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Biomedical subjects

T Miyatake

Publications and source records attributed to T Miyatake.

At least 109 records · Page 6Linked to original sources
PubMed1993

Identification of amyloid precursor protein in synaptic plasma membrane.

Although the etiology of Alzheimer's disease has not been elucidated yet, dysfunction and loss of synapses are believed to cause dementia. Recent studies suggest that the primary cause of the disease is closely related to the aberrant processing of the amyloid precursor protein (APP). To investigate the localization of APP at synaptic sites, we obtained synaptic plasma membrane and synaptic vesicles from rat brain. Enhanced chemiluminescence (ECL) western blot analysis using two specific polyclonal antibodies against APP revealed strong APP immunoreactivity in the synaptic plasma membrane, but not in the synaptic vesicle fraction. These data indicate that APP is localized at the synaptic plasma membrane and may play a role in physiological synaptic activity. Alternative localization or aberrant processing of APP at the synaptic site may cause impairment of synaptic function in Alzheimer's disease.

Amyloid beta-Protein Precursor↗
PubMed1993

Novel lacto-ganglio type gangliosides with GM2-epitope in bovine brain which react with IgM from a patient of the amyotrophic lateral sclerosis-like disorder.

A motor neuron disorder resembling that of amyotrophic lateral sclerosis was found in a patient who had received the intramuscular administration of a mixture of bovine brain gangliosides (Yuki, N., Sato, S., Miyatake, T., Sugiyama, K., Katagiri, T., and Sasaki, H. (1991) Lancet 337, 1109-1110). A very high titer of anti-GM2 IgM was detected in the patient's serum and the patient quickly recovered after plasmapheresis. The clinical course of the patient appeared to be different from amyotrophic lateral sclerosis and the anti-GM2 IgM was thought to be the culprit. The IgM reacted with GM2, GM1b-GalNAc, SPG(alpha 2-3)-GalNAc, and GD1a-GalNAc, but not with GA2 or GD2, meaning that the epitope recognized by the IgM was the GM2-like terminal structure, GalNAc beta 1-4(Neu-Ac alpha 2-3)Gal beta 1-. In this study, we found two novel GM2-epitope containing gangliosides, X1 and X2, in bovine brain gangliosides by TLC immunostaining using the patient's IgM. They were characterized as unique lacto-ganglio type gangliosides containing the following branching structures. [formula: see text] Their unusual structures may be immunogenic to humans to induce anti-GM2 antibody.

Aged↗
PubMed1993

Anti-B-series ganglioside-recognizing autoantibodies in an acute sensory neuropathy patient cause cell death of rat dorsal root ganglion neurons.

To examine the cytotoxicity of a patient's serum with an acute relapsing sensory neuropathy syndrome, dorsal root ganglion neurons from young adult rats were cultured in the presence of the patient's serum which had an extremely higher-titer monoclonal IgM antibody recognizing B-series gangliosides, GD2, GD1b, GT1b and GQ1b. By the addition of the inactivated patient's serum, the relatively larger cells died after undergoing of metamorphosis during several hours of culture, whilst the smaller cells survived. The IgM fraction isolated from the patient's serum showed similar cytotoxicity towards the neurons as the inactivated whole serum. No cytotoxicity was observed with the IgM fraction-containing medium after it had been absorbed with ganglioside GD1b. The results suggested that the anti-B-series ganglioside-directed antibody is the causal agent for the human neurologic disease.

Acute Disease↗
PubMed1993

Subpial beta/A4 peptide deposits are closely associated with amyloid angiopathy in the elderly.

In order to clarify the significance of subpial beta/A4 peptide deposits (SP beta PD), we examined the brains of 160 consecutive autopsied cases (average age 84.4 +/- 7.7 years) with or without dementia of the Alzheimer type (DAT) pathologically and immunohistochemically. SP beta PD and amyloid angiopathy (AA) showed a significant positive correlation in their severities, both in the DAT and non-DAT groups. AA was present in most cases with SP beta PD, but was absent in all cases without SP beta PD. Our results suggest that SP beta PD and AA would be the related lesions, and that SP beta PD would be formed previous to AA.

Aged↗
PubMed1993

Cerebellar nitric oxide synthase activity is reduced in nervous and Purkinje cell degeneration mutants but not in climbing fiber-lesioned mice.

We measured nitric oxide synthase activity in nervous, Purkinje cell degeneration mutant mice and 3-acetylpyridine-treated mice to determine the cellular localization of nitric oxide synthase in the cerebellum. Nitric oxide synthase activity per cerebellum was reduced to less than 50% of that of controls in nervous and Purkinje cell degeneration mutants, while in 3-acetylpyridine-treated mice there was no reduction.

Afferent Pathways↗
PubMed1993

Reduced membrane-associated protein kinase C(beta) immunoreactivity in the hippocampus of reserpinized rat brain.

Protein kinase C(beta) immunoreactivity was determined in the membrane and cytosol fractions of the hippocampus, frontal cortex and cerebellum after repetitive, intraperitoneal administration of reserpine. A marked decrease in the immunoreactivity was observed in the membrane of the hippocampus, while no significant change was found in any other subfractions of the frontal cortex or cerebellum. These findings suggest a novel mechanism regulating the distribution of protein kinase C. The topographical selectivity in the present study may indicate the importance of the alteration of protein kinase C in the pathophysiological mechanism in Alzheimer's disease.

Animals↗
PubMed1993

Human leukocyte antigens in Fisher's syndrome.

We performed human leukocyte antigens (HLA) typing for class I antigens on 19 Japanese patients with Fisher's syndrome. We demonstrated a statistically significant association between the disease and the HLA-B39 antigen.

Disease Susceptibility↗
PubMed1993

Stereotyped hand clasping: an unusual tardive movement disorder.

We report an 83-year-old woman with vascular parkinsonism who presented with stereotyped rhythmical hand-clasping movements after 18 months exposure to neuroleptics. Although stereotypical rhythmical orolinguomasticatory and limb movements are the most common tardive dyskinesia in the elderly, we feel this woman's hand clasping represents another unusual expression of a tardive movement disorder.

Aged↗
PubMed1993

Association of IgG anti-GD1a antibody with severe Guillain-Barré syndrome.

We earlier reported cases of 2 patients with severe acute Guillain-Barré syndrome (GBS) associated with high-IgG anti-GD1a antibody titer. We now have investigated the autoantibody against GD1a or GM1 in 37 GBS patients using the enzyme-linked immunosorbent assay and have found a statistically significant association between IgG anti-GD1a antibody and the severity of the disease (need of a respirator for more than 1 month and a poor functional prognosis 3 months after neurologic onset). An autopsy which showed severe GBS associated with IgG anti-GD1a antibody produced the following findings: (1) severe axonal degeneration and segmental demyelination of peripheral nerves; (2) lymphocytic infiltration; and (3) marked central chromatolysis of the lower motoneurons.

Adolescent↗
PubMed1993

Expression of the large myelin-associated glycoprotein isoform in rat oligodendrocytes around cerebral infarcts.

An immunohistochemical method that uses two specific antisera-distinguishable myelin-associated glycoprotein (MAG) isoforms showed an expression of large MAG isoform (L-MAG) protein in the oligodendrocyte cytoplasms in the white matter around experimental cerebral infarcts produced by occlusion of the left middle cerebral artery in the rat. L-MAG protein also was detected in the white matter on the contralateral side. This protein appears prior to S-MAG protein in myelination and remyelination in the central and peripheral nervous systems, and is believed to function in myelin formation. Because L-MAG protein has been found in the oligodendrocyte cytoplasm only in the early development period, its appearance in this cytoplasm after ischemic insult is evidence of MAG regeneration.

Animals↗
PubMed1993

Expression of myelin-associated glycoprotein isoforms after sciatic nerve crush injury in mice.

The large myelin-associated glycoprotein isoform (L-MAG) protein and small myelin-associated glycoprotein isoform (S-MAG) protein were demonstrated after sciatic nerve crush injury in mice by an immunoblotting technique using specific antibodies to the L-MAG protein and the S-MAG protein, respectively. Immunoblots indicated a rapid decrease in expression of both isoform proteins in the crushed sciatic nerves to < 10% of the control side. By 13 d after injury, L-MAG protein expression had quickly recovered to 100% of the control level. Following the increase in L-MAG protein expression, S-MAG protein expression recovered to 100% by 20 d after injury. It has been reported that the developmental maximum expression of L-MAG protein precedes that of S-MAG protein in both central and peripheral nervous system (CNS and PNS). Our previous work demonstrated that L-MAG mRNA was characteristically induced at the time of most active myelination, including remyelination in the CNS. We here have shown the expression of L-MAG protein precedes that of S-MAG protein during active remyelination in the PNS. This suggests that it plays an important role in the early stage of myelin formation.

Animals↗
PubMed1993

Effects of smoking in patients with early-onset Parkinson's disease.

Smoking a cigarette relieved symptoms in 6 patients with early-onset Parkinson's disease. In these patients smoking reduced tremor, rigidity, bradykinesia, and gait disturbance including frozen gait. These effects lasted for about 10-30 min, and relieved parkinsonian symptoms in the off-period. Nicotine chewing gum had a lesser effect. Nicotine is thought to activate the nigrostriatal dopaminergic pathway and increase the release of dopamine in the striatum, and this can explain the effects of smoking in these patients.

Adult↗
PubMed1993

An immunologic abnormality common to Bickerstaff's brain stem encephalitis and Fisher's syndrome.

The nosological position of Bickerstaff's brain stem encephalitis (BBE) has yet to be established, and its etiology is not clear. Because anti-GQ1b antibody frequently occurs in patients with Fisher's syndrome (FS) and there are clinical similarities between FS and BBE, we investigated anti-ganglioside antibodies in sera from 3 BBE patients who had transient long tract signs in addition to acute ophthalmoplegia and cerebellar-like ataxia in order to clarify the etiology and nosological position of BBE. High IgG anti-GQ1b antibody titers were present in all 3 sera samples but decreased with the clinical course of the illness. In contrast, no anti-GQ1b antibody was found in sera from patients with other neurologic diseases which were able to produce transient brain stem disturbance: multiple sclerosis, neuro-Behçet's disease, brain stem infarction, herpes simplex virus encephalitis, and Wernicke's encephalopathy. The finding that BBE and FS shared common autoantibody suggests that autoimmune mechanism common to FS is likely in BBE, and that both conditions represent a distinct disease with a wide spectrum of symptoms that include ophthalmoplegia and ataxia.

Adult↗
PubMed1993

Cerebral amyloid angiopathy: a significant cause of cerebellar as well as lobar cerebral hemorrhage in the elderly.

We investigated consecutive 1000 autopsied cases (average age 82.9 years) clinicopathologically in order to reveal the significance of cerebral amyloid angiopathy (CAA) as a cause of senile intracranial hemorrhages. We found 101 cases with intracerebral hemorrhages, and CAA accounted for 10.9% of them (31.0% of lobar cerebral hemorrhages, and 14.3% of cerebellar ones). In contrast to hypertensive hemorrhages, CAA-related ones (1) ruptured into the subarachnoid space without exception, (2) often coexisted with dementia of Alzheimer's type, and (3) frequently occurred in the night without elevated blood pressure at onset. The cerebrovascular amyloid was strongly immunoreactive with antibody to beta-protein in all of the cases with CAA-related hemorrhages, and less intensively with antibody to cystatin C in 91% of them. Our data indicate that CAA is an important etiological factor of cerebellar hemorrhages, as well as lobar cerebral hemorrhages, in normotensive, aged patients.

Aged↗
PubMed1993

Molecular cloning of rat growth inhibitory factor cDNA and the expression in the central nervous system.

Human growth inhibitory factor (GIF) is a new metallothionein-related molecule whose expression is markedly reduced in Alzheimer's disease (AD) brain. We have recently isolated a full-length cDNA for human GIF that has a striking homology to metallothioneins (MTs). As an initial step to better understanding of the biological functions of GIF, we have isolated a full-length cDNA for rat GIF. Comparison of the predicted amino acid sequence with that of human GIF revealed a strikingly high homology (84% identity). Rat GIF cDNA also showed a striking homology to rat MT-1 and MT-II (66% and 62% identities on amino acid sequences, respectively). All cysteine residues were conserved among rat GIF, human GIF and MTs, indicating that cysteine residues play an important function in these molecules. Compared to mammalian MTs, there were 3 bp and 12 bp insertions near the amino-terminal and carboxy-terminal regions in the rat GIF. The rat GIF mRNA was found to be expressed exclusively in the central nervous system, being expressed predominantly in rat cortical astrocytes in primary culture. Although the rat GIF mRNA expression was low during the fetal stage, a dramatic increase of the rat GIF mRNA expression was demonstrated during the postnatal period of 10-17 days. These results indicate that transcriptional regulation of the rat GIF gene is quite different from that of MTs despite its strikingly high homology with MTs.

Amino Acid Sequence↗
PubMed1993

Soluble derivatives of beta/A4 amyloid protein precursor in human cerebrospinal fluid are both N- and O-glycosylated.

The linkage of the glycan chain to the beta/A4 amyloid protein precursor (APP) in cerebrospinal fluid (CSF) was studied by Western blot analysis. The apparent molecular weight of APP in CSF was reduced from 103 to 100 kDa by N-glycanase, and to 96 kDa by O-glycanase treatment, respectively. These data indicate that APP is both N- and O-glycosylated in one molecule. The extent of glycosylation of APP was not altered in the CSF from patients with Alzheimer's disease.

Adult↗
PubMed1993

Inhibitory spectra of purified protease nexin-II and related proteins towards cellular proteinases.

Amyloid beta protein (beta/A4) is deposited in senile plaques of patients with Alzheimer's disease. This protein is derived from a larger membrane-associated protein, termed amyloid precursor protein (APP). The constitutive processing of APP occurs at the central portion of beta/A4, resulting in the release of large N-terminal peptides. We have purified these peptides from the culture medium of cDNA-transfected COS-1 cells. Some of the isoforms contain the Kunitz-type protease inhibitor (KPI) domain and strongly inhibit trypsin, chymotrypsin and plasmin, but do not inhibit kallikrein, prolyl endopeptidase or granzyme A. The peptides also do not inhibit cysteine proteases such as cathepsin B or calpain. Soluble APPs lacking the KPI domain fail to inhibit any of these proteases. The results indicate that the KPI domain in soluble APPs has protease inhibitory activity against certain serine proteases.

Amino Acid Sequence↗