HUMAN BIOCHEMICAL GENETICS

(1)我们证明了白细胞中溶酶体胱氨酸转运缺陷， 来自中间（青少年）和良性的患者的成纤维细胞 （成人）胱氨酸病的变种。 在其他研究中，胱氨酸载体是 在大鼠甲状腺衍生细胞中起作用，需要蛋白质合成， 非N-连接的糖基化用于其生产。 (2)25个孩子 与胱氨酸病贡献的数据对一项全国性的研究表明， 口服半胱胺促进生长和延缓肾功能衰竭疗效观察 失败 同时，胱氨酸病的晚期并发症是 描述，包括脑萎缩，唾液功能受损，糖尿病 肺功能受限，角膜糜烂， 视觉敏锐度 一名患者接受了角膜移植， 开始用半胱胺滴眼液治疗角膜糜烂。 口服 半胱胺被提供给肾移植后的患者。 肉毒碱缺乏与范可尼综合征的个人正在接受治疗 口服肉毒碱，在恢复肌肉正常方面取得了一些成功， 组织学 (3)第二种溶酶体贮积症是由于 小分子穿过溶酶体膜的转运是萨拉 疾病，一种以精神发育迟滞为特征的芬兰疾病。 萨拉 成纤维细胞在其溶酶体内储存游离唾液酸， 带电荷的糖。 唾液酸流出速度异常 富含溶酶体的颗粒分数随着负荷的增加而增加， 温度（Q10=2.3）。 (4)Lowe（眼脑肾）综合征成纤维细胞 显示透明质酸和蛋白多糖合成的正常速率， 硫酸盐化，在正常人中具有很大程度的变异性。 (5)使用 反转运，酪氨酸和其他的溶酶体转运系统 对培养的大鼠甲状腺细胞的中性氨基酸进行表征。 该系统的Q10为1.9，酪氨酸的表观Km为100 M、 类似于质膜L系统。 (6)I细胞（粘脂沉积症II型） 成纤维细胞显示胱氨酸的溶酶体清除受损。 吡哆醇无反应的同型胱氨酸尿患者用甜菜碱治疗 来研究它对骨密度的影响

(1) We demonstrated defective lysosomal cystine transport in leucocytes and fibroblasts from patients with the intermediate (juvenile) and benign (adult) variants of cystinosis. In other studies, the cystine carrier was functional in rat thyroid-derived cells, and required protein synthesis but non N-linked glycosylation for its production. (2) Twenty-five children with cystinosis contributed data toward a national study demonstrating the efficacy of oral cysteamine therapy in enhancing growth and retarding renal failure. At the same time, late complications of cystinosis were described, including cerebral atrophy, impaired salivary function, diabetes mellitus, restrictive pulmonary function, corneal erosions, and reduced visual acuity. One patient received a corneal transplant, and a protocol for treating corneal erosions with cysteamine eyedrops was initiated. Oral cysteamine is being offered to post-renal transplant patients. Carnitine-deficient individuals with Fanconi syndrome are being treated with oral carnitine with some success in normalizing their muscle histology. (3) The second lysosomal storage disorder due to defective transport of a small molecule across the lysosomal membrane is Salla disease, a Finnish disease characterized by psychomotor retardation. Salla fibroblasts store free sialic acid within their lysosomes due to impaired egress of the charged sugar. Egress velocity of sialic acid out of normal lysosome-rich granular frctions increased with increasing loading and temperature (Q10=2.3). (4) Lowe (oculocerebrorenal) syndrome fibroblasts manifested normal rates of hyaluronic acid and proteoglycan synthesis and sulfation, with a large degree of variability among normals. (5) Using counter-transport, a lysosomal transport system for tyrosine and other neutral amino acids was characterized for rat thyroid cells in culture. The system, with a Q10 of 1.9 and apparent Km for tyrosine of 100 M, resembles the plasma membrane L system. (6) I-Cell (Mucolipidosis II) fibroblasts demonstrated impaired lysosomal clearance of cystine. Pyridoxine-nonresponsive homocystinuric patients are treated with betaine to study its effect on bone density.