Pathology/Immunology Core

病理学/免疫学核心

基本信息

批准号：
8319521
负责人：
MARTHA CAMPBELL-THOMPSON
金额：
$ 15.65万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8319521
关键词：
Acute Algorithms Alkaline Phosphatase Animal Model Antibodies Antigens Apoptosis Area Autoantibodies Autopsy Biological Assay Canis familiaris Cell Cycle Cells Clinical Derivation procedure Detection Development Diabetes Mellitus Direct immunofluorescence Disease Dose Duct (organ) structure Elements Endocrine Environment Evaluation Eye Fixatives Florida Freezing Frozen Sections Functional disorder Genetic Predisposition to Disease Glucagon Glutamate Decarboxylase Goals Histocytochemistry Histology Histopathology Human Human Resources IA-2-autoantibody Immune response Immune system Immunofluorescence Immunologic Immunohistochemistry Immunologics Immunology In Situ Hybridization Indirect Immunofluorescence Inflammation Inflammatory Insulin Insulin-Dependent Diabetes Mellitus Intervention Investigation Kidney Label Laboratories Lymphoid Measures Messenger RNA Methods Modeling Molecular Molecular Immunology Monoclonal Antibodies Morphology Mus Organ Pancreas Pancreatic Polypeptide Paraffin Paraffin Embedding Pathogenesis Pathology Patients Performance Peroxidases Prevention strategy Primates Principal Investigator Procedures Process Rattus Reagent Research Research Personnel Risk Risk Assessment Safety Sampling Serum Site Somatostatin Spleen Staging Staining method Stains Standardization Techniques Testing Therapeutic Tissue Microarray Tissues Training Universities cytotoxicity disorder prevention experience ghrelin human subject immune function improved interest lymph nodes molecular pathology polyclonal antibody preclinical study prevent programs research study response sample fixation treatment duration treatment effect

项目摘要

The Molecular Pathology and Immunology Core of the University of Florida currently assists multiple investigators participating in Projects aimed at an improved understanding of the pathogenesis of type 1 diabetes, as well as the development of agents capable of reversing and/or preventing the disease. Specifically, the Core supports these investigations by performing pathological and immunological analyses that characterize the host's immune system and cell/tissue response, including those involving treatments proposed or currently used in experimental and preclinical studies. This goal has and will continue to be accomplished by performance of three specific aims: 1) Determine tissue morphology in the context of histopathology in order to evaluate treatment effects with respect to administration site, dose, and treatment duration. 2) Determine the potential beneficial effects of treatments in murine models of diabetes; with assessment of the pancreas as well other organs related to type 1 diabetes. 3) Perform immunologic evaluations in animal models and human subjects that characterize aspects related to the humoral and cellular immune response, as well as providing genetic susceptibility to type 1 diabetes. The morphological studies are vital in order to evaluate whether a given Project's intervention successfully ameliorates the pro- inflammatory environment within the pancreas, lymph node, spleen, and other organs and to determine the extent to which any intervention induces acute inflammation or cytotoxicity. Centralization of the morphological studies, and standardization of the histopathological and toxicological determinants, enables rigorous assessment of cellular responses. Procedures include standard histology on paraffin and frozen materials, special stains, histochemistry, immunohistochemistry, and immunofluorescence. In terms of analysis of human samples, the Core laboratory will build upon more that two decades of experience in terms of evaluating for the presence of autoantibodies in serum of patients with or at increased-risk of type 1 diabetes, as well as determining the genetic susceptibility for the disease by performance of HLA typing. In addition to providing a critical element for assurance of therapeutic safety and improved mechanistic understanding, the Core should provide information that will enhance the feasibility and efficacy of preclinical trials to prevent or reverse type 1 diabetes.

佛罗里达大学的分子病理学和免疫学核心目前协助多个参与旨在加深对 1 型发病机制了解的项目的研究人员糖尿病，以及开发能够逆转和/或预防该疾病的药物。具体来说，核心通过进行病理学和免疫学分析来支持这些研究表征宿主免疫系统和细胞/组织反应，包括涉及治疗的反应提议或目前用于实验和临床前研究。这个目标已经并将继续通过实现三个具体目标来实现：1）确定组织形态组织病理学，以评估给药部位、剂量和治疗的治疗效果期间。 2) 确定治疗对糖尿病小鼠模型的潜在有益效果；和评估胰腺以及与 1 型糖尿病相关的其他器官。 3) 进行免疫学检查对动物模型和人类受试者的评估，表征与体液和细胞免疫反应，以及提供对 1 型糖尿病的遗传易感性。形态学研究对于评估特定项目的干预措施是否成功改善亲健康至关重要胰腺、淋巴结、脾脏和其他器官内的炎症环境，并确定任何干预诱发急性炎症或细胞毒性的程度。集中化形态学研究以及组织病理学和毒理学决定因素的标准化使得严格评估细胞反应。程序包括石蜡和冷冻的标准组织学材料、特殊染色、组织化学、免疫组织化学和免疫荧光。按照核心实验室将基于二十多年的人类样本分析经验评估 1 型患者或高风险患者血清中是否存在自身抗体的术语糖尿病，以及通过 HLA 分型确定该疾病的遗传易感性。在除了提供确保治疗安全和改进机制的关键要素之外理解，核心应提供能够提高临床前可行性和有效性的信息预防或逆转 1 型糖尿病的试验。