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Biomedical subjects

M Arita

Publications and source records attributed to M Arita.

At least 217 records · Page 12Linked to original sources

A comparative study of once-a-day morning and once-a-day bedtime administration of 40 mg famotidine in treating gastric ulcers.

A randomized controlled study comparing once-a-day morning and once-a-day bedtime administration of 40 mg famotidine in treating gastric ulcers was carried out in 179 Japanese patients. Endoscopic examinations were performed at the baseline and repeated at 4-wk intervals until healing was confirmed. One hundred and sixty-four patients fulfilled the evaluation criteria (81 in the morning group and 83 in the bedtime group). The healing rates were 50.7% after 4 wk and 88.9% after 8 wk in the morning group and 46.5% after 4 wk and 74.7% after 8 wk in the bedtime group. The difference was statistically significant after 8 wk. Significant reductions from baseline for overall pain, beginning during the first 3 days, were likewise found in the two treatment groups. However, the pain severity in hunger state 1 wk after treatment was significantly higher in the bedtime group than in the morning group. Thus, once-a-day morning administration of 40 mg famotidine seems to be superior to once-a-day bedtime administration of 40 mg famotidine in treating gastric ulcers.

Adult↗

Species differences in the distribution and coexistence ratio of serotonin and substance P in the monkey, cat, rat and chick spinal cord.

Serotoninergic raphe-spinal motor neuron projections exhibit wide species differences in both innervation pattern and coexistence of serotonin and substance P. The coexistence ratios vary widely ranging from more than 80% (rat) to less than 1% (chick). Serotonin and substance P positive fibers are also unevenly distributed in the ventral horn of different species: dense clusters of serotonin and substance P positive fibers were preferentially located in the motor neuron pools of extensor muscles of the hip joint (chick) as well as antigravity muscles of the forelimb (cat and rat).

Animals↗

Antitumor activity of 2'-deoxy-2'-methylidenecytidine, a new 2'-deoxycytidine derivative.

The antitumor activity of 2'-deoxy-2'-methylidenecytidine (DMDC), an inhibitor of DNA synthesis, was examined and compared with that of 1-beta-D-arabinofuranosylcytosine (ara-C) against various murine tumors and human tumor xenografts. Against P388 murine leukemia, repeated treatments of DMDC were more effective than its single administration. Interestingly, DMDC was effective against colon 26 murine carcinoma, M5076 murine reticulum cell sarcoma, LX-1 human lung cancer xenograft, and SK-Mel-28 human melanoma xenograft, which are less sensitive or refractory to ara-C, while DMDC was not more potent against murine leukemias P388 and L1210 than ara-C. The in vitro cytotoxic effects of DMDC and ara-C against L1210 leukemia cells were prevented dose dependently by deoxycytidine, suggesting that DMDC, like ara-C, may require phosphorylation by deoxycytidine kinase for antitumor activity. DMDC was effective against human and murine experimental tumor models, especially nonleukemic tumors refractory to ara-C, suggesting that DMDC will be a promising agent for the treatment of cancer.

Animals↗

Trimetazidine inhibits Na+,K(+)-ATPase activity, and overdrive hyperpolarization in guinea-pig ventricular muscles.

The effect of trimetazidine on Na+,K(+)-ATPase activity or the Na+,K+ pump was studied in guinea pig ventricular muscles with the use of biochemical and electrophysiological methods. The effect of trimetazidine on enzyme activity was compared with that in the liver, jejunum and kidney obtained from the same species. Na+,K(+)-ATPase activity in the heart and liver was significantly and concentration dependently decreased by trimetazidine (above 1.5 x 10(-5) M). Even the highest concentration (1.5 x 10(-4) M) of trimetazidine failed to decrease the Na+,K(+)-ATPase activity in the jejunum and kidney. The membrane potential was recorded in the ventricular muscle with a microelectrode. The hyperpolarization which followed 1-min overdrive stimulation (3.3 Hz) was decreased by trimetazidine (1.5 x 10(-4) M), but the depolarization during the stimulation was not affected by this drug. Ouabain, a potent Na+,K+ pump inhibitor, markedly decreased the overdrive hyperpolarization and increased the depolarization during the stimulation (10(-7), 5 x 10(-7), 10(-6) M). Therefore, the effect of trimetazidine and ouabain on the Na+,K+ pump-mediated alteration in the resting potential is different, suggesting that trimetazidine has additional direct membrane effects, e.g. a decrease in K+ conductance. In conclusion, trimetazidine inhibits Na+,K(+)-ATPase activity and thus the Na+,K+ pump in the ventricular muscles but with an inhibitory effect about 300 times less than that of ouabain. Trimetazidine inhibited the Na+,K(+)-ATPase in the liver as well, but not that in jejunum and kidney.

Animals↗

Purification and characterization of a heat-stable enterotoxin of Vibrio mimicus.

A heat-stable enterotoxin produced by Vibrio mimicus (VM-ST) was studied. VM-ST was purified from a culture supernatant of V. mimicus strain AQ-0915 by ammonium sulfate fractionation, hydroxyapatite treatment, ethanol extraction, column chromatography on both SP-Sephadex C-50 and DEAE-Sephadex A-25, and HPLC, and the recovery rate was about 15%. Purified VM-ST was heat-stable. VM-ST activity was cross-neutralized by anti-STh antiserum. The amino acid composition of the purified VM-ST was determined 17 amino acid residues in the following sequence: Ile-Asp-Cys-Cys-Glu-Ile-Cys-Cys-Asn-Pro-Ala-Cys-Phe-Gly-Cys-Leu-Asn. This composition and sequence were identical to those of V. cholerae non-O1-ST. These results clearly demonstrate the production of a characteristic VM-ST by V. mimicus.

Amino Acid Sequence↗

Acetylcholine reverses isoproterenol-induced depression of Vmax in residual Na channel-dependent action potentials of guinea-pig cardiac muscles.

We examined effects of acetylcholine (ACh) on isoproterenol (ISP)-induced changes of the upstroke velocity of the action potential (Vmax) in isolated 13.5 mM K(+)-depolarized atrial muscles from guinea-pigs, using conventional glass microelectrode techniques. In some experiments, ventricular muscles were also used, for purposes of comparison. ISP (0.1 microM) decreased the fast component of Vmax (Vmax,fast) and increased the slow component of Vmax (Vmax, slow) of the atrial muscle, as has been noted in ventricular muscle. ACh (0.1 microM) reversed or antagonized these effects of ISP. However, in the presence of atropine (0.1 microM), the antagonism disappeared. In the presence of the Ca2+ channel blocker, D600 (1 microM), the depressant effect of ISP on the Vmax,fast was augmented while ACh exerted a much less restorative effect on the ISP-induced, depressed Vmax,fast. Similar findings were obtained in low (0.36 and 0.072 mM) Ca2+ media. To investigate the possible involvement of GTP-binding protein (Gi) on these ACh effects, we performed similar experiments using atrial muscles obtained from guinea pigs pre-treated with pertussis toxin (150 micrograms/kg) for 48 h. In these preparations, the depressant effect of ISP on the Vmax,fast remained unaffected, while the reversing effect of ACh on the ISP-induced depression of Vmax,fast either specifically diminished or disappeared. These results show that ACh antagonizes the ISP-induced Vmax changes via stimulation of muscarinic ACh receptors and that this effect is presumably mediated by Gi and modified by intracellular Ca2+. Clinical implications are discussed.

Acetylcholine↗

Nicorandil suppresses early afterdepolarisation and ventricular arrhythmias induced by caesium chloride in rabbits in vivo.

STUDY OBJECTIVE: Outward K current of cardiac membrane has been shown to be suppressed by caesium chloride (Cs) and enhanced by nicorandil, a coronary vasodilator. The aim of this study was to assess the effects of nicorandil on the Cs induced early afterdepolarisations and associated ventricular arrhythmias in the rabbit heart in vivo. DESIGN: Intravenous bolus injections of Cs (1 mmol.kg-1) were given three times at 20 min intervals. Monophasic action potentials of the left ventricular endocardium and the ECG (lead II) were recorded simultaneously over 60 min, under the intrinsic (sinus node) cardiac rhythm. EXPERIMENTAL MATERIAL: Eight rabbits were treated with Cs alone (control group); seven other rabbits were first treated with an intravenous infusion of nicorandil (0.2 mg.kg-1) (nicorandil treated group) and the effects of Cs were then examined. MEASUREMENTS AND MAIN RESULTS: In the control group, Cs produced early afterdepolarisations, premature ventricular beats and ventricular tachycardias. The ventricular tachycardias included two different types: (1) non-sustained polymorphic ventricular tachycardia mimicking the torsade de pointes in patients with long QT syndrome; (2) sustained monomorphic ventricular tachycardia. In the nicorandil treated group, the amplitude of the early afterdepolarisations and the incidence of ventricular tachycardias were significantly less than in the control group. CONCLUSIONS: Nicorandil suppresses the early afterdepolarisations and ventricular tachyarrhythmias induced by Cs, possibly by increasing the membrane K conductance.

Action Potentials↗

Cholera enterotoxin production in Vibrio cholerae O1 strains isolated from the environment and from humans in Japan.

Vibrio cholerae O1 strains isolated from various sources in Japan over the years 1977 through 1987 were examined to confirm the presence or absence of the cholera enterotoxin (CT) gene and production of CT and to determine the kappa-phage type. The CT gene was detected in none of 225 isolates from natural waters but was present in all of the 10 isolates from environmental waters implicated in domestic cholera cases, in 64 strains (26.6%) of the 241 isolates from imported seafoods, in 43 strains (95.6%) of the 45 isolates from domestic cholera cases, and in 119 strains (93.7%) of the 127 isolates from imported cholera cases. The results suggest that the CT gene-positive strains of V. cholerae O1 have been imported into Japan through seafoods and/or by travelers. Sporadic cholera cases have resulted in contamination of the surrounding environment, but the CT gene-positive strains may not have persisted in natural waters to serve as a reservoir for epidemic cholera. The commercially available VET-RPLA kit (a latex agglutination kit for immunological detection of CT) detected production of CT in all of the CT gene-positive strains, indicating that there was no silent CT gene in the test strains. There was a strong correlation between the kappa-phage type and the presence or absence of the CT gene, suggesting a significant clonal difference between CT gene-positive and -negative strains. Five CT gene-negative strains isolated from imported cholera cases (travelers with mild diarrhea) induced a considerable amount of fluid accumulation in rabbit and/or suckling mouse intestines, indicating production of an enterotoxic factor(s) other than CT.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Purification and characterization of a new heat-stable enterotoxin produced by Vibrio cholerae non-O1 serogroup Hakata.

The possible production of a heat-stable enterotoxin (Vc-H-ST) by Vibrio cholerae non-O1 serogroup Hakata was investigated, and the purified Vc-H-ST was characterized. It has a unique amino acid sequence, LIDCCEICCNPACFGCLN. This sequence is quite similar to that of the heat-stable enterotoxin (NAG-ST) produced by V. cholerae non-O1 except for one amino acid (leucine) residue excess at the N terminus. Other characteristics, including biological activity, are compatible with those of NAG-ST.

Amino Acid Sequence↗

Heart rate-dependent alteration of the frequency and coupling interval of ventricular arrhythmias as measured by 24-hour ECG monitoring.

Twenty-four hour ECG recordings of 132 patients with frequent (greater than 1000/day) ventricular premature contractions (VPCs) were analyzed using a computerized system, designed to evaluate the relationships between 1) the VPC frequency and heart rate (HR) (VPC-HR relation), 2) the coupling interval (CI) of VPCs and HR (CI-HR relation), and 3) the incidence of ventricular tachycardia (VT) and HR (VT-HR relation). The patterns of the VPC-HR relation included: 1) an increase in VPCs with increasing HR (positive correlation, 43 patients), 2) an increase in VPCs at low HR range and a decrease at high HR range, with increasing HR (bidirectional correlation, 74 patients), 3) a decrease in VPCs with increasing HR (negative correlation, 7 patients) and 4) constant VPCs over all HRs (flat correlation, 8 patients). Patients were divided into 2 broad categories according to whether they had a positive correlation (P group, 43 patients) or the other correlations (non-positive or NP group, 89 patients). Of 132 patients, the CI-HR relation was negative in 129 (98%) and positive in only 3 (2%). Patients with frequent VTs (10 or more events over 24h) were significantly more frequent in the P (9 patients, 21%) than in the NP group (7 patients, 8%, p less than 0.05). However, mean HR, mean CI, total VPC counts and the slope of CI-HR relation were not significantly different between the groups. The VT-HR relation observed in 16 patients with frequent VTs were positive in 9 of the P group and in 2 of the NP group and non-positive in 5 of the NP group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Effects of calcium antagonist, angiotensin-converting enzyme inhibitors and beta-blocker on hemodynamic and sympathetic nerve responses to exercise in essential hypertension].

To investigate the effects of antihypertensive drugs on hemodynamic and sympathetic nerve responses to exercise, graded ergometer exercise tests were performed before and after two-week administration of nifedipine, captopril and metoprolol in 18 patients with essential hypertension. The arterial pressure, heart rates (HR), and left ventricular functions as obtained by echocardiography, and the plasma norepinephrine (PNE) levels, were evaluated at rest and during submaximal exercise before and after two-week treatment with nifedipine (40 mg/day, 5 cases), captopril (37.5-75 mg/day, 6 cases) and metoprolol (60 mg/day, 7 cases). These 3 drugs significantly reduced systolic (SBP) and diastolic (DBP) blood pressures but caused no significant changes in resting PNE levels. Nifedipine produced no significant changes in HR and cardiac output (CO) at rest, but augmented the increase in HR (delta HR) and SBP (delta SBP) during submaximal exercise. The increase in PNE (delta PNE) was also augmented by nifedipine. Captopril reduced left ventricular end-diastolic volume and CO without changes in HR and fractional shortening (FS) at rest; whereas, it did not affect delta HR, delta CO, delta SBP or delta PNE during exercise. Metoprolol reduced HR and CO at rest, and also resulted in a decrease in delta FS and delta CO during submaximal exercise. delta SBP was unchanged and delta PNE was increased by treatment with metoprolol. These results indicate that, in hypertensive subjects, the effects on the hemodynamic and sympathetic nerve responses to exercise are different among these 3 antihypertensive drugs despite their identical effects on blood pressure.

Adrenergic beta-Antagonists↗

[Clinical significance of specific IgG4 antibody in serum].

Specific IgG4 antibodies in sera were measured by ELISA in allergic patients who were diagnosed as susceptible to one or more allergens among mite, milk, soybean or egg white, and also in a non-allergic control group, and their diagnostic significance was investigated. The results obtained were as follows. 1. The level of specific IgG4 antibody was significantly higher in each allergic group than in the non-allergic group. 2. The positive rates in the specific IgG4 antibody determination were higher than those in RAST in the milk-, soybean- and egg white-allergic groups. 3. In each allergic group, the causative allergens were detected more accurately by measuring both specific IgG4 antibody and IgE antibody (RAST) than IgE alone. 4. The positive rates in the specific IgG4 antibody determination were higher than those in the skin test in each allergic group. 5. It was demonstrated that the combination of the skin test with specific IgG4 antibody measurement ensured a more accurate detection of causative allergens than the skin test alone. These results indicated that the measurement of the specific IgG4 antibody is a helpful method to detect the causative allergens in allergic patients.

Adolescent↗

[A double blind study of the effectiveness of ketotifen in preventing the development of asthma in atopic dermatitis patients].

Many asthmatic children have experienced atopic dermatitis in their younger days. As it is very difficult to cure childhood asthma we attempted to determine the anti-allergic drug effects in preventing the development of asthma by using ketotifen on atopic dermatitis patients. The study was designed as a placebo controlled double blind trial of 128 atopic dermatitis patients aged from 2-34 months. 91 patients were given complete analysis in the study, 33 patients were given only a safety rate and 4 patients were dropped. The 91 patients were followed for 52 weeks. Our primary finding was that the development of bronchial asthma was inhibited in the ketotifen group compared to the placebo controlled group with a statistically significant degree (p less than 0.001). We also found that clinical symptoms of atopic dermatitis were significantly improved in the ketotifen group (p less than 0.001). Only 5 patients complained of mild side effects.

Age Factors↗

Two pyridine analogues with more effective ability to reverse multidrug resistance and with lower calcium channel blocking activity than their dihydropyridine counterparts.

Four pyridine analogues and their dihydropyridine counterparts were examined for their ability to reverse drug resistance in a multidrug-resistant human carcinoma cell line, KB-C2. Two pyridine analogues were more able to reverse drug resistance than their dihydropyridine counterparts. The other two pyridine analogues had an effect on drug resistance similar to their dihydropyridine counterparts. The calcium channel-blocking activity of all the pyridine analogues was considerably lower than that of the dihydropyridine analogues. Of the pyridine analogues, 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl 5-(trans-4,6-dimethyl-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4 -(3- nitrophenyl)-3-pyridinecarboxylate P-oxide (PAK-104P) was the most effective in reversing multidrug resistance. PAK-104P (1 and 5 microM) completely reversed the drug resistance in KB-8-5 and KB-C2 cells, respectively. The reversing effect of PAK-104P was greater than that of other multidrug resistance-reversing agents, cepharanthine, verapamil, nimodipine, and nicardipine. PAK-104P at 1 microM increased about 10-fold the accumulation of vinblastine in KB-C2 cells, whereas verapamil at the same concentration increased the accumulation about 2-fold. The inhibition of [3H]azidopine photolabeling of P-glycoprotein by the pyridine and dihydropyridine analogues except 2-[methyl(phenyl-methyl)amino]ethyl 4-(2-chlorophenyl)-5-(4-methyl-1,3,2-dioxaphosphorinan-2-yl)-1,4-d ihydro-2,6- dimethyl-3-pyridinecarboxylate P-oxide correlated with the reversing of drug resistance by the analogues. Some newly synthesized pyridine analogues seemed to have lower calcium channel-blocking activity and more potent resistance-reversing ability than verapamil and other calcium channel blockers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Demonstration of enterotoxigenic Escherichia coli in diarrheic broiler chicks.

An investigation was made to survey the possible presence of enterotoxigenic Escherichia coli (ETEC) in the stools of diarrheal chicks. We analyzed two outbreaks of diarrhea in broiler chicks at two independent farms in the Philippines, from which no pathogens other than Escherichia coli were found. In one outbreak at Farm #1, all 42 isolates produced heat-labile enterotoxin (LT), with 3 of these isolates also producing heat-stable enterotoxin (ST). The O serotypes of 15 strains tested randomly could not be identified as any known serotype (0-antigen; 1-170). In another outbreak at Farm #2, 7 out of 52 isolates produced only LT, their subtypes being identified as O-149 or O-8, common serotypes in pig ETEC. Strains from Farm #1 did not produce any pili usually found in human ETEC. We believe this to be the first isolation of ETEC from diarrheal chicks.

Animals↗

Conotoxin GIIIA: selective inhibition of 22Na influx via voltage-dependent Na channels in adrenal medullary cells.

Conotoxin GIIIA and GIIIB from the marine snail Conus geographus have been reported to inhibit voltage-dependent Na channels in skeletal muscle and postganglionic sympathetic neuron, but have no effect on Na channels in brain, giant axon and heart. In eel electroplax, conotoxins were also shown to share the common binding sites with saxitoxin (see review Gray et al. 1988). In bovine adrenal medullary cells, conotoxin GIIIA inhibited veratridine-induced influx of 22Na, 45Ca and secretion of catecholamines with an IC50 of 6 mumols/l while saxitoxin suppressed veratridine-induced responses with an IC50 of 6.3 nmol/l. [3H]Saxitoxin binding to the cells was inhibited by unlabeled saxitoxin with an IC50 of 5.1 nmol/l, but was slightly reduced by 10 mumols/l conotoxin GIIIA. Conotoxin GIIIA, at 10 mumols/l, did not alter carbachol-induced influx of 22Na, 45CA and secretion of catecholamines as well as high K-induced 45Ca influx and catecholamine secretion. These results indicate that conotoxin GIIIA, at concentrations 950 fold higher than saxitoxin, inhibits Na influx via voltage-dependent Na channels, but has no effect on the nicotinic receptor-ion channel complex or the voltage-dependent Ca channels. Conotoxin GIIIA seems to bind at the sites which are distinct from saxitoxin, but are functionally linked to the voltage-dependent Na channels. Conotoxins may be useful for the classification of Na channels in excitable cell membranes.

Adrenal Medulla↗

Clinical assessment of specific enzyme immunoassay for the human cardiac myosin light chain II (MLC II) with use of monoclonal antibodies.

A highly specific enzyme-linked "sandwich" immunoassay was developed for determining cardiac myosin light chain II (MLC II) in serum by using an anticardiac MLC II monoclonal antibody and a solid phase consisting of glass rods coated with another monoclonal antibody. We can detect as little as 0.2 ng of cardiac MLC II per assay. The measurable range of cardiac MLC II concentration in serum is 1 to 30 micrograms/L. The assay demonstrated no cross-reactivity with a skeletal muscle MLC within the measurable range. The mean coefficients of variation were 6.1% within assay and 5.1% between assay. The concentration of cardiac MLC II in sera from healthy subjects ranged from 0 to 4.0 micrograms/L (mean 0.75 micrograms/L and median 0 micrograms/L). The concentrations of cardiac MLC II in serum of patients with skeletal muscle disease due to various causes (n = 15) and patients with effort angina (n = 25), in general, were not significantly elevated above normal. In all patients with myocardial infarction, the concentrations of cardiac MLC II were over 4.0 micrograms/L at 12 h after onset. The mean (+/- 1 SD) peak concentration of cardiac MLC II was 16.2 (+/- 4.4) micrograms/L at 90 h (mean) after onset. On the 5th day, the cardiac MLC II concentrations in all patients with myocardial infarction were significantly elevated above normal; none showed abnormal MB-creatine kinase (CK-MB) activity at this time. Thus, the measurement of cardiac MLC II concentration in serum may be useful to provide a specific and sensitive diagnosis of myocardial necrosis at any time period following myocardial infarction.

Adult↗