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Biomedical subjects

M Arita

Publications and source records attributed to M Arita.

At least 163 records · Page 9Linked to original sources
PubMed1995

Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein.

Ataxia with isolated vitamin E deficiency (AVED) is an autosomal recessive neurodegenerative disease which maps to chromosome 8q13. AVED patients have an impaired ability to incorporate alpha-tocopherol into lipoproteins secreted by the liver, a function putatively attributable to the alpha-tocopherol transfer protein (alpha-TTP). Here we report the identification of three frame-shift mutations in the alpha TTP gene. A 744delA mutation accounts for 68% of the mutant alleles in the 17 families analysed and appears to have spread in North Africa and Italy. This mutation correlates with a severe phenotype but alters only the C-terminal tenth of the protein. Two other mutations were found in single families. The finding of alpha TTP gene mutations in AVED patients substantiates the therapeutic role of vitamin E as a protective agent against neurological damage in this disease.

Africa, Northern↗
PubMed1995

Mexiletine-induced shortening of the action potential duration of ventricular muscles by activation of ATP-sensitive K+ channels.

A class Ib antiarrhythmic drug, mexiletine (100 microM) significantly shortened the action potential duration (APD) of guinea-pig ventricular muscles and this effect was completely abolished in the presence of glibenclamide (50 microM), a blocker of the ATP-sensitive K+ channel (KATP). Mexiletine significantly increased the open probability of uridine diphosphate-primed KATP channels, recorded in inside-out patches of the ventricular cells. The results suggest that mexiletine shortens the APD of ventricular muscles, at least in part, via activation of KATP.

Action Potentials↗
PubMed1995

Purification and characterization of a cell-associated hemagglutinin of Vibrio parahaemolyticus.

We found a positive correlation between cell-associated mannose-sensitive hemagglutination and adherence of Vibrio parahaemolyticus to rabbit enterocytes by investigating 35 strains of V. parahaemolyticus for cell-associated hemagglutinin (cHA) and for the ability to adhere to the enterocytes. We purified a mannose-sensitive cHA from a Kanagawa phenomenon-positive clinical strain of V. parahaemolyticus that exhibited a high level of mannose-sensitive hemagglutination and strongly adhered to the enterocytes. The purified cHA is a heat-labile, tetrameric protein consisting of four identical subunits of approximately 26 kDa each. The adherence to rabbit enterocytes was inhibited in a dose-dependent manner by pretreatment of the bacterial cells with D-mannose and with the Fab fraction of immunoglobulin G against the purified cHA. Furthermore, pretreatment of the enterocytes with the purified cHA inhibited the adherence of V. parahaemolyticus. Immunogold electron microscopy revealed that the cHA is located on the bacterial cell surface and is not associated with pili. These results suggest that cHA is involved in the adherence mechanisms of V. parahaemolyticus to the enterocytes and that the receptors for cHA on the enterocyte appear to be a D-mannose-containing compound.

Animals↗
PubMed1995

Abnormalities of K+ and Ca2+ currents in ventricular myocytes from rats with chronic diabetes.

Ionic mechanisms related to the prolongation of cardiac action potential in rats with chronic diabetes mellitus were studied using whole cell voltage-clamp techniques. Diabetes was induced by injection of streptozotocin (STZ; 65 mg/kg body wt) into the tail vein, and ventricular myocytes were isolated from STZ-injected rats (24-30 wk) and from age-matched normal rats. The current densities of transient outward current (Ito), a steady-state outward current, and L-type Ca2+ current (ICa) were significantly smaller in cells from diabetic animals. In addition, the kinetics of Ito of diabetic cells were modified. 1) The decay of Ito was well fitted by a sum of two exponential components in normal cells; there was only one (slow) component in the diabetic cells. 2) The steady-state inactivation curve of Ito in diabetic cells shifted by 5 mV in the negative direction. 3) Recovery from inactivation of Ito was slower in cells from diabetic animals. These alterations in Ito and the steady-state outward current can account for most of the action potential prolongation heretofore documented. The decrease of ICa may possibly be related to the depressed contraction seen in chronic diabetic mellitus.

Animals↗
PubMed1995

Long-term follow-up of the reproducibility of carotid sinus hypersensitivity in patients with carotid sinus syndrome.

The reproducibility of carotid sinus hypersensitivity to carotid sinus massage was studied in the long-term follow-up of 8 patients with carotid sinus syndrome. A cardioinhibitory response was induced in 7 patients, while a vasodepressor response was found in the remaining patient. The 7 patients were treated with dual-chamber pacemaker implantation and the remaining patient was treated with propranolol. All of the patients remained asymptomatic during a follow-up period of 48 +/- 11 months. Carotid sinus massage during the follow-up period in patients with a cardioinhibitory response revealed asystolic intervals of 3 s or longer in 4 patients and in 3 patients at the second and third follow-up examinations, respectively, although there were no significant differences in the ventricular asystolic intervals between before, and 34 +/- 11 months and 48 +/- 11 months after treatment. However, each patient showed a wide variation in asystolic intervals. The differences in asystolic intervals between prior to treatment (first) and the third test were significantly greater than those between the first and the second test (2.4 +/- 1.2 s vs 0.7 +/- 0.6 s; p < 0.05). The one patient with a vasodepressor response had a decreased systolic blood pressure greater than 50 mmHg by carotid sinus massage at all three occasions. In conclusion, most patients with carotid sinus syndrome showed abnormal and variable responses to carotid sinus massage during long-term follow-up period although there was no recurrence of symptoms after treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

[Predictable factors in healing of gastric ulcer, comparative analysis of local morphologic factor of gastric ulcer and suppression of intragastric pH].

Predictable factors in healing of 48 patients with gastric ulcer by PPI or H2-RA on 4 and 8 weeks of treatment were investigated. We evaluated the following factors such as patient's profile, local morphologic factors of gastric ulcer and suppression rate of 24 hr intragastric pH between healed and unhealed patients using single and multiple variable analysis. Results obtained from multiple variable analysis, the significant and independent factors of intractable gastric ulcers on the 4th week of treatment were ulcer size in over 20 mm and solitary ulcer. On the contrary, those of 8th week of treatment were shortage of holding time of intragastric pH over pH4 (less than 16.7 hrs) during treatment, the site of ulcer at lesser curvature of gastric angle and the shape of ulceration which showed mucosal overhanging. Considering with single and multiple variable analysis, we concluded that, in early phase, local shapes of the ulceration were important predictors in the healing of gastric ulcer, and the after that, the inhibition of intragastric acidity were significant factors in healing process of gastric ulcer.

Female↗
PubMed1995

Voltage dependent inhibition of ATP sensitive potassium channels by flecainide in guinea pig ventricular cells.

OBJECTIVE: The aim was to examine the effects of flecainide, a class Ic antiarrhythmic drug, on the ATP sensitive potassium channel (KATP channel) current in guinea pig ventricular cells, using the inside-out patch clamp technique. METHODS: KATP channel activities were recorded from inside-out membrane patches with 140 mM KCl solution bathing both the external and internal surfaces of the membrane (20-22 degrees C). Flecainide was added to the intracellular medium (ATP-free, pH = 7.3). RESULTS: Flecainide (1-300 microM) inhibited the outward KATP channel current evoked at the holding potential of +40 mV, in a concentration dependent manner. The flecainide concentration for half maximum inhibition of the channel activity (IC50) and Hill coefficient of the flecainide inhibition were estimated to be 17.3 microM and 1.1, respectively. However, flecainide did not affect the inwardly directed KATP channel current measured at the potential of -40 mV. When the inhibitory effects of flecainide on the outward current were examined under conditions in which pH was decreased from 7.3 (control) to 6.8, the IC50 and Hill coefficient became 27.3 microM and 1.2, respectively. Furthermore, in the presence of 0.1 mM ADP on the cytosolic side of the membrane (pH = 7.3), flecainide blocked the outward currents with the IC50 of 47.0 microM and a Hill coefficient of 0.9. After 1 min exposure of the cytoplasmic side of the membrane to trypsin (1 mg.ml-1), glibenclamide (2 microM) did not inhibit the KATP channel currents, while flecainide (30 microM) reversibly inhibited this trypsin enhanced KATP channel activity. CONCLUSIONS: Flecainide at relatively high concentrations blocks the cardiac KATP channels only when the currents are directed outward, and in a concentration dependent manner. The potency of flecainide in blocking KATP channels decreased under conditions of increased H+ or ADP concentrations on the cytosolic side of the membrane, as may occur in myocardial ischaemia or hypoxia.

Adenosine Diphosphate↗
PubMed1995

Effects of catecholamines on the residual sodium channel dependent slow conduction in guinea pig ventricular muscles under normoxia and hypoxia.

OBJECTIVE: The aim was to study the effects of catecholamines (isoprenaline and noradrenaline) on the action potential upstroke and conduction velocity in guinea pig ventricular papillary muscles. METHODS: The upstroke velocity and the conduction velocity of the action potential were recorded by conventional two-microelectrode techniques in the guinea pig ventricular papillary muscle superfused with normoxic and hypoxic Tyrode solution of various potassium concentrations ([K+]o 2.7-16.7 mM), stimulated at 0.2 Hz. RESULTS: Under normoxic conditions, the upstroke of action potentials is composed of two components, dV/dtmax,fast followed by dV/dtmax,slow, when the muscle were perfused with relatively high [K+]o (10.8-16.7 mM). The dV/dtmax,fast is a measure of the residual (mostly inactivated) sodium current, while the dV/dtmax,slow is a measure of calcium current. The conduction velocity at 13-17 mM [K+]o ranged from 30-40 cm.s-1 (slow conduction) with depolarised membrane potentials of about -60 mV. Isoprenaline in increasing concentrations (0.01-1 microM) did not significantly alter the conduction velocity but altered the ionic channels responsible for the slow conduction from residual sodium channel to calcium channel. In the presence of D600 (2 microM) or 1-verapamil (2.2 microM), isoprenaline (0.1 microM) rapidly decreased dV/dtmax,fast without increasing dV/dtmax,slow and a conduction block occurred. In the presence of pindolol (2 microM), all the effects of isoprenaline on dV/dtmax,fast, dV/dtmax,slow, and conduction velocity were abolished. Noradrenaline has the same effects as isoprenaline, although the potency was much less. Under hypoxic conditions, the effects of catecholamines on the dV/dtmax,fast was the same as under normoxic conditions. CONCLUSIONS: Catecholamines alter the ionic channel responsible for the slow conduction of reentry circuit from residual sodium to calcium channel, or vice versa, depending on the local concentrations of catecholamines. In the presence of a calcium antagonist, catecholamines strongly depress the (dV/dtmax,fast dependent) slow conduction, leading to a complete block of conduction, under both normoxia and hypoxia.

Action Potentials↗
PubMed1995

[Angiotensin I].

Explore the source record for details and available documents.

Angiotensin I↗
PubMed1994

Correlation between cell-associated mannose-sensitive hemagglutination by Vibrio parahaemolyticus and adherence to a human colonic cell line Caco-2.

Cell-associated hemagglutination (cHA) activity with human erythrocytes was examined for 468 clinical and 71 environmental strains of Vibrio parahaemolyticus. Approximately 95% of the strains tested were cHA positive irrespective of source or Kanagawa phenomenon. 75% of clinical strains showed relatively strong mannose-sensitive hemagglutination (MSHA), whereas 88% of the environmental strains showed relatively weak mannose-resistant hemagglutination (MRHA). Adherence of V. parahaemolyticus to Caco-2 cells was also determined. A clear positive correlation between cell-associated MSHA and adherence to Caco-2 cells was observed.

Bacterial Adhesion↗
PubMed1994

Molecular cloning and expression of chick embryo Gal beta 1,4GlcNAc alpha 2,6-sialyltransferase. Comparison with the mammalian enzyme.

DNA clones encoding beta-galactoside alpha 2,6-sialyltransferase have been isolated from chick embryonic cDNA libraries using sequence information obtained from the conserved amino acid sequence of the previously cloned enzymes. The cDNA sequence revealed an open-reading frame coding for 413 amino acids, and the deduced amino acid sequence showed 57.6% identity with the sequence of rat liver Gal beta 1,4GlcNAc alpha 2,6-sialyltransferase. The primary structure of this enzyme suggested a putative domain structure, similar to structures found in other glycosyltransferases, consisting of a short N-terminal cytoplasmic domain, a signal-membrane anchor domain, a proteolytically sensitive stem region and a large C-terminal active domain. The identity of this enzyme was confirmed by construction of a recombinant sialyltransferase in which the N-terminus part including the cytoplasmic tail, signal anchor domain and stem region was replaced with an immunoglobulin signal peptide sequence. The expression of this recombinant protein in COS-7 cells resulted in secretion of a catalytically active and soluble form of the enzyme into the medium. The expressed enzyme exhibited activity only towards the disaccharide moiety of Gal beta 1,4GlcNAc in glycoproteins.

Amino Acid Sequence↗
PubMed1994

Effects of cibenzoline, a new class Ia antiarrhythmic drug, on various membrane ionic currents and action potentials of guinea-pig ventricular cells.

We examined the effects of cibenzoline, a new class Ia antiarrhythmic drug, on various membrane ionic currents and action potentials of guinea-pig single ventricular cells, using patch clamp techniques in whole-cell configuration. Action potentials and the membrane currents were evoked at a clamping rate of 0.2 Hz, and all experiments were performed at 32-33 degrees C. 1) Cibenzoline (5, 10 and 30 microM) decreased the Na+ current (INa), in a concentration-dependent manner. The concentration of the half-maximal inhibition (Kd) for INa was estimated to be 7.8 microM. 2) In addition to the inhibition of INa, this drug (5, 10, and 30 microM) decreased, in a concentration-dependent manner, all other membrane currents examined, such as L-type Ca2+ current (ICa), delayed rectifier K+ current (IK), and inward rectifier K+ current (IK1). The Kd (apparent dissociation constant) values were 14.4 microM for ICa, 23.0 microM for IK, and 33.7 microM for IK1 respectively. 3) Cibenzoline (5, 10, and 30 microns) significantly shortened the action potential duration measured at both 30% and 90% repolarization without altering the resting membrane potential. From these findings, we conclude that apart from potent inhibitory effects on INa, cibenzoline possesses multiple blocking effects on other currents, e.g., ICa, IK and IK1, with a different potency (INa > ICa > IK > IK1) and with essentially the same efficacy. These effects may explain, at least in part, the alleged, potent antiarrhythmic effects of this drug.

Action Potentials↗
PubMed1994

Modification of cardiac sodium current by intracellular application of cAMP.

We examined the effects of intracellular perfusion of cyclic adenosine monophosphate (cAMP) on the sodium current (INa) of guinea-pig ventricular myocytes, using the whole-cell clamp technique. INa was elicited by depolarizing voltage steps (-20 mV) from a variety of holding potentials (-120 to -50 mV), under conditions of 60 mM extracellular Na+ concentration ([Na+]o) and at the temperature of 24-26 degrees C. Intracellular perfusion of cAMP decreased the INa elicited from the holding potentials less negative than -90 mV. In the presence of 1 mM cAMP, for example, the peak INa elicited from -80 mV decreased from 6.0 +/- 2.0 nA to 4.0 +/- 2.2 nA (mean +/- SD, P < 0.02, n = 7) within 3-6 min. In the presence of extracellular 3-isobutyl-1-methylxanthine (IBMX, 20 microM), much lower concentrations of cAMP (0.2 mM) yielded a comparable effect. On the other hand, intracellular perfusion of cAMP increased the INa elicited from very negative holding potentials (< -100 mV). For instance, the application of cAMP (1 mM) increased the INa elicited by step depolarizations from -120 mV (to -20 mV), from 9.9 +/- 2.1 nA to 11.0 +/- 3.1 nA (P < 0.05, n = 5). The former effect was attributed to a marked shift of the steady-state inactivation curve of INa to the negative direction; the voltage of half-inactivation shifted from -77.9 +/- 1.0 to -83.5 +/- 1.4 mV, or by -5.6 mV. The latter effect may be explained by increases in maximum available conductance of INa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Rate-dependent prolongation of action potential duration in single ventricular myocytes obtained from hearts of rats with streptozotocin-induced chronic diabetes sustained for 30-32 weeks.

We examined the characteristics of the action potentials of single ventricular myocytes obtained from the hearts of rats with chronically-induced diabetes. Male Wistar rats were made diabetic by injecting streptozotocin (65 mg/kg) and 30-32 weeks later the hearts were excised and used for an electrophysiological study. Action potentials were recorded from isolated right ventricular myocytes by an electrode fabricated for patch clamp in the whole-cell recording configuration. The action potential durations (APDs) of steady state chronic diabetic rat myocytes were longer than those of age-matched normal rat myocytes at all levels of repolarization (APD25, APD50, APD75, and APD90). As the stimulation frequency was increased (0.2-2 Hz), the APDs were lengthened in both diabetic and normal rats, and the difference of APDs between the groups was greater when the stimulation frequency was higher. When we examined alterations of APDs under conditions of train stimulation (2Hz, 20 stimuli), (1) the APDs in both groups were prolonged, and (2) the degree of prolongation of APD was significantly greater and the rate of APD prolongation was significantly faster in myocytes from the diabetic rats. The prolongation of APD in these heart cells is probably secondary to alteration of the transient outward current Ito, and sheds light on repolarization abnormality in cases of diabetic cardiomyopathy.

Action Potentials↗