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Biomedical subjects

K Saeki

Publications and source records attributed to K Saeki.

At least 253 records · Page 14Linked to original sources

Electrophysiologic effects of E-4031, a class III antiarrhythmic agent, on re-entrant ventricular arrhythmias in a canine 7-day-old myocardial infarction model.

Effects of E-4031, a class III antiarrhythmic agent, on re-entrant ventricular arrhythmias were studied in eight dogs with a 7-day-old myocardial infarction. Epicardial mapping and local refractory periods were obtained using 47-channel bipolar electrodes attached to the epicardium. The induction of sustained ventricular tachycardia by programmed electrical stimulation was not suppressed by i.v. infusion of E-4031 at 1 microgram/kg/min, but was suppressed markedly by infusion at 10 micrograms/kg/min in six of seven dogs. During the infusion of E-4031 at 10 micrograms/kg/min, epicardial conduction velocity in the normal ventricle did not change (0.7 +/- 0.12 to 0.71 +/- 0.13 m/sec, n = 6), whereas slowed conduction in the infarct zone improved (0.58 +/- 0.10 to 0.77 +/- 0.13 m/sec, n = 6). E-4031 at 10 micrograms/kg/min prolonged effective refractory periods (ERP) in the normal zone (139 +/- 8 to 164 +/- 18 msec, P less than .01, n = 8), nontransmural infarct zone (145 +/- 7 to 177 +/- 15 msec, P less than .01, n = 8) and transmural infarct zone (156 +/- 14 to 191 +/- 22 msec, P less than .01, n = 8). The degrees of ERP prolongation were almost equal in all zones. On epicardial mapping, the areas of longer ERP and delayed conduction were observed to become inexcitable after the administration of E-4031. These results demonstrated that E-4031 effectively prevented the induction of re-entrant ventricular tachycardia in canine myocardial infarction model, and suggested that E-4031 rendered re-entrant circuits inexcitable by marked ERP prolongation in both normal and infarct zones.

Animals↗

[Two cases of cardiac rupture after myocardial hemorrhagic infarct].

Two patients, both of whom were men over 65 years of age who had no history previous myocardial infarcts, had sudden chest pain. One of the men died due to cardiogenic shock on the first day, and the other died on the fourth hospital day. Each autopsy disclosed transmural myocardial infarct with hemorrhage, resulting in cardiac rupture. Hemorrhage was recognized in the necrotic area of the myocardial infarcts. Each cardiac rupture was found in the center of the hemorrhagic infarcts. The ruptures were tear-like slits. The healing process of the infarct was much more delayed in the hemorrhagic area than in the anemic area. These two cases suggest that hemorrhagic infarct may be one of the risk factors of cardiac ruptures.

Aged↗

alpha-Fluoromethylhistidine decreases the histamine content of the rat right atrium under the influence of sympathetic activity.

alpha-Fluoromethylhistidine (alpha-FMH; 65 mg/kg, i.p.), a specific inhibitor of histidine decarboxylase, significantly decreased the histamine content of the rat right atrium in a time-dependent manner; the maximal decrease of 22.2% was observed 4 h after injection. However, alpha-FMH had no significant effect on the histamine content of the left atrium or the ventricles. The alpha-FMH-induced decrease in the right atrial histamine content was not observed in rats pretreated with 6-hydroxydopamine (25 mg/kg, i.p.). Two i.p. injections of 10 and 5 mg/kg of propranolol and the cardioselective beta 1-adrenoceptor antagonist metoprolol almost completely inhibited the alpha-FMH-induced histamine decrease. On the other hand, phentolamine (10 mg/kg, i.p.) had no influence on the histamine-decreasing action of alpha-FMH. These results suggest that in the rat right atrium there is a histamine pool where a rapid turnover of histamine is maintained by normal sympathetic activity.

Animals↗

Production of bovine identical twins via transfer of demi-embryos without zonae pellucidae.

Embryos were collected nonsurgically from nåturally-cycling or superovulated donors 7 d after estrus. Forty-four morulae, early blastocysts and blastocysts classified as good to excellent were bisected using a fine glass needle to produce forty-four identical demi-embryos. The bisected demi-embryos, without zonae pellucidae, were nonsurgically transferred, either by twin or single transfer. An additional forty-eight embryos were collected from the same donors and transferred as a control. Among the twin transfers, 8 of the 13 recipients became pregnant (61.5%). Seven of them conceived twin fetuses (87%) and one a single fetus. However, only two sets of normal identical twin calves were obtained. Among the single transfers, 72.6% (45/62) of bisected embryos without zonae pellucidae resulted in pregnancy, of which 48.4% (30/62) were identical twins, and 24.2% (15/62) were singletons. Another 27.4% (17/62) of the recipients did not became pregnant. The pregnancy rate for whole embryos with zonae pellucidae was 72.9% (35/48). These data show that there was no significant difference between the pregnancy rates of bisected embryos without zonae pellucidae and whole embryos with zonae pellucidae transferred 7 d after estrus. Bisection of bovine embryos was simplified and even morula stage embryos were transferred without zonae pellucidae.

Journal Article↗

Corticotrigeminal motor pathway in the rat--II. Anterio- and retrograde HRP labeling.

1. Horseradish peroxidase (HRP) injection into the rat cortical jaw motor area (JMA) disclosed direct projection fibers in and around the motor trigeminal nucleus (MTN), primarily contralaterally. 2. Descending axons were found in the ventromedial half of the cerebral peduncle and MTN-projecting axons were concentrated near the descending facial nerve root. 3. HRP injection into the peduncle could label 1257 cells in the JMA, 128 cells in the taste area and 1409 cells in the neck-forelimb motor area ipsilaterally. 4. Some MTN-terminated axons could be traced from the peduncle in serial sections.

Animals↗

Corticotrigeminal motor pathway in the rat--I. Antidromic activation.

1. The rat corticotrigeminal motor pathway was electrophysiologically investigated. 2. Fifty-one cortical neurons were antidromically activated by stimulation of the contralateral motor trigeminal nucleus (MTN). 3. Twenty-eight of the neurons were examined to see whether they were pyramidal tract (PT) neurons and seven were the PT neurons. 4. Forty peduncular axons were antidromically activated by stimulation of the contralateral MTN and eight of them were the PT axons. 5. Most MTN projecting axons showed slower conduction velocities than their stem anons.

Animals↗

New method to prepare single-headed heavy meromyosin with high purity and a high yield.

We have developed a new method to prepare single-headed heavy meromyosin with high purity and a high yield. To examine whether the two heads on the same myosin molecule work cooperatively or not, it is important to prepare pure single-headed heavy meromyosin. Myosin was extracted from myofibrils treated with a solution containing CyDTA, a strong divalent cation chelator. CyDTA treatment was essential to the production of sHMM. Then such myosin was digested with chymotrypsin in the presence of divalent cations at high ionic strength. Crude sHMM was separated from double-headed HMM by affinity chromatography using an ADP-column. Contaminating S1 was removed by gel filtration. Heavy chain of sHMM obtained by the present method had no nick. Purified sHMM showed normal EDTA-ATPase and Ca-ATPase. It interacted with thin filament and its ATPase was activated by actin normally.

Adenosine Triphosphatases↗

Ferredoxin and rubredoxin from Butyribacterium methylotrophicum: complete primary structures and construction of phylogenetic trees.

Complete amino acid sequences of ferredoxin and rubredoxin from Butyribacterium methylotrophicum, a methylotrophic hetero-acetogen, were determined by combination of protease digestion, Edman degradation, carboxypeptidase digestion, and/or partial acid hydrolysis. The ferredoxin was composed of 55 amino acids with a molecular weight of 5,732 excluding iron and sulfur atoms and showed a typical 2[4Fe-4S]-type ferredoxin sequence with an internal repeat at the 14-23 and 42-51 positions. The rubredoxin was composed of 53 amino acids with a molecular weight of 5,672 excluding iron atom and showed a sequence similar to those of other anaerobic rubredoxins. The sequences were compared to those of corresponding proteins from six different bacteria to construct phylogenetic trees, which showed essentially the same topology. The relationships between the ferredoxin sequences from this bacterium and those of Clostridium thermoaceticum and Methanosarcina barkeri, both of which possess a carbonyl-dependent acetyl-CoA metabolic system, are also discussed.

Amino Acid Sequence↗

Changes in histamine metabolism in the brains of mice with streptozotocin-induced diabetes.

Histamine (HA) metabolism in the brain of mice with streptozotocin (STZ)-induced diabetes was examined. The levels of tele-methylhistamine (t-MH), a major metabolite of brain HA, significantly increased 3 and 4 weeks after STZ injection. However, the HA turnover rates in the diabetic mice, determined from the accumulation of t-MH after the administration of pargyline, were not different from the control values when the animals were allowed free access to food. When the mice were starved for 15 h 4 weeks after STZ treatment, the brain levels of L-histidine decreased significantly, whereas HA turnover increased significantly. Such changes were not observed in starved control mice. Histidine decarboxylase or HA N-methyltransferase activity did not change after starvation in either diabetic or control mice. These results show that the histaminergic (HAergic) activity in the brains of diabetic mice remains within normal range as long as the animals are allowed free access to food. However, they also indicate that a marked enhancement of HAergic activity accompanied by a decrease in the brain L-histidine level occurs in starved diabetic mice.

Animals↗

Effects of the histamine H3-agonist (R)-alpha-methylhistamine and the antagonist thioperamide on histamine metabolism in the mouse and rat brain.

To study the feedback control by histamine (HA) H3-receptors on the synthesis and release of HA at nerve endings in the brain, the effects of a potent and selective H3-agonist, (R)-alpha-methylhistamine, and an H3-antagonist, thioperamide, on the pargyline-induced accumulation of tele-methylhistamine (t-MH) in the brain of mice and rats were examined in vivo. (R)-alpha-Methylhistamine dihydrochloride (6.3 mg free base/kg, i.p.) and thioperamide (2 mg/kg, i.p.), respectively, significantly decreased and increased the steady-state t-MH level in the mouse brain, whereas these compounds produced no significant changes in the HA level. When administered to mice immediately after pargyline (65 mg/kg, i.p.), (R)-alpha-methylhistamine (3.2 mg/kg, i.p.) inhibited the pargyline-induced increase in the t-MH level almost completely during the first 2 h after treatment. Thioperamide (2 mg/kg, i.p.) enhanced the pargyline-induced t-MH accumulation by approximately 70% 1 and 2 h after treatment. Lower doses of (R)-alpha-methylhistamine (1.3 mg/kg) and thioperamide (1 mg/kg) induced significant changes in the pargyline-induced t-MH accumulation in the mouse brain. In the rat, (R)-alpha-methylhistamine (3.2 mg/kg, i.p.) and thioperamide (2 mg/kg, i.p.) also affected the pargyline-induced t-MH accumulation in eight brain regions and the effects were especially marked in the cerebral cortex and amygdala. These results indicate that these compounds have potent effects on HA turnover in vivo in the brain.

Amygdala↗

tele-Methylhistamine levels and histamine turnover in nuclei of the rat hypothalamus and amygdala.

An HPLC method using fluorescence detection for the determination of tele-methylhistamine (t-MH) was improved to a sensitivity level which enabled the detection of 0.05 pmol of tissue t-MH. The t-MH contents and the histamine turnover rates in various nuclei of the rat hypothalamus and amygdala were subsequently measured. The histamine turnover rates were estimated from pargyline-induced t-MH accumulation. Both the t-MH levels and the histamine turnover rates were shown to be relatively high in the nuclei dorsomedialis and premammillaris ventralis of the hypothalamus, and also in the nucleus medialis of the amygdala. The steady-state t-MH levels in various nuclei of the hypothalamus and amygdala correlated well with the histamine turnover rates in these nuclei.

Amygdala↗

Changes in polyamine concentrations in amygdaloid-kindled rats.

Concentrations of the polyamines putrescine, spermidine, and spermine were investigated in the left and right amygdala and in the remaining cerebrum, in which kindling was induced by repeated application of electrical stimulation of the left amygdala of rats. In kindled rats, the concentrations of spermidine and spermine increased slightly, but elevations did not reach significant levels in any brain regions. The most profound increase was detected in the putrescine concentration in all parts of the cerebrum 1-8 h after the final stimulation. These results suggest that the increases in concentrations of polyamines, particularly of putrescine, are involved in the pathogenesis of amygdaloid kindling.

Amygdala↗

Purification and properties of ferredoxin and rubredoxin from Butyribacterium methylotrophicum.

A ferredoxin and a rubredoxin from Butyribacterium methylotrophicum, which displays a carbonyl-dependent acetyl-coenzyme A synthesis, were purified to electrophoretic homogeneity. The two electron carriers showed absorption spectra similar to those in Clostridium species. The ferredoxin displayed absorption peaks at 280 and 391 nm, while rubredoxin displayed absorption peaks at 279, 382, and 482 nm. Minimum molecular weights calculated from the respective amino acid compositions were 5,727 for ferredoxin and 5,488 for rubredoxin, excluding iron and inorganic sulfur atoms. Both electron carriers were isolated as monomers, according to gel-filtration data. Electron spin resonance analysis revealed that the ferredoxin was a 2[4Fe-4S]-type and that both clusters had a midpoint redox potential value of -410 mV, whereas rubredoxin contained one acid-stable iron and had a redox value of -40 mV. The coupling of these electron carriers to hydrogenase and carbon monoxide dehydrogenase activities was investigated. Rubredoxin showed higher activity towards carbon monoxide dehydrogenase, whereas ferredoxin showed higher activity towards hydrogenase.

Aldehyde Oxidoreductases↗

Effect of MCI-186 on ischemia-induced changes in monoamine metabolism in rat brain.

We examined the effects of MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one), a novel free radical scavenger and an inhibitor of ischemia-induced brain edema, on monoamine metabolism in the brains of both normal and ischemic rats. In normal rats, 3 mg/kg i.v. MCI-186, a dose that prevents ischemic brain edema, had no significant effect on brain concentrations of dopamine, norepinephrine, 5-hydroxytryptamine, or their metabolites. After the injection of 5 microliters of 3% polyvinyl acetate into the left internal carotid artery, concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid markedly increased, but that of norepinephrine decreased, in the left telencephalon of embolized rats compared with control rats injected with vehicle; the concentration of 5-hydroxyindoleacetic acid also increased slightly. These effects were maximal 2 hours after embolization. The turnover rate of dopamine between 6 and 8 hours after embolization was significantly higher but that of norepinephrine was slightly lower than that in vehicle-treated rats. When rats were treated with 3 mg/kg i.v. MCI-186 immediately after the injection of polyvinyl acetate, the embolization-induced changes in monoamine metabolism were less marked. Our results suggest that MCI-186 attenuates ischemia-induced changes in brain monoamine metabolism, probably due to its free radical scavenging action, although it has no marked effect in normal rats.

3,4-Dihydroxyphenylacetic Acid↗

[Pharmacological effects of reiousan on experimental hepatic injuries and hepatic functions].

Pharmacological effects of Reiousan, a crude drug preparation consisting of bezoar and ginseng, on experimental hepatic injuries and hepatic functions were studied. After administration of Reiousan, carbon tetrachloride, d-galactosamine and alpha-naphthylisothiocyanate-induced experimental hepatic injuries in rats were inhibited. Facilitation of recovery from increased retention rate of sulfobromophthalein in hepatectomized rats, increase in hepatic blood flow, inhibition of superoxide anions, and decrease in blood ethanol concentration in rats administered ethanol were observed after application of Reiousan. Inhibitory effects of Reiousan on experimental hepatic injuries may result from the increase in hepatic blood flow and inhibition of superoxide anions.

1-Naphthylisothiocyanate↗

Effect of acute treatment of mice with L-histidine on the brain levels of amino acids.

The brain histidine level in mice dose-dependently increased 1 and 2 hr after an i.p. injection of 0.5-1.5 g/kg of L-histidine. The treatment with 1.0 and 1.5 g/kg but not 0.5 g/kg of L-histidine significantly decreased the brain levels of tyrosine, phenylalanine and some other amino acids 1 hr later. A complete recovery or a rebound rise of amino acid levels was observed 2 hr after treatment. These results indicate that there is a change in the transport of amino acids into the brain after treatment with large doses of L-histidine.

Amino Acids↗

Effects of nociceptive stimuli on brain histamine dynamics.

The effects of nociceptive stimuli on the metabolism of brain histamine (HA) were examined, because of a previous observation that the exposure of mice to electric foot shock increased the brain HA turnover. In mice, the exposure to tail pinch markedly increased the brain level of tele-methylhistamine (t-MH), a predominant metabolite of brain HA, while the level of HA was not changed. The HA turnover, measured either by the accumulation of t-MH after pargyline injection or by the HA depletion after the treatment with alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase, was enhanced by the exposure to tail pinch, like the enhancement produced by the exposure to foot shock. The exposure of rats to tail pinch increased the t-MH level in the telencephalon and the midbrain. Other types of noxious stimuli, such as placing mice on a hot plate or subjecting mice to acetic acid-induced writhing, also significantly elevated the level of t-MH but not that of HA in the mouse brain. These results suggest that nociceptive stimuli produce an increase in the brain HA turnover.

Animals↗

Effects of isofloxythepin on central and peripheral histamine systems.

The effects of isofloxythepin, a dibenzo[b,f]thiepin derivative, on the central and peripheral histamine systems were compared with those of chlorpromazine and haloperidol. The three drugs examined all inhibited both the histamine-induced contraction of guinea pig ileum and the specific [3H]mepyramine binding to guinea pig brain membranes in a dose-dependent manner. The effectiveness in inhibiting these reactions was in the order of: chlorpromazine greater than isofloxythepin greater than haloperidol. The histamine-induced relaxation of rat uterus, which is mediated by H2-receptors, was not affected by isofloxythepin. The effect of isofloxythepin on the pargyline-induced accumulation of tele-methylhistamine in the mouse brain was indicative of a decrease in histamine turnover, whereas chlorpromazine and haloperidol were devoid of such effects. Isofloxythepin inhibited both the lethal effect of histamine injected i.v. in mice and histamine-induced edema in rat hind paws far more strongly than chlorpromazine or haloperidol did. These results show that isofloxythepin is a neuroleptic with H1-antagonist properties, which are intermediate in potency between those of chlorpromazine and haloperidol, and also it may have an inhibitory action on histamine turnover in the brain. Protection against the lethal effect of histamine and the inhibition of histamine edema by isofloxythepin may largely be due to mechanisms other than the blocking of H1-receptors.

Animals↗