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Biomedical subjects

T Someya

Publications and source records attributed to T Someya.

At least 91 records · Page 5Linked to original sources
PubMed1995

No increases in chromosome aberrations in human diploid fibroblasts following exposure to low concentrations of sodium fluoride for long times.

To study whether exposure to fluoride at low concentrations for long times induces chromosome aberrations in human cells, human diploid fibroblasts in the quiescent phase were treated with sodium fluoride (NaF) at 1-10 micrograms/ml (equivalent to fluoride ion at 0.45-4.5 ppm) for 1-3 weeks. Quiescent cells were obtained by a 10-day culture in medium containing 1% serum following overnight incubation of cells in the logarithmic phase. Significant levels of cytotoxicity, as determined by a decrease in the number of cells, were not induced by treatment of the cells with NaF at 5 or 10 micrograms/ml for 1-3 weeks. No increase in the frequency of chromosome aberrations was elicited in cultures treated for 1-3 weeks with NaF over the range of doses examined. In contrast, a dose-dependent increase in the frequency of chromosome aberrations was observed in cultures treated with N-methyl-N'-nitro-N-nitrosoguanidine, used as a positive control. The results indicate that fluoride might be not clastogenic to human fibroblasts when exposed at low levels, equivalent to those in the communal water supplies.

Cells, Cultured↗
PubMed1995

Metabolism of clomipramine in a Japanese psychiatric population: hydroxylation, desmethylation, and glucuronidation.

We measured the concentrations of clomipramine and its metabolites, N-desmethylclomipramine, 8-hydroxy-N-desmethylclomipramine, 8-hydroxyclomipramine by high-performance liquid chromatography in 108 Japanese psychiatric patients receiving clomipramine hydrochloride PO. The concentrations of the glucuronide conjugates of 8-hydroxyclomipramine and 8-hydroxy-N-desmethylclomipramine were assayed via enzymatic hydrolysis. Although there were large interindividual variations of concentrations of parent, intermediate metabolic compounds, and glucuronide conjugates, significant positive correlations were observed between these drug concentrations and daily doses of clomipramine hydrochloride (mg/kg body weight). Although the metabolic ratios for desmethylation, hydroxylation, and glucuronidation that were calculated from steady-state drug concentrations varied substantially with 36-, 14-, and 28-fold interindividual variations, respectively, apparent poor desmethylators, poor hydroxylators, or poor glucuronidators were not found.

Adolescent↗
PubMed1995

Interindividual variations of desmethylation and hydroxylation of amitriptyline in a Japanese psychiatric population.

We measured the concentrations in plasma of amitriptyline and its metabolites, nortriptyline and geometric isomers of 10-hydroxynortriptyline and 10-hydroxyamitriptyline, in 73 Japanese psychiatric patients receiving amitriptyline hydrochloride (Tryptanol; Banyu Pharmaceutical Co. Ltd., Tokyo, Japan) by high-performance liquid chromatography. Although there were large interindividual variations of total drug concentrations and concentrations of parent or intermediate metabolic compounds in plasma, significant positive correlations were observed between these drug concentrations and daily doses of amitriptyline hydrochloride (milligrams per kilogram of body weight). The metabolic ratios for both hydroxylation and desmethylation varied substantially with approximately 8- to 19-fold interindividual variations. Frequency distribution histograms and probit analyses of these parameters identified neither definite poor hydroxylators nor poor desmethylators of amitriptyline.

Adult↗
PubMed1993

Relation of plasma and red blood cells reduced haloperidol concentrations to haloperidol reductase activity assayed in red blood cells in psychiatric population.

1. Haloperidol (HAL) reductase activity in red blood cells (RBC) was determined by a newly developed assay method in 120 blood samples from 75 Japanese psychiatric patients receiving HAL. 2. Plasma concentrations of HAL and reduced haloperidol (RHAL), a reductive metabolite of haloperidol, were also measured in these samples. 3. RBC concentrations of HAL and RHAL were measured in 62 of these samples. 4. No significant correlations were found between HAL reductase activity in RBC vs plasma or RBC RHAL/HAL ratios, which may represent activity of the enzyme metabolizing HAL into RHAL. 5. RHAL concentrations were three times higher in RBC than in plasma, though HAL concentrations were at the same level in both tissues. This may reflect accumulation of RHAL in RBC.

Adolescent↗
PubMed1993

Functional brain imaging of a catatonic type of schizophrenia: PET and SPECT studies.

A brain imaging study was conducted in the case of a catatonic type of schizophrenia (DSM-IIIR) by applying (i) positron emission tomography (PET) and (ii) single photon emission computed tomography (SPECT). A PET study using [18F]-2-fluoro-2-deoxy-D-glucose revealed a lower glucose utilization in the dorsal frontal and parietal lobes of both cerebral hemispheres. Correlative SPECT studies using [123I]-iodoamphetamine showed a diminished regional cerebral blood flow in similar regions of the cerebral hemisphere. A three-dimensional volume rendering method of the SPECT images (TITAN) identified the dorsal region of the fronto-parietal lobe as the most severely affected region. These patterns of deficits implicated the role of the dorsal frontal and parietal lobes in the pathogenesis of catatonic syndromes.

Activities of Daily Living↗
PubMed1992

Haloperidol metabolism in psychiatric patients: importance of glucuronidation and carbonyl reduction.

In 39 patients who received haloperidol regularly we measured plasma concentrations of haloperidol glucuronide (HAL-GL), reduced haloperidol glucuronide (RHAL-GL), haloperidol (HAL), reduced haloperidol (RHAL), and HAL reductase activity in red blood cells. Plasma HAL-GL concentrations were significantly higher than HAL, RHAL, or RHAL-GL concentrations. Concentration ratios of total glucuronide to nonglucuronide and RHAL/HAL ratios were calculated as indices of glucuronidation and reduction capacity in each patient. The plasma glucuronidation ratios showed a significant negative correlation (r = -0.63, p less than 0.001) with the dose, while the reduction ratios showed a positive correlation (r = 0.75, p less than 0.001). No correlations were found between the HAL reductase activity in red blood cells and either the dose or RHAL/HAL. Based on these findings we suggest that glucuronidation of HAL is the major metabolic pathway of HAL in humans and its activity is important in determining steady-state plasma HAL concentrations. Glucuronidation may also be a major contributing factor in the interindividual variability of HAL metabolism.

Adolescent↗
PubMed1991

Calyculin A increases voltage-dependent inward current in smooth muscle cells isolated from guinea pig taenia coli.

The effects of a potent phosphatase inhibitor, calyculin A (CL-A), on inward currents in guinea pig taenia coli smooth muscle cells were examined. CL-A increased the inward current, and this effect of CL-A was inhibited by a protein kinase C inhibitor, H-7, and by nifedipine. Phorbol 12,13-dibutyrate, an activator of protein kinase C, also increased the inward current and this effect was antagonized by H-7. These results suggest that in guinea pig taenia coli smooth muscle cells CL-A may facilitate the opening of the L-type Ca2+ channels through the protein kinase C-dependent phosphorylation system.

Animals↗
PubMed1991

Haloperidol reductase activity in red blood cells from oriental patients on haloperidol.

1. We measured haloperidol reductase activity in red blood cells in 87 samples collected from 50 Japanese psychiatric patients on HAL. HAL reductase activities in the patients were in a range of 7.9-26.1 pmol/hr/10(6) RBC (mean = 13.4, S.D. = 3.4). Interindividual variability was as large as 25.4% (CVs), while intraindividual CVs were small (8.9%). 2. Distribution of HAL reductase activities was normal but their values were slightly lower in the patients than those in the normal controls, though the difference between these two groups was not significant. 3. No significant correlations were found between HAL reductase activity in RBC vs dose of HAL per body weight, or plasma and RBC RHAL/HAL ratio.

Adolescent↗
PubMed1991

Conversion of bromperidol to reduced bromperidol in human liver.

Bromperidol (BRP) is an analog of haloperidol, a potent butyrophenone neuroleptic. Reductive conversion of BRP carbonyl group to reduced bromperidol (RBRP) was confirmed in vitro using human liver. This NADPH-dependent reduction of BRP showed a similar inhibition pattern and Michaelis constants to haloperidol carbonyl reductase.

Alcohol Oxidoreductases↗
PubMed1990

Reduced haloperidol/haloperidol ratios in plasma: polymorphism in Japanese psychiatric patients.

We measured plasma concentrations of haloperidol (HAL) and its metabolite, reduced haloperidol (RHAL), by high performance liquid chromatography (HPLC) in 45 Japanese psychiatric patients receiving HAL. Plasma levels of HAL had a highly positive correlation with daily dose per body weight. Plasma RHAL/HAL ratios had also a dose-dependent relationship, but their distribution was nonnormal and a bimodal pattern with an antimode at 0.7 was apparent by probit analysis. There were 8 subjects (18%) with high RHAL/HAL ratios (mean = 1.26, SD = 0.41) and 37 subjects (82%) with low RHAL/HAL ratios (mean = 0.42, SD = 0.13). RHAL/HAL ratios showed little intraindividual variability (+/- 10.6%), while interindividual variability was large. This may suggest that pharmacogenetic factors are involved in the metabolism of HAL and RHAL.

Adolescent↗
PubMed1990

Measurement of haloperidol reductase activity in red blood cells and reduced haloperidol/haloperidol ratios in plasma in oriental psychiatric patients.

1. The authors established a method for measuring haloperidol (HAL) reductase activity in human red blood cells. 2. Characteristics of the HAL reductase in red blood cells were examined. This enzyme reaction was NADPH dependent, and the optimum pH was at 8.2-8.9. Vmax and Km were calculated as 25-150 pmol/hr/10(6) RBC and 160-2600 microM respectively. 3. HAL reductase activities in red blood cells from 14 patients treated with HAL were in a range of 9.7-20.8 pmol/hr/10(6) RBC. So far we did not find any significant correlation between HAL reductase activities and reduced HAL/HAL ratios in plasma.

Adult↗
PubMed1990

Antiproliferative effect of hyperthermia and ACNU on cultured human malignant melanoma cells.

Human malignant melanoma cultured cells were treated either with ACNU (1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chlorethyl)-3-nitro sourea hydrochloride), hyperthermia, or the combination of ACNU and hyperthermia. The combination treatment inhibited the cell growth to a slightly synergistic degree compared to the respective single treatments. The present in vitro experimental results support in part the finding of our previous report that the combination treatment with ACNU and hyperthermia have a significantly synergistic antitumor effect to human melanoma transplanted to nude mice. However, the synergistic effect was much less intense in the present in vitro experiment. The difference may have resulted from the environmental differences between in vitro and in vivo experimental systems.

Cell Count↗
PubMed1990

Nerve sheath myxoma. An immunohistochemical study of a case.

An 18-year-old Japanese male presented with a normal-skin-colored, dome-shaped, slightly tender tumor on his left palm. Histopathologically, the tumor consisted of distinct lobules, which were separated by fibrous connective tissue. Each lobule was composed of spindle or round cells within a myxoid matrix, pathognomonic of nerve sheath myxoma. The mucinous material was positively stained by Alcian blue (pH 2.5) and toluidine blue (pH 4.0). Immunohistochemically, the majority of spindle cells were positive for S-100 protein (beta-subunit) and neuron-specific enolase. Our findings lend further support to the hypothesis that nerve sheath myxoma is derived from Schwann cells.

Adolescent↗
PubMed1989

Two types of Ca channels in smooth muscle cells isolated from guinea-pig taenia coli.

1) Two types of voltage dependent Ca channels with different conductances and inactivation kinetics were identified from cell-attached patch clamp recordings. One type, with a larger conductance of 25pS, had a threshold of activation near -40mV and the mean current inactivated slowly. A second type of Ca channel, with a smaller conductance of 12pS channel, but the averaged mean current inactivated rapidly. 2) Cadmium ions inhibited the large conductance Ca channel currents, while the small conductance Ca channel currents was not blocked. 3) Large conductance Ca channel current selectively inhibited by dihydropyridine derivative, Nifedipine. Small conductance Ca channel current is abolished in dose dependent manner by pyrethroid insecticide, tetranethrine.

Animals↗