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M Horie

Publications and source records attributed to M Horie.

At least 73 records · Page 4Linked to original sources
PubMed1998

Metabolic inhibition impairs ATP-sensitive K+ channel block by sulfonylurea in pancreatic beta-cells.

The effect of metabolic inhibition on the blocking of beta-cell ATP-sensitive K+ channels (KATP channels) by glibenclamide was investigated using a patch-clamp technique. Inhibition of KATP channels by glibenclamide was attenuated in the cell-attached mode under metabolic inhibition induced by 2,4-dinitrophenol. Under a low concentration (0.1 microM) of ATP applied in the inside-out mode, KATP channel activity was not fully abolished, even when a high dose of glibenclamide was applied, in contrast to the dose-dependent and complete KATP channel inhibition under 10 microM ATP. On the other hand, cibenzoline, a class Ia antiarrhythmic agent, inhibits KATP channel activity in a dose-dependent manner and completely blocks it, even under metabolic inhibition. In sulfonylurea receptor (SUR1)- and inward rectifier K+ channel (Kir6.2)-expressed proteins, cibenzoline binds directly to Kir6.2, unlike glibenclamide. Thus, KATP channel inhibition by glibenclamide is impaired under the condition of decreased intracellular ATP in pancreatic beta-cells, probably because of a defect in signal transmission between SUR1 and Kir6.2 downstream of the site of sulfonylurea binding to SUR1.

2,4-Dinitrophenol↗
PubMed1998

Cloning of a novel gene (ING1L) homologous to ING1, a candidate tumor suppressor.

The ING1 gene encodes p33(ING1), a putative tumor suppressor for neuroblastomas and breast cancers, which has been shown to cooperate with p53 in controlling cell proliferation. We have isolated a novel human gene, ING1L, that potentially encodes a PHD-type zinc-finger protein highly homologous to p33(ING1). Fluorescence in situ hybridization and radiation-hybrid analyses assigned ING1L to human chromosome 4. Both ING1 and ING1L are expressed in a variety of human tissues, but we found ING1L expression to be significantly more pronounced in tumors from several colon-cancer patients than in normal colon tissues excised at the same surgical sites. Although the significance of this observation with respect to carcinogenesis remains to be established, the data suggest that ING1L might be involved in colon cancers through interference with signal(s) transmitted through p53 and p33(ING1).

Adenocarcinoma↗
PubMed1998

Successful radiofrequency current catheter ablation of accessory atrioventricular pathway after tricuspid replacement in Ebstein's anomaly.

A 15-year-old female with Ebstein's anomaly was referred to hospital for radiofrequency (RF) current catheter ablation of her refractory paroxysmal supraventricular tachycardia (PSVT) after tricuspid valve replacement. A surface ECG showed ventricular preexcitation of type B Wolff-Parkinson-White (WPW) syndrome. In a baseline electrophysiological study, two types of PSVT with left and right bundle branch block (LBBB and RBBB) configurations were induced. The LBBB type was antidromic and the RBBB type was orthodromic atrioventricular reciprocating tachycardia (AVRT) with a right posterolateral accessory pathway. RF current was successfully delivered at the posterolateral site above the prosthetic valve (V-delta interval = -30 msec). The patient has been free from arrhythmias during a follow-up period of 9 months. RF current ablation seems to be useful for AVRT patients with corrected Ebstein's anomaly.

Adolescent↗
PubMed1998

Dietary balance chart for an on-line computerized graphical support system in MHTS.

Dietary habits are believed to play an important role in the etiology of adult disease. For this reason, it is necessary to include effective dietary guidance in multiphasic health testing and services (MHTS) programmes for primary disease prevention. We have developed such a programme of simple dietary advice, using a computer system for the MHTS. Examinees' dietary habits are checked using optical character record (OCR) questionnaire forms, and the results are displayed on the screen of a colour display terminal. They are required to prepare a menu of their usual daily dietary intake in terms of quantity and type of food. Thus the data collected relate to the nutritional composition of the examinee's usual diet. Nutritional requirements of the Japanese according to sex, height, and level of physical activity, in accordance with criteria set by the Japanese Ministry of Health and Welfare, are fed into the computer in advance. For each examinee, these criteria and the results of the assessment of the diet are displayed together on the screen in the form of colour graphs for comparison.

Adult↗
PubMed1997

Myocardial ischemia induces differential regulation of KATP channel gene expression in rat hearts.

The cardiac ATP-sensitive potassium (KATP) channel is thought to be a complex composed of an inward rectifier potassium channel (Kir6.1 and/or Kir6.2) subunit and the sulfonylurea receptor (SUR2). This channel is activated during myocardial ischemia and protects the heart from ischemic injury. We examined the transcriptional expression of these genes in rats with myocardial ischemia. 60 min of myocardial regional ischemia followed by 24-72 h, but not 3-6 h, of reperfusion specifically upregulated Kir6.1 mRNA not only in the ischemic (approximately 2.7-3.1-fold) but also in the nonischemic (approximately 2.0-2.6-fold) region of the left ventricle. 24 h of continuous ischemia without reperfusion also induced an increase in Kir6.1 mRNA in both regions, whereas 15-30 min of ischemia followed by 24 h of reperfusion did not induce such expression. In contrast, mRNAs for Kir6.2 and SUR2 remained unchanged under these ischemic procedures. Western blotting demonstrated similar increases in the Kir6.1 protein level both in the ischemic (2.4-fold) and the nonischemic (2.2-fold) region of rat hearts subjected to 60 min of ischemia followed by 24 h of reperfusion. Thus, prolonged myocardial ischemia rather than reperfusion induces delayed and differential regulation of cardiac KATP channel gene expression.

ATP-Binding Cassette Transporters↗
PubMed1997

Functional compartmentalization of ATP is involved in angiotensin II-mediated closure of cardiac ATP-sensitive K+ channels.

BACKGROUND: The effects of angiotensin II (Ang II) on ATP-sensitive K+ channels (K(ATP)) were investigated in ventricular myocytes enzymatically isolated from adult guinea pig heart. METHODS AND RESULTS: In the whole-cell and cell-attached configurations (including open-cell-attached mode) of the patch-clamp technique, K(ATP) currents (I(KATP)) were activated through metabolic poisoning by the use of inhibitors of both glycolytic and oxidative ATP productions at 37 degrees C. In the whole-cell mode, I(KATP) were reversibly suppressed by increasing extracellular glucose and Ang II (1 nmol/L). In the cell-attached mode, Ang II concentration-dependently inhibited single K(ATP) activities with an IC50 value of 3.2+/-0.5 pmol/L (Hill coefficient=1.3+/-0.3). CV11974 (100 nmol/L), an angiotensin 1 (AT1) receptor-selective antagonist, blocked the inhibitory action of Ang II. Preincubation of myocytes with pertussis toxin (5 microg/mL for > 120 min at 37 degrees C) virtually prevented subsequent Ang II action. The inhibitory effect of Ang II was also abolished in the open-cell-attached mode (achieved by a prior perfusion of streptolysin-O, 0.08 U/mL). In this mode, through tiny membrane holes, the intracellular ATP concentration can be controlled by bathing extracellular solutions containing a known ATP concentration. CONCLUSIONS: The inhibitory actions of Ang II on K(ATP) appear to be mediated by an increase in the subsarcolemmal ATP concentration that results from the inhibition of adenylate cyclase activities via AT1 receptors/PTX-sensitive G proteins.

Adenosine Triphosphate↗
PubMed1997

Identification and characterization of a novel human phosphatidylinositol 4-kinase.

The extensive sequence homology that exists among the catalytic domains of phosphatidylinositol 3- and 4-kinases allowed us to clone a novel human gene encoding a putative phosphatidylinositol kinase, NPIK. Among other known phosphatidylinositol 3- and 4-kinases, NPIK was most closely related to yeast PIK1 phosphatidylinositol 4-kinase. Several forms of NPIK cDNAs were isolated, and expression of NPIK message was detected in a wide variety of tissues. Fluorescence in situ hybridization and radiation hybrid analyses assigned the NPIK gene to human chromosome 1. Recombinant NPIK protein catalyzed a conversion from phosphatidylinositol to phosphatidylinositol 4-phosphate. The catalytic activity of NPIK was augmented by Triton X-100, and was reduced in the presence of adenosine. Using green fluorescent protein system we determined that NPIK is localized in the cytoplasm. Taken together, the data suggest that NPIK may play a pivotal role in regulating the synthesis of phosphatidylinositol 4-phosphate at the site(s) accessible from cytoplasm.

1-Phosphatidylinositol 4-Kinase↗
PubMed1997

Cloning and characterization of a novel member of the human Mad gene family (MADH6).

MAD (mothers against decapentaplegic)-related proteins (MADRs) are intracellular components that play critical roles in signal-transduction pathways involving the transforming growth factor beta (TGFbeta) superfamily. Some Mad genes are candidates for tumor-suppressor functions. From a human fetal brain cDNA library we have isolated a novel Mad-related gene. Two alternatively transcribed mRNAs encode deduced 430- and 467-amino-acid peptides that showed high levels of similarity to MADR1/Smad1/hMAD1 (about 80% identity at the amino acid level). This gene, which we designated MADH6, resides on 13q12-q14 between BRCA2 and RB, a region that frequently displays loss of heterozygosity in breast, liver, and prostate cancers.

Amino Acid Sequence↗
PubMed1997

Angiotensin II inhibits protein kinase A-dependent chloride conductance in heart via pertussis toxin-sensitive G proteins.

BACKGROUND: Angiotensin II receptors are reported to be abundant in the guinea pig ventricle; their coupling to adenylate cyclase in the heart, however, remains controversial. Therefore, we investigated the effect of angiotensin II on Cl- conductance activated by cAMP-dependent protein kinase. METHODS AND RESULTS: After minimizing the contribution of other ionic currents, exposure of single guinea pig ventricular cells to isoproterenol (40 to 50 nmol/L; 36 degrees C) elicited a typical protein kinase A-dependent Cl- conductance. Subsequent application of angiotensin II reduced the isoproterenol-induced conductance with an IC50 of 0.24 +/- 0.08 nmol/L. Angiotensin II also inhibited the Cl- currents, which were activated through stimulation of adenylate cyclase by forskolin and histamine receptors. CV-11974 (1 mumol/L), an antagonist selective for the angiotensin type 1 receptor, prevented the effect of angiotensin II. Angiotensin II did not inhibit the current that had been persistently activated by intracellular GTP gamma S (100 mumol/L), a nonhydrolyzable guanine nucleotide, plus isoproterenol. In addition, prior incubation of myocytes with pertussis toxin prevented the angiotensin II inhibitory action. Cl- conductance, when activated directly by intracellular dialysis with cAMP (1 mmol/L), was not affected by angiotensin II. Radioimmunologic measurement of cellular cAMP in the dissociated myocytes showed that angiotensin II inhibited the isoproterenol-induced increase of cAMP. CONCLUSIONS: Angiotensin II receptors negatively couple to adenylate cyclase via pertussis toxin-sensitive G proteins, thereby inhibiting cardiac protein kinase A-dependent Cl- conductance.

Adenylate Cyclase Toxin↗
PubMed1997

Endothelin-1 inhibition of cardiac ATP-sensitive K+ channels via pertussis-toxin-sensitive G-proteins.

OBJECTIVE: Secretion of endothelin-1 (ET-1) and activation of cardiac ATP-sensitive K+ (KATP) channels are facilitated under myocardial metabolic stress. The aim of this study was to investigate the effects of ET-1 on KATP channels and to assess underlying mechanisms in ventricular myocytes. METHODS: Single channel currents were measured with the voltage-clamp technique in cell-attached patches from enzymatically-isolated single guinea pig ventricular myocytes. In some experiments, the open-cell-attached mode was employed by permeating the membrane with streptolysin-O. RESULTS: ET-1 concentration-dependently inhibited single KATP channel currents, which had been activated by metabolic poisoning, with an IC50 of 3.8 +/- 0.7 pM. BQ-123, an ETA receptor-selective antagonist, reduced the effects of ET-1. ET-1 effects were largely abolished in the myocytes pre-incubated with pertussis toxin. In the open-cell-attached mode, where the intracellular ATP concentration ([ATP]) could be virtually controlled, the effects of ET-1 were abolished. Muscarinic receptor stimulation inhibited the channels in a similar manner to ET-1, whereas beta-adrenoceptor stimulation accelerated channel activation. By analogy, ouabain also inhibited KATP channel activity under metabolic stress presumably because inhibition of the Na+/K+ pump spares subsarcolemmal ATP. ET-1 inhibited the KATP channels that had been reactivated in the continuous presence of ouabain. CONCLUSIONS: ET-1 reversibly inhibited KATP channels. This effect appears to be mediated by an increase in subsarcolemmal [ATP] which results from inhibition of adenylate cyclase activities through PTX-sensitive G-proteins coupled to ETA receptors.

Adenosine Triphosphate↗
PubMed1997

Insulin secretion and its modulation by antiarrhythmic and sulfonylurea drugs.

Cardiovascular drugs such as antiarrhythmic agents with Vaughan Williams class Ia action have been found to induce a sporadic hypoglycemia. Recent investigation has revealed that these drugs induce insulin secretion from pancreatic beta-cells by inhibiting ATP-sensitive K+ (KATP) channels in a manner similar to sulfonylurea drugs. The mechanism underlying block of KATP channels by antiarrhythmic drugs was different, however, from that of sulfonylureas: firstly, because binding of radioactive glibenclamide could not be inhibited by unlabelled antiarrhythmic agents, and vice versa; secondly, because the two compounds differ in the kinetics and sidedness of drug action-antiarrhythmic drugs act on the channel from the inner surface of the cell membrane, whereas glibenclamide binds through the intramembrane pathway; finally, it was shown that functional KATP channels in beta-cells are composed of two distinct molecules-a sulfonylurea receptor (SUR) and a channel pore-forming subunit, an inwardly-rectifying K channel with two transmembrane regions (Kir6.2). Antiarrhythmic drugs reversibly inhibit the K+ conductance displayed by the Kir6.1 (a putative KATP channel clone)-transfected NIH3T3 cells. Therefore they appear to interact directly with the pore-forming subunit, thereby inhibiting KATP channel currents and exerting an insulinotrophic effect.

3T3 Cells↗
PubMed1997

Comparison of the accuracy of the lithium dilution technique with the thermodilution technique for measurement of cardiac output.

A new indicator dilution technique for measurement of cardiac output is described. Lithium chloride is injected via a central venous catheter and its dilution curve measured in arterial blood using a lithium-selective electrode. We assessed the lithium dilution cardiac output measurement (LiDCO) and a conventional thermodilution cardiac output measurement (ThDCO) by comparing the results of both with cardiac output determined by electromagnetic flowmetry (EMCO) under controlled laboratory conditions in 10 swine. They were monitored with a pulmonary artery catheter, femoral artery catheter and electromagnetic flowmeter placed around the ascending aorta. LiDCO, ThDCO and EMCO measurements were determined at baseline, in a hyperdynamic state produced by administration of dobutamine, at a second baseline and finally in a hypodynamic state induced by propranolol during deep anaesthesia. Data were analysed by linear regression analysis and the comparison method described by Bland and Altman; bias and precision of both LiDCO and ThDCO compared with EMCO were calculated by the method of Sheiner and Beal. The correlation coefficient between LiDCO and EMCO (0.95) was higher than that between ThDCO and EMCO (0.87). The precision value of LiDCO (0.04) was significantly less (i.e. better) than that of ThDCO (0.09). The results of this study indicated that LiDCO was more reliable compared with conventional ThDCO.

Animals↗
PubMed1997

Actions of taurine on the L-type Ca2+ channel current in guinea pig ventricular cardiomyocytes.

Effects of taurine on the L-type channel in isolated guinea pig ventricular cardiomyocytes were examined at different Ca2+ concentrations by using whole-cell and cell-attached voltage-clamp modes. All experiments were performed at 36 degrees C. In whole-cell voltage-clamp experiments, test pulses were applied between -20 to +60 mV from a holding potential of -40 mV. When [Ca]i was pCa 6, addition of 10 and 20 mM taurine to the bath solution reduced the Ca2+ current (I(Ca)) at 0 mV by 14.4 +/- 2.0% (n = 8; p < 0.01) and 31.5 +/- 2.2% (n = 8; p < 0.001), respectively. In contrast, when [Ca]i was pCa 8, I(Ca) at +10 mV was enhanced by 10.1 +/- 2.2% (n = 7; p < 0.05) at 10 mM taurine and by 41.7 +/- 2.1% (n = 7; p < 0.001) at 20 mM taurine. Taurine increased the time constants (tau(f) and tau(s)) of inactivation phase for I(Ca) current at both pCa 8 and 6. In cell-attached voltage-clamp experiments, taurine (20 mM) decreased the open probability of unitary Ba2+ current from 0.63 +/- 0.06 to 0.39 +/- 0.09 (n = 5; p < 0.01) at 5.4 mM [Ca]o, whereas taurine increased it from 0.21 +/- 0.04 to 0.48 +/- 0.07 (n = 4; p < 0.01) at 0.9 mM [Ca]o. Taurine did not affect the channel conductance. In addition, taurine (20 mM) increased the time constants (tau(of) and tau(os)) of the open time and decreased tau(cs) of the closed time at 0.9 mM [Ca]o. At 5.4 mM [Ca]o, the tau(os) and tau(cs) were also increased and decreased, respectively. tau(of) and tau(cf) were unaffected. These results indicate that taurine modulates the open probability of L-type Ca2+ channel dependent on [Ca]i and [Ca]o, thereby maintaining the normal [Ca]i level.

Animals↗
PubMed1997

Cloning, expression and mapping of a novel RING-finger gene (RNF5), a human homologue of a putative zinc-finger gene from Caenorhabditis elegans.

The RING-finger is a unique zinc-chelating domain involved in mediating protein-protein interactions. The extensive sequence homology within the RING-finger domain allowed us to clone a novel member of the RING-finger family of genes. This cDNA clone, designated RNF5 (Ring-finger protein 5), contained an open reading frame of 540 nucleotides. Its predicted amino acid sequence revealed significant homology to a hypothetical protein encoded by Caenorhabditis elegans cosmid C16C10.7. The expression of RNF5 was detected in a variety of human tissues. The RNF5 gene was mapped by fluorescence in situ hybridization to chromosome 6p21.31. Radiation hybrid mapping further assigned RNF5 to a region proximal to the major histocompatibility complex (MHC) on chromosome 6. RNF5 is the third RING-finger gene identified in the region proximal to MHC raising the possibility that the RING-finger family of genes may exist as a cluster in this region.

Animals↗
PubMed1997

Endothelin-1 inhibits the slow component of cardiac delayed rectifier K+ currents via a pertussis toxin-sensitive mechanism.

Endothelin-1 (ET-1) is a 21-amino acid peptide hormone released from myocardial and endothelial cells, whose receptors (both ETA and ETB are expressed in the myocardium. We report here that ET-1 inhibits the cardiac delayed rectifier K+ current (IK) via a pertussis toxin (PTX)-sensitive mechanism. Ventricular myocytes enzymatically isolated from guinea pig hearts were voltage-clamped by the conventional whole-cell and nystatin-perforated patch technique (intrapipette and extrapipette K+ concentrations, 150 and 5.4 mmol/L, respectively) in the presence of nifedipine (2 mumol/L). Amplitudes of tail and steady state (2-second pulse) currents were measured as IK. ET-1 suppressed the basal IK by 20.9 +/- 2.3% in a concentration-dependent manner, with an IC50 of 1.1 +/- 0.3 nmol/L (n = 19), although it did not suppress the basal IK using the nystatin method. E-4031 (5 mumol/L), a blocker of the rapid component of IK (IKr), did not prevent the inhibitory action of ET-1. ET-1 reduced by 63.4 +/- 6.5% the slow component of IK (IKs) that had been enhanced to approximately 2-fold by isoproterenol (ISO, 20 nmol/L). The action was concentration dependent, with an IC50 of 0.7 +/- 0.4 nmol/L (n = 22), and was also observed using the nystatin method. The effect of ET-1 appeared to be mediated by an ETA receptor, because it was prevented by FR139317, an ETA-selective antagonist (1 mumol/L, n = 4), and sarafotoxin s6c, an ETB-selective agonist (100 nmol/L, n = 4), could not inhibit the ISO-enhanced IK. ET-1 antagonized IKs enhanced by histamine (250 nmol/L, n = 7) and forskolin (500 nmol/L, n = 7) but did not inhibit IKs enhanced by the internal application of cAMP (100 mumol/L, n = 6). Preincubation of myocytes with PTX (5 micrograms/mL for > 60 minutes at 36 degrees C) completely abolished the inhibitory action of ET-1 on the ISO-enhanced IKs (n = 4). Thus, nanomolar ET-1 inhibits IKs via the ETA receptor/PTX-sensitive G protein/PKA pathway.

Animals↗
PubMed1997

Exercise-induced second-degree atrioventricular block.

In this report we describe 2 patients with exercise-induced, second-degree atrioventricular (AV) block. Case 1 was a 49-year-old man with normal AV conduction at rest but who developed dyspnea on exertion. Treadmill testing showed an exercise-induced 2:1 AV block. Electrophysiologic study (EPS) demonstrated rate-dependent, presumably intrahissian, AV block. Case 2 was a 31-year-old woman with first-degree AV block and complete right bundle branch block with dyspnea on exertion and occasional syncope. She had twice undergone surgical patch closure of an ostium primum atrial septal defect. Exercise testing induced type II second-degree AV block. Atrial pacing during EPS did not disclose rate-dependent type II AV block, but disopyramide induced second-degree AV block.

Adult↗
PubMed1997

[Clinical efficacy of post-TUR prophylactic chemotherapy for superficial bladder cancer--the result of co-operative prospective randomized trial].

We have performed a prospective randomized clinical trial of post-operative prophylactic therapy for superficial bladder cancer since October in 1991. The criteria were as follows; age < or = 80 y.o., Ta/T1, TCC G1/G2, without CIS lesion and resectable cancer by TUR. The therapeutic arm was divided into three as follows: arm A intracystic instillation with Epirubicin; arm B: oral administration with 5-FU; arm C: combination of arm A and arm B. The number of registered patients were 20 in arm A, 18 in arm B, and 18 in arm C. The patient characteristics in every group were not significantly different. The prophylactic efficacy of arm A was superior to that in the other two groups.

Administration, Intravesical↗