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Specificity of ubiquitin-positive inclusions in amyotrophic lateral sclerosis

肌萎缩侧索硬化症中泛素阳性包涵体的特异性

基本信息

批准号：
05670578
负责人：
MIZUTANI Tomohiko
金额：
$ 1.28万
依托单位：
Nihon University School of Medicine
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 1994
项目状态：
已结题

项目摘要

Ubiquitin-positive filamentous inclusions have been considered to represent abnormalities specific to amyotrophic lateral sclerosis (ALS). However, the inclusions have not yet been fully investigated in other neurological diseases and non-neurological controls. To evaluate the specificity of the filamentous inclusions, we studied, both immunohistochemically and immunoelectron microscopically, the motor neurons of the lumbosacral cords from 23 patients with ALS,31 patients with 19 different kinds of other neurological diseases (non-ALS) and 37 controls. We stained paraffin-embedded sections of the spinal cords by the avidin-biotin complex method using polyclonal anti-ubiquitin anti-bodies, and examined the anterior horn motor neurons. In ALS,we found 3 kinds of inclusions, i.e.filamentous and granular inclusions, and dense round bodies corresponding to Lewy bodies. Filamentous inclusions were observed in 19 of 23 patients with ALS,and in 1 of 31 non-ALS patients, but were not found in any of the 37 controls. Filamentous inclusions were more frequently observed in ALS patients than in non-ALS patients or controls (p<0.01). The non-ALS patient with filamentous inclusions had a B cell lymphoma which infiltrated the proximal parts of the peripheral nerves, causing marked central chromatolysis in the anterior horn motor neurons. On immunoelectron microscopy, the granular inclusions in ALS contained not only the constituents similar to those of the filamentous inclusions in ALS,but also lipofuscin granules, whereas the filamentous inclusions in the lymphoma patient showed the involvement of ribosomes. Although our data regarding the frequency of the filamentous inclusions further indicate the specificity of the inclusions in ALS,similar, if not identical, inclusions may also be observed in non-ALS patients. This suggests that ubiquitin-positive filamentous inclusions are characteristic of, but not pathognomonic of ALS.

泛素阳性丝状包涵体被认为代表肌萎缩侧索硬化症 (ALS) 特有的异常。然而，这些内含物尚未在其他神经系统疾病和非神经系统控制中得到充分研究。为了评估丝状包涵体的特异性，我们通过免疫组织化学和免疫电子显微镜研究了 23 名 ALS 患者、31 名患有 19 种不同神经系统疾病（非 ALS）的患者和 37 名对照者的腰骶索运动神经元。我们使用多克隆抗泛素抗体，通过亲和素-生物素复合物方法对脊髓的石蜡包埋切片进行染色，并检查前角运动神经元。在ALS中，我们发现了3种包裹体，即丝状包裹体和粒状包裹体，以及与路易体相对应的致密圆体。在 23 名 ALS 患者中的 19 名和 31 名非 ALS 患者中的 1 名中观察到丝状包涵体，但在 37 名对照中均未发现丝状包涵体。与非 ALS 患者或对照组相比，ALS 患者更常见丝状包涵体 (p<0.01)。具有丝状包涵体的非 ALS 患者患有 B 细胞淋巴瘤，该淋巴瘤浸润了周围神经的近端部分，导致前角运动神经元出现明显的中央染色质溶解。免疫电镜观察，ALS的颗粒状包涵体不仅含有与ALS丝状包涵体相似的成分，而且还含有脂褐质颗粒，而淋巴瘤患者的丝状包涵体则显示核糖体的参与。尽管我们关于丝状内含物频率的数据进一步表明了 ALS 中内含物的特异性，但在非 ALS 患者中也可能观察到类似（如果不相同）的内含物。这表明泛素阳性丝状包涵体是 ALS 的特征，但不是其特征。