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Biomedical subjects

I Kanazawa

Publications and source records attributed to I Kanazawa.

At least 19 recordsLinked to original sources
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

Anti-GQ1b antibody as a factor predictive of mechanical ventilation in Guillain-Barré syndrome.

Compared with 87 unventilated patients with Guillain-Barré syndrome (GBS), 44 ventilated patients with GBS more frequently had multiple cranial nerve involvement (91 vs 50%; p < 0.001) and IgG anti-GQ1b antibody (27 vs 8%; p = 0.006). In GBS patients without ophthalmoparesis, the presence of IgG anti-GQ1b antibody was associated with respiratory failure (12 [3/25] vs 0% [0/67]; p = 0.04). The presence of the antibody may be a factor predictive of respiratory failure in GBS.

Adult↗
PubMed2004

Japanese SCA families with an unusual phenotype linked to a locus overlapping with SCA15 locus.

The authors identified two Japanese spinocerebellar ataxia (SCA) families characterized by postural and action tremor and a very slow progression rate. A genome-wide linkage analysis revealed linkage to chromosome 3p26.1-25.3 with the highest multipoint lod score at D3S3728 (Zmax = 3.31 at theta = 0.00). The candidate region was 14.7 cM flanked by D3S1620 and D3S3691, which was partly overlapping with the locus of SCA15 characterized by pure cerebellar ataxia. Despite the difference in phenotypes, there remains a possibility that the causative gene for these Japanese SCA is allelic to SCA15.

Adult↗
PubMed2003

GalNAc-GD1a in human peripheral nerve: target sites of anti-ganglioside antibody.

BACKGROUND: The authors previously reported that immunoglobulin G (IgG) antibody to the ganglioside N-acetylgalactosaminyl GD1a (GalNAc-GD1a) is associated with the pure motor variant of Guillain-Barré syndrome (GBS). Elucidation of the localization of GalNAc-GD1a in human peripheral nerve tissue may lead to understanding of the pathogenetic role of anti-GalNAc-GD1a antibody in GBS. METHODS: IgG anti-GalNAc-GD1a-monospecific antibody was purified from anti-GalNAc-GD1a antibody-positive rabbit sera through an affinity column. Anti-neurofilament-200 monoclonal and anti-HNK-1 monoclonal antibodies were used as the markers for axon and myelin. Immunohistochemical study using double fluorescence labeling technique was conducted in human ventral roots (VR), dorsal roots (DR), intramuscular nerves, and sural nerves. Human teased ventral fibers also were studied. RESULTS: Anti-GalNAc-GD1a antibody immunostained an inner part of compact myelin and additionally a periaxonal-axolemma-related portion in the VR, small-diameter DR fibers, and IM nerves. In sural nerves, small fibers were selectively stained. In VR, the staining was localized in the paranodal region. CONCLUSION: Anti-GalNAc-GD1a antibodies in patients' sera may bind to those regions in the VR and IM nerves where GalNAc-GD1a is localized, and may function in the pathogenesis of pure motor type GBS. Further investigation is needed to explain the discrepancy between the immunolocalization of GalNAc-GD1a in sensory nerves and the absence of sensory disturbance in patients with GBS with IgG anti-GalNAc-GD1a antibodies.

Animals↗
PubMed2003

Benefit of IVIG for long-standing ataxic sensory neuronopathy with Sjögren's syndrome. IV immunoglobulin.

Ataxic sensory neuronopathy with Sjögren's syndrome is a devastating neurologic complication for which there is no established treatment. IV immunoglobulin (IVIG) was given to five patients with severe disabilities for an average of 12 years. Four patients showed remarkable improvement, two of whom responded after the first course. The authors conclude that IVIG is safe and effective to treat even chronically debilitated patients who have the disease, presumably because it ameliorates smoldering inflammation.

Aged↗
PubMed2003

Neurotoxicity of an endogenous brain amine, 1-benzyl-1,2,3,4-tetrahydroisoquinoline, in organotypic slice co-culture of mesencephalon and striatum.

Organotypic slice co-culture of the ventromedial portion of the mesencephalon and striatum was used to evaluate the neurotoxicity of 1-benzyl-1,2,3,4-tetrahydroisoquinoline, an endogenous brain amine related to Parkinson's disease. 1-Benzyl-1,2,3,4-tetrahydroisoquinoline is specifically increased in the cerebrospinal fluid of patients with Parkinson's disease and induces parkinsonian features in the monkey and mouse. Here, it decreased the dopamine content of the cultured mesencephalon in both dose- (10-100 microM) and time- (24 h to 7 days) dependent manners. This result suggests that the neurotoxicity of 1-benzyl-1,2,3,4-tetrahydroisoquinoline is correlated with the overall exposure (concentration multiplied by exposure time). Culture with 100 microM 1-benzyl-1,2,3,4-tetrahydroisoquinoline for 24 h irreversibly reduced the dopamine content. Furthermore, culture with 100 microM 1-benzyl-1,2,3,4-tetrahydroisoquinoline for 10 days caused morphological changes, including cell body shrinkage and distortion of dendritic morphology, in tyrosine hydroxylase-positive cells in the mesencephalon and reduced the number of cells by half. The increase in lactate dehydrogenase activity in the media produced by 1-benzyl-1,2,3,4-tetrahydroisoquinoline was significant in culture of the mesencephalon alone or its co-culture with striatum, but not in cultures of other brain regions. We suggest that 1-benzyl-1,2,3,4-tetrahydroisoquinoline is toxic to tyrosine hydroxylase-positive cells in the ventral mesencephalon and that it is correlated with the integral of the concentration by time of exposure. Thus a low concentration of 1-benzyl-1,2,3,4-tetrahydroisoquinoline may first induce a decrease in the dopamine content then shrinkage of the cell body, followed by the slow death of dopaminergic neurons over a long period. This is the first report that indicates 1-benzyl-1,2,3,4-tetrahydroisoquinoline exerts neurotoxicity at the cellular level, and reveals in part the character of its neurotoxicity.

Animals↗
PubMed2002

Distal myopathy with rimmed vacuoles: novel mutations in the GNE gene.

The authors present three novel missense mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene, the causative gene for hereditary inclusion body myopathy, in Japanese patients with distal myopathy with rimmed vacuoles. Seven out of nine patients had homozygous V572L mutation, one was a compound heterozygote with C303V and V572L mutations, and the remaining patient bore homozygous A631V mutation.

Adolescent↗
PubMed2002

PQBP-1 increases vulnerability to low potassium stress and represses transcription in primary cerebellar neurons.

PQBP-1 is a polyglutamine tract binding protein implicated in transcription. We previously reported that PQBP-1 and mutant ataxin-1, product of the spinocerebellar atrophy type 1 (SCA1) causative gene, cooperatively induce cell death in culture cells. Simultaneously, we showed that mutant ataxin-1 promoted interaction between PQBP-1 and RNA polymerase II and enhanced repression of the basal transcription by PQBP-1. In this study, we have examined the effects of overexpression of PQBP-1 to the primary-cultured cerebellar neurons. Our results indicate that overexpression of PQBP-1 inhibits the basal transcription in cerebellar neurons and increases their vulnerability to low potassium conditions.

Animals↗
PubMed2002

Hemiparkinsonism associated with a mesencephalic tumor.

A 66-year-old woman presented with a 3-year history of progressive right-sided hemiparkinsonism manifested by a right-hand resting tremor and right-sided bradykinesia. Magnetic resonance imaging (MRI) of the brain revealed a non-enhanced polycystic mass in the left midbrain. (11)C-methylspiperone ((11)C-NMSP) and (18)F-fluorodopa ((18)F-DOPA) positron emission tomography (PET) revealed a striatal hypometabolism that was restricted to the left side. These findings are consistent with a dysfunction in the left nigrostriatal dopaminergic pathway that is presumably induced by the cystic mass in the left midbrain. This case is significant due to the paucity of reports regarding the occurrence of a relatively pure parkinsonism that is associated with a mesencephalic space-occupying lesion.

Brain Stem Neoplasms↗
PubMed2002

In vitro formation of corticospinal synapses in an organotypic slice co-culture.

In order to study biological properties of the corticospinal tract, we have reconstructed this system in an in vitro slice culture preparation. Motor cortex and spinal cord slices, prepared from newborn rats, were co-cultured on pored membranes for 16-24 days. Anterograde labeling with biocytin showed that substantial neural connections had formed between the cortex and spinal cord slices. Retrograde labeling with horseradish peroxidase or 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate demonstrated that the parent cells were located primarily in the deeper layer of the cortex, as is found in vivo. Stimulation of the deep layer of the cortex elicited extracellular postsynaptic responses and intracellular excitatory postsynaptic potentials (EPSPs) in the co-cultured spinal cord that were mediated by the 1-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/ kainate-type glutamate receptor. The intracellular injection of biocytin after EPSPs were recorded showed that one-third of these cells were large stellate cells, which are thought to be motoneurons, while a large portion of the remaining labeled cells were bipolar cells of smaller sizes. Using this reconstructed in vitro preparation, we recorded field EPSPs (fEPSPs) along a 100-microm-interval lattice in the spinal gray matter, which allowed the quantitative evaluation of synapse formation. The fEPSP amplitudes were more than two-fold larger when the forelimb cortex was co-cultured with cervical cord rather than lumbar cord. However, hindlimb cortex did not show this preference. The fEPSP amplitudes were more than twice as large when the dorsal side of the spinal cord was adjacent to the cortex than the ventral side. In summary, we have reconstructed the corticospinal projection and synapses in vitro using cortical and spinal explants. This system allows for an efficient quantitative evaluation of synapse formation and for studies of postsynaptic cells. Our results suggest that synapse formation shows preferences along and perpendicular to the neuraxis of the spinal cord.

Animals↗
PubMed2002

Homozygous Machado-Joseph disease presenting as REM sleep behaviour disorder and prominent psychiatric symptoms.

A male patient carrying the homozygous gene for Machado-Joseph disease (MJD) presented at age 43 with sleep disturbances and psychiatric symptoms followed by ataxic speech and gait. A polysomnogram (PSG) showed decreased rates of sleep time and stage rapid eye movement (REM) and an increased rate of 'stage 1-REM with tonic EMG' (Tachibana et al., 1975); all compatible with REM sleep behaviour disorder (RBD). Molecular gene analysis at age 59 showed that the CAG repeat units in the MJD gene were 60 and 60, smaller than the reported lengths for homozygous MJD patients (63-70 and 66-72). In addition to sleep disturbances, in particular RBD, psychiatric symptoms may be important clinical features in both heterozygous and homozygous MJD.

Diagnosis, Differential↗
PubMed2001

Stiff-person syndrome associated with invasive thymoma: a case report.

We report a case of a 40-year-old female with continuous muscle stiffness and painful muscle spasms. The symptoms worsened over a two-week period after onset. Electrophysiological examinations revealed continuous muscle discharge, which was markedly reduced by intravenous administration of diazepam. High levels of anti-glutamic acid decarboxylase (GAD) antibodies were detected in both serum and cerebrospinal fluid, suggesting that the patient suffered from stiff-person syndrome. Steroid pulse therapy and immunoadsorption therapy alleviated the clinical symptoms and decreased the anti-GAD antibody titer. A chest CT revealed the presence of an invasive thymoma. Neither anti-acetylcholine receptor (AChR) antibodies nor symptoms of myasthenia gravis (MG) were observed. The patient underwent a thymectomy and postoperative radiotherapy. These treatments further alleviated the clinical symptoms. The present case is the first that associates stiff-person syndrome with invasive thymoma, and not accompanied by MG. The autoimmune mechanism, in this case, may be triggered by the invasive thymoma.

Adult↗
PubMed2001

Upregulation of the pro-apoptotic BH3-only peptide harakiri in spinal neurons of amyotrophic lateral sclerosis patients.

DNA fragmentation and activation of caspase-1, implicating involvement of apoptosis, have been reported in the spinal cord of amyotrophic lateral sclerosis (ALS) patients and transgenic mouse models of ALS. Because BH3-only members of the Bcl-2 family have pro-apoptotic activity, we examined the expression of the BH3-only peptide harakiri (Hrk) in the spinal cord of ALS patients. In situ expression of Hrk mRNA and immunoreactivity against the Hrk peptide were verified in the spinal neurons. In the immunoblot analysis, upregulated Hrk protein migrated at 16 kDa. Heterodimerization of Hrk with Bcl-2 was detected by immunoprecipitation, which suggests the competition of Hrk and anti-apoptotic Bcl-2. These findings suggest that Hrk plays a role in apoptotic events in ALS pathogenesis.

Adult↗
PubMed2001

A new splicing variant for human tyrosine hydroxylase in the adrenal medulla.

It has been reported that several mRNA isoforms of tyrosine 3-monooxygenase (tyrosine hydroxylase; TH) occur only in primates. New TH isoforms produced by skipping of exon 3 in the adrenal medulla of patients with progressive supranuclear palsy (PSP) have recently been reported, J. Neurochem. 67 (1996) 19. Here, we looked for the presence of new TH isoforms in control brains and adrenal medulla and in brains from patients with PSP. We found a novel type of TH mRNA in the adrenal medulla from one of the control subjects. The mRNA lacked exon 4, resulting in a premature stop codon at amino acid 147. This result suggests the importance of alternative splicing in the regulation of TH activity.

Adrenal Medulla↗
PubMed2001

alpha-Synuclein affects the MAPK pathway and accelerates cell death.

Insoluble alpha-synuclein accumulates in Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy. However, the relationship between its accumulation and pathogenesis is still unclear. Recently, we reported that overexpression of alpha-synuclein affects Elk-1 phosphorylation in cultured cells, which is mainly performed by mitogen-activated protein kinases (MAPKs). We further examined the relationship between MAPK signaling and the effects of alpha-synuclein expression on ecdysone-inducible neuro2a cell lines and found that cells expressing alpha-synuclein had less phosphorylated MAPKs. Moreover, they showed significant cell death when the concentration of serum in the culture medium was reduced. Under normal serum conditions, the addition of the MAPK inhibitor U0126 also caused cell death in alpha-synuclein-expressing cells. Transfection of constitutively active MEK-1 resulted in MAPK phosphorylation in alpha-synuclein-expressing cells and improved cell viability even under reduced serum conditions. Thus, we conclude that alpha-synuclein regulates the MAPK pathway by reducing the amount of available active MAPK. Our findings suggest a mechanism for pathogenesis and thus offer therapeutic insight into synucleinopathies.

14-3-3 Proteins↗
PubMed2001

Single cell analysis of CAG repeat in brains of dentatorubral-pallidoluysian atrophy (DRPLA).

Somatic mosaicism of an expanded repeat is present in tissues of patients with triplet repeat diseases. Of the spinocerebellar ataxias associated with triplet repeat expansion, the most prominent heterogeneity of the expanded repeat is seen in dentatorubral-pallidoluysian atrophy (DRPLA). The common feature of this somatic mosaicism is the difference in the repeat numbers found in the cerebellum as compared to other tissues. The expanded allele in the cerebellum shows a smaller degree of expansion. We previously showed by microdissection analysis that the expanded allele in the granular layer in DRPLA cerebellum has less expansion than expanded alleles in the molecular layer and white matter. Whether this feature of lesser expansion in granule cells is common to other types of neurons is yet to be clarified. We used a newly developed excimer laser microdissection system to analyze somatic mosaicism in the brains of two patients, one with early- and another with late-onset DRPLA, and used single cell PCR to observe the cell-to-cell differences in repeat numbers. In the late onset patient, repeat expansion was more prominent in Purkinje cells than in granule cells, but less than that in the glial cells. In the early onset patient, repeat expansion in Purkinje cells was greater than in granule cells but did not differ from that in glial cells. These findings suggest that there is a difference in repeat expansion among neuronal subgroups and that the number of cell division cycles is not the only determinant of somatic mosaicism.

DNA Mutational Analysis↗
PubMed2001

Anti-Gal-C antibodies in GBS subsequent to mycoplasma infection: evidence of molecular mimicry.

The authors previously reported the presence of antibody against galactocerebroside (Gal-C) in sera from patients with Guillain-Barré syndrome subsequent to Mycoplasma pneumoniae infection. Anti-Gal-C antibody activities in these sera were inhibited specifically by the M. pneumoniae reagent. A rabbit anti-Gal-C antibody recognized several glycolipids in M. pneumoniae. These data show that a Gal-C-like structure is present in M. pneumoniae, indicative of molecular mimicry between a major myelin glycolipid, Gal-C, and M. pneumoniae.

Animals↗