Studies of porphyrin metabolic disorder and early diagnosis in porphyria with photodermatological manifestation.

卟啉代谢紊乱的研究和具有光皮肤病表现的卟啉症的早期诊断。

基本信息

批准号：
60570473
负责人：
KONDO Masao
金额：
$ 0.83万
依托单位：
The Institute of Public Health
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1986
项目状态：
已结题

项目摘要

1. The development of method in early stage of porphyria. I established a method of simultaneaus measurement of urinary, pheripheral blood, and fecal porphyrins by high-performance liquid chromatography. This method can be used as a routine method for mass screening of diagnosis in patients with porphyria.2. The mechanism of abnormalities of porphyrin metabolism in four types of porphyria with photodermatological manifestation.Approximately 60 cases in porphyrias obtained were subjected to the clinical and biological investigations, in which the activities of five enzymes out from the eight heme biosynthetic enzymes and also the content of porphyrins and two precursors, ALA and PBG in the bioptic materials from liver, bone marrow and peripheral blood were determined. Several methods and experimental techniques were newly devised or developed during this study.Hepatic ALA dehydratase activity in PCT patients were markedly decreased. Summarizing the present experiments on ALA dehydratase enzyme, the decrease activity to be caused by a decreased in the enzyme protein. From the present rat experiments, it was found that alcohol, estrogen and hexachlorobenzene treated rats showed no change in hepatic ALA dehydratase activity compared to controls, postulating an enzymatic discrepancy between PCT patients and experimental PCT.Two cases that markedly decreased of erythrocyte URO'gen decarboxylase activity was found in PCT patients.The enzymes activities and porphyrin metabolites of heme biosynthesis were determined in 15 patients in EPP, 6 cases of VP and 7 cases of CP. As the results, ALA synthase activity was found to be markedly increased in VP. Furthermore, author made a basic data for diagnosis of porphyrias.3. The clinical statistics in porphyrias. All the cases of porphyria ever reported in Japan were collected and subjected to clinical statistics and epidemiological observation in order to summarize the current informations about porphyrias in Japan.

1. 卟啉症早期方法的开发。我建立了一种用高效液相色谱法同时测定尿液、外周血和粪便中卟啉的方法。该方法可作为卟啉症患者大规模筛查诊断的常规方法。 2．四种具有光皮肤病表现的卟啉症的卟啉代谢异常机制。对获得的约60例卟啉症进行了临床和生物学研究，其中8种血红素生物合成酶中5种酶的活性以及测定了肝脏、骨髓和外周血活检材料中的卟啉和两种前体 ALA 和 PBG。本研究期间新设计或开发了几种方法和实验技术。PCT患者的肝脏ALA脱水酶活性显着降低。总结目前对ALA脱水酶的实验，活性降低是由于酶蛋白的减少造成的。从目前的大鼠实验中发现，与对照组相比，酒精、雌激素和六氯苯治疗的大鼠的肝脏 ALA 脱水酶活性没有变化，推测 PCT 患者和实验性 PCT 之间存在酶学差异。两例红细胞 URO'gen 显着降低在PCT患者中发现了脱羧酶活性。对15名患者中血红素生物合成的酶活性和卟啉代谢物进行了测定。 EPP 6 例，VP 6 例，CP 7 例。结果发现，VP中ALA合酶活性显着增加。此外，作者还为卟啉症的诊断奠定了基础数据。 3．卟啉症的临床统计。收集日本所有报告的卟啉症病例，进行临床统计和流行病学观察，总结日本卟啉症的最新信息。