Publications by authors named "Ishii I"

Pimobendan, 4, 5-dihydro-6-(2-(4-methoxyphenyl)-1H-benzimidazol-5-yl)-5-methyl-3( 2-H )-pyridazinone, is a new inotropic drug that augments Ca(2+) sensitivity and inhibits phosphodiesterase in cardiomyocytes. Pimobendan is well absorbed after oral administration and is metabolized in the liver to the O-demethyl metabolite, which is also active. This study was conducted to identify the cytochrome P-450 (CYP) isoform(s) responsible for the pimobendan O-demethylation in human liver microsomes.

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Receptors belonging to the LDL receptor (LDLR) family are thought to play key roles in lipoprotein metabolism in a variety of tissues, including the arterial wall. Here, we report that the expression of a 250-kDa mosaic LDLR family member, which we called LR11 for the presence of 11 ligand-binding repeats, is markedly induced during the process of atherogenesis in 2 animal models. Analysis by reverse transcription-polymerase chain reaction and RNase protection assays revealed that LR11 transcript levels rise in rabbit aortas displaying atheromatous lesions after the rabbits have been fed a high-cholesterol diet.

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Asexual plants of Eupatorium makinoi is frequently infected with tobacco leaf curl geminivirus (TLCV). The host range of TLCV is narrow, and ORF C4 is considered to function as a host range determinant. Using this TLCV-Eupatorium system, we tested the expectation that the rate of amino acid replacements will be accelerated in ORF C4 if resistant genes of the host plants drive molecular evolution in ORF C4.

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A new inhibitor of acyl CoA:cholesterol acyltransferase (ACAT), HL-004 [N-(2, 6-diisopropylphenyl)tetradecylthioacetamide], suppressed the synthesis of cholesterol [14C]oleate at 10(-9) approximately 10(-7) M in a concentration-dependent manner in both THP-1 cell-derived macrophages and foam cells prepared from aortic intima of rabbits fed a high cholesterol diet. Incorporation of [3H]cholesterol oleate-beta very low density lipoproteins was not inhibited by HL-004 at 10(-9) approximately 10(-7) M. Release of radioactivity from the cells loaded with [3H]cholesterol oleate-beta very low density lipoproteins was increased by the inhibition of ACAT activity with HL-004.

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A case of choroidal malignant melanoma in which N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) scintigraphy was useful for diagnosis is reported. A 62-year-old man first visited our hospital 3 years ago complaining of decreases in left eyesight. CT showed a tumor with an arcuate high attenuation area on the aural side of the optic disk in the left eye.

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Human fetal CYP3A7 and human NADPH-cytochrome P450 reductase were coexpressed in insect cells, TN-5, infected with a recombinant baculovirus carrying both cDNAs. The expression of reductase in TN-5 cells was shown to be sufficient for the CYP3A7 dependent 16 alpha-hydroxylation of dehydroepiandrosterone. However, the extra addition of cytochrome b5 and phospholipid was necessary to obtain a maximal activity of CYP3A7 catalyzing the reaction.

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The catalytic properties of CYP3A7 in the metabolism of endogenous and exogenous substrates were compared with those of CYP3A4 and CYP3A5 using COS-7 expressing enzymes. The highest activities of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone 3-sulfate (DHEA-S) 16alpha-hydroxylase were observed in COS-7 cells expressing CYP3A7. In contrast, the activity of testosterone 6beta-hydroxylase of CYP3A7 expressed in COS-7 cells was much less than that of CYP3A4 expressed in COS-7 cells.

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Agonist-induced sequestration, recycling, and resensitization of platelet-activating factor (PAF) receptor were characterized in transfected Chinese hamster ovary cells. Exposure of the cells to PAF led to rapid sequestration of the receptors into the intracellular compartment and desensitization of the response to PAF. The sequestration was inhibited by pretreatments that perturbed the clathrin-mediated pathway.

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The N-demethylation of dacarbazine in liver microsomes was significantly increased by treatment of rats with beta-naphthoflavone, dexamethasone, or phenobarbital. However, the extent of increase in the N-demethylation observed in beta-naphthoflavone-treated rats was much greater than that observed in dexamethasone-treated rats. A good correlation between N-demethylation of dacarbazine and O-deethylation of phenacetin was observed when a low concentration of phenacetin was used.

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Arterial thrombi are primarily composed of platelets. Platelets are bound to injured endothelial cells, sub-endothelial matrices, and other platelets by a range of adhesive proteins. Some of these reactions are governed by shear forces.

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N4G3, a cell line that overexpresses translation initiation factor eIF4G, one of the components of eIF4F, was made by stable transfection of the human eIF4G cDNA into NIH3T3 cells. The cells expressed 80-100 times greater levels of eIF4G mRNA than did NIH3T3 cells. N4G3 cells formed transformed foci on a monolayer of cells, showed anchorage-independent growth, and formed tumors in nude mice.

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The GST Fpi and GST Ppi, pi class glutathione S-transferase (GST), were purified from human fetal livers and placentas, respectively. Both GST enzymes were indistinguishable each other in their subunit molecular weights, immunochemical properties and substrate specificities. Three clones (pFGP-1, pFGP-2 and pFGP-3) coding for the pi class GST purified from fetal livers were isolated from a human fetal liver cDNA library.

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There are several major groups of multidrug resistance mechanisms. 1) The multidrug resistant phenotype. 2) Glutathione S-transferences (GST) and detoxification mechanisms.

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To determine ligand-binding sites of a platelet-activating factor (PAF) receptor, alanine-scanning mutagenesis was carried out. All 23 polar amino acids in the putative 7-transmembrane (TM) domains of a guinea pig PAF receptor were individually replaced with alanine. The ligand-binding properties of mutant receptors were determined after transient expression in COS-7 cells.

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Cefetamet pivoxil (CEMT-PI), a drug of pivaloyloxymethyl group, was investigated for its impact on the carnitine blood homeostasis and renal excretion upon administering CEMT-PI alone, and CEMT-PI simultaneously with carnitine. 500 mg of CEMT-PI (group A) and 500 mg of CEMT-PI and an equimolar amount (200 mg of carnitine) of levocarnitine chloride (group B) were administered twice a day for 7 and 1/2 consecutive days to 5 healthy volunteers (group A) and 3 healthy volunteers (group B). No serious side effects nor abnormal values in physical and laboratory tests were observed throughout the study in both groups.

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The protective effects of ticlopidine and d,l-lysine acetylsalicylate (L-ASA), used alone and in combination, on the pathogenesis of thrombosis in cerebral blood vessels were investigated in a rat animal model using a He-Ne laser method. Ticlopidine and L-ASA, given orally at a concentration from 100 mg/kg, inhibited thrombus formation in a dose-dependent manner. Ticlopidine (300 mg/kg p.

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The effect of phospholipids on cholesteryl ester hydrolysis by neutral cholesterol esterase in alveolar macrophages was studied. Among the phospholipids used as emulsifiers, those with a negative charge, such as phosphatidylserine, phosphatidic acid, phosphatidylinositol, and cardiolipin, gave a higher level of hydrolysis by neutral cholesterol esterase than other less negatively charged phospholipids, such as phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, and sphingomyelin. Phospholipase D treatment of liposomes emulsified with phosphatidylcholine produced phosphatidic acid and enhanced cholesteryl ester hydrolysis.

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The antithrombotic effect of long-term aerobic exercise was studied in rat cerebral blood vessels using an argon (Ar) laser-induced thrombosis technique. Rats were subjected to treadmill exercise at 70% VO2max for 2 and 4 months. The number of laser irradiations required to form an occlusive thrombus in the exercise group was significantly increased compared to that of the control group after 2- and 4-month training periods.

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Cholesterol metabolism in macrophages from atherosclerosis-prone C57BL/6J mice was compared with that in macrophages from atherosclerosis-resistant C3H/HeN mice. Plasma total cholesterol levels of both types of mice were significantly increased, but HDL cholesterol level was increased only in C3H/HeN mice when a high-cholesterol diet (1% cholesterol) was fed for 5 weeks. After incubation of macrophages from male and female mice on the high-cholesterol diet with beta-VLDL for 24 hours, cholesterol content in macrophages from C57BL/6J was approximately 1.

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The metabolism of beta-very-low-density lipoproteins (beta-VLDL) in macrophages from the blood monocytes of rabbits, which had been administered macrophage colony-stimulating factor (M-CSF) in vivo, was investigated in order to clarify the mechanism of the suppressive effect of M-CSF on cholesterol accumulation in macrophages. Cholesterol ester content after incubation with beta-VLDL, and [3H]cholesterol oleate-beta-VLDL incorporation remarkably increased in cultured macrophages from blood monocytes in the high cholesterol diet control group compared to those in the normal diet control group. Those in macrophages from M-CSF-treated groups, both normal diet and high cholesterol diet, were the same as in the normal diet control group.

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Bacillus subtilis 168M contained a large amount of spermidine during the logarithmic phase of growth, but the amount decreased drastically during the stationary phase. The extracts, prepared from B. subtilis cells harvested in the logarithmic phase, contained activity of arginine decarboxylase (ADC) rather than the activity of ornithine decarboxylase.

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Induction of transglutaminase was analyzed based on increases in the maximal enzymic activity and in the Northern blots of mRNA during culture of mouse resident peritoneal macrophages with active forms of hydrophobic vitamins and steroid hormones. The enzyme was induced by 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) or retinoic acid but not by steroid hormones. The induction by 1 alpha,25-(OH)2D3 was characterized by its slow onset and marked synergism with retinoic acid induction.

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The effect of monocyte colony stimulating factor (M-CSF) on the beta-very low density lipoprotein (beta-VLDL) metabolism in THP-1 cells (human leukemia cell line) was studied. THP-1 cells treated with M-CSF decreased Latex Bead phagocytosis, but the cells incubated with 12-tetradecanoyl-phorbol-13-acetate (TPA) enhanced phagocytosis 2.5-fold.

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Culture of mouse resident peritoneal macrophages with retinoic acid resulted in increased expression of the tissue transglutaminase gene as revealed by increases in the maximal velocity of the enzyme reaction in the cytosol and in the enzyme mRNA level. Protein kinase C-activating phorbol esters and okadaic acid, both of which were without effect on the enzyme induction by themselves, enhanced the retinoic acid-induced gene expression, which was in turn inhibited partially by pertussis toxin and totally by inhibitors of protein kinase C in either the presence or absence of phorbol esters. Retinoic acid was more effective in the "conditioned" medium, in which macrophages had been cultured for a time longer than 4 h, than in the "fresh" medium.

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