9 results on '"Ikeuchi T"'
Search Results
2. Sporadic ALS with compound heterozygous mutations in the SQSTM1 gene.
- Author
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Shimizu H, Toyoshima Y, Shiga A, Yokoseki A, Arakawa K, Sekine Y, Shimohata T, Ikeuchi T, Nishizawa M, Kakita A, Onodera O, and Takahashi H
- Subjects
- Adaptor Proteins, Signal Transducing metabolism, Aged, Amyotrophic Lateral Sclerosis diagnosis, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Heterozygote, Humans, Inclusion Bodies metabolism, Male, Motor Neurons metabolism, Motor Neurons pathology, Mutation genetics, Sequestosome-1 Protein, Adaptor Proteins, Signal Transducing genetics, Amyotrophic Lateral Sclerosis genetics, Genetic Predisposition to Disease genetics
- Abstract
Accumulating evidence suggests that heterozygous mutations in the SQSTM1 gene, which encodes p62 protein, are associated with amyotrophic lateral sclerosis (ALS). Here, we report a Japanese patient with sporadic, late-onset ALS who harbored compound heterozygous SQSTM1 mutations (p.[Val90Met];[Val153Ile]). Autopsy examination revealed that although TDP-43 pathology was rather widespread, the selective occurrence of p62-positive/TDP-43-negative cytoplasmic inclusions in the lower motor neurons (LMNs) was a characteristic feature. No Bunina bodies were found. Ultrastructurally, p62-positive cytoplasmic inclusions observed in the spinal anterior horn cells were composed of aggregates of ribosome-like granules and intermingled bundles of filamentous structures. Another feature of interest was concomitant Lewy body pathology. The occurrence of distinct p62 pathology in the LMNs in this patient indicates the pathogenic role of SQSTM1 mutations in the development of a subset of ALS.
- Published
- 2013
- Full Text
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3. Involvement of Onuf's nucleus in Machado-Joseph disease: a morphometric and immunohistochemical study.
- Author
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Shimizu H, Yamada M, Toyoshima Y, Ikeuchi T, Onodera O, and Takahashi H
- Subjects
- Adult, Aged, Ataxin-3, DNA-Binding Proteins metabolism, Female, Humans, Inclusion Bodies metabolism, Inclusion Bodies pathology, Intranuclear Inclusion Bodies metabolism, Intranuclear Inclusion Bodies pathology, Machado-Joseph Disease complications, Machado-Joseph Disease genetics, Male, Middle Aged, Motor Neurons classification, Motor Neurons pathology, Nerve Tissue Proteins metabolism, Nuclear Proteins metabolism, Repressor Proteins metabolism, Statistics, Nonparametric, Trinucleotide Repeat Expansion genetics, Ubiquitin metabolism, Urinary Incontinence etiology, Cell Nucleus metabolism, Cell Nucleus pathology, Machado-Joseph Disease pathology, Motor Neurons ultrastructure, Spinal Cord pathology
- Abstract
Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disease caused by an expansion of CAG repeats in the MJD1 gene, in which lower urinary tract dysfunction is known to be the most commonly encountered autonomic failure. However, it remains unclear whether Onuf's nucleus (ON), which plays major roles in the micturition reflex and voluntary continence, degenerates during the disease process. In the present study, we conducted a morphometric and immunohistochemical study of ON, together with the lateral nuclear group (LNG) of the sacral anterior horns, in seven patients with MJD. When compared with controls, the number of lower motor neurons in both ON and LNG was significantly smaller in the MJD patients, the former being inversely correlated with the size of the expanded CAG repeats. Notably, MJD patients with a large CAG-repeat expansion showed an ON-predominant pattern of neuronal loss, while in the remaining patients, ON and LNG were affected to a similar degree, or rather an LNG-predominant pattern of neuronal loss was evident. Moreover, when adjusted for age, the degree of neuronal loss in both ON and LNG was significantly correlated with the extent of expansion of the CAG repeats. In MJD, the remaining lower motor neurons in ON often exhibited ataxin-3- or 1C2-immunoreactive (ir) neuronal intranuclear inclusions, while no pTDP-43-ir neuronal cytoplasmic inclusions were present in these neurons. In conclusion, the present findings strongly suggest that neuronal loss in ON, the degree of which is highly influenced by the extent of expansion of CAG repeats, is a consistent feature in MJD.
- Published
- 2010
- Full Text
- View/download PDF
4. Sporadic four-repeat tauopathy with frontotemporal lobar degeneration, Parkinsonism, and motor neuron disease: a distinct clinicopathological and biochemical disease entity.
- Author
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Fu YJ, Nishihira Y, Kuroda S, Toyoshima Y, Ishihara T, Shinozaki M, Miyashita A, Piao YS, Tan CF, Tani T, Koike R, Iwanaga K, Tsujihata M, Onodera O, Kuwano R, Nishizawa M, Kakita A, Ikeuchi T, and Takahashi H
- Subjects
- Adult, Aged, Astrocytes metabolism, Astrocytes pathology, Astrocytes ultrastructure, Brain metabolism, Brain pathology, Brain ultrastructure, Cytoplasm metabolism, Cytoplasm pathology, Cytoplasm ultrastructure, Frontotemporal Lobar Degeneration metabolism, Frontotemporal Lobar Degeneration pathology, Humans, Japan, Male, Middle Aged, Motor Neuron Disease metabolism, Motor Neuron Disease pathology, Neurofibrillary Tangles metabolism, Neurofibrillary Tangles pathology, Neurofibrillary Tangles ultrastructure, Neuroglia metabolism, Neuroglia pathology, Neuroglia ultrastructure, Neurons metabolism, Neurons pathology, Neurons ultrastructure, Parkinsonian Disorders metabolism, Parkinsonian Disorders pathology, Spinal Cord metabolism, Spinal Cord pathology, Spinal Cord ultrastructure, Tauopathies metabolism, Tauopathies pathology, tau Proteins genetics, tau Proteins metabolism, Frontotemporal Lobar Degeneration complications, Motor Neuron Disease complications, Parkinsonian Disorders complications, Tauopathies complications
- Abstract
Tau is the pathological protein in several neurodegenerative disorders classified as frontotemporal lobar degeneration (FTLD), including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). We report an unusual tauopathy in three Japanese patients presenting with Parkinsonism and motor neuron disease (neuroimaging revealed frontotemporal cerebral atrophy in two patients who were examined). At autopsy, all cases showed FTLD with the most severe neuronal loss and gliosis evident in the premotor and precentral gyri. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. In the spinal cord, loss of anterior horn cells and degeneration of the corticospinal tract were evident. In addition, the affected regions exhibited neuronal cytoplasmic inclusions resembling neurofibrillary tangles. Immunostaining using antibodies against hyperphosphorylated tau and 4-repeat tau revealed widespread occurrence of neuronal and glial cytoplasmic inclusions in the central nervous system; the astrocytic tau lesions were unique, and different in morphology from astrocytic plaques in CBD, or tufted astrocytes in PSP. However, immunoblotting of frozen brain samples available in two cases revealed predominantly 4R tau, with the approximately 37-kDa and 33-kDa low-molecular mass tau fragments characteristic of CBD and PSP, respectively. No mutations were found in the tau gene in either of the two cases. Based on these clinicopathological, biochemical, and genetic findings, we consider that the present three patients form a distinct 4R tauopathy associated with sporadic FTLD.
- Published
- 2010
- Full Text
- View/download PDF
5. Selective occurrence of TDP-43-immunoreactive inclusions in the lower motor neurons in Machado-Joseph disease.
- Author
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Tan CF, Yamada M, Toyoshima Y, Yokoseki A, Miki Y, Hoshi Y, Kaneko H, Ikeuchi T, Onodera O, Kakita A, and Takahashi H
- Subjects
- Adult, Aged, Aged, 80 and over, Blotting, Western, Brain metabolism, Brain pathology, Cell Death, Female, Fluorescent Antibody Technique, Humans, Immunohistochemistry, Inclusion Bodies pathology, Machado-Joseph Disease pathology, Male, Microscopy, Immunoelectron, Middle Aged, Motor Neurons pathology, Muscular Atrophy, Spinal metabolism, Muscular Atrophy, Spinal pathology, Spinal Cord metabolism, Spinal Cord pathology, DNA-Binding Proteins metabolism, Inclusion Bodies metabolism, Machado-Joseph Disease metabolism, Motor Neurons metabolism
- Abstract
Pathological transactivation-responsive DNA-binding protein 43 (TDP-43) has been identified as a component of ubiquitinated inclusions in frontotemporal lobar degeneration with motor neuron disease, as well as in sporadic and some forms of familial amyotrophic lateral sclerosis. To clarify whether pathological TDP-43 is present in other neurodegenerative diseases involving the motor neuron system, we immunohistochemically examined the brain and spinal cord affected by two CAG repeat (polyglutamine) diseases, Machado-Joseph disease (MJD) and spinal and bulbar muscular atrophy (SBMA), using polyclonal antibody against TDP-43. In all the MJD cases, TDP-43-immunoreactive (ir) neuronal cytoplasmic inclusions (NCIs), although few in number, were found only in the lower motor neurons in the brainstem and spinal cord. TDP-43-ir NCIs appeared as linear wisp-like, skein-like, or thick, somewhat rod-like bodies. These inclusions were also visualized with antibodies against phosphoserines 409 and 410 of TDP-43, and ubiquitin, but were not recognized by antibody against expanded polyglutamine stretches or ataxin-3. The ultrastructure of the TDP-43-ir NCIs was similar to that of the inclusions seen in sporadic ALS, consisting of bundles of parallel filaments. None of the SBMA cases showed abnormal TDP-43 immunoreactivity in any of the regions examined. Immunoblot analysis failed to recognize hyperphosphorylated TDP-43 at ~23 kDa in two MJD cases examined. However, the immunohistochemical findings strongly suggested that in MJD, in addition to the polyglutamine-dependent disease process, TDP-43-related pathogenesis is associated with degeneration and death of the lower motor neurons.
- Published
- 2009
- Full Text
- View/download PDF
6. Cardiac sympathetic denervation in Parkinson's disease linked to SNCA duplication.
- Author
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Orimo S, Uchihara T, Nakamura A, Mori F, Ikeuchi T, Onodera O, Nishizawa M, Ishikawa A, Kakita A, Wakabayashi K, and Takahashi H
- Subjects
- Aged, Aged, 80 and over, Denervation, Female, Ganglia, Sympathetic metabolism, Heart innervation, Humans, Immunohistochemistry, Lewy Bodies metabolism, Lewy Bodies pathology, Male, Middle Aged, Mutation, Parkinson Disease genetics, Parkinson Disease metabolism, Polymerase Chain Reaction, Tyrosine 3-Monooxygenase metabolism, alpha-Synuclein metabolism, Ganglia, Sympathetic pathology, Gene Duplication, Parkinson Disease pathology, alpha-Synuclein genetics
- Published
- 2008
- Full Text
- View/download PDF
7. Analysis of the expression level of alpha-synuclein mRNA using postmortem brain samples from pathologically confirmed cases of multiple system atrophy.
- Author
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Ozawa T, Okuizumi K, Ikeuchi T, Wakabayashi K, Takahashi H, and Tsuji S
- Subjects
- Aged, Cerebral Cortex pathology, Humans, Middle Aged, Multiple System Atrophy pathology, Nerve Fibers, Myelinated metabolism, Nerve Fibers, Myelinated pathology, Neurons metabolism, Neurons pathology, Oligodendroglia metabolism, Oligodendroglia pathology, Reverse Transcriptase Polymerase Chain Reaction, Synucleins, alpha-Synuclein, Cerebral Cortex metabolism, Multiple System Atrophy genetics, Multiple System Atrophy metabolism, Nerve Tissue Proteins genetics, RNA, Messenger metabolism
- Abstract
To determine whether multiple system atrophy (MSA) is associated with altered expression levels of the alpha-synuclein messenger RNA (mRNA), we performed quantitative reverse transcription polymerase chain reaction for alpha-synuclein mRNA using postmortem brain samples from 11 cases of MSA and 14 age-matched control subjects. The brain specimens used in this study contained both the gray matter and white matter, which were dissected from the frontal, temporal or occipital lobe. The expression levels of alpha-synuclein mRNA in the brain specimens of MSA cases were not different from those of the control subjects. These results suggest that the transcriptional regulation of the alpha-synuclein gene is unlikely to be affected in MSA brains.
- Published
- 2001
- Full Text
- View/download PDF
8. Hereditary dentatorubral-pallidoluysian atrophy: detection of widespread ubiquitinated neuronal and glial intranuclear inclusions in the brain.
- Author
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Hayashi Y, Kakita A, Yamada M, Koide R, Igarashi S, Takano H, Ikeuchi T, Wakabayashi K, Egawa S, Tsuji S, and Takahashi H
- Subjects
- Adult, Aged, Brain Diseases metabolism, Humans, Inclusion Bodies metabolism, Inclusion Bodies pathology, Middle Aged, Neuroglia metabolism, Neuroglia pathology, Neurons metabolism, Neurons pathology, Ubiquitins metabolism, Brain Diseases genetics, Brain Diseases pathology, Dentate Gyrus pathology, Globus Pallidus pathology, Red Nucleus pathology
- Abstract
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.
- Published
- 1998
- Full Text
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9. Autosomal dominant cerebellar ataxia (SCA6): clinical, genetic and neuropathological study in a family.
- Author
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Takahashi H, Ikeuchi T, Honma Y, Hayashi S, and Tsuji S
- Subjects
- Aged, Aged, 80 and over, Cerebellar Ataxia genetics, Cerebellar Ataxia pathology, Cerebellum pathology, DNA, Neoplasm analysis, DNA, Neoplasm genetics, Female, Genome, Histocytochemistry, Humans, Male, Middle Aged, Pedigree, Tomography, X-Ray Computed, Cerebellar Ataxia physiopathology
- Abstract
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.
- Published
- 1998
- Full Text
- View/download PDF
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