PubMed Health⌕ Search

Biomedical subjects

H Nakura

Publications and source records attributed to H Nakura.

At least 37 records · Page 2Linked to original sources
PubMed1997

Opposite effects of isoniazid and fasting on the expression of CYP2E1 protein and mRNA in house musk shrew (Suncus murinus).

The effects of isoniazid and fasting on hepatic CYP2E1 in the suncus were investigated. Aniline hydroxylation and N-nitrosodimethylamine demethylation, which are known to be catalyzed by CYP2E1, in liver microsomes were induced and suppressed by the treatment with isoniazid and the fasting, respectively. Immunoblot analysis indicated that CYP2E1 protein in liver microsomes from isoniazid-treated suncus was increased in contrast to the result with the fasting of the suncus. Northern blot analysis showed that the treatment of suncus with isoniazid increased the expression of CYP2E1 mRNA in livers although the fasting of the suncus significantly decreased CYP2E1 mRNA. These results suggest that the regulation of hepatic CYP2E1 in the suncus by treatment with isoniazid and fasting was different from that in rats.

Amino Acid Sequence↗
PubMed1997

Halothane inhalation inhibits the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits.

We demonstrated the inhibitory effect of halothane (HAL) inhalation on the metabolism of chlorzoxazone (CZZ), a substrate for CYP2E1, in a bolus and a continuous injection study in rabbits receiving artificial ventilation. In a bolus injection study, the inhalation of 1.0% HAL significantly increased the half-life and the area under the curve and decreased the clearance of CZZ compared with those variables in midazolam administration. In a continuous injection study, the effect of various concentrations of inhaled HAL on plasma CZZ concentration at steady state was compared. Systolic and diastolic arterial blood pressure were decreased dose-dependently after 0.5%, 1.0%, or 2.0% HAL was inhaled. Although the plasma concentration of CZZ was increased 2.5-fold after 3 h of HAL inhalation, there was no significant difference in mean plasma concentrations among the groups treated with 0.5%, 1.0%, or 2.0% HAL. In contrast, the plasma concentration of lidocaine, a substrate for CYP3A, remained unchanged after 1.0% HAL was inhaled. These results suggest that general anesthesia obtained with HAL inhalation will affect the metabolism of drugs administered concomitantly when the drug is a substrate for CYP2E1.

Anesthesia, Inhalation↗
PubMed1997

Enhancement of the affinity of androgen receptor in the adrenal medulla of spontaneously hypertensive rats.

We investigated the alteration of tyrosine hydroxylase (TH) mRNA expression and androgen receptor in the adrenal medulla of spontaneously hypertensive rats (SHR). The TH mRNA expression in the adrenal medulla of SHR was higher than that of Wistar Kyoto rats (WKY). The testosterone increased the TH mRNA expression of SHR, but not WKY. The affinity of androgen receptor in the adrenal medulla of SHR was higher than that of WKY; however, the number of androgen receptor was not different. These results suggested that the increased binding affinity of the androgen receptor of SHR may be related to TH gene transcription in the adrenal medulla.

Adrenal Medulla↗
PubMed1996

The activity of dihydropyrimidine dehydrogenase from rat liver was not affected by any of five 5-hydroxytryptamine antagonists.

We estimate the influence of five 5-hydroxytryptamine receptor (5-HT3) antagonists on the activity of dihydropyrimidine dehydrogenase (DPDase), the rate-limiting enzyme in 5-fluorouracil (5FU) metabolism. The activity of DPDase from the rat liver was compared in the cytosol mixture of 5FU incubated with or without each of five 5-HT3 antagonists. DPDase activity was not altered in the presence of any 5-HT3 antagonist studied here. It may be inferred from these results that the any 5-HT3 receptor antagonist examined in this study has little or no effect on fluorouracil catabolism.

Animals↗
PubMed1996

Preliminary examination of the influence of incubation time or cytosolic protein concentration on dihydropyrimidine dehydrogenase activity.

We examined the influence of incubation time or cytosolic protein concentration on the metabolite production of 5-fluorouracil (5FU). Although the activity of dihydropyrimidine dehydrogenase (DPDase) from rat liver is considered to be retained for up to 60 min, the production rate of 5FU metabolites was reduced, probably due to depletion of the substrate in 40 mumol/l and lower concentration of 5FU. Since the ratio of the metabolite production rate to the cytosolic protein became smaller in higher concentrations of cytosolic protein, the DPDase activity should be compared in the same concentration of cytosolic protein. The production rate of 5FU metabolites was considered to be linear up to 40 mumol/l 5FU incubated with 500 micrograms cytosolic protein. The rate of the metabolite production calculated by one-point sampling significantly correlated with the enzyme activity by the multi-point sampling method. Minimizing sampling points to determine the DPDase activity would save time and expense.

Animals↗
PubMed1996

A cardiotonic steroid bufalin-induced differentiation of THP-1 cells. Involvement of Na+, K(+)-ATPase inhibition in the early changes in proto-oncogene expression.

Human monocytic leukemia THP-1 cells were induced to differentiate into macrophage-like cells by treatment with cardiotonic steroid bufalin, which was previously shown to interact with the Na+, K+-ATPase with similar kinetics to ouabain, a specific inhibitor of the enzyme. This induction of differentiation was characterized by loss of proliferation, cell adherence, increased ability to reduce Nitro Blue tetrazolium (NBT), and increased expression of interleukin 1 beta (IL-1 beta). During this process, bufalin downregulated c-myb and c-myc expressions and induced c-fos and Egr-1 transcripts. Ouabain also caused similar changes in proto- oncogene expression and induced phenotypic markers of differentiated cells at concentrations comparable to bufalin. The 12-O-tetradecanoyl phorbol-13-acetate resistant THP-1 cell variant, which was unresponsive to this agent as to growth inhibition and proto-oncogene expression, responded to bufalin. The finding that protein kinase inhibitor H7 failed to bufalin-mediated c-fos induction further supports the theory that the signal transduction machinery caused by bufalin is separable from the phorbol ester. The cytotoxic effect of high doses of bufalin apparently disappeared in the medium where Na+ was replaced with choline ions. Furthermore, bufalin failed to induce c-fos expression and to downregulate c-myb transcripts in the low-Na+ medium. These findings indicate that an increased intracellular Na+ concentration resulting from the Na+, K(+)-ATPase inhibition possibly triggers the change in proto-oncogene expression evoked by bufalin.

Bufanolides↗
PubMed1996

Alteration of c-fos gene methylation in human gliomas.

In an attempt to find a common DNA alteration occurring in human glioma, we examined DNA methylation in 34 gliomas of various pathological grades and compared them with those in normal cerebral subcortex DNA. The total methylated cytosine levels in the genome did not differ appreciably between the tumors and the normal tissues; however, the degree of DNA methylation in several proto-oncogenes and suppressor oncogenes showed some alterations. Among them, the c-fos gene demonstrated deviation from that of normal tissues in all cases examined, suggesting that the alteration of c-fos gene methylation plays a role in the early steps of human glioma development.

Adult↗
PubMed1996

Elevated tyrosine hydroxylase mRNA levels in medulla oblongata of spontaneously hypertensive rats.

The present study has investigated the expression of tyrosine hydroxylase (TH) mRNA and its activity in medulla oblongata of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). The TH mRNA levels were determined by Northern blot and dot blot analyses. The TH activity and the expression of TH mRNA in medulla oblongata of SHR were significantly higher than those of WKY. These results suggest that the hypertension of SHR may be related to the high activity of TH due to the high level of TH mRNA which increases norepinephrine levels in the medulla oblongata.

Animals↗
PubMed1995

Evidence for the lack of hepatic N-acetyltransferase in suncus (Suncus murinus).

The abilities of liver cytosol fractions from the suncus and Sprague-Dawley (SD) rats to N-acetylate aniline, p-aminobenzoic acid, p-aminosalicylic acid and 2-aminofluorene (AF) were compared. The cytosol from rats N-acetylated these substrates at efficient rates, whereas the cytosol from the suncus did not N-acetylate these substrates at detectable rates. When AF was given to the suncus, 2-acetylaminofluorene (AAF), a metabolite of AF formed by N-acetyltransferase (NAT), was not detectable in serum, whereas the metabolite was seen clearly in rats. Northern blot and Southern blot analyses, using cDNAs coding for human NATs as probes, indicated that not only the transcripts but also the genes of the enzymes were undetectable in suncus. These results suggest that the suncus is among the few species known to lack NATs.

2-Acetylaminofluorene↗
PubMed1995

Effects of submaxillariectomy on ovarian androgen and estrogen production in adult female rats.

Submaxillariectomy causes an increase in uterine weight in adult female rats. This increase is due to the elevation of the plasma 17 beta-estradiol (E2) level which is brought on by enhancement of ovarian E2 production. Furthermore, enhancement of ovarian E2 production is due to the enhancement of testosterone and androstenedione production which are the precursors of ovarian E2. However, submaxillariectomy did not affect ovarian progesterone and 17 alpha-hydroxyprogesterone levels. These findings suggest that the submaxillary gland may inhibit the production of ovarian E2 mainly because of the inhibition of ovarian androgen production. Thus the submaxillary gland may play a physiological role in female reproductive systems caused by the change in ovarian steroidogenesis.

17-alpha-Hydroxyprogesterone↗
PubMed1995

Influence of androgen on tyrosine hydroxylase mRNA in adrenal medulla of spontaneously hypertensive rats.

We investigated the effects of castration and testosterone propionate on tyrosine hydroxylase mRNA, its activity, and catecholamine synthesis in the adrenal medulla of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Four-week-old male rats were castrated. Testosterone propionate (500 micrograms per rat) was administered subcutaneously twice a week to castrated rats (between 14 and 25 weeks of age). Systolic pressure was measured at the age of 25 weeks, and rats were decapitated. The systolic pressure of castrated SHR was significantly lower than that of control and testosterone-replaced SHR. Epinephrine and norepinephrine levels, tyrosine hydroxylase activity, and tyrosine hydroxylase mRNA in the adrenal medulla of castrated SHR were significantly lower than in control and testosterone-replaced SHR. Systolic pressure and epinephrine and norepinephrine levels, tyrosine hydroxylase activity, and tyrosine hydroxylase mRNA levels in the adrenal medulla of WKY showed no significant differences among the control, castrated, and testosterone-replaced groups. These results suggest that androgens contribute to the development and maintenance of hypertension in SHR via sustained enhancement of tyrosine hydroxylase synthesis in the adrenal medulla, leading to increased epinephrine and norepinephrine levels.

Actins↗
PubMed1994

Activities of drug-metabolizing enzymes in the liver of Suncus murinus: possible lack of N-acetyltransferase activity in liver cytosol.

The amounts of several drug-metabolizing enzymes in livers of Suncus murinus (suncus) were studied in comparison with rats. The content of cytochrome P450 in suncus was less than one third that seen in rats. Activities of glutathione S-transferase, UDP-glucuronyltransferase and arylhydroxycarbon hydroxylase in suncus were less than half those in rats. Activity of flavin-containing monooxygenase in suncus was 71% that of rats. Interestingly, N-acetyltransferase (NAT) activity in suncus liver cytosols was not detectable: no detectable activities were seen with aniline, p-aminobenzoic acid and p-amino-salicylic acid as substrates. We propose that suncus is a unique animal possibly lacking NAT in liver cytosol.

Animals↗
PubMed1993

Multifunctional effects of anticomplementary agent K-76 on carrageenan-induced colitis in the rabbit.

In this study the effect of K-76, a sesquiterpene compound with anticomplementary activity isolated from a fungus culture, on carrageenan-induced colitis was studied from biochemical, histological and immunohistopathological aspects. K-76 suppressed epithelial cell loss, crypt abscess formation, inflammatory cell infiltration, mucosal atrophy, and ulceration. Immunohistochemical examination of the colonic mucosa showed that the number of IgG- and IgM-positive plasma cells and the staining intensity for IgG and C3 were increased in carrageenan-induced colitis, but these changes were inhibited by K-76. Besides, serum mucoprotein concentrations and CH50 levels were lower in the animals treated with carrageenan alone. K-76 exerted multifunctional activity, although its mechanisms of action remain obscure.

Animals↗
PubMed1992

Decrease in the content of cytochrome P450IIE by fasting in liver microsomes of house musk shrew (Suncus murinus).

The effects of fasting on hepatic cytochrome P450 in the mature male house musk shrew, Suncus murinus (suncus), were studied by Western blot analyses and enzyme assays. The content of P450IIE protein was decreased, by fasting, to 24% of the control level in contrast to the results with rats, in which P450IIE protein was increased to 172% by fasting. These changes reflected on catalytic activities, such as aniline hydroxylase and N-nitrosodimethylamine demethylase activities, which were decreased to about 45% and 28%, respectively, of the control levels by fasting, while in fasting rats, the catalytic activities of these enzymes were 2-3-fold higher than in controls.

Aniline Hydroxylase↗
PubMed1991

Formation of an antibacterial metabolite from a new macrolide compound 23-O-benzyl-5-mycaminosyl-tylonolide (TMC-101), by a hepatic microsomal drug-metabolizing enzyme system.

Upon incubation of 23-O-benzyl-5-mycaminosyl-tylonolide (TMC-101) with liver microsomes in the presence of an nicotinamide adenine dinucleotide phosphate-generating system, at least four metabolites were formed: two of them were also formed by an enzyme(s) in rat serum. One of the metabolites formed by liver microsomes possessed antibacterial activity comparable to TMC-101 as examined by bioautography using Micrococcus luteus ATCC 9341 as a tester strain. Incubation of TMC-101 with rat serum degraded most of the parent compound and did not form the active metabolite. The capacity of liver microsomes to produce the active metabolite was increased by pretreatment of rats with 3-methylcholanthrene, phenobarbital and polychlorinated biphenyl. The metabolite with the antibacterial activity was estimated not to be formed by the N-demethylation of TMC-101, and was chemically unstable.

Animals↗
PubMed1987

Peculiar pattern of glial fibrillary acidic protein production in extracranial metastatic tumor cells of malignant astrocytoma.

An 83-year-old woman suffered from malignant astrocytoma originating in the temporal lobe. Autopsy revealed its extracranial metastasis to the liver, lung and bone marrow. The tumor tissue at the primary site was composed of plump, process-forming cells and small cells with scanty cytoplasm, and showed dural invasion. In the metastatic areas, most of the tumor cells were small cells, although proliferation of the plump cells in contact with perivascular connective tissue was marked, particularly in the liver. These plump cells were positively stained with antiserum to glial fibrillary acidic protein (GFAP), showing that the collagenous tissue was able to induce increased production of GFAP by the glial tumor cells.

Aged↗