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Biomedical subjects

T Watabe

Publications and source records attributed to T Watabe.

228 records · Page 13Linked to original sources
PubMedDate not supplied

Mouse liver microsomal cholesterol epoxide hydrolase: a specific inhibition of its activity by 5,6 alpha-Imino-5 alpha-cholestan-3 alpha-OL.

A comparative study on mouse liver epoxide hydrolase activities has been done by using enzyme inhibitors in order to obtain evidence for the specificity of microsomal cholesterol epoxide hydrolase. 5,6 alpha-Imino-5 alpha-cholestan-3 beta-ol (IC) strongly inhibited the microsomal hydrolysis of cholesterol alpha-epoxide and the other delta 5-steroid alpha-epoxides (0.1 mM each) at concentrations less than 1 microM but affected neither microsomal nor cytosolic hydrolysis of any other epoxides of endogenous and exogenous compounds (0.1 mM each). On the other hand, 3,3,3-trichloropropene 1,2-oxide (TCPO) did not inhibited the microsomal hydrolysis of delta 5-steroid alpha-epoxides but strongly inhibited both microsomal and cytosolic hydrolysis of the other epoxides used. The only exceptions for the epoxy substrates that were not affected by both inhibitors were 5 alpha-cholest-2-ene alpha- and beta-epoxides. The inhibition by IC of the microsomal cholesterol alpha-epoxide hydrolysis was competitive, but no significant inhibition of the enzyme activity was observed by the typical microsomal xenobiotic substrates, hexadecene oxide and benzo[a]pyrene 4,5-oxide. These results strongly suggest that the microsomal enzyme hydrolyzing cholesterol alpha-epoxide differs from the microsomal hydrolase for epoxides of various xenobiotic olefins and arenes.

Animals↗
PubMedDate not supplied

Sexual orientation of male mouse offspring prenatally exposed to ethanol.

Pregnant mice were intubated with either low (2 g/kg) or high (4 g/kg) dose of ethanol twice daily throughout the last third of the gestational period (from dg14 to dg18: gestational day; plug positive = dg 0). Ninety days after birth, the sexual orientation test was conducted on male offspring. This test was designed to observe a two-choice preference for either male or female partners in a setting in which the test animal could move freely between the two incentive compartments within which a stud male and an estrous female had been placed. We found that young adult males that had been exposed to ethanol prenatally have a decreased preference for the opposite sex and an increased preference for the same sex as a partner, although their physical development was apparently unaffected.

Alcoholic Intoxication↗
PubMedDate not supplied

MR angiography of intracranial aneurysms: a comparison of 0.5 T and 1.5 T.

The objective of this paper is to compare the diagnostic efficacy of 3 DFT time-of-flight MR angiography (MRA) at middle-field-strength and high-field-strength in diagnosis of intracranial aneurysms. Thirty-one patients, including 26 patients with angiographically confirmed intracranial aneurysms (n = 28), underwent MRA at 0.5 and 1.5 T. Images were interpreted by six trained observers who were blinded to diagnosis. Twelve projections of MRA of the circle of Willis, by maximum-intensity projection algorithm, were reviewed using continuous confidence-judgement scales. It was found that MRA at 1.5 T was more sensitive than that at 0.5 T in detection of aneurysms. The sensitivity of six observers ranged between 50 and 64% (mean 56%) at 0.5 T, and between 61 and 86 86% (mean 75%) at 1.5 T. In the smaller aneurysms less than 5 mm, the differences between the units became greater. The sensitivity for small aneurysms ranged from 23 to 54% (mean 32%) at 0.5 T, and from 31 to 69% (mean 58%) at 1.5 T. Our conclusion was that high field strength confers higher accuracy in the detection of intracranial aneurysms with MRA with current-generation MR imagers.

Algorithms↗
PubMedDate not supplied

Selective covalent binding of the active sulfate ester of the carcinogen 5-(hydroxymethyl)chrysene to the adenine residue of calf thymus DNA.

5-(Hydroxymethyl)chrysene (5-HCR) sulfate, an active metabolite of the carcinogen 5-HCR, bound significantly in a covalent manner to the purine bases of calf thymus DNA through its 5-methylene carbon with loss of a sulfate anion when incubated at pH 7.4 and 37 degrees C. From the DNA were isolated two purine base adducts by high-pressure liquid chromatography, and they were identified as N6-[(chrysen-5-yl)methyl]adenine and N2-[(chrysen-5-yl)methyl]guanine with the corresponding synthetic specimens. The purine base adducts, appearing in the ratio 1 to 27 for guanine to adenine in the chromatogram, accounted for about 60% of the total covalent binding of 5-HCR sulfate to the DNA. 5-HCR sulfate also reacted specifically with the exocyclic amino groups of the purine bases of 2'-deoxyadenosine 5'-phosphate and 2'-deoxyguanosine 5'-phosphate at much lower rates than did with those of calf thymus DNA. Denaturing the DNA by heating followed by rapid cooling, covalent binding of 5-HCR sulfate to it markedly decreased with the increasing ratio of N2-guanine to N6-adenine adducts (1:3.6). These results strongly suggest that secondary structure of DNA has an influence on the covalent binding of 5-HCR sulfate and that intercalation of the sulfate ester into DNA base pairs plays an important role in its preferential binding to N6 of the adenine residue of native DNA.

Adenine↗
PubMedDate not supplied

Activation and inactivation of carcinogenic dihaloalkanes and other compounds by glutathione S-transferase 5-5 in Salmonella typhimurium tester strain NM5004.

A newly developed tester Salmonella typhimurium NM5004 strain was constructed by introducing a plasmid containing both rat GSH S-transferase (GST) 5-5 cDNA and the umuC"lacZ operon into the host strain Salmonella typhimurium TA1535 and used to examine whether or not GST modified the genotoxic activities of several dihaloalkanes and other compounds. Twenty-nine chemicals that were suggested to be conjugated by GST were compared with regard to their abilities to induce umu gene expression and cause cytotoxicity responses in both the NM5004 strain and the original tester strain (S. typhimurium TA1535/pSK1002, which is devoid of GST activity toward 1,2-epoxy-3-(4'-nitrophenoxy)propane). Ten chemicals--1,2-dibromoethane,N-(2,3-epoxypropyl)phthalimide, 1,3-dichloroacetone, CH2I2, 1,2-epoxy-3-phenoxypropane, 2,3-epoxypropyl p-methoxyphenyl ether, 1-bromo-2-chloroethane, 1-bromo-2,3-dichloropropane, CH2BrCl, and CH2Br2--were found to enhance induction of umu gene expression in the NM5004 strain as compared with the TA1535/pSK1002 strain. 1,2-Epoxy-3-(4'-nitrophenoxy)propane and 2,3-dibromo-1-chloropropane were inactivated by GST 5-5 in the NM5004 tester strain, although these chemicals were cytotoxic in both tester strains. Roles of GST 5-5 were also examined for the inactivation of reactive metabolites of several procarcinogens that were formed through oxidation by liver microsomes of polychlorinated biphenyl-treated rats. The results suggest that reactive metabolites (possibly epoxides) of aflatoxin B1, sterigmatocystin, 1,2-dihydro-1,2-dihydroxy-6-aminochrysene, and (+)- and (-)-enantiomers of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene could be trapped as inactivated GSH conjugates in the NM5004 strain. High-performance liquid chromatographic analysis suggested that exo-aflatoxin B1-8,9-oxide--GSH conjugate was formed during the oxidation of aflatoxin B1 by rat and human liver microsomes in the presence of GSH and several GST enzymes including purified rat theta class GST Yrs-Yrs and rat liver GST (a mixture of alpha and mu class enzymes). Thus, the present results support the view that the theta class rat GST 5-5 enzyme participates in the activation and inactivation of potential environmental carcinogenic chemicals. This newly developed NM5004 tester strain is of use in the elucidation of roles of GST 5-5 in transformations.

Aflatoxin B1↗
PubMedDate not supplied

T1 and T2 measurements of meningiomas and neuromas before and after Gd-DTPA.

Seven patients with meningiomas and five patients with neuromas were examined with spin-echo sequences on a 0.35-T imaging system. Signal enhancement and relaxation rate increments with gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) were evaluated, as well as relaxation rate contributions, indicators of Gd-DTPA accessibility to the tissue water. The average signal enhancement rate with Gd-DTPA was higher in neuromas than in meningiomas, 148% and 84%, respectively, but this difference was poorly appreciated on enhanced images because of similar average postcontrast T1 values in both tumors. However, the average T1 relaxation increment was almost twofold higher in neuromas than in meningiomas, 318% and 162%, respectively, mainly deriving from longer intrinsic T1 values in neuromas. Also, there was a 25% increase in the average T2 relaxation rate in neuromas after Gd-DTPA together with a higher T2 contribution by Gd-DTPA, while such effects were hardly discernible in meningiomas, suggestive of greater accessibility of Gd-DTPA to the tissue water in neuromas. By electron microscopy, endothelial fenestration and open gap junctions are commonly found in capillaries of both tumors, functioning as the routes into the extracellular space where the major contrast effect of Gd-DTPA can be expected. However, the open gap junctions are short and straight in neuromas, while they are tortuous and sinusoid in meningiomas. This may provide greater access for contrast material into relatively larger extracellular spaces in neuromas and may cause a greater T1 relaxation rate increment with Gd-DTPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗