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H Inoue

Publications and source records attributed to H Inoue.

At least 1,405 records · Page 78Linked to original sources
PubMed1991

Sulfonylurea enhances insulin-induced acetyl coenzyme A carboxylase activity in rat adipocytes.

The effect of sulfonylurea on the activity of acetyl-coenzyme A carboxylase, a rate limiting enzyme of lipogenesis, was investigated using isolated rat adipocytes. Insulin significantly increased the enzyme activity by 170% of the control level, while glucagon and epinephrine decreased the activity of the enzyme by 53% and 64% of the control, respectively. In the presence of tolbutamide (10(-3) M) or glibenclamide (10(-6) M), a significant potentiation of insulin action was found in adipocytes. In addition, sulfonylurea restored the activity of acetyl-CoA carboxylase reduced by glucagon or epinephrine to the control level. Sulfonylurea enhancement of the acetyl-CoA carboxylase activity may offer one possible explanation for a mechanism of antilipolytic action of the drug in adipocytes.

Acetyl-CoA Carboxylase↗
PubMed1991

Antiarrhythmic drugs preferentially produce conduction block at the area of slow conduction in the re-entrant circuit of canine atrial flutter: comparative study of disopyramide, flecainide, and E-4031.

STUDY OBJECTIVE: The aim was to test whether antiarrhythmic drugs preferentially suppressed conduction in the area of slow conduction in the re-entrant circuit. DESIGN: Intravenous disopyramide [n = 8, plasma concentrations: 1.4 (SEM 0.2) micrograms.ml-1], flecainide [n = 8, 0.6(0.1) micrograms.ml-1], and E-4031, a new class III antiarrhythmic drug [n = 8, 5.6(1.0) ng.ml-1], were investigated for their effects on atrial flutter due to re-entry in dogs with intercaval crush. In three dogs, detailed atrial activation sequence during atrial flutter was determined with a hand held bipolar electrode and an epicardial isochronal map was drawn. EXPERIMENTAL MATERIAL: 24 anaesthetised adult mongrel dogs were used. MEASUREMENTS AND MAIN RESULTS: There was an area of slow conduction during atrial flutter in the low right atrium. Atrial flutter was terminated in all dogs except for one treated with flecainide. In 92% of the dogs, conduction block occurred in the low right atrium in which the area of slow conduction was located. Increase in local conduction time was greater in the area of slow conduction than other parts of the atria (percent ratio to the increase in cycle length of atrial flutter: 63% with disopyramide, 52% with flecainide, and 99% with E-4031). CONCLUSION: These data suggested antiarrhythmic drugs preferentially suppressed conduction at the area of slow conduction in the re-entrant circuit leading to termination of atrial flutter in this canine model, irrespective of electrophysiological effects of antiarrhythmic drugs.

Animals↗
PubMed1991

Genetic and molecular properties of human and rat renin-binding proteins with reference to the function of the leucine zipper motif.

The presence of a leucine zipper motif was recognized in the deduced amino acid sequences of human and rat renin-binding proteins (RnBPs) on cloning and sequence analysis of the RnBP cDNAs. The in vitro synthesized RnBPs, with the respective cDNAs, formed heterodimers with porcine renin and homodimers. On comparison of these properties with those of porcine RnBP, the leucine zipper motif was suggested to be a functional domain common to animal RnBPs. In addition to the motif, a hydrophobic domain adjacent to the motif and 10 cysteine residues were also well conserved in the three RnBPs. Moreover, about 85% of their amino acid sequences were identical. The RnBP mRNAs were expressed in the kidneys as the same size of 1.5-kb and the genes are suggested to exist as single copies in the genomes. Despite the high similarities in genetic and molecular properties, the molecular weights of human and rat RnBPs were 43,000, which is 1,000 larger than that of porcine RnBP. The immunoreactivities of human and rat RnBPs toward anti-porcine RnBP antiserum were 88 and 8% that of porcine RnBP, respectively, and the affinities of the two RnBPs for porcine renin were remarkably less than that of porcine RnBP. Moreover, the human and rat RnBP homodimers were partly dissociated under the conditions under which porcine RnBP existed as a dimer. These results indicate distinct differences in the molecular properties among the three RnBPs, in spite of their being highly similar structurally and functionally.

Amino Acid Sequence↗
PubMed1991

Effects of pentisomide and E-4031 on canine atrial flutter due to reentry: a comparative study with disopyramide and propafenone.

Effects of new antiarrhythmic drugs, pentisomide [3.5 +/- 0.5 mg/kg intravenously (i.v.) n = 8], and E-4031 (5.6 +/- 1.0 micrograms/kg, n = 8), a class III drug, on atrial flutter (AF) caused by reentry were compared with those of disopyramide (1.6 +/- 0.2 mg/kg, n = 8) and propafenone (2.2 +/- 0.2 mg/kg, n = 8). AF was induced with burst atrial pacing after we made an intercaval crush in anesthetized, open-chest dogs. Termination of AF did not differ among test drugs (8 of 8 with disopyramide, 7 of 8 with propafenone, 6 of 8 with pentisomide, and 8 of 8 with E-4031). Cycle length (CL) of AF was prolonged more with propafenone (57 +/- 10%) and pentisomide (41 +/- 5%) than with E-4031 (12 +/- 3%, p less than 0.05). This was also true for increase in interatrial conduction time determined at a pacing CL of 150 ms. Increase in atrial effective refractory period (ERP) determined at a basic pacing CL of 300 ms did not differ among test drugs. Changes in CL of AF correlated significantly with those in interatrial conduction time (r = 0.84, p less than 0.001), but not with those of ERP (r = 0.10, NS). Reinitiation of AF was significantly greater in propafenone (7 of 7) and pentisomide (5 of 6) groups than in disopyramide (1 of 8) and E-4031 (0 of 8) groups (p less than 0.001). Pentisomide and E-4031 were effective in terminating canine AF due to reentry, as were disopyramide and propafenone. Reinitiation of AF was greater in dogs treated with antiarrhythmic drugs that had more prominent effects on conduction time than on ERP.

Animals↗
PubMed1991

Effects of methylthiodeoxyadenosine and its analogs on in vitro invasion of rat ascites hepatoma cells and methylation of their phospholipids.

The relationship between tumor invasiveness in vitro and methylation of plasma membrane phospholipids was investigated. For this purpose, two hepatoma cell lines, C1-30 and LC-AH, were used which show specific penetration to below cultured monolayers of mesothelial cells from rat mesentery and endothelial cells from calf pulmonary artery, respectively. Methylthiodeoxyadenosine (MTA) and five of its analogs, difluoro-MTA, deoxyadenosine, sinefungin, phenylthiodeoxyadenosine and fluorophenylthiodeoxyadenosine, inhibited the invasion of the tumor cells without affecting their proliferation. This inhibition was associated with reduction in the incorporation of radioactivity of [methyl-3H]methionine into cellular phosphatidylethanolamine derivatives without changes in the labelings of RNA and DNA and carboxylmethylation of protein. These compounds also decreased the membrane fluidity of the tumor cells, measured by a steady-state fluorescence polarization method. Three other MTA analogs (fluorodideoxyadenosine, fluoroazidodideoxyadenosine and fluoroaminodideoxyuridine) did not affect the invasiveness of the tumor cells or alter their phospholipid methylation or membrane fluidity at concentrations that did not inhibit proliferation. These results suggest that the decrease in invasiveness of tumor cells by MTA and its analogs is due to alterations in the phospholipid composition and fluidity of the tumor cell membranes.

Animals↗
PubMed1991

Do diagnostic procedures other than inhalation challenge predict immediate bronchial responses to inhaled allergen?

To investigate the relationships between allergen inhalation challenge and other diagnostic procedures, inhalation challenge with house dust (HD) allergen, intradermal skin tests with HD allergen, inhalation challenge with methacholine and circulating HD allergen-specific IgE levels were examined in 104 patients with bronchial asthma. Using the single exposure method, allergen inhalation challenge was performed. Forty-three patients had positive bronchial responses to allergen and 61 patients had negative bronchial responses. With serially diluted HD allergen (10(-3) to 10(-6), w/v), skin-test sensitivity was expressed as the highest dilution required to produce a weal of more than 9 x 9 mm. With the continuous exposure method, bronchial responsiveness to methacholine was evaluated as the number of units of inhaled methacholine (PD35-Grs) from the start to the point at which Grs had decreased by 35% from its baseline value. The level of circulating HD allergen-specific IgE was measured with the Phadebas RAST system and the results were assessed as a RAST score. Using discriminant analysis, in which the independent variables were skin-test sensitivity, PD35-Grs and the RAST score, only in 30% of all patients was bronchial responsiveness to inhaled HD allergen predictable. Therefore, we suggest that inhalation challenge with allergen is an essential test for determining the role of a specific allergen in airways at present.

Administration, Inhalation↗
PubMed1991

Doppler echocardiographic evaluation of an infant with HCM during ACTH therapy.

Adrenocorticotropic hormone (ACTH) therapy is useful in the treatment of patients with West syndrome, and hypertrophic cardiomyopathy (HCM) in association with ACTH therapy has recently been reported. We describe the Doppler echocardiographic evaluation of an infant who had West syndrome and HCM. ACTH therapy produced increases in the interventricular septal thickness, the pressure gradient of the left ventricular outflow tract, and the heart rate. Doppler echocardiographic examination was found to be much more sensitive for monitoring the cardiac changes than either 2-dimensional echocardiography or the heart rate.

Adrenocorticotropic Hormone↗
PubMed1991

Effects of porcine relaxin on contraction, membrane response and cyclic AMP content in rat myometrium in comparison with the effects of isoprenaline and forskolin.

1. The longitudinal muscle from the uterus of oestrogen-treated rats was quiescent in Mg-free Krebs solution. Electrical stimulation generated phasic contraction, which was depressed to 35% and 18% by 50 mu and 150 mu porcine relaxin, respectively. 2. The phasic contractions were more strongly depressed to 26% by 50 mu relaxin in solution containing 0.6 mM Mg, and the depression lasted for more than 4 h after the removal of relaxin. During the persisting depression, raising the external Ca to 7.5 mM did not restore the contraction, but the contraction was restored by removal of Mg. 3. The depression of the phasic contraction by relaxin, examined in Mg-free solution, was enhanced and reduced by pretreatment of the tissue with 0.6 mM Mg and 0.6 mM Mn, respectively, for about 15 min. In contrast, the depression of contraction by isoprenaline or forskolin was enhanced by pretreatment with either Mg or Mn. 4. The cellular content of cyclic AMP was measured in Krebs solution containing 0.6 mM Mg. The values were 1.24 (pmol mg-1 protein) in control solution, and 2.31 and 1.56 when the tissues were treated with 150 mu relaxin and 10(-9) M isoprenaline, respectively. 5. The cyclic AMP production in response to 10(-7) M forskolin measured in Mg-free solution was enhanced when the tissue was pretreated with either 0.6 mM Mg or Mn for 15 min. The cyclic AMP production in response to 100 mu relaxin was increased when the tissue was pretreated with 0.6 mM Mg, and was unchanged by pretreatment with Mn. The cyclic AMP production in response to 10(-9) M isoprenaline was unchanged by pretreatment with the divalent cations. 6. The membrane potential of the muscle was -60.8 mV in Krebs solution containing 0.3 mM Mg, and electrical stimulation induced an action potential which consisted of spike and plateau components. Application of 150 mu relaxin reduced the duration of the plateau; the contractions were progressively depressed. The resting membrane potential and membrane resistance were unchanged by application of 150 mu relaxin. The membrane was hyperpolarized by 2.8 mV, accompanied by a decrease in membrane resistance, when 10(-9) M isoprenaline was applied. 7. Although there were several differences between the effects of relaxin and isoprenaline, it is probable that some process, which is cyclic AMP-dependent, accelerated by Mg and depressed by Mn, is involved in the depressant action of relaxin on contraction.

Adrenergic beta-Agonists↗
PubMed1991

Rat primary embryo fibroblast cells suppress transformation by the E6 and E7 genes of human papillomavirus type 16 in somatic hybrid cells.

The E6 and E7 genes of human papillomavirus type 16 (HPV-16) transform established lines of rat cells but not rat cells in primary culture irrespective of the expression of the two genes. The reason for this difference between the susceptibilities of cell lines and primary cells was examined by using hybrid cells obtained by somatic cell fusion of rat cell lines transformed by the E6 and E7 genes of HPV-16 and freshly isolated rat embryo fibroblast cells. In these hybrid cells, transformed phenotypes, including colony formation in soft agar, saturation density, and tumorigenicity in nude mice, were suppressed, whereas hybrid cells between E6/E7-transformed cell lines and normal rat cell lines retained these transformed phenotypes. RNA analysis showed that the E6 and E7 genes were transcribed in both types of hybrid cells. These results suggest that primary rat cells possess intracellular functions that cause posttranscriptional suppression of induction of the transformed phenotypes by the E6 and E7 genes of HPV-16.

Animals↗
PubMed1991

Effects of immunization against VIP on neurotransmission in cat trachea.

To examine the possible role of vasoactive intestinal polypeptide (VIP) in excitatory and inhibitory neurotransmission and physiological function of coexistence VIP and acetylcholine at vagus nerve terminals in the cat trachea, we immunized five cats each against conjugate of VIP-bovine serum albumin (BSA) and BSA, respectively. A booster injection of VIP-BSA given 3 wk after the primary one elevated antibodies against VIP, as detected by enzyme-linked immunosorbent assay, but not in the control cats identically injected with BSA. After immunization, in vitro, summation phenomena observed in the amplitude of contractions and excitatory junction potentials of the trachea evoked by repetitive field stimulation were markedly enhanced, whereas the amplitude of phasic relaxation evoked by repetitive field stimulation in the presence of serotonin, atropine, and guanethidine was markedly reduced. In contrast, in vivo, the change in pulmonary resistance evoked by vagal stimulation was not affected in the immunized cats. We conclude that antibodies against neurotransmitter VIP are a potential modulatory factor in excitatory and inhibitory neurotransmission in airway smooth muscle at tissue or cellular levels. The lack of correlation between in vivo and in vitro conditions was discussed in relation to VIP autoantibodies in normal and asthmatic humans.

Animals↗
PubMed1991

Effects of procaterol, a beta-2-adrenoceptor stimulant, on neuroeffector transmission in human bronchial tissue.

It has been reported that low concentrations of noradrenaline or isoprenaline reduce the resting tension of the smooth muscle cells and suppress acetylcholine release from the vagal nerve terminals through activation of beta 2-adrenoceptors. Procaterol, beta 2-adrenoceptor stimulant, has a high potency and selectivity for airway smooth muscle tissues. However, there is little documentation on the prejunctional actions of this chemical in airway smooth muscle, especially in man. In the present study, the effects of procaterol on excitatory neuroeffector transmission in the human bronchus were investigated. Procaterol (10(-10) to 10(-7) M) dose dependently reduced the amplitude of the contractions evoked by electrical field stimulation in the presence of indomethacin (10(-5) M), FPL-55712 (10(-6) M), and guanethidine (10(-6) M). By contrast, procaterol (10(-10) to 10(-9) M) had no effect on the postjunctional response of smooth muscle cells to exogenously applied acetylcholine. Pretreatment with ICI-118551 (10(-7) M), a beta 2-adrenoceptor-blocking agent, reduced the inhibitory action of procaterol on the amplitude of twitch contractions evoked by field stimulations in the human bronchus. These results indicate that procaterol at low concentrations has a prejunctional action, inhibiting the excitatory neuroeffector transmission and presumably suppressing transmitter release from the vagal nerve terminals through beta 2-adrenoceptors in the human bronchial tissue. The prejunctional action of procaterol explains partly its potent bronchodilator effects in clinical use.

Acetylcholine↗
PubMed1991

Mortality, body weight, food and water consumption, and clinical signs in F344/DuCrj rats in studies of chronic toxicity and carcinogenicity.

In vivo historical control data, including mortality, body weight, food and water consumption, and clinical signs in F344/DuCrj rats were obtained from 11 long-term toxicity and carcinogenicity studies conducted at the Biosafety Research Center, Foods, Drugs and Pesticides, (An-Pyo Center) during the last five years. Survival at 109 weeks of age was 80.2% (min: 74%, max: 90%) in males and 80.5% (min: 72%, max: 92%) in females. The maximum mean body weights of males and females were 443.3 +/- 15.8 g (mean +/- S. D.) and 295.7 +/- 13.3 g respectively. Male rats attained their maximum body weight at 82.6 +/- 5.3 weeks of age, the females at 103.5 +/- 2.5 weeks of age. Clinical symptoms increased with age, particularly after 84 weeks of age, and included: wasting, piloerection, palpable subcutaneous and abdominal masses, and decreased spontaneous movement. Lowered body temperature and auricular pallor occurred commonly in moribund animals. The nature and grade of toxicity in the treated animals were generally disclosed by comparing with the behavior and signs in the control animals. The use of in-house, historical control data can be useful in subsequent evaluations of chronic toxicity and carcinogenicity studies.

Animal Husbandry↗
PubMed1991

[Relaxin and myometrial activity].

The research on intracellular signal transduction and the smooth muscle contraction have made much progress since 1970. Effects of relaxin, a peptide hormone mainly produced and released from ovary, are reviewed in the above point of view. Cyclic AMP content in myometrial cells is increased by relaxin. One site of relaxin action can be the suppression of myosin light chain kinase activity. Another effect of relaxin is the suppression of action potential, whereby the Ca-influx is reduced. However, relaxin up to 300 mU does not hyperpolarize the myometrial membrane of estrogen-primed rat, which differs from the adrenergic beta-action. Unrealed signal transduction seems involved in the relaxin action.

Action Potentials↗
PubMed1991

Bilirubin conjugation and biliary bilirubin excretion after intravenous bilirubin injection in dogs.

This study was undertaken to investigate the bilirubin clearance, bilirubin conjugation and biliary bilirubin excretion after an intravenous single bilirubin injection (5 mg/kg or 10 mg/kg) in 10 mongrel dogs. Serum total bilirubin concentration increased after the bilirubin injection, and then it immediately decreased. Biliary excretion of loaded bilirubin induced a rapid increase of the bile total bilirubin concentration and bilirubin-monoconjugate. In the 10 mg/kg group, the increase was larger than in the 5 mg/kg group and remained high up to 4 hr after injection, whereas in the 5 mg/kg group these bile components tended to decrease and returned to the preinjection levels within 4 hr. The total bile acid concentration in the bile remained unchanged in both groups. The bile flow did not change in the 5 mg/kg group, but in the 10 mg/kg group it decreased after bilirubin loading. Significantly positive correlations were observed between total bilirubin and bilirubin monoconjugate concentrations in bile both before and 1 hr after injection, but the slopes of regression lines were markedly different from each other. These results suggest that a bilirubin load surpassing the conjugating capacity of the hepatocytes increases bile bilirubin monoconjugate and also enhances the conjugating activity in the liver.

Animals↗
PubMed1991

8-Hydroxyguanine, a DNA adduct formed by oxygen radicals: its implication on oxygen radical-involved mutagenesis/carcinogenesis.

Oxygen radicals have been suggested to be involved in mutation/carcinogenesis. The C-8 position of guanine residues in DNA is hydroxylated to produce 8-hydroxyguanine (8-OH-Gua) in DNA in vitro by various oxygen radical producing agents. The formation of 8-OH-Gua was also observed in cellular DNA in vivo by radiation or oxygen radical forming carcinogens. The 8-OH-Gua residue in DNA is often misread in the position of 8-OH-Gua residue itself but also at neighboring residues next to 8-OH-Gua. When second guanine in codon 12 was specifically replaced with 8-OH-Gua and transferred to NIH3T3, the recipient cells were transformed to malignant cell type. E. coli was found to contain an endonuclease which specifically recognizes 8-OH-Gua residue and cleave DNA strand before and after the modified base. The data obtained imply that 8-OH-Gua formed in DNA in vivo is recognized as an abnormal modified base which, if not repaired, play a role in the mediation of oxygen radical-involved mutation/carcinogenesis.

Animals↗