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Y Yamanouchi

Publications and source records attributed to Y Yamanouchi.

At least 19 recordsLinked to original sources
PubMed2007

Possible association of beta-arrestin 2 gene with methamphetamine use disorder, but not schizophrenia.

Recent investigations suggest that the AKT/glycogen synthase kinase 3 (GSK3) signaling cascade may be associated with the pathophysiology of schizophrenia and methamphetamine (METH) use disorder. One important molecule related to this cascade is beta-arrestin 2 (ARRB2). We therefore conducted a genetic case-control association analysis of the gene for ARRB2 with schizophrenia and METH use disorder in a Japanese population (547 people with schizophrenia, 177 with METH use disorder and 546 controls). A possible association of 'tag single nucleotide polymorphisms (SNPs)' was found in METH use disorder (rs1045280: P(genotype) = 0.0118, P(allele) = 0.00351; rs2036657: P(allele) = 0.0431; rs4790694: P(genotype) = 0.0167, P(allele) = 0.0202), but no association was found with schizophrenia. We also evaluated the gene-gene interactions among ARRB2, AKT1, and GSK3B, which we previously reported for each of these diseases. However, no interaction was seen in our samples. This is the first association analysis of ARRB2, and our results indicate that ARRB2 may play a role in the pathophysiology of METH use disorder.

Adult↗
PubMed2006

Association study between kynurenine 3-monooxygenase gene and schizophrenia in the Japanese population.

Several lines of evidence suggest that metabolic changes in the kynurenic acid (KYNA) pathway are related to the etiology of schizophrenia. The inhibitor of kynurenine 3-monooxygenase (KMO) is known to increase KYNA levels, and the KMO gene is located in the chromosome region associated with schizophrenia, 1q42-q44. Single-marker and haplotype analyses for 6-tag single nucleotide polymorphisms (SNPs) of KMO were performed (cases = 465, controls = 440). Significant association of rs2275163 with schizophrenia was observed by single-marker comparisons (P = 0.032) and haplotype analysis including this SNP (P = 0.0049). Significant association of rs2275163 and haplotype was not replicated using a second, independent set of samples (cases = 480, controls = 448) (P = 0.706 and P = 0.689, respectively). These results suggest that the KMO is unlikely to be related to the development of schizophrenia in Japanese.

Aged↗
PubMed2005

No association of serotonin transporter gene (SLC6A4) with schizophrenia and bipolar disorder in Japanese patients: association analysis based on linkage disequilibrium.

Serotonin transporter gene (SLC6A4) is one of the most promising candidate genes for psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BP). Two functional polymorphisms, 5HTTLPR and 5HTTVNTR, have been a focus for genetic association analyses; however, no conclusive results have been obtained. We conducted, 1) a mutation search of SLC6A4, 2) LD mapping to select 'tagging' markers (10 SNPs and 5HTTVNTR, while 5HTTLPR was treated as an independent marker because of its allelic form), and 3) association analysis of these 'tagging' markers and independent markers (5HTTLPR and Asn605Lys) with SCZ and BP in Japanese patients. In this mutation search, a nonsynonymous SNP, Asn605Lys, was detected. No associations of 'tagging' markers and independent markers with such conditions were found. These results indicate that SLC6A4 might not play a major role in SCZ and BP in Japanese patients, a finding that agrees with both the common disease-common variant hypothesis and common disease-rare variant hypothesis.

Adult↗
PubMed2005

No association with the calcineurin A gamma subunit gene (PPP3CC) haplotype to Japanese schizophrenia.

Calcineurin, one of the serine/threonine protein phosphatase, comprises more than 1% of the total protein content in brain. This evidence points towards important roles of calcineurin in neural function. Miyakawa et al. reported that forebrain-specific calcineurin knockout mice showed the behavioral abnormalities that are often observed in schizophrenia patients. Based on this evidence, they suggested that calcineurin dysfunction could be involved in schizophrenia pathogenesis. Thereafter this report, Gerber et al. performed transmission disequilibrium test (TDT) studies and showed an evidence for a nominally significant over-transmission of a common haplotype of the human calcineurin A gamma subunit gene (PPP3CC). We performed association analysis of PPP3CC in Japanese sample of 457 schizophrenia cases and 429 controls. To our regret, we could not confirm the association with Japanese schizophrenia to PPP3CC including core at-risk haplotype. Our result suggests that PPP3CC may not play a major role in Japanese schizophrenia.

Calcineurin↗
PubMed2005

Association study of the frizzled-3 (FZD3) gene with schizophrenia and mood disorders.

Two research groups have recently reported a significant association between schizophrenia and genetic variants of Frizzled-3 (FZD3) gene. We examined a possible association in a Japanese sample of schizophrenia, bipolar disorder, unipolar depression and controls with four single nucleotide polymorphisms (SNPs), tested in previous reports. We failed to find significant association in the four SNPs or haplotype analysis. The FZD3 gene might not play a role in conferring susceptibility to major psychosis in our sample.

Adult↗
PubMed2005

Haplotype association between GABAA receptor gamma2 subunit gene (GABRG2) and methamphetamine use disorder.

Psychostimulant use disorder and schizophrenia have a substantial genetic basis. Evidence from human and animal studies on the involvement of the gamma-aminobutyric acid (GABA) system in methamphetamine (METH) use disorder and schizophrenia is mounting. As we tested for the association of the human GABA(A) receptor gamma 2 subunit gene (GABRG2) with each diagnostic group, we used a case-control design with a set of 178 subjects with METH use disorder, 288 schizophrenics and 288 controls. First, we screened 96 controls and identified six SNPs in GABRG2, three of whom we newly reported. Next, we selected two SNPs, 315C>T and 1128+99C>A, as representatives of the linkage disequilibrium blocks for further case-control association analysis. Although no associations were found in either allelic or genotypic frequencies, we detected a haplotypic association in GABRG2 with METH use disorder, but not with schizophrenia. This finding partly replicates a recent case-control study of GABRG2 in METH use disorder, and thus indicates that GABRG2 may be one of the susceptibility genes of METH use disorder.

Adolescent↗
PubMed2005

Blood lead and erythrocyte protoporphyrin levels in association with smoking and personal hygienic behaviour among lead exposed workers.

AIMS: To investigate the effects of smoking and personal hygienic behaviour on blood lead (BPb) and free erythrocyte protoporphyrin levels (FEP) in lead exposed workers. METHODS: Subjects were 105 lead exposed male workers in a battery recycling plant during the years 2000-03. BPb and FEP were measured as part of the ongoing occupational surveillance. Each worker completed a questionnaire for assessment of smoking and four measures of personal hygienic behaviour (glove and mask use, hand and face washing before meals during working hours). RESULTS: Statistically significant decreases in mean BPb and FEP occurred during the three years. The proportion of BPb reduction in the non-smoking workers was significantly higher (mean 24.3%) than in the smoking workers (15.3%). When the workers were classified into three groups (excellent, good, and poor) based on the four personal hygienic behavioural indicators, the greatest decreases of BPb and FEP were observed in the non-smoking workers of the excellent group. CONCLUSIONS: The consistent use of protection devices and cleanliness at work appeared to contribute to the lowering of BPb and FEP. Cessation of smoking in the workplace was also of importance.

Adult↗
PubMed2004

Association analysis of the -308G>A promoter polymorphism of the tumor necrosis factor alpha (TNF-alpha) gene in Japanese patients with schizophrenia.

Two research groups have thus far reported a significant association between schizophrenia and a promoter polymorphism (-308G > A) of the gene encoding tumor necrosis factor alpha (TNF-alpha), while contradictive negative results have also been reported. We examined the possible association in a Japanese sample of 297 schizophrenia cases and 458 controls. Allele frequencies of both the patients and controls were very low (1.5% and 0.8%, respectively), and the difference was not statistically significant. We conclude that the effect of the -308G > A polymorphism on the development of schizophrenia is, if any, weak and the majority of Japanese schizophrenics are unrelated to the -308G > A polymorphism of the TNF-alpha gene.

Adenine↗
PubMed2004

Effect of propofol and isoflurane anaesthesia on the immune response to surgery.

There are two major subpopulations of peripheral helper T lymphocytes: T helper 1 (Th1) and T helper 2 (Th2) cells. Surgical stress increases the number of Th2 cells, and decreases that of Th1 cells, resulting in a decrease in the Th1/Th2 ratio, and, consequently, in suppressed cell-mediated immunity. Since anaesthesia can suppress the stress response to surgery, it may inhibit the decrease in the Th1/Th2 ratio. Using flow cytometry, we studied whether propofol anaesthesia (n = 9) or isoflurane anaesthesia (n = 9) had more effect on the decrease in the Th1/Th2 ratio after surgery in patients undergoing craniotomy. The Th1/Th2 ratio decreased significantly after isoflurane anaesthesia (p = 0.011), while it did not change after propofol anaesthesia. The ratio was significantly lower with isoflurane than propofol (p = 0.009). Propofol anaesthesia attenuated the surgical stress-induced adverse immune response better than isoflurane anaesthesia.

Adult↗
PubMed2003

Association of a haplotype in the serotonin 5-HT4 receptor gene (HTR4) with Japanese schizophrenia.

The serotonin 5-HT(4) receptor (5-HT(4)) is implicated in cognitive function, of which impairment is hypothesized as one of the core disturbances of schizophrenia. Linkage analysis shows that 5q33.2, in which HTR4 is located, is schizophrenia-susceptibility loci. We therefore hypothesized that variation in the 5-HT(4) receptor gene (HTR4) modifies genetic susceptibility to schizophrenia. HTR4 coding regions and introns that include the branch sites of HTR4 were investigated in 96 unrelated Japanese schizophrenics using denaturing high-performance liquid chromatography analysis. One silent single nucleotide polymorphism (SNP) within the coding region and six intronic SNPs were detected. 353 + 6G > A was located in the branch site that could be effect to RNA splicing. None of the four SNPs, in which rare-allele frequencies were more than 10% was associated with 189 schizophrenics, in comparison to 299 controls. However, a highly significant association between schizophrenia and haplotype A-T (OR = 0.13 [0.03-0.58]) was detected. These findings suggest that haplotype A-T itself may inhibit the occurrence of schizophrenia, or that another susceptible genetic variants may exist within linkage disequilibrium.

DNA Mutational Analysis↗
PubMed2003

Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone.

Risperidone is a widely used atypical antipsychotic with certain advantages over typical antipsychotics. Although variations in the efficacy of treatment with risperidone have been observed, no specific predictable marker has been identified as of yet. In all, 73 Japanese patients with schizophrenia were given risperidone for 8 weeks, and clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Six candidate polymorphisms (HTR2A -1438G>A, 102T>C, H452Y; DRD2 -141delC, Taq I A; COMT V158M) were genotyped. The diplotype configuration for each individual was estimated by the maximum-likelihood method. Multiple linear regressions were used to analyze the effects of these haplotypes/genotype and other prognostic factors on PANSS scale performance. After adjustment for the effects of patient-related variables, HTR2A diplotype and COMT genotype, as well as other potential prognostic factors, did not significantly influence the clinical performance. A DRD2 haplotype tended to correlate with better clinical performance. Compared with patients who had Ins-A2/Ins-A2 diplotype (n=25), PANSS total scores of patients with Ins-A2/Del-A1 diplotype (n=10) showed 40% greater improvement (P=0.03). The PANSS total scores of patients with HTR2A A-T/A-T diplotype (n=22) tended to show 15% worse improvement compared with A-T/G-C diplotype (n=33) (P=0.06). These results should be treated with caution because of limitations due to small sample size, heterogeneity of patients with respect to past antipsychotic use history, and no correction for multiple corrections. However, the present findings generate important hypotheses in a sample of Japanese schizophrenia patients that may lay the foundation for future pharmacogenomics investigations in other populations.

Adult↗
PubMed2001

A novel apolipoprotein E5 variant with a 24-bp insertion causing hyperlipidemia.

A tandem 24-bp insertion in the apolipoprotein E (apo E) gene was detected in a patient with elevated triglyceride, apolipoprotein (apo) CII, and apo CIII levels. This novel variant, apo E5ss, showed in position apo E5 by isoelectric focusing and was of larger molecular weight than apo E3 during two-dimensional gel electrophoresis. Polymerase chain reaction-single strand conformation polymorphism analysis using the primer pairs that cover all the coding regions was useful for rapid detection of the variant of the apo E allele. Apo E5ss may have a 24-bp insertion caused by slipped mispairing, resulting in a tandem duplication of amino acid residues 135-142 [APOE, 24-BP INS, DUP CODONS 135-142]. The proband was the only person with apo E5ss among the 806 Japanese males that we examined. We inspected six other reported apo E5 variants in the literature.

Amino Acid Sequence↗
PubMed2001

The mechanisms of the vulnerable window: the role of virtual electrodes and shock polarity.

Vulnerability and defibrillation are mechanistically dependent upon shock strength, polarity, and timing. We have recently demonstrated that shock-induced virtual electrode polarization (VEP) may induce reentry. However, it remains unclear how the VEP mechanism may explain the vulnerable window and polarity dependence of vulnerability. We used a potentiometric dye and optical mapping to assess the anterior epicardial electrical activity of Langendorff-perfused rabbit hearts (n = 7) during monophasic shocks (+/-100 V and +/-200 V, duration of 8 ms) applied from a transvenous defibrillation lead at various coupling intervals. Arrhythmias were induced in a coupling interval and shock polarity dependent manner: (i) anodal and cathodal shocks induced arrhythmias in 33.2 +/- 30.1% and 53.1 +/- 39.3% cases (P < 0.01), respectively, and (ii) the vulnerable window was located near the T-wave. Optical maps revealed that VEP was also modulated by the coupling interval and shock polarity. Recovery of excitability produced by negative polarization, known as de-excitation, and the resulting reentry was more readily achieved during the relative refractory period than the absolute refractory period. Furthermore, anodal shocks produced wavefronts propagating in an inward direction with respect to the electrode, whereas cathodal shocks propagated in an outward direction. Wavefronts produced by anodal shocks were more likely to collide and annihilate each other than those caused by cathodal shocks. The probability of degeneration of the VEP-induced phase singularity into a sustained arrhythmia depends upon the gradient of VEP and the direction of the VEP-induced wavefront. The VEP gradient depends upon the coupling interval, while the direction depends upon shock polarity; these factors explain the vulnerable window and polarity-dependence of vulnerability, respectively.

Action Potentials↗
PubMed2001

Renin-angiotensin system plays an important role in the regulation of water transport in the peritoneum.

The present study was carried out to investigate changes in the expression of aquaporins (AQPs) in the peritoneum. The effects of the renin-angiotensin system on the expression of AQPs with and without angiotensin converting enzyme inhibitor (ACEI) or angiotensin II type 1a receptor blocker (ARB) were then examined. We divided 20 male Wistar Kyoto (WKY) rats into four groups, dialyzed with these solutions: saline; 10% glucose (TZ); 10% glucose plus benazepril (ACEI: 4 mg/kg daily); and 10% glucose plus valsartan (ARB: 10 mg/kg daily). The ACEI and ARB were administered into the peritoneum for 7 days. Expression of AQP-1-AQP-4 mRNA was studied by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR). Ultrafiltration volume (UFV) and peritoneal function were measured by peritoneal equilibration test (PET). In the TZ group, expression of AQP-1 and AQP-4 was enhanced in parallel with an increment in UFV. Expression of AQP-1 and AQP-4 was also observed in the mesothelium by immunofluorescence microscopy. On the other hand, in ACEI- and ARB-treated rats, expression of AQP-1 and AQP-4 was significantly suppressed, accompanied by loss of UFV. Our results suggest that the renin-angiotensin system plays an important role in the regulation of water transport in the peritoneum. Administration of ACEI or ARB in patients undergoing continuous ambulatory peritoneal dialysis should be carried out with caution.

Angiotensin II↗
PubMed2001

New animal models for encapsulating peritoneal sclerosis--role of acidic solution.

OBJECTIVE: Encapsulating peritoneal sclerosis (EPS), in which all or part of the intestine is enveloped in a fibrous ball resembling a cocoon, is a serious complication of peritoneal dialysis (PD). The aim of the present study was to investigate whether pH-neutral or acidic dialysis solutions induce peritoneal fibrosis. DESIGN: We divided 18 male Wistar-Kyoto (WKY) rats into three groups and dialyzed them with various solutions as follows: group I, 10 mL acidic dialysis solution (pH 3.8, containing 1.35% glucose), n = 6; group II, 10 mL pH 5.0 dialysis solution, n = 6; and group III, 10 mL neutral dialysis solution (pH 7.0), n = 6. Peritoneal catheters were inserted, and dialysis solution was injected every day for 40 days. At the end of the experiment, a peritoneal equilibration test (PET) was performed. Expression of mRNA of aquaporins 1 and 4 (AQP-1 and AQP-4) in the peritoneum were studied by semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: In rats treated with pH 3.8 dialysis solution, necropsy findings revealed features identical to those of EPS. The typical appearance was of granulation tissue or fibrotic tissue (or both) covering multiple surfaces. Multiple adhesions were present. In microscopic examinations, peritoneal fibrosis and loss of mesothelium were found. In rats treated with pH 7.0 dialysis solution, no signs of EPS were seen. In rats treated with pH 5.0 dialysis solution, milder changes (subserosal thickening and partial adhesion of the peritonea) were observed. The mRNA of AQP-1 and AQP-4 were expressed in the peritonea of the rats. The expression of the AQPs was significantly suppressed in rats treated with pH 3.8 dialysis solution. CONCLUSIONS: In rats, long-term intraperitoneal injection of acidic dialysis solution produced features typical of EPS in humans. Newly developed neutral dialysis solutions protected the against the development of EPS during peritoneal dialysis in rats.

Animals↗
PubMed2000

Structural analysis of a rare rearranged Y chromosome and its bearing on genotype-phenotype correlation.

We report on a 9-year-old boy with a rare rearranged Y chromosome and borderline short stature (-2.0 SD). Standard metaphase chromosome analysis indicated a 46,X,i(Y)(q1O) karyotype, but high resolution G-banding showed an asymmetric band pattern for the rearranged Y chromosome. FISH and DNA studies for a total of 15 different Y chromosomal loci or regions showed that the rearranged Y chromosome was accompanied by: 1) a partial deletion of the short arm pseudoautosomal region (PAR1) involving SHOX, with the breakpoint distal to DXYS85; and 2) a partial duplication of Yq, with the breakpoint proximal to DAZ. The karyotype was determined as 46,X,?i(Y)(q1O).ish der(Y)(Yqter--> Yp11.3::Yq11.2-->Yqter)(DAZ++,DYZ3+,SRY +, SHOX-). The X chromosome and the autosomes were normal. The results suggest that haploinsufficiency of SHOX is primarily responsible for the borderline short stature, and that the deletion of the PAR1 may result in spermatogenic failure due to defective X-Y pairing and recombination in the PAR1.

Child↗
PubMed2000

Girl with accelerated growth, hearing loss, inner ear anomalies, delayed myelination of the brain, and del(22)(q13.1q13.2).

We report on an 18-month-old Japanese girl with 46,XX,del(22)(q13.1q13.2). To our knowledge, this is the first report of a case of interstitial deletion of a 22q13.1-q13.2 segment. Clinical features included hearing loss accompanied by inner ear anomalies, hypotonia and minor anomalies, such as a long philtrum, full eyelids, epicanthus, left transverse palmar crease and psychomotor developmental delay. Despite the chromosomal deletion, her physical growth was accelerated: her height was between the 75th and 90th percentiles for her age. Her brain MRI showed signs of delayed myelination. The three-dimensional MRI of the inner ear showed abnormalities of the cochlea and vestibule in both ears. Clinical features of the patient are similar to those of a patient with a del(22)(q13.1q13.33) karyotype previously reported by Romain et al.

Abnormalities, Multiple↗