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T Miyatake

Publications and source records attributed to T Miyatake.

At least 145 records · Page 8Linked to original sources
PubMed1993

[Mutation analysis of amyloid precursor protein in early-onset familial Alzheimer's disease].

Recently, three different mutations have been found at codon 717 of the amyloid precursor protein (APP) gene, changing the native valine to isoleucine, phenylalanine and glycine in some familial Alzheimer's disease (FAD) kindreds. More recently, some other mutations have also been reported at codons 670 and 671 (double mutation), and codon 692. As analysis of coding region except exon 16 and 17 has been insufficient in previous reports, we analyzed entire coding region of the APP gene of 6 Japanese early-onset FAD kindreds using automated sequencer. Three FAD families showed known 717 Val to Ile mutation, whereas no novel mutations were detected.

Age of Onset↗
PubMed1993

[Absence of linkage disequilibrium at amyloid precursor protein gene locus in Japanese familial Alzheimer's disease with 717Val-->Ile mutation].

To date, eleven independent early onset familial Alzheimer's disease (EOFAD) pedigrees with the 717Val-->Ile mutation of amyloid precursor protein (APP) gene have been identified. Interestingly, five pedigrees have been of Japanese origin. The apparent ethnic prediction of this mutation raises the possibility that there is a founder effect in Japan. If the hypothesis holds true, we can expect the presence of linkage disequilibrium at the APP locus. We did not, however, observe any significant linkage disequilibrium at any locus of APP or the adjacent GT12 locus in the five Japanese EOFAD probands with the 717Val-->Ile mutation. The result indicates that a founder effect would probably not be present in Japanese EOFAD pedigrees with the 717Val-->Ile mutation.

Age of Onset↗
PubMed1992

Secretory pathway of beta/A4 amyloid protein precursor in familial Alzheimer's disease with Val717 to Ile mutation.

To determine whether the secretory pathway of beta/A4 amyloid protein precursor (APP) was altered in familial Alzheimer's disease (FAD) with a mutation of Val717 to Ile, cerebrospinal fluid was studied by Western blotting. The ratio of the density of the bands labeled with the antibody against the amino-terminal part of beta/A4 protein to that with the antibody against amino-terminal part of beta/A4 protein to that with the antibody against amino-terminal part of APP was not decreased. The present result suggests that the secretory pathway is not altered by the mutation in such a way that amyloidogenic full-length beta/A4 protein is generated.

Alzheimer Disease↗
PubMed1992

Remote astrocytic response of prefrontal cortex is caused by the lesions in the nucleus basalis of Meynert, but not in the ventral tegmental area.

The nucleus basalis of Meynert (nbM) was lesioned by injection of ibotenic acid, in 200 g male Wistar rats. The rats were killed 1, 3, 7 or 21 days after surgery, the brains were removed and the prefrontal cortices were subjected to immunohistochemical and Western blot analysis for the expression of glial fibrillary acidic protein (GFAP). In some rats, vehicle was injected into the nbM and in others 6-hydroxydopamine (6-OHDA) was injected into the ventral tegmental area (VTA). Quantitative Western blot analysis revealed significantly greater immunoreactivity for GFAP in the prefrontal cortex of nbM-lesioned rats. Immunohistochemical examination revealed fibrous and hypertrophic GFAP-positive astrocytes even one day after surgery, and this reaction was stronger at 3 days after surgery. After this peak, GFAP-immunoreactivity of the astrocytes decreased from 7 days to 21 days. In contrast, GFAP-positive astrocytes were not observed in the brains of vehicle-injected or VTA-lesioned rats, even 21 days after surgery. The present results indicate that cortical astrocytes respond to cholinergic deafferentation. In addition, our findings provide new insights into the abnormalities of cortical glial cells after cholinergic deafferentation in Alzheimer's disease.

Acetylcholine↗
PubMed1992

A novel exon mutation in the human beta-hexosaminidase beta subunit gene affects 3' splice site selection.

The molecular basis of a dramatically decreased steady state level of beta-hexosaminidase beta subunit mRNA in a patient with juvenile Sandhoff disease was investigated. Nucleotide sequence analysis of the HEXB gene coding for the beta subunit revealed two single base substitutions, one in exon 2 (A to G, a known polymorphism) and the other in exon 11 (C to T). Analysis of the beta subunit mRNA species demonstrated activation of a cryptic splice site in exon 11 as well as skipping of the exon. A transfection assay using a chimeric gene containing intron 10 flanked by cDNA sequences carrying the mutation confirmed that the single base substitution located at position 8 of exon 11 inhibits the selection of the normal 3' splice site. The results demonstrate a new type of exon mutation affecting 3' splice site selection.

Adult↗
PubMed1992

Molecular cloning of human growth inhibitory factor cDNA and its down-regulation in Alzheimer's disease.

In previous studies, we discovered a growth inhibitory factor (GIF) that was abundant in normal human brain, but greatly reduced in Alzheimer's disease (AD) brain. Molecular cloning of a full-length cDNA for human GIF revealed that the GIF had striking homology to metallothioneins. Furthermore, it was determined that the GIF gene was on chromosome 16, as are the metallothionein genes. GIF, in contrast to metallothioneins, was found to be expressed exclusively in the nervous system. The GIF protein produced by Escherichia coli harboring the GIF cDNA in a prokaryotic expression vector inhibited the growth of neonatal rat cortical neurons. These results indicate that GIF is a new member of the metallothionein family with distinct tissue-specific expression and functions. Northern blot analysis revealed that expression of the GIF mRNA is drastically decreased in AD brains. The result raises the possibility that down-regulation of the GIF gene in AD brain plays an important role in the pathogenesis of AD.

Alzheimer Disease↗
PubMed1992

Severe acute axonal form of Guillain-Barré syndrome associated with IgG anti-GD1a antibodies.

We report cases of 2 patients with pure motor Guillain-Barré syndrome of explosive onset who required mechanical ventilation for more than 2 months. Their electrophysiologic findings and poor clinical recoveries suggested severe axonal degeneration involving the motor nerves. Enzyme-linked immunosorbent assay and thin-layer chromatogram-immunostaining showed the sera of both patients had high IgG antibody titer against GD1a ganglioside. Their titers decreased with the clinical course of the illness. GD1a as well as GM1, appears to be the target pathogenic antigen in motor axon disorders. Elevated IgG anti-GD1a antibody titer may prove useful for predicting severe GBS.

Acute Disease↗
PubMed1992

Ataxic polyneuropathy and anti-Pr2 IgM kappa M proteinemia.

A case of ataxic neuropathy associated with IgM kappa M proteinemia is reported. Double filtration plasmapheresis effectively treated the neuropathy. The IgM kappa antibody had anti-Pr2 cold agglutinin activity. We demonstrated reactivities of the IgM kappa antibody to sialosyl paragloboside, sialosyl lactosaminyl paragloboside, GT1b, GD1a, GD1b, GM3 and GD3 on high-performance thin-layer chromatography immunostaining and enzyme-linked immunosorbent assay, which is previously unreported antigenic specificity of the M proteins in cases of paraproteinemic neuropathy. IgM M protein with anti-Pr2 cold agglutinin activity may play a pathogenetic role in peripheral nerve demyelination, because the target antigens of the M protein are present in myelin and possibly in endothelial cells of the peripheral nervous system.

Ataxia↗
PubMed1992

An adenosine uptake blocker, propentofylline, reduces glutamate release in gerbil hippocampus following transient forebrain ischemia.

In the present study, the effect of the adenosine uptake blocker, propentofylline (HWA 285) on the extracellular concentration of several amino acids including glutamate, glycine and taurine following 10 min of forebrain ischemia in gerbil hippocampus was investigated using in vivo microdialysis. Pretreatment with HWA 285 (20 mg/kg i.p.) significantly reduced the extracellular concentration of glutamate following ischemia but did not significantly alter levels of other amino acids such as glycine and taurine. These findings suggest that the neuroprotective effect of HWA 285 may be associated with inhibition of glutamate release in the gerbil hippocampus.

Adenosine↗
PubMed1992

Genomic organization of a cDNA (QM) demonstrating an altered mRNA level in nontumorigenic Wilms' microcell hybrid cells and its localization to Xq28.

Using a cosmid clone derived from human Xq28 as a probe which shows cross-species homology, we isolated cDNA clones and the nucleotide sequence analysis of the cDNA revealed that the cDNA is identical to QM cDNA. The QM cDNA has recently been reported as a cDNA with down-regulation in tumorigenic Wilms' tumor microcell hybrid. Comparison of the nucleotide sequences of the cDNA with those of the genomic DNA allowed us to determine the genomic organization of the QM gene. The QM gene consists of at least 7 exons and is located at Xq28. Southern blot analysis of a somatic cell hybrid panel indicates that the QM genes are scattered at least to chromosome 2, 3, 6, 14, 16, and possibly to other chromosomes. Northern blot analysis demonstrated the QM gene is expressed in all the examined adult human tissues as well as cell lines including HeLa cells, fibroblasts, and somatic cell hybrids with increased expression in liver, spleen, testis, and adrenal gland. The results suggest that the QM gene belongs to a new multi-gene family with yet undetermined function.

Amino Acid Sequence↗
PubMed1992

IgG antibody against GM1, GD1b and asialo-GM1 in chronic polyneuropathy following Mycoplasma pneumoniae infection.

Serum IgG in a patient with chronic polyneuropathy after Mycoplasma pneumoniae infection reacted with ganglioside GM1, GD1b and asialo-GM1 on thin-layer chromatograms using an immunostaining technique as well as an enzyme-linked immunosorbent assay, suggesting that the galactosyl (beta 1-3)N-acetylgalactosaminyl moiety could be a target antigen in this patient. Serum IgG reacting with these glycolipids may be involved in the pathogenesis of both motor and sensory neuropathies in this patient.

Adolescent↗
PubMed1992

Acute relapsing sensory neuropathy associated with IgM antibody against B-series gangliosides containing a GalNAc beta 1-4(Gal3-2 alpha NeuAc8-2 alpha NeuAc)beta 1 configuration.

We report a patient with a relapsing form of the acute sensory neuropathy syndrome associated with IgM-kappa type monoclonal gammopathy of undetermined significance. He rapidly developed marked sensory ataxia without weakness following an upper respiratory tract infection at age 44. The symptoms reached their maximum in a few days, followed by subsequent gradual improvement over a few weeks. However, unsteady gait remained as a chronic deficit. Stepwise progression of his symptoms occurred over 15 years with 10 similar relapses. Sensory nerve conduction studies showed the absence of action potentials, and sural nerve biopsy revealed the marked loss of large myelinated fibers. The patient's serum had an extremely high titer of an IgM monoclonal antibody directed against gangliosides GD2, GD1b, GT1b, and GQ1b.

Acute Disease↗
PubMed1992

A patient with severe iron-deficiency anemia and memory disturbance.

A 56-year-old woman presented with severe iron-deficiency anemia and memory disturbance. She had been in a state of severe iron deficiency for many years due to an unbalanced diet. Aerobic exercise test revealed an abnormal elevation of lactate and pyruvate reflecting mitochondrial dysfunction. After iron replacement therapy, WAIS verbal IQ score improved from 63 to 83, and levels of lactate and pyruvate on aerobic exercise test were normalized. We raise the possibility that severe and long-term iron deficiency anemia may cause memory disturbance due to mitochondrial dysfunction.

Anemia, Hypochromic↗