Search PubMed⌕ Search

Biomedical subjects

R Kato

Publications and source records attributed to R Kato.

At least 487 records · Page 27Linked to original sources
PubMed1987

Suppression by muscarinic M2 stimulation of the contractile mechanism via histamine H1 receptors in the longitudinal muscle of guinea pig ileum.

The longitudinal muscle of the guinea pig ileum is well known to contract in response to stimulation of either muscarinic or histamine H1 receptors. However, we found that simultaneous application of agonists to both receptors, methacholine (MeCh) and histamine (Hist), at their maximum concentrations (both at 10(-5) M), induced a contraction of the muscle with a pattern very similar to that observed with MeCh alone. In the muscle contracted by MeCh, a muscarinic antagonist, atropine, caused a transient relaxation, but a histamine H1 blocker, pyrilamine, had no effect on the tension. Experiments using pirenzepine indicated that muscarinic-M1 receptors did not seem to be involved in the mechanism of this phenomenon. The atropine-induced relaxation was not affected by phentolamine (10(-6) M), propranolol (10(-6) M) or tetrodotoxin (10(-6) M). After pretreatment of the muscle with 10(-5) M MeCh for 10 min, the contractile effect of 10(-5) M Hist was suppressed intensely for a certain time period, but that of 10(-5) M MeCh was not diminished. On the other hand, pretreatment of the muscle with 10(-5) M Hist for 10 min did not influence the contraction by either MeCh or Hist. The suppression by MeCh of the Hist action developed dependently on the concentration of MeCh and the time length of exposure to MeCh, and the persistence was temperature-dependent. Furthermore, this suppression was not surmounted by the elevation of Hist concentration. A similar phenomenon was also observed in the muscle which was immersed in the nutrient solution without CaCl2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

[Clinical significance of a physical activity index based on calorimetry in the assessment of quality of life after total gastrectomy].

In order to characterize the objective diagnostic criteria concerning quality of life (QL) of patients after total gastrectomy, a physical activity index (PAI) or a concept of daily physical activity was developed. Sixty patients of gastric cancer, of whom 38 patients underwent long loop Roux-en-Y gastrojejunostomy (LLRY) procedure after total gastrectomy, 13 patients gastroduodenostomy (Billroth I) and 9 patients gastrojejunostomy (Billroth II) after subtotal gastrectomy, respectively, were evaluated as part of this study. In addition, 3 cases of pancreatoduodenectomy (PD) and 5 cases of total esophagectomy were also evaluated. The evaluation of QL was based upon a clinical assessment and administration of patient questionnaire. The assessment of the PAI was performed by measuring the individual's whole day energy expenditure based upon 24 hour heart rate ratio (24h-HRR) method and the basal metabolic energy expenditure. The daily physical activity was graded into four categories according to the PAI value; light, moderate, moderately heavy and heavy. The results obtained were as follows: The value of the energy expenditure predicted by 24h-HRR method and that based on the results of bicycle ergometry (VO2/HR method) showed close correlation. There was no significant difference in the whole day energy expenditure among four operative procedure groups (Billroth I, Billroth II, LLRY and total esophagectomy). More than 80 per cent of LLRY patients, whose QL was evaluated as "excellent" or "good", showed no less than "moderate" PAI. In addition, one of the four patients whose QL was "fair" was categorized into "light" and the remaining three were "moderate".(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1986

Differential effects of protein kinase C activators on carbamylcholine- and high K+-induced rises in intracellular free calcium concentration in cultured adrenal chromaffin cells.

Pretreatment of adrenal chromaffin cells with protein kinase C activators, i.e. 12-O-tetradecanoyl phorbol-13-acetate (TPA) and 1-oleoyl 2-acetyl glycerol (OAG), partially inhibited carbamylcholine (CCh)-induced rise in intracellular free Ca2+ concentration ([Ca2+]i). The apparent IC50 values of TPA and OAG were 3 nM and 25 microM, respectively. The effect of TPA on the CCh-induced rise in [Ca2+]i was overcome by pretreatment of the cells with a protein kinase C inhibitor, 1-(5-isoquinidinesulfonyl)-2-methylpiperazine hydrochloride (H-7). In contrast, KCl-induced rise in [Ca2+]i was not affected by pretreating the cells with TPA or OAG. An inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate failed to affect the CCh-induced rise in [Ca2+]i. CCh-induced 45Ca2+ uptake was also partially inhibited by pretreatment of the cells with TPA or OAG, but KCl-induced 45Ca2+ uptake was not affected by these pretreatments. These results indicate that protein kinase C activation causes an uncoupling of signal transduction between the nicotinic receptors and Ca2+ channels.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1986

Generation of cytotoxic T lymphocytes from thymocyte precursors to trinitrophenyl-modified self antigens. II. Establishment of a T cell hybrid clone constitutively producing killer-helper factor(s) (KHF) and functional analysis of released KHF.

T cell hybridoma lines were constructed by fusion of Mycobacterium tuberculosis-primed and boosted BALB/c T cells with the AKR-derived T lymphoma cell line BW5147. Certain of the hybridomas prepared in this manner secreted constitutively into their culture supernatants biologically active molecules that displayed precursors of cytotoxic T cell activating properties characteristic of killer-helper factor (KHF). Cell surface analysis revealed that the hybridomas were indeed somatic cell hybrids between the two respective partner cells used for fusion. KHF properties of these hybridoma supernatants were verified by their capacity to stimulate peanut agglutinin-binding (PNA+) C3H/He thymocytes to respond in vitro to 2,4,6-trinitrophenyl(TNP)-modified syngeneic stimulator cells in conjunction with suboptimal doses (10 U/ml) of interleukin 2 (IL 2) for the generation of H-2-restricted, TNP-reactive cytotoxic T cells. The biologically active molecules secreted by a T cell hybrid clone (2Y4) were, like conventional KHF, distinct from IL 1, IL 2, or immune interferon (IFN-gamma). The partially purified KHF derived from 2Y4 cells shows activity at apparent m.w. range of 34,000 to 60,000 on gel permeation, and is relatively homogeneous with respect to isoelectric point, which was approximately 4.5 to 4.7. The partially purified 2Y4-KHF is able to augment proliferation of as well as the expression of IL 2 receptors on PNA+ thymocytes in conjunction with IL 2. Finally, addition of 2Y4-KHF on day 0, followed by the addition of IL 2 on day 2 for 7 days of culture was effective in generating potent CTL responses, whereas addition of IL 2 on day 0, followed by the addition of 2Y4-KHF on day 2 to the culture was ineffective.

Animals↗
PubMed1986

Potentiation of prostaglandin E1-stimulated cAMP formation by 12-O-tetradecanoylphorbol-13-acetate in BALB/c mouse 3T3 cells.

Prostaglandin E1 (PGE1: 0.1-100 microM), forskolin (0.1-100 microM), and cholera toxin (20 ng/ml) stimulated cAMP formation of BALB/c 3T3 cells. The pretreatment of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) enhanced PGE1 (10 microM)-stimulated cAMP formation in a concentration- and a time-dependent manner. If the cells were pretreated with TPA (0.1 microM) for only 1 hr, the above augmentation was not observed. Maximal enhancement was observed by pretreatment of the cells for 5 hr with 0.1 microM TPA. Basal cAMP formation was not affected by TPA pretreatment. Other tumor promoters, such as teleocidin and mezerein, showed a potentiating effect similar to that of TPA on the PGE1-stimulated cAMP formation. However, phorbol which is not a tumor promoter, failed to potentiate PGE1 action significantly. These results suggest that the above TPA action may share some common mechanisms with the tumor-promoting action of this agent. On the other hand, the forskolin- and cholera toxin-stimulated cAMP formations were not changed by pretreatment of the cells with TPA. Therefore, our results indicate that the potentiating action of TPA on PGE1-stimulated cAMP formation in 3T3 cells is not due to the activation of the catalytic unit or the stimulatory guanine nucleotide binding protein (Ns) of adenylate cyclase (AC) system by this agent. It is highly likely that TPA induces some alterations on PGE1 receptors or on PGE1 receptor-Ns coupling systems and consequently induces an augmentation of PGE1-stimulated cellular cAMP response.

Adenylyl Cyclases↗
PubMed1986

A new assay for N-hydroxyarylamine O-acetyltransferase: reduction of N-hydroxyarylamines through N-acetoxyarylamines.

A simple fluorometric assay for N-hydroxyarylamine O-acetyltransferase is described and compared with a nucleic acid-binding assay. The assay method is based on the finding that the highly mutagenic 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-OH-Glu-P-1) was reduced to the corresponding amine, 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), through N-acetoxy-Glu-P-1 as the reactive intermediate in the presence of N-hydroxyarylamine O-acetyltransferase, acetyl-CoA, and a sulfhydryl compound. The formation of Glu-P-1 was determined by its characteristic fluorescence intensity at 445 nm with excitation wavelength at 376 nm. The reductive reaction was inhibited by the addition of tRNA, DNA, and poly(G), to which the enzymatic product, N-acetoxy Glu-P-1, bound effectively due to its electrophilic nature. Since the fluorometric assay for the O-acetyltransferase is rapid, simple, and sensitive as compared with the nucleic acid-binding method using radioisotope-labeled N-hydroxyarylamine, this method is applicable to the general assay for the formation of reactive N-acetoxy-Glu-P-1.

Acetyltransferases↗
PubMed1986

Nicotinic receptor-mediated intracellular calcium release in cultured bovine adrenal chromaffin cells.

When cultured bovine adrenal chromaffin cells were stimulated by a nicotinic agonist, carbamylcholine (0.3 mM) or 1,1-dimethyl-4-phenylpiperazinium (50 microM), in the Ca2+-free medium containing 0.1 mM ethyleneglycoltetraacetic acid, intracellular free Ca2+ concentration ([Ca2+]i) rose from approximately 90 to 149 nM. High K+ (56 mM) and veratridine (50 microM) had no effect on the [Ca2+]i in Ca2+-free medium. The carbamylcholine-evoked rise in [Ca2+]i was blocked by hexamethonium (0.1 mM) but not by atropine (1 microM). Furthermore, the carbamylcholine-evoked rise in [Ca2+]i was inhibited by an intracellular Ca2+ antagonist, 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxy-benzoate hydrochloride (10 microM) but not by a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (20 microM). These results show the existence of intracellular Ca2+ store sites, from which Ca2+ is released upon nicotinic receptor stimulation, in cultured adrenal chromaffin cells.

Adrenal Glands↗
PubMed1986

Strain difference in the effects of morphine on the rectal temperature and respiratory rate in male mice.

Effects of morphine on the rectal temperature and respiratory rate, and [3H]naloxone binding to brain membranes from seven brain regions were compared among six strains of male mice, including DBA/2N, C57BL/6N, BALB/c, C3H/HeN, A/J and ICR. The administration of 10 and 20 mg/kg doses of morphine HCl to these strains of mice decreased rectal temperature and respiratory rate. However, there was a significant strain difference in these two measures of the effect of morphine. The DBA/2N strain was the most sensitive in both measures of morphine action. The magnitude of hypothermia was positively correlated with respiratory depression among six strains of mice after the administration of 10 and 20 mg/kg morphine HCl, suggesting common mechanisms. Strain difference in naloxone binding in the brain regions could not explain that of the morphine responses, because there was no correlation between the intensity of morphine-induced hypothermia or respiratory depression and the regional [3H]naloxone binding for the mouse strains.

Animals↗
PubMed1986

Effects of bepridil on the electrophysiologic properties of isolated canine and rabbit myocardial fibers.

Bepridil hydrochloride is a relatively new calcium antagonist which appears to have a complex pharmacologic profile, but its concentration-response characteristics with respect to its electrophysiologic properties of varying concentrations (0.1 to 10.0 micrograms/ml) of the drug were therefore determined in rabbit and canine myocardial fiber preparations in vitro by standard microelectrode techniques. The following were measured: sinus cycle length (SCL), action potential amplitude (APA), maximum diastolic potential (MDP), threshold potential (TP), slope of phase 4 depolarization, action potential duration (APD), and dV/dtmax of phase O depolarization (Vmax) in rabbit sinoatrial (SA) node. Also measured were APA, membrane resting potential (MRP), Vmax, APD at 50% and 90% repolarization (APD50 and APD90), and effective refractory period (ERP) in rabbit atria and canine Purkinje fibers and ventricular muscle. At the lowest concentrations bepridil selectively prolonged SCL by reducing the slope of phase 4 and decreased APA and MDP in a concentration-dependent manner in the sinus node. At higher concentrations, bepridil exerted additional effects in producing concentration-dependent decreases in APA and Vmax in rabbit atria and in canine Purkinje fibers and ventricular muscle. During superfusion with 1.0 micrograms/ml bepridil, Vmax fell by 22.2% (p less than 0.05) in Purkinje fibers and by 11.8% (NS) in ventricular muscle; at 10.0 micrograms/ml, Vmax fell by 46.5% (p less than 0.01), respectively. The depression of Vmax was frequency dependent. There was a differential effect of bepridil on repolarization in Purkinje fibers as compared to that in ventricular muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1986

Electropharmacology of amiodarone: absence of relationship to serum, myocardial, and cardiac sarcolemmal membrane drug concentrations.

Plasma concentrations are often of major consideration in the evaluation of therapeutic efficacy of cardiovascular drugs. This approach is based on the assumptions that the concentration of the drug in the cardiac muscle is in equilibrium with the plasma drug level and that pharmacologic efficacy is proportional to the myocardial drug concentration. The more pronounced pharmacologic efficacy of amiodarone following chronic administration, despite low plasma drug concentrations, and the lesser effects of the drug after acute intravenous administration, when drug levels are maximum, has not been explained on the basis of the pharmacokinetic behavior of the drug. Data obtained from the transmembrane action potential recordings from rabbit ventricular myocardium were therefore correlated with drug concentrations in the serum, myocardium, and myocardial sarcolemma following acute intravenous administration and after 4 weeks of oral administration of 20 mg/kg/day of amiodarone. Following 15 minutes of acute drug administration, when amiodarone concentrations were maximal in the serum (4.72 +/- 1.23 micrograms/ml), cardiac muscle (34.5 +/- 7.6 micrograms/gm), and sarcolemma (1.94 mg/gm protein), the electrophysiologic changes were insignificant. However, following chronic treatment, when levels of amiodarone were low in the serum (0.05 +/- 0.01 micrograms/ml amiodarone, 0.25 +/- 0.08 micrograms/ml desethylamiodarone), cardiac muscle (1.91 +/- 0.9 micrograms/gm amiodarone, 1.35 +/- 1.33 micrograms/gm desethylamiodarone), and myocardial membranes (0.043 mg/gm protein [amiodarone], 0.097 mg/gm protein [desethylamiodarone], there was a 54.3% increase in action potential duration at 90% repolarization (p less than 0.01) and 65% increase in the effective refractory period (p less than 0.01) of rabbit ventricular myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗
PubMed1986

Inhibition of acetyl-coenzyme A dependent activation of N-hydroxyarylamines by phenolic compounds, pentachlorophenol and 1-nitro-2-naphthol.

Pentachlorophenol (PCP) and 1-nitro-2-naphthol were found to be potent inhibitors of enzymatic acetyl-CoA dependent activation, which is suggested as proceeding through direct O-acetylation, of N-hydroxyarylamines to tRNA binding by liver cytosolic enzymes from hamsters and rats. IC50 values of PCP for the activation of 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-OH-Glu-P-1), 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (N-OH-Trp-P-2) and N-hydroxy-2-aminofluorene (N-OH-AF) were 20, 25 and 17 microM, respectively, in hamster cytosol system. Similar inhibition was observed with rat liver cytosol (IC50 values of PCP and 1-nitro-2-naphthol were 13 and 12 microM, respectively, for the binding of N-OH-Glu-P-1). PCP is known as an inhibitor of sulfotransferase; however, another potent inhibitor of sulfotransferase, 2,6-dichloro-4-nitrophenol, did not inhibit the acetyl-CoA dependent binding. Antibiotic thiolactomycin, which inhibits bacterial O-acetyltransferase, did not affect the activation by hamster and rat cytosol, indicating the difference in property between bacterial and mammalian enzymes. The kinetic data obtained with hamster cytosol suggested the competitive inhibition of PCP with substrate, N-OH-Glu-P-1, and non-competitive inhibition with acetyl-CoA. In addition to the O-acetylation, PCP and 1-nitro-2-naphthol also inhibited N-acetylation of arylamines and N,O-acetyltransfer reaction of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) by hamster cytosol. IC50 values for these two types of acetyltransfer reactions, however, were slightly higher than those observed for acetyl-CoA dependent activations of N-hydroxyarylamines.

Acetyl Coenzyme A↗