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Biomedical subjects

R Kato

Publications and source records attributed to R Kato.

At least 541 records · Page 30Linked to original sources
PubMed1985

Inhibition of mouse epidermal 12-lipoxygenase by 2,3,4-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinon e (AA861).

2,3,5-Trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861) strongly inhibited epidermal lipoxygenase activity which was determined by the formation of [14C]12-hydroxy-5,8,10,14-eicosatetraenoic acid by incubating [14C]arachidonic acid with cytosol fraction of epidermal homogenate of CD-1 mice. AA861 failed to inhibit epidermal cyclooxygenase activity. The present results indicate that AA861 is a potent inhibitor of 12-lipoxygenase in mouse epidermis (IC50 1.9 microM).

Animals↗
PubMed1985

Effects of hypoxia on the cellular electrical activity of adult and neonatal canine ventricular myocardium.

Standard microelectrode techniques were utilized to evaluate the effects of acute hypoxia on the cellular electrical activity of neonatal and adult ventricular myocardium. Control action potential parameters from adult and neonatal tissues were not significantly different. Thirty minutes of acute hypoxic superfusion significantly (p less than 0.05) reduced all adult action potential indices. In neonatal preparations, only action potential duration at 50% repolarization (-17%) and action potential duration at 90% repolarization (-12%) were reduced significantly. After 60 min of hypoxia, action potential amplitude, maximum diastolic potential, and phase 0 upstroke velocity from neonates were still not reduced significantly. The alteration in neonatal action potential parameters induced by 1 h of hypoxic superfusion (5.5 mM glucose) were all reversed by 16.5 mM glucose despite continued hypoxia. Exclusion of glucose from the hypoxic superfusate did not greatly affect the response of neonatal tissues to hypoxia. In adult action potentials, the degree of decrease for each action potential parameter was markedly greater compared to the hypoxic solution with normal (5.5 mM) glucose. Following hypoxic superfusion of neonatal preparations with 0 mM glucose, reoxygenation with 16.5 mM glucose resulted in action potential parameters with exceeded control values by 4 to 25%. Our data indicate a greater resistance of developing myocardium to the detrimental effects of hypoxia on cellular electrical activity. This seems to be related to a greater glycolytic activity of neonatal myocardium compared to adult hearts.

Action Potentials↗
PubMed1985

Problems of artificial pacemaker therapy.

Four hundred and sixty-seven cases with implantation of an artificial pacemaker were studied. The postoperative survival rate was 63% for 15 years. Seventy-two percent of type III patients of the sick sinus syndrome were free from postoperative thromboembolism and the lowest of the three types of the sick sinus syndrome. Comparing postoperative physical activity, cardiothoracic ratio and exercise tolerance time, physiological pacing was superior to ventricular pacing in hemodynamic effects and clinical symptoms. In a hundred cases of physiological pacing, complications and problems of physiological pacing were discussed. Atrial sensing failure and over-sensing were observed in seven and two cases respectively. A low amplitude of atrial potential and use of unipolar atrial leads were considered to be the main causes of these complications. Bipolar lead should be used as the atrial lead to avoid such complications, because the atrial potential by bipolar leads is not less than that by unipolar leads. Atrial sensing may be more sensitive without electromagnetic interference. The fixed A-V delay time whenever the atrium is sensed or paced, often results in a ventricular fusion beat and hemodynamic change on every beat, according to the interval of atrial and ventricular contractions. The A-V delay time should be changed in accordance with atrial sensing or pacing.

Cardiac Pacing, Artificial↗
PubMed1985

Inhibition of teleocidin-caused epidermal ornithine decarboxylase induction by phospholipase A2-, cyclooxygenase- and lipoxygenase-inhibitors.

Teleocidin (5 micrograms/mouse), a potent tumor promoting indole alkaloid from Streptomyces, induced epidermal ornithine decarboxylase (ODC) in CD-1 mice. Teleocidin-caused ODC induction was inhibited by the treatment of indomethacin (2 mumol/mouse), a selective cyclooxygenase inhibitor, and p-bromophenacyl bromide (BPB) (30 mumol/mouse), a phospholipase A2 inhibitor. Teleocidin-caused ODC induction inhibited by indomethacin was completely restored by concurrent application of prostaglandin E2 (PGE2) (140 nmol/mouse). On the other hand, teleocidin-caused ODC induction inhibited by BPB was not restored by the treatment of mice with PGE2, but partially restored by the treatment with arachidonic acid (1 mumol/mouse). Treatment of mice with lipoxygenase inhibitors such as BW755C (30 mumol/mouse), nordihydroguaiaretic acid (NDGA) (30 mumol/mouse), quercetin (10 mumol/mouse), and 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861) (10 mumol/mouse) clearly suppressed ODC induction by teleocidin. Moreover, both NDGA (30 mumol/mouse) and quercetin (10 mumol/mouse) inhibited the restoring effect of PGE2. Therefore, our present results suggest that arachidonate metabolites, i.e., not only cyclooxygenase product(s) but also lipoxygenase product(s), are involved in the mechanism of ODC induction by teleocidin.

Animals↗
PubMed1985

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced increase in vascular permeability in mouse skin by lipoxygenase inhibitors.

The painting of mouse dorsal skin with 12-O-tetradecanoylphorbol-13-acetate (TPA) (0.2-2.5 nmol/mouse) induced a dose-related increase in vascular permeability, which was determined by pontamine sky blue exudation into the skin 5 hr after the TPA treatment. Marked infiltration of neutrophils in the dermal interstitium was also observed 5 hr after TPA treatment. Treatment of mice with nordihydroguaiaretic acid (NDGA) (10 mumol/mouse). 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861) (10 mumol/mouse) and quercetin (3 mumol/mouse) significantly inhibited the TPA-induced dye exudation. However, indomethacin (250-1000 nmol/mouse) tended to inhibit the TPA-induced dye exudation, but the inhibition was not statistically significant. Treatment with AA861 (10 mumol/mouse) also caused a marked inhibition of TPA-induced neutrophil infiltration. Quercetin, NDGA and AA861 inhibited epidermal lipoxygenase activity, but indomethacin failed to inhibit it. On the other hand, indomethacin inhibited epidermal cyclooxygenase, but quercetin, NDGA and AA861 failed to inhibit it. The present study suggests involvement of a lipoxygenase product(s) in the mechanism of the TPA-induced increase in vascular permeability in the dorsal skin of mice.

Animals↗
PubMed1985

Fast-atom bombardment and electron-impact mass spectrometry of N-hydroxyarylamines, active intermediates of mutagenic aromatic amines.

Thermally labile N-hydroxyarylamines, which are the active metabolites of carcinogenic/mutagenic aromatic amines and show potent direct mutagenicity, were studied by fast-atom bombardment (F.A.B.) mass spectrometry and electron-impact (E.I.) mass spectrometry. The protonated molecular ion [M + H]+ and the molecular ion [M]+ were observed at high intensity in the F.A.B. mode. The fragment ions corresponding to [M + H-16]+, [M + H-17]+ and [M-16]+, [M-17]+, [M + H-32]+ and [M-32]+ were also observed characteristically. The quasimolecular ion peaks were shifted up by the numbers of active hydrogens in molecules after the hydrogen-deuterium exchange with [hydroxy--2H3]glycerol and 2H2O. The formation of the ions continued stably throughout the period of measurement, and the decomposition of the samples did not occur in the F.A.B. ion source, compared with the E.I. mode. Hence, it is suggested that the F.A.B. technique is useful for the analysis of the heat-labile toxicologically important N-hydroxyarylamines.

Amines↗
PubMed1985

[Gated blood pool imaging in the diagnosis and management of arrhythmia].

The usefulness of multigated cardiac blood pool imaging in evaluating left ventricular function and ventricular activation was studied in patients with cardiac arrhythmias. Subjects consisted of 12 patients with the Wolff-Parkinson-White (WPW) syndrome; 20 with ventricular premature contractions (VPC); 21 with various modes of artificial pacemakers; and two normal controls. Phase analysis was useful in localizing the bypass tract in patients with the WPW syndrome. In four patients with the WPW syndrome and five with VVI pacing, the phase difference between the posterolateral wall of the left ventricle (LV) and the right ventricular apex correlated significantly with the activation time difference between these two regions as assessed by endocardial electrograms (r = 0.94, p less than 0.001). Images of VPC were obtained using the bad beat rejection program in an ADAC computer system. The origin of VPCs evaluated by phase image coincided with results of standard 12-lead electrograms. It was in the right ventricle in four patients, the LV in one, and probably in the interventricular septum in one. The LV ejection fraction (LVEF) decreased significantly (p less than 0.001) after the injection of lidocaine (-3.7%) or disopyramide (-6.2%). The percent reduction in LVEF was significantly greater with disopyramide than with lidocaine (-15.1 vs -11.2%). The plasma concentration of disopyramide was higher in four patients with organic heart diseases than in 11 without. There was a significant correlation between the percent reduction in LVEF and the disopyramide plasma concentrations (r = -0.62, p less than 0.001). The influence of the pacing mode and exercise on LV function was studied in 21 patients with artificial pacemakers. In the VDD and DDD modes, end-diastolic volume (EDV) and cardiac output (CO) decreased after converting to VVI mode. CO increased markedly to approximately 250% of the control value in the VDD and DDD, and moderately in the VVI and AAI modes during ergometer exercise. In conclusion, multigated cardiac pool imaging is considered useful in diagnosing and managing patients with cardiac arrhythmias.

Arrhythmias, Cardiac↗
PubMed1985

Lipoxygenase inhibitors and cyclic AMP-mediated insulin secretion caused by forskolin, theophylline and dibutyryl cyclic AMP.

Forskolin caused a marked and a concentration-dependent elevation of cyclic AMP content in isolated pancreatic islets (EC50, 10 microM). Cyclic AMP level reached a plateau within 30 min after the addition of 10 microM forskolin. In a low glucose (3.3 mM) medium, forskolin induced slight but significant insulin secretion in a concentration-dependent manner (EC50, 0.3 microM). When the glucose concentration was increased to 5.5 mM, marked enhancement of insulin secretion was observed with forskolin (EC50, 0.5 microM). Lipoxygenase inhibitors, such as nordihydroguaiaretic acid, 3-amino-1-(trifluoromethylphenyl)-2-pyrazoline and 1-phenyl-3-pyrazolidinone failed to affect the forskolin-stimulated cyclic AMP generation. The selective cyclooxygenase inhibitor indomethacin also had no influence on forskolin-stimulated cyclic AMP generation. Insulinotropic effects of forskolin, however, were suppressed by these lipoxygenase inhibitors but not by indomethacin. Both nordihydroguaiaretic acid and 1-phenyl-3-pyrazolidinone also prevented the insulinotropic effects of theophylline and dibutyryl cyclic AMP, whereas indomethacin failed to inhibit them. It seems conceivable that a lipoxygenase product(s) is involved in the insulin secretory process distal to cyclic AMP generation, or that alternatively a lipoxygenase product(s) is permissively involved in the insulin secretory process independently from the cyclic AMP-mediated process.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1985

Age-related alteration in the activities of drug-metabolizing enzymes and contents of sex-specific forms of cytochrome P-450 in liver microsomes from male and female rats.

Age-related changes in the amounts of sex-specific forms of cytochrome P-450 as well as the activities of drug-metabolizing enzymes in liver microsomes of Fischer-344 rats of different ages ranging from 3 to 30 months were studied. Activities of 7-propoxycoumarin O-depropylase and benzo(a)pyrene hydroxylase in male rats, which were higher than those in female rats in younger adults (3-12 months), decreased with increasing age, resulting in the loss of sex differences after 25 months. The male-specific form of cytochrome P-450, namely P-450-male, present in younger adults, was not detectable in older ages. In old male rats, the female-specific form of cytochrome P-450, namely P-450-female, appeared instead of P-450 male. In liver microsomes of young and old female rats, rather constant levels of P-450-female were observed, whereas P-450-male was not detectable. Serum concentrations of testosterone and estradiol were also quantitated. The ratio of testosterone to estradiol concentrations decreased with age in male rats whereas the ratio was not changed in female rats. Based on these results, we propose that the age-related decrease in the activities of drug-metabolizing enzymes in male rats is attributable to the change in the population of cytochrome P-450, especially P-450-male and P-450-female, probably owing to the alteration of the levels of gonadal hormones.

Aging↗
PubMed1985

Catalysis of the covalent binding of 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole to DNA by a L-proline- and adenosine triphosphate-dependent enzyme in rat hepatic cytosol.

An enzymatic mechanism involved in the activation of 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (N-hydroxy-Trp-P-2), a mutagenic intermediate of a tryptophan pyrolysate, was studied in vitro. In hepatic cytosol supplemented with adenosine triphosphate and L-proline, N-hydroxy-Trp-P-2 was converted to a form which reacts readily with DNA. The enzyme responsible for the activation was partially purified and identified as prolyl transfer RNA synthetase as judged by their cofactor requirements, inhibition by pyrophosphate or adenosine monophosphate, and copurification of their activities. The prolyl transfer RNA-dependent covalent binding of N-hydroxy-Trp-P-2 to DNA of hepatic cytosol was highest in rats, followed by mice, hamsters, rabbits, and guinea pigs in that order. The capacity for the binding of N-hydroxy-Trp-P-2 was largely consistent with their prolyl transfer RNA synthetase activity. With regard to the ultimate form of N-hydroxy-Trp-P-2 for the covalent binding, a possible formation of N,O-prolyl-3-amino-1-methyl-5H-pyrido[4,3-b]indole was proposed.

Adenosine Triphosphate↗
PubMed1985

Does pleural bronchial wrapping improve wound healing in right sleeve lobectomy?

The effect of bronchial circulation on wound healing at the site of anastomosis after right upper sleeve lobectomy was studied in dogs. In two dogs (Group I), the bronchial arteries were carefully preserved during the sleeve lobectomy. In 16 dogs (Group II), only sleeve lobectomy was performed after all bronchial arteries in the hilum were ligated. In three dogs (Group III), the site of anastomosis was wrapped by a Penrose drain after sleeve lobectomy. In three other dogs (Group IV), the site of anastomosis was wrapped with a free pleural flap after sleeve lobectomy. In another group of 11 dogs (Group V), the anastomotic site was wrapped with a pedicled pleural flap. The dogs in Group I were put to death immediately and bronchial arterial circulation was recognized to consist primarily of systemic arterial blood. In Group II dogs, bronchial arteries distal to the anastomosis filled with pulmonary arterial blood immediately after the sleeve lobectomy. Although the majority of bronchial arteries became filled with systemic arterial blood with time, some vessels were filled with pulmonary arterial blood even 7 days after the sleeve lobectomy. In Group III dogs, wound healing at the site of anastomosis was severely delayed, and 7 days after the sleeve lobectomy the majority of bronchial arteries in the bronchial wall distal to the anastomosis were filled with pulmonary arterial blood. In Group IV dogs, the state of wound healing at the bronchial anastomotic site was similar to that of Group III dogs. In Group V, although the state of wound healing at the anastomosis was relatively good in most of the animals, the pedicled pleural wrap did not significantly improve bronchial circulation over that of Group II.

Animals↗