Atypical clinical presentations of X-linked spinal and bulbar muscular atrophy in patients with mild CAG expansions in androgen receptor gene.
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Aged↗
Biomedical subjects
T Inuzuka
Publications and source records attributed to T Inuzuka.
Changes in anti-HuD antibody titers in the long-term course in paraneoplastic sensory neuropathy.
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Aged↗
Immunoreactivity of growth inhibitory factor in normal rat brain and after stab wounds--an immunocytochemical study using confocal laser scan microscope.
The growth inhibitor factor (GIF) is a new member of the metallothionein family that is downregulated in Alzheimer's disease brain. Using a confocal laser scan microscope with polyclonal and monoclonal antibodies to GIF, and monoclonal antibodies to glial fibrillary acidic protein (GFAP) and MAP-2, we demonstrated that GIF immunoreactivity was expressed primarily in astrocytes and much less in neurons. In astrocytes of normal rat brain GIF immunoreactivity was detected mainly in the cell bodies, while GFAP immunoreactivity was detected mainly in the processes. GIF immunoreactivity was more strongly expressed in reactive astrocytes. These findings were confirmed with both polyclonal and monoclonal antibodies. Following stab wounds, a number of GIF-positive reactive astrocytes were detected around the wounds at 3 days postoperation. After 7 days GIF immunoreactivity was detected in cell bodies and processes of reactive astrocytes. The number of GIF-positive astrocytes and the intensity of the immunoreactivity remained elevated over the control levels at least through 28 days. These immunocytochemical findings correlated well with changes in GIF protein and mRNA levels. Not only changes in GIF protein and mRNA levels but also intracellular localization of GIF in normal rat brain and after stab wounds in rat brain were different from those of GFAP. These results support the concept that GIF plays an important role in the processing of reconstruction after brain damage.
Animals↗
Subcellular localization of growth inhibitory factor in rat brain: light and electron microscopic immunohistochemical studies.
The subcellular localization of growth inhibitory factor (GIF), a brain-specific member of the metallothionein family, was determined in the rat brain by electron microscopic immunohistochemistry using a rabbit antiserum against a synthetic polypeptide specific for rat GIF. The major cell type that expressed a high level of GIF immunoreactivity was the astrocytes. In these cells, dense labelling was observed throughout the soma and the fine processes, in association with the free ribosomes, rough endoplasmic reticulum, small vesicles, the outer membrane of the mitochondria and part of the plasma membrane. Astrocytic end-feet around blood vessels exhibited intense immunoreactivity. Another cell type exhibiting GIF immunolabelling was the neurons. However, this immunoreactivity was restricted to a subset of the neuronal population, and in contrast to the astrocytic pattern, the labelling was localized predominantly in the processes including axons and dendrites, in association with microtubules, ribosomes, the outer membrane of the mitochondria and the plasmalemma. Synaptic elements, including dendritic spines, also showed definite immunoreactivity in association with synaptic vesicles and post-synaptic densities. No labelling was observed in the oligodendrocytes or microglia. The present data suggest that GIF is expressed in both astrocytes and neurons, and plays rather specific roles in each phenotype.
Animals↗
Instability of mutant Cu/Zn superoxide dismutase (Ala4Thr) associated with familial amyotrophic lateral sclerosis.
In about 20-25% of cases of familial amyotrophic lateral sclerosis (FALS) patients have mutations in the Cu/Zn superoxide dismutase (SOD1) gene. The mechanism through which the mutations in the SOD1 gene cause ALS still remain unknown. We performed pulse-chase experiments using a system for the transient expression of human SOD1 in COS7 cells to examine whether the Ala4Thr mutation, which we previously reported, decreases the stability of SOD1. The expression vector (pEF-BOS) carrying the wild-type or mutant (Ala4Thr) human SOD1 cDNA was transfected into COS7 cells, and transiently expressed human SOD1 was then metabolically radiolabeled. Half-lives of the wild-type and the Ala4Thr mutant SOD1 were determined to be 78 h and 18 h, respectively. These results suggest that the Ala4Thr mutation in SOD1 decreases the stability of SOD1 and that this instability may play an important role in the pathogenesis of the degeneration of motor neurons in FALS.
Amyotrophic Lateral Sclerosis↗
Patterns of growth inhibitory factor (GIF) and glial fibrillary acidic protein relative level changes differ following left middle cerebral artery occlusion in rats.
Growth inhibitory factor (GIF) has been identified as a new metallothionein-like protein, the level of which is decreased in the Alzheimer's disease brain. GIF and glial fibrillary acidic protein (GFAP) have been reported to be expressed in reactive astrocytes in the rat brain following stab wounds. Moreover, strong expression of GIF mRNA in reactive astrocytes after ventricular injection of kainic acid has been demonstrated. To clarify the biological functions of GIF and GFAP in repair of the CNS, we examined changes in their relative levels to sham control using a Western blotting technique in the rat left hemisphere following occlusion of the left middle cerebral artery, for 28 days after surgery. The GIF relative level declined to 56% of the sham-operated control value on day 7. Thereafter the GIF relative level increased and returned to the normal relative level by days 21-28. The GFAP relative level increased from day 3 and reached a maximum of 120% of the sham-operated control value on days 14-21. While GIF and GFAP were both detected in reactive astrocytes, an increase in the GFAP relative level occurred prior to an increase in GIF relative level following the ischemia. The patterns of changes in relative expression levels of GIF and GFAP were quite similar to those in our previous studies on effects of cerebral stab wounds in rats, although the changes were more rapid in the previous studies. GIF and GFAP appear to play different roles in the repair of the CNS. The present results also indicated that GIF could play an important role in CNS repair after cerebral ischemia and provide new insights into the mechanism of gliosis investigated mainly from the viewpoint of GFAP.
Animals↗
Hypertrophic neuritis due to chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): a postmortem pathological study.
A postmortem pathological study of a 65-year-old woman with hypertrophic neuritis associated with hand tremor and limb ataxia is described. There were many onion bulbs and loss of myelinated nerve fibers in the peripheral nerves, including the facial and subserosal visceral nerves. The hypertrophic neuritis was caused by chronic inflammatory demyelinating neuropathy (CIDP), in which interstitial amorphous substances in the endoneurium and onion bulb formation might contribute to nerve swelling. We speculate that visceral autonomic nerves as well as somatic peripheral nerves are involved in patients with a long clinical CIDP course and that peripheral nerve pathology in this disorder shows more heterogeneous changes than previously recognized.
Aged↗
Decrease in benzodiazepine receptor binding in a patient with Angelman syndrome detected by iodine-123 iomazenil and single-photon emission tomography.
A receptor mapping technique using iodine-123 iomazenil and single-photon emission tomography (SPET) was employed to examine benzodiazepine receptor binding in a patient with Angelman syndrome (AS). AS is characterized by developmental delay, seizures, inappropriate laughter and ataxic movement. In this entity there is a cytogenic deletion of the proximal long arm of chromosome 15q11-q13, where the gene encoding the GABAA receptor beta3 subunit (GABRB3) is located. Since the benzodiazepine receptor is constructed as a receptor-ionophore complex that contains the GABAA receptor, it is a suitable marker for GABA-ergic synapsis. To determine whether benzodiazepine receptor density, which indirectly indicates changes in GABAA receptor density, is altered in the brain in patients with AS, we investigated a 27-year-old woman with AS using 123I-iomazenil and SPET. Receptor density was quantitatively assessed by measuring the binding potential using a simplified method. Regional cerebral blood flow was also measured with N-isopropyl-p-[123I]iodoamphetamine. We demonstrated that benzodiazepine receptor density is severely decreased in the cerebellum, and mildly decreased in the frontal and temporal cortices and basal ganglia, a result which is considered to indicate decreased GABAA receptor density in these regions. Although the deletion of GABRB3 was not observed in the present study, we indirectly demonstrated the disturbance of inhibitory neurotransmission mediated by the GABAA receptor in the investigated patient. 123I-iomazenil with SPET was useful to map benzodiazepine receptors, which indicate GABAA receptor distribution and their density.
Adult↗
Disaggregation of polyribosomes in the spinal anterior horn cells in a patient with X-linked spinal and bulbar muscular atrophy.
The spinal anterior horn cells (AHCs) in a patient with X-linked spinal and bulbar muscular atrophy (SBMA) were examined by light and electron microscopy, giving special attention to alterations in the rough endoplasmic reticulum (ER). Seven age-matched subjects were used as controls. The patient with SBMA showed a severe decrease of AHCs, but the Nissl substance in the remaining AHCs appeared well preserved on light microscopy. Electron microscopy revealed a relatively well preserved parallel lamellar pattern of ER and marked disaggregation of the polyribosomes surrounding the ER in the remaining AHCs. These findings indicate that the Nissl substance was affected in spite of its light microscopic appearance in SBMA, and that the AHCs degenerate through disaggregation of the polyribosomes of the ER.
Anterior Horn Cells↗
[An autopsy case of amyotrophic lateral sclerosis with concomitant Alzheimer's and incidental Lewy body diseases].
We report a 72-year-old man with sporadic amyotrophic lateral sclerosis (ALS) who showed concomitant histopathology of Alzheimer's disease (AD) and incidental Lewy body disease. The patient presented at the age of 70 years with distal upper limb amyotrophy. Thereafter, gait disturbance and respiratory distress progressed. Neuropathological examination showed mild frontal lobe and anterior spinal root atrophy. There was moderate loss of upper and lower motor neurons, and Bunina bodies and skein-like inclusions were present in the spinal anterior horns and facial and hypoglossal nuclei, confirming the pathology of ALS. In addition, however, numerous amyloid plaques were observed throughout the entire cerebral neocortex, nucleus accumbens and amygdaloid body. Many neurofibrillary tangles were also evident in the medial temporal cortex. Moreover, the substantia nigra showed mild degeneration, and Lewy bodies were found in the substantia nigra, locus ceruleus, basal nucleus of Meynert and peripheral autonomic ganglia. Although neither parkinsonism nor dementia was noted during the clinical course, our final neuropathological diagnosis was sporadic ALS, AD and incidental Lewy body disease (or presymptomatic Parkinson's disease). Whether or not the coexistence of these three diseases in the same patient was merely coincidental is of considerable interest.
Aged↗
[Paraneoplastic neurological syndrome: diagnosis and therapy].
Neurological symptoms often preceded diagnosis of malignancy. Anti-cancer therapy and immunological treatments are relatively effective for Lambert-Eaton myasthenic syndrome, but often disappointing for subacute cerebellar degeneration or sensory neuropathy. Examination of anti-neuronal antibodies, which are characteristic of some clinical type of this syndrome, is very important for early diagnosis of the malignancy and treatment for neurological symptoms.
Humans↗
Changes of growth inhibitory factor after stab wounds in rat brain.
The growth inhibitory factor (GIF) is a new metallothionein (MT)-like protein that is downregulated in Alzheimer's disease (AD) brain. The biological function of GIF has not been fully clarified yet. We have raised an antibody to the synthetic polypeptide that is specific for rat GIF. The purified antibody reacted to recombinant GIF and native rat GIF but not to MT or maltose-binding protein. Using the antibody and GIF cDNA probe, we investigated changes of GIF and GIF mRNA by Western and Northern blotting techniques in rat brains after stab wounds. The levels of GIF and GIF mRNA began to increase 4 days postoperation, reached a maximum at 14-21 days and sustained the increased level at least through 28 days. While both glial fibrillary acidic protein (GFAP) and GIF were recognized in astrocytes, the increases of these 2 proteins after stab wounds showed different patterns. The results indicated that GIF could play an important role in the repair after brain damage and also produce new insights into the mechanism of gliosis investigated mainly from the viewpoint of GFAP.
Alzheimer Disease↗
[A case of consciousness disorder, convulsion, meningeal stimulation, ocular motility disorder and ataxia induced by cyclosporin].
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Adolescent↗
Atypical motor neuron disease with severe ophthalmoloplegia: a report of two cases.
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Aged↗
Expression of growth inhibitory factor (GIF) in normal and injured rat brains.
Immunohistochemical study on growth inhibitory factor (GIF) in rat brain has revealed that a glial cell layer on the surface of cerebral cortex and the cells surrounding Purkinje cells has been reported. In addition, neurons in gray matter were weakly immunostained for GIF. In situ hybridization using digoxigenin-labeled single-strand RNA probes also demonstrated that most of the neurons and small round cells, which were presumably astrocytes, expressed GIF mRNA in the cerebral cortex of rat brain. These findings indicate that GIF is produced in neurons as well as in astrocytes. The most prominent findings in this study are, a very strong reaction of GIF and GIF mRNA in the reactive astrocytes around the site of injury induced by stab wound or kainic acid injection. These results raised the possibility that GIF may act as an acute-phase protein in reactive astrocytes and have a role in tissue repair.
Animals↗
A novel mutation in Cu/Zn superoxide dismutase gene in Japanese familial amyotrophic lateral sclerosis.
Recently, several missense mutations in the Cu/Zn superoxide dismutase gene (SOD1) have been reported as a putative cause of chromosome-21q-linked familial amyotrophic lateral sclerosis (FALS). We have discovered a novel missense mutation (substitution of Thr for Ala4) in exon 1 (GCC to ACC) in two FALS patients from one Japanese FALS family. No mutations were found in 17 cases of sporadic ALS. The enzyme activity of recombinant fusion protein containing the Cu/Zn superoxide dismutase (SOD) with the Ala4-to-Thr mutation was significantly reduced in E. coli. On the other hand, in the expression system in insect cells using Baculovirus, the mutant SOD expressed an enzyme activity as high as wild-type SOD. These results suggest that the stability of SOD with the Ala4-to-Thr mutation is disrupted especially in the fusion protein. Autopsy was carried out on one of the two patients, and the pathological findings were typical of FALS with posterior column involvement. These results raise the possibility that mutation of the SOD1 is responsible for FALS with broader pathological involvement.
Amino Acid Sequence↗
Motor neuron disease with multi-system involvement presenting as tetraparesis, ophthalmoplegia and sensori-autonomic dysfunction.
We carried out a postmortem examination on two Japanese patients, 64- and 80-year-old men whose survival was prolonged with an artificial respirator. They had no family history of neuropsychiatric disorders and were suspected, clinically, as having a motor neuron disease that differed from amyotrophic lateral sclerosis (ALS). As well as upper and lower motor neuron impairment, they showed a variety of symptoms, such as sensory disturbances, hypohidrosis, impotence, ophthalmoparesis and/or atonic neurogenic bladder, and their protein content in cerebrospinal fluid was elevated markedly. Pathological examination revealed the following extensive nervous system involvement: (1) the upper and lower voluntary motor systems, including the IIIrd, IVth and VIth cranial nerve nuclei: (2) the reticular formation and its major afferent pathways; (3) the vestibulospinal and tectospinal systems; (4) the spinocerebellar system and the exteroceptive somatic afferent pathways; (5) the dentatorubral and pallidoluysian systems; and (6) the substantia nigra, locus ceruleus and intermediolateral and Onufrowicz's nuclei. Neither Bunina bodies, Lewy body-like hyaline inclusions nor ubiquitin immunoreactive skein-like structures were observed. The distribution of the lesions was quite different from that in patients with ALS and the other known related diseases. Recently, seven autopsied cases with clinical and histopathological similarities to our patients have been reported in Japan. Our conclusion is that our two and these seven patients should be classified as having a new motor neuron disease entity, which can be is differentiated from ALS.
Aged↗
Familial amyotrophic lateral sclerosis with a mutation in the Cu/Zn superoxide dismutase gene.
Several missense mutations within exons 1, 2, 4 and 5 of the gene for Cu/Zn-binding superoxide dismutase (SOD1) have been discovered to be involved in the development of chromosome 21q-linked familial amyotrophic lateral sclerosis (FALS). We describe here an autopsied patient with FALS, in whom we have recently identified a novel missense mutation in exon 1 of the SOD1 gene. The neuropathological findings were compatible with those described previously in patients with FALS with posterior column involvement. This suggests that mutations of the SOD1 gene may be responsible for this form of FALS.
Adult↗