CORE--PATHOLOGY

核心--病理学

• 批准号: 6898586
• 负责人: ANDREW P EVAN
• 金额: $ 13.63万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6898586
• 关键词: animal tissue; biomedical facility; biopsy; clinical research; computed axial tomography; electron microscopy; histopathology; human tissue; immunocytochemistry; infrared spectrometry; light microscopy; nephrolithiasis; pathology; polymerase chain reaction; transmission electron microscopy

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方面非常成功， 在三种不同类型的人类结石患者（普通CaOx、患有肾结石的肥胖症的肠旁路患者和透钙磷石）和GHS大鼠中表征矿物沉积的位点以及晶体类型。在更新过程中，该核心将监督和执行Lingeman和Evans项目的所有形态分析，使用1）特殊染色的光学显微镜，以表征我们新的人类结石形成者（磷灰石，包括RTA，原发性甲状旁腺功能亢进， 回肠造口术、胱氨酸尿症、尿酸结石、肥胖症和高尿pH值的CaOx（> pH 6.3），2）光和透射电子显微镜免疫组织化学，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、原凝血酶片段1、胎球蛋白-A和bikunin），3）μ CT成像以定量，在整个肾脏或活检样本中定位和表征晶体沉积的新位点的矿物类型。4)μ FTIR和电子衍射检测技术，以鉴定人活检样品和GHS大鼠肾脏中晶体沉积的特定位点，5）RT-PCR技术，以确定常见CaOx结石形成者与肠旁路或肥胖症结石形成者的骨中成骨细胞样转录物的存在，6）确定成骨细胞样转录物的存在， 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速率，7）向Project by Coe提供皮质活检样品，用于VDR分析和活检位置验证，以及8）评估GHS大鼠的斑块形成。Lingeman的项目将从预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。Dr. Willis将为Project by Coe进行血清和尿锂分析。