GLYCOCONJUGATES AND BLADDER DISORDERS OF WOMEN

糖复合物和女性膀胱疾病

• 批准号: 2147182
• 负责人: VEER P. BHAVANANDAN
• 金额: $ 18.33万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2147182
• 关键词: biochemistry; biopsy; electrophoresis; enzyme activity; enzyme linked immunosorbent assay; female; glycosidases; human tissue; immunocytochemistry; interstitial cystitis; laboratory rabbit; mucins; mucopolysaccharides; proteoglycan; urinary bladder disorder; urinary bladder epithelium; urinary incontinence; urinary tract infection; urine

The overall objectives of she research are: (a) the detailed biochemical characterization of the glycoconjugates of the mammalian bladder epithelium; (b) to determine the role of the bladder mucosal glycoconjugates in the pathogenesis of urinary bladder disorders of women such as interstitial cystitis, urinary tract infections and urinary incontinence. Because of the limitations of the availability of human bladders, parallel basic studies on both human and rabbit bladders will be conducted to elucidate the biochemical nature of mammalian bladder glycoconjugates. The focus will be on mucins, to test the hypothesis that they, rather than the other ladder glycoconjugates (proteoglycans/glycosaminoglycans, N-linked glycoproteins and glycolipids), play a crucial role in the protection of bladder against invasion by pathogenic microorganisms and injury from 'toxic' substances in the urine. Previously, we have discovered and partially characterized a mucin glycoprotein (named epitectin) which is a component of human urothelium and which can be readily isolated from human urine. The specific experiments proposed are: 1) to determine the glycoconjugate composition as well as to purify and biochemically characterize the mucin(s) of rabbit bladder mucosal layer; 2) to investigate the relationship between rabbit urine and bladder glycoconjugates. The information gathered will enable us to determine whether all human bladder glycoconjugates are likely to be represented in human urine (a readily available source for research); 3) quantitative analysis of mucins and glycosaminoglycans of urine from patients with various bladder disorders and normal adult controls. Epitectin levels will be estimated by ELISA, other mucins and glycosaminoglycans will be quantitated by gel and cellulose acetate electrophoresis; 4) to biochemically characterize the mucin(s) and glycosaminoglycans purified from urine of interstitial cystitis female patients and bladder disease-free women; 5) to examine normal and pathologic human bladder glycoconjugates by immunocytochemical and metabolic labeling techniques using biopsy specimens; 6) to measure the levels of glycosaminoglycan and mucin catabolic enzymes in the urine of patients with bladder disorders and of normal adult controls and determine whether the decreased concentration of urinary glycosaminoglycans in IC patients noted by other investigators could be the result of increased degradation.

她研究的总体目标是：（a）详细的生化 哺乳动物膀胱的糖缀合物的表征 上皮； （b）确定膀胱粘膜的作用 女性膀胱疾病的发病机理中的糖缀合物 例如间质性膀胱炎，尿路感染和尿液 失禁。 由于人类可用性的局限性 膀胱，对人类和兔子膀胱的平行基础研究将是 进行的旨在阐明哺乳动物膀胱的生化性质 糖缀合物。重点将放在粘蛋白上，以检验以下假设。 他们，而不是其他梯子糖缀合物 （蛋白聚糖/糖胺聚糖，N连接的糖蛋白和 糖脂），在保护膀胱侵害中起着至关重要的作用 病原微生物和“有毒”物质受伤的侵袭 在尿液中。 以前，我们发现并部分表征 粘蛋白糖蛋白（称为表染料），它是人的一个成分 尿路上皮可以很容易地与人类尿液中分离出来。 这 提出的具体实验是：1）确定糖缀合物 成分以及纯化和生化表征 兔膀胱粘膜层的粘蛋白； 2）调查 兔尿液和膀胱糖缀合物之间的关系。这 收集的信息将使我们能够确定是否所有人类膀胱 糖缀合物可能在人类尿液中表示 可用的研究来源）； 3）粘蛋白和 来自各种膀胱疾病的患者的尿液的糖胺聚糖 和正常的成人对照。 ELISA将估计营养素水平， 其他粘蛋白和糖胺聚糖将由凝胶和 乙酸纤维素电泳； 4）生化表征 粘蛋白（S）和糖胺聚糖从间质尿液中纯化 膀胱炎女性患者和无膀胱病女性； 5）检查 通过免疫细胞化学的正常和病理性的人膀胱糖缀合物 使用活检标本的代谢标记技术； 6）测量 尿液中糖胺聚糖和粘蛋白分解代谢酶的水平 患有膀胱疾病和正常成人对照的患者 确定尿液浓度降低 其他研究者注意的IC患者中的糖胺聚糖可能是 降解增加的结果。