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Biomedical subjects

T Watabe

Publications and source records attributed to T Watabe.

At least 109 records · Page 6Linked to original sources
PubMed1986

Hepatic microsomal cholesterol epoxide hydrolase: selective inhibition by detergents and separation from xenobiotic epoxide hydrolase.

Cholesterol epoxide hydrolase (CEHase) activities of mouse liver microsomes were completely inhibited by Emulgen 108 and Lubrol PX and approximately half by cholate, Triton WR-1339, and Tween 80 when preincubated with 0.1% of these detergents, while their xenobiotic epoxide hydrolase (XEHase) activities were markedly enhanced under the same preincubation conditions. The CEHase and XEHase activities were separately eluted from a gel column applied with mouse liver microsomes which were solubilized in a phosphate buffer containing cholate, glycerol, urea, dithiothreitol, and EDTA.

Animals↗
PubMed1986

Covalent binding of a mercaptan S-sulfate to hepatic cytosolic proteins and its inhibition by glutathione.

4-Nitrobenzyl mercaptan (NBM) S-sulfate, a new type of the sulfate conjugate enzymatically formed from NBM in the presence of 3'-phosphoadenosine 5'-phosphosulfate in rat liver cytosol, bound covalently to rat liver cytosolic proteins at pH 7.4. The protein binding of NBM S-sulfate was strongly retarded by GSH. GSH not only played a role as a scavenger for NBM S-sulfate with formation of NBM and GSSG via S-(4-nitrobenzyl)thioglutathione, but also cleaved the covalent bonds, possibly disulfides formed from NBM S-sulfate and sulfhydryl groups of the cytosolic proteins. Thus, evidence was provided that NBM S-sulfate be a new type of the reactive metabolite.

Animals↗
PubMed1986

Epoxidation of androsta-5,16-dien-3 beta-ol by hepatic microsomal lipid peroxidation.

Male rat liver microsomes oxidized androsta-5,16-dien-3 beta-ol (delta 16-ANDO) to delta 16-ANDO-5,6 alpha-, -5,6 beta-, -16,17 alpha-, and -16,17 beta-epoxides and delta 16-ANDO-5 alpha,6 beta-, -16 alpha,17 beta-, and -16 beta,17 alpha-glycols in the presence of an NADPH-generating system and the microsomal lipid peroxidation accelerator, Fe2+-ADP. The hepatic microsomes hydrolyzed all the delta 16-ANDO epoxides to the glycols. delta 16-ANDO-5 alpha,6 beta-glycol was the sole metabolite from both 5,6 alpha- and 5,6 beta-epoxides. Microsomal epoxide hydrolase also hydrolyzed delta 16-ANDO-16,17 alpha-epoxide specifically to the 16 beta,17 alpha-glycol and the isomeric 16,17 beta-epoxide to the 16 alpha,17 beta- and 16 beta,17 alpha-glycols approximately in the equal ratio. The delta 5-epoxidation of delta 16-ANDO by microsomes occurred only under the conditions that lipid peroxidation took place. Direct evidence was obtained for the participation of microsomal lipid hydroperoxides in the epoxidation of delta 16-ANDO by using photochemically prepared hydroperoxides of phospholipids separated from the hepatic microsomes. The hydroperoxides generated active oxygens, tentatively assigned as alk(ylper)oxy radicals, by the action of ferrous ion and epoxidized delta 16-ANDO to afford the 5,6- and 16,17-epoxides. The Fe2+-ADP-mediated epoxidation of delta 16-ANDO by the phospholipid hydroperoxides occurred preferentially at delta 5 to delta 16 and afforded the 5,6 beta-epoxide in a higher ratio than the 5,6 alpha-epoxide, similar to the Fe2+-ADP-mediated microsomal epoxidation, while the alpha-epoxide was preferentially formed to the beta-epoxide for delta 16 in the epoxidation by both systems.

Androstenols↗
PubMed1986

Regioselective glutathione conjugation of the carcinogen, 7, 12-dihydroxymethylbenz[a]anthracene, via reactive 7-hydroxymethyl sulfate ester in rat liver cytosol.

Potent mutagenicity of 7,12-dihydroxymethylbenz[a]anthracene (DHBA) toward Salmonella typhimurium TA 98 in the presence of rat liver cytosol fortified with 3'-phosphoadenosine 5'-phosphosulfate (PAPS) was completely retarded by the addition of glutathione (GSH). The reactive and intrinsically mutagenic metabolite, DHBA 7-sulfate, formed by hepatic cytosolic sulfotransferase disappeared from the incubation mixture by the addition of GSH. Non-mutagenic S-(12-hydroxymethylbenz[a]anthracen-7-yl)methylglutathione was isolated from the incubation mixture consisting of the hepatic cytosol, DHBA, PAPS, and GSH and proved to be formed by GSH S-transferase directly from DHBA 7-sulfate as an obligatory intermediate.

Animals↗
PubMed1986

A 7-hydroxymethyl sulphate ester as an active metabolite of the carcinogen, 7-hydroxymethylbenz[a]anthracene.

7-Hydroxymethylbenz[a]anthracene (7-HBA) showed potent mutagenicity towards Salmonella typhimurium TA 98 in the presence of untreated rat liver cytosol fortified with the PAPS-generating system, sodium sulphate and ATP. No mutagenic activity was observed either when the cytosol was boiled or when sodium sulphate or ATP was omitted from the assay medium. A highly reactive sulphate ester of 7-HBA was isolated and identified from the medium. It had a half-life of 3.5 min at 37 degrees C and pH 7.4 in water and showed potent, intrinsic mutagenicity towards TA 98. The mutagenicity of 7-HBA sulphate was almost completely retarded in the presence of the cytosol and glutathione. From the biological systems containing glutathione a non-mutagenic and stable glutathione conjugate was isolated that was assigned as S-(benz[a]anthracen-7-yl)methylglutathione. 7-HBA sulphate covalently bound to calf thymus DNA and cytosolic proteins. A fluorospectroscopic study indicated that the carcinogen bound to the biomacromolecules through its 7-methylene group with loss of a sulphate anion as a leaving group.

Animals↗
PubMed1986

[Clinical evaluation of ceftizoxime intravenous administration in severe infections associated with hematologic disorders. Niigata Infection Study Group].

Seventy-one patients with severe infections associated with hematologic disorders including leukemia, lymphoma and aplastic anemia were treated with ceftizoxime (CZX) in daily doses of 4-6 g for an average of 20.1 days. Infections associated with hematologic disorders consisted of sepsis and pneumonia, and most of the causative organisms appeared to be Gram-negative bacteria. Of the 64 patients who completed the trial, excellent response was observed in 16 and moderate response in 26. The rate of clinical effectiveness was 65.6%. Side effects observed during the treatment included skin rash in only 1 patient, and hepatic disorders in 6 patients. However, the relationship between CZX and these abnormal findings was not established. These results indicate that CZX is a therapeutically effective and safe antibiotic for the treatment of severe infections associated with hematologic disorders.

Adult↗
PubMed1985

The S-sulfate formation from 4-nitrobenzyl mercaptan in rat liver cytosol.

4-Nitrobenzyl mercaptan (NBM) was enzymatically transformed at pH 6.0 into its S-sulfate in rat liver cytosol fortified with 3'-phosphoadenosine 5'-phosphosulfate. At pH 7.4, the S-sulfate was not detected from the incubation mixture. 4-Nitrobenzyl alcohol was also transformed under the same incubation conditions into the corresponding O-sulfate at a higher rate at pH 6.0 than at pH 7.4. Under the incubation conditions used, NBM S-sulfate reacted with the substrate NBM at a significant rate to afford 4-nitrobenzyl disulfide. The disulfide formation from NBM and the S-sulfate occurred more readily at pH 7.4 than at pH 6.0, so that biologically formed NBM S-sulfate was strongly suggested not to remain unchanged in the incubation mixture at pH 7.4.

Animals↗
PubMed1985

A reactive hydroxymethyl sulfate ester formed regioselectively from the carcinogen, 7,12-dihydroxymethylbenz[alpha]anthracene, by rat liver sulfotransferase.

The carcinogen, 7,12-dihydroxymethylbenz[alpha]anthracene (DHBA), was regioselectively conjugated in the presence of 3'-phosphoadenosine 5'-phosphosulfate by male rat liver cytosolic sulfotransferase to DHBA 7-sulfate. The sulfate ester was highly reactive and showed a potent, intrinsic mutagenicity toward Salmonella typhimurium TA 98.

Animals↗
PubMed1985

The obligatory intermediacy of 16,17 alpha- and 16,17 beta-epoxides in the biotransformation of androsta-5,16-dien-3 beta-ol to androst-5-ene-3 beta, 16 alpha, 17 beta- and -3 beta, 16 beta, 17 alpha-triols by male rat liver microsomes.

The C16-double bond of the biolefinic steroid, androsta-5,16-dien-3 beta-ol (delta 16-ANDO), was regioselectively oxidized by male rat liver microsomes in the presence of NADPH and EDTA to 16 alpha, 17 alpha-epoxyandrost-5-en-3 beta-ol (delta 16-ANDO 16,17 alpha-epoxide), 16 beta,-17 beta-epoxyandrost-5-en-3 beta-ol (delta 16-ANDO 16,17 beta-epoxide), androst-5-ene-3 beta, 16 alpha, 17 beta-triol (delta 16-ANDO 16 alpha, 17 beta-glycol), and androst-5-ene-3 beta, 16 beta, 17 alpha-triol (delta 16-ANDO 16 beta, 17 alpha-glycol). The microsomes hydrolyzed delta 16-ANDO 16,17 alpha-epoxide specifically to the 16 beta, 17 alpha-glycol and delta 16-ANDO 16,17 beta-epoxide to the 16 beta, 17 alpha-glycol and the 16 alpha, 17 beta-glycol in an equal ratio. delta 16-ANDO 16,17 alpha-epoxide was much more susceptible to microsomal hydrolysis than the 16,17 beta-epoxide. The xenobiotic epoxide hydrolase inhibitor, 3,3,3-trichloropropene 1,2-oxide, potently inhibited microsomal hydrolysis of delta 16-ANDO 16,17-epoxides as well as of benzo[a]pyrene 4,5-epoxide and styrene 7,8-epoxide. Addition of 3,3,3-trichloropropene 1,2-oxide accumulated the 16,17-epoxides formed from delta 16-ANDO in the reaction medium with concomitant decrease in the amounts of the 16,17-glycols formed, leading to a conclusion that the 16,17-epoxides played a role as obligatory intermediates in the microsomal delta 16-oxidation of delta 16-ANDO to the 16,17-glycols. Epoxidation of delta 16-ANDO was stereoselectively mediated by a cytochrome P-450 with quite unique properties to form the 16,17 alpha-epoxide as the major oxidation product and the 16,17 beta-epoxide as the minor. The epoxidation was strongly inhibited with CO, activated with 2-diethylaminoethyl 2,2-diphenylvalerate hydrochloride more than twice as much, and little affected with metyrapone and 7,8-benzoflavone. A pretreatment of the animals with 3-methylcholanthrene induced the delta 16-ANDO-epoxidizing activity of their microsomes 1.5 times higher than those from the control animals. However, a pretreatment with phenobarbital reduced the enzyme activity to one-half of the control microsomes. Under the same conditions, microsomal activities of hydroxylation of benzo[a]pyrene and N-demethylation of benzphetamine were significantly induced by the pretreatments with 3-methylcholanthrene and phenobarbital, respectively.

Androstenols↗
PubMed1985

Enantioselectivity in glutathione conjugation of 1,2-epoxy-1,2,3,4-tetrahydronaphthalene by hepatic glutathione S-transferase.

Enantiomers of 1,2-epoxy-1,2,3,4-tetrahydronaphthalene (ETN) were conjugated with glutathione (GSH) specifically at their benzylic oxiran carbons, with a marked difference in rate [(1R,2S)-(+)- less than (1S,2R)-(-)-ETNs] as well as in affinity for GSH S-transferase [Km: (1S,2R)-(-)- less than (1R, 2S)-(+)-ETNs], in rat liver cytosol to yield two diastereomeric S-(2-hydroxy-1,2,3,4-tetrahydronaphth-1-yl)glutathiones which were separable by reverse partition hplc. Enzymatic GSH conjugation of racemic ETN occurred preferentially with the (1S,2R)-(-)-component as a result of its retarding effect on the conjugation of the (1R,2S)-(+)-counterpart, one half of which remained in enantiomerically pure form in the incubation medium when the (1S,2R)-(-)-component had been completely conjugated.

Animals↗
PubMed1985

Nonsurgical retrieval of an accidentally dislodged vent catheter retention ring.

During open mitral commissurotomy in a patient with mitral stenosis, a vent catheter retention ring was accidentally slipped off into the left atrium and lodged near the orifice of the right renal artery. Nonsurgical retrieval of this intraarterial foreign body was performed successfully under fluoroscopic guidance in the operating room using a combined approach of angiographic catheters and guidewire, these being inserted via the arteriotomy site of the right femoral artery created for cardiopulmonary bypass.

Catheterization↗
PubMed1985

Effect of liver S9 from 3,4,5,3',4'-pentachlorobiphenyl-pretreated rats on the mutagenic activity of the various carcinogens toward Salmonella typhimurium TA 98.

Effects of liver 9000 X g supernatant fraction from 3,4,5,3',4'-pentachlorobiphenyl- and 2,4,5,2',4',5'-hexachlorobiphenyl-pretreated rats (PenCB-S9 and HexCB-S9, respectively) on the mutagenic activities of well-known carcinogens, benzo-[a]pyrene (BP), Glu-P-1 (2-amino-6-methyldipyrido [1,2-a:3',2'-d]imidazole), Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole), and aflatoxin B1 (AFB), toward Salmonella typhimurium TA 98 have been described. Although the mutagenic activities of all of these carcinogens were enhanced by these S9, PenCB-S9 especially highly activated BP, Glu-P-1, and Trp-P-1. The ability of PenCB-S9 to activate the carcinogens was much higher than that of liver 9000 X g supernatant fraction from 3-methylcholanthrene-pretreated rats (MC-S9). PenCB-S9 enhanced the mutagenic activity of BP 8 times higher than MC-S9, while Glu-P-1 and Trp-P-1 were activated by PenCB-S9 twice as much as by MC-S9. Effect of HexCB-S9 on the mutagenic activities of the above-mentioned three carcinogens was much less than those of PenCB- and MC-S9 and a little higher than that of 9000 X g supernatant fraction from rats pretreated with phenobarbital. As for AFB, phenobarbital was the most potent inducer, and HexCB and PenCB were next to this. Data suggest that PenCB is a strong inducer of P-448 species which activate environmental toxicants.

Aflatoxin B1↗