PIGMENT GALLSTONES: COMPOSITION AND FORMATION

对大多数胆结石的横断面分析显示， 结石成分表明胆汁成分经历了波动 在石头的侵蚀和生长过程中。这项研究的总体目标是 考察一些蛋白质持续或间歇性地起作用的论点 捕获钙盐和胆固醇，为石头提供骨架 孕育和生长。胆汁蛋白质组分将被识别出来， 表征并与结石中的蛋白质相关联以确定机制 使石块成分沉淀的地方。控制胆汁成分的 这一过程将评估它们对蛋白质结合的影响 钙盐在体外和动物体内对结石成分的影响。这一过程 将在人类身上进行检查，以提供相关的框架，并在动物身上进行检查，以 提供可再生和可控制的条件。具体目标是 TO：1.通过检测胆汁pH值对结石生长的影响 胆红素钙酸性盐和中性盐在人体内的分布 石材使用傅里叶变换红外光谱(FTIR)。2.审查， 利用FTIR，将胆结石表面的成分与 周围的胆汁。确定其微观结构和成分 用扫描电子显微镜观察胆固醇-钙盐晶体-能量 色散X射线分析(SEM-EDXA)。确定以下项目的分布 用傅立叶变换红外光谱检测结石中的蛋白质。3.利用扫描电子显微镜-能谱仪对石材进行检测 显微结构和成分、结石孔隙度和蛋白质晶体 互动。4.使用胆囊外植体系统来确定效果 离子钙、胆红素和磷酸盐对粘蛋白产生和 分泌物。5.观察分级胆汁淤积对胆汁的影响 功能、胆汁分泌和棕色色素结石的形成及检查 结石过程中胆汁中存在酸性微环境的假说 在结石生长过程中，会间歇性地发生硝化。6.量化和 表征胆汁和胆汁中蛋白质的钙盐结合特性 通过混合实验考察了氧化抑制和促进作用 用Fine Performance分离其他胆汁蛋白的性质 凝胶过滤色谱柱。这些研究的结果 研究将检验这一理论，即各种不同的蛋白质 结合亲和力，与其他蛋白质一起作为抑制剂或 促进剂，解释胆固醇和钙盐的独特比例 在不同病人的多组胆结石中发现。

Cross-section analysis of most gallstones shows repeated cyclic patterns in stone composition suggesting that bile composition undergoes fluctuations during stone nidation and growth. The overall aim of this study is to examine the thesis that some proteins act consistently or intermittently as traps for calcium salts and cholesterol and provide a skeleton for stone nidation and growth. Biliary protein fractions will be identified, characterized and correlated with proteins in stones to identify mechanisms by which stone components precipitate. Biliary components that control this process will be assessed for their effect on protein binding of calcium salts in vitro and on stone composition in animals. This process will be examined in man to provide a relevent framework and in animals to provide reproducible and controllable conditions. The specific aims are to: 1. Determine the influence of biliary pH on stone growth by examining the distribution of the acidic and neutral salts of calcium bilirubinate in stone using Fourier Transform Infrared Spectroscopy (FTIR). 2. Examine, using FTIR, the composition of gallstone surfaces in comparison with the surrounding bile. Identify the microstructure and composition of cholesterol-calcium salt crystals using scanning electron microscopy-energy dispersive x-ray analysis (SEM-EDXA). Identify the distribution of proteins in stones using FTIR. 3. Use SEM-EDXA to examine stone microstructure and composition, stone porosity and protein-crystal interactions. 4. Use a gallbladder explant system to determine the effects of ionized calcium, bilirubinate and phosphate on mucin production and secretion. 5. Examine the effects of graded biliary stasis on gallbladder function, bile secretion and brown pigment stone formation and to examine the hypothesis that an acid microenvironment exists in bile during stone nidation and intermittently during stone growth. 6. Quantitate and characterize the calcium salt binding properties of proteins in bile and through mixing experiments to examine the nidation inhibition and promation properties of other biliary proteins separated using Fine performance liquid chromatography on gel filtration columns. The results of these studies will test the theory that a variety of proteins of different binding affinities, together with other protein acting as inhibitors or promoters, explains the unique proportions of cholesterol and calcium salts found in sets of gallstones from different patients.