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Biomedical subjects

H Satoh

Publications and source records attributed to H Satoh.

At least 397 records · Page 22Linked to original sources
PubMed1996

Modulation of Ca(2+)-activated K+ current by isoprenaline, carbachol, and phorbol ester in cultured (and fresh) rat aortic vascular smooth muscle cells.

1. Effects of isoprenaline (ISO), carbachol, and phorbol ester on the outward K+ currents in single cultured (or fresh) rat aortic vascular smooth muscle (A7r5 and A-10) cells were examined using a whole-cell voltage-clamp (at room temperature 22 degrees C). 2. With 10 mM EGTA in the pipette solution, the delayed rectifier K+ current (IK) was activated by Ca2+ at pCa 7 more than at pCa 10, and was TEA (10 mM) and apamin (200 nM) sensitive, which represents a Ca(2+)-activated K+ current (IKCa). 3. In cultured A7r5 cells, isoprenaline (1 and 5 microM) and carbachol (0.1 and 1 microM) inhibited IKCa. Phorbol ester, 4-beta-phorbol-12, 13-dibutyrate (PDB), at 0.1 and 1 microM also inhibited IKCa, and increased the inhibitory effects induced by isoprenaline (1 microM). 4. In fresh aortic cells, these drugs, at the same concentrations, also produced the similar effects. 5. In A-10 cells, PDB (1 microM) enhanced the transient outward current (4-AP-sensitive), but ISO (1 microM) inhibited the current. 6. These results suggest that the IKCa current would be inhibited by cyclic nucleotides (cAMP and cGMP) and also by PK-C stimulation, and thereby be directly contributed to excitation-contraction coupling of the vascular smooth muscle cells.

Adrenergic beta-Agonists↗
PubMed1996

Enhancement of K+ currents by stimulation of protein kinase C in the uterine smooth muscle cells of the pregnant rat.

1. Effects of phorbol esters on the K+ currents in isolated rat uterine smooth muscle cells during (18-day) pregnancy were examined using whole-cell voltage-clamp modes. All experiments were performed at room temperature. 2. Test pulses were applied between -20 to + 90 mV from a holding potential of -40 mV. Initially, a transient outward current (ITO) was activated, and outward K+ current (IK) was followed. Threshold potential was - 10 to 0 mV, and the activation was voltage-dependent. At - 80 mV, ITO and IK were 17.8 +/- 3.3 and 13.2 +/- 2.6 pA/pF as a current density. Membrane capacitance was 64.0 +/- 11.5 pF (n = 8). 3. At 0.1 microM, 12-O-tetradecanoylphorbol-13-acetate (TPA) and 4-beta-phorbol-12-13-dibutyrate (PDB) enhanced IK at +80mV by 14.5 +/- 2.0% (n = 8, P < 0.05) and 23.5 +/- 2.2% (n = 7, P < 0.01). Also, ITO at +80mV was increased by 22.1 +/- 2.1% (n = 8, P < 0.01) at 1 microM TPA and by 22.7 +/- 3.0 (n = 7, P < 0.05) at 0.1 microM PDB, significantly. 4. These results indicate that the IK and ITO currents are present in the uterine smooth muscle cells of pregnant rat, and PK-C stimulation modulates the K+ currents, resulting in the regulation of physiological contraction of the uterine muscle during pregnancy.

Animals↗
PubMed1996

Direct inhibition by taurine of the ATP-sensitive k+ channel in guinea pig ventricular cardiomyocytes.

1. Effects of taurine on the ATP-sensitive K+ channel in isolated guinea pig ventricular cardiomyocytes were examined using an inside-out patch voltage-clamp mode. All experiments were performed at 36 degrees C. 2. The ATP-sensitive K+ channel was activated outwardly. ATP-free and 140 mM K+ solution in the bath and 140 mM K+ in the pipette solution were used. The amplitude was 2.2 +/- 0.3 pA (n = 9) at + 50 mV. The channel conductance was 31 +/- 3 pS (n = 9). Glibenclamide (1 microM) blocked the channel opening. 3. Taurine decreased the open probability (as a mean patch current for 30 sec) of the channel by 21.5 +/- 2.4% (n = 8, P < 0.01) at 10 mM, and almost blocked it (n = 8, P < 0.001) at 20 mM. 4. Taurine did not affect the channel conductance; these responses were reversible. 5. These results suggest that taurine directly modulates the open probability of the ATP-sensitive K+ channel, resulting in regulation of the cell functions.

Adenosine Triphosphate↗
PubMed1996

Cardiac mechanical and electrophysiologic modulations of guinea-pig by caffeine and thapsigargin.

1. The effects of caffeine and thapsigargin on the contractile force and the action potential in guinea-pig papillary muscles were examined. 2. Caffeine (1 to 10 mM) initially increased contractile force in a concentration-dependent manner. Subsequently, 1 mM caffeine decreased it as compared with precaffeine level (but not significantly). At 5 mM or 10 mM, caffeine also decreased contractile force, but the decrease was still positive as compared with control level. 3. Exchange to low [Ca]o (0.9 mM) or high [K]o (8 mM) decreased steady-state value during exposure to 1 mM caffeine. Addition of 1 microM thapsigargin (TG) decreased the steady-state value during exposure to 1 mM caffeine, but enhanced it with 5 mM and 10 mM caffeine. TG (1 microM) alone increased the force. 4. In electrophysiologic, studies, caffeine shortened the action potential duration (APD) in a concentration-dependent manner. In the presence of caffeine (1 mM), high [K]o shortened APD and decreased the action potential amplitude and resting potential. 5. These results suggest that in the presence of caffeine and/or thapsigargin calcium overload might not occur in the left ventricular papillary muscles of the guinea-pig heart.

Action Potentials↗
PubMed1996

Surface:volume relationship in cardiac myocytes studied with confocal microscopy and membrane capacitance measurements: species-dependence and developmental effects.

The quantitative analysis of the contribution of ion fluxes through membrane channels to changes of intracellular ion concentrations would benefit from the exact knowledge of the cell volume. It would allow direct correlation of ionic current measurements with simultaneous measurements of ion concentrations in individual cells. Because of various limitations of conventional light microscopy a simple method for accurate cell volume determination is lacking. We have combined the optical sectioning capabilities of fluorescence laser scanning confocal microscopy and the whole-cell patch-clamp technique to study the correlation between cell volume and membrane capacitance. Single cardiac myocytes loaded with the fluorescent dye calcein were optically sectioned to produce a series of confocal images. The volume of cardiac myocytes of three different mammalian species was determined by three-dimensional volume rendering of the confocal images. The calculated cell volumes were 30.4 +/- 7.3 pl (mean +/- SD) in rabbits (n = 28), 30.9 +/- 9.0 pl in ferrets (n = 23), and 34.4 +/- 7.0 pl in rats (n = 21), respectively. There was a positive linear correlation between membrane capacitance and cell volume in each animal species. The capacitance-volume ratios were significantly different among species (4.58 +/- 0.45 pF/pl in rabbit, 5.39 +/- 0.57 pF/pl in ferret, and 8.44 +/- 1.35 pF/pl in rat). Furthermore, the capacitance-volume ratio was dependent on the developmental stage (8.88 +/- 1.14 pF/pl in 6-month-old rats versus 6.76 +/- 0.62 pF/pl in 3-month-old rats). The data suggest that the ratio of surface area:volume of cardiac myocytes undergoes significant developmental changes and differs among mammalian species. We further established that the easily measurable parameters of cell membrane capacitance or the product of cell length and width provide reliable but species-dependent estimates for the volume of individual cells.

Animals↗
PubMed1996

Seasonal variation in blood pressure in normotensive women studied by home measurements.

1. The factors influencing the seasonal variation in blood pressure measured at home in normotensive women were examined. 2. Sixteen female subjects (56.3 +/- 7.9 years old, mean +/- SD) measured their blood pressure and pulse rate at home each morning for more than 20 times per month for at least 1.5 years. Blood pressure and body weight were also determined in the office once or twice a month in that period. Monthly means of outdoor and indoor temperatures and daytime length were obtained from the Meteorological Observatory. The single cosinor method was used to evaluate circannual rhythm. 3. We observed a biphasic seasonal variation in self-recorded blood pressure measured at home, environmental temperature and daytime length but found no apparent seasonal variation in body weight and blood pressure measured in the office. The lowest levels of systolic and diastolic blood pressure measured at home were observed in July. The longest daytime length was recorded in June, while the highest outdoor temperature and indoor temperature were recorded in August, indicating that the longest daytime length preceded and the highest environmental temperature lagged behind the lowest level of blood pressure. The shortest daytime length is in December. The lowest outdoor and indoor temperature were observed in January, while the highest levels of self-recorded systolic blood pressure and diastolic blood pressure were in January and December, respectively. Half-amplitudes of self-recorded systolic and diastolic blood pressure were 2.6 +/- 1.0 mmHg and 2.0 +/- 0.8 mmHg, respectively. 4. These findings indicate the importance of a seasonal effect, i.e. daytime length and the environmental temperature, on the blood pressure of individuals.

Adult↗
PubMed1996

Evaluation of bone density in newborn infants by computed x-ray densitometry.

We evaluated bone density in term and preterm infants using computed x-ray densitometry, which permits measurement of bone density with minimal disturbance to the infants in their incubators. Bone density, bone width, and bone length of the right radius were determined in 155 infants of appropriate weights for their gestational ages (23 to 41 weeks). A curve for intrauterine bone growth was extrapolated from these data. The mean coefficients of variations for variabilities for intra- and interobserver error for all measurements were < 3.5%. In 18 infants, measurements of the right forearm were obtained in two positions to confirm the validity of densitometric measurements. The mean coefficients of variation were 3.42% for bone density, 3.48% for bone width, and 0.21% for bone length. Bone density was significantly correlated with gestational age (r = 0.924) and birth weight (r = 0.921). Bone width and length were also correlated with gestational age (r = 0.866 and 0.937) and birth weight (r = 0.878 and 0.954). Our results suggest that computed x-ray densitometry is a useful method for evaluation of bone density in preterm infants, including those in an intensive care environment.

Absorptiometry, Photon↗
PubMed1996

Effects of Mg2+ on Ca2+ waves and Ca2+ transients of rat ventricular myocytes.

It has been shown that the occurrence of the transient inward current, which is responsible for triggered activity, was often associated with propagating regions of increased intracellular Ca2+ concentration ([Ca2+]i), i.e., the "Ca2+ wave." To investigate the mechanism of antiarrhythmic action of Mg2+, we have studied effects of high concentrations of Mg2+ on Ca2+ waves in isolated rat ventricular myocytes. [Ca2+]i was estimated using the Ca(2+)-indicating probe indo 1. Ca2+ waves in myocytes, stimulated at 0.2 Hz, were induced by perfusion of isoproterenol (10(-7) M). High Mg2+ concentration suppressed Ca2+ waves in a concentration-dependent manner (36% at 4 mM, 70% at 8 mM, and 82% at 12 mM). The Ca2+ channel blocker verapamil also suppressed Ca2+ waves in a similar way. In contrast with marked depression of Ca2+ transients by verapamil, Ca2+ transients were not affected by high Mg2+ concentration (8 mM). High Mg2+ concentration also reduced frequencies of Ca2+ waves in the absence of electrical stimulation, whereas verapamil failed to reduce frequencies of Ca2+ waves. Reduction in frequency of Ca2+ waves by high Mg2+ concentration was associated with slowing of propagation velocity of Ca2+ waves. To examine whether suppressive effects of high Mg2+ concentration on Ca2+ waves were related to an increase in intracellular Mg2+ concentration ([Mg2+]i), the effect of high-Mg2+ solution on [Mg2+]i was examined in myocytes loaded with mag-fura 2. An increase in extracellular Mg2+ concentration from 1 to 12 mM increased [Mg2+]i from 1.06 +/- 0.16 to 1.87 +/- 0.22 mM (P < 0.01) in 30 min. To examine the effect of high Mg2+ concentration on amount of releasable Ca2+ in the sarcoplasmic reticulum, the effect of high Mg2+ concentration on the Ca2+ transient induced by a rapid application of caffeine was examined. High-Mg2+ solution increased the peak of the caffeine-induced Ca2+ transient. These results suggest that the inhibitory effect of Mg2+ on Ca2+ waves was not due to inhibition of the sarcolemmal Ca2+ channel but could be due to a decreased propensity for the sarcoplasmic reticulum to divest itself of excess Ca2+.

Animals↗
PubMed1996

Effects of FK-506 on contraction and Ca2+ transients in rat cardiac myocytes.

FK-506 binding protein (FKBP) has been reported to be closely associated with the ryanodine receptor in skeletal and cardiac muscle and to modulate sarcoplasmic reticulum (SR) Ca2+ release channel gating in isolated channels. FK-506 can inhibit the activity of FKBP, thereby reversing its effects on SR Ca2+ release. We investigated the function of FKBP during normal contractions and Ca2+ transients in intact rat ventricular myocytes loaded with fluorescent Ca2+ indicators. FK-506 significantly increased steady state twitch Ca2+ transients and contraction amplitudes even under conditions in which the SR Ca2+ load and Ca2+ current were unaltered, suggesting that FK-506 increases the fraction of SR Ca2+ released during excitation-contraction (E-C) coupling. Action potentials were somewhat prolonged, consistent with the larger Ca2+ transients causing greater inward Na(+)-Ca2+ exchange current. FK-506 did not affect SR Ca2+ uptake but modestly decreased Ca2+ extrusion via Na(+)-Ca2+ exchange in intact cells (although no effect on Na(+)-Ca2+ exchange was seen in sarcolemmal vesicles). In most cells, FK-506 caused an increase in SR Ca2+ content during steady state stimulation, as assessed by caffeine-induced contractures. This was probably due to the inhibition of Ca2+ efflux via Na(+)-Ca2+ exchange. FK-506 also accelerated the rest decay of SR Ca2+ content and increased the frequency of resting Ca2+ sparks about fourfold. The increase in frequency of these basic Ca2+ release events was not associated with changes in the amplitude or duration of the Ca2+ sparks. We conclude that FK-506 increases the fraction of SR Ca2+ released during normal twitches and enhances the rate of SR Ca2+ release during rest. FK-506 also inhibits Na(+)-Ca2+ exchange, although this effect may be indirect. These effects are consistent with an important SR-stabilizing effect of FKBP in intact rat ventricular myocytes.

Animals↗
PubMed1996

Nocturnal blood pressure and silent cerebrovascular lesions in elderly Japanese.

BACKGROUND AND PURPOSE: We conducted a cross-sectional epidemiological survey using ambulatory blood pressure monitoring and brain MRI in a cohort from northern Japan to determine whether an inappropriately low nocturnal blood pressure, or an excess fall in nocturnal blood pressure, might be responsible for silent cerebrovascular lesions in the elderly. METHODS: Untreated subjects over 55 years and under 64 years of age (late middle age; 24 men and 46 women, 60% of eligible people) and over 65 years and under 75 years of age (elderly; 29 men and 52 women, 91% of eligible people) participated in the study. We evaluated the relationship between the amplitude (Daytime Average-Nighttime Average) or the rate ([Daytime Average-Nighttime Average]/Daytime Average) of the fall in nocturnal blood pressure and the incidence of silent cerebrovascular lesions on MRI (number of lacunar infarctions or extent of periventricular hyperintensity). RESULTS: The amplitude or the rate of the fall in nocturnal blood pressure in elderly women with one or two lacunar infarctions was significantly higher than that in those without such infarctions. There was a significant positive correlation between the amplitude or the rate of the fall in nocturnal blood pressure and the extent of periventricular hyperintensity in the elderly women. This relationship was observed in women, but not in men, of late middle age; this was not seen in elderly men. CONCLUSIONS: Results indicate that an inappropriately low nocturnal blood pressure, or an excessive fall in nocturnal blood pressure, is associated with ischemic silent cerebrovascular lesions, at least in elderly women. Treatment of hypertension in such women should be administered with care and with regard to nocturnal blood pressure.

Age Distribution↗
PubMed1996

How is embryo size genetically regulated in rice?

It is unclear how embryo size is genetically regulated in plants. Since cereals have a large persisting endosperm, it is expected that embryo size is affected by endosperm development. Nine single recessive mutations, four reduced embryo mutations representing three loci, REDUCED EMBRYO1, REDUCED EMBRYO2 and REDUCED EMBRYO3, four giant embryo mutations derived from a single locus GIANT EMBRYO, and one endospermless mutation endospermless1-2 were analyzed. Every reduced embryo mutation caused reduction of all the embryonic organs including apical meristems and the enlargement of the endosperm. The giant embryo mutants have a reduced endosperm and an enlarged scutellum. However, shoot and radicle sizes were not affected. All the reduced embryo and giant embryo mutations did not largely affect postembryonic development. Accordingly, the expression of genes analyzed are seed-specific. In reduced embryo and giant embryo mutations, abnormalities were detected in both embryo and endosperm as early as 2 days after pollination. endospermless1-1 resulted in an early loss of endosperm, yielding a giant embryo, suggesting that embryo growth was physically limited by the endosperm. A double mutant between giant embryo-2 and club-shaped embryo1-1, which has a normal endosperm and a minute undifferentiated embryo, resulted in a club-shaped embryo1-1 embryo and a reduced endosperm of giant embryo-2, indicating that GIANT EMBRYO regulates the endosperm development. Double mutants between giant embryo-2 and three reduced embryo mutants exhibited the reduced embryo phenotype in both embryo and endosperm, suggesting that reduced embryo mutations cause the enlarged endosperm. Further, a double mutant of reduced embryo3 and endospermless1-1 showed the enlarged embryo in endospermless seed. This confirms that reduced embryo3 does not regulate embryo size but enlarges endosperm size. Together with the results of the other double mutant analysis, REDUCED EMBRYO1, REDUCED EMBRYO2, REDUCED EMBRYO3 and GIANT EMBRYO are concluded to regulate endosperm development.

Genes, Plant↗
PubMed1996

In vitro and in vivo antitumor activity of a novel nucleoside, 4'-thio-2'-deoxy-2'-methylidenecytidine.

The in vitro and in vivo antitumor activity of a novel nucleoside, 4'-thio-2'-deoxy-2'-methylidenecytidine (4'-thio-DMDC), was examined. 4'-Thio-DMDC inhibited the growth of various cell lines established from human solid cancers, particularly the growth of lung and bladder carcinomas and melanomas. 4'-Thio-DMDC exhibited potent antitumor activity against subcutaneously implanted murine sarcoma S-180 and human fibrosarcoma HT-1080 xenografts. It was shown that 4'-thio-DMDC suppressed cell growth by inhibiting cellular DNA synthesis, and phosphorylation of the 5'-position of its deoxyribose by deoxycytidine kinase was needed for its antitumor activity. 4'-Thio-DMDC is a poor substrate for cytidine deaminase, thus it is a promising agent for the treatment of malignant solid tumors because it will not be converted into its inactive uridine form.

Animals↗
PubMed1996

Bioavailability and diuretic effect of furosemide following administration of tablets and retarded capsules to human subjects.

Two kinds of dosage forms (tablets and retarded capsules) of furosemide (F) were compared in vitro dissolution profile and in vivo absorption studies. The dissolution of F from retarded capsules was extremely restricted in the first fluid of the JP XII disintegration test (within 0.8%), while the dissolution of F from tablets and retarded capsules in the second fluid of JP XII disintegration test were both complete. Metabolite specific assay of F showed F, conjugation of F with glucuronic acid (FG) and acyl migration isomers of FG (FG-iso) in urine or plasma. The mean cumulative urinary excretion of F following administration of the tablets during 24 h was twice that of retarded capsules. The mean area under the plasma concentration-time curve (AUC) of F following administration of tablets was 1.5 times that of retarded capsules. The mean cumulative urine volume during 24 h, however, was not significantly different between the two dosage forms. Clockwise hysteresis relationships between the diuretic response and the urinary excretion rate of F was observed after administration of retarded capsules. A straight relation between logarithm of the diuresis and logarithm of the urinary excretion of F was observed after maximum excretion rate of F following administration of both dosage forms.

Absorption↗
PubMed1996

[Developmental aspects of electrophysiology in cardiac muscle].

Electrical properties of the cardiac muscles drastically change with development. The changes in the current density of ionic currents of cardiomyocytes are inconsistent among species. In cultured embryonic chick ventricular myocytes, the developmental changes in the fast Na+ channel properties (3- to 17-day-old) are reviewed. The sensitivity to TTX, with a KD as high as 2 nM, remains unchanged. The limiting conductance (GNa) increased by 8-10-fold. The activation kinetics such as the steady-state activation (m infinity) and time constant of activation (tau m) remain unchanged. The voltage-dependence of inactivation kinetics such as the steady state inactivation (h infinity) and time constant (tau h) shift in the hyperpolarizing direction. The window conductance tends to be reduced. On the other hand, the L-type Ca2+ channel is important during the development of rat heart, and also the fe-type current (dihydropyridine-resistant) is important in the fetal stage. In chick embryo cardiomyocytes, the L-type channel exhibits long-lasting opening behavior. The behavior is gradually abolished during development, cAMP-dependent protein kinase enhances the Ca2+ channel current on and after the late fetal/embryonic stage. cGMP-dependent protein kinase markedly inhibits the Ca2+ channel current in the fetal/embryonic stage, compared with adult heart. These changes would play an important role for cardiac functions during development.

Animals↗
PubMed1996

[Developmental changes in the pacemaker current and membrane currents of the guinea pig myocardium].

The pacemaker current (I(f)) in embryonic chick ventricular myocytes is present, but decreases during development. beta-Adrenergic agonists stimulate I(f), whereas muscarinic cholinergic agonists inhibit I(f) and reverse beta-adrenoceptor stimulation. G-proteins directly and indirectly couple autonomic receptors to I(f) channels in embryonic ventricular cells. The I(f) may contribute partly to the electrogenesis of the pacemaker potential. On the other hand, Ito current, voltage-dependent and 4-AP-sensitive, exists even in young embryonic cardiomyocytes, but not in all cells. The Ito increases during development, resulting in modulation of the action potential configuration. The action potential duration of guinea pig ventricular myocardium decreases during the late fetal period and increases postnatally. Single cell voltage clamp analyses revealed that the decrease and increase in action potential duration are due to developmental increases in the current densities of the calcium current and delayed rectifier potassium current, respectively. The role of the sarcoplasmic reticulum in contraction and relaxation of the guinea pig myocardium increases during fetal development.

Action Potentials↗
PubMed1996

[Effects of lansoprazole on indomethacin-induced gastric bleeding and mucosal lesions in rats].

The effects of lansoprazole given intravenously on indomethacin-induced gastric bleeding and mucosal lesions were investigated in rats in comparison with those of omeprazole, famotidine and ranitidine. Lansoprazole inhibited gastric bleeding induced by indomethacin with an ID50 value of 0.29 mg/kg. Omeprazole and famotidine significantly inhibited gastric bleeding, but ranitidine provided negligible inhibition. A correlation was found between the inhibitory action of lansoprazole on gastric bleeding, and acid secretion, and its inhibitory action on gastric bleeding was almost completely abolished by adding 50 mM-HCl to the gastric perfusate, suggesting that lansoprazole's inhibitory action on gastric bleeding was mainly due to its antisecretory action. Lansoprazole inhibited the development of gastric lesions induced by indomethacin with an ID50 value of 0.10 mg/kg, whereas histamine H2-receptor antagonists did not display a potent inhibitory effect. ID50 values for omeprazole, famotidine and ranitidine were 0.69, 2.58 and 24.6 mg/kg, respectively. These results indicate that lansoprazole has a potent inhibitory action on indomethacin-induced gastric bleeding and mucosal lesions and that it is useful in the treatment of acute gastric mucosal lesions.

2-Pyridinylmethylsulfinylbenzimidazoles↗