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Biomedical subjects

N Miyata

Publications and source records attributed to N Miyata.

At least 163 records · Page 9Linked to original sources

Nucleotide sequence of SN-07 chromophore binding site.

DNase I footprinting was used to investigate binding sites for SN-07 chromophore on DNA fragments prepared from pBR322. Six sites were protected on about 150 base pair DNA fragments by SN-07 chromophore, but not by related anthracycline antibiotics from DNase I digestion. All the protected sites contained the dinucleotide sequence 5'-GC-3', but no other regularities could be discerned. A drug-induced conformational change of DNA was suggested by enhancement of DNase I sensitivity between the protected sites. These results support covalent interaction of the carbinolamine function of SN-07 chromophore to 2-amino group of guanine residues.

Anthracyclines↗

Involvement of endothelial cells in relaxation and contraction responses of the aorta to isoproterenol in naive and streptozotocin-induced diabetic rats.

Experiments were designed to investigate the importance of the endothelium in the relaxation of isolated rat aorta caused by a beta adrenoceptor agonist. Mechanical removal of the endothelium attenuated the relaxation induced by isoproterenol (ISO) and did not affect the relaxation produced by forskolin and by sodium nitroprusside. High concentrations of ISO produced an increase in the resting tension of aortic strips with and without endothelium in a concentration-dependent manner. Mechanical removal of the endothelium or treatment with methylene blue enhanced the maximal contraction induced by ISO. Phentolamine antagonized the contractile responses induced by ISO. In the case of streptozotocin-induced diabetic rats, both aortic strips with and without endothelium generated concentration-response curves for ISO-induced relaxation that were shifted to the right. The relaxant responses to forskolin and sodium nitroprusside were not significantly different between vessels from diabetic and age-matched control rats. In both aortic strips with and without endothelium, the maximal contraction in response to high concentrations of ISO was significantly enhanced in strips from diabetic rats. These results suggest that ISO-induced relaxation of aortic strips with endothelium is mediated by beta adrenoceptors on both the endothelium and the smooth muscle, and high concentrations of ISO produce an increase in the resting tension through alpha adrenoceptors. It is further suggested that the decreased relaxant response of the aorta to ISO in diabetes may be due to decreased density or affinity of beta adrenoceptors on the smooth muscle.

Animals↗

[Evaluation of typical and atypical retinal pigmentary dystrophy by three dimensional analysis (XY plane and time) of averaged electroretinograms].

Retinal functional imaging of patients with typical and atypical retinal pigmentary dystrophies was investigated by three dimensional (XY plane and time) analysis of ERG topography by comparing visual field and fluorescein angiographic findings. The three dimensional analysis revealed that the area of maximal amplitude deviated to the skin area closest to the dominant location of the retinal pigmentary dystrophy (the so-called paradoxical localization). In patients with temporoinferior sectorial retinal pigmentary dystrophy, for example, the maximal amplitude of the a-, b-waves and retinal oscillatory potentials deviated toward the temporoinferior side on the surface topography. These characteristic phenomena of a- and b-waves were found in 60.8% of all patients. Flicker topography with a stimulus frequency of 30 Hz was especially successful in showing the existence and location of paramacular involvement of retinal dystrophy within the area surrounding temporal vascular arcades. The detectability of macular asymmetric involvement was 65.2%. No significant topographic changes were detected in cases in the early stage with no remarkable visual field defects, or in the end stage with remarkable concentric field defects and complicated glaucomatous visual field defects. A comparative study of topographic changes, visual field changes and fluorescein angiographic findings showed that topographic changes in the a-, b-waves, retinal oscillatory potentials and 30Hz flicker components coincided more closely with visual field changes than fluorescein angiographic findings. We proposed that retinal pigmentary dystrophy is not a homogeneous lesion in its progression and believe that the ERG topography method can, by the imaging of dominant locations, detect this disease as well as visual field testing.

Adult↗

[Three dimensional analysis (XY plane and time) 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 investigated by three dimensional analysis of ERG topography. The three dimensional analysis revealed that the area of maximal amplitude deviated to the skin area closest to the location of the retinal detachment (paradoxical localization). In temporal retinal detachment, for example, the maximal amplitude of the a- and b-waves deviated toward the temporal side on the surface topography. The depth of the retinal detachment was clearly indicated by differential ERG topography. Flicker ERG with a stimulus frequency of 30Hz was especially successful in showing the existence and location of macular detachment within the area surrounding the temporal vascular arcades. ERG topography also indicated the meridional extent of retinal detachment. When there was detachment in two quadrants (e.g., two inferior quadrants), deviation in the surface topography of a- and b-waves appeared in the same quadrants. When detachment expanded into three quadrants, deviation of the amplitude of a- and b-waves closely resembled the extent of the detachment. In addition, however, there was inverse a- and b-wave surface topography on the opposite skin area. When there were two quadrants of retinal detachment, there were two quadrants of inverse a-and b-waves. When there were three quadrants of retinal detachment, there was only one quadrant of inverse a- and b-waves. No inverse a- and b-waves were detected when there was only one quadrant of retinal detachment. In such cases, however, deviation in the surface topography covered three quadrants. These abnormalities were detected in 90.6% of all cases with the retinal detachment disappeared after the retina was reattached. While the buckling procedure and argon laser retinopexy had little effect on the topographical distribution, it was markedly distorted by cryoretinopexy. No remarkable changes in the topographical distribution of a- and b-waves were detected in pathological conditions related to rhegmatogenous retinal detachment. This new method for functional imaging of the retina should be valuable for objective clinical evaluation of retinal detachment.

Adult↗

Mechanisms of increased responses of the aorta to alpha-adrenoceptor agonists in streptozotocin-induced diabetic rats.

To investigate the influence of diabetes on the responsiveness of the cardiovascular system, we have examined the effects of various agents on the reactivity of the vascular smooth muscle of aortic strips obtained from age-matched control and diabetic rats. Norepinephrine (NE) contracted the aortic strips obtained from age-matched control and diabetic rats in a concentration-dependent manner, but maximal contraction of aortic strips in response to NE was enhanced in diabetic rats. The EC50 value for NE in the diabetic aortic strips was similar to that in the aorta from age-matched controls. Ca-induced contracture of the aortic strips which were depolarized with isotonic K+ (60 mM) was potentiated in aortic strips from diabetic rats, when compared with those from age-matched controls. Ca-induced contracture of aortic strips, preincubated with 10(-6) M NE and 10(-6) M nicardipine in Ca2+-free Krebs-Henseleit solution (KHS), was not significantly different in age-matched control and diabetic rats. Bay K 8644, an activator of calcium channels, produced an increase in the force of contraction of the slightly depolarized aorta from diabetic rats. Phasic contraction induced by phenylephrine (PE) in the presence of 10(-6) M nicardipine in Ca2+-free KHS was significantly enhanced in aortic strips obtained from diabetic rats. These results demonstrate that NE-induced contraction of the aortic strips obtained from diabetic rats was significantly enhanced, and that this increased contractile response of the aorta to NE may be due to an increased influx of extracellular calcium through the voltage-dependent Ca2+ channels, but not through the receptor-operated Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)

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

[A study of CDDP in the treatment of patients with gastric and esophageal cancers, with special reference to the evaluation of renal functions before and after CDDP administration].

Although CDDP has been widely used for cancer chemotherapy in recent years, the problem is that it causes a renal dysfunction as a side effect. As briefly reported here, we have currently used this drug for the treatment of stomach esophageal cancers as a part of multidepartmental therapy, and obtained a finding on the therapeutic usefulness, particularly for monitoring the renal function before and after administration. The subjects were 6 patients with stomach and 11 with esophageal cancer given CDDP at the dose of 50 mg 2 courses, in principle, a single course per week. Blood transfusion was carried out in an amount of 1,000 ml before administration, 2,500 ml on the day of treatment and 1,000 ml for 3 days after administration. When the effects of CDDP on urinary BUN, Na, K, Cl, Mg, NAG, beta 2 microglobulin, Ccr and FENa levels were measured for the determination of renal functions before and after administration, NAG and beta 2 microglobulin levels were conceivably found to be useful indices.

Adult↗

Mechanisms of action of a novel macromolecular antitumor antibiotic, SN-07, on mouse leukemia L1210 cells in culture.

The mechanisms of action of a novel macromolecular antitumor antibiotic (SN-07) were examined using cultured mouse lymphoid leukemia L1210 cells. A shoulder exponential-type cytotoxicity was observed when the cells were treated with 3.13 to 100 ng/ml SN-07 for 1 hr and surviving colonies were counted after a 14-day incubation. It was found that 500 ng/ml SN-07 inhibited both RNA and DNA syntheses significantly at 40 and 80 min, respectively, while 8,000 ng/ml did not affect protein synthesis at 80 min. Treatment with a low concentration (80 ng/ml) of SN-07 for 1 hr inhibited both RNA and DNA syntheses after a 24-hr post-incubation. The alkaline elution technique revealed that 8,000 ng/ml SN-07 induced DNA interstrand cross-links time-dependently for 1 to 4 hr, and a 1-hr treatment with 80 to 8,000 ng/ml SN-07 induced DNA breaks after a 24-hr post-incubation. According to flow cytometric analysis, most L1210 cells progressed to the G2 phase in the cell cycle at a cytostatic concentration (25 ng/ml) of SN-07, and typical inhibition of the cell cycle progression was observed at a cytocidal concentration (200 ng/ml).

Animals↗

A novel macromolecular antibiotic, SN-07. Taxonomy of producing organism, isolation, characterization and biological activities.

A novel macromolecular antibiotic SN-07 was obtained from the cultural supernatant of Actinomadura roseoviolacea var. miuraensis nov. var. The antibiotic was soluble in water, had a molecular weight of 18,000-22,000 daltons in 50 mM Tris-HCl buffer, pH 7.0, containing 2.0 M KCl as compared with authentic proteins. Its major constituents were nucleic acids. The substance had antibacterial activity against Gram-positive bacteria. It was also effective against lymphocytic leukemia P388 in vivo.

Actinomycetales↗