INTRAVESICAL PRESSURE AND BLADDER DEVELOPMENT

膀胱内压力和膀胱发育

• 批准号: 2017280
• 负责人: Deborah Erickson
• 金额: $ 10万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 1999-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2017280
• 关键词: histogenesis; laboratory mouse; organ culture; urinary bladder; urinary tract motility /pressure; vesicle /vacuole

THIS IS A SHANNON AWARD PROVIDING PARTIAL SUPPORT FOR THE RESEARCH PROJECTS THAT FALL SHORT OF THE ASSIGNED INSTITUTE'S FUNDING RANGE BUT ARE IN THE MARGIN OF EXCELLENCE. THE SHANNON AWARD IS INTENDED TO PROVIDE SUPPORT TO TEST THE FEASIBILITY OF THE APPROACH; DEVELOP FURTHER TESTS AND REFINE RESEARCH TECHNIQUES; PERFORM SECONDARY ANALYSIS OR AVAILABLE DATA SETS; OR CONDUCT DISCRETE PROJECTS THAT CAN DEMONSTRATE THE PI'S RESEARCH CAPABILITIES OR LEND ADDITIONAL WEIGHT TO AN ALREADY MERITORIOUS APPLICATION. THE ABSTRACT BELOW IS TAKEN FROM THE ORIGINAL DOCUMENT SUBMITTED BY THE PRINCIPAL INVESTIGATOR. DESCRIPTION (Taken from applicant's Abstract) The broad, long-term research interests for the principal investigator are (1) correlations between normal bladder structure and function (both epithelium and bladder wall are of interest), (2) pathophysiology leading to abnormal structure, (3) relationships between abnormal structure and functions. The specific focus of this project will be how bladder wall smooth muscle and connective tissue development is affected by increased intravesical pressure (created by ligating the urethra and ureters of fetal bladders in organ culture). The project will also include normal bladder development because little is currently known about normal development. The underlying hypothesis is that normal bladder development follows a specific program of changes, and that this program is accelerated by ligation. The changes include (1) decreased ratio of collagen to smooth muscle, (2) shift in collagen fiber type and organization to promote flexibility, (3) increase in elastin fibers, (4) increase in smooth muscle a and g actin isoforms while b actin decreases, (5) replacement of fetal-type myosin light chain (LC-23) with adult type (LC-17), (6) change in myosin light chain phosphorylation from fetal to adult pattern. The plan is to evaluate bladder structure on macroscopic, microscopic and ultrastructural levels, and to compare the above features under different conditions of bladder development. Specific Aim 1 will determine the normal in situ developmental program. Aim 2 will compare in situ bladders with bladders grown in organ culture. Aim 3 will compare bladders in organ culture: unligated vs. with the urethra and ureters ligated. In Aim 3, intravesical pressure will also be compared for the two conditions. The project has clinical relevance because intravesical pressure changes are thought to affect bladder wall smooth muscle and collagen in several disease states such as spina bifida and benign prostatic hyperplasia. In addition, useful extension are planned including (1) correlation of structural with functional changes in this model and (2) expanding this model to study bladder epithelial development and the roles of stromal- epithelial interactions.

这是香农奖，为这项研究提供部分支持 项目低于指定研究所的资助范围，但 都在最优秀的边缘。香农奖旨在提供 支持测试该方法的可行性；开发进一步的测试 并改进研究方法；进行二次分析或可用 数据集；或执行可演示PI的离散项目 研究能力或为已经功成名就的 申请。下面的摘要摘自原始文件 由首席调查员提交。 描述(摘自申请者摘要)概括的、长期的 首席调查员的研究兴趣是(1)相关性 在正常的膀胱结构和功能之间(上皮和 膀胱壁感兴趣)，(2)导致异常的病理生理 结构；(3)异常结构与功能的关系。 这个项目的具体焦点将是膀胱壁的平滑肌 而结缔组织的发育受到膀胱内增加的影响 压力(通过结扎胎儿膀胱的尿路和输尿管而产生 器官培养)。该项目还将包括正常膀胱 发展，因为目前对正常发展知之甚少。 潜在的假设是，正常的膀胱发育遵循 具体的变化计划，这个计划被加速了 结扎术。这些变化包括：(1)胶原与滑膜的比例降低 肌肉，(2)促进胶原纤维类型和组织的转变 弹性，(3)弹性蛋白纤维增加，(4)光滑程度增加 肌肉a和g肌动蛋白异构体，而b肌动蛋白减少，(5)替代 胎儿型肌球蛋白轻链(LC-23)与成人型肌球蛋白轻链(LC-17)，(6) 肌球蛋白轻链磷酸化从胎儿到成人型的变化。 计划从宏观、微观和微观三个方面评价膀胱结构。 超微结构水平，并比较不同条件下的上述特征 膀胱发育状况。具体目标1将决定 正常的原位发育程序。AIM 2将比较原位膀胱 膀胱是在器官培养中生长的。《目标3》将比较 器官培养：未结扎与结扎尿路和输尿管。在AIM 3、两种情况下的膀胱内压力也将进行比较。 该项目具有临床意义，因为膀胱内压会改变 被认为在几个方面影响膀胱壁的平滑肌和胶原 疾病状态，如脊柱裂和良性前列腺增生症。在……里面 此外，还计划进行有用扩展，包括(1)关联 该模型中的结构和功能变化以及(2)扩展该模型 研究膀胱上皮细胞发育和间质的作用的模型 上皮性相互作用。