HUMAN BIOCHEMICAL GENETICS

人类生化遗传学

• 批准号: 3878038
• 负责人: W A GAHL
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3878038
• 关键词: I cell disease; Menkes' syndrome; aminoacid metabolism; aminoacid transport; carnitine; child (0-11); copper; cysteamine; cystine; cystinosis; deToni Fanconi syndrome; eye agent; heterozygote; high performance liquid chromatography; homocystinuria; human subject; human therapy evaluation; human tissue; inborn biological transport disorder; inborn lysosomal enzyme disorder; inborn metabolism disorder; iodotyrosine; lysosomes; metabolism disorder chemotherapy; molecular genetics; oculocerebrorenal syndrome; sialate; thyrotropin; tissue /cell culture; tyrosine; vision disorders

1.Seventy-five cystinosis patients are seen in the Human Genetics Branch and most are treated with cysteamine or phosphocysteamine. In pre- transplant patients, cysteamine therapy is maintaining renal function and assisting growth. In post-transplant patients, complications of long-term cystine accumulation are described. These include myopathy, neurological involvement, and severe swallowing difficulties. Cysteamine eyedrops (0.5%) dissolve corneal cystine crystals in young children and remove the haziness from the eyes of older children, with relief of photophobia. 2.Impaired lysosomal egress of free sialic acid has been demonstrated as the basic defect in Infantile Free Sialic Acid Storage Disease (ISSD). ISSD fibroblasts also store glucuronic acid due to impaired egress out of the lysosome. 3.The basic defect in sialuria has been demonstrated to be impaired feedback inhibition by CMP sialic acid of UDP N-acetylglucosamine 2-epimerase. Cytosolic free sialic acid levels can be reduced by treatment of the fibroblasts with cytidine. 4.The human kidney filters but does not reabsorb free sialic acid. This was demonstrated by studying patients with different filtered loads of free sialic acid. 5.Copper metabolism is impaired in Menkes' disease and Indian Childhood Cirrhosis cells. A 23 Kd protein with copper-binding activity is being characterized using normal human fibroblasts. Copper histidinate therapy of Menkes' disease is being pursued by a clinical protocol. 6.Unknown lysosomal storage disorders are investigated by carbohydrate analysis performed by pulsed ampermetric detection, and by lipid analysis performed by HPLC separation and Varex analysis. 7.Lysosomal membrane carriers are being investigated by reconstitution of proteoliposomes to be used as a test system for functional transport.

1.在人类遗传学分支 并且大多数用cysteamine或磷西汀治疗。在pre- 移植患者，cysteamine疗法正在维持肾功能和 协助增长。在移植后患者中，长期并发症 描述了胱氨酸的积累。这些包括肌病，神经学 参与和严重的吞咽困难。赛岛眼（0.5％） 溶解幼儿的角膜胱氨酸晶体并去除朦胧 从大儿童的眼中，缓解恐惧症。 2.自由唾液酸的溶酶体出口受损已被证明为 婴儿游离唾液酸储存疾病（ISSD）的基本缺陷。 ISSD 成纤维细胞还储存了由于出口受损而导致的葡萄糖醛酸 溶酶体。 3.已证明Sialuria的基本缺陷受到损害 CMP唾液酸对UDP N-乙酰葡萄糖的反馈抑制作用 2- epimerase。可以通过治疗降低胞质唾液酸水平 与胞苷的成纤维细胞。 4.人类肾脏过滤器，但不能吸收not鼠唾液酸。这是 通过研究具有不同过滤量的自由载荷的患者证明 唾液酸。 5.肥胖代谢在Menkes疾病和印度童年时期受到损害 肝硬化细胞。具有铜结合活性的23 kD蛋白 使用正常的人成纤维细胞进行表征。铜制疗法治疗 临床方案正在追求Menkes的疾病。 6.碳水化合物研究了溶酶体储存障碍 分析通过脉冲的安培检测和脂质分析进行 通过HPLC分离和VAREX分析进行。 7.正在通过重组调查渗透膜膜载体 蛋白脂质体用于功能运输的测试系统。