Mechanism of amyloid formation in amyloidosis : Clinical, biochemical, and pathological study

淀粉样变性中淀粉样蛋白形成的机制：临床、生化和病理学研究

• 批准号: 06670660
• 负责人: ANDO Yukio
• 金额: $ 1.34万
• 依托单位: KUMAMOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670660/
• 关键词: FAP; Amyloidosis; Transthyretin; Liver transplantation; Lipoprotein; LDL; Gene mutation; Polyneuropathy; Lipoprotein; トランスジェニックマウス; 自律神経

We found out that variant transthyretin (TTR) circulates bound to both HDL and LDL.In HDL from FAP patients, almost the same levels of normal and variant TTR was detected while only variant TTR was observed in extracted LDL : 0.6% of the circulated TTR was associated with LDL.This phenomenon was also seen in LDL from other points of mutation, such as Gln89, Pro36, and Thr34. Incubation of extracted LDL and with variant and normal TTR revealed that variant form of TTR increased the affinity to LDL.Five FAP patients underwent liver transplantation at Huddinge Hospital, Sweden, and Brisbane Princess Alexandra Hospotal. They all had good clinical couese 5-24 months after the operation. As we reported previously, especially autonomic dysfunction improved significantly.Gene hunting for TTR mutations in FAP was also tried to perfom using low and high temperature controlling water bath.

我们发现，在FAP患者的HDL中，正常和变异TTR的水平几乎相同，而在提取的LDL中仅观察到变异TTR：0.6%的循环TTR与LDL相关。这种现象也见于其他突变点的LDL，如Gln 89，Pro36和Thr 34。提取的LDL与变体和正常TTR的孵育显示，TTR的变体形式增加了对LDL. FAP患者的亲和力在瑞典的Huddinge医院和布里斯班公主Alexandra Hospotal接受肝移植。术后5-24个月临床疗效良好。如我们以前报道的那样，尤其是植物神经功能紊乱明显改善。我们还尝试了用低温和高温控制水浴进行FAP中TTR突变的基因狩猎。

项目成果

Ando Yukio: "Radiolabelled metaiodobenzylguanidine in assessment of autonomic dysfunction." Lancet. 343. 984-985 (1994)

Ando Yukio：“放射性标记的间碘苄胍用于评估自主神经功能障碍。”

Tashima K,Ando Y,Tanaka Y,Uchino M,Ando M.: "Change in the age of onset in patients with familial amyloidotic polyneuropathy Type I." Internal Med. 34. 748-750 (1995)

Tashima K、Ando Y、Tanaka Y、Uchino M、Ando M.：“I 型家族性淀粉样变性多发性神经病患者发病年龄的变化。”

Ando Y: "Radiolabelled meta-iodobenzylguanidine in assessment of autonomic dysfunction." Amyloid. 2. 183-187 (1995)

Ando Y：“放射性标记的间碘苄基胍用于评估自主神经功能障碍。”

安東 由喜雄: "家族性アミロイドーシス患者の自律神経障害" 末梢神経. 5. 15-21 (1995)

安藤幸雄：“家族性淀粉样变性患者的自主神经病变”《周围神经》，5. 15-21 (1995)。

Ando Y: "Change in variant transthyretin levels in patients with familial amyloidotic polyneuropathy Type I following liver transplantation." Biochem Biophys Res Commun. 211. 354-358 (1995)

Ando Y：“肝移植后 I 型家族性淀粉样变性多发性神经病患者变异转甲状腺素蛋白水平的变化。”