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H Mizusawa

Publications and source records attributed to H Mizusawa.

At least 19 recordsLinked to original sources
PubMed2006

16q-linked autosomal dominant cerebellar ataxia: a clinical and genetic study.

The autosomal dominant cerebellar ataxias (ADCAs) comprise a genetically and clinically heterogenous group of neurodegenerative disorders. Very recently, a C-to-T single nucleotide substitution in the puratrophin-1 gene was found to be strongly associated with a form of ADCA linked to chromosome 16q22.1 (16q-linked ADCA; OMIM 600223). We found the C-to-T substitution in the puratrophin-1 gene in 20 patients with ataxia (16 heterozygotes and four homozygotes) and four asymptomatic carriers in 9 of 24 families with an unknown type of ADCA. We also found two cases with 16q-linked ADCA among 43 sporadic patients with late-onset cortical cerebellar atrophy (LCCA). The mean age at onset in the 22 patients was 61.8 years, and that of homozygous patients was lower than that of heterozygous ones in one family. Neurological examination revealed that the majority of our patients showed exaggerated deep tendon reflexes in addition to the cardinal symptom of cerebellar ataxia (100%), and 37.5% of them had sensorineural hearing impairment, whereas sensory axonal neuropathy was absent. The frequency of 16q-linked ADCA was about 1/10 of our series of 110 ADCA families, making it the third most frequent ADCA in Japan.

Age of Onset↗
PubMed2006

Time profile of eosinophilic neurons in the cortical layers and cortical atrophy.

Eosinophilic neurons (ENs) appear in the post-ischemic cortex; however, whether there are differences in the time profile for different cortical layers and the fate of the cortex with ENs is largely unknown. We examined the time profile of ENs in different cortical layers and evolution of cortical atrophy after transient cerebral ischemia in Mongolian gerbils. Unilateral forebrain ischemia was induced twice by 10-minute unilateral common carotid artery occlusions. Brains at 24 hours, 4 days, and 2, 4, and 16 weeks post-ischemia were prepared for morphometric analysis. Quantitative analysis of ENs in regions of interest in the rostral and caudal cortex showed the highest number of ENs at 4 days post-ischemia in layers 3 and 6. Reduction in ENs after this peak was slower in layer 6 than in layer 3 in both rostral and caudal cortex, and this difference was significant in layer 6 of the caudal cortex. Infarcts with significant atrophy appeared in the rostral cortex. In the caudal cortex, only selective neuronal death with mild but distinct atrophy was observed. We observed a significant difference between cortical layers in the time profile of ENs in the post-ischemic cortex. Selective neuronal death without infarction was sufficient to induce cortical atrophy after transient cerebral ischemia.

Animals↗
PubMed2006

Long-term cognitive and neuropsychological symptoms after global cerebral ischemia in Mongolian gerbils.

The objective of this study was to establish a rodent model of vascular dementia that showed long-term cognitive and neuropsychological deficits, and to correlate those behavioral deficits with the patterns of ischemic lesions, thus providing a platform for future testing of potential therapeutic agents. In Mongolian gerbils, either 5-minute single bilateral common carotid artery occlusion (SBCCAO) or repetitive bilateral common carotid artery occlusion (two 7-minute occlusions, RBCCAO) was induced, and the behavioral deficits were evaluated using 2 tests: a modified open-field test with an escape zone to evaluate changes in anxiety and locomotor activity, and a T-maze test to assess cognitive dysfunction. SBCCAO did not induce anxiety changes but caused transient locomotor hyperactivity and mild cognitive deficits. Only pyramidal neuronal death was found in the bilateral CA1 sector of the hippocampus following SBCCAO. In contrast, RBCCAO induced persistent locomotor hyperactivity, reduced anxiety, and caused severe cognitive deficits at 4 weeks post-ischemia. RBCCAO caused significant atrophy associated with diffuse selective neuronal death in the bilateral cerebral cortex and caudate nucleus, as well as the CA1 region. The repetitive ischemia model appears to be a potentially useful platform for the long-term analysis of cognitive and neuropsychological symptoms associated with vascular dementia.

Animals↗
PubMed2005

A clinical, genetic, and neuropathologic study in a family with 16q-linked ADCA type III.

Presented is the new kindred with autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 (16q-ADCA type III) associated with progressive hearing loss. By haplotype analysis, the critical interval was slightly narrowed to three megabase regions between GATA01 and D16S3095. Neuropathologic study of 16q-ADCA type III demonstrated characteristic shrinkage of Purkinje cell bodies surrounded by synaptophysin-immunoreactive amorphous material containing calbindin- and ubiquitin-positive granules.

Adolescent↗
PubMed2005

Clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease.

BACKGROUND: No method for the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease (sCJD) has been established except for pathologic examination. OBJECTIVE: To identify a reliable marker for the clinical diagnosis of MM2-type sCJD. METHODS: CSF, EEG, and neuroimaging studies were performed in eight patients with MM2-type sCJD confirmed by neuropathologic, genetic, and western blot analyses. RESULTS: The eight cases were pathologically classified into the cortical (n = 2), thalamic (n = 5), and combined (corticothalamic) (n = 1) forms. The cortical form was characterized by late-onset, slowly progressive dementia, cortical hyperintensity signals on diffusion-weighted imaging (DWI) of brain, and elevated levels of CSF 14-3-3 protein. The thalamic form showed various neurologic manifestations including dementia, ataxia, and pyramidal and extrapyramidal signs with onset at various ages and relatively long disease duration. Characteristic EEG and MRI abnormalities were almost absent. However, all four patients examined with cerebral blood flow (CBF) study using SPECT showed reduction of the CBF in the thalamus as well as the cerebral cortex. The combined form had features of both the cortical and the thalamic forms, showing cortical hyperintensity signals on DWI and hypometabolism of the thalamus on [18F]2-fluoro-2-deoxy-d-glucose PET. CONCLUSION: For the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease, cortical hyperintensity signals on diffusion-weighted MRI are useful for the cortical form and thalamic hypoperfusion or hypometabolism on cerebral blood flow SPECT or [18F]2-fluoro-2-deoxy-d-glucose PET for the thalamic form.

14-3-3 Proteins↗
PubMed2005

Association of a polymorphism of the transforming growth factor-beta1 gene with cerebral amyloid angiopathy.

BACKGROUND: A recent study showed that transforming growth factor-beta1 (TGF-beta1) induces amyloid-beta deposition in cerebral blood vessels and meninges of a transgenic mouse model of Alzheimer's disease (AD), and that TGF-beta1 mRNA levels are correlated with cerebral amyloid angiopathy (CAA) in human AD brains. A T/C polymorphism at codon 10 in exon 1 of the TGF-beta1 gene has been reported to be associated with the serum TGF-beta1 concentration. We investigated whether the TGF-beta1 polymorphism is associated with the risk of CAA. METHODS: The association between the severity of CAA and the T/C polymorphism at codon 10 in exon 1 of the TGF-beta1 was investigated in 167 elderly Japanese autopsy cases, including 73 patients with AD. The apolipoprotein E (APOE) genotype was also determined. RESULTS: The genotypes (TT/ TC/ CC) were associated with the severity of CAA significantly in all patients (p = 0.0026), in non-AD patients (p = 0.011), and APOE non-epsilon4 carriers (p = 0.0099), but not in AD patients or APOE epsilon4 carriers. The number of the T alleles positively correlated with the severity of CAA in all patients (p = 0.0011), non-AD patients (p = 0.0026), and APOE non-epsilon4 carriers (p = 0.0028), but not in AD patients or APOE epsilon4 carriers. The polymorphism was not significantly associated with AD. CONCLUSIONS: Our results suggest that the polymorphism in TGF-beta1 is associated with the severity of CAA, especially in non-AD patients and APOE non-epsilon4 carriers.

Aged↗
PubMed2005

Inter- and intra-specific gene-density-correlated radial chromosome territory arrangements are conserved in Old World monkeys.

Recently it has been shown that the gene-density correlated radial distribution of human 18 and 19 homologous chromosome territories (CTs) is conserved in higher primates in spite of chromosomal rearrangements that occurred during evolution. However, these observations were limited to apes and New World monkey species. In order to provide further evidence for the evolutionary conservation of gene-density-correlated CT arrangements, we extended our previous study to Old World monkeys. They comprise the remaining species group to be analyzed in order to obtain a comprehensive overview of the nuclear topology of human 18 and 19 homologous CTs in higher primates. In the present study we investigated four lymphoblastoid cell lines from three species of Old World monkeys by three-dimensional fluorescence in situ hybridization (3D-FISH): two individuals of Japanese macaque (Macaca fuscata), crab-eating macaque (Macaca fascicularis), and an interspecies hybrid individual between African green monkey (Cercopithecus aethiops) and Patas monkey (Erythrocebus patas). Our data demonstrate that gene-poor human 18 homologous CTs are located preferentially close to the nuclear periphery, whereas gene-dense human 19 homologous CTs are oriented towards the nuclear center in all cell lines analyzed. The gene-density-correlated positioning of human 18 and 19 homologous CTs is evolutionarily conserved throughout all major higher primate lineages, despite chromosomal inversions, fusions, fissions or reciprocal translocations that occurred in the course of evolution in these species. This remarkable preservation of a gene-density-correlated chromatin arrangement gives further support for a functionally relevant higher-order chromatin architecture.

Animals↗
PubMed2004

Distal myopathy with rimmed vacuoles (DMRV): new GNE mutations and splice variant.

Study of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene (GNE) revealed that almost all cases of distal myopathy with rimmed vacuoles were caused by GNE mutations. Seven new mutations were identified, including M712T, which is the most common mutation in Jewish hereditary inclusion body myopathy. In addition, a splice-variant characteristic of the skeletal muscle was found, whereas the difference of the expression level between GNE-mutated and -nonmutated patients was not apparent.

Adolescent↗
PubMed2004

Extrapyramidal motor symptoms versus striatal infarction volume after focal ischemia in mongolian gerbils.

Few behavioral tests are available to evaluate extrapyramidal dysfunctions after focal cerebral ischemia in rodents, although extrapyramidal motor dysfunctions are often observed clinically in patients with cerebral infarction. We evaluated the methamphetamine (MP)-induced rotation test for the detection and quantification of extrapyramidal motor dysfunction induced by striatal infarction in gerbils after focal cerebral ischemia. Mongolian gerbils (n=79) underwent the left common carotid artery occlusion (CCAO) for 10, 15, or 20 min. Spontaneous and MP-induced rotation tests were repeated postischemia, and the results compared with the extent of ischemic tissue injury. The density of dopaminergic neurons immunostained with a tyrosine hydroxylase antibody in the substantia nigra pars compacta (SNpc) also was measured. Histological examination revealed selective neuronal death of the hippocampal cornu ammonis 1 (CA1) sector in 10-min CCAO animals, infarction confined to the striatum and hippocampal neuronal death in 15-min CCAO animals, and widespread hemispheric infarction in 20-min CCAO animals. Dopaminergic neurons in the SNpc were preserved in 10- and 15-min CCAO animals but were significantly reduced in 20-min CCAO animals. In MP-induced rotation tests, 15-min CCAO animals showed biased rotation ipsilateral to the lesioned side. Biased rotation persisted 4 weeks postischemia, and the number of rotations significantly correlated with the regional infarction volume of the striatum. Twenty-minute CCAO animals showed biased rotation contralateral to the lesioned side; rotation number was not correlated with the infarction volume. Our results show that biased rotation behavior is a sensitive parameter of the extent of striatal injury after focal cerebral ischemia provided the lesion is not extended to the ipsilateral cortex. MP-induced rotation in rodents probably coordinates with the extrapyramidal motor dysfunction after striatal infarction in patients with vascular Parkinsonism.

Animals↗
PubMed2004

A Japanese patient with distal myopathy with rimmed vacuoles: missense mutations in the epimerase domain of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene accompanied by hyposialylation of skeletal muscle glycoproteins.

Hereditary inclusion body myopathy and distal myopathy with rimmed vacuoles are both caused by mutations of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. Here we report a Japanese patient with compound heterozygous missense mutations in the epimerase domain of GNE gene, 89 G to C and 578 A to T. Biochemical analysis demonstrated decreased reactivity of skeletal muscle glycoproteins with the lectins recognizing sialic acid residues. The results suggest that hyposialylation of glycoproteins may be involved in the pathogenesis of muscle dysfunction in this patient.

Adult↗
PubMed2004

Chronic inflammatory demyelinating polyneuropathy: decreased claudin-5 and relocated ZO-1.

OBJECTIVES: To clarify the dynamics of molecules composing the blood-nerve barrier (BNB) in inflammatory neuropathies. METHODS: The expression of four tight junction (TJ) proteins-claudin-1, claudin-5, occludin, and ZO-1-was analysed immunohistochemically in sural nerve biopsy specimens obtained from patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). RESULTS: Claudin-1 was detected only in perineurial cells, whereas claudin-5 was present in endothelial cells, irrespective of vessel location or size. Occludin and ZO-1 were found in perineurial cells, in addition to some epineurial and endoneurial endothelial cells. In CIDP, percentages of endoneurial small vessels immunoreactive for claudin-5 were significantly decreased, as were ZO-1 immunoreactive endoneurial small vessels, with staining localised to interfaces between cells. Claudin-1 and occludin immunoreactivity did not differ appreciably between the neuropathies examined. CONCLUSIONS: The downregulation of claudin-5 and altered localisation of ZO-1 seen in CIDP specimens may indicate that BNB derangement occurs in inflammatory neuropathies. Further investigation of TJ molecules may suggest new treatments based on properties of the BNB.

Adolescent↗
PubMed2003

A comparison of long-term neurological symptoms after two different focal ischemic models in Mongolian gerbils.

The aim of the present study was to elucidate the relationship between specific tasks and the responsible ischemic lesions after experimentally induced cerebral hemispheric ischemia in Mongolian gerbils. We used the elevated body swing test (EBST) to evaluate asymmetry motor behavior, the bilateral asymmetry test (BAT) to evaluate sensory dysfunction, and the T-maze test to assess cognitive deficit during 4 weeks after either 10-min single unilateral carotid artery occlusion (sCCAO) or 10-min repeated unilateral occlusion (rCCAO). rCCAO produced persistent sensorimotor and severe cognitive deficits. Infarction was confined to the ipsilateral cerebral cortex, hippocampus, dorsolateral nucleus of thalamus and caudate nucleus. sCCAO did not induce sensorimotor abnormalities, but did produce mild cognitive deficits; these animals also showed increased locomotor activity during the early post-ischemic period. In sCCAO, neuronal death was confined to the ipsilateral CA1 sector of the hippocampus. Thus, unilateral CA1 neuronal death was sufficient for evolution of cognitive deficits in this model of experimental focal ischemia. Ischemic lesions extending to the ipsilateral cerebral cortex, basal ganglia, and hippocampus produced persistent and severe sensorimotor impairment accompanying severe cognitive deficits. These findings regarding region-specific behavioral tasks in cerebral ischemia will facilitate improved assessment of stroke therapy.

Animals↗
PubMed2003

The role of capsaicin-sensitive afferents in autonomic dysreflexia in patients with spinal cord injury.

OBJECTIVES: To determine whether capsaicin-sensitive nerves in the bladder form the afferent limb involved in autonomic dysreflexia (AD) in patients with spinal cord injury (SCI). PATIENTS AND METHODS: Seven men with SCI (five cervical cord, two thoracic cord) with AD and detrusor hyper-reflexia (DH) were enrolled. Under general anaesthesia, capsaicin solution (100 mL of 2 mmol/L in 10% ethanol) was instilled in the bladder and retained for 30 min. The patients were assessed by medium-fill cystometry (CMG) just before and 50 min after the capsaicin treatment. Intra-arterial blood pressure (BP) and heart rate were monitored continuously throughout the procedure; 10% ethanol was instilled before capsaicin treatment in four patients as a control. Serum catecholamines were measured during bladder filling and capsaicin treatment, and the blood ethanol concentration also measured after instillation in all patients. The CMG with concomitant monitoring of BP and heart rate was repeated 1 week, 1, 3, 6, 12 and 24 months after instillation. In two patients the instillations were repeated 5 and 12 months after the first because of recurrence of DH. Urodynamic variables assessed were maximum cystometric capacity (MCC), maximum amplitude of uninhibited detrusor contraction (UICmax), the bladder capacity at 40 cmH2O detrusor pressure (Cdp40) and a systolic BP of> 140 mmHg or diastolic BP of> 90 mmHg (C(HT)). RESULTS: There was an increase in BP and a decrease in heart rate in all patients during bladder filling before capsaicin treatment. Instillation of capsaicin produced a significant increase in both systolic and diastolic BP and a significant decrease in heart rate. The maximum cardiovascular effects were at 5-10 min after instillation and gradually returned to baseline within 40 min. The vehicle had negligible effects on either BP or heart rate. After capsaicin treatment, the responses of BP and heart rate to bladder distension were significantly reduced. Both serum catecholamine values and the blood ethanol concentration remained within normal limits. The mean (range) follow-up after the first treatment was 15 (6-30) months. One month after treatment all seven patients became continent and their episodes of AD became negligible and well tolerable between catheterizations (for 3-4 h); the effects lasted for >or= 3 months in all. MCC was significantly increased at 4 weeks and 3 months, and UICmax significantly decreased at 4 weeks after treatment. Both mean Cdp40 and C(HT) increased 1 week, 1 and 3 months after treatment. Two patients received a second instillation, and have been continent with no symptomatic AD for 6 and 24 months. The remaining five patients have been continent with no symptomatic AD for 6-12 months. CONCLUSION: These results indicate that intravesical capsaicin, but not the vehicle, acutely triggers AD in patients with SCI, suggesting involvement of bladder capsaicin- sensitive afferents in AD in these patients. The results also suggest that intravesical capsaicin may be a promising therapy for both AD and DH in such patients. Further long-term follow-up studies are needed to evaluate the duration of its effect.

Administration, Intravesical↗
PubMed2003

Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency?

Acute axonal polyneuropathy and Wernicke-Korsakoff encephalopathy developed simultaneously in three patients. Nerve conduction studies (NCS) detected markedly decreased compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs) with minimal conduction slowing; sympathetic skin responses (SSRs) were also notably decreased. Sural nerve biopsies showed only mild axonal degeneration with scattered myelin ovoid formation. The symptoms of neuropathy lessened within two weeks after an intravenous thiamine infusion. CMAPs, SNAPs, and SSRs also increased considerably. We suggest that this is a new type of peripheral nerve impairment: physiological conduction failure with minimal conduction delay due to thiamine deficiency.

Acute Disease↗
PubMed2003

Association of neprilysin polymorphism with cerebral amyloid angiopathy.

OBJECTIVES: The risk of sporadic cerebral amyloid angiopathy (CAA) may be associated with genetic polymorphisms of molecules related to anabolism or catabolism of amyloid beta protein (Abeta). The authors investigated whether a polymorphism of the gene (NEP) coding for neprilysin, an enzyme catabolising Abeta, is associated with CAA. METHODS: The study analysed the GT repeat polymorphism in the enhancer/promoter region of NEP and severity of CAA in 164 necropsied elderly Japanese subjects. RESULTS: The subjects had NEP polymorphisms with 19 to 23 GT repeats and were classified into nine genotypes. CAA severity was significantly higher in the subjects with up to 40 repeats in total than those with more than 40 repeats (p=0.005). There was a significant correlation between the number of the shorter alleles (19 or 20 repeats) and CAA severity (p=0.024). In addition, there was no interaction between the NEP polymorphism and apolipoprotein E genotype. CONCLUSIONS: These results suggest the association between the NEP polymorphism and the risk of CAA. Further study using more samples from populations with different ethnic backgrounds is necessary.

Aged↗