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Biomedical subjects

N Miyata

Publications and source records attributed to N Miyata.

At least 127 records · Page 7Linked to original sources
PubMed1992

Effects of CD-349 and 8-BrcGMP on isoproterenol-induced relaxation in rabbit aorta precontracted with endothelin-1.

We investigated the effects of CD-349, a dihydropyridine derivative, on isoproterenol (Iso)-induced relaxation in rabbit aorta precontracted with endothelin-1 (ET-1). The Iso (10(-8)-10(-5) M)-induced relaxation responses in rabbit aorta precontracted with 1-2 x 10(-7) M ET-1 were augmented by pretreatment with CD-349 (10(-9)-10(-5) M) in a concentration-dependent manner. The effects of CD-349 on Iso-induced relaxation of the aortic strips precontracted with ET-1 were inhibited by treatment with methylene blue (10(-5) M) and oxyhemoglobin (10(-5) M), whereas they were augmented by treatment with N omega-nitro-L-arginine (10(-4) M). The Iso-induced relaxation responses were also augmented by pretreatment with 8-Br-guanosine 3',5'-cyclic monophosphate (cGMP) (3 x 10(-6)-3 x 10(-4) M) in a concentration-dependent manner. However, nifedipine (10(-5) M) and nicardipine (10(-5) M) had no effect on Iso-induced relaxation responses of the aortic strips precontracted with 10(-7) M ET-1. CD-349 also augmented forskolin (10(-8)-10(-5) M)-induced relaxation responses of rabbit aorta in a concentration-dependent manner. CD-349 (10(-7)-10(-5) M) increased the levels of cGMP but not of adenosine 3',5'-cyclic monophosphate (cAMP) in a concentration-dependent manner in rabbit aorta without endothelium. Both CD-349 (10(-5) M) and 8-BrcGMP (3 x 10(-5) M) augmented the Iso-induced elevations of cAMP in rabbit aorta without endothelium. These results indicate that CD-349 and 8-BrcGMP can augment Iso-induced relaxation responses by enhancing the accumulation of cAMP.

Animals↗
PubMed1992

Electrical stimulation-evoked release of endogenous taurine from slices of the hippocampus, cerebral cortex and cerebellum of the rat.

Release of endogenous taurine by electrical stimulation of slices of the hippocampus, cerebral cortex, cerebellum and medulla oblongata of the rat was studied and compared with that of alanine and/or gamma-aminobutyric acid (GABA). Electrical stimulation caused a calcium-dependent release of taurine from slices of the hippocampus, cerebral cortex and cerebellum but not from slices of the medulla oblongata. The stimulus-evoked release of taurine in the hippocampus was rapid in onset and declined to baseline fast, which was essentially similar to the time course pattern of the stimulus-evoked release of GABA. In addition, there were distinct regional differences in the relative amounts of taurine released. Electrical stimulation did not release alanine from any regions examined. These results support the hypothesis that taurine plays a neurotransmitter role in the hippocampus, cerebral cortex and cerebellum of the rat.

Alanine↗
PubMed1992

The metabolism of 1,6-dinitropyrene in rat hepatocytes.

This paper reports investigations using hepatocytes to study the metabolism and DNA binding of the environmental contaminant, 1,6-dinitropyrene. Since 1,6-dinitropyrene is not believed to be mutagenic per se, metabolites were synthesized and the metabolism of 1,6-dinitropyrene was subsequently studied in rat hepatocytes. The mode of activation of dinitropyrenes is reduction of one of the nitro groups. Nitroreduction has been shown previously to be oxygen sensitive and therefore the effect of oxygen on the metabolic pattern and DNA binding was investigated by comparing results from aerobic and anaerobic conditions. The binding of [14C]1,6-dinitropyrene equivalents to rat hepatocyte DNA was increased by 15% in the presence of oxygen. Although there was little difference in the rate of 1,6-dinitropyrene metabolism, with or without O2, there was a difference in the metabolic pattern. Under anaerobic conditions there was an increase in the level of the terminal reduction product 1-amino-6-nitropyrene.

Animals↗
PubMed1991

Enhanced contractile effect of phorbol dibutyrate in portal veins from hypertensive rats.

The effects of phorbol 12,13-dibutyrate (PDBu) on portal veins from hypertensive (SHRSP0 and normotensive (WKY) rats were examined. PDBu contracted the strips from SHRSP and WKY in a concentration-dependent manner. However, both twitch contraction and tonic contraction of strips in response to PDBu were enhanced in SHRSP. Treatment with staurosporine reduced contractile response to PDBu in strips from SHRSP. It appears that the activity of protein kinase C in vascular smooth muscle is increased in SHRSP.

Alkaloids↗
PubMed1991

Changes in responsiveness of the canine basilar artery to endothelin-1 after subarachnoid hemorrhage.

The effect of endothelin-1 (ET-1) on the basilar arteries from control and subarachnoid hemorrhage (SAH) dogs were examined. The maximal contraction of the basilar artery in response to ET-1 was markedly decreased in the SAH group. Treatment with 10(-8)M phorbol 12-myristate 13-acetate (PMA) reduced the contractile responses to ET-1 in the basilar arteries from control dogs. ET-1-induced contractions of the basilar arteries from control dogs were similar to those in strips from SAH dogs by the treatment with 10(-8) M PMA. Ca(2+)-induced contraction of the basilar arteries which were depolarized with isotonic K+ (64 mM) were significantly attenuated in SAH dogs. Treatment with PMA also reduced the contractile responses to Ca2+ in the basilar arteries from control dogs. These results indicate that decreased contractile responses of the basilar arteries to ET-1 and Ca2+ in the SAH group may be related to changes in the activity of the protein kinase C in vascular smooth muscle.

Animals↗
PubMed1991

Clastogenicity of 1-nitropyrene, dinitropyrenes, fluorene and mononitrofluorenes in cultured Chinese hamster cells.

The chromosomal aberration test using a Chinese hamster lung cell line (CHL) was carried out on 1-nitropyrene (NP), 3 dinitropyrenes (DNPs), fluorene and 4 mononitrofluorenes with and without metabolic activation (rat S9 mix). The 3 DNPs (1,3-, 1,6- and 1,8-DNP) induced chromosomal aberrations in the absence of S9 mix. The frequencies of cells with aberrations after treatment for 48 h were 43% at 2 micrograms/ml of 1,3-DNP, 55% at 0.1 microgram/ml of 1,6-DNP and 45% at 0.025 microgram/ml of 1,8-DNP, indicating the order of clastogenic potency as 1,8- greater than 1,6- greater than 1,3-DNP. On the other hand, 1-NP, which is known to be a direct-acting mutagen in bacteria, was negative in the chromosomal aberration test without S9 mix, but clearly positive with S9 mix. This effect was dependent on the concentration of the S9 fraction in the reaction mixture. High-pressure liquid chromatography analysis showed that 1-NP was converted by S9 mix to several metabolites, including 1-aminopyrene (AP). The clastogenic activity of 1-AP, however, was equivocal without S9 mix, suggesting that active clastogens other than 1-AP exist. Fluorene induced chromosomal aberrations only in the presence of S9 mix (61.8% at 25 micrograms/ml). 1-, 2-, 3- and 4-nitrofluorene (NF) were more clastogenic in the presence of S9 mix than in the absence of S9 mix, suggesting that NFs were converted to more active clastogens by S9 mix.

Animals↗
PubMed1991

Detection of 3,6-dinitrobenzo[a]pyrene in airborne particulates.

3,6-Dinitrobenzo[a]pyrene, a new mutagen, was detected in airborne particulates collected in Santiago (Chile). The quantity of the compound in the airborne particulates was very small, accounting for 0.01 micrograms/g of total particulates (0.002 ng/m3 of air) at the lowest concentration. It was found that 3,6-dinitrobenzo[a]pyrene is readily decomposed by UV irradiation at 312 nm. The decomposed product was identified as 3-nitrobenzo[a]pyrene-6-quinone by means of mass spectrometry and proton nuclear magnetic resonance analysis. The mutagenicity of 3,6-dinitrobenzo[a]pyrene was 137,000 revertants/nmole for Salmonella typhimurium strain TA98, less than that for strain TA98/1,8-DNP6, an acetyltransferase-deficient mutant, and more than that for strain YG1024, an acetyltransferase-rich mutant.

Air Pollutants↗
PubMed1991

DNA damage in forestomach epithelium from male F344 rats following oral administration of tert-butylquinone, one of the forestomach metabolites of 3-BHA.

DNA damage in the forestomach epithelium of male F344 rats was tested by alkaline elution assay following oral administration of 3-tert-butyl-4-hydroxyanisole (3-BHA) and its free metabolites. Although 1% 3-BHA and 0.001% tert-butylhydroquinone (BHQ) caused no detectable DNA damage, a tert-butylquinone (BQ) treated group showed a significantly higher elution rate than the corn oil and 3-BHA group. Dose-dependent induction of DNA damage in forestomach epithelium by 3-BHA metabolites was compared. BQ showed DNA damaging activity from 0.0001% (1 microgram/ml). On the other hand, BHQ showed the activity at greater than 100 times higher concentration than that of BQ. Six other quinones related to the BQ have been synthesized and examined in vivo for their activity in single strand breaks in forestomach epithelium DNA. The order of the DNA damage was not always correlated with the order of the first reduction potentials of the quinones. 2-Benzylthio-5-tert-butyl-p-benzoquinone (BQSBn-2), 2-phenyl-1,4-benzoquinone and 2,5-di-tert-butyl-p-benzoquinone had higher DNA damaging activity than BQ. The effects of ethylacrylate (EA) pretreatment on the DNA damage by BQ and BQSBn-2 were compared. The DNA damage by BQ was decreased by increasing the EA concentrations. On the other hand, BQSBn-2 had a DNA damaging activity following the EA pretreatment. In order to examine whether 3-BHA is metabolized in forestomach, 3-BHA and BQ levels in the mucosa of forestomach were measured by HPLC with an electrochemical detector. The concentrations of BQ in mucosa correlated with the 3-BHA dose levels from 0.01% to 0.1% 3-BHA. The concentration of BQ in mucosa was approximately 1/4000 of the concentration of 3-BHA in mucosa at the dose level of 1% 3-BHA. The present results indicate that BQ and its thiol conjugates are the active metabolites from 3-BHA in forestomach and may play an important role in inducing carcinogenicity of 3-BHA in F344 rats.

Acrylates↗
PubMed1991

Protein kinase C-mediated contraction in rabbit aorta is inhibited by CD-349, a dihydropyridine derivative.

We investigated the effects of nitroglycerin (NTG), atrial natriuretic peptide (ANP), and CD-349 on phorbol dibutyrate (PDBu)-induced contraction in rabbit aorta. In the presence of endothelium, both NTG (10(-8)-10(-5) M) and ANP (10(-10)-10(-7) M) inhibited the PDBu-induced contraction in a concentration-dependent manner. CD-349 (10(-8)-10(-5) M) also inhibited the PDBu-induced contraction in a concentration-dependent manner. This inhibitory effect of CD-349 was independent of the existence of endothelium. Inhibitory effects of both NTG and CD-349 but not ANP were antagonized by treatment with methylene blue. However, nifedipine (10(-5) M), nicardipine (10(-5) M), and diltiazem (10(-5) M) had little or no effect on PDBu-induced contraction. Furthermore, NTG, ANP, and CD-349 inhibited endothelin-induced contraction, which may be mediated through activation of protein kinase C. These results indicate that PDBu-induced and endothelin-induced contractions in rabbit aorta are inhibited by agents known to elevate vascular cyclic GMP content.

Animals↗
PubMed1991

Effects of CD-349, a dihydropyridine derivative, on contraction induced by vasoactive agents in canine basilar artery after subarachnoid hemorrhage.

We investigated the effects of CD-349, a dihydropyridine derivative, on contraction induced by vasoactive agents in canine basilar artery after subarachnoid hemorrhage (SAH). Ca(2+)-induced contraction of basilar arterial strips preincubated with serotonin (5-HT, 3x10(-6)M) was potentiated in strips from SAH. However, Ca(2+)-induced contraction of arterial strips which were depolarized with isotonic K+ (64mM) was attenuated in strips from SAH. These Ca(2+)-induced contractions of the basilar arteries preincubated with 5-HT and K+ from both control and SAH dogs were significantly inhibited by CD-349 and nicardipine, both dihydropyridine derivatives. 5-HT contracted the basilar arterial strips in a concentration-dependent manner; however, the maximal contraction of the basilar arterial strips to 5-HT was enhanced in SAH. Endothelium-dependent relaxation in response to substance-P was attenuated in SAH when compared to that in control dogs. Early treatment with CD-349 (1 or 2mg/kg/day, i.m.) for 1 week reversed not only the enhanced contraction of the basilar artery in response to 5-HT but also the impairment of endothelium-dependent relaxation in response to substance-P in SAH. It is expected that CD-349 may be a useful agent for the treatment of cerebrovascular diseases such as SAH.

Animals↗
PubMed1991

[Clinical evaluation of modifications of the SRK formula].

It was previously reported that the axial length and the refractive error were analyzed in selecting intraocular lens powers which were calculated by the SRK formula. Moreover, the predicted postoperative refraction was compared with the actual postoperative refraction. Two modifications of the SRK formula were derived from these relationships as follows; Modified SRK formula 1: R = 0.98 (P-I)-0.16L + 4.48, Modified SRK formula 2: R = 0.82 (P-I)-0.21L + 5.39. The modifications of the SRK formula were evaluated in 200 other eyes after posterior chamber lens implantation. As a result, the average refractive error was + 0.397 +/- 0.585D by the standard SRK formula, but it decreased by an average numbers of + 0.037 +/- 0.557D and + 0.047 +/- 0.547D respectively by modified SRK formulae 1 and 2. While the incidence of deviation within +/- 1.0D was 87.0% for the standard SRK formula, it was 94. 5% for both modified SRK formulas. The refractive errors, moreover, were less dependent on the axial length with both modified SRK formulae. The predicted postoperative refraction was more accurate by modified SRK formulae, especially between emmetropia and myopia up to 0.5 diopters.

Adult↗
PubMed1990

[Primary leiomyosarcoma of the pancreas].

Primary leiomyosarcoma of the pancreas is a very rare malignant tumor, with only 12 cases reported. A case of primary pancreatic leiomyosarcoma in a 55 year-old female with diabetes mellitus is described. US and CT demonstrated tumor masses in the head and tail of the pancreas. By angiography, abundant tumor vessels corresponding to the pancreatic tumor masses were revealed in the pancreas. The patient underwent surgical resection of the tumor in the tail of the pancreas, and then, microscopically it was diagnosed as leiomyosarcoma. The tumor in the head of the pancreas was not resected on account of the presence of diabetes mellitus and the possibility of poor prognosis. Macroscopically, it seemed to be the same as the tumor in the pancreatic tail. By operative findings, there was invasion from the pancreatic head to the duodenum and there was nothing to justify suspicion of the extra-ductal growing type of primary leiomyosarcoma of the duodenum. There were no metastases noted at the time.

Diagnosis, Differential↗
PubMed1990

[Effects of radiation on the human renal cell carcinoma transplantable to the nude mice].

Effects of irradiation were studied using human renal cell carcinoma (AM-RC-3) implanted subcutaneously in nude mice. Tumors were irradiated locally with 60Co gamma-ray as a single dose of 5, 10, 15 and 20 Gy, then the tumor volume was measured periodically. Efficacy of irradiation was determined using Battelle Columbus Standard. The data obtained are as follows: 1) Tumor growth in every irradiated groups was delayed significantly (p less than 0.01) as compared with control group. 2) There was a significant difference in tumor growth between 10 and 15 Gy group, but no significant difference among any other groups. 3) The ratio of RV (relative mean tumor volume) of irradiated to that of unirradiated group (T RV/C RV) obtained from the tumor growth curve was 42% or less in all groups except in the 5 Gy group. A dose more than 15 Gy was particularly effective and the tumor mass was reduced to a T RV/C RV of 5.3% and 5.2% by 15 and 20 Gy, respectively.

Animals↗
PubMed1990

[Radiosensitization of Lewis lung tumor by perfluorochemical emulsion comparison between single and fractionated irradiation].

Previously perfluorochemical emulsion (FDAS) was shown to enhance tumor growth delay, when applied together with breathing carbogen (95% O2+5% CO2) before and during irradiation. In the present paper, radiosensitizing effects of FDAS in tumor bearing mice were examined on a single (10 Gy) and fractionated irradiation (4 Gy, 4 times) and on the dose of administration. The results were as follows; 1) All groups of single irradiation with injection of FDAS 10-40 ml/kg could enhance the radiosensitivity of LLC bearing mice. 2) Tumor growth of even fractionated irradiation groups was significantly delayed by administration of FDAS more than 5 ml/kg. 3) In case of fractionated irradiation, the minimum effective dose of FDAS was estimated to be 5 ml/kg per irradiation, which coincided with that of single irradiation. It was concluded that FDAS in fractionated irradiation could increase the radiosensitivity in tumor bearing mice with more than 5 ml/kg injection. Therefore, FDAS may be useful as a radiosensitizer for clinical application in fractionated radiation therapy. Furthermore, since irradiation doses of single (10 Gy) and even fractionated irradiation (4 Gy X 4 times) were approximately iso effective dose, it may be considered that administration of more than 5 ml/kg (minimum effective dose) FDAS at each irradiation gave similar radiosensitizing effects to both single and fractionated irradiation.

Animals↗
PubMed1990

Mutagenicity of 3-tert-butyl-4-hydroxyanisole (BHA) and its metabolites in short-term tests in vitro.

The mutagenicity of 3-tert-butyl-4-hydroxyanisole (BHA) and its metabolites was investigated in the reverse mutation assay using S. typhimurium strains and the chromosomal aberration test in vitro using a Chinese hamster fibroblast cell line, CHL. BHA, tert-butylhydroquinone (BHQ), tert-butylquinone (BQ) and BHA dimer (diBHA) did not show any mutagenic potential with and without S9 mix in the reverse mutation assay. In addition to the above 4 chemicals, 3-tert-butyl-4,5-dihydroxyanisole (BHA-OH), 3-tert-butylanisole-4,5-quinone (BHA-o-Q), and tert-butylquinone oxide (BQO) were tested in the chromosomal aberration test. BHA, BHQ and BQ induced chromosomal aberrations only in the presence of S9 mix, while BHA-OH, BHA-o-Q and BQO induced chromosomal aberrations only without S9 mix. DiBHA, however, showed no clastogenic potential with and without S9 mix. The present findings suggest that BHA-OH, BHA-o-Q or BQO may contribute to the clastogenicity of BHA in the presence of S9 mix.

Animals↗
PubMed1990

Effects of endothelin on the portal vein from spontaneously hypertensive and Wistar Kyoto rats.

The effects of endothelin, a novel potent vasoconstrictor peptide, on isolated portal veins were examined in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Endothelin contarcted the portal vein from SHR and WKY, in a concentration-dependent manner. However, both twitch contraction and tonic contraction of portal veins in response to endothelin were significantly enhanced in SHR. In contrast to the effects of endothelin, twitch contractile responses to Bay K 8644 were not significantly different between vessels from SHR and WKY. These results indicate that endothelin is a potent vasoconstrictor peptide in the portal vein, and that the increased sensitivity in SHR may be due to an increase in the activity of voltage-dependent Ca2+ channels which is modulated by endothelin, but not to an increase in the activity of voltage-dependent Ca2+ channels which can be stimulated by Bay K 8644.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗