Search PubMed⌕ Search

Biomedical subjects

T Hishinuma

Publications and source records attributed to T Hishinuma.

80 records · Page 5Linked to original sources
PubMed1985

Monoclonal antibodies against a high spin form of rat cytochrome P-448.

Ten monoclonal antibodies reactive with a high spin form of rat cytochrome P-448 (P-448-H) were obtained from hybridoma clones established by a fusion between P3X63Ag8.653 mouse myeloma cells and spleen cells of a BALB/c mouse hyperimmunized with the cytochrome. One monoclonal antibody recognized an epitope characteristic for P-448-H. Five monoclonal antibodies were cross-reactive with a low spin form of rat cytochrome P-448, but not with cytochrome P-450. Reactivity of these monoclonal antibodies with microsomes of rats pretreated with drug metabolizing inducers and Western blots of the microsomal cytochrome P-450 components are also demonstrated.

Animals↗
PubMed1985

Sex-dependent induction of hepatic enzymes for mutagenic activation of a tryptophan pyrolysate component, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]-indole, by feeding in mice.

Male and female BALB/c X DBA/2 F1 mice were treated with a diet containing 0.02% 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]-indole (Trp P-1), a hepatocarcinogenic tryptophan pyrolysate component, and the capacities of subcellular fractions of the liver to catalyze the mutagenic activation of Trp P-1 and its analogue Trp P-2 (4-demethylated Trp P-1) were examined by the in vitro Salmonella test with strain TA 98. In mice on control diet, both 9000 X g supernatant (S-9) and microsomal fractions from female mice livers displayed only 1.1- to 1.3-fold higher capacities for the mutagenic activation of either Trp P-1 or Trp P-2 than did those from male mice livers. When mice were treated with the Trp P-1 diet for 1 week, the S-9 activity in male mice for the Trp P-1 mutagenesis did not change, but that in females was increased to 2.5-fold of the female control. Treatment of mice with the dietary Trp P-1 for 2 weeks increased the S-9 activities to 2.8-fold in males and 4.9-fold in females of the same sex controls and the increased S-9 activities were not significantly changed by additional Trp P-1 feeding for 2 weeks. Similar changes in the S-9 activity were observed for the Trp P-2 mutagenesis. The overall changes in the S-9 activities induced by feeding Trp P-1 were reflected in the isolated microsomes. However, microsomes derived from the same volume of S-9 used exhibited only about one-half (Trp P-1) or one-third (Trp P-2) of the activity of the respective complete S-9 mixtures. Addition of liver cytosolic fractions (105,000 X g supernatants) from untreated or Trp P-1-treated mice to microsomes resulted in enhanced activities. Cytosols alone did not activate the compounds to mutagens. The microsome-mediated mutagenicity of either Trp P-1 or Trp P-2 was diminished by removal of NADPH from the assay system. It was also inhibited by addition of 7,8-benzoflavone and to a lesser extent by SKF 525A. Enzyme(s) for the mutagenic activation of Trp P-1 was induced by an i.p. injection of 3-methylcholanthrene to mice and to a lesser extent by an injection of phenobarbital, but no sex differences were observed in these enzyme inductions as opposed to the Trp P-1 feeding.(ABSTRACT TRUNCATED AT 400 WORDS)

Aminopyrine N-Demethylase↗
PubMedDate not supplied

Effect of diabetic sera on the conversion of eicosapentaenoic acid (EPA) to prostaglandin I3 by cultured bovine aortic endothelial cells.

The effects of sera from diabetic patients and healthy donors on the synthesis of prostaglandin I2 (PGI2) and PGI3 in vitro were studied in confluent bovine aortic endothelial cells cultured with EPA. The products 6-keto-PGF1 alpha and delta 17-6-keto-PGF1 alpha were measured by GC/SIM as markers of PGI2 and PGI3 formation in growth medium after 60 min of incubation. PGI2 and PGI3 synthesis with 10% diabetic sera were less than with sera from healthy donors (p < 0.05). However, the total prostacyclin production (PGI2 and PGI3) in the cell cultures incubated with 10 microM EPA and 10% diabetic sera approximated that of the cultures incubated with the sera of healthy donors without EPA. These results suggest that the diabetic sera inhibits PGI2 and PGI3 synthesis in the cultured endothelial cells, and that EPA intake may reduce the complications of diabetes mellitus, such as microangiopathy and vaso-occlusive diseases, and enhances the production of PGI3 which seems to exert a strong anti-aggregatory effect.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

A study of periventricular hyperintensity. I. Normal brain aging.

Fifty-two patients with cerebrovascular risk factors without neurological abnormalities were examined by magnetic resonance imaging and were evaluated for their periventricular hyperintensity (PVH) on T2-weighted images. We assumed that PVH was not a mere focal finding of the brain but a kind of marker for condition related to arteriosclerosis and cerebral ischemia, and we tried to devise a model screening test, using common parameters available in most ordinary hospitals, to predict PVH. Multiple regression analysis was performed by setting up the PVH% (the volume percentage of PVH to cranial cavity) as a dependent variable and twenty-seven variables associated with general medical examination and brain atrophy as explanatory variables. We found that arteriosclerotic changes in the body as well as brain atrophy were significantly correlated with PVH, and that PVH could be predicted with a high contribution ratio of 0.70. It is clinically important to examine the elderly with our screening test to predict PVH in order to detect the early stages of ischemia.

Journal Article↗
PubMedDate not supplied

Difference in urinary 11-dehydro TXB2 and LTE4 excretion in patients with rheumatoid arthritis.

Thromboxane and leukotrienes have been implicated in inflammation. However, the production level of these eicosanoids in patients with rheumatoid arthritis is still unclarified. In the present study, endogenous synthesis of thromboxane and cysteinyl leukotrienes in patients was investigated. The production of eicosanoids in patients is assessed by measuring stable urinary metabolites,11-dehydro thromboxane B2 and leukotriene E4, using gas chromatography/selected ion monitoring and liquid chromatography/tandem mass spectrometry. The level of urinary thromboxane in patients was significantly higher than that in healthy volunteers (P < 0.05). Furthermore, we investigated the effects of administered drugs on the production of these eicosanoids. The urinary thromboxane level of the untreated group (1630 +/- 613 pg/mg creatinine) was much higher than that of healthy volunteers (342 +/- 263 pg/mg creatinine). The level in the group receiving NSAID alone was similar to that in healthy volunteers, and the group receiving steroid alone showed slightly lower thromboxane levels than the untreated group. On the other hand, the leukotriene E4 level in patients (280 +/- 360 pg/mg creatinine) was also significantly higher than that in healthy volunteers (59 +/- 54 pg/mg creatinine, P < 0.05). In particular, the group receiving methotrexate (904 +/- 685 pg/mg creatinine) had higher leukotriene levels than not only healthy volunteers but also other medicated groups. These findings demonstrated that endogenous thromboxane and leukotriene production in patients with rheumatoid arthritis are enhanced, and the effects of medication on the production of these eicosanoids differed in thromboxane and leukotriene E4.

Aged↗
PubMedDate not supplied

Genetic variation in ABCB1 influences paclitaxel pharmacokinetics in Japanese patients with ovarian cancer.

Paclitaxel, an antineoplastic agent used for the treatment of ovarian cancer, is metabolized by cytochrome P450 (CYP)3A4 and CYP2C8 and is excreted from cells by ATP-binding cassette (ABCB1) (multi-drug resistance [MDR1], P-glycoprotein). Expression of these proteins is regulated by pregnane X receptor (PXR). Although there are common genetic polymorphisms in the genes encoding these proteins, their effect on the clinical efficacy of paclitaxel is unclear. We therefore examined the relationship of the paclitaxel pharmacokinetics in 13 patients with ovarian cancer to polymorphisms in CYP2C8, CYP3A5, ABCB1, and PXR. We found high interindividual variability in the plasma concentrations of two metabolites, 6alpha-hydroxypaclitaxel and p-3'-hydroxypaclitaxel. All the patients were genotyped as CYP2C8*1/*1. Neither the CYP3A5 A6986G (CYP3A5*3) nor the PXR C-25385T alleles were associated with altered plasma concentrations of paclitaxel and its metabolites. ABCB1 T-129C, T1236C, and G2677(A,T), however, was associated with lower area under the plasma concentration-time curve (AUC) of paclitaxel. We also observed a significant correlation between the AUC (r=-0.721) or the total clearance of paclitaxel (CL(tot)) (r= 0.673) and the ABCB1 mutant allele dosage in each patient. Taken together, our findings suggest that interindividual variability in paclitaxel pharmacokinetics could be predicted by ABCB1 genotyping.

ATP Binding Cassette Transporter, Subfamily B↗
PubMedDate not supplied

Effects of eicosapentaenoic acid (EPA) on prostacyclin production in diabetics: GC/MS analysis of PGI2 and PGI3 levels.

The enzymatic metabolites, 6-keto-PGF1 alpha and delta 17-6-keto-PGF1 alpha, were measured by gas chromatography/high resolution-selected ion monitoring (GC/HR-SIM) as markers of prostaglandin I2 (PGI2) and prostacyclin (PGI3) production in human sera. Eicosapentaenoic acid (EPA) ethyl ester (1.8 g/day) was administered to 12 noninsulin-dependent diabetes mellitus (NIDDM) patients for 2 weeks. Forty patients with similar NIDDM were followed as a control group. PGI3 production in sera was significantly increased in the EPA intake group in comparison with the control group. These findings suggest that EPA intake prevents complications of diabetes mellitus, such as microangiopathy and vaso-occlusive diseases.

6-Ketoprostaglandin F1 alpha↗