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Biomedical subjects

F Ishida

Publications and source records attributed to F Ishida.

At least 91 records · Page 5Linked to original sources
PubMed1990

Effect of simvastatin (MK-733) on sterol and bile acid excretion in rabbits.

The effects of Simvastatin (MK-733), an inhibitor of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, on fecal and biliary excretion of sterols and bile acids were examined using rabbits. Multiple doses of MK-733 (10 mg/kg/day) for 7 days were found to increase fecal concentrations of neutral sterols in cholesterol-fed rabbits, but not to affect those of bile acids. Multiple doses of cholestyramine (750 mg/kg/day), a bile acid sequestrant, for 7 days increased fecal concentrations of neutral sterols and bile acids in normally fed and cholesterol-fed groups. MK-733 did not affect biliary neutral sterols and total bile acids in normally fed and cholesterol-fed groups. Cholestyramine decreased biliary concentrations of neutral sterols in both diet groups. Cholestyramine altered fecal and biliary composition of bile acids, but MK-733 did not. It was considered that MK-733 inhibited the absorption of cholesterol, resulting in an increase of the fecal concentration of neutral sterols in cholesterol-fed rabbits. The mechanism of action of MK-733 in the inhibition of cholesterol absorption is considered to be clearly different from that of cholestyramine. These results confirmed the conclusion in the previous experiment.

Animals↗
PubMed1990

Effects of simvastatin (MK-733) on branched pathway of mevalonate.

The effects of simvastatin (MK-733), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on the branched pathway of mevalonate metabolism were studied in Hep G2 cells. The synthesis of cholesterol, ubiquinone and dolichol were examined using various radiolabeled precursors. The effect on DNA synthesis was also determined. MK-733 at a concentration of 1 microM potently inhibited the incorporation of [3H]acetate into cholesterol (84%) without affecting that from [3H]mevalonolactone. Under these conditions, MK-733 reduced the incorporation of L-[14C]tyrosine into ubiquinone slightly (14%), although it did not suppress that from [3H] acetate. The incorporation of [3H]acetate into dolichol was slightly reduced by MK-733. On the contrary, the incorporation of [3H]mevalonolactone into ubiquinone and dolichol was increased by MK-733. This apparent increase in incorporation was thought to be largely due to the higher specific radioactivity of the intracellular pool of mevalonate. The present study demonstrated that MK-733 slightly suppressed the synthesis of ubiquinone and dolichol in Hep G2 cells. However, the extent of their reduction was far less than the effect on cholesterol synthesis, suggesting that there were differences in substrate affinity between the enzymes participating in the cholesterol synthetic pathway and those in the ubiquinone or dolichol synthetic pathway. Furthermore, MK-733 did not affect DNA synthesis even at a concentration of 10 microM.

Animals↗
PubMed1990

[Granular lymphocyte leukemia of natural killer cell type; association with 47 XY, +8 by interleukin 2 (IL-2)-stimulated chromosomal analysis].

A 28-year-old male was admitted to our hospital because of hepatosplenomegaly and granular lymphocytosis. His peripheral leukocyte count was 3,000/microliters with 43% of granular lymphocytes (GL). These GLs were immunologically phenotyped as CD2+CD3-CD4-CD8-CD16+CD56+HLA-DR+ and were found that TcR genes coding beta and gamma chains were not rearranged. Chromosomal analysis of his GLs stimulated with IL-2 showed 47 XY, +8. This patient was diagnosed as a granular lymphocyte leukemia of natural killer cell type. Blood chemistry showed elevation of serum GOT, GPT and LDH values. The fever persisted until administration of prednisolone was initiated. But 40 days after, high fever appeared again and the liver and spleen were extremely enlarged. Combined chemotherapy was then started but resulted in no effects. He died of hepatic failure on the 77th day from admission. 47 XY, +8, that has been reported in acute non-lymphocytic leukemia and myelodysplastic syndrome, may be related to the pathogenesis in some cases of granular lymphocyte leukemia.

Adult↗
PubMed1989

Effects of MK-733 (simvastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on intestinal acylcoenzyme A:cholesterol acyltransferase activity in rabbits.

MK-733 (simvastatin), a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, was found to inhibit the absorption of cholesterol from the gastrointestinal tract in cholesterol-fed rabbits (Ishida et al. (1988) Biochim. Biophys. Acta 963, 35-41). To clarify the mechanism of action, the effects of MK-733 on acyl coenzyme A:cholesterol acyltransferase (ACAT) and cholesterol esterase activities, which are thought to participate in the absorption of cholesterol, were examined. Dietary administration (0.03% in a 1% cholesterol diet for 7 days, approx. 10 mg/kg) of MK-733 to cholesterol-fed rabbits was found to inhibit the increase in serum total cholesterol levels, and caused a 70% reduction in ACAT activity in microsomes of intestinal mucosa relative to those observed in concurrent control rabbits. MK-733 did not affect cholesterol esterase activity in the cytosol of the intestinal mucosa. The inhibitory effect of MK-733 on cholesterol absorption in cholesterol-fed rabbits is though to be related to a reduction in microsomal ACAT activity in the intestinal mucosa.

Animals↗
PubMed1989

Vascular plexus around intrahepatic bile ducts in normal livers and portal hypertension.

Vessels around the intrahepatic large bile ducts (peribiliary vascular plexus) were examined by histologic, immunohistochemical and scanning electron microscopic observations. The vessels within duct walls were mainly capillaries, while those around the duct walls were composed of capillaries and venules. A majority of vessels was positive for factor VIII-related antigen and Ulex europaeus lectin I. Scanning electron microscopy of hepatic arterial and biliary casts revealed that bile ducts were surrounded by the vascular plexus derived from hepatic arterial branches, and serial section observations in addition disclosed the vessels connecting the peribiliary plexus with portal venous branches ('internal roots'). The peribiliary vascular plexus was increased considerably in livers with portal hypertension, especially idiopathic portal hypertension, extrahepatic portal venous obstruction and hepatocellular carcinoma with portal venous tumor thrombi. Internal roots were also frequently found in the livers with portal hypertension. These results suggest that altered intrahepatic hemodynamics in portal hypertensive conditions involves the peribiliary vascular plexus, resulting in an increase of the number and frequent occurrence of 'internal roots', these vessels probably operating as intrahepatic collaterals.

Bile Ducts, Intrahepatic↗
PubMed1989

Inhibition of acyl coenzyme A: cholesterol acyltransferase by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

Relatively high concentrations of MK-733 (simvastatin) and MK-803 (lovastatin, mevinolin), which are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, were found to inhibit acyl coenzyme A: cholesterol acyltransferase (ACAT) of rabbit intestinal microsomes with IC50's of 2.0 x 10(-5) and 3.6 x 10(-5) M, respectively. Dihydroxy acid forms of both MK-733 and MK-803 did not inhibit ACAT activity. A kinetic analysis using a Lineweaver-Burk plot indicated that MK-733 is a competitive inhibitor of ACAT, with a Ki value of 1.2 x 10(-5) M.

Acyl Coenzyme A↗
PubMed1989

Preventive effect of MK-733 (simvastatin), an inhibitor of HMG-CoA reductase, on hypercholesterolemia and atherosclerosis induced by cholesterol feeding in rabbits.

MK-733 was found to prevent an increase of serum cholesterol levels in cholesterol-fed rabbits, and lovastatin also markedly inhibited their increase. MK-733 and lovastatin inhibited the increase of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol, and it slightly affected the high density lipoprotein (HDL) cholesterol levels. MK-733 and lovastatin suppressed the increase of serum phospholipid levels and slightly affected the triglyceride levels. MK-733 suppressed the development of atherosclerosis in coronary arteries and aorta, and lovastatin also diminished their development.

Animals↗
PubMed1989

Histologic and scanning electron microscopic observations of intrahepatic peribiliary glands in normal human livers.

The three-dimensional configuration of the intrahepatic peribiliary glandular system was examined in normal autopsied livers by scanning electron microscopic observations of the intrahepatic biliary tract casts. Biliary tract casts were made by injection of resin into the biliary tree and subsequent corrosion of the hepatic parenchyma. There were many projections on the surface of the biliary casts and they could be morphologically classified into pouchlike and treelike projections. These projections tended to be arranged on opposite sides of the biliary casts. The treelike projections from the large bile ducts at the bifurcation frequently anastomosed each other. By comparing the findings of biliary casts with histologic findings as well as the measuring of these projections and thickness of bile duct wall, it was suggested that the treelike projections correspond to the extramural peribiliary glands and the pouchlike ones to the intramural ones, both of which are normally present around the intrahepatic biliary tree. Thus, it was suggested stereologically in this study that substance(s) produced in the intrahepatic peribiliary glands may be secreted into the bile ductal lumen and thereby participate in the modification of bile composition.

Bile Ducts, Intrahepatic↗
PubMed1988

Effects of MK-733, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, on absorption and excretion of [3H]cholesterol in rabbits.

Effects of MK-733 on the absorption and excretion of cholesterol in rabbits were examined using [3H]cholesterol. The animals were divided into six groups; three groups were fed a normal diet, and the other groups a cholesterol diet. MK-733 was administered orally as a single dose of 10 mg/kg on day 8, or multiple doses of 10 mg/kg once a day for 14 days. On the 8th day, [3H]cholesterol was given orally to each animal. In the groups fed a normal diet, single and consecutive administration of MK-733 did not affect the absorption and excretion of [3H]cholesterol. In the cholesterol-fed groups, however, single administration of MK-733 decreased the serum 3H radioactivity slightly, but did not affect the fecal excretion of [3H]cholesterol. However, the consecutive treatment with MK-733 clearly reduced the serum 3H radioactivity. The cumulative excretion of the fecal radioactivity of [3H]cholesterol in the MK-733 group (multiple) was higher than that in the control group. From these results, it is concluded that MK-733 inhibits the absorption of cholesterol from the gastrointestinal wall in cholesterol-fed rabbits.

Administration, Oral↗
PubMed1987

Mutagenic evaluation of etintidine (BL-5641), a novel histamine H2-receptor antagonist, using the chromosome aberration test in CHL cells and the micronucleus test in mice.

The mutagenic effects of etintidine (BL-5641), a novel histamine H2-receptor antagonist, was assessed using the chromosome aberration test in CHL cells and the micronucleus test in mice. (1) Etintidine did not show any chromosome aberrations in the presence or absence of S9 mix at any concentration tested. (2) Etintidine did not increase the frequency of micronuclei in polychromatic erythrocytes even at the dose of 50% of the LD50 at single (24 h) and chronological preparation after drug administration.

Animals↗
PubMed1987

Mutagenic evaluation of etintidine (BL-5641), a novel histamine H2-receptor antagonist, using reverse mutation tests in bacteria and forward mutation tests in V79 Chinese hamster cells.

The mutagenic effects of etintidine (BL-5641), a novel histamine H2-receptor antagonist, were assessed using mutation in Salmonella typhimurium, Escherichia coli, and V79 Chinese hamster cells (V79 cells). Etintidine did not increase the revertant colonies in the presence or absence of S9 mix at concentrations from 5 to 5000 micrograms/plate in either of the bacterial tester strains. Etintidine also did not increase 6-thioguanine- and ouabain-resistant colonies in V79 cells in the presence or absence of S9 mix even at 37% cellular survival concentration. There was no evidence that etintidine had any mutagenic activity in any of the tests.

Animals↗