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Kazutaka Shimoda

Publications and source records attributed to Kazutaka Shimoda.

11 recordsLinked to original sources
PubMed2006

Association study of putative promoter polymorphisms in the neuroplastin gene and schizophrenia.

A previous study revealed a number of methamphetamine (METH) and phencyclidine (PCP)-reactive tags in a rat brain through serial analysis of gene expression. The present study extends this previous study by investigating whether two genes, which deduced from METH/PCP-reactive tags, were identified as those encoding human transmembrane proteins of the immunoglobulin (Ig) superfamily, neuroplastin (NPTN) and basigin (BSG), confer genetic susceptibility to schizophrenia by analyzing single nucleotide polymorphisms (SNPs). There were nominally significant differences between the two groups in their allelic frequencies (T Ins/Del, chi2=4.910, d.f.=1, P=0.040) and genotypic distributions (T/T or T/Del, chi2=5.116, d.f.=1, P=0.036) of rs3840846 in the 5'-upstream of NPTN. The two groups differed significantly also in their allelic frequencies (G/T, chi2=4.229, d.f.=1, P=0.044), but not genotypic distributions of rs3743500 in the 5'-upstream of NPTN. The haplotypes constructed from the three SNPs (rs3840846, rs3826047 and rs3743500, in order) in the 5'-upstream of NPTN showed a significant association with schizophrenia (permutation P=0.036), in that T-G-T (permutation P=0.028) and del-G-G (permutation P=0.040) were under-represented and over-represented, respectively, in schizophrenia. A reporter construct driven by the 5'-upstream region containing any haplotype consisting of the three SNPs had substantial transcriptional activity. Notably, a reporter construct containing a haplotype T-G-T had significantly lower transcriptional activity as compared with one having a haplotype T-G-G or T-A-G. There was no significant difference between the two groups regarding allelic frequencies, genotypic distribution or the adopted SNP-combinatory haplotype for BSG. These results suggest that NPTN may be involved in genetic susceptibility to schizophrenia.

Adult↗
PubMed2006

The impact of CYP2D6 genotypes on the plasma concentration of paroxetine in Japanese psychiatric patients.

The authors investigated the impact of the CYP2D6 genotypes on the plasma concentration of paroxetine (PAX) in 55 Japanese psychiatric patients. They were administered 10 to 40 mg/day (24+/-10.0 mg/day) of PAX and maintained at the same daily dose for at least two weeks to obtain the steady-state concentrations. The plasma levels of PAX were 15.8+/-15.0, 47.4+/-32.0, 101.2+/-59.9 and 177.5+/-123.6 ng/ml at the daily dose of 10, 20, 30 and 40 mg, respectively, which suggested dose dependent kinetics of PAX. The allele frequencies of the CYP2D65, CYP2D610 and CYP2D641 were 1.8%, 41.8% and 1.8%, respectively. Significantly higher PAX concentrations were observed in the patients having one functional allele compared with those with two functional alleles (150.9+/-20.6 vs. 243.6+/-25.2 ng/ml mg(-1) kg(-1), p<0.05, Newman-Keuls multiple comparison test) or no functional (243.6+/-25.2 vs. 76.7+/-6.1 ng/ml mg(-1) kg(-1), p<0.05, Newman-Keuls multiple comparison test) in the subjects with 30 mg/day of paroxetine. The same trend of findings as in the subjects treated with 30 mg/day were observed in the subjects with 40 mg/day of PAX. The present results suggest that having one non-functional allele is the marker for high plasma concentration of PAX when relatively high daily dose of PAX is administered.

Adult↗
PubMed2005

The relation between negative emotional suppression and emotional distress in breast cancer diagnosis and treatment.

Our objective was to investigate differences in emotional distress between negative emotional suppression and expression patients in the progress of medical treatment, including the operation. We studied the differences in affective response between patients who suppress negative emotion and those who express negative emotion by using Profile of Mood States (McNair, Lorr, & Droppleman, 1971) at four sessions: (a) at the first visit to the clinic, (b) immediately after being told the diagnosis of breast cancer, (c) after the operation, and (d) at 3 months after discharge. Our results showed that emotional suppression patients tended to report more emotional distress (in particular, anxiety, depression, and anger) than did emotional expression patients on 3 sessions, the exception being after the operation. Also, patients who suppress anger and anxiety felt strong psychological distress. We suggest that it is essential to encourage suppressive patients to express both negative and positive emotion clearly and appropriately.

Adult↗
PubMed2004

[Effect of smoking on pharmacokinetics of antipsychotics].

The population of Japanese smokers has decreased; however, the prevalence of smokers among psychiatric patients has been reported to be as high as 80% in schizophrenic patients. Although the impact of smoking on the pharmacokinetics of antipsychotics has been reported, results have been controversial. At first, the impact of smoking on plasma haloperidol (HAL) concentrations was investigated in Japanese male schizophrenic inpatients treated with HAL per os. Smokers had approximately 20% lower HAL concentrations/daily dose of HAL/kg body weight than non-smokers. The impact of genetic polymorphism of CYP1A2 that are related to the induction of the isozyme on the plasma levels of HAL in male smokers with schizophrenia was also investigated. A point mutation from C to A in intron 1 at position 734 and a point mutation from G to A at position--2964 in the 5'-flanking region of CYP1A2 were identified by the PCR-RFLP method. Regarding C/A polymorphism in intron 1 at position 734, no significant difference was found in the plasma concentrations of HAL corrected for dose and weight among the subjects with A/A, A/C and C/C genotypes. Regarding G/A polymorphism at position--2964 in the 5'-flanking region, no significant difference was found in the plasma concentrations of HAL corrected for dose and weight between subjects with G/G and G/A.

Antipsychotic Agents↗
PubMed2003

Effect of CYP2D6 genotypes on the metabolism of haloperidol in a Japanese psychiatric population.

We investigated the effect of CYP2D6 genotypes on plasma levels of haloperidol (HAL) and reduced haloperidol (RHAL) in 88 Japanese schizophrenic inpatients being treated with HAL. Some subjects carrying CYP2D6*5 allele (CYP2D6*1/CYP2D6*5, CYP2D6*5/CYP2D6*10) showed extremely high concentrations of both HAL and RHAL, and the groups with CYP2D6*5 allele seemed to have higher plasma concentrations of HAL (1.14+/-0.69 ng/ml/mg) and RHAL (1.10+/-1.05 ng/ml/mg) than the other groups. Among those without CYP2D6*5 allele, there were no significant differences in plasma concentrations of HAL and RHAL between those without CYP2D6*10 allele (HAL=0.68+/-0.31 ng/ml/mg, RHAL=0.28+/-0.37 ng/ml/mg), those with one CYP2D6*10 (HAL=0.70+/-0.23 ng/ml/mg, RHAL=0.31+/-0.16 ng/ml/mg) and those with two CYP2D6*10 alleles (HAL=0.69+/-0.14 ng/ml/mg, RHAL=0.40+/-0.09 ng/ml/mg), although there was a tendency of higher plasma concentration of RHAL in those with two CYP2D6*10 alleles. At a lower daily dosage of HAL (<10 mg/day), the subjects with two or one CYP2D6*10 allele(s) showed significantly higher plasma concentrations of RHAL (0.43+/-0.23 ng/ml/mg, 0.34+/-0.16 ng/ml/mg) than those without CYP2D6*10 allele (0.18+/-0.16 ng/ml/mg). The results of this study indicate that CYP2D6*10 allele plays significant but modest role in HAL metabolism in Japanese; nevertheless, we should not lump CYP2D6*10 allele with CYP2D6*5 allele because these two mutated alleles seem to have different impacts in the metabolism of HAL.

Adult↗
PubMed2003

Effects of concomitant fluvoxamine on the metabolism of alprazolam in Japanese psychiatric patients: interaction with CYP2C19 mutated alleles.

OBJECTIVES: Administration of fluvoxamine (FLV) with concomitant benzodiazepines is common in clinical situations. We studied the effects of the coadministration of FLV on plasma concentrations of alprazolam (ALP). We also studied the effects of CYP2C19(*)2 or CYP2C19(*)3 on these drug interactions. METHODS: The subjects were 23 Japanese outpatients all concomitantly treated with FLV either before or after monotherapy with ALP. We measured the plasma concentrations of ALP and FLV using a column-switching, high-performance liquid chromatographic method with ultraviolet detection. The CYP2C19(*)2 or CYP2C19(*)3 alleles were identified using a polymerase chain reaction analysis. RESULTS: Coadministration with FLV produced significant, on average 58%, increases in the plasma concentrations of ALP ( P<0.001). There were, however, wide variations in the interactive effects of the coadministration of FLV on the plasma concentrations of ALP. While there were some subjects who had greater increases in plasma ALP concentrations, more than 100%, in response to the coadministration of FLV among the subjects with no mutated or one mutated allele, there are no subjects who had increases in plasma ALP concentrations of more than 50% among the subjects with two mutated alleles. The differences of these variances among the three genotype groups reached a level of significance ( P<0.05). CONCLUSION: Coadministration of FLV significantly increased the plasma concentrations of ALP compared with ALP monotherapy. Wide variations were observed in the drug interactions, with the CYP2C19 genotype possibly being related to these interactions.

Adult↗
PubMed2003

Differences in emotional distress between breast tumor patients with emotional inhibition and those with emotional expression.

The differences in affective status between patients who restrain their negative emotion and those who express negative emotion after being given their breast cancer diagnosis were studied using the Profile of Mood States (POMS) at two sessions: (i) at the first visit to the outpatient surgery clinic, and (ii) immediately after being given the diagnosis of breast cancer. Eighty-seven patients completed the POMS and the Courtauld Emotional Control Scale (CECS) at the first visit to the outpatient surgery clinic at Shiga University of Medical Science Hospital. They also completed the POMS immediately after being given the diagnosis of breast cancer. Breast cancer patients who restrain their negative emotion (n = 8) were highly anxious, depressed and confused after being given the diagnosis compared to breast cancer patients who express negative emotion (n = 8). Emotional distress in benign breast tumor patients was reduced after being given the diagnosis regardless of the trend of emotional inhibition. That is, emotional distress in patients who restrain their emotions was considerably increased compared with that of patients who expressed their emotions when they were faced with a life-threatening disease. These results suggest that it may be therapeutic to advise breast cancer patients to express their negative emotion.

Adaptation, Psychological↗
PubMed2002

Lack of impact of CYP1A2 genetic polymorphism (C/A polymorphism at position 734 in intron 1 and G/A polymorphism at position -2964 in the 5'-flanking region of CYP1A2) on the plasma concentration of haloperidol in smoking male Japanese with schizophrenia.

The impact of genetic polymorphism of CYP1A2 that are related to the induction of the isozyme on the plasma levels of haloperidol (HAL) in 40 male smokers with schizophrenia was investigated. A point mutation from C to A in intron 1 at position 734 and a point mutation from G to A at position -2964 in the 5'-flanking region of CYP1A2 were identified by polymerase chain-reaction-restricted fragment length polymorphism method. Regarding C/A polymorphism in intron 1 at position 734, no significant difference was found in the plasma concentrations of HAL corrected for dose and weight among the subjects with A/A (n = 21), A/C (n = 14) and C/C (n = 5) genotypes (one-way analysis of variance: 63.1 +/- 18.5, 47.8 +/- 12.5 and 50.8 +/- 15.1 ng/ml/mg/kg, respectively, F(2,37) = 2.556, P = .09). Regarding G/A polymorphism at position -2964 in the 5'-flanking region, no significant difference was found in the plasma concentrations of HAL corrected for dose and weight between subjects with G/G (n = 24) and G/A (n = 15) (two-tailed t test: G/G and G/A = 51.2 +/- 16.6 and 59.0 +/- 17.6 ng/ml/mg/kg, respectively, df = 28, P = .22). The present study suggests that the genotyping of CYP1A2 cannot predict the steady state plasma levels of HAL in male smoking schizophrenics.

5' Flanking Region↗
PubMed2002

The impact of CYP2C19 and CYP2D6 genotypes on metabolism of amitriptyline in Japanese psychiatric patients.

We investigated the effect of the CYP2C19 and CYP2D6 genotypes on the metabolism of amitriptyline (AT) in Japanese psychiatric patients. Steady-state concentrations of AT and its metabolites (nortriptyline [NT], trans-10-hydroxy-nortriptyline [EHNT], cis-10-hydroxy-nortriptyline [ZHNT], trans-10-hydroxy-amitriptyline [EHAT], and cis-10-hydroxy-amitriptyline [ZHAT]) in 50 patients were determined by high-performance liquid chromatography. Significantly higher plasma concentrations of AT corrected for dose and body weight in the subjects with two mutated alleles of CYP2C19 than in those with no mutated alleles of CYP2C19 were observed (no mutated alleles vs. two mutated alleles: 36.0 +/- 18.2 vs. 64.0 +/- 25.2 ng/mL/mg/kg, p = 0.025). A significantly higher AT/NT ratio was seen in the subjects with two mutated alleles of CYP2C19 than in those with no mutated alleles of CYP2C19 (no mutated alleles vs. two mutated alleles: 1.27 +/- 0.59 vs. 3.40 +/- 1.02, p = 0.001). A trend for higher NT/EHNT ratio in the subjects with two mutated alleles of CYP2D6 than in those with no mutated alleles of CYP2D6 was observed (no mutated alleles vs. two mutated alleles: 0.73 +/- 0.39 vs. 1.31 +/- 0.81, p = 0.068). A trend for higher plasma concentrations of total hydroxylated metabolites of AT (EHAT + ZHAT) corrected for dose and body weight in the subjects with two mutated alleles of CYP2C19 than in those with no mutated alleles of CYP2C19 was found (no mutated alleles vs. two mutated alleles: 9.5 +/- 5.8 vs. 17.8 +/- 8.9, p = 0.051). Therefore, the genotype of CYP2C19 is one of the important determinants of the plasma concentrations of AT and the capacity to desmethylate AT. Mother compound AT is shunted via hydroxylation pathways from AT to EHAT and ZHAT in the subjects with homozygotes of mutated alleles of CYP2C19 in order to compensate for the decreased capacity to desmethylate AT.

Adolescent↗
PubMedDate not supplied

Anxiety, emotional suppression, and psychological distress before and after breast cancer diagnosis.

The authors examined the influence of anxiety and emotional suppression on psychological distress in 21 patients with breast cancer and 72 patients with benign breast tumor. The patients with breast cancer who suppressed emotion and had chronically high levels of anxiety felt higher levels of emotional distress both before and after the diagnosis. Such patients need psychological interventions, including encouragement to express and communicate their emotions, immediately after disclosure of the diagnosis to help maintain psychological adjustment in the face of the disease.

Adaptation, Psychological↗