Biliary Atresia clinical Research Consortium

胆道闭锁临床研究联盟

• 批准号: 7244308
• 负责人: ROSS W SHEPHERD
• 金额: $ 24.18万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7244308
• 关键词: Affect; Biliary; Biliary Atresia; Biological Markers; Biopsy Specimen; Child; Child Care; Childhood; Cholestasis; Classification; Clinical; Clinical Data; Clinical Research; Collection; Core Facility; Data; Data Collection; Data Storage and Retrieval; Databases; Defect; Diagnosis; Diagnostic Procedure; Digestive System Disorders; Disease; Disease Progression; Electronics; Environmental Risk Factor; Epithelial Cells; Evaluation; Fibrosis; Freezing; Gene Expression; Genes; Genetic Markers; Genomics; Goals; Hepatic; Hepatic Fibrogenesis; Hepatocyte; In Situ Hybridization; Infant; Inflammation; Injury; International; Joints; Life; Liver; Liver Fibrosis; Liver diseases; Longitudinal Studies; Medical center; Methods; Molecular; Molecular Profiling; Natural History; Neonatal; Obstruction; Organ Transplantation; Outcome; Paraffin; Pathogenesis; Pathway interactions; Patients; Pattern; Procedures; Proteins; Proteomics; Registries; Research; Research Personnel; Sampling; Serum; Serum Proteins; Severities; Specimen; Staging; Staining method; Stains; System; Techniques; Technology; Time; Tissues; Variant; age group; cell type; experience; fibrogenesis; genetic profiling; improved; infancy; injured; laser capture microdissection; liver biopsy; liver transplantation; member; neonatal hepatitis; novel diagnostics; outcome forecast; programs; response; transmission process

DESCRIPTION (provided by applicant): The creation of a multi-center collaborative consortium provides an unprecedented opportunity to improve the lives of children with neonatal liver disease. This Clinical Center application from four pediatric medical centers describes the collective clinical expertise, collaborative research experience, and outstanding institutional core facilities needed to be productive contributing members to this consortium. This application proposes participation in the consortium in three ways: 1. Clinical Data Collection: A uniform, concise data form and electronic collection system will be developed to manage clinical data. Relevant clinical data and tissue specimens will be contributed to the Consortium. The two research programs and four clinical programs collaborating in this proposal can contribute data from approximately 25 new patients with biliary atresia (BA)/year and 12 patients with neonatal hepatitis (NH)/yr. 2. Short-term study: Using available and accumulated specimens, we will study the pathogenesis, natural history, and clinical correlates of hepatic fibrogenesis in patients with biliary atresia and NH. A variation of the Knodell hepatic fibrosis scale will be used to determine the extent of hepatic fibrosis at the time of the Kasai procedure. Immunohistochemical and in situ hybridization techniques will be used to quantify the expression of specific molecular markers of hepatic fibrosis and inflammation. The severity of fibrosis or specific staining patterns will be correllated with patient diagnosis and response to the Kasai procedure. 3. Long-term study: To identify patterns of protein and gene expression that are unique to biliary atresia or that predict response to the Kasai procedure, gene expression profiles will be determined in wedge liver biopsies as well as in hepatocytes and biliary epithelial cells isolated by laser capture microdissection (LCM). Modern proteomic techniques will also be applied to serum samples to identify proteins synthesized and released by the injured liver. Similar to the genetic profile, the pattern of proteins will be correlated with clinical data to identify patterns of serum proteins that are disease specific or predict prognosis.

描述（由申请人提供）： 创建一个多中心协作财团为改善新生儿肝病儿童的生活提供了前所未有的机会。来自四个儿科医疗中心的临床中心应用程序描述了集体临床专业知识，协作研究经验以及杰出的机构核心设施，需要为该财团的成员提供富有成效的贡献。该申请通过三个方面提议参与财团： 1。临床数据收集：将开发统一的简洁数据形式和电子收集系统来管理临床数据。相关的临床数据和组织标本将有助于财团。在该提案中合作的两个研究计划和四个临床计划可以从大约25名胆道闭锁（BA）/年的新患者和12例新生儿肝炎（NH）/年患者提供数据。 2。短期研究：使用可用的和累积的标本，我们将研究胆道闭锁和NH患者肝纤维发生的发病机理，自然史和临床相关性。 Knodell肝纤维化量表的变化将用于确定Kasai手术时肝纤维化的程度。免疫组织化学和原位杂交技术将用于量化肝纤维化和炎症的特定分子标记的表达。纤维化的严重程度或特定的染色模式将与患者诊断和对Kasai手术的反应相关。 3。长期研究：为了鉴定胆汁闭锁所独有的蛋白质和基因表达模式，或者预测对Kasai程序的反应，将在楔形肝活检以及肝细胞以及通过激光捕获微排除（LCM）分离的肝细胞和胆道上皮细胞中确定基因表达谱。现代蛋白质组学技术也将应用于血清样品，以鉴定受伤的肝脏合成和释放的蛋白质。与遗传特征相似，蛋白质的模式将与临床数据相关，以识别特定于疾病或预测预后的血清蛋白质模式。