CORE--PATHOLOGY

核心--病理学

• 批准号: 7490032
• 负责人: ANDREW P EVAN
• 金额: $ 12.92万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7490032
• 关键词: Apatites; Bariatrics; Biopsy; Biopsy Specimen; Calculi; Crystal Formation; Cystinuria; Deposition; Detection; Electrons; Fluorescence Microscopy; Genetic; Growth; Human; Hyperparathyroidism; Ileostomy; Image; Immunohistochemistry; Intestinal Bypasses; Kidney; Kidney Calculi; Label; Light; Lithium; Localized; Location; Measurement; Microscopic; Minerals; Obesity; Osteoblasts; Papillary; Pathology; Patients; Pattern; Proteins; Rate; Rattus; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Serum; Site; Spectroscopy, Fourier Transform Infrared; Staining method; Stains; Standards of Weights and Measures; Techniques; Tetracycline; Tetracyclines; Tissues; Transcript; Transmission Electron Microscopy; Uric Acid; Urine; alpha-Fetoproteins; bikunin; brushite; human tissue; hypercalciuria; inhibitor/antagonist; kidney cortex; light microscopy; light transmission; osteopontin; particle; prothrombin fragment 1; tongue papilla; urinary

The Pathology Core has been highly successful in the identification of tissue changes and characterizing sites of mineral deposition as well as crystal type in three different type of human stone patients (common CaOx, intestinal bypass patients for obesity with renal stones and brushite) and the GHS rats. In the renewal, this core will oversee and conduct all morphological analyses for Projects by Lingeman and Evans using 1) light micrscopy with special stains to characterize the histopathological patterns and mineral composition of crystal deposition in our new groups of human stone formers (apatite including RTAs, primary hyperparathyroidism, ileostomy, cystinuria, uric acid stones, bariatric and CaOx with high urine pH (> pH 6.3), 2) light and transmission electron microscopic immunohistochemistry to detect the presence of a select group of known inhibitor proteins of crystal formation (osteopontin, prothombin fragment 1, fetuin-A and bikunin) in the interstitium and at the stone-plaque interface, 3) mu CT imaging to quantitate, localize and characterize mineral type of new sites of crystal deposition in whole kidneys or biopsies samples. 4) mu FTIR and electron diffraction detection techniques to identify specific sites of crystal deposition in human biopsy samples and GHS rat kidneys, 5) RT-PCR techniques to determine the presence of osteoblast-like transcripts in the interstitium of the common CaOx stone formers vs intestinal bypass or bariatric stone formers, 6) determine the mechanisms of crystal particle formation and coalescence in CaOx stone formers by quantitating particle growth/coalescence and performing double labeling, tetracyline studies to determine the rate of crystal formation, 7) provide cortical biopsy samples to Project by Coe for VDR analysis and verification of biopsy location, and 8) to assess the GHS rat for plaque formation. Project by Lingeman will supply biopsy samples from the kidney (cortex to papilla) of predetermined groups of human stone formers. Dr. Willis will perform serum and urinary lithium analyses for Project by Coe.

病理学核心在识别组织变化和 表征三种不同类型的人类结石患者（普通 CaOx、患有肾结石和透钙磷石的肥胖肠绕道患者）和 GHS 大鼠的矿物质沉积部位和晶体类型。在更新中，该核心将监督和进行 Lingeman 和 Evans 项目的所有形态分析，使用 1) 具有特殊染色的光学显微镜来表征我们新的人类结石形成者组中晶体沉积的组织病理学模式和矿物成分（磷灰石，包括 RTA、原发性甲状旁腺功能亢进症、 回肠造口术、胱氨酸尿症、尿酸结石、肥胖症和高尿液 pH 值 (> pH 6.3) 的 CaOx，2) 光和透射电子显微镜免疫组织化学，检测间质和结石斑块中一组选定的已知晶体形成抑制剂蛋白（骨桥蛋白、凝血酶原片段 1、胎球蛋白-A 和 bikunin）的存在 接口，3) mu CT 成像，用于对整个肾脏或活检样本中晶体沉积的新位点的矿物类型进行定量、定位和表征。 4) mu FTIR 和电子衍射检测技术，用于识别人类活检样本和 GHS 大鼠肾脏中晶体沉积的特定位点，5) RT-PCR 技术，用于确定常见 CaOx 结石形成者与肠旁路或减肥结石形成者的间质中是否存在成骨细胞样转录物，6) 确定 通过定量颗粒生长/聚结并进行双标记、四环素研究以确定晶体形成的速率，研究 CaOx 结石形成物中晶体颗粒形成和聚结的机制，7) 向 Project by Coe 提供皮质活检样本以进行 VDR 分析和活检位置验证，以及 8) 评估 GHS 大鼠的斑块形成。 Lingeman 的项目将为预先确定的人类结石形成者群体的肾脏（皮质到乳头）提供活检样本。 Willis 博士将为 Project by Coe 进行血清和尿液锂分析。