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Biomedical subjects

Shigetoshi Kuroda

Publications and source records attributed to Shigetoshi Kuroda.

At least 19 recordsLinked to original sources
PubMed2006

A genetic variant of the serine racemase gene is associated with schizophrenia.

BACKGROUND: Serine racemase (SRR) is a brain-enriched enzyme that converts L-serine to D-serine, which acts as an endogenous ligand of N-methyl D-aspartate (NMDA) receptors. Dysfunction of SRR may reduce the function of NMDA receptors and susceptibility to schizophrenia. METHODS: We genotyped three single-nucleotide polymorphisms (SNPs) of the 5' region of the SRR gene in 525 patients with schizophrenia and 524 healthy controls. Effects of SNPs on the promoter activity and on serum levels of total and D-serine were examined. RESULTS: We found a significant excess of the IVS1a+465C allele of the SRR gene in schizophrenia, especially in the paranoid subtype (p = .0028). A reporter assay showed that the IVS1a+465C allele had 60% lower promoter activity than did the IVS1a+465G allele. CONCLUSIONS: The IVS1a+465C allele of the SRR gene, which reduces expression of the gene, is a risk factor for schizophrenia, especially the paranoid subtype.

Adult↗
PubMed2006

Amyotrophic lateral sclerosis with dementia: an autopsy case showing many Bunina bodies, tau-positive neuronal and astrocytic plaque-like pathologies, and pallido-nigral degeneration.

We report the case of a 54-year-old woman with mental retardation who developed frontotemporal dementia and amyotrophic lateral sclerosis (ALS) in the presenium. She presented with dementia at age 48, and motor neuron signs developed at age 53. She had no family history of dementia or ALS. Postmortem examination disclosed histopathological features of ALS, including pyramidal tract degeneration, mild loss of motor neurons, and many Bunina bodies immunoreactive for cystatin C, but not ubiquitin-positive inclusions. Unusual features of this case included severe neuronal loss in the substantia nigra and medial globus pallidus. The subthalamic nucleus, limbic system, and cerebral cortex were well preserved. In addition, neurofibrillary tangles (NFTs) were found in the frontal, temporal, insular, and cingulate cortices, nucleus basalis of Meynert, and locus coeruleus, and to a lesser degree, in the dentate nucleus, cerebellum, hippocampus, and amygdala. No ballooned neurons, tufted astrocytes, or astrocytic plaques were found. Tau immunostaining demonstrated many pretangles rather than NFTs and glial lesions resembling astrocytic plaques in the frontal and temporal cortices. This glial tau pathology predominantly developed in the middle to deep layers in the primary motor cortex, and was frequently associated with the walls of blood vessels. NFTs were immunolabeled with 3-repeat and 4-repeat specific antibodies against tau, respectively. Although the pathophysiological relationship between tau pathology and the selective involvement of motor neurons, substantia nigra, and globus pallidus was unclear, we considered that it might be more than coincidental.

Amyotrophic Lateral Sclerosis↗
PubMed2006

Quality of life for patients with schizophrenia in a Japanese psychiatric hospital.

Providing a good quality of life (QOL) has recently been recognized as a central purpose of health care in psychiatry. In this study, we performed a detailed evaluation of the subjective QOL of schizophrenic inpatients and examined the relationship of QOL to various patient characteristics. This study was conducted on schizophrenic inpatients and nursing staff members in a Japanese private psychiatric hospital. As a result, only depression showed a weak, but significant, relationship with subjective QOL. Other characteristics showed no meaningful correlation to subjective QOL. Comparison between the schizophrenic group and the nursing staff group revealed that schizophrenic inpatients showed a lower QOL in the domains of physical health and social relationships. Schizophrenia itself and/or accompanying disabilities might induce lower subjective QOL. It is difficult to determine what the important factors are, except for depression, for subjective QOL of schizophrenic inpatients. However, depression should receive more attention for the QOL in the physical health and psychological health domains.

Activities of Daily Living↗
PubMed2006

Frequency and clinicopathological characteristics of alcoholic cerebellar degeneration in Japan: a cross-sectional study of 1,509 postmortems.

Alcoholic cerebellar degeneration (ACD) is a pivotal neurological complication in alcoholics. However, although there are a few autopsy reports and some data on its frequency, it is considered very rare in Japan. The aims of this study were (1) to estimate the frequency of the disease in Japanese autopsy cases, and (2) to examine the clinicopathological features of symptomatic and asymptomatic cases of ACD. We reviewed the records of 1,509 Japanese autopsies obtained from three autopsy series in Japan, and selected all 55 cases (3.6%) with alcoholism. On neuropathological reexamination, ACD was confirmed in six male alcoholics [0.4% of all subjects; 10.9% of all alcoholics; mean age at death 59.3+/-13.4 years (+/- SD)], including three asymptomatic cases. These frequencies were much lower than some previous Western findings, but more common than that has been expected in Japan. The frequencies of memory impairment and ataxia in ACD cases were significantly higher than those in alcoholics without any alcohol-related pathologies. In ACD cases, loss of Purkinje cells, narrowing of the width of the molecular layer, and tissue rarefaction in the granular layer were observed in the anterior and superior portions of the vermis of the cerebellum. In adjacent regions, the Purkinje cell and molecular layers were more mildly affected. The distribution of severely affected regions was more restricted in the asymptomatic cases than in the symptomatic cases. This study confirmed the frequency of asymptomatic cerebellar degeneration in alcoholics, suggesting that early intervention in alcoholism in the subclinical phase is important to prevent the development of cerebellar symptoms.

Adult↗
PubMed2006

G(olf) protein levels in rat striatum are increased by chronic antidepressant administration and decreased by olfactory bulbectomy.

There are many studies of the mechanisms of antidepressants; however, most of these studies were conducted on the hippocampus or frontal cortex. In the present study, we hypothesized that the nucleus accumbens and caudate/putamen might be major targets for antidepressant effects. Thus, we focused on G(olf) protein, a stimulant alpha-subunit of G protein that is coupled with the dopamine D1 receptor and specifically expressed in the striatum (nucleus accumbens, caudate/putamen and olfactory tubercle) in the rat brain. We examined the effects of chronic administration of imipramine, fluvoxamine, maprotiline and, as a negative control, cocaine on the level of G(olf) protein in the rat striatum. We also examined the effect of olfactory bulbectomy. Chronic imipramine treatment (10 mg/kg for 2 or 4 weeks) significantly increased the level of G(olf) in the striatum (by 17% or 18%, respectively), although this increase was not apparent after only 1 week of treatment. The time course of these changes corresponded well to that of the clinical efficacy of imipramine. Chronic fluvoxamine and maprotiline treatment (20 mg/kg for 2 weeks) also significantly increased the level of G(olf) (by 9% and 25%, respectively), but cocaine did not alter it significantly. Bulbectomy decreased the G(olf) protein level by 9%. The increases in G(olf) protein after chronic administration of these three different classes of antidepressants and the decrease after bulbectomy suggest that G(olf) protein may play an important role in the antidepressant effect.

Adrenergic Uptake Inhibitors↗
PubMed2006

Genetic variant of prodynorphin gene is risk factor for methamphetamine dependence.

Previous studies have indicated that genetic factors substantially affect development of substance use disorders, including methamphetamine dependence. Prodynorphin (PDYN) is an opioid peptide precursor that yields dynorphins, endogenous kappa opioid-receptor agonists that play important roles in substance abuse. A physiologically active polymorphism of 1-4 repeats of a 68-bp element in the promoter region of the PDYN gene has been identified. We analyzed this polymorphism of the PDYN gene by a case-control association study in 143 patients with methamphetamine dependence and 209 healthy controls in the Japanese population. A 3- or 4-repeat allele in the PDYN gene promoter was found significantly more frequently in patients with methamphetamine dependence than in controls (chi(2)=9.45, p=0.0021). A 3- or 4-repeat allele in the PDYN gene promoter, which was shown to produce significantly higher transcription activity of the PDYN gene than a 1- or 2-repeat allele, is a genetic risk factor for development of methamphetamine dependence (odds ratio: 1.83, 95% CI=1.24-2.68).

Adult↗
PubMed2006

Effect of YM872, a selective and highly water-soluble AMPA receptor antagonist, in the rat kindling and rekindling model of epilepsy.

We examined antiepileptogenic and anticonvulsant effects of [2,3-dioxo-7-(1H-imidazol-1-yl)-6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl]-acetic acid monohydrate (YM872), a potent and highly water-soluble alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor antagonist, in the rat amygdala kindling model of epilepsy. Administration of YM872 significantly suppressed fully kindled seizures. Daily pretreatment with YM872 markedly retarded development of kindling during drug sessions. We also used the rekindling method to investigate the antiepileptogenic effect of YM872 in an attempt to differentiate between true and false effects in the conventional method of daily administration. The results using the rekindling method suggested that the effect of YM872 was truly antiepileptogenic, indicating its possible clinical usefulness as an antiepileptogenic drug. We also affirmed the importance of AMPA receptors in the seizure expression mechanism and development of kindling-induced epileptogenesis.

Animals↗
PubMed2006

Analysis of magnetic source localization of P300 using the multiple signal classification algorithm.

The authors studied the localization of P300 magnetic sources using the multiple signal classification (MUSIC) algorithm. Six healthy subjects (aged 24-34 years old) were investigated with 148-channel whole-head type magnetencephalography using an auditory oddball paradigm in passive mode. The authors also compared six stimulus combinations in order to find the optimal stimulus parameters for P300 magnetic field (P300m) in passive mode. Bilateral MUSIC peaks were located on the mesial temporal, superior temporal and parietal lobes. Interestingly, all MUSIC peaks in these regions emerged earlier in the right hemisphere than in the left hemisphere, suggesting that the right hemisphere has predominance over the left in the processing activity associated with P300m. There were no significant differences among the six stimulus combinations in evoking those P300m sources. The results of the present study suggest that the MUSIC algorithm could be a useful tool for analysis of the time-course of P300m.

Adult↗
PubMed2006

Medial profrontal cortex and anterior cingulate cortex in the generation of alpha activity induced by transcendental meditation: a magnetoencephalographic study.

Previous EEG studies have shown that transcendental meditation (TM) increases frontal and central alpha activity. The present study was aimed at identifying the source of this alpha activity using magnetoencephalography (MEG) and electroencephalography (EEG) simultaneously on eight TM practitioners before, during, and after TM. The magnetic field potentials corresponding to TM-induced alpha activities on EEG recordings were extracted, and we attempted to localize the dipole sources using the multiple signal classification (MUSIC) algorithm, equivalent current dipole source analysis, and the multiple spatio-temporal dipole model. Since the dipoles were mapped to both the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC), it is suggested that the mPFC and ACC play an important role in brain activity induced by TM.

Adult↗
PubMed2005

Chronic lithium treatment decreases tau lesions by promoting ubiquitination in a mouse model of tauopathies.

Lithium, a widely used drug for treating affective disorders, is known to inhibit glycogen synthase kinase-3 (GSK-3), which is one of the major tau kinases. Thus, lithium could have therapeutic benefit in neurodegenerative tauopathies by reducing tau hyperphosphorylation. We tested this hypothesis and showed that long-term administration of lithium at relatively low therapeutic concentrations to transgenic mice that recapitulate Alzheimer's disease (AD)-like tau pathologies reduces tau lesions, primarily by promoting their ubiquitination rather than by inhibiting tau phosphorylation. These findings suggest novel mechanisms whereby lithium treatment could ameliorate tauopathies including AD. Because lithium also has been shown to reduce the burden of amyloid-beta pathologies, it is plausible that lithium could reduce the formation of both amyloid plaques and tau tangles, the two pathological hallmarks of AD, and thereby ameliorate the behavioral deficits in AD.

Animals↗
PubMed2005

The ZDHHC8 gene did not associate with bipolar disorder or schizophrenia.

The zinc finger and DHHC domain-containing protein 8 (ZDHHC8) gene is located on chromosome 22q11, which several genome scans have provided repeated evidence for a significant linkage with bipolar disorder (BPD) and schizophrenia. A recent study revealed that a single nucleotide polymorphism (SNP), rs175174, which has potential effects on splicing, in intron 4 of the ZDHHC8 gene is associated with susceptibility to patients with schizophrenia in US and South Africa. We examined three SNPs of the ZDHHC8 gene, including rs175174, by case-control association in Japanese patients with BPD (N=172) and controls (N=298) or patients with schizophrenia (N=407) and controls (N=497). No significant association with BPD or schizophrenia was observed. After stratification by subcategories, bipolar I and II of BPD, and paranoid and disorganized types of schizophrenia, no significant association was found, nor was a significant association with either disorder found after dividing by gender. These data suggest that the ZDHHC8 gene may not be associated with susceptibility to BPD or schizophrenia, at least in a Japanese population.

Acyltransferases↗
PubMed2005

Exon 3 insert of tau protein in neurodegenerative diseases.

Microtubule-associated protein tau is the major component of the filamentous neurofibrillary lesions of Alzheimer's disease (AD) and other tauopathies. Recently, it has been reported that tau isoforms lacking both N-terminal exon 2 and exon 3 do not form straight filament- or paired helical filament-like filaments in vitro, and that the N-terminal exons facilitate assembly of full-length tau. However, neuropathological and biological studies on the N-terminal region of tau protein in human tissue have been limited. We performed a biochemical study on the abnormally phosphorylated tau in brains affected by AD and corticobasal degeneration (CBD), and an immunohistochemical study on tau-positive structures in neurodegenerative diseases, to clarify whether tau with the exon 3 insert was present in abnormal tau-positive structures. On immunoblots of sarkosyl-insoluble tau, anti-exon 3 antibody (anti-E3 Ab) recognized two bands of 68 and 72 kDa in AD and only one band of 72 kDa in CBD. Immunohistochemically, anti-E3 Ab recognized most parts of the neurofibrillary tangles (NFT) in AD and Pick bodies in Pick's disease. In progressive supranuclear palsy (PSP) and CBD, most NFT and pretangles were positive for anti-E3 Ab, as were a small number of glial inclusions. These results indicate that abnormally phosphorylated tau containing the exon 3 insert is present in both PSP and CBD brain, and that CBD cannot be distinguished from PSP by immunoreactivity for anti-E3 Ab. Although most intraglial inclusions were negative for anti-E3 Ab, a few were positive. Therefore, tau isoforms containing the exon 3 insert are expressed at low levels in glial cells.

Aged↗
PubMed2005

The GABA type A receptor alpha5 subunit gene is associated with bipolar I disorder.

Several genetic studies have revealed that bipolar disorders are linked with the chromosomal locus of 15q11-q13, where the gamma-aminobutyric acid (GABA) receptor alpha5 subunit gene (GABRA5) locates. GABA is one of the major neurotransmitters that may be involved in the pathogenesis of bipolar disorder. Five polymorphisms in the GABRA5 gene, -754C>T in the promoter region, IVS1-21G>A, IVS2-26T>A, (*)302C>T in 3'-UTR of exon 5, and a CA repeat polymorphism in the 3' flanking region were examined in a Japanese population. IVS1-21G>A exhibited significant differences in the distribution of the genotype and allele frequency in bipolar I disorder patients but not in bipolar II disorder patients, compared with control subjects. The haplotype analysis showed that IVS1-21G>A/IVS2-26A>T was associated with bipolar I disorder, and the IVS1-21A/IVS2-26T haplotype was a negative risk factor for susceptibility to the disorders (odds ratio: 0.57, 95% confidence interval: 0.44-0.73). These results suggest that the GABRA5 gene may confer susceptibility to bipolar I disorder.

Bipolar Disorder↗
PubMed2005

A variant of the sigma receptor type-1 gene is a protective factor for Alzheimer disease.

OBJECTIVE: Some preclinical evidence suggests that the sigma receptor type 1, which plays several roles in learning and memory, may also be involved in the pathogenesis of Alzheimer disease (AD). The authors provide here genetic evidence that the sigma receptor type 1 (SIGMAR1) gene is involved in susceptibility to AD. METHODS: Two polymorphisms of the SIGMAR1 gene, G-241T/C-240T and Q2P, were analyzed in a Japanese sample of 239 patients with AD and 227 comparisons subjects. These two polymorphisms were in complete linkage disequilibrium with each other, resulting in only two haplotypes, GC-241-240Q2 and TT-241-240P2. RESULTS: There was a significant association between AD and the TT-241-240P2 haplotype of the SIGMAR1 gene and its homozygote, found with late-onset, but not early-onset AD. After stratification by epsilon4 allele status of the apolipoprotein E gene, TT-241-240P2 homozygosity of the SIGMAR1 gene reduced the risk of AD in epsilon4 allele carriers by three-fourths. CONCLUSION: The present study suggests that the TT-241-240P2 haplotype of the SIGMAR1 gene, which decreases expression of the gene, may have a protective role against susceptibility to AD.

Aged↗
PubMed2005

Delusion of theft and phantom intruder delusion in demented elderly patients in Japan.

Delusion of theft and phantom intruder delusion are among the most frequent delusions in dementia. The purpose of this study was to clarify the clinical characteristics of patients with these symptoms. The authors conducted a questionnaire survey; items included age, gender, dementia diagnosis, cognitive function, and activities of daily living. Other clinical characteristics were evaluated using the quality of life questionnaire for dementia. A total of 217 patients with dementia were rated. Frequencies of delusion of theft were as follows: frequent, 7%; sometimes, 11%; rare, 16%; and none, 66%. Frequencies of phantom intruder delusion were as follows: frequent, 4%; sometimes, 10%; rare, 9%; and none, 77%. Comparison between positive and negative groups with these symptoms revealed that positive groups had higher scores in 2 of 6 domains of the quality of life questionnaire for dementia, namely, negative affect and actions, and restlessness. The positive group with delusion of theft had higher scores in cognitive function and activities of daily living than did the negative group. These results suggest that negative affect and action and restlessness might be related to delusion of theft or phantom intruder delusion and that delusion of theft frequently occurs in the early stage of dementia.

Activities of Daily Living↗
PubMed2004

A nonsynonymous polymorphism in the human fatty acid amide hydrolase gene did not associate with either methamphetamine dependence or schizophrenia.

Genetic contributions to the etiology of substance abuse and dependence are topics of major interest. Acute and chronic cannabis use can produce drug-induced psychosis resembling schizophrenia and worsen positive symptoms of schizophrenia. The endocannabinoid system is one of the most important neural signaling pathways implicated in substance abuse and dependence. The fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme of endocannabinoids. To clarify a possible involvement of FAAH in the etiology of methamphetamine dependence/psychosis or schizophrenia, we examined the genetic association of a nonsynonymous polymorphism of the FAAH gene (Pro129Thr) by a case-control study. We found no significant association in allele and genotype frequencies of the polymorphism with either disorder. Because the Pro129Thr polymorphism reduces enzyme instability, it is unlikely that dysfunction of FAAH and enhanced endocannabinoid system induce susceptibility to either methamphetamine dependence/psychosis or schizophrenia.

Adult↗
PubMed2004

Atypical properties of several classes of antipsychotic drugs on the basis of differential induction of Fos-like immunoreactivity in the rat brain.

Acute administration of typical and atypical antipsychotics has been reported to induce regionally distinct patterns of c-Fos expression in the rat forebrain. Furthermore, atypical index, the difference in the extent of increased Fos-like immunoreactivity (Fos-LI) in the nucleus accumbens (NAc) shell versus the dorsolateral striatum (DLSt), has been proposed to classify antipsychotics into typical or atypical antipsychotics. The present study was conducted to investigate the atypical properties of 24 antipsychotics that are used in Japan and blonanserin, a novel 5-HT2A and D2 receptor antagonist. We systematically examined the effects of the drugs on Fos-LI in the NAc and DLSt in the rat brain using immunohistochemistry and calculated the atypical index, comparing with those of haloperidol and clozapine. Floropipamide, oxypertine, nemonapride, pimozide and mosapramine, as well as clozapine, olanzapine, quetiapine and risperidone, showed high positive atypical index. Zotepine, perospirone, sulpiride, moperone, sultopride, thioridazine, carpipramine, clocapramine and blonanserin showed moderate ones. In contrast, fluphenazine, bromperidol, timiperone, spiperone, propericiazine, perphenazine, chlorpromazine and levomepromazine had negative atypical index like haloperidol. These results suggest that not only so-called atypical antipsychotics, but also several conventional drugs, possess atypical properties.

Animals↗