Search PubMed⌕ Search

Biomedical subjects

K Munakata

Publications and source records attributed to K Munakata.

At least 91 records · Page 5Linked to original sources
PubMed1983

Characteristics and possible mechanism of ventricular arrhythmia dependent on the dispersion of action potential durations.

The arrhythmogenic role of increased dispersion of repolarization (dispersion) was studied in 23 open-chest dogs using six simultaneously recorded monophasic action potentials (MAPs) from the ventricular surface and programmed ventricular premature stimulation (VPS). Increased dispersion was induced by generalized hypothermia (29 degrees C) and regional warm blood (38-43 degrees C) perfusion through a coronary artery branch. Hypothermia and regional warm blood perfusion increased maximum dispersion from 13 +/- 10 to 111 +/- 16 msec (p less than 0.001), predominantly because of the increased MAP duration difference (10 +/- 15 vs 97 +/- 16 msec, p less than 0.001). The maximal difference between activation times was not significantly changed, but the QRS duration increased from 47 +/- 6 to 52 +/- 7 msec (p less than 0.01). Ventricular arrhythmia did not occur spontaneously but was induced by a single VPS in all 23 dogs during hypothermia and regional warm blood perfusion when dispersion reached a critical magnitude. The critical magnitude of dispersion required to induce ventricular arrhythmia was documented in 16 dogs by stepwise increments or decrements of dispersion. In four dogs, an increase in atrial pacing rate of 24 beats/min prevented induction of ventricular arrhythmia by decreasing dispersion from a critical magnitude of 103 +/- 5 msec to a nonarrhythmogenic value of 86 +/- 9 msec (p less than 0.05). In six dogs, we compared the stimulation site-dependent effects of VPS applied in the region with short and long MAPs. In all dogs, ventricular arrhythmia was inducible only by VPS from the region with a short MAP. Premature impulses from this region propagated more slowly than those from the region with a long MAP. Our results show that the large dispersion of repolarization facilitates the development of a conduction delay necessary to induce sustained arrhythmia by an early premature stimulus applied at the site with a short MAP.

Action Potentials↗
PubMed1982

Metabolism of benzo(a)pyrene in epidermal keratinocytes and dermal fibroblasts of humans and mice with reference to variation among species, individuals, and cell types.

The metabolism of benzo(a)pyrene (BP) in epidermal keratinocytes and dermal fibroblasts of humans and mice was investigated with emphasis on variation among species, individuals, and cell types. Human epidermal and dermal cells were isolated from the skin of normal subjects by trypsinization at 4 degrees overnight, followed by separation of the epidermis from the dermis with forceps. In confirmation of previous studies metabolic activity of human epidermal cells on BP was consistently demonstrated by cell-mediated assay, in which V79 Chinese hamster cells were plated on top of sheets of epidermal cells and treated with BP for 48 hr. Mutation of the V79 cells, measured as ouabain resistance, was induced in a dose-related fashion, although the extent of induced mutation varied from 5 to 22 ouabain-resistant colonies per 10(6) survivors/10 microM BP in cultures derived from different individuals. The most striking observation was that human dermal fibroblasts did not activate BP to a form that was mutagenic to cocultured V79 cells. This was observed without exception in all nine cultures of dermal fibroblasts and the one culture of embryo fibroblasts (MR-90) tested. Analysis by high-pressure liquid chromatography indicated that human epidermal and dermal cells both metabolized BP, producing almost the whole series of known metabolites of BP. The amount of BP 7, 8-dihydrodiol, a proximate metabolite of BP, produced by human dermal cells varied from 0.2 to 2.7% of the total BP added and seemed to be enough to induce mutation. Furthermore, human dermal cells not necessarily activated exogenously added BP 7,8-dihydrodiol to a form being mutagenic to V79 cells. These observations suggest that further metabolism of BP 7,8-dihydrodiol is partially or entirely blocked in human fibroblasts. In contrast to human fibroblasts, mouse fibroblasts isolated from the dermis of embryos did activate BP and induced mutation in cocultured V79 cells to a higher extent than did mouse epidermal cells, indicating interspecies variation in metabolic activation of BP between human and mouse fibroblasts.

Adolescent↗
PubMed1982

Variable effects of isoproterenol on action potential duration in guinea-pig papillary muscle: differences between nonsteady and steady state; role of extracellular calcium concentration.

The effect of three different isoproterenol (ISP) concentrations (10(-6), 10(-7) and 10(-8) M) on action potential duration (APD) was studied in guinea-pig papillary muscles at low (0.6-0.9 mM), intermediate (1.8 mM) and high (3.6 mM) calcium concentrations (Ca++)0. All three ISP concentrations produced (Ca++)0-dependent changes during both nonsteady (NSS) and steady state (SS). During NSS, initial prolongation of APD occurred in 22 of 22 experiments at low, in 16 of 36 experiments at intermediate and 0 of 15 experiments at high (Ca++)0. In the remaining experiments, APD became progressively shorter. The NSS-APD changes were associated with increase in plateau amplitude attributed to slow inward current (isi). However, we found no correlation between the amplitude of plateau and APD change. This suggests that the (Ca++)0-dependent differences were due more likely to differences in the rat of isi inactivation than to differences in the absolute isi magnitude. The SS-APD was also dependent on (Ca++)0 but, during progression from NSS to SS, plateau amplitude did not change, whereas the force of contraction increased. This supports the hypothesis that the dependence of SS-APD on (Ca++)0 is mediated by the time-independent K conductance controlled by intracellular calcium concentration. Thus, the early and the late ISP effects on APD appeared to differ in their mechanism, but both depended on (Ca++)0.

Action Potentials↗
PubMed1981

Therapy for urolithiasis with hydroxamic acids. IV. Prevention of infected urinary stone formation with N-(pivaloyl)glycinohydroxamic acid.

With the aim of finding a prospective therapeutic compound with a promising potential for the treatment of urolithiasis, we evaluated the effectiveness of a new potent inhibitor of urease, N-(pivaloyl)glycinohydroxamic acid. The present study revealed that N-(pivaloyl)glycinohydroxamic acid effectively inhibited the alkalinization of urine and the stone formation in vitro and in vivo, due to its strong inhibitory potency against the ureolytic activity of intact Proteus mirabilis. The possibility of the clinical application of this compound in the prevention of struvite stone formation caused by infection of urea-splitting bacteria awaits evaluation of the safety of this compound.

Animals↗
PubMed1980

Therapy for urolithiasis by hydroxamic acids. II. Urease inhibitory potency and urinary excretion rate of hippurohydroxamic acid derivatives.

The apparent I50 values of various hippurohydroxamic acids against urease activity of sword bean were mostly 0.5 to 2.0 microM regardless of hydrophobicity of their substituents. However, the marked increase of hydrophilicity caused by substitution of trimethoxy groups conspicuously decreased the inhibitory potency. Methylation at alpha-position of the hydroxamic acid group in these compounds remarkably decreased the inhibitory potency, probably owing to steric hindrance by the alpha-methyl group. Thenoyl-, furoyl- and nicotino-glycinohydroxamic acids which are bioisostereomers of hippurohydroxamic acid had I50 values of 0.64, 1.3 and 5.3 microM, respectively. Furthermore, the inhibitory potency of some substituted hippurohydroxamic acids against the ureolytic activity of intact Proteus mirabilis isolated from patients with urinary tract infection, were half to one-tenth of those against urease activity of sword bean. On the other hand, m- and p-nitro-, m- and p-methoxy-, m- and p-acetylamino-hippurohydroxamic acid and furoylglycinohydroxamic acid showed high urinary excretion rates of 14 to 16% of the doses administered orally to rats, while most of the others had excretion rates of about 3 to 5%.

Fabaceae↗
PubMed1980

Therapy for urolithiasis by hydroxamic acids. III. Urease inhibitory potency and urinary excretion rate of N-acylglycinohydroxamic acids.

Hydroxamic acid, a potent urease inhibitor, having a high urinary excretion rate is expected to be a therapeutic agent for urolithiasis caused by urea-splitting bacterial infection of the urinary tract. Twenty-one new derivatives of N-aliphatic-acylglycinohydroxamic acids (GHAs) were synthesized, and their inhibitory potencies against the urease activity of sword bean in a phosphate buffer and against the ureolytic activity of Proteus mirabilis in human urine, and their urinary excretion rates in rats were also measured for this purpose I50 values of most of GHAs against the urease activity of sword bean were about 1 to 10 microM and 2-ethyl-n-butyroyl GHA was the most potent inhibitor with the value of 0.79 microM. I50 values of most of the GHAs against the ureolytic activity of Proteus mirabilis were about 5 to 50 microM and n-nonaroyl GHA was the most potent inhibitor with the value of 3.6 microM. 2,2-Dimethylpropionyl GHA had the highest urinary excretion rate with the recovery of 11%. Routes of administration of 2,2-dimethylpropionyl GHA and sex of rats used did not affect the amount of urinary excretion at all. The results in this report suggest that DL 2-methyl-n-butyroyl, 2-ethyl-n-butyroyl and 2,2-dimethylpropionyl GHA are the most hopeful therapeutic agents for urolithiasis among them.

Animals↗
PubMed1980

Quantitative structure-activity relationships between hydroxamic acids and their urease inhibitory potency.

Quantitative structure activity relationships between physico-chemical properties of four series of more than sixty hydroxamic acids [R-(CONHCH2)n-CONHOH, R=aromatic or aliphatic, n=1 or 0) and their urease inhibitory activities were examined. The best improved regression equation primarily indicated that the inhibitory activities of hydroxamic acids were parabolically varied with the hydrophobic variable, pi of the R moiety and the optimal pi value was calculated to be 2.58. Furthermore, the inhibitory activities of congeners were found to be significantly affected by the B1 variable representing the minimum width of steric size of the R moiety. Besides, it was clarified by using two indicator variables that inhibitory activities were not affected by the R moiety, whether aromatic or aliphatic, but positively affected by the presence of the -CONHCH2-group between the R moiety and the hydroxamic acid group.

Chemical Phenomena↗
PubMed1980

Mutagenicity of N-acylglycinohydroxamic acids and related compounds.

The mutagenic activity of twenty-nine new N-acylglycinohydroxamic acids and related compounds was tested on Bacillus subtilis (Rec(+), Rec(-)) and Salmonella typhimurium (TA 98, TA 100). All the N-(substituted-benzoyl)glycinohydroxamic acids, except 3-acetylaminobenzoyl-derivative, were shown to be mutagenic to both test bacteria, whereas most of the N-aliphatic acylglycinohydroxamic acids were found to be non-mutagenic. In the present study, we discussed out observations focussing on the structure-activity correlation between their chemical structures and mutagenic activities.

Bacillus subtilis↗
PubMed1978

Histologic studies of rectocolic aganglionosis and allied diseases.

It is well-known that some patients exhibiting the symptoms of Hirschsprung's disease are shown to have intramural ganglia in the distal myenteric plexus. Some of them have been described as "pseudo-Hirschsprung's disease". It is likely that a variety of conditions have been included in this group. Using a silver impregnation technique we have made a detailed histologic study of the rectum and large bowel in a number of cases with provisional clinical diagnosis of Hirschsprung's disease but in which rectal biopsy showed small ganglia in Meissner's plexus demonstrated by acetylcholinesterase (Ach-E) staining. Three histologic variations were shown that may be called hypoganglionosis, immaturity of ganglia, and hypogenesis. An attempt is made to relate their clinical picture to the histologic findings.

Colon↗