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Biomedical subjects

N Shimamoto

Publications and source records attributed to N Shimamoto.

At least 55 records · Page 3Linked to original sources
PubMed1990

Effects of pretreatment with 2-O-octadecylascorbic acid, a novel free radical scavenger, on reperfusion-induced arrhythmias in isolated perfused rat hearts.

The effects of pretreatment with 2-O-octadecylascorbic acid (CV-3611), a novel liposoluble free radical scavenger, on reperfusion-induced arrhythmias were studied in isolated perfused rat hearts (n = 15 per group). The hearts were subjected to 10 min of coronary artery occlusion and 3 min of reperfusion. Pretreatment with CV-3611 (5 and 20 mg/kg) reduced the incidence of ventricular fibrillation (VF; reversible plus sustained) from its control value of 93% to 47% (p less than 0.05). Furthermore, CV-3611 reduced the incidence of sustained VF in a dose-dependent manner, from 67% in the control group to 13% in the CV-3611, 20 mg/kg treated group (p less than 0.01). CV-3611 (5 and 20 mg/kg) reduced the incidence of ventricular tachycardia (VT) from its control value of 93% to 73%. Pretreatment with ascorbic acid (5 mg/kg) had no effect on VF and VT. The myocardial content of CV-3611 was proportional to the dosage. We concluded that CV-3611 could reduce significantly the susceptibility to reperfusion-induced arrhythmias, especially VF, and that its effect may be due to the elimination of oxygen-derived free radicals by CV-3611 present in the membrane and the capture of lipid radicals, thereby inhibiting lipid peroxidation.

Animals↗
PubMed1989

Cardiovascular effects of endothelin in dogs: positive inotropic action in vivo.

Endothelin, administered i.v. to anesthetized dogs, dose dependently increased the cardiac output, left ventricular systolic pressure (LVSP), and maximum upstroke velocity (max dp/dt) of the LVSP for about 10 min without changing the heart rate. Thereafter the cardiac output decreased to below the control level but max dp/dt decreased to the control level. The arterial pressure and total peripheral resistance showed an initial, transient decrease followed by a sustained increase. These results suggest that endothelin has positive inotropic and long-lasting vasoconstrictive effects preceded by transient vasodilatation in vivo.

Anesthesia↗
PubMed1989

Purification of an autocrine growth factor in conditioned medium obtained from primary cultures of scleral fibroblasts of the chick embryo.

Scleral fibroblasts of the chick embryo were found to secrete autocrine growth factors. One of the factors was purified from conditioned medium collected from growing-phase cultures of these cells by DEAE-Sepharose column chromatography and following non-denaturing polyacrylamide gel electrophoresis. The specific activity was increased 1100-fold by this purification. The chromatographically purified growth factor was still active after incubation at 95 degrees C, at pH 10 or pH 3, or with glycosidase H, but inactive after incubation with dithiothreitol or trypsin. An active protein having a molecular weight of 32 kDa was found to be the major component of the final preparation.

Animals↗
PubMed1989

Positive inotropic and vasoconstrictive effects of endothelin-1 in in vivo and in vitro experiments: characteristics and the role of L-type calcium channels.

Cardiac and vascular effects of endothelin-1 (ET-1) were studied in hemodynamic models in vivo and in isolated artery and heart tissues. The hemodynamic changes induced by ET-1 (30-300 pmol/kg i.v.) in dogs were increases in blood pressure, cardiac output, and ventricular contractility. Ring preparations of canine coronary artery and rabbit thoracic aorta showed vasoconstrictive responses to ET-1 (10(-10) M and over) with an EC50 of 3-10 x 10(-9) M. Nifedipine 10(-5) M did not reverse these effects completely. ET-1 had positive inotropic effects from 10(-10) M in rabbit papillary muscles. It lengthened the action potential duration by 16% and increased the developed tension by 180% (10(-8) M). In contrast, Bay K 8644 (10(-7) M) produced similar lengthening (17%) in the duration with only a 37% increase in the tension. This suggests a difference in the mechanisms of the positive inotropic effects between these two agents. We conclude that ET-1 has positive inotropic and vasoconstrictive effects, and that these ET-1-induced contractions in ventricular muscles and arteries cannot be explained thoroughly by the increase in currents through voltage-dependent calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Studies on scavengers of active oxygen species. 1. Synthesis and biological activity of 2-O-alkylascorbic acids.

A novel series of 2-O-alkylascorbic acids (5a-u) was synthesized, and their scavenging activities against active oxygen species as well as their suppressive effects on the arrhythmias in rat heart ischemia-reperfusion models were evaluated. Some 2-O-alkylascorbic acids (5e-1) exhibited potent inhibiting activities against lipid peroxidation in rat brain homogenates and in alleviating effects in the ischemia-reperfusion models. Studies on the structure-activity relationship demonstrated that a free 3-enolic hydroxyl group and the longer alkyl chains substituted on the 2-hydroxyl group of ascorbic acid were beneficial for the biological and pharmacological activities. 2-O-Octadecylascorbic acid (5k, CV-3611), one of the most potent and promising compounds, markedly inhibited lipid peroxidation (IC50 = 4.3 X 10(-6) M) and alleviated myocardial lesions induced by ischemia-reperfusion at an oral dose of 1 mg/kg in rats.

Animals↗
PubMed1987

Catch-relaxing peptide isolated from Mytilus pedal ganglia.

A peptide that relaxes catch tension of the anterior byssus retractor muscle of Mytilus edulis was purified from pedal ganglion extracts of the mussel. Its primary structure was determined to be H-Ala-Met-Pro-Met-Leu-Arg-Leu-NH2. This peptide was found to have not only catch-relaxing action on the byssus retractor muscle but also modulatory actions on contractions in various molluscan muscles.

Animals↗
PubMed1987

Specific and cooperative binding of E. coli single-stranded DNA binding protein to mRNA.

Fluorometric titration of E. coli single-stranded DNA binding protein with various RNAs showed that the protein specifically and cooperatively binds to its own mRNA. The binding inhibited in vitro expression of ssb and bla but not nusA. This inhibition takes place at a physiological concentration of SSB. The function of the protein in gene regulation is discussed.

Binding Sites↗
PubMed1987

Coronary hyperperfusion and myocardial metabolism in isolated and intact hearts.

We determined the independent influence of coronary hyperperfusion on myocardial metabolism in isolated and intact hearts. In an isovolumic blood-perfused rat heart preparation working against a left ventricular (LV) balloon, the effect of increasing coronary perfusion pressure from 100 to 150 mmHg was assessed. In three groups of rat hearts LV volume was fixed to obtain LV peak pressures of 42 +/- 3, 101 +/- 5, and 130 +/- 6 mmHg. With coronary hyperperfusion, LV pressure increased 27, 18, and 16%, LV maximum time derivative of pressure (dP/dt) increased 39, 20, and 22%, and myocardial O2 consumption (VO2) increased 16, 17, and 33%, respectively. In a fourth group, LV peak pressure was held constant at 92 +/- 4 mmHg during coronary hyperperfusion by decreasing LV volume. In this group, despite an increase in coronary blood flow of 48%, there was no significant difference in LV maximum dP/dt or myocardial VO2. Thus, in isolated rat hearts, coronary hyperperfusion was not an independent stimulus to myocardial VO2. To further test this, the effect of coronary hyperperfusion on myocardial metabolism was studied in an intact working swine heart preparation where the cardiac output was fixed with a right heart bypass circuit. Fatty acid oxidation in the left anterior descending bed was assessed by production of 14CO2 from [14C(U)]palmitate. A comparison of coronary perfusion 106 +/- 5 vs. 197 +/- 5 mmHg resulted in no significant change in global LV function, including LV internal diameter. Despite a 70% increase in coronary blood flow, there was no significant change in myocardial VO2 or fatty acid utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Release of the sigma subunit of Escherichia coli DNA-dependent RNA polymerase depends mainly on time elapsed after the start of initiation, not on length of product RNA.

To elucidate the mechanism of sigma release in the transcript by Escherichia coli DNA-dependent RNA polymerase, we obtained the time courses of sigma release and elongation of product RNA by a rapid kinetic technique; transcription was synchronously initiated from A1 promoter on T7 DNA by the addition of four substrates to a stoichiometric mixture of holoenzyme and template DNA, and then quenched by the addition of EDTA. The elongation rate was changed by limiting the concentration of one of four substrates, GTP. At reduced GTP concentration, elongation was decelerated, but the time course of sigma release was unchanged. No connection between sigma release and length of RNA product was found. The results lead to the conclusion that sigma is released depending only on time elapsed after initiation, not on the length of RNA product. We propose a two-step model for sigma release with a rapid triggering and a slow dissociation of about 5 s. This dissociation, the rate-determining step of sigma release, is independent of the rate of elongation.

DNA-Directed RNA Polymerases↗
PubMed1985

Enhanced responsiveness of the coronary blood vessel of the dog heart-lung preparation to PGI2 after chronic chemical sympathectomy.

Chronic chemical denervation of the sympathetic nervous system with 6-OH dopamine resulted in an augmentation of the coronary blood flow (CBF) increase inherent in the canine heart-lung preparation, but not in an augmented accumulation of 6-keto PGF1 alpha in the circulating blood. In denervated HLP, 6-keto PGF1 alpha was lower and the vasodilator response to PGI2 larger at the start of the experiments. It was concluded that exaggerated increase in CBF was due to a potentiation of the vasodilator response to PGI2.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Multiple conformational transitions of hen egg-white lysozyme in aqueous acetic acid solutions.

Circular dichroism measurements revealed that hen egg-white lysozyme underwent multiple conformational transitions upon the addition of acetic acid. The transitions were reversible as judged from complete recoveries of enzymatic activity, electrophoretic mobility in SDS-polyacrylamide gel, and of ellipticity. Two transitions, with the mid-concentrations of 26 and 38% (v/v), were observed with the CD spectra in the amide absorption region. The two transitions were essentially athermal in the temperature ranges, 0 to 25 degrees C for the former and -10 to 10 degrees C for the latter. The trough ellipticity for the product of the transition at the higher acetic acid concentration (DII form) very closely approached the value for the synthetic polypeptides in the beta-conformation as the temperature was lowered. Molecular weight measurements by sedimentation equilibrium indicated that the products were both monomeric. Measurements of CD spectra in the aromatic absorption region showed another transition, whose mid-concentration varied with temperature from 26% (v/v) (at about 25 degrees C) to 38% (v/v) (at -10 degrees C). A change in the hydrodynamic volume detectable by exclusion chromatography was associated with this transition only.

Acetates↗
PubMed1984

Cerebral circulatory and cardiac effects of vinpocetine and its metabolite, apovincaminic acid, in anesthetized dogs.

Cerebral circulatory and cardiac actions of vinpocetine and its metabolite, apovincaminic acid (AVA), were studied in anesthetized dogs. Injections of vinpocetine (0.03 to 1.0 mg/dog) into the vertebral or coronary artery produced dose-dependent increases in the blood flow of each artery. The action was more prominent in the vertebral than in the coronary artery. Intravenous bolus injections of vinpocetine (0.3 and 1.0 mg/kg) transiently increased vertebral flow and superior sagittal sinus flow velocity in a dose-dependent manner. Femoral flow was slightly increased with a fall in diastolic pressure. AVA (1.0 to 5.0 mg/kg) did not significantly increase vertebral, but increased femoral flow, which was accompanied by systemic hypotension. A similar trend of actions was noted after i.v. infusion of both agents (0.15 and 0.5 mg/kg/min for 30 min). An i.d. administration of vinpocetine (10 mg/kg) increased vertebral and regional cerebral cortical flows, accompanying with a fall in diastolic blood pressure. Femoral flow was not affected. An i.v. bolus injection of vinpocetine (1, 3 and 10 mg/kg) transiently decreased systemic blood pressure, left ventricular maximum dp/dt and heart rate in a dose-dependent manner. Cardiac output tended to be increased, and total peripheral resistance decreased. Coronary flow was transiently increased at 1 and 3 mg/kg, but tended to be decreased at 10 mg/kg. AVA, in the same dose range, decreased systemic blood pressure and total peripheral resistance, and increased cardiac output and coronary flow in a dose-dependent manner. An i.v. infusion of vinpocetine (0.5 mg/kg/min for 30 min) decreased systemic blood pressure, left ventricular maximum dp/dt, total peripheral resistance and heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1983

Mechanism and role of cooperative binding of bacteriophage fd gene 5 protein to single-stranded deoxyribonucleic acid.

The highly cooperative binding of fd gene 5 to single-stranded DNA was studied kinetically by rapid photo-cross-linking and stopped-flow UV absorption measurements. The observed change in absorbance was shown to be due to the binding by direct evidence of rapid photo-cross-linking of the bound proteins to fd DNA. The bimolecular rate constant obtained for the association was 1.6 X 10(10) M-1 s-1 (in terms of the molecular concentration of DNA), which was concluded to be diffusion controlled. The breakdown of cluster complexes on fd DNA was induced by the addition of large excess amounts of short single-stranded DNA. The breakdown took place in about 1 s. The kinetic process of redistribution of dissociated proteins was monitored by rapid photo-cross-linking and subsequent electrophoresis of the cross-linked complex. The dissociated proteins first formed isolated complexes, but later they were again converted into the cluster. The kinetic results showed that the cooperativity originated from the stabilization of the protein-DNA complex by the cluster formation, not from the accelerated association in the cluster formation. This kind of cooperative binding was shown to perform negative feedback control in the cluster formation. On the basis of the kinetic results obtained, we proposed a model for the regulatory role of the fd gene 5 protein in the synthesis of single-stranded fd DNA.

Animals↗
PubMed1983

Preventive effect of a quinonyl derivative of N-acetylmuramyl dipeptide, QMDP-66, against adriamycin-induced ECG abnormalities in rats.

The effects on adriamycin cardiotoxicity of an immunoadjuvant, 2-[2-acetamido-2-deoxy-6-0-[10-(2,3-dimethoxy-5-methyl-1, 4-benzo-quinon-6-yl) decanoyl]-D-glucopyranos-3-0-yl]-D-propionyl-L-valyl D-isoglutamine methyl ester (QMDP-66), and a reference compound, ubiquinone-10, were studied in Wistar Kyoto (WKY) rats. Adriamycin, 1 mg/kg/day intra-peritoneally (i.p.) for 23 days, elicited cardiotoxicity, as judged by widening of the QRS complexes in ECGs. Electron microscopic examination of myocytes from the treated rats revealed many cytoplasmic vacuoles possibly originating from deranged endoplasmic reticula or mitochondria. In addition, the treatment significantly inhibited body weight gain, and decreased ventricular weight. QMDP-66 alone, 1 mg/kg/day i.p. for 23 days, had no effect on the parameters described above. When QMDP-66 (1 mg/kg/day, i.p.) or ubiquinone-10 (3 mg/kg/day, i.p.) was administered together with adriamycin, the widening of the QRS complexes was significantly depressed, and cytoplasmic vacuoles in myocytes were rarely observed. The QMDP-66 or ubiquinone-10 treatment, however, did not alleviate the decrease in body weight gain or ventricular weight due to adriamycin. Heart rate was not significantly changed by any of the treatments. These findings suggest that QMDP-66 is an effective antidote against adriamycin cardiotoxicity.

Acetylmuramyl-Alanyl-Isoglutamine↗