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Biomedical subjects

N Kurata

Publications and source records attributed to N Kurata.

At least 91 records · Page 5Linked to original sources

[Heterogeneity of anticardiolipin antibody].

The antibody to cardiolipin(ACA) was tested in patients with systemic rheumatic disease. The frequency of IgG ACA was 46/100(46.0%) in systemic lupus erythematosus(SLE). In other rheumatic disease, this was less than 20%. Significant correlation between the presence of IgG ACA and thrombosis and/or thrombocytopenia was found in patients with SLE. Eight sera containing high titered IgG ACA from lupus patients were selected for further inhibition study. Inhibitors were consisted of cardiolipin(CL), phosphatidyl(p-)serine, p-inositol, p-glycerol, p-ethanolamine, p-choline, ds-DNA, ss-DNA, fresh platelets(PLT)and fresh red blood cells(RBC). All sera were markedly inhibited by negatively charged phospholipids. In 4 sera(group B), there was moderate inhibition by ss-DNA, ds-DNA, PLT and RBC. In another 4 sera(group A), mild but significant inhibition was obtained by PLT alone. The number of platelet in group A was less than that in group B. There were some differences in inhibitory activity, suggesting heterogeneity of antibody to CL. It may be possible to speculate that heterogeneity of IgG ACA cause various combination of clinical features such as thrombocytopenia and thrombosis.

Abortion, Spontaneous↗

Measurement of ethyl carbamate in blood by capillary gas chromatography/mass spectrometry using selected ion monitoring.

Methodology is presented for convenient, reproducible and direct measurement of blood concentrations of ethyl carbamate, an experimental animal carcinogen. Extraction techniques requiring 20 microliters of blood and selected ion monitoring using ethyl (13C, 15N)carbamate as internal standard enabled quantification of ethyl carbamate concentrations ranging from 50 ng ml-1 to 100 micrograms ml-1. Coefficients of variation at several representative concentrations averaged less than 4%. The method was used to determine the time course of elimination of ethyl carbamate from mice receiving doses of 125 mumol kg-1.

Animals↗

Dose-dependent regulation of macrophage differentiation by mos mRNA in a human monocytic cell line.

The proto-oncogene c-mos was expressed during differentiation of the human monocytic cell line U937 into macrophages. To investigate a possible role of the mos oncogene, we introduced the v-mos gene under an inducible promoter, MT-I, into U937 cells. The v-mos transformed cells expressed mos mRNA at an amount proportional to the concentration of Zn2+ ions. The induction of the v-mos gene caused growth inhibition and macrophage differentiation in these cells. The differentiation of v-mos transformed monocytes into macrophages required continuous expression of the v-mos gene. The extent of expression of phenotypic characteristics of macrophages, such as phagocytosis, cell surface antigens and typical morphology, depends on the amount of mos mRNA present. We were therefore able to demonstrate that the expression of only one oncogene, mos, determines monocyte differentiation into macrophages.

Antigens, Surface↗

Long-term effects of phenobarbital on rat liver microsomal drug-metabolizing enzymes and heme-metabolizing enzyme.

Long-term effects of phenobarbital on changes of rat hepatic enzymes involved in drug and heme metabolism were examined by employing two different treatment schedules which produce tolerance (tolerant group) and/or dependence (dependent group) against the drug. In both treatment groups, phenobarbital produced a marked and persistent induction of cytochrome P-450 and aminopyrine N-demethylase; the response was greater in the tolerant group than that in the dependent group at the early time periods. Thereafter, the magnitude of the induction of drug-metabolizing enzymes gradually decreased and finally was maintained at two-fold of the corresponding control levels. Likewise, the induction of cytochrome P-450b+e content, one of the major phenobarbital inducible species, was maintained at 40% of the total cytochrome P-450 content. Phenobarbital treatment resulted in increase of delta-aminolevulinate synthetase (ALAS) activity and a decrease in heme oxygenase (HO) activity. Changes of these enzymes involved in heme metabolism coincided with changes of the drug-metabolizing enzymes. Finally, the changes of enzyme content and activity after terminating phenobarbital treatment were determined and enzyme biological half-lives were calculated employing protein synthesis inhibitors. No significant differences in the changes of cytochrome P-450 and cytochrome P-450b+e content between the groups were observed after terminating phenobarbital treatment. However, changes of ALAS and HO activities after terminating the drug were significantly different between the groups; changes in the dependent group corresponded to the decrease in serum phenobarbital levels. On the other hand, biological half-lives of microsomal drug-metabolizing enzymes were longer in the tolerant group than in the dependent group.

5-Aminolevulinate Synthetase↗

Small intestinal perforation in Wegener's granulomatosis.

Wegener's granulomatosis is a disease characterized by necrotizing vasculitis and granulomatous inflammation. Gastrointestinal (GI) involvement is uncommon in this disorder. Only a few cases of perforation of GI tract have been reported, but vasculitis has not been demonstrated to be a cause of perforation in these cases. We report a case of Wegener's granulomatosis in which a single perforation in the terminal ileum was disclosed on laparotomy and active necrotizing vasculitis was found in the submucosal layer of the resected specimen.

Adult↗

The effects of malotilate on hepatic drug metabolizing systems in different strains of rats.

1. In Sprague-Dawley (SD) rats treated for 7 days with malotilate (MAL:250 mg/kg, p.o.), cytochrome P-450 and b5 contents, aminopyrine N-demethylase and heme oxygenase activities were significantly increased. In Wistar rats, cytochrome b5 content and heme oxygenase and delta-aminolevulinic acid synthetase activities were found to be significantly increased. 2. Among the antipyrine metabolites excreted in urine during the 24 hr after antipyrine (100 mg/kg, i.p.) administration, norantipyrine increased significantly in Sprague-Dawley rats, while a significant increase of 4-hydroxyantipyrine was observed in Wistar rats. 3. The serum dimethadione/trimethadione ratio was only found to be significantly increased in Sprague-Dawley rats. 4. These results indicate that malotilate may have inducible effects on hepatic drug metabolizing enzymes, and that it affects the various cytochrome P-450 isozymes from different strains of rat in different ways.

Alkaline Phosphatase↗

Induction of cytochrome P-450 and related drug-oxidizing activities in muscone (3-methylcyclopentadecanone)-treated rats.

In the present study, we investigated the effects of muscone on both in vitro and in vivo parameters of the hepatic microsomal drug-metabolizing enzyme system and other enzyme activities in rats. In the in vivo study, the serum dimethadione (DMO)/trimethadione (TMO) ratios at 2 hr after oral administration of TMO (100 mg/kg) were significantly increased in both male and female rats treated with 75 and 150 but not 40 mg muscone/kg. Antipyrine metabolite profile in 24 hr urine of rats pretreated with muscone (150 mg/kg) was examined. The results showed that the excretion of norantipyrine was significantly increased as compared to the control group. In the in vitro study, we found that the content of cytochrome P-450, and activities of aminopyrine, N-demethylase, aniline hydroxylase and delta-aminolevulinic acid (ALA) synthetase were significantly increased as compared to the controls in both male and female rats treated with muscone (75 and 150 mg/kg). This type of induction of the hepatic metabolizing enzymes was similar to that seen after treatment with a prototype drug, phenobarbital.

5-Aminolevulinate Synthetase↗

Production of recombinant rat viruses as a method of oncogene isolation in coculture medium.

A simple oncogene isolation was proved using the SD1-T rat embryonic cell line. The SD1-T cell line, which releases endogenous rat leukemia virus, was cocultured with (a) normal rat kidney cells transformed by cloned v-mos DNA, (b) the rat mammary tumor cell line (63SP), or (c) normal rat kidney cells transformed by 63SP DNA. Within 1 mo, oncogenic viruses were recovered from all three coculture supernatants. During this period, increase of oncogenic transcripts was observed in the cocultured cells. The oncogenic viruses appeared to contain the mos gene in cocultures (a) and ras-related sequences in cocultures (b) and (c). The emergence of virus containing mos from mos DNA-mediated normal rat kidney transformants demonstrated "rescue" of the active cellular oncogene by the rat leukemia virus. This coculture system seems to facilitate "rescue" of oncogenes functioning in the tumor and transformed cells.

Animals↗

Response of pancreatic tumor to intraoperative radiotherapy: medical imaging and pathologic system approach.

For analyzing the local reaction of pancreatic carcinoma to electron intraoperative radiotherapy, successive computed tomography scanning for tumor volumetry was employed, together with surgical clip localization for tumor area using orthogonal x-rays. Soon after radiotherapy the tumor volume and clipped tumor region began to decrease. After a certain interval, computed tomography volumetry revealed that the irradiated tumor had started to increase in size again, whereas the clipped area had not. Autopsies demonstrated that the increase related chiefly to cancer regrowth outside the primary radiation field.

Aged↗

A factor inducing differentiation of the human monocytic cell line U-937 produced by 12-O-tetradecanoylphorbol 13-acetate-treated U-937.

A new factor capable of inducing differentiation of human leukemic cell line U-937 into macrophages was found and partially purified from the conditioned medium of U-937 previously treated with 12-O-tetradecanoylphorbol 13-acetate. The purification procedure included ultrafiltration, DEAE-Sephacel and butyl-Toyopearl column chromatography. The purified factor gave a major band of protein with a molecular weight of 67,000 daltons which coincided with the biological activity of differentiation-inducing factor, and it was not adsorbed on a concanavalin A column. These results suggest that this factor is distinct from other differentiation-inducing factors.

Cell Differentiation↗

Influence of short-term water deprivation on kinetics of trimethadione and its metabolite in rats.

The effects of acute (24-, 48- or 72-hr) water deprivation on the disposition kinetics of trimethadione (TMO) and its only metabolite, dimethadione (DMO), and on the microsomal hepatic drug-oxidizing enzyme activities were investigated in male rats. The DMO/TMO ratios in the serum at 2 hr after intravenous administration of 100 mg/kg TMO were significantly decreased in 48- and 72-hr water-deprived rats, but in 24-hr water-deprived rats, the DMO/TMO ratios were not changed as compared to controls and food restrictions. In the 48- and 72-hr water-deprived rats, contents of cytochrome p-450 and activities of aminopyrine N-demethylase were significantly decreased. On the other hand, activities of aniline hydroxylase in these rats were significantly increased as compared to controls and food restrictions. These results suggest that the effects of water deprivation on drug metabolism not only depend on the time of water deprivation but also vary with the indicator substrate.

Aminopyrine N-Demethylase↗

Localization of prostatic basic protein ("probasin") in the rat prostates by use of monoclonal antibody.

Isolated nuclei of the rat prostates contain a unique androgen-dependent basic protein, "probasin". Despite that it was hardly detectable in the cytosol centrifugally prepared from the prostates, immunofluorescent histological analysis of whole tissues using monoclonal antibody, which was raised against probasin purified from the nuclei, revealed that probasin was abundantly localized in the lumen and acinal regions of the epithelium, but hardly in the nuclei. Previous extraction of secretory fluid from the prostates caused about 60% decrease in the probasin content of isolated nuclei. These suggest that probasin was originally a secretory component in the prostates, being redistributed from the secretory fluid and granule into nuclei during fractionation of subcellular components.

Androgen-Binding Protein↗

The effect of indomethacin on hepatic drug-oxidizing capacity in the rat: trimethadione and antipyrine metabolism as an indicator.

In this study, trimethadione (TMO) and antipyrine were chosen as model drugs to investigate the extent of hepatic drug-oxidizing capacity. It was also studied whether pretreatment of rats with indomethacin affected the formation of antipyrine metabolite. Pretreatment with indomethacin in a dose of 5 mg/kg/d for 3 d did not change the serum half-life (T1/2), the total body clearance (CL), and the apparent volume of distribution (Vd) of TMO and antipyrine. However, in the rat treated with 8.5 mg/kg/d for 3 d of indomethacin, these parameters were significantly decreased as compared to controls except to Vd values in antipyrine kinetics in vivo. The contents of cytochrome P-450, and the activities of aminopyrine N-demethylase and aniline hydroxylase were not changed by 5 mg/kg/d for 3 d of indomethacin. However, in the rat treated with 8.5 mg/kg/d for 3 d of indomethacin, these enzyme activities were significantly decreased as compared to controls. The activities of heme oxygenase were significantly increased as compared to controls in the rat treated with 5 and 8.5 mg/kg/d for 3 d of indomethacin, in vitro. The excretions of 4-hydroxyantipyrine and 3-hydroxymethyl antipyrine were not changed in the rat treated with 8.5 mg/kg for 3 d of indomethacin as compared to controls, whereas the excretion of norantipyrine was significantly decreased. These results, together with the previous findings, indicate that indomethacin treatment inhibited N-demethylation pathway of TMO and antipyrine metabolism.

Animals↗