Search PubMed⌕ Search

Biomedical subjects

Heii Arai

Publications and source records attributed to Heii Arai.

47 records · Page 3Linked to original sources

Expression of Fyn, a non-receptor tyrosine kinase in prefrontal cortex from patients with schizophrenia and its correlation with clinical onset.

Fyn is a member of the non-receptor tyrosine kinase family, which is known to be closely involved in signal transduction in neurons and has an important role in the development and organisation of the central nervous system. In order to explore the possible role of Fyn in schizophrenia, the expression of Fyn messenger RNA (mRNA) and protein were investigated in the postmortem prefrontal cortex of brains from normal and 'schizophrenic' cases. There was an increase in both total area Fyn mRNA signal (17.7%, P<0.05) and cellular mRNA content (15.7%, P<0.05) in the schizophrenic group relative to controls. In parallel the content of Fyn protein detected by immuno-autoradiography was also increased in the schizophrenic cases (21.8% P<0.05). In addition, the cellular Fyn mRNA signal was negatively correlated with the age of onset (r=-0.94, P=0.0026). These results suggest that an increase in Fyn expression may contribute to the pathophysiology of schizophrenia.

Aged↗

Haloperidol plasma concentration in Japanese psychiatric subjects with gene duplication of CYP2D6.

AIMS: The cytochrome P-450 2D6 (CYP2D6) gene duplication/multiduplication producing an increase in enzyme activity, and the common Japanese mutation, CYP2D6*10A producing a decrease of enzyme activity were screened in a large number of Japanese psychiatric subjects (n = 111) in order to investigate whether these mutated alleles affected the plasma concentration of haloperidol. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed to identify the CYP2D6*10A and CYP2D6*2 genotypes in subjects who had been taking haloperidol. For the screening of duplicated active CYP2D6 gene, allele-specific long PCR was performed. Plasma concentration of haloperidol was measured by the enzyme immunoassay, and expressed as "plasma concentration dose ratio" to normalize individual differences. RESULTS: The plasma concentration-dose ratio showed large interindividual differences of approximately 18-fold. PCR-RFLP methods revealed that 29 (26.1%), 10 (9.0%), 39 (35.1%), 0 (0%), seven (6.3%) and 26 (23.4%) cases possessed the CYP2D6 genotypes *1/*1, *1/*2, *1/*10A, *2/*2, *2/*10A and *10 A/*10A, respectively. Six cases (5.4%) had duplicated CYP2D6 genes. There were no significant differences of plasma concentration-dose ratio between the groups classified by CYP2D6*10A and *2 genotypes (Kruskal-Wallis test; P = 0.37), even in those cases whose daily doses were lower than 20 mg (n = 90, P = 0.91). Subjects having duplicated genes (n = 6) did not show significant differences of plasma concentration-dose ratio by comparison with subjects who had no duplicated genes (Mann-Whitney U-test; P = 0.80). CONCLUSIONS: Gene duplication, and the common Japanese mutation CYP2D6*10A on CYP2D6 gene are not likely to be the main modulatory factors of plasma concentration of haloperidol in Japanese psychiatric subjects.

Administration, Oral↗

Repeated cocaine administration differentially affects NMDA receptor subunit (NR1, NR2A-C) mRNAs in rat brain.

We investigated the effects of intermittent intraperitoneal (i.p.) injections of cocaine (20 mg/kg) on subunit mRNAs of N-methyl-D-aspartate (NMDA) receptors (NR1/NR2A-2C) in the rat brain by in situ hybridization using phosphor screen analysis. The level of NR1 subunit mRNA significantly increased in hippocampal complexes 1 h after a single i.p. injection of cocaine. After repeated cocaine injection, the mean scores of stereotyped behavior were increased with the number of injections. The level of NR1 subunit mRNA was obviously decreased in the striatum and cortices 24 h (early withdrawal) after a final injection following 14 days of subchronic administration. During the early withdrawal period, the amount of the NR1 subunit decreased in the nucleus accumbens, globus pallidus, and subiculum. In the dentate gyrus, the NR1 mRNA level significantly increased during early withdrawal in rats subchronically treated with cocaine. Levels of NR2B subunit mRNA were reduced in the cortices and striatum. During late withdrawal from cocaine, the level of NR2C subunit mRNA in the cerebellum was also reduced. These findings suggest that the disruption of NR1, NR2B, and NR2C subunits in the discrete brain regions occurs under the cocaine-related behavioral abnormalities and would be closely implicated in the initiation and expression of behavioral sensitization induced by repeated cocaine administration. Further studies on the changes in non-NMDA receptors are required to elucidate the biological significance of glutamate receptors for the mechanisms underlying the development of behavioral sensitization.

Anesthetics, Local↗

Effect of IL-6 polymorphism on risk of Alzheimer disease: genotype-phenotype association study in Japanese cases.

Interleukin-6 (IL-6), an inflammatory cytokine might be involved in the pathophysiology of Alzheimer disease (AD); several studies have reported that the "C allele of IL-6 variable number of tandem repeat polymorphism" (IL-6vntr) delayed initial onset of AD and also decreased its risk per se. Another polymorphism, G/C allele of IL-6 gene promoter region (IL-6prom), is also a candidate because it has an influence on the regulation of plasma IL-6 concentration. We examined these IL-6 polymorphisms in 128 Japanese AD cases and 83 control cases using a PCR-RFLP method. The results showed the frequency of the IL-6prom G allele was significantly increased in AD, although IL-6vntr polymorphism was not. Plasma IL-6 concentration of the AD cases was also significantly higher than that of the control cases. Moreover, the IL-6prom G allele-positive AD patients showed a tendency to have higher IL-6 concentration in the AD group. These findings suggest that the IL-6prom G allele which may affect plasma IL-6 concentration might be a risk factor for sporadic AD in Japanese.

Aged↗

The effect of IL4 +33C/T polymorphism on risk of Japanese sporadic Alzheimer's disease.

Interleukin-4 (IL4) is an anti-inflammatory cytokine that may play a role in the inflammation pathology observed surrounding senile plaques, and may also associate with Alzheimer's disease (AD) pathogenesis. Recently, it has been reported that a single nucleotide polymorphism in the IL4 gene promoter region, IL4 +33C/T polymorphism, associates with its phenotype. It was thought that the IL4 +33C/T polymorphism causing high IL4 production may reduce the risk for AD. In the present study, therefore, we investigated this mutation in 108 healthy controls and in 178 sporadic AD cases by the polymerase chain reaction restriction fragment length polymorphism method in a Japanese AD population. Allelic frequencies with +33C/T polymorphism in the gene were 35.6 and 32.6% in the control and AD groups, respectively. Our results failed to demonstrate an association between this polymorphism and Japanese sporadic AD. We also tested whether the IL4 functional variants were regulated by this polymorphism in a portion of the subjects (16 AD cases and 13 control cases). We could not find any relationship between the IL4 +33C/T polymorphism and plasma IL4 concentration.

Adult↗

Gene expression analysis in schizophrenia: reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22.

We screened a custom-made candidate gene cDNA array comprising 300 genes. Genes chosen have either been implicated in schizophrenia, make conceptual sense in the light of the current understanding of the disease, or are located on high-susceptibility chromosome locations. The array screen using prefrontal cortex tissue from 10 schizophrenia and 10 control brains revealed robust up-regulation of apolipoprotein L1 (apo L1) by 2.6-fold. The finding was cross-validated in a blinded quantitative PCR study using prefrontal cortex tissue from the Stanley Foundation brain collection, Bethesda, MD. This collection consists of 15 schizophrenia, 15 bipolar disorder, 15 major depression, and 15 control individuals, all 60 brains being well-matched on conventional parameters, with antipsychotic drug exposure in the schizophrenia and bipolar disorder groups. Significant up-regulation of apo L1 gene expression in schizophrenia was confirmed. Using quantitative PCR, expression profiles of other members of the apo L family (apo L2-L6) were investigated, showing that apo L2 and L4 were highly significantly up-regulated in schizophrenia. Results were then confirmed in an independent set of 20 schizophrenia and 20 control brains from Japan and New Zealand. Apo L proteins belong to the group of high density lipoproteins, with all six apo L genes located in close proximity to each other on chromosome 22q12, a confirmed high-susceptibility locus for schizophrenia and close to the region associated with velocardiofacial syndrome that includes symptoms of schizophrenia.

Apolipoprotein L1↗

Clinical significance of sleep-related breathing disorder in narcolepsy.

Both the influence of comorbid obstructive sleep apnea-hypopnea syndrome (OSAHS) on daytime sleepiness and its pathological mechanism in 10 narcoleptic patients was studied. Mild elevation of esophageal negative pressure and obstruction in the velopharyngeal area, as observed by upper airway magnetic resonance imaging, during apneic episodes was observed in the subjects. Severity of the disorder was correlated positively with body mass index, and the latencies of the multiple sleep latency tests were not improved with nasal continuous positive airway pressure treatment in subjects. Pathogenesis of OSAHS in narcolepsy was thought to be almost similar to typical OSAHS, and that the disorder seemed to lack a pathological influence on daytime sleepiness.

Adult↗

Subjective sleep quality and suggested immobilization test in restless leg syndrome and periodic limb movement disorder.

The severity of restless leg syndrome (RLS) and/or periodic limb movement disorder (PLMD) was investigated by using a suggested immobilization test (SIT) and by measuring the influence of these disorders on the subjective sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI). Patients with RLS and those with both RLS and PLMD showed remarkably high values for PSQI and SIT, whereas patients with PLMD only showed normal values for PSQI. These findings suggest that there is only a small pathological significance for periodic limb movements, and demonstrate the efficacy of SIT and PSQI for evaluating the severity of these disorders.

Electromyography↗

Response of Japanese patients to the change of department name for the psychiatric outpatient clinic in a university hospital.

There has long been controversy over the stigma associated with mental illness and psychiatric facilities. In Japan, the department name "Department of Psychiatry" (in Japanese, Seishin-ka) itself evokes the lay public's and psychiatric patients' feelings of stigma. This phenomenon may hamper psychiatric treatment of adequate duration and quality. On July 1st, 1999, the Juntendo University Hospital changed the department name from "Department of Psychiatry and Neurology" (in Japanese, Seishin-Shinkei-ka) to Mental Clinic, accompanied by an increased number of new outpatients, as reported previously. In the present study, we turn our attention to the opinions of those patients who have received treatment in the department under both names. Questionnaires asking for their opinions about the department names revealed that the majority have feelings of stigma associated with the name "Department of Psychiatry and Neurology." This result did not correlate with demographic factors or the length of psychiatric treatment. However, those who experienced psychiatric admission were significantly less uncomfortable with the name than those who did not. It was also revealed that the change in the name lessened their feelings of stigma and negative self-image as patients of a general hospital. These results suggest the importance of the name of the psychiatric department in general hospitals, in Japan, from therapeutic, psychosocial and ethical viewpoints.

Adult↗

Risperidone withdrawal-related respiratory dyskinesia: a case diagnosed by spirography and fibroscopy.

Risperidone is a frequently used member of a new class of atypical antipsychotics-the serotonin-dopamine antagonists (SDAs)-due to its comparatively high efficacy and low D2/5HT2 binding ratio, which results in a low incidence of extrapyramidal side effects including tardive dyskinesia (TD). The authors present an elderly patient with mixed dementia who developed TD at multiple sites, (including respiratory dyskinesia [RD], limb dyskinesia, and orofacial dyskinesia) following abrupt withdrawal of risperidone therapy. RD is not a rare condition, but is often misdiagnosed and is potentially lethal. Therefore, clinicians should pay close attention to possible onset of RD in patients with multiple risk factors for TD, even when SDA therapy is used. If RD is suspected, assessment should include spirography combined with fibroscopy for examination of irregularities in the rate, rhythm, and depth of respiration.

Aged↗