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Biomedical subjects

N Miyata

Publications and source records attributed to N Miyata.

At least 145 records · Page 8Linked to original sources
PubMed1990

Mechanisms of inhibitory effects of CD-349 and K(+)-channel activators on noradrenaline-induced contraction and changes in levels of cyclic GMP in rat aorta.

1. CD-349 inhibited the noradrenaline (NA)-induced contraction of aortas in Ca2(+)-free medium. 2. This inhibitory effect was completely antagonized by pretreatment with methylene blue. 3. Nicorandil and cromakalim also inhibited the NA-induced contraction of aortas in Ca2(+)-free medium. 4. The inhibitory effects of nicorandil, but not those of cromakalim, were partially antagonized by pretreatment with methylene blue. 5. The methylene blue-insensitive effects of nicorandil and the effects of cromakalim were antagonized by pretreatment with glibenclamide. 6. These results indicate that the inhibitory effect of CD-349 and nicorandil on NA-induced contraction of aortic strips in Ca2(+)-free medium is mediated through increased levels of cyclic GMP. 7. Furthermore, the inhibitory effect of cromakalim and the partial inhibitory mechanism of nicorandil may be mediated through glibenclamide-sensitive K(+)-channels.

Animals↗
PubMed1990

DNA breaks and repair in the mouse leukemia L1210 cells exposed to three different types of interstrand DNA cross-linkers.

DNA breaks and repair in mouse leukemia L1210 cells treated with 3 different types of cross-linkers, mitomycin C (MMC), 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitroso ure a hydrochloride (ACNU) and SN-07 (a macromolecular antibiotic), were studied. Measured in D37 values, MMC gave the highest number of cross-links per lethal 'hit' directly after the 1-h treatment in the alkaline elution assay, followed by ACNU and SN-07. A good dose-response increase in induced interstrand DNA cross-linking frequency was observed in cells treated with 2.5-10 micrograms/ml MMC and with 10-100 micrograms/ml ACNU for 1 h with and without 24-h post-incubation. After 6-h post-incubation, the highest frequency of cross-linking was observed in cells treated with 2.5 micrograms/ml MMC and 30 micrograms/ml ACNU, while cross-link production continued in the cells treated with SN-07 for 12-h post-incubation. No significant increase in DNA breaks was observed in cells treated with MMC throughout 24-h post-incubation. The highest frequency of single-strand DNA breaks in cells treated with ACNU was observed immediately after the treatment and they disappeared after 6-h post-incubation. After 24-h post-incubation, a marked enhancement of the DNA breaks was observed in cells treated with SN-07 and the cells contained double-strand DNA breaks also. RNA synthesis was not affected in the cells treated with 10 micrograms/ml MMC and slightly inhibited to 70% of control in those treated with 100 micrograms/ml ACNU, while DNA synthesis in both cells was significantly inhibited after 24-h post-incubation. By contrast, both RNA and DNA synthesis were completely inhibited in cells treated with 8.0 micrograms/ml SN-07.

Animals↗
PubMed1990

Initiating activity of 3-tert-butyl-4-hydroxyanisole (3-BHA) and its metabolites in two-stage transformation of BALB/3T3 cells.

3-tert-Butyl-4-hydroxyanisole (3-BHA) and its metabolites, tert-butyl-1,4-benzoquinone (BQ) and 3-tert-butyl-5-methoxy-1,2-benzoquinone (BHAoQ), were tested for initiating activity in a two-stage transformation assay using BALB/3T3 cells. Cells were treated first with a test chemical and then with the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). In the absence of TPA the test chemicals did not induce cell transformation. With the promoting treatment, 3-BHA and BQ induced dose-dependent cell transformation. There were statistically significant increases in the proportion of dishes with transformed foci in the cultures treated with 30 micrograms/ml 3-BHA plus TPA (15 of 24 dishes, P less than 0.005) and with 0.4 microgram/ml BQ plus TPA (12 of 22 dishes, P less than 0.02) as compared to the cultures treated with DMSO plus TPA (5 of 24 dishes). BHAoQ caused a non-significant increase in transformation frequency in the presence of TPA. In conclusion, 3-BHA and BQ had an initiating activity in the cell transformation system and the potency of BQ was approximately 100 times higher than that of 3-BHA.

Animals↗
PubMed1990

Impairment of endothelium-dependent relaxation and changes in levels of cyclic GMP in carotid arteries from stroke-prone spontaneously hypertensive rats.

Endothelium-dependent relaxation of carotid arteries and changes in levels of cyclic (c)GMP between stroke-prone spontaneously hypertensive (SHRSP) and Wistar-Kyoto (WKY) rats have been compared. The concentration-response curve for acetylcholine (ACh)-induced relaxation was shifted to the right in carotid arteries from SHRSP. Relaxation responses produced by calcimycin (A 23187) and melittin, both endothelium-dependent agents, were depressed in carotid arteries from SHRSP. Relaxation responses produced by sodium nitroprusside and 8-Br-cGMP were similar to those in strips from WKY. ACh-induced production of cGMP was significantly decreased in carotid arteries from SHRSP when compared with the level for similarly treated strips from WKY. These results suggest that functional changes in endothelium, but not guanylate cyclase activity or cGMP sensitivity in the carotid arteries, may occur in hypertension. Thus, impaired endothelium-dependent relaxation in SHRSP may play an important role in hypertensive vascular diseases such as stroke.

Acetylcholine↗
PubMed1990

Differences in vascular responses to vasoactive agents of basilar artery and aorta from rabbits with alloxan-induced diabetes.

Responses of the basilar artery and aorta to vasoactive agents in alloxan-induced diabetic and age-matched control rabbits were examined. There were no significant differences in the reactivity of the basilar artery to norepinephrine (NE), 5-hydroxytryptamine (5-HT), and K+ between age-matched control and diabetic rabbits. The maximal contraction of the aorta with endothelium in response to NE was significantly enhanced in the case of the aorta from diabetic rabbits. Pretreatment with 10(-6) M methylene blue or removal of the endothelium enhanced the contractile response of aorta to NE from control rabbits and, after such treatment, the concentration-response curve to NE was almost identical to that of aorta from diabetic rabbits. Basal levels of cyclic GMP but not cyclic AMP in the diabetic aorta with endothelium were significantly lower than those in the control aorta with endothelium. These results demonstrate that the cerebral artery is resistant to diabetes mellitus within 10 weeks as compared with the peripheral artery. The enhancement in the contractile response of aorta to NE in diabetic rabbits is due to the attenuation of the spontaneous release of endothelium-derived relaxing factor, through an impairment of the function of endothelial cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Synthesis, chemical properties and mutagenicity of 1,6- and 3,6-dinitrobenzo[a]pyrenes.

Nitration of benzo[a]pyrene (BaP) with HNO3 (d = 1.38) produced a mixture of dinitroBaPs (1,6- and 3,6-isomers) and mononitroBaPs (1-, 3- and 6-isomers). Pure 1,6-dinitroBaP and 3,6-dinitroBaP were obtained by the reduction of the dinitroBaPs mixture with NaSH to yield the separable products 1-amino-6-nitroBaP and 3-amino-6-nitroBaP, followed by conversion to dinitroBaPs via the the diazonium salts. The half-wave potentials (E1/2) corresponding to the one-electron reduction of dinitroBaPs were measured and the relationship of these values to the mutagenicity is discussed.

Benzopyrenes↗
PubMed1990

Decrease in endothelium-dependent relaxation and levels of cyclic nucleotides in aorta from rabbits with alloxan-induced diabetes.

To investigate the influence of diabetes mellitus on vascular relaxation response, acetylcholine (ACh)-induced relaxation and production of cyclic GMP and cyclic AMP in aortic rings with endothelium were compared between alloxan-induced diabetic and control rabbits. ACh-induced relaxation was significantly attenuated in the aortic rings of diabetic rabbits. Concentration-response curve for ACh-induced relaxation in the aortic rings of control rabbits was shifted to the right by the pretreatment with hemoglobin, and this concentration-response curve was almost identical to that in the aorta from diabetic rabbits. Sodium nitroprusside (SNP)-induced relaxation in the aortic rings without endothelium from diabetic rabbits was similar to that in the aortic rings without endothelium from control rabbits. Basal levels of cyclic GMP and ACh-induced production of cyclic GMP were markedly lower in diabetic rabbits than those in control rabbits. On the other hand, there were no differences in basal and ACh-induced production of cyclic AMP between diabetic and control aorta. These results suggest that impairment of endothelium but not guanylate cyclase activity may be occurred in the aorta of diabetic rabbits. This impairment leads to the decrease in production of cyclic GMP through the attenuation of endothelium-derived relaxing factor (EDRF) release, and this may be responsible for the decreased endothelium-dependent relaxation of ACh.

Acetylcholine↗
PubMed1990

[Experience of air-CT cisternography].

Ten patients were examined with air-CT cisternography. Two acoustic neurinomas protruding into the cistern were visualized as filling defects in the air. Air-CT cisternography identified the 2 tumors with a sensitivity rate of 100%. This retrospective study is aimed to assess the diagnostic efficacy of Air-CT in relation to MRI, enhanced CT and other radiographic studies.

Adult↗
PubMed1990

Three-dimensional analysis of averaged electroretinograms for the evaluation of rhegmatogenous retinal detachment and related pathological conditions.

Retinal functional imaging in patients with rhegmatogenous retinal detachment and related pathological conditions was undertaken in 62 eyes of 44 cases by means of three-dimensional analysis (X-Y plane and time) of electroretinogram (ERG) topography. The analysis revealed that the area of maximal amplitude in both dominantly photopic and scotopic conditions deviated to the skin area closest to the location of the retinal detachment (hereafter referred to as paradoxical localization). In temporal retinal detachment, for example, the location of the maximal amplitude of the a- and b-waves deviated toward the temporal side on surface topography. Flicker ERG with a stimulus frequency of 30 Hz was especially successful for disclosing the existence and the location of posterior involvement of retinal detachment within the area surrounding the temporal vascular arcades. The mechanisms of paradoxical localization were considered to be changes in the axis of the equivalent dipole in detachment eyes. These abnormalities disappeared after the retina was reattached. Although the buckling procedure and argon laser retinopexy had little effect on the topographical distribution of the a- and b-waves, it was markedly distorted by cryoretinopexy. No remarkable changes in the topographical distribution of the waves were detected in pathological conditions predisposing to rhegmatogenous retinal detachment. This new method for functional imaging of the retina promises to be valuable for objective clinical evaluation of retinal detachment.

Adult↗
PubMed1990

Three-dimensional analysis of averaged electro-retinograms: normal appearance and bioelectric artifacts.

In 10 normal subjects, three-dimensional analysis (X-Y plane and time) was carried out of the dominantly photopic and scotopic components of the electroretinograms (ERG) for the purpose of functional imaging of the retina, after having evaluated bioelectric artifacts. The study of the artifacts had revealed that the major causes of distorting the topographical distribution were blinking, myogenic activities, eye movement, eye position and background activities of the electroencephalograms. In normal subjects, the maximal amplitude of the dominantly scotopic components was located around the lower eyelid, while that of the dominantly photopic components was situated around the upper eyelid. The mechanisms of the equivalent dipole axis of the dominantly photopic and scotopic components were different. However, similar changes in the equivalent dipole axes were found during the periods of eccentric eye positions. Similar topographical characteristics were noted in the latency mapping. The isopotential line of the dominantly scotopic components had a steep gradient and were suggestive of a superficial (peripheral retinal) origin, while that of the dominantly photopic components had a gradual gradient and seemed to be of deep (central retinal) origin. ERG topography would make functional imaging of the retina possible and would be of great diagnostic value.

Adult↗
PubMed1989

Functional changes in potassium channels in aortas from rats with streptozotocin-induced diabetes.

The effects of K+ activators on aortas from control and diabetic rats were examined. The concentration-response curves for the relaxant effects of cromakalim were shifted to the right in diabetic rats. The relaxation responses of diabetic aortas to nicorandil did not differ from those of the controls. Treatment with oxyhemoglobin significantly reduced the relaxation responses to nicorandil in aortas from diabetic rats. It appears that the activity of aortic potassium channels is reduced in diabetic rats.

Animals↗
PubMed1989

[Minimal effective dose of perfluorochemical emulsion as a radiosensitizer].

Perfluorochemical emulsion can dissolve large amount of oxygen, carry it into tissues, and consequently enhance the response of hypoxic tumor cells to radiation. Previously we reported on the radiosensitizing effect of perfluorochemical emulsion. In the present study, the minimal effective dose of Fluosol-DA Saline 20% (FDAS), one of preparations of perfluorochemical emulsion, was determined. Mice bearing Lewis lung carcinoma in their thighs were injected in single i.v. of FDAS (1.25-20 ml/kg) and were allowed to breath carbogen (95% O2 + 5% CO2) for 30 min. before and during irradiation (15 Gy). The effect of FDAS was measured by the growth delay of the treated tumor. Administration of FDAS at over 5 ml/kg together with carbogen breathing significantly (p less than 0.01) enhanced the tumor growth delay as compared with treatment of carbogen breathing without FDAS. There was a significant difference (p less than 0.05) in the radiosensitizing effect between injection of FDAS at 5 ml/kg and 20 ml/kg, while there were not significant differences between injection of FDAS at 5 ml/kg and 10 ml/kg, or 10 ml/kg and 20 ml/kg, respectively. These results indicate that the minimal effective dose of FDAS is 5 ml/kg, which could be applied to clinical fractionated irradiation therapy as a standard FDAS-dose.

Animals↗
PubMed1989

Modes of genotoxicity of a macromolecular antibiotic, SN-07, a novel type of interstrand DNA cross-linker.

The modes of genotoxicity of a novel macromolecular antitumor antibiotic (SN-07) were examined using both prokaryotic and eukaryotic cells in vitro. The antibiotic induced a frameshift-type reverse mutation in Ames Salmonella typhimurium TA98 at 1.6-400 ng/plate with and without S9 mix. SN-07 also induced chromosomal aberrations and a forward mutation (6-TGr) in Chinese hamster V79 cells after 1 h treatment at 12.5-100 ng/ml without metabolic activation. The alkaline elution technique revealed that SN-07 induced interstrand DNA cross-linking dose-dependently after treatment with 2.5-10 micrograms/ml for 1 h followed by elution at pH 12.1, but it did not induce the dose-dependent cross-linking after the same treatment followed by elution at pH 12.6. It was also found that SN-07 induced single-strand DNA breaks (pH 12.1) and alkali-labile (pH 12.6) sites after treatment with 0.1-10 micrograms/ml for 1 h followed by 24-h post-incubation.

Animals↗
PubMed1989

Impairment of endothelium-dependent relaxation and changes in levels of cyclic GMP in aorta from streptozotocin-induced diabetic rats.

1. Acetylcholine (ACh)-induced relaxation of aortic strips with endothelium and production of cyclic GMP between streptozotocin-induced diabetic and age-matched control rats were compared. 2. The concentration-response curve for ACh-induced relaxation was shifted to the right in diabetic rats. IC50 values for ACh were 4.57 +/- 0.67 x 10(-8) M and 1.00 +/- 0.87 x 10(-7) M in aortic strips from age-matched control and diabetic rats, respectively (n = 6, P less than 0.05). 3. Relaxations produced by atrial natriuretic peptide (ANP) in diabetic aortae were similar to those in age-matched vessels. 4. Relaxations produced by sodium nitroprusside (SNP) in diabetic aortae were similar to those in age-matched vessels. 5. Basal levels of cyclic GMP and ACh-induced production of cyclic GMP were significantly decreased in diabetic rats. 6. These results suggest that functional changes in endothelium but not in guanylate cyclase activity in the aorta may occur in diabetes, and thus, spontaneous and ACh-induced formation of cyclic GMP may be decreased. This decrease in production of cyclic GMP may be responsible for the decreased response of the aorta to the relaxant effect of ACh.

Acetylcholine↗