1 0 0 0 OA 日本のValosin-containing protein関連筋萎縮性側索硬化症
1 0 0 0 OA 洞機能不全症候群および起立性頻脈症候群をきたした多発性硬化症の1例
- 著者
- 谷掛 万里 降矢 芳子 形岡 博史 川原 誠 平野 牧人 上野 聡
- 出版者
- 公益社団法人 日本リハビリテーション医学会
- 雑誌
- The Japanese Journal of Rehabilitation Medicine (ISSN:18813526)
- 巻号頁・発行日
- vol.45, no.8, pp.535-540, 2008-08-18 (Released:2008-09-18)
- 参考文献数
- 16
- 被引用文献数
- 1
A 19-year-old girl was admitted to our hospital with nausea, vomiting, hiccups, constipation and syncope. After hiccups or vomiting sinus arrest developed and lasted more than 5-8 seconds. She lost consciousness every one hour. Based on an electrocardiographic diagnosis of sick sinus syndrome (SSS), a temporary pacemaker was implanted. The next day, although her syncope and bradycardia disappeared, she had orthostatic tachycardia of over 120 beats/minute and swelling of the legs, which led to a diagnosis of postural orthostatic tachycardia syndrome (POTS). Neurologically, she showed the right-sided tongue deviation and parasympathetic system disorders revealed by coefficient of variation of R-R interval (CVR-R), the Achner eye-ball pressure test, the valsalva ratio, and the head-up-tilt test. Brain MRI disclosed a small hyperintense lesion on a T2-weighted image with gadolinium enhancement in the right dorsal medulla including the hypoglottis nucleus and the posterior nucleus of vagus. After steroid pulse therapy (methyl prednisolone 1 g/day×3 days, 5 times) was administered, this lesion became smaller and finally disappeared. Before the lesion disappeared, she was able to begin rehabilitation by wearing elastic stockings and treatment with midodrine hydrochloride. The following year, she developed other MRI-proven brain lesions, suggestive of demyelination. Such a spinal and temporal distribution of lesions led to a diagnosis of multiple sclerosis (MS). A case of POTS caused by MS has not been reported previously, however, MS often affects the medullary paraventricular regions associated with autonomic failures. Autonomic failures often prevent patients from experiencing early rehabilitations. We should promptly give symptomatic treatment against autonomic failures, which leads to good patient recovery not only in patient vitality but also functionality.
1 0 0 0 OA 神経変性疾患原因蛋白の核内輸送と発症機序解明
本研究の目的は種々の神経変性疾患原因蛋白の核内輸送に関して、運動ニューロン病様Triple A症候群(AAAS)の原因である核膜孔蛋白アラジンに依存性であるかを検討し、本疾患で障害を受けやすい古典的な核局在シグナル(NLS)以外の輸送シグナル同定と輸送機序の解明である。本研究により小脳失調原因蛋白アプラタキシンのみAAASの輸送障害を受け、他の原因蛋白は障害を受けないことが判明した。また、核内輸送障害を受けないDNA修復蛋白であるXRCC1において、輸送障害を改善するために重要なのは、古典的NLS(239-266残基)の下流267-276残基であることを同定した。この部位を含む新規NLS(239-276残基)38アミノ酸配列をminimum essential sequence of stretched nuclear localization signal(mstNLS)と名付けた。mstNLSを融合すると、輸送障害を受けていた小脳失調原因蛋白アプラタキシンはAAAS患者細胞の核内に効率よく輸送された。さらに、mstNLSは酸化ストレス下の正常細胞においても、強力な核局在シグナルとなることが証明された。以上から本研究成果は、AAASの病態機序改善のみならず、核内輸送研究に貢献しうると考えられる。