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Biomedical subjects

T Watabe

Publications and source records attributed to T Watabe.

At least 181 records · Page 10Linked to original sources

Cholesterol alpha- and beta-epoxides as obligatory intermediates in the hepatic microsomal metabolism of cholesterol to cholestanetriol.

A high performance liquid chromatographic method for the good separation and direct determination of cholesterol alpha-epoxide (5,6 alpha-epoxy-5 alpha-cholestan-3 beta-ol) and beta-epoxide (5,6 beta-epoxy-5 beta-cholestan-3 beta-ol) was introduced to the study of microsomal lipid peroxidation-mediated oxygenation of the cholesterol double bond. In the presence of NADPH, FeSO4, and ADP, bovine liver microsomes converted [4-14C] cholesterol to the alpha-epoxide, beta-epoxide, and cholestanetriol (5 alpha-cholestane-3 beta,5,6 beta-triol) in the ratio 1.0:4.3:0.7. Obligatory intermidiacy of both cholesterol alpha- and beta-epoxides and essential role of microsomal cholesterol epoxide hydratease in the conversion of cholesterol to cholestanetriol were established by using the isotope trapping method as well as the cholesterol epoxide hydratase inhibitor, 5,6 alpha-imino-5 alpha-cholestan-3 beta-ol. Hepatic microsomal P-450 played no appreciable role in the epoxidation of cholesterol. Microsomal cholesterol epoxide hydratase was with no doubt found to differ in nature from microsomal xenobiotic epoxide hydratase. Microsomal hydrolysis of styrene oxide and safrole oxide (0.1 mM each) was almost completely inhibited by 3,3,3-trichloro-1-propene oxide (1 mM) but not by 5,6 alpha-imino-5 alpha-cholestan-3 beta-ol (1 mM). However, microsomal hydrolysis of both cholesterol alpha- and beta-epoxides was remarkably accelerated by 3,3,3-trichloro-1-propene oxide and inhibited by 5,6 alpha-imino-5 alpha-cholestan-3 beta-ol.

Animals↗

Differential mutagenicities of 6 N-nitroso-N-alkylurea derivatives in Escherichia coli strains with different DNA-repair capacities.

Reverse mutations to prototrophy by, and killing effects of, 6 N-nitroso-N-alkylurea derivatives such as NMU, NEU, NPU, NBU, NIBU and NAU were studied with E. coli strains H/r30R (wild-type), Hs30R (uvrA-), O16 (polA-) and NG30 (recA-). Both strains polA- and recA- were far more sensitive to killing by the 6-compounds than were the wild-type and uvrA- strains, and there was no difference in the sensitivity between the latter 2 strains. NMU was mutagenic in all 4 strains; wild-type, uvrA- and polA- strains were almost equally mutable but the compound was slightly mutagenic in the recA- strain. The other 5 compounds, NEU, NPU, NBU, NIBU and NAU, caused hardly any mutation in the recA- strain. NEU, NPU and NBU were equally mutagenic in the wild-type, uvrA- and polA- strains; however, NIBU and NAU were more mutagenic in the uvrA- than in the wild type or polA-. From the differential mutagenicities and lethalities induced by the 6 N-nitroso-N-alkylureas into the 4 tester strains, mutational patterns of the compounds can be classified into 3 types.

DNA Repair↗

Cholesterol diet increases plasma and liver concentrations of cholesterol epoxides and cholestanetriol.

Cholesterol alpha-epoxide (5, 6 alpha-epoxy-5-alpha-cholestan-3 beta-ol), cholesterol beta-epoxide (5, 6 beta-epoxy-5 beta-cholestan-3 beta-ol), and cholestanetriol (5 alpha-cholestane-3 beta, 5, 6 beta-triol) were isolated from plasma and liver of rabbits by high performance liquid chromatography and identified by gas-chromatography-mass spectrometry. The 5, 6-oxygenated cholestanols in the plasma and liver of rabbits fed for two months on a diet supplemented with cholesterol wee elevated to 2-5 times and 5-8 times for normal level, respectively. Among the 5, 6-oxy-generated steroids, the beta-epoxide existed at the highest level in tissues of both control and cholesterol-fed rabbits. The ratios of the beta-epoxide to the alpha-epoxide were 2-3 in all the examined biological specimens just as the previously demonstrated ones in the vitro lipid peroxidation-mediated reaction of cholesterol. These results strongly suggest that the epoxidation of the cholesterol double bond in the animal may be mediated by lipid peroxidation. The elevated 5, 6-oxygenated cholestanol levels on long term cholesterol feeding will be discussed in relation to a possible physiological role of cholestanetriol in regulation of tissue cholesterol levels.

Animals↗

Clinical application of cardiovascular computed tomography.

The application of computed tomography to cardiovascular diagnosis was attempted. One hundred and four consecutive patients with various cardiovascular diseases were studied with a third-generation computed tomographic three-second whole body scanner. Identification and evaluation of abnormalities of the great vessels, atria, ventricles and interventricular septum were possible by cardiac computed tomography. Sizes and locations of intracardiac thrombi were accurately assessed by computed tomography. Computed tomography was valuable for the evaluation of pericardial effusion because distribution of the effusion as well as the gross nature of the fluid could be estimated by the CT number.

Cardiovascular Diseases↗

Non-communicating hydrocephalus caused by dural arteriovenous malformation.

The case of a female infant with a non-communicating hydrocephalus caused by an enormously dilated straight sinus and the dilated posterior one third of the sagittal sinus is presented. These sinuses drained a torcular dural arteriovenous malformation. Conray ventriculography revealed a complete obstruction of the junction of the aqueduct and fourth ventricle with cephaloventral displacement of the ventricular system by the dilated sinuses. Placement of a ventriculoperitoneal shunt was followed by artificial embolization, by selective catheterization, into the dural feeding arteries.

Arteries↗