Ataxia with isolated vitamin E deficiency and retinitis pigmentosa.
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Ataxia↗
Biomedical subjects
S Tsuji
Publications and source records attributed to S Tsuji.
Progressive atrophy of cerebellum and brainstem as a function of age and the size of the expanded CAG repeats in the MJD1 gene in Machado-Joseph disease.
Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disease characterized by cerebellar ataxia associated to varying degrees with pyramidal signs, extrapyramidal signs, or peripheral amyotrophy. It is caused by unstable expansion of the CAG repeat in the MJD1 gene on chromosome 14q32.1. To determine how the neurodegenerative process in the central nervous system of patients with MJD correlates with the size of expanded CAG repeats in the MJD1 gene and other factors, we performed detailed quantitative analyses of findings of magnetic resonance imaging of the central nervous system of 21 patients with MJD of various ages and with various sizes of expanded CAG repeats. We found that atrophy of the brainstem and cerebellar vermis in MJD patients is closely correlated not only with the size of expanded CAG repeat in the MJD1 gene but also with patient age, which suggests that the neurodegenerative process in MJD is regulated by the size of expanded CAG repeats as well as by the patient age.
Adult↗
Genetic polymorphism of the tau gene and neurodegenerative diseases with tau pathology among Japanese.
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Humans↗
No ataxia and no Purkinje cell loss in newborn young of SJL mice with anti-Yo antibody.
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Animals↗
Failure to detect cytotoxic T cell activity against recombinant Yo protein using autologous dendritic cells as the target in a patient with paraneoplastic cerebellar degeneration and anti-Yo antibody.
Paraneoplastic neurological syndromes are believed to be autoimmune neuronal degenerations that develop in some patients with systemic cancer. Although a high titer of anti-Yo antibody has been found in the sera and cerebrospinal fluid of patients with paraneoplastic cerebellar degeneration (PCD), the role of anti-Yo antibody in Purkinje cell loss has not been shown. Previously we found that all of nine Japanese patients with PCD who harbored anti-Yo antibody had HLA A24. In this present study we have examined cytotoxic T cell (CTL) activity against recombinant Yo protein in peripheral blood of a patient with PCD and anti-Yo antibody using autologous dendritic cells as the target. We did not detect CTL activity against Yo protein, though, this study does not exclude the possibility of the involvement of CTL in the development of PCD.
Autoantibodies↗
Asymmetries of benzodiazepine receptor binding potential in the inferior medial temporal lobe and cerebellum detected with 123I-iomazenil SPECT in comparison with 99mTc-HMPAO SPECT in patients with partial epilepsy.
We examined the relation between regional 123I-iomazenil (IMZ) parameters and cerebral blood flow (CBF) to evaluate the difference between the quantitative parameters of IMZ and the CBF in detecting epileptic abnormality. Seventeen patients with unilateral partial epilepsy were subjected to 99mTc-hexamethylpropylene amine oxime (HMPAO) SPECT, and early and delayed IMZ SPECT. Then we quantitatively obtained the blood-to-brain transfer constants (K1) and binding potentials (BP) for nine regions of interest, and the regional CBF was also by using the simple angiographic method. From our data, significant asymmetries of BP in the inferior medial temporal lobe and cerebellum were shown and may be related to a remote effect such as crossed cerebellar diaschisis. In conclusion, the asymmetry of BP with iomazenil SPECT was demonstrated in patients with unilateral epilepsy that was not detectable by HMPAO SPECT.
Adult↗
99mTc-tetrofosmin uptake in bone metastases from breast cancer.
99mTc-tetrofosmin myocardial imaging was performed in a 62-year-old woman who had undergone standard radical mastectomy for right breast cancer 6 years ago. Although the result was negative for the ischemic heart disease, it showed abnormal accumulation corresponding to the bone metastases in the spine. We believe that 99mTc-tetrofosmin imaging is helpful in detecting bone metastases from breast cancer.
Bone Neoplasms↗
Pick's disease: selective occurrence of apolipoprotein E-immunoreactive Pick bodies in the limbic system.
We carried out immunohistochemical examination of apolipoprotein E (apoE) in brains from two patients with Pick's disease. In these cases 1 and 2, the APOE genotypes were epsilon 3/4 and epsilon 3/3, respectively. In both cases, numerous argyrophilic globular intraneuronal inclusions, Pick bodies (PBs), were distributed widely throughout the brain, and immunohistochemically were occasionally positive for apoE. Interestingly, such apoE-immunoreactive PBs were virtually restricted to neurons in the limbic system; in the dentate gyrus, the proportion of apoE-immunoreactive PBs relative to the total number of argyrophilic PBs was 5.0% in case 1 and 2.7% in case 2, whereas in the frontal and temporal neocortices it was less than 0.1% in both cases. Diffuse cytoplasmic immunoreactivity for apoE was found in only a few limbic system neurons without PBs in both cases. In conclusion, it is considered that apoE may not be positively involved in the process of PB formation and that the preferential distribution of apoE-immunoreactive PBs in the limbic system may reflect the presence of certain regional factors associated with the synthesis or metabolism of apoE in this particular system.
Aged↗
Autosomal dominant cerebellar ataxia (SCA6): clinical, genetic and neuropathological study in a family.
We describe a family with dominantly inherited ataxia of late adult onset. Expansion of a CAG repeat in the gene encoding the alpha1A voltage-dependent calcium channel was identified at autopsy in one patient, a 65-year-old woman with a disease duration of 11 years. In this patient, pathological changes were confined to the cerebellar cortex and inferior olivary complex. The cerebellar cortex showed severe loss of Purkinje cells with proliferation of Bergmann's glia, being more pronounced in the superior parts of the vermis and hemispheres. In the inferior olivary complex, a reduced neuronal cell population, which could be interpreted as a change secondary to the cerebellar cortical lesion, was evident. We conclude that the pathological phenotype of this newly classified autosomal dominant cerebellar ataxia, SCA6, is cerebello-olivary atrophy, or more strictly cerebellar cortical atrophy.
Aged↗
Apolipoprotein E epsilon4 allele and progression of cortical Lewy body pathology in Parkinson's disease.
To elucidate whether the apolipoprotein E epsilon4 allele (APOE4) affects cortical neuropathology in Parkinson's disease (PD), we determined APOE genotypes and quantified the densities of cortical Lewy bodies (LBs), amyloid plaques and neurofibrillary tangles in 22 autopsy-proven PD cases (12 with dementia; 10 without dementia) that were not accompanied by Alzheimer's disease. The APOE4 frequency in the demented patient group was 0.21, which was significantly higher than that in Japanese controls (P < 0.04). LB densities in demented PD patients were significantly higher than those in non-demented PD patients, despite the shorter disease duration in the former. Moreover, plaque density in the temporal cortex and LB density in the cingulate cortex were significantly higher in the group with APOE4 than in that without the allele. There was no difference in tangle density between these two groups. These results suggest that APOE4 may influence the increase in the number of cortical LBs and amyloid plaques in PD. It is possible that when PD occurs in individuals with APOE4, concomitantly evolving cortical LB pathology in a proportion of cases results in limbic (transitional) or neocortical-type LB disease.
Aged↗
Hereditary dentatorubral-pallidoluysian atrophy: ubiquitinated filamentous inclusions in the cerebellar dentate nucleus neurons.
We examined the cerebellar dentate nucleus (CDN) in 16 patients with hereditary dentatorubral-pallidoluysian atrophy (DRPLA), one of the neurodegenerative diseases caused by expansion of a CAG repeat encoding a polyglutamine tract in the disease protein. In all patients, some CDN neurons were found to contain ubiquitinated filamentous inclusions in their cytoplasm. On hematoxylin and eosin preparations, these filamentous inclusions were eosinophilic, basophilic or amphophilic, and were often found in areas of pale cytoplasm. Electron microscopy revealed that they consisted of bundles of filaments that were somewhat thicker than neurofilaments. These features of the present inclusions were indistinguishable from those of skein-like inclusions (SLI) previously described in the lower motor neurons in sporadic amyotrophic lateral sclerosis. We conclude that SLI can also occur in the CDN in DRPLA and believe that they reflect a characteristic pathological process in this disease.
Adolescent↗
Autosomal dominant diffuse Lewy body disease.
We describe a Japanese family with parkinsonism and later-onset dementia. The proband developed parkinsonism at the age of 61 years, followed by dementia starting when she was 67. Her uncle, who was also her husband, died at the age of 78 years after 7- and 5-year histories of parkinsonism and dementia, respectively. Pathological examination of these two patients showed marked neuronal loss with Lewy bodies (LBs) in the brain stem pigmented nuclei and numerous cortical LBs and ubiquitin-positive hippocampal CA2/3 neurites were observed. The proband also had many amyloid plaques. Their two sons developed similar parkinsonism at the ages of 39 and 28 years and also suffered later-on-set dementia. The apolipoprotein E genotype of the proband, her uncle and one of their sons was epsilon3/4 and that of the other son was epsilon4/4. These findings strongly suggest that this family has autosomal dominant diffuse LB disease.
Aged↗
Dentatorubropallidoluysian atrophy: clinicopathological study of dementia and involvement of the nucleus basalis of Meynert in seven autopsy cases.
This report concerns a clinicopathological study including a quantitative pathological study on the nucleus basalis of Meynert (nbM) of seven Japanese autopsy cases (four male, three female) of dentatorubropallidoluysian atrophy (DRPLA) with special reference to the clinicopathological correlation of dementia in DRPLA. In each case the pattern of the inheritance was consistent with that of an autosomal dominant trait. The neurological examination revealed that all seven individuals had cerebellar signs. Six patients had epilepsy and choreoathetoid involuntary movement; myoclonus was evident in five patients. Dementia was noted in all seven patients. Degeneration of the globus pallidus (particularly the lateral segment) and of the dentate nucleus was the principal pathological feature. Brain weights at autopsy ranged from 1020 to 1400 g (average 1241 g: male 1320 g, female 1135 g). The quantitative evaluation revealed no significant loss of neurons in the nbM as compared with a control group. There was no clinicopathological correlation between dementia and involvement of the nbM. We suggest that the dementia of DRPLA is due not to the involvement of the nbM, but to - as yet - unidentified pathology elsewhere.
Adolescent↗
Hereditary dentatorubral-pallidoluysian atrophy: detection of widespread ubiquitinated neuronal and glial intranuclear inclusions in the brain.
We examined the brains and spinal cords of seven patients with clinicopathologically and genetically confirmed hereditary dentatorubral-pallidoluysian atrophy (DRPLA) using an antibody against ubiquitin, and found small, round immunoreactive intranuclear inclusions in both neurons and glial cells in various brain regions. Ubiquitinated neuronal intranuclear inclusions (uNIIs) were consistently found in the striatum, the pontine nuclei, the inferior olivary complex, the cerebellar cortex and the dentate nucleus. Ubiquitinated glial intranuclear inclusions (uGIIs) were found less frequently than uNIIs. Most of the inclusion-bearing nuclei were of an astrocytic nature. Immunostaining with an antibody against DRPLA protein revealed similar immunoreactive neuronal and glial intranuclear inclusions, but in much smaller in numbers compared with uNIIs and uGIIs. Electron microscopy showed that such inclusions were composed of granular and filamentous structures. These findings strongly suggest that, in DRPLA, the occurrence of uNIIs and uGIIs is directly related to the causative gene abnormality (an expanded CAG repeat encoding polyglutamine), that neurons are affected much more widely than previously recognized and that glial cells are also involved in the disease process.
Adult↗
Transcortical sensory aphasia following left frontal infarction.
Two right-handed patients who exhibited language disability after left frontal infarction are described. The patients spoke fluently and exhibited excellent repetition ability from the onset of infarction without exhibiting any oral apraxia, but had deficits in auditory comprehension, naming, reading and writing. In both patients, brain magnetic resonance imaging (MRI) revealed infarction in the left inferior frontal gyrus, the middle frontal gyrus and the anterior part of the lower precentral gyrus. Single photon emission computed tomography (SPECT) revealed decreased blood flow in the same regions as those shown to be infarcted by MRI. The MRI and SPECT findings and the symptoms of these patients suggest that left frontal lesions that encompass Broca's area produce fluent aphasia if the posterior part of the left precentral gyrus or motor cortex remains intact and that lesions anterior to Broca's area and the middle frontal gyrus produce a deficit in auditory comprehension of single words as well as sentences.
Aphasia, Wernicke↗
Dermatofibrosarcoma protuberans with fibrosarcomatous areas. Molecular abnormalities of the p53 pathway in fibrosarcomatous transformation of dermatofibrosarcoma protuberans.
Fibrosarcomatous (FS) change in a rare, but well-known phenomenon encountered in dermatofibrosarcoma protuberans (DFSP), and an increased chance in an adverse outcome has been suggested in patients with DFSP having FS areas (DFSP-FS). As altered p53 pathway has been suggested as having a potential role in tumour progression, we analysed the p53 gene and p53 protein together with the p53-related protein mdm2 and p21Waf1 in 5 cases of DFSP-FS and 13 of DFSP to ascertain whether the p53 pathway correlates to the fibrosarcomatous transformation of DFSP. Three of the five DFSP-FSs overexpressed p53 protein immunohistochemically, and one of them had a "missense" mutation of the p53 gene without immunohistochemical overexpression of mdm2 or p21Waf1. The other two DFSP-FSs with p53 overexpression demonstrated increased labelling indices of both mdm2 and p21Waf1. The three DFSP-FS patients with overexpression of p53 protein had frequent local recurrences, ranging from 3 to 5 in number with increasingly short intervals (mean 4.5 years), while one of the other two had no recurrences and the other, only one. None of the 13 DFSPs showed any alterations in the p53 gene or overexpressions of p53, mdm2 and p21Waf1, except for one DFSP having a "silent" mutation of the p53 gene. Three DFSPs had local recurrences once or twice with longer intervals to recurrence (mean 10.3 years). Although the number of cases examined is limited, the results suggest that alterations in the p53 pathway, such as overexpression of p53 protein by a mutated gene and mdm2 overexpression, are involved in fibrosarcomatous transformation in a subset of fibrohistiocytic tumours and possibly correlated with its more locally aggressive behaviour than that without p53 alterations or ordinary DFSP.
Adolescent↗
Refinement of the gene locus for autosomal recessive juvenile parkinsonism (AR-JP) on chromosome 6q25.2-27 and identification of markers exhibiting linkage disequilibrium.
Autosomal recessive juvenile parkinsonism (AR-JP) (MIM 600116) is a hereditary neurodegenerative disorder characterized by levodopa-responsive parkinsonism with a mean age at onset of 23.2 years. We recently mapped the AR-JP gene locus to a 17-cM interval on chromosome 6q25.2-27. To further narrow the candidate region of the AR-JP gene, we performed detailed linkage analysis using densely placed genetic markers in this region (D6S437, D6S1581, D6S1579, D6S305, D6S411, SOD2, D6S253, D6S1599, D6S1719 and D6S264). Pairwise linkage analysis revealed the highest cumulative maximal lod score of 9.13 at D6S1579 (theta = 0.05), and multipoint linkage analysis revealed the highest cumulative lod score of 12.4 at the locus 3 cM telomeric to D6S1599. Observation of obligate recombination events narrowed the candidate region to a 13-cM region between D6S1579 and D6S264. Furthermore, we identified two marker loci, D6S1579 and D6S1599, which exhibit strong linkage disequilibrium with the AR-JP locus: chi 2 (2 x n table) = 84.22; P < 0.0001, chi 2 [likelihood-ratio test (LRT)] = 20.66; P < 0.0001, lambda = 0.40 and chi 2 (2 x n table) = 63.37; P < 0.0001, chi 2 (LRT) = 10.32; P < 0.0001, lambda = 0.30, respectively. These results suggest that the candidate region for the AR-JP gene is most likely located near the 4-cM region encompassing D6S1579 and D6S1599.
Adult↗
Detection of SYT-SSX fusion transcripts in synovial sarcoma by reverse transcription-polymerase chain reaction using archival paraffin-embedded tissues.
The reciprocal translocation t(X;18)(p11;q11) is known to be highly characteristic of synovial sarcoma, and its consequence, an SYT-SSX fusion gene, is expected to be a diagnostic molecular marker. In this study, we conducted a reverse transcription-polymerase chain reaction-based assay to detect the SYT-SSX fusion gene transcripts using archival formalin-fixed, paraffin-embedded tumor specimens from a series of 32 synovial sarcoma cases including 6 tumors found in unusual anatomical sites. The SYT-SSX fusion transcripts could be detected in 30 of 32 paraffin-embedded specimens (94%). A subsequent sequence analysis using the polymerase chain reaction products confirmed that the detected messages were derived from either the SYT-SSX1 (22 cases) or SYT-SSX2 (8 cases) fusion gene. Of 23 SYT-SSX-positive monophasic tumors, 16 tumors had an SYT-SSX1 fusion transcript. Fusion transcripts were detectable in all the 7 biphasic tumors analysed, one of which had an SYT-SSX2 fusion transcript. All of the six tumors at unusual locations (lung; 3, metastasis to the abdominal cavity from a tumor of retroperitoneal origin; 1, sacral region; 1, iliopsoas muscle; 1) contained detectable messages. Our results indicate that this molecular assay can be applied to archival formalin-fixed, paraffin-embedded tumor tissues as a feasible and reliable molecular technique for the diagnosis of synovial sarcoma.
Adolescent↗