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Biomedical subjects

H Suwaki

Publications and source records attributed to H Suwaki.

At least 19 recordsLinked to original sources
PubMed1998

Modification of behavioral responses induced by electrical stimulation of the ventral tegmental area in rats.

To investigate the role of the ventral tegmental area (VTA), a source of the mesolimbic dopaminergic pathway, in paranoid psychosis, a detailed analysis of the behavioral responses induced by electrical stimulation of the VTA was made. Abnormal behavior induced by bilateral high-frequency stimulation of the VTA consisted of two components: forward locomotion and exploration. Similar responses were obtained when the nucleus accumbens (NAC) or prefrontal cortex (PFC) were stimulated. The expression of behavioral responses to stimulation was significantly attenuated by dopamine (DA) receptor or antagonists, such as haloperidol, YM-09151-2 and SCH23390. These results indicate that VTA stimulation causes a transient hyperdopaminergic state in the brain, that resembles psychostimulant-induced abnormal behavior. The effects of chronic administration of methamphetamine (MAP) on the behavioral responses to electrical stimulation of the VAT were also investigated. Although an acute administration of MAP did not affect the behavioral responses to electrical stimulation of the VTA, chronic treatment with MAP (for 2 weeks) caused a long-lasting reduction in the electrical threshold for the induction of abnormal behavior, compared with chronic saline-treated rats. It is suggested that a lasting enhancement in the behavioral response to stimulation of VTA neurons may contribute to the etiology of paranoid schizophrenia and amphetamine psychosis.

Animals↗
PubMed1998

Time-dependent and regional expression of GABA transporter mRNAs following amygdala-kindled seizures in rats.

To investigate the role played by GABA transporters in epileptic seizures, we examined time-dependent and regional changes in expression of GAT-1 and GAT-3 GABA transporter mRNA in amygdala-kindled rat brain using an in situ hybridization method. GAT-1 mRNA was significantly increased bilaterally in the hippocampal dentate gyrus (111-116%) at 1 h after kindled generalized seizures. GAT-1 mRNA was also significantly increased bilaterally in the hippocampal subfields (CA1-4 and dentate gyrus [110-117%]) at 4 h after kindled seizures. There were no significant changes in GAT-1 mRNA level in the amygdalar nuclei, pyriform cortex or cerebral cortex either ipsilaterally or contralaterally at any time after kindled seizures. In contrast, GAT-3 mRNA was significantly increased bilaterally in the amygdalar nuclei and in the contralateral pyriform cortex and cerebral cortex 1 h after seizures. Since all these changes returned to control levels by 8 or 24 h after kindled seizures, the increases in GABA transporter mRNA appeared to be transient responses to seizure activity. These findings indicate that GAT-1 subtype transporter is specifically involved in seizure activity in the hippocampus, while GAT-3 subtype transporter is mainly involved in seizure activity in the amygdalar nuclei and pyriform cortex following amygdala-kindled generalized seizures.

Amygdala↗
PubMed1998

Positive and negative syndromes, and Borna disease virus infection in schizophrenia.

The relationship between Borna disease virus (BDV) infection and positive and negative syndromes in schizophrenia was investigated. By nested RT-PCR and Western blotting, BDV-specific RNA and anti-BDV antibodies were examined in blood from 67 schizophrenic patients (DSM-III-R) in Japan, and the psychometric properties of the Positive and Negative Syndrome Scale (PANSS) were analyzed. There were significant (p < 0.05) differences in the composite index denoting the positive minus negative difference indicating a dominant contribution by negative items, and the proportion of negative type (positive minus negative value below zero) patients, between patients positive and negative for anti-BDV p24 antibodies. It is possible that BDV infection with induction of BDV p24 antibodies may be associated with negative syndromes in schizophrenic patients.

Adult↗
PubMed1998

[A clinical study of substance dependence patients combined with other psychiatric disorders].

The present study was conducted for clarifying the comorbidity of substance dependence and other psychiatric disorders in outpatients of four psychiatric hospitals in May, 1995. The results were as follows; 7.4% (N = 234) of the total 3155 psychiatric outpatients were diagnosed as substance dependence. Among those substance dependence patients, alcohol dependence accounted for 82.5% and the percentage of the other substance dependence were very small, i.e., methamphetamine dependence 6.4%, solvent dependence 1.7%, multiple substance dependence 9.4%, respectively. The percentage of comorbidity of substance dependence and psychiatric disorders was 23.9% (N = 56) of 234 substance dependence patients. The percentage of co-morbid alcohol dependence patients with affective disorder in all affective disorder patients was 5.0%; the percentage of comorbidity of alcohol dependence in neurotic patients 4.1%; the percentage of alcohol dependence comorbidity in schizophrenic patients 0.7%. In many cases, onsets of substance dependence and psychiatric disorders were within 2 years, which suggests the common backgrounds for substance dependence and psychiatric disorders, such as disruption of family and occupational life, stress and individual vulnerability, and substance use for self-medication. The study indicates that the percentages of diagnosed comorbidity of substance dependence and psychiatric disorders are generally smaller in Japan than in the U.S., which may be based on the differences of diagnostic standards between the two countries. Further studies are needed on the comorbidity of substance dependence and psychiatric disorders in other general hospital and psychiatric clinic patients.

Adult↗
PubMed1997

Phenytoin kinetics in Japanese adult epileptics: phenotype of phenytoin slow metabolizers.

Phenytoin pharmacokinetics in 18 of 126 Japanese epileptic patients were investigated using the Michaelis-Menten equation. Five of these (4% of total) patients, who showed significantly high plasma concentrations of phenytoin even when administered a relatively low daily dose of phenytoin, were classified as slow metabolizers; 13 of these, who showed lower plasma concentrations, were classified as normal metabolizers. Comparison of slow and normal metabolizers revealed that the maximum rate of metabolism, Vmax, differed significantly between the two groups, the borderline Vmax value between the two groups being approximately 4.5-4.8 mg/kg/day. The mean Vmax value of slow metabolizers was calculated to be 70% that of normal metabolizers. It is possible that one means of phenotyping slow and normal phenytoin metabolizers is by analysis of phenytoin pharmacokinetics, with estimation of Vmax values.

Adolescent↗
PubMed1997

Antiepileptic effects of tiagabine, a selective GABA uptake inhibitor, in the rat kindling model of temporal lobe epilepsy.

PURPOSE: We determined the antiepileptic profile of tiagabine (TGB), a selective gamma-aminobutyric acid (GABA) uptake inhibitor, in the rat kindling model of temporal lobe epilepsy (TLE). METHODS: The anticonvulsant and adverse effects of TGB were examined in amygdala- or hippocampal-kindled rats and compared with those of other GABA uptake inhibitors (SKF89976A and NNC-711) and conventional antiepileptic drugs [AEDs: valproate (VPA) and carbamazepine (CBZ)]. In addition, the antiepileptogenic effects of TGB on amygdala kindling development were examined. RESULTS: TGB (2.5-40 mg/kg intraperitoneally, i.p.) had potent and dose-dependent anticonvulsant effects on both amygdala- and hippocampal-kindled seizures. The order of anticonvulsant potency of the three GABA uptake inhibitors tested was: NNC-711 > TGB > SKF-89976A and paralleled the in vitro GABA uptake efficacy. In addition, daily treatment with TGB 10 mg/kg for 10 days significantly retarded kindling development. Although adverse effects of TGB on motor systems were significantly less than those of VPA and CBZ, high toxic doses of TGB often caused EEG paroxysm and myoclonus. CONCLUSIONS: Our results indicate the clinical usefulness of TGB for treatment of drug-resistant TLE.

Amygdala↗
PubMed1997

Clinical investigation of the relationship between Borna disease virus (BDV) infection and schizophrenia in 67 patients in Japan.

The relationship between Borna disease virus (BDV) infection and schizophrenia in the clinical time course was investigated. By nested reverse-transcribed polymerase chain reaction (RT-PCR) and Western blotting, BDV-specific RNA and anti-BDV antibodies were examined in the EDTA-treated blood from 67 schizophrenic patients (according to DSM-III-R) in Japan. A significantly higher proportion (45%) of anti-BDV antibody and/or BDV RNA carriers were found among these 67 schizophrenic patients than in 26 controls (0%). There were no apparent associations of BDV infection with age, age at onset, period of hospitalization, accompanying somatic diseases, a past history of tuberculosis, a history of transfusion, a family history, or doses of psychotropic drugs. It is possible that, at least, BDV infection in schizophrenic patients may not be a nosocomial (hospital-acquired) infection, although the route of BDV infection in humans remains unidentified. More studies on the relationship between BDV infection and clinical psychosomatic features should be performed in order to elucidate the pathogenesis of schizophrenia.

Animals↗
PubMed1997

No linkage of the cytochrome P-450IIE1 (CYP2E1) C1/C2 polymorphism to schizophrenia.

We investigated, using PCR-SSCP analysis, the relationship between schizophrenia and the polymorphism of d-benzphetamine N-demethylase (cytochrome P-450j or CYP2E1), which metabolizes psychotropic substances such as d-benzphetamine and alcohols. Among 41 patients with schizophrenia, no statistically significant change in the frequency of the mutant (C2) allele relative to in controls was found, and no novel structural mutation in the CYP2E1 gene, which would be expected to alter the CYP2E1 protein, was found. This could be explained by no linkage of the CYP2E1 gene (mutations in the exon 1-9, and C1/C2 polymorphism) to schizophrenia.

Adult↗
PubMed1997

[Acetaldehyde adducts in the cerebral cortex of ethanol-fed mice].

To investigate the neurotoxicity of acetaldehyde covalent adducts, immunohistochemical staining for acetaldehyde adducts using the antibody against acetaldehyde adducts, was performed in the cerebral cortex of ethanol-fed (withdrawal) mice. In the ethanol-fed mice, the degeneration in the cerebral cortex was found, while the protein epitope related to acetaldehyde was found in the cerebral cortex, liver and adrenal cortex. No histochemical and immunohistochemical changes in the tissues from the control mice were found. It is possible that acetaldehyde adducts may effect on the cerebral cortex as the neurotoxicity which cause psychosis such as delirium and hallucination after alcohol drinking.

Acetaldehyde↗
PubMed1997

[Relationship between alcoholism and CYP2E1 genotypes].

The genotype of the CYP2E1 loci in 36 alcoholic and 42 non-alcoholic (healthy) Japanese were investigated to examine the relationship between the polymorphisms of CYP2E1 (C/D) and the susceptibility to alcohol dependence. There was a significant (df = 1, chi 2 = 4.39, p < 0.05) difference in CYP2E1 CD (heterozygote) genotype frequency between alcohol dependents (56%) and controls (33%), suggesting that the CD (heterozygote) genotype of CYP2E1 may have something to the risk of developing alcoholism in Japanese, whereas DD (homozygote) genotype was high among controls.

Adult↗