alagramam in the development of RNA extraction using laser capture microdissection, and with Dr. Allen Ryan in the application of in situ hybridization on formalin-fixed paraffin-embedded sections.

描述（由申请人提供）：人类颞骨研究对我们对听力和平衡障碍的病理生理学的理解做出了重大贡献。然而，尽管以前努力阐明参与颞骨疾病发病机制的潜在机制，但仍然非常需要从患有明确的临床听觉和前庭疾病的患者中创建和研究颞骨标本，这些患者接受了定量听觉和前庭检查。功能测试，并由经验丰富的神经病学家进行检查。我们认为，颞骨科学的进步需要一种系统的、前瞻性的临床病理学相关方法，结合旨在保存抗原和形态学的快速固定和组织处理方案，以及应用最先进的方法来阐明听前庭疾病背后的分子和细胞病理生理学。用于定量和鉴定蛋白质和 mRNA 基因表达病理变化的现代准确可靠的方法。为了实现这一目标，我们在目标 1 中建议通过招募捐赠者并获得详细的临床病史和对所有承诺颞骨进行测试来扩大国家颞骨听力和平衡资源登记处，在目标 2 中建议进一步开发新型人类颞骨处理技术最大限度地保存形态学、抗原性和核酸，目标 3 应用免疫组织化学、公正体视学、原位杂交和显微解剖人颞骨 RNA 提取等现代技术标本。此外，还将进行传统的组织病理学关联。将分析 DNA 的易感基因以及 DMA 和 RNA 表达之间的相关性。在目标 4 中，我们计划培训颞骨科学和神经学领域的临床科学家和博士后学生。在目标5中，我们计划对图像进行系统分类和数字化以允许数据共享，并计划与颞骨研究联盟以及其他颞骨研究实验室充分合作。我们将与 Kumar Alagramam 博士合作开发使用激光捕获显微切割进行 RNA 提取，并与 Allen Ryan 博士合作在福尔马林固定石蜡包埋切片上应用原位杂交。