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Biomedical subjects

J Kuroki

Publications and source records attributed to J Kuroki.

30 records · Page 2Linked to original sources
PubMed1989

Cardiovascular effects of the new cardiotonic agent 1,2-dihydro-6-methyl-2-oxo-5-(imidazo[1,2-a]pyridin-6-yl)-3-pyridine carbonitrile hydrochloride monohydrate. 1st communication: studies on isolated guinea pig cardiac muscles.

Cardiotonic effects and the mechanism of action of 1,2-dihydro-6-methyl-2-oxo-5-(imidazo[1,2-a]pyridin-6-yl)-3-pyridine carbonitrile hydrochloride monohydrate (E-1020), a new cardiotonic agent, were investigated in vitro. E-1020 (10(-7)-10(-4) mol/l) produced a concentration-dependent positive inotropic effect in papillary muscles. E-1020 also caused an increase in contractile force in the right atria which was accompanied by small increases in spontaneous beating rate. The inotropic effect of E-1020 on papillary muscles was not altered by treatment with beta-adrenoceptor or histamine H2-receptor blockade, but was attenuated by the muscarinic agonist, carbachol. E-1020, like isoprenaline (isoproterenol, Iso), restored the contraction of papillary muscles which had been arrested in a high-potassium solution. The inotropic response of papillary muscles to Iso was potentiated by pretreatment with E-1020 at a minimally-effective inotropic concentration (3 x 10(-7) mol/l). E-1020 did not affect the activity of dog kidney Na+, K+-ATPase. On the other hand, the compound specifically inhibited the cyclic AMP-specific isoenzyme (fraction III) of phosphodiesterase and caused an elevation of cyclic AMP content in guinea pig hearts. These results indicate that E-1020 is a potent cardiotonic agent with a minor chronotropic effect and that its inotropic action is mainly mediated by the rise in cardiac cyclic AMP content due to the inhibition of cyclic AMP-specific phosphodiesterase.

Adrenergic beta-Antagonists↗
PubMed1985

Accumulation, excretion and effects on hepatic enzymes of polychlorinated quaterphenyl congeners in rats.

Six skeletal congeners of polychlorinated quaterphenyls (PCQs), namely polychlorinated o-quaterphenyl (2,2'-PCQ), 2,3'-diphenylbiphenyl (2,3'-PCQ), 2,4'-diphenylbiphenyl (2,4'-PCQ), m-quaterphenyl (3,3'-PCQ), 3,4'-diphenylbiphenyl (3,4'-PCQ) and p-quaterphenyl (4,4'-PCQ), were orally administered to Wistar rats at a dose of 10 mg/rat. On the 5th day after administration of PCQs, the rats were examined for accumulation of PCQ congeners, hepatic enzyme activities and organ weight changes. Accumulation of 3,3'-PCQ, 3,4'-PCQ and 4,4'-PCQ were 1.5-3.2% of dose in the liver, while those of 2,2'-PCQ, 2,3'-PCQ and 2,4'-PCQ were only 0.1 to 0.2%. The amount of 4,4'-PCQ accumulated in the mesenteric adipose tissue, 20 micrograms/rat, was much higher than those of other PCQ congeners. Large amounts of the PCQ congeners administered were excreted in the feces on the first day, accounting for 96 to 98% of dose for 2,2'-PCQ and 4,4'-PCQ, and 55 to 75% for the other PCQ congeners, and the daily excretions of PCQs after the second day were very small, less than 10% of the dose. Benzo [a] pyrene 3-hydroxylase activity was significantly depressed by the treatment with 3,3'-PCQ, 3,4'-PCQ and 4,4'-PCQ, contrasting to the toxic congeners of polychlorinated biphenyls and dibenzofurans which enhanced markedly this enzyme activity. DT-Diaphorase activity was also depressed by the treatment with 2,3'-PCQ, 2,4'-PCQ and 3,4'-PCQ. Significant atrophy of the thymus was observed by the treatment with 4,4'-PCQ.

Adipose Tissue↗
PubMed1985

Inductive effect on hepatic enzymes and toxicity of congeners of PCBs and PCDFs.

The present paper describes a marked induction of liver microsomal cytochrome P-450 and cytosolic DT-diaphorase to cause possible disorder of steroid homeostasis and promotion of carcinogenicity of 4-nitroquinoline N-oxide (4-NQO) in rats by pretreatment with 3,4,5,3',4'-pentachlorobiphenyl (PenCB) or 2,3,4,7,8-pentachlorodibenzofuran (PenCDF). The animals were sacrificed 5 days after the pretreatment. These induction experiments showed that 7 alpha-hydroxylation of both progesterone and testosterone in liver microsomes was selectively increased to a great extent, but hydroxylations at the 2 alpha-, 6 beta- and 16 alpha-positions were depressed, together with 5 alpha-reduction. From the same microsomes, three of the strongly induced P-450 isozymes, i.e., high- and low-spin P-448s and P-452, were purified. The last isozyme was most responsible for 7 alpha-hydroxylation of testosterone. The pretreatment, also increased activity of DT-diaphorase and reduction of 4-NQO about 10-fold in liver 9000g supernatants. This reduction of 4-NQO was solely catalyzed by DT-diaphorase and the only product was 4-hydroxylaminoquinoline N-oxide, a proximate carcinogen, indicating that the pretreatment strongly increased production of a proximate carcinogen from 4-NQO. Such an enhancement of the metabolic activation of 4-NQO by the pretreatment was also observed to some extent in the lung and the skin. Persistency of PenCB and PenCDF in the liver of rats was also discussed.

4-Nitroquinoline-1-oxide↗
PubMed1984

High accumulation of 2,3,4,7,8-pentachlorodibenzofuran to hepatic microsomes of rats.

The tissue and subcellular distributions of 14C-2,3,4,7,8-pentachlorodibenzofuran (PenCDF), one of the most important causal agents of yusho, were studied using rats. More than 60% of the radioactivity given orally was accumulated in the liver after 5 d and this high percentage persisted over a period of 3 weeks. Subcellular fractionation of the liver homogenate showed unusual separation by PenCDF-pretreatment, but the distribution of radioactivity was just parallel to those of cytochrome P-450 content and glucose-6-phosphatase (EC3.1.3.9) activity. Gas chromatographic analysis provided evidence that the extracts from the liver and its subcellular fractionations contained only unchanged PenCDF. Those results strongly suggest that PenCDF has some affinity to endoplasmic reticulum of rat liver.

Animals↗
PubMedDate not supplied

Quantitative reverse transcription-PCR-HPLC for nerve growth factor mRNA using a deletion RNA as an internal standard.

We have developed a convenient method for the routine measurement of the absolute amount of nerve growth factor (NGF) mRNA in tissue samples. The method consists of RNA extraction, amplification by reverse transcription-PCR and detection by high-performance liquid chromatography. The addition of a deletion mutant RNA to tissue samples as an internal standard enabled correction for RNA recovery during extraction, and the target mRNA and the internal standard were both amplified with the same PCR primers. The conditions were optimized so that the procedure was conducted in the region where the calibration curve was linear, thereby allowing high reproducibility and reliability. The method was applied to the measurement of NGF mRNA in tissues such as skin and skeletal muscle, where the levels are too low to be easily detected by Northern blotting analysis: skin, 14.1 +/- 4.6 fg/mg tissue and skeletal muscle, 11.0 +/- 2.2 fg/mg tissue (mean +/- SD, n = 10). The coefficient of variation of this method was less than 2.8%. This approach should also be applicable to the routine assay of the absolute amount of other mRNAs present at low levels in tissues.

Animals↗
PubMedDate not supplied

Relationship between the classification of vascular invasion severity and the prognosis of uterine endometrial cancer.

The objective of this research is whether the classification of vascular invasion severity can be used as a prognostic factor in cases of uterine endometrial cancer. Sixty-five patients with stage I to III uterine endometrial cancer were included in the study. All patients were seen between 1987 and 1997, and the types of their cancers were histologically confirmed. The degree of vascular invasion was classified according to three different systems: (1). positive or negative; (2). negative, mild, or severe; and (3). negative, mild, moderate, or severe. For each classification, the disease-free survival rate was calculated according to various pathologic factors using the Wilcoxon test; multivariate analyses were performed using the Cox proportional hazard model. Patients with severe vascular invasion showed a significantly lower disease-free survival rate than did patients with moderate or less severe invasion. In the multivariate analysis, severe vascular invasion was shown to be an independent prognostic factor indicating a high relative risk. We conclude that the severity of vascular invasion is an important histopathologic factor in determining the prognosis of uterine endometrial cancer. Vascular invasion classification systems employing three subjective or four objective categories may be more appropriate than a positive/negative classification system for judging the prognosis in cases of uterine endometrial cancer.

Adult↗