Biomedical subjects

O Ohmori

Publications and source records attributed to O Ohmori.

31 records · Page 2Linked to original sources

PubMed1999

Dopamine D1 receptor gene polymorphism and schizophrenia in Japan.

We studied the relationship between schizophrenia and the DdeI polymorphism in the 5' untranslated region (5'UTR) of the dopamine D1 receptor (DRD1) gene. This polymorphism is an A (A1 allele) to G (A2 allele) transition in the 5' UTR of exon 2 at bp -48 (A-48G). One hundred forty-eight schizophrenics and 148 control subjects were investigated. No significant differences in genotypic counts and allele frequencies between schizophrenics and controls were found. Although a significant difference between the patients classified as disorganized type and the controls was discovered both in genotypic counts and allele frequencies, neither association proved significant when a Bonferroni correction was used. Moreover, there were no differences in scores of main symptoms of schizophrenia based on the Manchester Scale between patients with A1/A1 genotype and those with A1/A2 genotype. These findings suggest that this gene may not be involved in the pathogenesis of schizophrenia.

Adolescent↗

PubMed1999

Association study of the 5-HT6 receptor gene in schizophrenia.

Serotonergic (5-hydroxytryptamine; 5-HT) transmission may play an important role in the treatment and/or pathogenesis of schizophrenia. Previous studies reported that several atypical antipsychotic agents have high affinities for the 5-HT6 receptor. The 5-HT6 receptor gene polymorphism might contribute to the genetic background of this disorder. One hundred and fifty unrelated patients with schizophrenia and 150 unrelated healthy controls were genotyped for a biallelic polymorphism (267C/T) at the 5-HT6 receptor gene. No significant positive association between the 5-HT6 receptor genotype and schizophrenia was observed. Our results suggests that the 267C/T polymorphism of the 5-HT6 receptor gene may not be involved in the susceptibility to schizophrenia.

Adult↗

PubMed1999

Shifted cytosolic NADP+-dependent isocitrate dehydrogenase on 2-D gel in the brain of genetically epileptic E1 mice.

We observed a spot on two-dimensional (2-D) gel in the epileptic mutant strain E1 mice with a similar molecular weight but with a different isoelectric point of approximately 0.2, compared with its mother strain ddY mice. The collected protein from the E1 mice was identified as cytosolic NADP+-dependent isocitrate dehydrogenase by internal amino acid sequencing. The enzyme is known to be maximally active during the development of the brain and to play an important role in NADPH production for fatty acids and cholesterol synthesis. In addition, alterations in cholesterol synthesis early in the development of the mammalian brain have been reported to lead to chronic epilepsy. The results in the present study therefore suggest that cytosolic NADP+-dependent isocitrate dehydrogenase might be involved in the epileptogenesis of the E1 mouse.

Amino Acid Sequence↗

PubMed1999

A simpler and more accurate equation to predict daily lithium dose.

Recently, the authors suggested that the lithium dose prediction equation created by Zetin and associates cannot always accurately predict a required lithium dose and that the inclusion of renal function data may improve the accuracy of the equation. The charts of 70 patients were reviewed to obtain data regarding factors thought to affect serum lithium concentrations, including renal function, and an equation to estimate the dose intended to achieve an expected concentration was derived by stepwise multiple linear regression. The equation was also applied to 30 other patients to evaluate its accuracy. The authors obtained the following equation: daily lithium carbonate dose (in milligrams) = 100.5 + 752.7 x (expected lithium concentration in millimoles per liter) - 3.6 x (age in years) + 7.2 x (weight in kilograms) - 13.7 x (blood urea nitrogen [BUN] in milligrams per deciliter). When the equation was applied to 30 patients, the mean +/- SD of deviations from the expected concentration was 0.15 +/- 0.30 mmol/L, and 19 patients (63%) had deviations of less than 0.20 mmol/L. On the other hand, when the equation set forth by Zetin and associates was applied to the same patients, the mean +/- SD of deviations from the expected concentration was 0.52 +/- 0.42 mmol/L, and only 6 patients (20%) had deviations of less than 0.20 mmol/L. Although it is necessary to measure BUN levels before starting lithium, this equation may be simpler and more accurate than that offered by Zetin and associates.

Adolescent↗

PubMed1999

A puzzling case of seizures and visual hallucinations during clomipramine treatment with a high dose but causing a low serum concentration.

We present a puzzling case of a 25-year-old depressive man suffering from seizures and visual hallucinations during clomipramine treatment with a high dose but causing a low serum concentration. We examined alleles of cytochrome P450 (CYP) isozymes. It was revealed that he was not an ultrarapid metabolizer for CYP2D6, and that the genotypes were homozygous for CYP2D6J and heterozygous for CYP2C19m1. Throughout the treatment period, his compliance was good. Since he was a smoker, it seems likely that his low clomipramine level was due to smoking-induced CYP1A2 activity. These findings suggest that smoking-induced CYP1A2 activity overcomes the possibly inhibiting effects of homozygosity for CYP2D6J and heterozygosity for CYP2C19m1, and that high-dose clomipramine is not always a direct cause of seizures.

Adult↗

PubMed1998

Apolipoprotein E regulatory region genotype in schizophrenia.

Clinical observations indicate that a proportion of patients with schizophrenia experience cognitive impairment, which suggests that a neurodegenerative basis might be involved in the etiology of schizophrenia. Apolipoprotein E (ApoE), which has been confirmed to be genetically associated with Alzheimer's disease, is thus highlighted as a candidate gene for schizophrenia. Recently, novel functional polymorphisms in the ApoE transcriptional regulatory region have been found. To investigate whether these polymorphisms are associated with the risk of schizophrenia, we genotyped 144 patients with schizophrenia and 134 controls for two polymorphisms (-491A/T and -219G/T). No significant positive associations between both polymorphisms and schizophrenia were observed. Our findings exclude the regulatory region of the ApoE gene as a locus that might confer increased susceptibility to schizophrenia.

Apolipoproteins E↗

PubMed1998

Tardive dyskinesia and debrisoquine 4-hydroxylase (CYP2D6) genotype in Japanese schizophrenics.

Previous studies have shown that many neuroleptics are metabolized by debrisoquine 4-hydrolase (CYP2D6), which exhibits genetic polymorphisms. In Oriental populations, poor metabolizers (PMs) with a lack of CYP2D6 activity are rare, although the CYP2D6*10 allele, which is associated with decreased CYP2D6 activity, is commonly found. The authors examined the relationship between tardive dyskinesia (TD) and CYP2D6 polymorphisms, including the CYP2D6*10 allele. Subjects consisted of 100 Japanese schizophrenics. TD was evaluated using the Abnormal Involuntary Movement Scale (AIMS). Genotyping for the presence of the CYP2D6*3, CYP2D6*4 and CYP2D6*10 alleles was performed using allele-specific PCR amplification and endonuclease digestions. The frequency of the CYP2D6*10 allele was 0.52, and only one allele showed the PM genotype. There was a significant difference in the allelic distribution of CYP2D6*10 between subjects with and without TD. We also found significant genotypic and allelic associations with dichotomized total AIMS scores of 6 or more (moderate or severe abnormal movements) and with scores of less than 6 (mild or no movements). After these associations were adjusted for confounding variables (gender, age, duration of illness and neuroleptic dose) by regression analysis, the CYP2D6*10 genotype showed significant association with the total AIMS score, and a modest association with TD occurrence. These results indicate that the CYP2D6*10 genotype may play a role in the development of moderate or severe abnormal movements.

Alleles↗

PubMed1998

Association study of a functional catechol-O-methyltransferase gene polymorphism in Japanese schizophrenics.

Catechol-O-methyltransferase (COMT) is an enzyme which inactivates catecholamine neurotransmitters by methylation, and is considered a candidate for involvement in schizophrenia. A functional COMT gene polymorphism influencing the enzyme activities, the high activity (val-108) and the low activity allele (met-108), was recently confirmed. We investigated a genetic association between schizophrenia and the COMT gene polymorphism in 150 Japanese schizophrenics and controls. We detected the low activity met-108 allele more frequently in schizophrenics than in the controls, and found that subjects sharing the met-108 allele (val/met and met/met) are significantly more common in the patients than in the controls. The results suggest that the low activity met-108 allele may be involved in susceptibility for schizophrenia.

Alleles↗

PubMed1997

Effect of serum cholesterol levels on meta-chlorophenylpiperazine-evoked neuroendocrine responses in healthy subjects.

This study was undertaken to test the hypothesis that serum cholesterol levels might be associated with serotonergic receptor function. The participants were 10 healthy male subjects. After an overnight fast, the subjects received meta-chlorophenylpiperazine (m-CPP) or identical placebo capsules orally in a randomized, double-blind, cross-over design. Blood was obtained for measurement of prolactin, cortisol, adrenocorticotropic hormone (ACTH), and cholesterol. There were some significantly positive correlations between serum cholesterol levels and hormonal responses to m-CPP administration. These results suggest that serum cholesterol levels may be positively associated with serotonergic receptor function.

Adrenocorticotropic Hormone↗

PubMed1997

Granule cell disinhibition in dentate gyrus of genetically seizure susceptible El mice.

Paired-pulse inhibition was investigated electrophysiologically in the dentate gyrus using hippocampal slices from epileptic El mice. At short interpulse intervals (IPIs), the inhibition was 30% in the El, and 90% in the control ddY mice at the ages of 10 and 15 weeks. No difference in inhibition was observed at the age of 5 weeks. Bicuculline, a GABAA receptor antagonists, attenuated the inhibition during short IPIs n the ddY mice, while in the El mice, phenobarbital and flunitrazepam, which enhance GABAA receptor function, restored the inhibitory activity comparable to that of the ddY. The disinhibition progressed with growth, closely correlating with seizure development in El mice. These results suggest that decrease in the GABAergic inhibition occurs in the dentate gyrus of the El mice with growth. GABA concentration in the hippocampus was also quantified using HPLC. In El mice, GABA level was significantly lower than that in ddY mice at the ages of 5 and 15 weeks. Thus, the disinhibition observed in the El dentate gyrus at 15 weeks of age does not appear to be directly related to the content of GABA. GABAergic disinhibition suggests possible loss of unknown inhibition control factor(s) in the El dentate gyrus as growth progresses. The growth-dependent disinhibition in the granule cells may be prerequisite for epileptogenesis in El mice.

Aging↗

PubMed1997

Recurrent brief depression in Prader-Willi syndrome: a case report.

Prader-Willi syndrome is caused by a deletion of 15q11-13 or maternal disomy of chromosome 15. A female patient with Prader-Willi syndrome, who was 19 years of age at the first onset of her recurrent brief episodes, is described. The episodes showed a near-monthly rhythm and were followed by a spontaneous remission in 7-18 days. The symptoms during the episodes were anorexia, insomnia, guilt feelings, ideas of being doomed, ostracized and persecuted, and stupor alternating with agitation.

Adult↗

PubMed1996

Down-regulation of S-adenosylhomocysteine hydrolase in the active methyl transfer system in the brain of genetically epileptic El mice.

To study the role of cerebral methylation in epileptogenesis, we investigated the active methyl transfer pathway in the brain of genetically epileptic El mice. We examined S-adenosylhomocysteine (AdoHcy) hydrolase activity (by high performance liquid chromatography), the corresponding mRNA levels (by competitive reverse transcription-polymerase chain reaction), as well as S-adenosylmethionine (AdoMet) and AdoHcy levels in epileptic El and non-epileptic control ddY mice. The level of AdoHcy, a potent feedback inhibitor in the methyl transfer system, was relatively high throughout growth, particularly in 15 week old El mice where it was increased approximately 20% compared to control ddY mice. AdoHcy hydrolase activity in the El mice brain did not increase during growth, which was confirmed by the finding that mRNA synthesis from the hydrolase gene behaved likewise. In contrast, ddY mice exhibited a gradual increase in the mRNA synthesis up to three fold and 20% increase in the enzyme activity at 15 weeks of age compared to those of El mice in which the seizure frequency was 100%. The levels of AdoMet, a versatile methyl donor, did not change throughout growth. We concluded that the down-regulation of AdoHcy hydrolase results in the accumulation of AdoHcy, possibly inducing an unstable state including seizures in the El mouse brain. El mice predisposed to epilepsy may be characterized by disordered feedback regulation of the AdoMet-dependent methyl transfer pathway.

Adenosylhomocysteinase↗

PubMedDate not supplied

Negative association between T102C polymorphism of the 5-HT2a receptor gene and schizophrenia in Japan.

Serotonin (5-hydroxytryptamine, 5-HT) may play an important role in the pathogenesis of schizophrenia. Previous studies suggested that the efficacy of atypical neuroleptic drugs (e.g., risperidone and clozapine) on negative symptoms may be related to the 5-HT2a receptor. Although association studies between MspI polymorphism (T102C) and the 5-HT2a receptor gene and schizophrenia have been reported, their results are still controversial. The aim of this study was to examine the association between T102C polymorphism of the 5-HT2a receptor gene and schizophrenia as well as the association between the polymorphism and negative symptoms in a Japanese population (106 patients with schizophrenia and 109 healthy controls). No significant positive associations were observed. Our results suggest that the 5-HT2a receptor gene is not involved in the pathogenesis of schizophrenia or negative symptoms.

Adolescent↗