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Biomedical subjects

M Arita

Publications and source records attributed to M Arita.

At least 307 records · Page 17Linked to original sources
PubMed1986

Effects of trimetazidine on action potentials and membrane currents of guinea-pig ventricular myocytes.

The effects of trimetazidine on membrane potentials and membrane currents of enzymatically isolated guinea-pig ventricular cells were studied with the use of giga-seal suction pipettes for patch clamp. Trimetazidine (3 X 10(-5) M) decreased the action potential duration from 433 +/- 179 ms (mean and S.D., n = 9) to 319 +/- 156 ms within 8 mins. In voltage clamp experiment, trimetazidine at a concentration of 1.5 X 10(-4) M decreased the peak amplitude of calcium current by 40% (0.92 +/- 0.46 nA to 0.55 +/- 0.19 nA, mean +/- S.D., n = 5). The effect on calcium current was rate-dependent, e.g., at 1 Hz, trimetazidine blocked a larger fraction of the calcium current than at 0.2 Hz. The drug decreased the conductance of potassium current which flows via inward rectifier potassium channel from 28 +/- 11 nS to 19 +/- 10 nS, n = 5, P less than 0.05). Trimetazidine shifted the steady state current-voltage relationship outward at potentials positive to -20 mV. This shift was not due to the enhanced time- and voltage-dependent outward current (Ik). From these findings, it was concluded that trimetazidine shortens action potential duration by blocking the calcium channels with increases in steady state outward current or a possible blockade of non-inactivated component of the calcium current, at the plateau potentials. The reduction of calcium current and of inward rectifier potassium current may protect the cardiac cells from accumulation of calcium ions and from loss of potassium ions, in the presence of ischemia.

Action Potentials↗
PubMed1986

Purification and characterization of Vibrio cholerae non-O1 heat-stable enterotoxin.

A toxin which causes rapid fluid accumulation in a suckling mouse assay and which was produced by Vibrio cholerae non-O1 was investigated. The toxin was purified from the culture supernatant of V. cholerae non-O1 (strain A-5) by ammonium sulfate fractionation, hydroxyapatite treatment, ethanol extraction, column chromatographies on SP-Sephadex C-50 and DEAE-Sephadex A-25, and high-pressure liquid chromatography on a Lichrosorb RP-8 column. About 1.4 X 10(5)-fold purification was achieved, with a recovery of about 12%. Although the crude preparation was heat labile, the purified toxin was heat stable. The minimum effective dose of purified toxin was about 5 ng in the suckling mouse assay. The amino acid composition of the purified toxin was determined to be Asp(3), Glu(1), Ala(1), half-Cys(6), Ile(2), Leu(1), Phe(1), and Pro(1). These data show the production of a new type of heat-stable enterotoxin (NAG-ST) by V. cholerae non-O1.

Amino Acids↗
PubMed1986

Genetic analysis of the attenuation phenotype of poliovirus type 1.

Seven different recombinant viruses from the virulent Mahoney and the attenuated Sabin parental strains of type 1 poliovirus were constructed in vitro by using infectious cDNA clones. Monkey neurovirulence tests (lesion score, spread value, and incidence of paralysis) using these recombinant viruses revealed that the loci influencing attenuation were spread over several areas of the viral genome, including the 5' noncoding region. In vitro phenotypic marker tests corresponding to temperature sensitivity of growth (rct marker), plaque size, and dependency of growth on bicarbonate concentration (d marker) were performed to identify the genomic loci of these determinants and to investigate their correlation with attenuation. Determinants of temperature sensitivity mapped to many areas of the viral genome and expressed strong but not perfect correlation with attenuation. Recombinant viruses with Sabin-derived capsid proteins showed a small-plaque phenotype, and their growth was strongly dependent on bicarbonate concentration, suggesting that these determinants map to the genomic region encoding the viral capsid proteins. Plaque size and the d marker, however, were found to be poor indicators of attenuation. Moreover, virion surface characteristics such as immunogenicity and antigenicity had little or no correlation with neurovirulence. Nevertheless, viruses carrying Sabin-derived capsid proteins had an apparent tendency to exhibit less neurovirulence in tests on monkeys compared with recombinants carrying Mahoney-derived capsid proteins. Our results suggest that the extent of viral multiplication in the central nervous system of the test animals might be one of the most important factors determining neurovirulence. Moreover, we conclude that the expression of the attenuated phenotype of the Sabin 1 strain of poliovirus is the result of several different biological characteristics. Finally, none of the in vitro phenotypic markers alone can serve as a good indicator of neurovirulence or attenuation.

Animals↗
PubMed1986

[Effect of mazindol on glucose absorption in everted rat small intestine].

Effect of an anorexiant, mazindol, on glucose absorption was investigated. Ten weeks-old female Sprague-Dawley rats were divided into mazindol treated (fed on powder diet containing 100 mg/kg of mazindol) and control groups. Four weeks later, experiments of continuous observation of glucose absorption and glucose transport were performed in each group using the everted sac method. During 180 min of continuous observation of glucose absorption, significantly lowered glucose concentrations of the serosal medium were observed in the mazindol treated group at oral and caudal ends of the upper, caudal end of the middle, and caudal ends of the lower small intestine, whereas no significant differences in glucose concentrations of the mucosal medium were observed between the two groups. After 60 min incubation for monitoring the glucose transport, significantly decreased glucose concentrations of serosal medium were observed in mazindol treated group at oral and caudal ends of the upper, caudal ends of the middle and caudal ends of the lower small intestine, whereas no significant differences in glucose concentrations of mucosal medium were observed. The results suggested that there is little effect on glucose absorption, but the metabolism of glucose or the remaining glucose in the small intestinal wall is increased by mazindol treatment.

Animals↗
PubMed1986

Na,K-ATPase activity and repolarization of ventricular action potentials in simian hearts.

We measured Na,K-ATPase activity and ATP content of 4 different areas of the left ventricular muscle of Japanese monkeys (Mucaca fuscata): The apex, base, and epicardium (Epi) and endocardium (Endo) of the free wall. We compared those values with electrical parameters such as action potential duration (APD) and the level of resing potentials. APDs of base and Endo were significantly longer than those of apex and Epi, respectively. There was no significant difference in ATP contents among the four tissues while Na,K-ATPase activity in Epi was significantly higher, thereby indicating that the maximum capacity of the Na,K-pump activity is greater in Epi than in Endo. This observation serves to explain the following differences in electrophysiology characteristics found between Epi and Endo: greater shortening of APD in Endo when the cycle length of stimulation was shortened (from 2,000 to 200 ms) or when ouabain (0.5-1 microM) was applied; larger amplitude of post-overdrive hyperpolarization in Epi; and marked ouabain-induced depolarization of the resting potential in Endo, as compared to Epi. We conclude that the difference in Na,K-ATPase activity accounts for the different electrical behavior observed in Epi and Endo of the simian ventricle.

Action Potentials↗
PubMed1986

[The pattern of left ventricular hypertrophy in hypertension and its relation to the hemodynamic and sympathetic responses to exercise].

A wide spectrum of cardiac hypertrophy has been observed in hypertensive patients. In this study, the responses of hemodynamics and sympathetic drives to exercise among hypertensive patients with various types of left ventricular hypertrophy were investigated. Twenty-five patients with untreated essential hypertension (WHO I and II) were classified as those with and without asymmetric hypertrophy (with AH, n = 7; without AH, n = 18) by their echocardiographic patterns. Ten normotensives served as controls. Exercise was performed on a braked bicycle ergometer; the initial work load was 50 watt. The work load increased progressively by 25 watt at three minute-intervals to the target heart rate, exhaustion, or positive ST.T changes. Blood pressure, heart rate, plasma norepinephrine and hemodynamic parameters by echocardiography were estimated at rest and during exercise. Systolic blood pressure and increased heart rate by exercise in all groups. In patients with AH, a rapid increase was observed, and the increase in systolic blood pressure at submaximum exercise was significantly greater than those in normotensives or patients without AH (p less than 0.05). During exercise, endsystolic dimension decreased in normotensives and in patients without AH (p less than 0.01), but the change was not significant in patients with AH. Percent fractional shortening and percent systolic wall thickening of the interventricular septum and left ventricular posterior wall increased significantly in normotensives and in patients without AH (p less than 0.05), but they were unaltered in patients with AH. Although plasma norepinephrine significantly increased in all groups by exercise, the increase in patients with ASH was greater than those in the other groups (p less than 0.05). These results suggest that hyperresponsiveness of systolic blood pressure and heart rate to exercise may play a role in the pathogenesis of AH, and that this type of hypertrophy could be associated with abnormalities of the sympathetic nervous system.

Adult↗
PubMed1986

Overcoming drug resistance in cancer cells with synthetic isoprenoids.

A cultured subline (P388/ADM) of mouse P388 leukemia resistant to doxorubicin, vinblastine, vincristine, dactinomycin, and daunorubicin became sensitive again when treated with noncytotoxic doses of either of two synthetic isoprenoids: N-solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine (SDB-ethylenediamine) and N-(p-methylbenzyl)decaprenylamine X HCI (PMB-decaprenylamine). The isoprenoids also reversed resistance to doxorubicin and vincristine in a cultured vincristine-resistant P388 leukemia subline (P388/VCR). Median lethal doses (LD50) for PMB-decaprenylamine and SDB-ethylenediamine administered ip were 123 and 350 mg/kg against mice, whereas the LD50 for verapamil, another modifier of cellular drug resistance, was about 7.6 mg/kg. In vivo experiments with P388/VCR-bearing mice showed that both SDB-ethylenediamine and verapamil overcame vincristine resistance, but PMB-decaprenylamine showed only slight activity. SDB-ethylenediamine was especially effective, overcoming the vincristine resistance at 1 mg drug/kg. Since the structure of SDB-ethylenediamine resembles that of verapamil, a calcium-blocking agent that overcomes drug resistance, it was checked for calcium-blocking activity. However, calcium channel-blocking activity was not observed with 20 micrograms isoprenoid/ml, whereas calcium channel activity was completely blocked by 1 microgram verapamil/ml.

Animals↗
PubMed1986

[Clinical evaluation of adriamycin ointment in advanced or local recurrent breast cancer].

For the purpose of local therapy for advanced and recurrent breast cancer, we have applied a new Adriamycin (ADR) ointment. This new ADR ointment has been prepared by the technique of a two-factor composite experimental design and includes PEG: 25%, CVP: 0.65%, HPC: 1.35% and ADR: 0.04%. We have applied it to three patients with advanced breast cancer and six patients with locally recurrent breast cancer. By using this ointment, the skin ulcers have become dry, bleeding has stopped and the sense of heat has been lost. In some cases, the neoplastic ulcers have diminished in size. Some problems with this ointment are easy bleeding at the time of removing the gauze and an unstable effect in diminishing the size of the neoplasm. We therefore think that the use of this ointment alone is very effective for controlling the symptoms of the local lesion, but not so effective for diminishing the size of the neoplasm.

Administration, Topical↗
PubMed1985

Amino acid sequence of heat-stable enterotoxin produced by Vibrio cholerae non-01.

The amino acid sequence of heat-stable enterotoxin, produced by Vibrio cholerae non-01 and isolated from its culture supernatant, was determined by both Edman degradation of native and reductively carboxymethylated enterotoxin and also a combination of fast atom bombardment mass spectrometry and carboxypeptidase Y digestion of native enterotoxin to be as follows: Ile-Asp-Cys-Cys-Glu-Ile-Cys-Cys-Asn-Pro-Ala-Cys-Phe-Gly-Cys-Leu-Asn. This sequence is very similar, but not identical, to those of heat-stable enterotoxins produced by enterotoxigenic Escherichia coli and Yersinia enterocolitica.

Amino Acid Sequence↗
PubMed1985

Antigenic variation and resistance to neutralization in poliovirus type 1.

Mutations have been identified in variants of poliovirus, type 1 (Mahoney) on the basis of their resistance to neutralization by individual monoclonal antibodies. The phenotypes of these variants were defined in terms of antibody binding; the pattern of epitopes expressed or able to be exploited for neutralization were complex. Single amino acid changes can have distant (in terms of linear sequence) and generalized effects on the antigenic structure of poliovirus and similarly constituted virions.

Amino Acid Sequence↗
PubMed1985

Pretreatment with coenzyme Q10 protects guinea pig ventricular muscle from hypoxia-induced deterioration of action potentials and contraction.

Effects of coenzyme Q10 (CoQ10) on hypoxia-induced changes in transmembrane action potentials and isometric tension were studied in isolated guinea pig ventricular papillary muscles. Guinea pigs were pretreated with CoQ10 (60 mg/kg/day i.p., n = 4) or the solvent (n = 4) for 3 consecutive days before the study. The hypoxia for 30 min (Po2 = 40 mmHg) was induced to the preparation twice with a 20 min normoxic perfusion (Po2 = 300 mmHg) intervention. The hypoxia markedly shortened action potential duration (APD) and decreased the developed tension, the effects being more pronounced during the second than the first-induced hypoxia. Pretreatment with CoQ10 or the solvent did not affect the membrane potentials and contractile tension under normoxic conditions. The decreases in APD and the developed tension produced by hypoxia were partially but significantly suppressed in the preparation obtained from CoQ10-pretreated animals. The results suggest that the pretreatment with CoQ10 partially protects the isolated ventricular muscle subjected to hypoxia from the deterioration of action potentials and contraction.

Action Potentials↗
PubMed1985

Isoproterenol inhibits residual fast channel via stimulation of beta-adrenoceptors in guinea-pig ventricular muscle.

When perfused with high K+ (8.1 to 14.9 mM)-Tyrode's solution, the upstroke of action potentials in the isolated guinea-pig ventricular muscle is composed of two components and there are two separable peaks in the first derivative, i.e., Vmax, fast and Vmax, slow. The Vmax, fast was a measure of activation of the residual fast channel, while the Vmax, slow was that of the slow channel. Isoproterenol depressed Vmax, fast with increase in Vmax, slow, in a concentration-dependent manner (10(-8) to 10(-6) M). This depression of Vmax, fast was greater at more depolarized levels of membrane potential. Therefore, the isoproterenol-induced depression of Vmax, fast may be due to a negative shift of the curve relating Vmax, fast to the take-off potential (Em) (Vmax--Em relationship), along the voltage axis. The negative shift of Vmax--Em relationship by isoproterenol was also recognized in small preparations the size of which is well within the space constant. The negative shift was inhibited in the presence of beta-blockers (pindolol 1 microgram/ml or atenolol 10 micrograms/ml) but not by a calcium antagonist, 1-verapamil (1 microgram/ml). These results suggest that isoproterenol blocks sodium channels in the depolarized ventricular muscle via stimulation of the beta-adrenoceptors and that the depression of Vmax, fast is not mediated by the well-known effects of isoproterenol on Vmax, slow, i.e., increased influx of Ca2+ ions.

Action Potentials↗
PubMed1985

A case of hemangiomyoma of the ureter in a child.

Herein a rare case of hemangiomyoma of the ureter in a child is reported. Benign mesodermal tumors of the ureter are not common, particularly in a child. Two cases of leiomyoma of the ureter in childhood have been reported to date. This is the first case of ureteral hemangiomyoma in a child. Nephroureterectomy was performed and the subsequent clinical course reveals no evidence of recurrence.

Child↗