PATHOLOGY CORE

病理学核心

• 批准号: 8231135
• 负责人: ANDREW P EVAN
• 金额: $ 27.31万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-20 至 2016-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8231135
• 关键词: Apatites; Area; Biopsy; Biopsy Specimen; Calcium; Calcium Oxalate; Calculi; Crystal Formation; Cystine; Deformity; Deposition; Distal renal tubular acidosis Type 1; Fibrosis; Funding; Histologic; Human; Hyperparathyroidism; Immunohistochemistry; Inflammation; Injury; Instruction; Intestinal Bypasses; Kidney Calculi; Learning; Location; Maps; Membrane Transport Proteins; Minerals; Nephrolithiasis; Obesity; Obstruction; Operative Surgical Procedures; Papillary; Pathogenesis; Pathology; Patients; Plague; Progress Reports; Proteins; Publishing; Quantitative Evaluations; Sampling; Site; Spectroscopy, Fourier Transform Infrared; Staining method; Stains; Techniques; Tissues; Transmembrane Transport; Transmission Electron Microscopy; Tubular formation; Western Blotting; brushite; human tissue; improved; inflammatory marker; inhibitor/antagonist; inorganic phosphate; interstitial; light microscopy; osteopontin; prevent; prothrombin fragment 1

PROJECT SUMMARY (See instructions): The Progress Report of Projects 1, 2 and 3 of this application illustrate the highly successful surgical, histologic and metablic analyses that were performed and published during this last funding peroid on seven different groups of stone formers, common CaOx stone formers (SF), intestinal bypass patients for obesity with kidney stones, brushite SF, cystine SF, ilesotomy patients, primary hyperparathyroidism with phosphate stones, distal renal tubular acidosis with phosphate stones (as well as non-SF). This core will conduct all the morphological/pathology analyses for Projects 1, 2, and 3. Human tissue collected by Project 2 from a highly selected and metabocally characterized patient pool will be studied using the following techniques: 1) specialized stains of biopsy material for light microscopy (LM), 2) transmission electron microscopy (TEM) of stone-plaque interface, 3) LM and TEM immunohistochemistry to detect the presence of a select group of known inhibitor proteins of crystal formation (osteopontin, prothrombin fragment 1) in stone-plaque interface, 4) LM and TEM immunohistochemistry to determine abundance and location of VDR, CaSR (Aim 3.5), markers of inflammation and fibrosis (Aim 3.3), and membrane transports (Aim 3.6), 5) micro-CT analysis to quantitate, localize and characterize mineral type of new sites of crystal deposition in biopsies samples, 6) micro-FTIR and Raman analysis to indentify specific sites of crystal deposition in human biopsy samples. Project 2 will supply Core B with all of the cortical and papillary biopsy samples required for the studies outlined in Projects 2 and 3, 7) Western blot analysis of VDR and CaSR on cortical and outer medullary biopsies (Aim 3.5), and 8) prepare video loops and micrographs to preform plaque mapping studies (Aims 3.1 and 3.4b) with Project 2. Core B will supply Project 1 and Core A with quantitative evaluation of glomerular and interstitial fibrosis values for all cortical samples, mineral analysis of all interstitial and tubular depsoits, quantitation of human VDR and CaSR, plaque area determinations, histopathogic scoring of papillary deformities, number of plugged IMCD and BD tubules, number of attached stones and their mineral analysis, presences of yellow plaque, and degree of papillary fibrosis.

项目总结（见说明）： 本申请的项目1、2和3的进展报告说明了在上一个资助期内对七组不同的结石形成者、普通CaOx结石形成者（SF）、患有肾结石的肥胖症的肠旁路患者、透钙磷石SF、胱氨酸SF、回肠切开术患者、患有磷酸盐结石的原发性甲状旁腺功能亢进症、远端肾小管酸中毒伴磷酸盐结石（以及非SF）。该核心将对项目1、2和3进行所有形态学/病理学分析。将使用以下技术研究项目2从高度选择和代谢局部表征的患者池中收集的人体组织：1） 用于光学显微镜（LM）的活组织检查材料的专门染色，2）结石-斑块界面的透射电子显微镜（TEM），3）LM和TEM免疫组织化学，以检测晶体形成的一组选择的已知抑制蛋白的存在（骨桥蛋白、凝血酶原片段1）4）光镜和透射电镜免疫组化测定VDR、CaSR的丰度和位置（目的3.5）、炎症和纤维化的标志物（目的3.3）和膜转运（目的3.6），5）显微CT分析，以定量、定位和表征活检样品中晶体沉积新位点的矿物质类型，6） 显微FTIR和拉曼分析，以识别人体活检样品中晶体沉积的特定部位。 项目2将为Core B提供项目2和3中概述的研究所需的所有皮质和乳头状活检样本，7）皮质和外髓活检组织的VDR和CaSR蛋白质印迹分析（目标3.5），以及8）准备视频循环和显微照片，以便与项目2一起进行斑块标测研究（目标3.1和3.4 B）。核心B将为项目1和核心A提供所有皮质样本的肾小球和间质纤维化值的定量评价、所有间质和肾小管凹陷的矿物质分析、人VDR和CaSR的定量、斑块面积测定、乳头状畸形的组织病理学评分、堵塞的IMCD和BD小管数量、附着结石数量及其矿物质分析、黄色斑块的存在，和乳头状纤维化的程度。