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疾病的病理生理学的理解做出了重大贡献。然而，尽管以前曾努力阐明参与颞骨疾病发病机理的潜在机制，但仍需要从具有定义明确的听觉和前庭疾病的患者中创建和研究颞骨标本，这些患者具有定量的听觉和前庭功能测试，并检查经验丰富的神经科学家。 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基因表达。为此，我们在目标1中提出，通过招募捐助者并获得详细的临床历史并在所有保证颞骨头上进行详细的临床历史和测试，以进一步发展人类的暂时性骨骼处理技术，以最大程度地扩展形态和抗原和抗原性和核心ACIE的行为，以实现现代技术，在AIM 2上开发了新型的人类临时骨处理技术，以实现现代技术，以实现现代技术，以实现现代技术，以实现现代技术，以实现现代技术，以实现现代技术，以实现现代技术，以实现现代技术，以实现现代的骨骼处理技术，从而在目标2上进行了现代技术，从而使现代化的技术在AIM 2中进一步扩展，我们提出了目标1来扩大国家的暂时骨骼听力和平衡资源注册表。 RNA在显微解剖的人颞骨标本上的原位杂交和提取。另外，将建立传统的组织病理学相关性。将分析DNA的易感基因以及DMA和RNA表达之间的相关性。在AIM 4中，我们计划培训颞骨科学和神经学领域的临床医生和博士后学生。在AIM 5中，我们计划系统地对图像进行分类和数字化以允许数据共享，并计划与颞骨研究联盟完全合作，并与其他颞骨研究实验室合作。我们将与Kumar Alagramam博士合作，使用激光捕获显微解剖来开发RNA提取，并与Allen Ryan博士在福尔马林固定的石蜡包裹的部分上应用原位杂交。