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Biomedical subjects

T Ohe

Publications and source records attributed to T Ohe.

At least 55 records · Page 3Linked to original sources
PubMed1999

Manumycin A, inhibitor of ras farnesyltransferase, inhibits proliferation and migration of rat vascular smooth muscle cells.

Restenosis after angioplasty is thought to be caused by proliferation and migration of vascular smooth muscle cells (VSMCs), and it is a most serious problem in medical treatment. A low dose (50 ng/ml) of manumycin A, an inhibitor of p21(ras) (ras) farnesylation, significantly inhibited proliferation of rat VSMCs stimulated by the platelet-derived growth factor (PDGF). The mitoinhibitory effect of manumycin A was dose- and time-dependent but was independent of cell density. Western blot analysis showed that manumycin A reduced the amount of functional ras localized at the cytoplasmic membrane and inhibited the phosphorylation of p42/44 mitogen-activated protein kinase (MAPK). Manumycin A also inhibited VSMC migration and disorganized alpha actin fibers, as shown by immnofluorecence staining. These results indicate that the interruption of the ras/MAPK signal transduction pathway and the disorganization of alpha actin fibers are the main cause of manumycin A inhibition of VSMC proliferation and migration induced by PDGF.

Alkyl and Aryl Transferases↗
PubMed1999

Mutation spectra in Salmonella TA98, TA100, and TA104 of two phenylbenzotriazole mutagens (PBTA-1 and PBTA-2) detected in the Nishitakase River in Kyoto, Japan.

Previous studies have identified two potent aromatic amine mutagens in the Nishitakase River, a tributary of the Yodo River, which serves as the main drinking water supply for the Osaka area in Japan. The two potent mutagens are 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)amino]-5-methoxyphenyl]-5-am ino-7-bromo-4-chloro-2H-benzotriazole (PBTA-1) and 2-[2-(acetylamino)-4-[N-(2-cyanoethyl)ethylamino]-5-methoxyphenyl]-5- amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-2). PBTA-1 and PBTA-2 are presumed to be formed from azo dyes discharged in a reduced form from dye factories to sewage treatment plants where they become chlorinated and are then discharged into the river. PBTA-1 and PBTA-2 account for 21% and 17% of the mutagenic activity of the Nishitakase River, respectively. Here we determined the mutation spectra induced by these two mutagens in TA98, TA100, and TA104 at 30-35, 8-10, and 2x, respectively, above the background. In TA98, the PBTA compounds produced identical mutation spectra, with 100% of the revertants containing the hotspot 2-base deletion of CG within the (CG)(4) sequence. In TA100, 73% of the revertants were GC-->TA transversions, with most of the remaining being GC-->AT transitions; the spectra produced by the two compounds in TA100 were not significantly different (p=0.8). In TA104, as in TA100, the majority (83%-87%) of the revertants were GC-->TA transversions, with most of the remaining revertants (11%-13%) being AT-->TA transversions. Thus, 83%-87% of the mutations induced by the PBTA compounds in TA104 were at G/C sites. The mutation spectra produced by the two compounds in TA104 were not significantly different (p0.08). PBTA-1 and PBTA-2 are structurally similar and have similar mutagenic potencies and mutation spectra in the respective strains. The mutation spectra produced by the PBTA compounds (100% hotspot deletion in TA98 and primarily GC-->TA transversions in TA100 and TA104) are similar to those produced by other potent aromatic amines, which is the class of compounds from which the PBTA mutagens derive.

Base Pairing↗
PubMed1999

Total Ca handling in canine mild Ca overload failing heart.

We analyzed total Ca handling of the left ventricle (LV) in the mildly failing heart preparation induced by a temporary intracoronary Ca overloading intervention in eight excised and cross-circulated canine hearts. This Ca intervention consisted of interruption of coronary blood perfusion by Ca-free oxygenated Tyrode perfusion for 10 min followed by high-Ca (16mmol/l) oxygenated Tyrode perfusion for 5 min. This intervention decreased the LV contractility index, Emax (end-systolic maximum elastance), by 40% after restoration of the blood cross-circulation. We expected a Ca overload or paradox failing heart resembling the postischemic stunned heart and being characterized by an increased O2 cost of Emax. However, LV O2 consumption under mechanically unloading conditions decreased by 30% from control without increasing the O2 cost of Emax. To obtain a mechanistic view of this failing heart, we investigated cardiac total Ca handling by our integrative analysis method. In this method, we obtained the internal Ca recirculation fraction (RF) from the decay beat constant of the postextrasystolic potentiation following each sporadic spontaneous extrasystole in these failing LVs. We combined the RF with the decreased Emax and the unchanged O2 cost of Emax in our recently developed formula of total Ca handling. We found that these failing LVs had a slightly but significantly increased RF accompanied by either a slightly increased futile Ca cycling or a slightly decreased Ca reactivity of Emax, or both. Any of these three possible changes can account for the unchanged O2 cost of Emax. This result indicates that the present mildly failing heart has not yet fallen into a typical Ca overload or paradox by the temporary Ca overloading intervention.

Animals↗
PubMed1999

Myocardial mechanical restitution and potentiation partly underlie alternans decay of postextrasystolic potentiation: simulation.

We have reported that the postextrasystolic potentiation (PESP) decays in alternans or monotonically, respectively, depending on whether the first postextrasystolic beat interval has a compensatory pause or not, in the canine left ventricle. To get better mechanistic insight into the alternans PESP decay, we hypothesized that the myocardial mechanical restitution and potentiation could partly account for both types of PESP decay. To test this hypothesis, we simulated PESP decay on a computer using a documented equation combining myocardial mechanical restitution and potentiation. We changed the first postextrasystolic beat interval after a fixed extrasystolic beat interval without changing regular and other postextrasystolic beat intervals. The simulated PESP decayed in alternans or monotonically as a function only of the first postextrasystolic beat interval. Thus, the myocardial mechanical restitution and potentiation could partly account for both alternans and monotonic decay of PESP. We conclude that myocardial mechanical restitution and potentiation may partly underlie the initial two alternating beats, the first beat being the most potentiated and the second beat being the most depressed, of alternans PESP decay in the canine heart.

Animals↗
PubMed1999

Effect of pilsicainide, a pure sodium channel blocker, on spiral waves during atrial fibrillation: theoretical analysis by numerical simulation.

This study investigated the effects of a particular type of sodium channel blocker, pilsicainide, on spiral waves, which are a possible mechanism of atrial fibrillation, by using numerical simulation. A meandering spiral wave was induced on a two-dimensional matrix corresponding to the isolated atrial myocardium. The model attempted to simulate the changes caused by pilsicainide. The conductivity was depressed and the refractory period was prolonged with little change in the action potential duration. The dynamic change in the refractory period depended on the preceding coupling interval. A blockline occurred and changed gradually because of the change in the refractory period. The spiral wave became a stable reentry rotating around the blockline, decreasing the excitation frequency in the matrix before rushing out of the matrix. The electrocardiogram showed a slow coarse wave, as well as a real electrocardiographic change by pilsicainide. This might, in part, explain how pilsicainide acts on atrial fibrillation. Key words: sodium channel blocker, pilsicainide, spiral wave, atrial fibrillation, computer simulation.

Anti-Arrhythmia Agents↗
PubMed1999

A positioning device to allow rotation for cine-MRI of the distal radioulnar joint.

'Cine-mode' magnetic resonance imaging (MRI) is useful in the diagnosis and treatment of patients with disorders of joint motion. We have designed a device for imaging of the distal radioulnar joint by cine-MRI. Five normal wrists and eight patients with rheumatoid arthritis were investigated prior to surgery for subluxation of the distal radioulnar joint. Normally, the radius moves in a constant arc around the ulna, whereas in rheumatoid wrists the centre of rotation varies continuously with increase in rotation. The device should prove helpful in imaging disorders of the distal radioulnar joint.

Arthritis, Rheumatoid↗
PubMed1999

Increase in beating rate of cultured chick cardiac myocytes by ethanol and inhibition of the increase by antiarrhythmic drugs.

Drinking alcohol sometimes causes cardiac arrhythmia, but the precise mechanism remains unknown. To study the mechanism, we investigated the effects of ethanol exposure on the beating rate of cultured chick cardiac myocytes. Primary cultures of cardiac myocytes were prepared from the ventricles of 14-day-old chick embryos and then treated with ethanol which, in the range of 0.3 to 1.5 vol%, increased the beating rate in a dose-dependent manner. Ethanol (0.6 vol%) caused an increase in the beating rate, but disopyramide (5 microg/ml) and procainamide (10 microg/ml), Na+ and K+ channel blockers, inhibited the increase in the beating rate significantly. Neither lidocaine (5 microg/ml) nor mexiletine (2 microg/ml), Na+ channel blockers, nor calcium antagonist verapamil (5 ng/ml) inhibited the increase. However, tetraethylammonium chloride (ranging from 15 to 30 mmol/l), a K+ channel blocker, inhibited the increase. These findings indicate that ethanol increases the beating rate of cultured chick cardiac myocytes via the activation of the K+ channel. This experimental model may be useful in studying the effect of ethanol on the K+ channel.

Animals↗
PubMed1999

Asymptomatic form of Brugada syndrome.

We describe a patient with the asymptomatic form of Brugada syndrome. His electrographical, electropharmacological, and electrophysiological characteristics were similar to those reported in patients with the symptomatic form of Brugada syndrome. We believe that he has the same arrhythmogenic substrate as that of patients with Brugada syndrome. The fact that he had no episode of spontaneous ventricular fibrillation might be explained by his absence of the triggering factors.

Adult↗
PubMed1999

Evaluation of direct respiratory modulation of the QT interval variability.

To investigate the direct respiration-mediated vagal modulation of the QT interval variability, spectral analyses of the RTp interval (from the R wave peak to the T wave peak) variability (RTpV) and the RR interval variability (RRV) were performed in 12 subjects with normal ventricular repolarization under three conditions while the respiration frequency was kept at 0.2 Hz: during sinus rhythm, during fixed atrial pacing, and during fixed atrial pacing with autonomic blockade. The cross-spectrum between the RRV and RTpV was quantified by the squared coherence. During sinus rhythm the RRV power spectrum showed two peaks: a broad peak in the low frequency (LF) band and a sharp peak at 0.2 Hz which corresponded to the controlled respiration frequency. The RTpV power spectrum showed corresponding peaks to the RRV peaks in both the LF and high frequency (HF) bands with high coherence (mean maximum values of the squared coherence in the LF band 0.59 +/- 0.22, and in the HF band 0.74 +/- 0.14). During atrial pacing mean total power of the RTpV decreased from during sinus rhythm (from 16.3 +/- 5.6 ms2 to 12.9 +/- 5.4 ms2, P < 0.05) and the RTpV spectral peaks were abolished in both the LF and HF bands concordant with disappearance of the RRV peaks. Autonomic blockade gave no additional change to the RTpV power spectrum independently of the RRV during fixed atrial pacing. The present study suggested that the direct respiration-mediated vagal modulation may not affect the short-term variability of the QT interval in subjects without repolarization abnormality.

Autonomic Nervous System↗
PubMed1999

Nicorandil abolished repolarisation alternans in a patient with idiopathic long QT syndrome.

A 23 year old woman with idiopathic long QT syndrome had repeated syncopal attacks associated with torsades de pointes. T wave alternans (TWA) was recorded and the QT interval was abnormally prolonged during treadmill exercise test. Monophasic action potential (MAP) alternans also appeared after an abrupt shortening of the cycle length in electrophysiological study. After intravenous administration of nicorandil 6 mg, both TWA and MAP alternans disappeared.

Adult↗
PubMed1999

O(2) cost of contractility but not of mechanical energy increases with temperature in canine left ventricle.

We investigated the effects of myocardial temperature on left ventricular (LV) mechanoenergetics in the excised, cross-circulated canine heart. We used the framework of the LV contractility (E(max))-pressure-volume area (PVA; a measure of total mechanical energy)-myocardial oxygen consumption (VO(2)) relationship. We have shown this framework to be useful to integrative analysis of the mechanoenergetics of a beating heart. In isovolumic contractions at a constant pacing rate, increasing myocardial temperature from 30 to 40 degrees C depressed E(max) and increased the oxygen cost of E(max), which was enhanced by dobutamine, in a linear manner. However, the slope of the VO(2)-PVA relation (reciprocal of contractile efficiency) and its VO(2) intercept remained constant. Q(10) values of E(max), the oxygen cost of E(max), and the oxygen cost of PVA were 0.4, 2.1 and 1.0, respectively, around normothermia. We conclude that the temperature-dependent processes of cross-bridge cycling and Ca(2+) handling integratively depress E(max) and augment its oxygen cost without affecting the oxygen cost of PVA as myocardial temperature increases by 10 degrees C around normothermia.

Animals↗
PubMed1999

Weibull distribution function for cardiac contraction: integrative analysis.

The Weibull distribution is widely used to analyze the cumulative loss of performance, i.e., breakdown, of a complex system in systems engineering. We found for the first time that the difference curve of two Weibull distribution functions almost identically fitted the isovolumically contracting left ventricular (LV) pressure-time curve [P(t)] in all 345 beats (3 beats at each of 5 volumes in 23 canine hearts; r = 0.999953 +/- 0.000027; mean +/- SD). The first derivative of the difference curve also closely fitted the first derivative of the P(t) curve. These results suggest the possibility that the LV isovolumic P(t) curve may be characterized by two counteracting cumulative breakdown systems. Of these, the first breakdown system causes a gradual pressure rise and the second breakdown system causes a gradual pressure fall. This Weibull-function model of the heart seems to give a new systems engineering or integrative physiological view of the logic underlying LV isovolumic pressure generation.

Animals↗
PubMed1999

Prognostic value of serum hepatocyte growth factor in patients with acute coronary syndromes.

The present study examined whether or not hepatocyte growth factor (HGF), an endothelium-specific growth factor that stimulates regeneration of the endothelium, is increased or has a prognostic significance in patients with acute coronary syndromes. HGF was measured in 106 patients with coronary artery disease (20 stable effort angina, 12 unstable angina without adverse events, 24 unstable angina with adverse events and 50 acute myocardial infarction) on admission and 21 normal volunteers. The measurements in all patients were recorded before administration of heparin, and in acute myocardial infarction patients they were recorded from days 2 to 6 after heparin discontinuation on day 1. HGF levels (ng/ml) were 0.30+/-0.06 for the controls, 0.31+/-0.08 for stable effort angina patients, 0.31+/-0.08 for unstable angina patients without adverse events, 0.40+/-0.20 for unstable angina patients with adverse events and in acute myocardial infarction patients they were 0.45+/-0.18 on day 0, 0.57+/-0.45 on day 2, 0.50+/-0.35 on day 3, 0.48+/-0.32 on day 4, 0.44+/-0.20 on day 5, and 0.38+/-0.14 on day 6. HGF plays a crucial role in the restoration of injured endothelial cells and is a predictor of adverse events in patients with acute coronary syndromes.

Acute Disease↗
PubMed1999

Purification and characterization of an esterase involved in cellulose acetate degradation by Neisseria sicca SB.

An esterase catalyzing the hydrolysis of acetyl ester moieties in cellulose acetate was purified 1,110-fold to electrophoretic homogeneity from the culture supernatant of Neisseria sicca SB, which can assimilate cellulose acetate as the sole carbon and energy source. The purified enzyme was a monomeric protein with a molecular mass of 40 kDa and the isoelectric point was 5.3. The pH and temperature optima of the enzyme were 8.0-8.5 and 45 degrees C. The enzyme catalyzed the hydrolysis of acetyl saccharides, p-nitrophenyl esters of short-chain fatty acids, and was slightly active toward aliphatic and aromatic esters. The K(m) and Vmax for cellulose acetate (degree of substitution, 0.88) and p-nitrophenyl acetate were 0.0162% (716 microM as acetyl content in the polymer) and 36.0 microM, and 66.8 and 39.1 mumol/min/mg, respectively. The enzyme was strongly inhibited by phenylmethylsulfonyl fluoride and diisopropyl fluorophosphate, which indicated that the enzyme was a serine esterase.

Amino Acid Sequence↗
PubMed1999

Quantification of two aromatic amine mutagens, PBTA-1 and PBTA-2, in the yodo river system.

The levels of two aromatic amine mutagens, 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)amino]-5-methoxyphenyl]-5-am ino-7-bromo-4-chloro-2H-benzotriazole (PBTA-1) and 2-[2-(acetylamino-4-[N-(2-cyanoethyl)ethylamino]-5-methoxyphenyl]-5-a mino-7-bromo-4-chloro-2H-benzotriazole (PBTA-2), were quantitatively analyzed in the Yodo River system in Japan. The river water samples were collected at nine sampling sites from the Yodo River system twice or three times between May and July in 1997. PBTA-1 and PBTA-2 in the river water samples were concentrated on blue rayon columns, partially purified by high-performance liquid chromatography (HPLC) on reverse-phase columns, then quantified by HPLC with an electrochemical detector. The amounts of PBTA-1 and PBTA-2 in the water samples were < 0.01-1.91 and < 0.01-2.25 ng/L, respectively. High levels of PBTA-1 and PBTA-2 were detected in the samples collected within 4 km downstream of two sewage plants, which are located along the banks of the Nishitakase River, a tributary of the Yodo River system, and these samples showed stronger mutagenicity in Salmonella typhimurium YG1024 with S9 mix than the other water samples. On the other hand, the river water samples from upstream of the sewage plant were weakly or not mutagenic and PBTA-1 and PBTA-2 were not detected. These results confirmed that a major source of PBTA-1 and PBTA-2 in the Yodo River system is effluent from the sewage plants and that discharged mutagens, including PBTA-1 and PBTA-2, are diluted and/or decomposed while moving down the Yodo River system.

Chromatography, High Pressure Liquid↗
PubMed1999

Attenuation of conduction delay by ischemic preconditioning reduces ischemia-induced ventricular arrhythmias.

Ischemic preconditioning has been acknowledged as a powerful method of decreasing ischemic injury. However, the antiarrhythmic mechanism of ischemic preconditioning during ischemia is unclear. We studied the effects of ischemic preconditioning on arrhythmias and cardiac electrophysiology during ischemia in Langendorff rat hearts (n = 44). In the non-preconditioned group (PC(-); n = 24), the hearts underwent 5-min zero-flow global ischemia without any prior ischemic preconditioning. In the preconditioned group (PC(+); n = 20), the hearts were preconditioned by three cycles of 3-min zero-flow global ischemia and 5-min reperfusion before undergoing 5-min global ischemia. Ischemic preconditioning reduced the incidence of ischemia-induced arrhythmias (PC(-); 38.9%, PC(+): 8.3%, p < 0.05), shortened monophasic action potential duration (MAPD, P < 0.05), attenuated conduction delay (conduction time; PC(-): 234.2%, PC(+): 173.4%, P < 0.05) and increased the ventricular fibrillation threshold. Although the shortening of MAPD in PC(-) hearts was not influenced by the presence or absence of arrhythmias, conduction time prolongation at 3-min was more obvious in PC(-) hearts with arrhythmia than in PC(-) hearts without arrhythmia (PC(-) with arrhythmia: 220.2%, PC(-) without arrhythmia: 190.7%, P < 0.05). We concluded that ischemic preconditioning could protect the rat hearts from ischemia-induced arrhythmias and postulated that attenuation of conduction delay during ischemia might be an important factor in the antiarrhythmic action of ischemic preconditioning.

Action Potentials↗
PubMed1999

Effects of ischemic preconditioning on reperfusion arrhythmias and electrophysiology in isolated rat hearts: it is not a role of KATP(+) channels.

OBJECTIVE: To investigate the effects of ischemic preconditioning (PC) and ATP sensitive K+ channels (KATP(+) opener nicorandil on reperfusion arrhythmias and electrophysiology. METHODS: Langendorff-perfused rat hearts were subjected to ischemic PC with three cycles of 2 minutes of global ischemia or infusion of KATP(+) opener nicorandil with subsequent 5 minutes global ischemia and reperfusion. The incidence of reperfusion arrhythmias, ventricular fibrillation threshold (VFT), effective refractory period (ERP) and monophasic action potential duration (MAPD) of the left and right ventricles were compared to those from control rat hearts. RESULTS: The results indicated that PC reduced the incidence of total arrhythmias and ventricular fibrillation during reperfusion (P < 0.05, vs controls). PC markedly delayed the onset of arrhythmia after reperfusion (P < 0.01, vs controls). PC significantly enhanced the VFT values during reperfusion and shortened the ERP and the MAPD during ischemia. VFT was restored more rapidly than that in controls. KATP+ opener nicorandil neither reduced the incidence of total arrhythmias and VF nor delayed arrhythmia onset. Nicorandil shortened ERP and MAPD90 without enhancing the VFT values, and VFT returned to normal as slowly as that in controls. CONCLUSIONS: We conclude that PC protects the globally ischemic rat hearts from reperfusion arrhythmias. The antiarrhythmic effect of PC is likely to be related to a significant increase of VFT. KATP(+) opener nicorandil has no potential antiarrhythmic action and KATP(+) channels may not play a major role in the antiarrhythmic effects of ischemic PC in isolated rat hearts.

Animals↗