Biomedical subjects

Jun Nakamura

Publications and source records attributed to Jun Nakamura.

At least 55 records · Page 3Linked to original sources

PubMed2005

Prediction of response to risperidone treatment with respect to plasma concencentrations of risperidone, catecholamine metabolites, and polymorphism of cytochrome P450 2D6.

In the present study, we examined the relationships between plasma concentrations of risperidone and clinical responses, extrapyramidal symptoms, plasma levels of cotinine and caffeine, or cytochrome (cyp)2D6 genotypes. In addition, we also investigated the relationships between plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) or homovanillic (HVA) acid and clinical responses to risperidone. One hundred and 36 patients (male/female: 58/78, age 37+/-13 years) who met DSM-IV criteria for schizophrenia, schizoaffective disorder, delusional disorder and brief psychotic disorder, and who were being treated with risperidone alone, were evaluated regarding their clinical improvement and extrapyramidal symptoms using the Positive and Negative Syndrome Scale (PANSS) and Simpson and Angus (SAS), respectively, and plasma levels of cotinine, caffeine, MHPG and HVA were analysed by high-performance liquid chromatography. The cyp2D6*5 and *10 alleles were identified using the polymerase chain reaction. There was a positive correlation between plasma levels of risperidone plus 9-hydroxyrisperidone (active moiety) and SAS scores, but not the PANSS. Pretreatment HVA levels in responders were higher than those in nonresponders. In addition, there was a negative correlation between changes in HVA levels and improvement in PANSS scores. There was no association between plasma levels of risperidone and plasma levels of cotinine or caffeine. Furthermore, there were no differences in the risperidone/9-hydroxyrisperidone ratio, clinical improvements and extrapyramidal symptoms among cyp2D6 genotypes. These results indicate that pretreatment HVA levels and plasma concentrations of active moiety might play a part in predicting the clinical response and occurrence of extrapyramidal symptoms, respectively, when treating patients with risperidone.

Adolescent↗

PubMed2005

Alcohol drinking frequency is more directly associated with alcohol use disorder than alcohol metabolizing enzymes among male Japanese.

The development of alcohol use disorder (AUD) is related to various social, economic, cultural, environmental and hereditary factors. Several potential risk factors have been proposed for AUD in addition to alcohol consumption, including alcohol dehydrogenase2 (ADH2), acetaldehyde dehydrogenase2 (ALDH2), marital status, educational, occupational or past medical history (e.g. diabetes mellitus, hypertension, lung, digestive tract, or chronic liver disease) or smoking habits. The present study was performed to investigate the relationship between the aforementioned potential risk factors and AUD in Japan. A case-control study was performed on 153 male Japanese AUD patients and age-, gender-, or other confounder-matched controls to investigate the relation multivariately between ADH2, ALDH2 or alcohol drinking and AUD. Genomic DNA were extracted from nail clippings by the guanidium method, and genotyping of ADH2 and ALDH2 were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Univariate analyses by the conditional logistic regression model revealed statistically significant odds ratios due to ADH2*1/1 genotype, ALDH2*1/1 genotype, middle school as the final school attended, longest occupations as farmers, fishermen, craftsmen, miners, production process or construction workers, and past histories of chronic liver disease and AUD. However, multivariate analyses under a hierarchically well-formulated model strategy with interaction and confounding assessment indicated that (i) heavy alcohol intake was a significant risk factor (odds ratio per 1.0 g of daily ethanol intake; 1.096, 95% confidence interval; 1.026-1.171) for developing AUD after adjusting for other confounders; and (ii) ADH2*1/1 genotype and ALDH2*1/1 genotype were not risk factors after adjusting for daily ethanol intake and other confounders. The present study shows that AUD was more directly and strongly associated with alcohol drinking than with alcohol metabolizing enzymes among male Japanese.

Adult↗

PubMed2004

Charles Bonnet syndrome and visual acuity--the involvement of dynamic or acute sensory deprivation.

A 61-year-old patient suffered from Charles Bonnet syndrome (CBS) while his visual acuity declined, whereas CBS subsided after he became blind. These findings suggest that reduction of visual acuity (dynamic or acute impairment) has a greater impact on the onset of CBS than low visual acuity (static or chronic impairment) per se in some patients. They may also explain why patients with low visual acuity do not always suffer from CBS. Although further studies are required, the present case highlights the importance of the differentiation between lowering and low visual acuity in the etiology of CBS.

Humans↗

PubMed2004

Symptomatological and cognitive predictors of insight in chronic schizophrenia.

Studies of schizophrenia show lack of agreement about the relationship of symptomatological and cognitive factors to insight. In this study, positive and negative symptomatology and cognitive function were assessed by the Positive and Negative Syndrome Scale (PANSS), the Wisconsin Card Sorting Test (WCST), and the Wechsler Adult Intelligence Scale Revised (WAIS-R) in male chronic schizophrenic patients in relation to level of insight measured with the Japanese version of the Schedule for the Assessment of Insight (SAI-J). Negative symptoms were significantly and negatively associated with overall insight, particularly with treatment compliance and recognition of mental illness. The present findings suggest that aspects of insight such as treatment compliance and recognition of mental illness are negatively associated with negative symptoms.

Adult↗

PubMed2004

Polymorphisms of dopamine degradation enzyme (COMT and MAO) genes and tardive dyskinesia in patients with schizophrenia.

Several lines of evidence suggest that tardive dyskinesia (TD) may be associated with altered dopaminergic neurotransmission. We hypothesized that deranged dopamine degradation enzyme activities might be related to the susceptibility to TD through altered dopaminergic neurotransmission in the central nervous system. In the present study, we investigated the relationship between the gene polymorphisms of three dopamine degradation enzymes and TD. We genotyped the valine/methionine polymorphism of codon 108/158 in the catechol-O-methyltransferase (COMT) gene, the 30-bp repeat polymorphism in the promoter of the monoamine oxidase A (MAOA) gene, and the A/G polymorphism in intron 13 of the monoamine oxidase B (MAOB) gene in 206 Japanese patients with schizophrenia. No significant difference was found in total scores on the Abnormal Involuntary Movement Scale (AIMS) among the subject groups, sorted according to the COMT, MAOA and MAOB genotypes. Moreover, no significant difference was found in allele frequencies between patients with TD and patients without TD for any of the polymorphisms. As both COMT and MAO genes are involved in degrading catecholamines, we also sought evidence for additive and epistatic effects, but none was observed. Our data, therefore, do not support the hypothesis that polymorphisms in COMT, MAOA, and MAOB genes are involved individually or in combination in the predisposition to TD.

Antipsychotic Agents↗

PubMed2004

Imbalanced base excision repair in response to folate deficiency is accelerated by polymerase beta haploinsufficiency.

The mechanism by which folate deficiency influences carcinogenesis is not well established, but a phenotype of DNA strand breaks, mutations, and chromosomal instability suggests an inability to repair DNA damage. To elucidate the mechanism by which folate deficiency influences carcinogenicity, we have analyzed the effect of folate deficiency on base excision repair (BER), the pathway responsible for repairing uracil in DNA. We observe an up-regulation in initiation of BER in liver of the folate-deficient mice, as evidenced by an increase in uracil DNA glycosylase protein (30%, p < 0.01) and activity (31%, p < 0.05). However, no up-regulation in either BER or its rate-determining enzyme, DNA polymerase beta (beta-pol) is observed in response to folate deficiency. Accordingly, an accumulation of repair intermediates in the form of DNA single strand breaks (37% increase, p < 0.03) is observed. These data indicate that folate deficiency alters the balance and coordination of BER by stimulating initiation without subsequently stimulating the completion of repair, resulting in a functional BER deficiency. In directly establishing that the inability to induce beta-pol and mount a BER response when folate is deficient is causative in the accumulation of toxic repair intermediates, beta-pol-haploinsufficient mice subjected to folate deficiency displayed additional increases in DNA single strand breaks (52% increase, p < 0.05) as well as accumulation in aldehydic DNA lesions (38% increase, p < 0.01). Since young beta-polhaploinsufficient mice do not spontaneously exhibit increased levels of these repair intermediates, these data demonstrate that folate deficiency and beta-pol haploinsufficiency interact to increase the accumulation of DNA damage. In addition to establishing a direct role for beta-pol in the phenotype expressed by folate deficiency, these data are also consistent with the concept that repair of uracil and abasic sites is more efficient than repair of oxidized bases.

Animal Feed↗

PubMed2004

Kinetics in surface reconstructions on GaAs(001).

We have successfully controlled the surface structures of GaAs(001) by changing incident As-molecular species. Under As4 fluxes, the c(4 x 4) reconstruction with Ga-As dimers [c(4 x 4)alpha structure] is obtained, but the formation of three As-As dimer structures [c(4 x 4)beta structure] is kinetically limited. On the other hand, the structure change from the (2 x 4), through c(4 x 4)alpha, to c(4 x 4)beta phases is observed under As2 fluxes. We found that the c(4 x 4)alpha structure is energetically metastable and provides a kinetic pathway for the structure change between the (2 x 4) and c(4 x 4)beta phases under As2 fluxes.

Journal Article↗

PubMed2004

Differences in mental health consultation between male and female workers in the health care center of a private enterprise.

This study attempted to clarify gender differences associated with mental health consultations at a health care center (X center) that services 40,638 (34,491 men and 6,147 women) workers and is operated by a Japanese company. Data from 940 subjects (790 men and 150 women) undergoing first-time consultation at the X center between April 1996 and March 2001 were collected from the database. After matching age (within 3 years) and occupation between the male and female groups by pairing, 58 men and 58 women were compared. There was no difference in work inefficiency and diagnosis between the two groups, but the referral route of the first consultation differed significantly: males were more frequently self-referred. Fewer female than male patients were found to have work-related complaints. With regard to these work-related complaints, inadequate relationships, and especially conflicts with superiors, were found to be the most frequent cause among patients of both genders, although differences in the content of these complaints did exist.

Adolescent↗

PubMed2004

Aldehydic DNA lesions in calf thymus DNA and HeLa S3 cells produced by bacterial quinone metabolites of fluoranthene and pyrene.

There is increasing concern that compounds formed during the chemical or biological transformation of pollutants in the environment may be more detrimental to human and environmental health than the original pollutant. In this study, two bacterial transformation products of polycyclic aromatic hydrocarbons (PAHs), pyrene-4,5-quinone (P45Q) and fluoranthene-2,3-quinone (F23Q), were evaluated for mutagenicity by measuring aldehydic DNA lesions (ADL) in calf thymus DNA and HeLa S3 cells. Both quinones caused oxidative DNA damage in vitro through a copper-mediated redox cycle and subsequent production of reactive oxygen species (ROS). Hydrogen peroxide and copper were essential for causing oxidative DNA damage and glutathione (GSH) prevented DNA damage from F23Q better than from P45Q. In experiments using HeLa cells, F23Q decreased cell viability, but did not produce measurable levels of ADL or base oxidation. To test the hypothesis that DNA damage was being prevented by conjugation of F23Q with GSH, GSH-depleted cells were treated with both quinones. GSH depletion did not increase the toxicity of F23Q or cause it to oxidize DNA. Treatment of HeLa cells with metal chelators did not decrease F23Q toxicity. It is therefore possible that F23Q affected cell viability through a ROS-independent mechanism, either by conjugation with essential cellular proteins or through cellular or mitochondrial membrane damage, which precluded oxidation of DNA. In contrast, P45Q caused both ADL and base oxidation in cells. Neocuproine reduced the amount of ADL caused by P45Q, indicating that copper was still important for the intracellular generation of damaging oxidants. P45Q is a novel metabolite and its effects on DNA have not been investigated previously. This study exemplifies the importance of considering not only primary environmental pollutants, but also their biologically or chemically generated transformation products.

Aldehydes↗

PubMed2004

Apurinic/apyrimidinic endonuclease (APE/REF-1) haploinsufficient mice display tissue-specific differences in DNA polymerase beta-dependent base excision repair.

Apurinic/apyrimidinic (AP) endonuclease (APE) is a multifunctional protein possessing both DNA repair and redox regulatory activities. In base excision repair (BER), APE is responsible for processing spontaneous, chemical, or monofunctional DNA glycosylase-initiated AP sites via its 5'-endonuclease activity and 3'-"end-trimming" activity when processing residues produced as a consequence of bifunctional DNA glycosylases. In this study, we have fully characterized a mammalian model of APE haploinsufficiency by using a mouse containing a heterozygous gene-targeted deletion of the APE gene (Apex(+/-)). Our data indicate that Apex(+/-) mice are indeed APE-haploinsufficient, as exhibited by a 40-50% reduction (p < 0.05) in APE mRNA, protein, and 5'-endonuclease activity in all tissues studied. Based on gene dosage, we expected to see a concomitant reduction in BER activity; however, by using an in vitro G:U mismatch BER assay, we observed tissue-specific alterations in monofunctional glycosylase-initiated BER activity, e.g. liver (35% decrease, p < 0.05), testes (55% increase, p < 0.05), and brain (no significant difference). The observed changes in BER activity correlated tightly with changes in DNA polymerase beta and AP site DNA binding levels. We propose a mechanism of BER that may be influenced by the redox regulatory activity of APE, and we suggest that reduced APE may render a cell/tissue more susceptible to dysregulation of the polymerase beta-dependent BER response to cellular stress.

Animals↗

PubMed2004

Suicide and occupation: further supportive evidence for their relevance.

In recent years, the relationship between occupation and suicide has been extensively investigated, but few definite conclusions regarding the nature of the relationship have been established. In the present study, this relationship was investigated by examining Japanese governmental statistics. First, correlations of suicide rate relative to industry categories were examined individually for primary industry (farmers, fishermen, and forest workers), secondary industry (construction workers, manufacture works, and miners), and tertiary industry (indoor workers) for all of the 47 prefectures of Japan. Second, in the industries that showed a significant correlation with suicide rate, the relationship to other factors was adjusted using possibly confounding factors. As a result, suicide rate was positively correlated with primary industry percentage, but not with secondary or tertiary industry percentages. Multiple regression analysis showed that suicide rate was positively associated with primary industry percentage with significant tendency while it was significantly and negatively associated with annual total sunshine. Limitations are that individual suicide rates according to occupational types were not available and direct correlations with the above variables could not be investigated. The present findings suggest a possibility that occupational factors associated with primary industry may be relevant to suicide, and that, additionally, annual total sunshine may affect suicide independently. Since workers with primary industry are likely to be exposed to sunshine than other workers, they may tend to be more affected by the decrease of annual total sunshine.

Adult↗

PubMed2004

Aging and visual hallucinations in elderly psychiatric outpatients.

Estimates of the reported prevalence of visual hallucinations in the elderly vary from study to study. The aim of the present investigation was to re-evaluate the prevalence of visual hallucinations in elderly psychiatric outpatients and to examine pertinent risk factors. One hundred and twenty-two elderly (> or =60 years old) consecutive outpatients at our university hospital were investigated with a questionnaire regarding visual hallucinations and the Mini-Mental State Examination. Twelve of 122 (10%) patients suffered from visual hallucinations. Although advanced age, lower MMSE scores and dementia were significantly associated with the presence of visual hallucinations, logistic regression analysis revealed that only advanced age showed a tendency to predict the presence of visual hallucinations. In 53 patients with dementia examined separately, only advanced age was significantly associated with visual hallucinations. The present findings suggest that the prevalence of visual hallucinations in the elderly is about 10% and that aging is an important risk factor in the development of visual hallucinations in dementia. Further studies are required in order to investigate the contribution of age-related factors such as lowering visual acuity, bereavement and loneliness to the presence of visual hallucinations.

Aged↗

PubMed2004

Clinical response to antidepressant treatment and 3-methoxy-4-hydroxyphenylglycol levels: mini review.

Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) may provide valuable information regarding central noradrenergic activity. In this article, we mainly reviewed about the associations between plasma MHPG levels and responses to antidepressant treatment. There exists heterogeneity of depression with regards to plasma levels of MHPG; in other words, depressed patients might be dichotomized into one group characterized by anxiety and/or perceptions of powerlessness with high plasma MHPG levels and another group characterized by psychomotor retardation with low plasma MHPG levels. In addition, it is possible that patients with lower pretreatment MHPG levels might respond to drugs that affect both noradrenergic neurons and serotonergic neurons or predominantly noradrenergic neurons. On the other hand, patients with higher pretreatment MHPG levels might respond to drugs that affect predominantly serotonergic neurons or GABAergic neurons. It is possible to predict the responses to antidepressant drugs by means of plasma MHPG levels in depressed patients.

Antidepressive Agents↗

PubMed2004

Predicting denial function of schizophrenic patients by the picture completion subtest of WAIS-R.

In the previous study, picture completion (PC) test scores of Wechsler Adult Intelligence Scale Revised (WAIS-R) were negatively associated with recognition of mental illness measured by Schedule for the Assessment of Insight (SAI). Therefore, it can be hypothesized that function measured by the PC test is positively associated with denial function. To investigate this hypothesis, we investigated the relationship between two picture tests (picture completion and picture arrangement) of the WAIS-R and denial function tests (lie scale, frequency scale and correction scale) of the Minnesota Multiphasic Personality Inventory (MMPI) in 26 schizophrenic patients. As a result, the lie scale score and the correction scale score were positively and significantly associated with picture completion whereas no scale score was significantly associated with picture arrangement. The present findings suggest that the positive association between function measured by the PC test and denial function measured by lie and correction scale scores. Further studies are warranted to investigate the usefulness of the PC test for the measurement of denial function in schizophrenia.

Adult↗

PubMed2004

No association between the Pro197Leu polymorphism in the glutathione peroxidase (GPX1) gene and schizophrenia.

OBJECTIVE: Oxidative stress such as free radical-mediated neuronal dysfunction may be involved in the pathophysiology of schizophrenia. The human glutathione peroxidase (GPX1) is a selenium-dependent enzyme, which plays an important role in the detoxification of free radicals. We therefore hypothesized that the GPX1 gene, which is located on chromosome 3p21.3, may be involved in the pathophysiology of schizophrenia. The aim of this study is to examine whether a potentially functional polymorphism, a proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) of the human GPX1 gene, is associated with susceptibility to schizophrenia. METHODS: We genotyped the Pro197Leu polymorphism in a total of 113 nuclear families that had a proband with schizophrenia. Genetic association was tested using the transmission disequilibrium test (TDT), the sib transmission disequilibrium test (STDT), and the family-based association test (FBAT). RESULTS: The minor allele (Leu) frequency was calculated to be 0.282. We could not find significant transmission disequilibrium of the alleles for the Pro197Leu polymorphism in the GPX1 gene in association with the presence of schizophrenia in our family sample (TDT, chi2=0.03, degrees of freedom=1, P=0.86; combined TDT-STDT, Z'=-0.052, P=0.47; FBAT, Z=0.000, P=1.000). CONCLUSION: The results of this study suggest that the GPX1 polymorphism is unlikely to be associated with susceptibility to schizophrenia.

Amino Acid Substitution↗

PubMed2004

Genetic association analysis of functional polymorphisms in the cytochrome P450 1A2 (CYP1A2) gene with tardive dyskinesia in Japanese patients with schizophrenia.

OBJECTIVE: Recent studies have revealed positive associations between tardive dyskinesia (TD) and genetic polymorphisms of several cytochrome P450 (CYP) subfamilies that are involved in pharmacokinetic process of antipsychotic drugs. In the present study, we analyzed the relationship between TD and two polymorphisms of the CYP1A2 gene, 734C/A and -2964G/A, in a sample of Japanese patients with schizophrenia. METHODS: We studied 199 Japanese patients with schizophrenia. We used the Abnormal Involuntary Movement Scale to evaluate TD. Two polymorphisms of the CYP1A2 gene, 734C/A and -2964 G/A were genotyped by means of polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Neither the 734C/A nor the -2964G/A polymorphism was associated with TD [734C/A genotype: chi2=0.02, degrees of freedom (df)=2, P=1.00; allele: chi2=0.02, df=1, P=0.89; -2964G/A genotype: chi2=0.21, df=2, P=0.90; allele: chi2=0.15, df=1, P=0.70]. In addition, CYP1A2 haplotype was associated with TD (chi2=0.24, df=3, P=0.97). Furthermore, in both the subgroup of smokers and the subgroup of patients receiving high-dosage antipsychotics (chlorpromazine equivalent >1000 mg), neither the 734C/A nor the -2964G/A polymorphism was associated with TD. CONCLUSIONS: We did not find significant associations between the 734C/A and -2964G/A polymorphisms of CYP1A2 gene and TD in Japanese patients with schizophrenia. Our results suggest that these CYP1A2 gene polymorphisms may not contribute to TD susceptibility.

Adult↗

PubMed2004

Associations between baseline plasma MHPG (3-methoxy-4-hydroxyphenylglycol) levels and clinical responses with respect to milnacipran versus paroxetine treatment.

The purpose of this study was to investigate the effects of milnacipran and paroxetine on plasma levels of catecholamine metabolites, and we attempted to elucidate the differences between the mechanisms of these drugs in catecholaminergic neurons. In depressed patients, we investigated the relationships among pretreatment levels of catecholamine metabolites, the changes in plasma catecholamine metabolite levels before and after administration of milnacipran or paroxetine, and clinical response to these drugs. Responders to milnacipran showed lower pretreatment levels of plasma 3-methoxy-4-hydroxyphenylglycol (pMHPG) than did nonresponders to milnacipran; there was also a positive correlation between changes in pMHPG levels and percent improvement of the score on the 17-item Hamilton Rating Scale for Depression (HRSD). On the other hand, responders to paroxetine showed higher pretreatment levels of pMHPG than did nonresponders to paroxetine, and a negative correlation was observed between changes in pMHPG levels and percent improvement of the HRSD score. However, a significant difference was not observed in the pretreatment plasma level of homovanillic acid between responders and nonresponders to treatment with milnacipran or paroxetine. These results suggest that there is an association between baseline pMHPG levels and clinical responses with respect to milnacipran versus paroxetine treatment.

Adult↗

PubMed2004

Genetic association analysis of neuronal nitric oxide synthase gene polymorphism with tardive dyskinesia.

Possible involvement of oxidative stress in the pathophysiology of tardive dyskinesia (TD) has been proposed. Long-term administration of neuroleptics alters dopaminergic turnover, yielding the increase of the formation of reactive oxygen species (ROS), which may lead to TD through neuronal toxicity as a consequence of oxidative stress. In the present study, the relationship between TD and a polymorphism of the neuronal nitric oxide synthase (NOS1) gene whose reaction product, nitric oxide (NO), is involved in oxidative stress was studied in 171 Japanese patients with schizophrenia, including 41 patients meeting TD criteria. The C/T polymorphism in exon 29 of the NOS1 gene was genotyped using polymerase chain reaction (PCR) amplification followed by restriction enzyme digestion. No significant difference in genotype frequencies was detected between subjects with and without TD (chi2 = 1.54, df = 2, p = 0.46). In addition, there was no difference in allele frequencies (chi2 = 0.42, df = 1, p = 0.51). These results suggest that the NOS1 gene polymorphism may not confer increased susceptibility to TD, although more investigations on other populations are warranted.

Aged↗