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Biomedical subjects

S Otsuki

Publications and source records attributed to S Otsuki.

At least 19 recordsLinked to original sources
PubMed2005

Possible link between glycolysis and apoptosis induced by sodium fluoride.

Fluoride has been used to prevent caries in the dentition, but the possible underlying mechanisms of cytotoxicity induction by this compound are still unclear. Since fluoride is known as an inhibitor of glycolytic enzymes, we investigated the possible connection between NaF-induced apoptosis and glycolysis in human promyelocytic leukemia HL-60 cells. NaF-induced apoptotic cell death is characterized by caspase activation, internucleosomal DNA fragmentation, loss of mitochondrial membrane potential, and production of apoptotic bodies. Higher activation of caspases-3 and -9, as compared with that of caspase-8, suggested the involvement of an extrinsic pathway. Utilization of glucose was nearly halted by NaF, whereas that of glutamine was rather enhanced. NaF enhanced the expression of Bad protein, but not that of Bcl-2 and Bax proteins, and reduced HIF-1alpha mRNA expression. Analysis of these data suggests a possible link between glycolysis and apoptosis.

Apoptosis↗
PubMed1999

Potentiation of vancomycin-induced histamine release by muscle relaxants and morphine in rats.

The intravenous injection of vancomycin sometimes causes anaphylactoid reactions, in which histamine release may play a major role. These reactions are more frequently manifested when vancomycin is injected into anesthetized patients. We examined the vancomycin-induced histamine release and the interaction of vancomycin with muscle relaxants or opioid in rats. In an in vitro study with rat peritoneal mast cells, treatment with vancomycin at concentrations of greater than 1.25 mM produced significant histamine release. Tubocurarine, vecuronium, pancuronium, succinylcholine, and morphine up to concentrations of 0.25, 1, 5, 30, and 5 mM, respectively, produced no significant histamine release. However, the nonsignificant histamine release induced by 0.5 mM vancomycin was clearly enhanced by combining vancomycin with any of these agents. In the in vivo study, the intravenous injection of vancomycin significantly increased the plasma histamine levels in rats when vancomycin was injected at 200 mg/kg of body weight (63.2 +/- 34.0 ng/ml [mean +/- standard deviation]) but not when it was injected at 100 mg/kg (30.8 +/- 20.2 ng/ml) compared with that in the saline-treated rats (22.5 +/- 11.4 ng/ml). Although the subcutaneous administration of morphine (10 mg/kg) never increased the plasma histamine levels, the intravenous injection of vancomycin (100 mg/kg) 30 min after this morphine treatment markedly increased the plasma histamine levels (56.0 +/- 26.9 ng/ml). These findings provide experimental evidence that the combination of muscle relaxants or an opioid with vancomycin may increase the risk of anaphylactoid reactions by enhancing the release of histamine.

Animals↗
PubMed1998

Schizophrenic psychoses and the CNTF null mutation.

Genetic susceptibility plays an important role in the development of schizophrenic psychoses, and the neural maldevelopment hypothesis is suggested by neuropathological and neuroimaging findings. We investigated the association between a null mutation in the ciliary neurotrophic factor (CNTF) gene and functional psychoses including schizophrenia and schizoaffective disorder. The frequency of mutant allele was significantly increased in patients with schizoaffective disorder, but not in those with schizophrenia in comparison with controls. The CNTF null mutation resulting in CNTF deficiency may confer potential susceptibility to schizoaffective disorder.

Adult↗
PubMed1997

Neurochemical studies of schizophrenia in Japan.

Neurobiological research in schizophrenia has been hampered by several confounding factors such as the heterogeneity of the illness and the paucity of biological markers. Recent progress in research methods, however, has enabled the improvement in our understanding its pathophysiology. This paper reviews recent neurochemical investigations of schizophrenia and its animal models which were conducted in Japan in the last decade. The research areas reviewed are (i) monoamine and their metabolites in body fluids, (ii) phospholipids and prostaglandins, (iii) neurochemistry in autopsy brains, (iv) immunological measures, (v) magnetic resonance spectroscopy, (vi) regional cerebral blood flows (rCBF), (vii) molecular genetics, and (viii) animal models. It is worth noting that there exist abnormalities of amino acidergic (glutamatergic and GABAergic) neurotransmission as well as monoaminergic (dopaminergic and serotonergic) one in postmortem schizophrenic brains. These abnormalities and also the findings of altered rCBF indicate the existence of disturbed neuronal circuits that contribute to the diverse symptoms of schizophrenia. Also, dysfunction of membrane phospholipids derived from studies on magnetic resonance spectroscopy may underlie negative symptoms in schizophrenia. Given that schizophrenia is considered to comprise a group of disorders with a diverse heterogeneity of etiologies, research in the next decade is expected to identify putative genes that are involved in vulnerability to schizophrenic phenotype.

Animals↗
PubMed1997

Noninsulin-dependent diabetes mellitus-related encephalopathy presenting with amnesia, personality change, and autonomic seizure.

We describe a patient with noninsulin-dependent diabetes mellitus presenting with an amnestic disorder, personality change, and autonomic seizure. Magnetic resonance images of the brain showed T2-high signal lesion in the hippocampi bilaterally and nonspecific white matter disease, while single photon emission computed tomography revealed a diffuse reduction of cerebral blood flow. Sensory and auditory evoked potentials revealed delayed impulse conduction velocities in the central nervous system. Degenerative changes caused by a microvascular angiopathy related to noninsulin-dependent diabetes mellitus may underlie the central nervous system manifestations in our patient.

Action Potentials↗
PubMed1996

sigma Receptor antagonists block the development of sensitization to cocaine.

The effects of putative sigma receptor antagonists, BMY-14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine), rimcazole and SR-31742A (cis-3-(hexahydroazepin-1-yl)1-(3-chloro-4- cyclohexylphenyl)propene-1), on the development of behavioral sensitization induced by repeated administration of cocaine were investigated. Acute intraperitoneal injection of 15 mg/kg cocaine in rats induced moderate hyperactivity which mainly consisted of sniffing and rearing. These acute effects of cocaine were hardly affected by co-administration of the sigma receptor antagonists, except that BMY-14802 enhanced, but not significantly cocaine-induced locomotion. While repeated cocaine administration induced a progressive increase in stereotyped behaviors and resulted in sensitization, every sigma receptor antagonists tested attenuated the development of sensitization to cocaine. These prophylactic effects of sigma receptor antagonists against cocaine-induced sensitization were confirmed by the challenge test with cocaine alone after an abstinence. These results were consistent with results of our previous study which revealed that BMY-14802 blocked the sensitization to methamphetamine, another psychostimulant. Therefore, sigma receptors play a crucial role in the development of the psychostimulant-induced sensitization phenomenon, which is a pharmacological model of schizophrenia.

Animals↗
PubMed1995

Plasma homovanillic acid levels and therapeutic outcome in schizophrenics: comparisons of neuroleptic-naive first-episode patients and patients with disease exacerbation due to neuroleptic discontinuance.

Plasma homovanillic acid (pHVA) levels were measured and the Brief Psychiatric Rating Scale (BPRS) scores were evaluated in 26 schizophrenic patients who had either never been medicated (neuroleptic-naive, first-episode subjects) or whose condition had become exacerbated following neuroleptic discontinuance (exacerbated subjects). All the subjects received medication with a fixed dose of a neuroleptic (haloperidol or fluphenazine, both 9 mg/day) for the first week and variable doses for the subsequent 4 weeks. In the neuroleptic-naive subjects, pHVA levels increased significantly 1 week after starting the protocol; this increase correlated significantly with clinical improvement of the BPRS positive symptom scores at week 5. In the neuroleptic-naive subjects, pHVA levels had declined to the baseline level by week 5. In the exacerbated subjects, there were no significant correlations between pHVA level changes at week 1 and later improvements of the BPRS positive symptom scores. These results suggest that the rise in pHVA levels occurring within 1 week after starting a fixed neuroleptic dose may predict a favorable clinical response in neuroleptic-naive schizophrenic patients.

Adult↗
PubMed1995

Changes in dopamine D2 and GluR-1 glutamate receptor mRNAs in the rat brain after treatment with phencyclidine.

In situ hybridization of slide-mounted brain sections from rats subjected to acute and chronic phencyclidine treatment was carried out using synthetic oligonucleotides complementary to dopamine D2-receptor and non-N-methyl-D-aspartate (NMDA) glutamate-receptor-subunit (GluR-1) mRNAs. There was no significant difference in either the D2-receptor or the GluR-1 mRNA levels in any brain region of the acute phencyclidine (10 mg/kg)-treated and control groups. However, chronic administration of phencyclidine (10 mg/kg/day, 14 days) significantly decreased the dopamine D2-receptor mRNA level in the caudate-putamen (by 27%, P < 0.01) and significantly increased the GluR-1 mRNA level in the prefrontal cortex (by 29%, P < 0.001). These results suggest that the chronic pharmaco-behavioral effects of phencyclidine may involve expression of both dopamine- and non-NMDA glutamate-receptor mRNAs.

Animals↗
PubMed1993

Characterization of a cloned rat serotonin 5-HT1A receptor expressed in the HeLa cell line.

We have previously isolated the rat serotonin (5-HT)1A receptor gene (G21Y2) and now report the expression and characterization of this receptor. The BamHI/Xbal fragment of this gene was cloned into Rc/RSV and stably transfected into HeLa cells by the calcium phosphate method. For determination of specific 5-HT1A receptor binding, [3H]8OH-DPAT was used as the radioligand and incubated with HeLa cell membranes. The cells expressed specific and saturable binding of [3H]8OH-DPAT with a Kd value of 0.3 nM and a Bmax value of 2 pmol/mg protein. GTP (50 microM) added to the incubation mixture increased the Kd value to 3 nM indicating that the expressed receptor is coupled to a G protein. The specific binding was inhibited by selective 5-HT1A partial agonists, such as buspirone, ipsapirone, gepirone, tandospirone, zalospirone and SUN8399 with Ki values of 1-30nM, whereas other neurotropic drugs except for spiperone (Ki = 46 nM) and nemonapride (Ki = 2.3 nM) were effective only at concentrations of more than 100 microM. The potencies of these compounds to inhibit [3H]8OH-DPAT from its specific binding sites were similar to their affinities determined in rat hippocampus binding studies. These data suggest that the expressed receptor is a 5-HT1A-type similar to 5-HT1A receptors in the rat hippocampus.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Antiepileptogenic action of 7-chlorokynurenic acid on amygdala kindling of rats.

To investigate the role of strychnine-insensitive glycine receptors in epilepsy, we studied the effects of 7-chlorokynurenic acid (7-CK), a selective strychnine-insensitive glycine receptor antagonist, on amygdala kindling development and previously amygdala-kindled seizures in rats. ICV administration of 7-CK (10 or 20 micrograms) suppressed amygdala kindling development, according to the motor seizure stage and afterdischarge development, in a dose-dependent manner. However, 7-CK had no significant effect on previously kindled seizures at either of these doses nor did 20 micrograms at any time (15 min, 30 min, 2 h, and 24 h) after injection studied. These results demonstrate that this selective strychnine-insensitive glycine receptor antagonist has antiepileptogenic activity and suggest a role for the glycine receptors in the contribution of the NMDA receptor complex to epileptogenic events.

Amygdala↗
PubMed1993

MELAS without ragged red fibers or lactic acidosis diagnosed by mitochondrial DNA testing.

A case of mitochondrial encephalomyopathy with lactic acidosis, a stroke-like episode (MELAS) without ragged red fiber, diagnosed by mitochondrial DNA testing, is reported. A 37-year-old woman experienced a sudden and recurrent headache with vomiting and stroke-like episodes. Brain CT and MRI showed multiple infarction in the temporal lobes, not corresponding to artery distribution. However, the plasma levels of lactate and pyruvate were normal, and showed no increased after aerobic exercise. Biopsied muscle showed no evidence of ragged red fibers and deficient activity of mitochondrial enzymes in the respiratory chain. The final diagnosis was made by mitochondrial DNA testing. A southern blot analysis after Apa I digestion revealed the A-to-G mutation in the tRNA(Leu(UUR)), which is specific to MELAS.

Acidosis, Lactic↗
PubMed1992

Enduring increase in membrane-associated protein kinase C activity in the hippocampal-kindled rat.

In a previous study we demonstrated that the membrane-associated protein kinase C (PKC) activity in the amygdala/pyriform cortex (AM/PC) and both the right and left hippocampus (HIPP) of rats kindled from the left HIPP increased significantly 4 weeks after the occurrence of the last seizure compared with control rats. In this study, we carried out further investigations into the enduring effect of HIPP-kindling on membrane-associated PKC activity, the protein concentrations and brain wet tissue weights of the AM/PC and right (contralateral) and left (ipsilateral) HIPP 15-16 weeks after the last generalized kindled seizure had occurred. In addition, we determined the membrane-associated PKC activity one week after the occurrence of the last partial (stage 1-3) seizure. Fifteen to sixteen weeks after the final kindled full seizure, the membrane-associated PKC activity which was expressed as mol/min per mg protein increased significantly in the AM/PC (by 62%, P < 0.02) and left HIPP (by 33%, P < 0.03) compared with control rats, whereas the cytosolic PKC activities did not differ in any brain region examined. The wet tissue weight increased significantly (by 10%, P < 0.04) in the left HIPP only. Furthermore, when it was expressed as pmol/min per mg wet tissue weight, the membrane-associated PKC activity increased significantly in the AM/PC (by 47%, P < 0.02), right HIPP (by 27%, P < 0.05) and left HIPP (by 35%, P < 0.03) compared with the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Ionotropic excitatory amino acid receptors in discrete brain regions of kindled rats.

A study was performed to examine the specific binding of excitatory amino acid (EAA) receptor subtypes in 5 brain regions of rats kindled from the amygdala or hippocampus, using extensively washed and Triton X-100-treated membranes. Seven days after the last amygdala kindled seizure, [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10- imine maleate ([3H]MK-801) binding, which labels N-methyl-D-aspartate (NMDA)-sensitive receptor-linked cation channels, decreased significantly only in the amygdala of kindled rats compared to that of controls under equilibrium assay conditions. There was no significant change in [3H]MK-801 binding in the amygdala or hippocampus 7 days after the last hippocampal kindled seizure, or 28 days after the last amygdala kindled seizure. Nor was there a significant change in NMDA-sensitive [3H]glutamate, strychnine-insensitive [3H]glycine, [3H]spermidine, [3H]kainate or [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA) binding in any brain region 7 days after the last amygdala kindled seizure, or in the hippocampus 28 days after the last amygdala kindled seizure. These results indicate that [3H]MK-801 binding sites labeling NMDA-sensitive receptor-linked cation channels in the amygdala undergo downregulation only transiently, but that none of the subcomponents of the NMDA receptor macromolecular complex exhibit enduring changes at steady state following the completion of amygdala kindling.

Amygdala↗
PubMed1992

Persistent supersensitivity of sigma receptors develops during repeated methamphetamine treatment.

Functional changes in sigma receptors were examined after behavioral sensitization induced by repeated methamphetamine treatment. Rats received either saline or 4 mg/kg methamphetamine for 14 days. (+)3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP), a sigma receptor agonist, was given as challenge after various periods of abstinence. (+)-3-PPP at doses greater than 6 mg/kg stimulated several forms of behavior in naive rats. (+)-3-PPP at 12 and 24 mg/kg produced more frequent rearing and more intense stereotyped sniffing and repetitive head movements in rats previously sensitized with methamphetamine than in saline-pretreated rats. The augmented response to (+)-3-PPP in methamphetamine-treated rats was maintained for at least one month. The augmented response to (+)-3-PPP was reversed by the combined administration of 100 mg/kg (+/-)-sulpiride, a D2 dopamine receptor antagonist, and 30 mg/kg BMY 14802, a sigma receptor antagonist. These results suggest that repeated methamphetamine treatment induces persistent supersensitivity in sigma receptors and that it may subsequently activate the dopamine system.

Animals↗
PubMed1992

Subchronic methamphetamine treatment enhances ouabain-induced striatal dopamine efflux in vivo.

The effect of manipulation of the Na+ gradient between the intracellular and extracellular media on striatal dopamine (DA) efflux under steady-state conditions after subchronic methamphetamine (MAP) treatment was investigated. Rats were injected with 4 mg/kg MAP or saline (i.p.), once daily for 14 days. Seven days after the last injection, ouabain (10(-4) M), a selective inhibitor of the Na+,K(+)-ATPase, was infused locally through a semi-permeable probe in the striatum. Ouabain induced a significantly greater (P less than 0.01) increase of the DA concentrations in the striatal perfusate in the subchronic MAP than the control group. The levels of 3,4-dihydroxyphenylacetic acid (DOPAC) (P less than 0.05) and 5-hydroxyindoleacetic acid (5-HIAA) (P less than 0.05) were significantly higher in the subchronic MAP than in the control group. Reserpine pretreatment (5 mg/kg, i.p.) did not affect the enhanced ouabain-induced DA efflux (P less than 0.01) in the subchronic MAP group, and the levels of DOPAC (P less than 0.01), 5-HIAA (P less than 0.01) and HVA (P less than 0.01) were also significantly higher in the subchronic MAP than in the control group. In contrast, alpha-methyl-p-tyrosine (250 mg/kg, i.p.) pretreatment abolished the ouabain-induced efflux of DA, DOPAC and HVA, but not 5-HIAA, in both groups. Specific striatal [3H]ouabain binding and striatal Na+,K(+)-ATPase activity in the subchronic MAP and control groups did not differ significantly. These results suggest that subchronic MAP treatment facilitates the efflux of newly synthesized DA, which is induced by the ouabain-induced decrease of the Na+ gradient between intracellular and extracellular media.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗