Ataxia with isolated vitamin E deficiency and retinitis pigmentosa.
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Ataxia↗
Biomedical subjects
T Shimohata
Publications and source records attributed to T Shimohata.
Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch.
To elucidate the molecular mechanisms whereby expanded polyglutamine stretches elicit a gain of toxic function, we expressed full-length and truncated DRPLA (dentatorubral-pallidoluysian atrophy) cDNAs with or without expanded CAG repeats in COS-7 cells. We found that truncated DRPLA proteins containing an expanded polyglutamine stretch form filamentous peri- and intranuclear aggregates and undergo apoptosis. The apoptotic cell death was partially suppressed by the transglutaminase inhibitors cystamine and monodansyl cadaverine (but not putrescine), suggesting involvement of a transglutaminase reaction and providing a potential basis for the development of therapeutic measures for CAG-repeat expansion diseases.
Animals↗
Close associations between prevalences of dominantly inherited spinocerebellar ataxias with CAG-repeat expansions and frequencies of large normal CAG alleles in Japanese and Caucasian populations.
To test the hypothesis that the frequencies of normal alleles (ANs) with a relatively large number of CAG repeats (large ANs) are related to the prevalences of the dominant spinocerebellar ataxias (SCAs)-SCA types 1, 2, 3 (Machado-Joseph disease), 6, and dentatorubral-pallidoluysian atrophy (DRPLA)-we investigated the relative prevalences of these diseases in 202 Japanese and 177 Caucasian families and distributions of the number of CAG repeats of ANs at these disease loci in normal individuals in each population. The relative prevalences of SCA1 and SCA2 were significantly higher in Caucasian pedigrees (15% and 14%, respectively) than in Japanese pedigrees (3% and 5%, respectively), corresponding to the observation that the frequencies of large ANs of SCA1 (alleles >30 repeats) and of SCA2 (alleles >22 repeats) were significantly higher in Caucasians than in Japanese. The relative prevalences of MJD/SCA3, SCA6, and DRPLA were significantly higher in Japanese pedigrees (43%, 11%, and 20%, respectively) than in Caucasian pedigrees (30%, 5%, and 0%, respectively), corresponding to the observation that the frequencies of large ANs of MJD/SCA3 (>27 repeats), SCA6 (>13 repeats), and DRPLA (>17 repeats) were significantly higher in Japanese than in Caucasians. The close correlations of the relative prevalences of the dominant SCAs with the distributions of large ANs strongly support the assumption that large ANs contribute to generation of expanded alleles (AEs) and the relative prevalences of the dominant SCAs.
Asian People↗
Sporadic cases of dentatorubral-pallidoluysian atrophy associated with maternal transmission.
We report siblings, a 21-year-old woman (proband) and her 26-year-old brother, with dentatorubral-pallidoluysian atrophy (DRPLA). There was no family history of DRPLA and no clinical abnormalities in their parents, who were both above the age of 50. Analysis of the DRPLA gene of leukocytes showed CAG repeat sizes to be 64/17 in the proband, 58/20 in her brother, and 56/8 in their mother. Sporadic cases of DRPLA can occur with maternal as well as paternal transmission.
Adult↗
[A case of late adult-onset dentatorubral-pallidoluysian atrophy (DRPLA) successfully treated with V-P shunt operation].
A 44-year-old Japanese man was diagnosed as having late adult-onset dentatorubral-pallidoluysian atrophy (DRPLA), whose CAG repeats in the DRPLA gene were 60 and 15. He developed gait disturbance, limb ataxia, pyramidal tract signs, dementia, and psychiatric symptoms including character changes within a few years of the above diagnosis. His T 2-weighted brain MRI showed symmetric high-signal lesions in the cerebral white matter and brain stem, in addition to cerebellar, brain stem, and cerebral cortical atrophy. Since the results of RI cisternography indicated that he manifested the clinical features of normal pressure hydrocephalus (NPH), V-P shunt operation was done. In a week after the operation, his gait disturbance, pyramidal tract signs, dementia and psychiatric symptoms were remarkably improved. White matter lesions have been thought to be concomitant with late adult-onset DRPLA patients, but some of these patients may have characteristics of NPH pathophysiology.
Adult↗
Atrophy of the cerebellum and brainstem in dentatorubral pallidoluysian atrophy. Influence of CAG repeat size on MRI findings.
To elucidate how the size of the expanded CAG repeat of the gene for dentatorubral pallidoluysian atrophy (DRPLA) and other factors affect the atrophy of the brainstem and cerebellum, and the appearance of high-intensity signals on T2-weighted MRI of the cerebral white matter of patients with DRPLA, we quantitatively analyzed the MRI findings of 26 patients with DRPLA, the diagnosis of which was confirmed by molecular analysis of the DRPLA gene. When we classified the patients into two groups based on the size of the expanded CAG repeat of the DRPLA gene (group 1, number of CAG repeat units > or = 66; group 2, number of CAG repeat units < or = 65), we found strong inverse correlations between the age at MRI and the areas of midsagittal structures of the cerebellum and brainstem in group 1 but not in group 2. Multiple regression analysis, however, revealed that both the patient's age at MRI and the size of the expanded CAG repeat correlated with the areas of midsagittal structures. Involvement of the cerebral white matter as detected on T2-weighted images was observed more frequently in patients belonging to group 2 than in group 1 patients. Furthermore it was demonstrated that high-intensity signals can be detected on T2-weighted images of the cerebral white matter of patients with a largely expanded CAG repeat (group 1) in their thirties. These results suggest that patient age as well as the size of the expanded CAG repeat are related to the degree of atrophy of the brainstem and cerebellum, and the white matter changes in patients with DRPLA.
Adolescent↗
[Adult onset Still's disease with a brainstem lesion demonstrated on MRI].
We report a 39-year-old man with seven-year history of adult onset Still's disease (AOSD) who developed left abducens palsy and ataxic gait. T2-weighted MRI demonstrated high-intensities in the left side of the lower pons, including nucleus abducens and the inferior cerebellar peduncle, and in the right anteromedial portion of the thalamus corresponding to his neurological abnormalities. He responded favorably to corticosteroid treatment, and the high-intensities in the T2-weighted MRI diminished subsequently. Previously, he had developed bilateral sensorineural hearing loss which had responded to corticosteroid treatment during an exacerbation of the disease. There was no evidence of multiple sclerosis or other systemic diseases affecting the central nervous system (CNS) in the laboratory findings. Although the precise reason for the MRI lesions was unclear, we thought they were CNS manifestations of Still's disease. We suggest that AOSD is one of the causes of focal CNS involvement in young adults, particularly who has a history of fever of unknown origin.
Abducens Nerve↗
Demonstration of serum-neutralising antibody to turkey rhinotracheitis virus in serum from chicken flocks in Japan.
Since between 1989 and 1991, broiler, broiler breeder and layer chickens reared in three different prefectures of Japan, Hyogo, Ibaraki, and Miyazaki, were diagnosed clinically as having swollen head syndrome (SHS) these flocks were survey for antibody to turkey rhinotracheitis (TRT) virus using a serum neutralisation (SN) test. TRT-specific SN antibody was found in flocks of chickens in 2 out of the 3 prefectures. Thereafter, particular in the summers of both 1993 and 1994 outbreaks of SHS occurred in almost all areas of major chicken production in Japan. Almost chicken flocks affected by SHS possessed TRT SN antibody. No chicken sera collected between 1972 and 1988 possessed any SN antibody to TRT virus. It is suggested that in Japan, TRT virus is widely prevalent in areas of major poultry production.
Animals↗
[A patient with aneurysm of extracranial internal carotid artery presenting lower cranial polyneuropathy similar to Tapia's syndrome].
Tapia's syndrome, first described in 1904 by A.G. Tapia, is considered to be a syndrome consisting of ipsilateral hemiplegia of larynx and tongue with spared movement of soft palate. A 61-year-old Japanese woman had been in good health until August 1991, when she developed hoarseness and atrophy of the left side of her tongue. Although she also showed mild disturbance of elevation of bilateral soft palates and loss of taste in the posterior third of her tongue as well, the main symptoms were the paralyses of the ipsilateral larynx and tongue without involvement of the ipsilateral sternocleidomastoid and trapezius muscles. We concluded that she had cranial polyneuropathy similar to that of Tapia's syndrome. A carotid angiography revealed that she has a large aneurysm, which originated from the extracranial internal carotid artery in the region near the skull base. No other abnormal findings were detected by any computed tomography, magnetic resonance imaging or 67Ga-scintigraphy. The patient's lower cranial polyneuropathy was considered to be caused by the aneurysm. A survey of the literature indicates that extracranial carotid aneurysm is an extremely rare cause of Tapia's syndrome. In this case, the location of the aneurysm, which was present considerably distant from the skull base, seems to be the reason for the sparing of the accessory nerve.
Aneurysm↗