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Biomedical subjects

T Watabe

Publications and source records attributed to T Watabe.

At least 163 records · Page 9Linked to original sources
PubMed1983

Studies on metabolism and toxicity of styrene--VI. Regioselectivity in glutathione S-conjugation and hydrolysis of racemic, R- and S-phenyloxiranes in rat liver.

Rat liver cytosol converted phenyloxirane enantiomers regioselectively to glutathione S-conjugates. R-(+)-Phenyloxirane was converted to S-(1-phenyl-2-hydroxyethyl)glutathione (conjugate 1) and S-(2-phenyl-2-hydroxyethyl)glutathione (conjugate 2) (ratio 6.1:1), and S-(-)-phenyloxirane to conjugates 1 and 2 (ratio 1:32). Racemic phenyloxirane was converted to conjugates 1 and 2 (ratio 1.8:1). The conjugates were separated by HPLC on an octadecylsilicone column and identified with synthetic specimens whose structures were assigned by 13C NMR spectrometry. R-(+)-, S-(-)- and racemic phenyloxiranes were hydrolyzed to R-(-)-, S-(+)- and racemic phenylethanediols by microsomal epoxide hydrolase without inversion of absolute configurations of their benzylic carbons. R-(+)-Phenyloxirane had much smaller Km and Vmax than the S-(-)-oxirane did. The R-(+)-oxirane potentially inhibited the microsomal hydrolysis of the S-(-)-oxirane and was preferentially hydrolyzed when the racemic oxirane was used as the substrate. Microsomal monooxygenase oxidized styrene to R-(+)- and S-(-)-phenyloxiranes (ratio 1.3:1), and the ratio was little changed by the pretreatment of the animal with phenobarbital, 3-methylcholanthrene and polychlorinated biphenyls.

Animals↗
PubMed1983

Plain radiographic diagnosis of thrombosis of left atrial appendage in mitral valve disease.

Conventional posteroanterior chest radiographs of 42 patients with mitral valve disease who had had surgery were analyzed, and particular attention was directed to the presence or absence of the convexity of the left lower midcardiac border (left atrial segment). The flatness or concavity of this segment, despite other evidence of left atrial enlargement, was observed in six (60%) of 10 patients who had left atrial thrombosis, and in three (9%) of 32 patients who did not have thrombosis (false positive diagnosis). Four of the 10 patients who had left atrial thrombosis did not show this finding on the radiographs (false negative diagnosis). One of these four had a thrombus only against the posterior wall of the body of the left atrium. Therefore, the accuracy in the diagnosis of thrombosis of the left atrial appendage was 66.7% (six of nine) for patients who had thrombosis of the appendage. Standard chest radiographs are important in the evaluation of the patient with thrombosis of the left atrial appendage.

Adult↗
PubMed1983

Cytoplasmic fine network and mitochondria in normal and abnormal cultured keratinocytes: an electron microscopic study using whole-cell observation technique.

The cytoplasmic fine structures of both normal human cultured keratinocytes (NHK) and squamous cell carcinoma cells (HSC) were examined by electron microscopy using the whole-cell preparation method and stereo-viewing techniques. The presence of cytoplasmic fine network (CFN) was confirmed in both NHK and HSC, but the structures of the two were found to be radically different. In particular, the mitochondria showed a number of distinct morphological differences. The introduction of cytochalasin B and colchicine into HSC partially destroyed the CFN, and, as a result, the morphology of the HSC mitochondria changed to become similar to those of NHK. It seems that the CFN may have an important role in determining the shape of the cell organelles, such as mitochondria, and that the shape of the mitochondria may perhaps be used as an indication of cell malignancy.

Carcinoma, Squamous Cell↗
PubMed1983

Effects of synthetic ovine corticotropin-releasing factor (CRF) on plasma ACTH and cortisol in 31 normal human males.

Responses of plasma ACTH and cortisol to corticotropin-releasing factor (CRF) were evaluated in 31 normal human males. 1.0 micrograms/ks of sterilized synthetic ovine CRF was administered to the subjects, aged 19 to 53 yr and weighing 50 to 78 kg, at between 9:30 a.m. and 10:30 a.m. as an intravenous bolus injection after an overnight fast. Blood specimens were drawn before and 15, 30, 60, 90 and 120 min after injection for later determination of plasma ACTH and cortisol concentrations by radioimmunoassays. Plasma ACTH and cortisol levels for all subjects rose significantly (p less than 0.001) from the basal level (mean +/- SEM, 26.8 +/- 4.5 pg/ml and 12.6 +/- 0.9 micrograms/dl) to peak levels (58.4 +/- 5.5 pg/ml and 22.9 +/- 1.0 micrograms/dl) at 30 min and at 60 min, respectively. Although the plasma concentrations of ACTH and cortisol thereafter declined gradually, the levels at 120 min (43.4 +/- 5.2 pg/ml and 18.9 +/- 0.9 micrograms/ml, respectively) were still significantly higher than the basal levels (p less than 0.001). Significant inverse correlations were observed between the basal levels of each hormone and the ratio of the peak level to the basal level (p less than 0.01), and the increases in plasma ACTH and cortisol concentrations were either not significant or much smaller for the individuals in whom the basal levels were higher than 65 pg/ml and 17.0 micrograms/dl, respectively. No serious subjective symptom was observed during the experimental period in any of the subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1982

A 7-hydroxymethyl sulfate ester as an active metabolite of 7,12-dimethylbenz[alpha]anthracene.

7-Hydroxymethyl-12-methylbenz[alpha]anthracene (7-HMBA), a carcinogenic major metabolite of 7,12-dimethylbenz[alpha]anthracene (DMBA) in liver, was transformed by liver cytosolic sulfotransferase to reactive 7-HMBA sulfate, which is mutagenic toward Salmonella typhimurium strain TA98. The mutagenicity of 7-HMBA in the presence of hepatic sulfotransferase was much higher than that of DMBA or 7-HMBA in the presence of hepatic monooxygenase.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Difference in liver homogenates from Donryu, Fischer, Sprague-Dawley and Wistar strains of rat in the drug-metabolizing enzyme assay and the Salmonella/hepatic S9 activation test.

Comparison studies for detecting differences between liver microsome and S9 preparations from 4 strains (Donryu, Fischer, Sprague-Dawley, Wistar) of young male rats were carried out with pretreatment of the animals by inducers such as PCBs and PB plus 5,6-BF. Each microsome fraction was assayed for the enzymic activity of metabolism of model substrates such as aniline, benzophetamine, BP, DMN and 7-ethoxycoumarin. The hepatic S9 sample was also compared, as regards its metabolizing ability to activate 9 pre-mutagens (2AA, AAF, o-AAT, BP, DAB, DMBA, DMN, m-PDA, quinoline) to directly acting mutagens in the Salmonella/hepatic S9 activation test by using TA98, TA100 and TA1537 strains with or without cytochrome P450 inhibitors (SKF-525A, metyrapone, 7,8-benzo-flavone). In the enzymic assay with PCBs-induced microsomes, BP hydroxylation a strain-specific difference: the microsomes from Fischer and Wistar rats were more effective for metabolizing BP than those from the other strains of rat. The effect of induction by BP plus 5,6-BF for Fischer rats showed relatively higher enzymic activity in the same induction group. Other microsomes prepared from rats with and without induction by PB plus, 5,6-BF did not show a clear-cut strain dependency in the enzymic activities assayed. In the mutation experiments with hepatic S9 samples, the examination of DAB and quinoline revealed a marked strain difference when S9 samples prepared from PCBs-pretreated and PB-plus-5,6-BF-induced rats were used: the S9 sample from Fischer rats was available for activating the two pre-mutagens to directly acting mutagens. No marked difference in the metabolic activation of the remaining 7-pre-mutagens was observed on other S9 preparations. In examinations of mutagenicity activities with the use of three inhibitors, the two S9 preparations made with the two induction methods showed inhibition profiles closely similar to each other. However, there were minor differences in the profiles by these inhibitors. From these findings it was concluded that Fischer rat-liver S9 is useful for detecting mutagens in the metabolic activation test, when induction by PB plus 5,6-BF was used in the Ames Salmonella test.

Animals↗
PubMed1982

Studies on metabolism and toxicity of styrene. IV. 1-Vinylbenzene 3, 4-oxide, a potent mutagen formed as a possible intermediate in the metabolism in vivo of styrene to 4-vinylphenol.

1-Vinylbenzene 3,4-oxide, a putative intermediate in the metabolism of styrene to 4-vinylphenol, was synthesized and examined for its obligatory intermediacy to the phenol, its physical properties, and its mutagenicity toward Salmonella typhimurium TA98 and TA100. The 3,4-oxide had a half-life of 4.3 sec at pH 7.4 in an aqueous solution, and yielded 4-vinylphenol quantitatively without concomitant formation of any trace amount of 3-vinylphenol. The 3,4-oxide had a potent mutagenicity toward the TA100 bacteria but not toward the TA98 strain, whereas it showed a potent cytotoxicity to both of them His+ revertant colonies induced by the 3,4-oxide were 7233/plate at a total dose of 1.0 micromole/plate when it was applied in a sequential manner to the bacterial suspension during the pre-incubation of the testing system. Under the same conditions, benzo[a]pyrene 4,5-oxide and phenyloxirane showed 1283 and 1657 of His+ revertant colonies/plate at 19 nmoles and 10 micromoles/plate, respectively, as the maximal activities. The isomeric arene oxide, 1-vinylbenzene 1,2-oxide, had a longer half-life (1.63 min) than the 3,4-oxide at pH 7.4 in aqueous solution and was specifically rearranged to 2-vinylphenol. The 1,2-oxide also showed more potent mutagenicity to the TA100 strain bacteria than phenyloxirane but weaker than the 3, 4-oxide. 4- and 2-vinylphenols were neither mutagenic nor cytotoxic to the bacteria at concentrations ranging up to 4 micromoles/plate.

Drug Stability↗
PubMed1982

Studies on metabolism and toxicity of styrene. V. The metabolism of styrene, racemic, (R)-(+)-, and (S)-(--)-phenyloxiranes in the rat.

Metabolism of styrene, racemic phenyloxirane, (R)-(+)-, and (S)-(--)-phenyloxiranes in rats has been described. The animals excreted phenylethanediol, mandelic acid, phenylglyoxylic acid, and two regioisomeric mercapturic acids in their urine after the intraperitoneal injection of the phenyloxiranes as well as styrene. The mercapturic acids were identified as N-acetyl-S-(1-phenyl-2-hydroxyethyl)cysteine (MA-1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)cysteine (MA-2). The ratios of the mercapturic acids to the other metabolites excreted in the urine were 1 to 1.8 and 1 to 1.5 for styrene and racemic phenyloxirane, respectively. A remarkable stereoselectivity was observed in the excretion of both types of the metabolites when optically active phenyloxiranes were administered. The rate of excretion of the mercapturic acids was 2.5 times higher than that of the other metabolites when the (R)-oxirane was injected, but the reverse was the case in the (S)-oxirane. The mercapturic acid, MA-1, was excreted at higher rate than the isomer, MA-2, on the administration of styrene and the phenyloxiranes. The most significant regioselectivity in the excretion of MA's was observed when styrene and (S)-phenyloxirane were administered.

Acetylcysteine↗
PubMed1982

The inadequacy of the Raney nickel desulfuration method for the structural elucidation of an epoxide-glutathione S-conjugate: desulfuration of phenyloxiran-glutathione S-conjugates to phenyloxiran.

Both of purely separated regioisomers of phenyloxiran-glutathione S-conjugates, conjugate 1 (S-(1-phenyl-2-hydroxyethyl)glutathione) and conjugate 2 (S-(2-phenyl-2-hydroxyethyl)glutathione), afforded phenyloxiran as a common intermediate to the major desulfuration products, phenethyl alcohol and ethylbenzene, and to the minor ones, methylphenylcarbinol and toluene, on the mild treatment with Raney nickel in boiling ethanol. Phenyloxiran formed was hydrogenated to stable phenethyl alcohol and unstable methylphenylcarbinol under the catalytic conditions used, the latter of which was readily deoxygenated to ethylbenzene. The present study indicated that the Raney nickel method, despite of its being recognized to be well established, could not be applicable to the structural assignment of epoxide-glutathione or epoxide-mercapturic acid conjugates.

Chemical Phenomena↗