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Biomedical subjects

K Ogino

Publications and source records attributed to K Ogino.

At least 19 recordsLinked to original sources

Role of Kupffer cells in rat liver injury induced by diethyldithiocarbamate.

The hepatotoxicity of diethyldithiocarbamate was examined using an in vitro rat liver slice system. Concentration- and time-dependent losses of intracellular K+ and adenosine triphosphate (ATP) levels were observed in rat liver slices incubated with diethyldithiocarbamate at concentrations between 1 and 10 mM over a 4-h period. Histological study revealed perivenous hepatocyte damage. To examine the involvement of Kupffer cells in diethyldithiocarbamate-induced cytotoxicity, rats were injected intravenously with 10 mg/kg of gadolinium chloride (GdCl3) which diminishes Kupffer cell function. Incubation of liver slice preparations from the GdCl3-treated rats with diethyldithiocarbamate showed marked inhibition of the cytotoxicity induced by diethyldithiocarbamate. Moreover, in vitro addition of manganese-superoxide dismutase, a superoxide anion scavenger, or dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, also showed potent inhibition. However, dexamethasone, an inhibitor of tumor necrosis factor, and N,N'-diphenyl-p-phenylenediamine (DPPD), an antioxidant, showed partial prevention of cytotoxicity. Formazan deposits formed as a result of nitro blue tetrazolium reduction were found in Kupffer cells at an early stage after diethyldithiocarbamate treatment, while lipid peroxidation occurred after 3 h. Both pretreatment with GdCl3 in vivo and addition of DMSO in vitro prevented the increase in lipid peroxidation within the liver slice preparations induced by diethyldithiocarbamate. These findings suggest that Kupffer cell function may be involved in the pathogenesis of diethyldithiocarbamate hepatotoxicity.

Adenosine Triphosphate

The determination of nitrite and nitrate in human blood plasma by capillary zone electrophoresis.

The determination of nitrite and nitrate in human blood plasma by capillary zone electrophoresis (CZE) is described. Electrophoresis was carried out in a 65 cm long, 75 microns wide silica capillary, using 750 mM sodium chloride containing 5% NICE-Pak OFM Anion-BT (an additive reversing the electroosmotic flow) as running buffer, at a potential of 20 kV, with on-column UV detection at 214 nm. Under these conditions, the two anions migrated in the order of nitrite and nitrate, completely resolved from each other. Forty-one samples of ultrafiltered blood plasma of healthy volunteers were analyzed. The concentrations of nitrite and nitrate were 0.15 +/- 0.07 mg/L and 3.2 +/- 1.6 mg/L (mean +/- SD), respectively, with a linear correlation in the range of 0.1-50 mg/L. The within-day and between-day coefficients of variation (CVs) for nitrite and nitrate were lower than 5% and 8%, respectively. The recovery was 97-114%. The estimated plasma volume needed for each determination was 108 nL.

Electrophoresis, Capillary

Nicorandil suppressed myocardial purine metabolism during exercise in patients with angina pectoris.

To elucidate the effect of Nicorandil on myocardial energy metabolism and myocardial sympathetic activity, we administered Nicorandil orally to eight patients with angina pectoris prior to exercise testing. Arterial and coronary sinus levels of lactate, ammonia, hypoxanthine (HX), adrenaline and noradrenaline were measured during exercise in order to determine the irrespective myocardial extraction ratios (MER). Compared to placebo, Nicorandil increased the time to development of significant ST depression (322 vs 390 s) while decreasing the maximum amplitude of ST depression (0.244 vs 0.216 mV). Heart rate, systolic blood pressure, and the rate pressure product during exercise were not significantly affected. The MER of lactate, measured during exercise, was significantly higher after Nicorandil than placebo (13.6 vs 27.9). Similarly, the MERs of ammonia and HX were significantly higher after Nicorandil (-46.0 vs 7.4% and -47.0 vs 9.9% respectively). Nicorandil, had no apparent effect on myocardial sympathetic activity as the MERs of adrenaline and noradrenaline were essentially unaffected. We conclude that Nicorandil decreased myocardial ischaemia and suppressed myocardial accelerated purine metabolism (a marker of cellular energy metabolism) during exercise in patients with angina pectoris. This effect appears not to be related to myocardial sympathetic activity.

Administration, Oral

An approach for an immunoaffinity AIDS sensor using the conservative region of the HIV envelope protein (gp41) and its monoclonal antibody.

A monoclonal antibody for the conservative region of gp41, which is one of the HIV envelope proteins, was produced. The antigen determining site of gp41 was examined using the epitope mapping technique, followed by an enzyme linked immunosorbent assay. Some peptides had comparable affinities for the monoclonal antibody, but the peptide EGIEE, having a slightly weaker immunoaffinity than gp41, was the most preferable for the construction of an immunoaffinity AIDS sensor. For the detection of gp41, EGIEE was labelled with catalase and used as a mimic antigen; it was bound to the antibody present on an immuno-membrane and, due to the replacement reaction of the mimic antigen by gp41, indirect quantitative measurement of gp41 was possible using an oxygen electrode. Anti-gp41 antibody was also detected using a mimic antibody, which was chemically modified with polyethylene glycol. An immunoaffinity AIDS sensor was constructed using the mimic molecules which were tailored to have a suitable immunoaffinity for HIV antigen and/or antibody.

Acquired Immunodeficiency Syndrome

Effects of zinc on production of active oxygen species by rat neutrophils.

The effects of zinc on the production of active oxygen species were investigated in rat neutrophils by chemiluminescence and spectrophotometric assays. The luminol-dependent chemiluminescence in unstimulated neutrophils showed a single peak. Zinc at concentrations lower than 0.1 mM augmented the intensity of chemiluminescence and showed a bimodal pattern, the first peak of which was inhibited by superoxide dismutase and catalase, while the second peak disappeared in the presence of catalase, but was unaffected by superoxide dismutase. At the same concentrations of zinc, O2- and H2O2 production increased, but secretion and activity of myeloperoxidase were not affected. Zinc at 0.1 mM enhanced the second peak of luminol-dependent chemiluminescence, and concomitantly O2- and H2O2 production of neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine. Homogenized neutrophils showed a bimodal pattern on induction by zinc, the second peak of which was inhibited slightly by catalase and completely by sodium azide, but was not inhibited by superoxide dismutase. Zinc-induced O2- production was inhibited by pertussis toxin, but was not significantly inhibited by a protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), or a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). These results suggest that zinc can augment luminol-dependent chemiluminescence by increasing O2- production through the classical signal transduction pathway, and by increasing H2O2 not via O2-.

Animals

The hemodynamic basis for the cardiac effects of parathyroid hormone (PTH) and PTH-related protein.

PTH and PTH-related protein (PTHrP) have been regarded to have positive inotropic effects on the heart as well as positive chronotropic and vasodilator effects. However, inotropy due to a direct effect of these peptides has not heretofore been distinguished from an indirect inotropic effect as a result of altered heart rate or coronary flow. The aim of this study was to determine whether PTH and PTHrP have direct inotropic effects in isolated perfused rat hearts. Three groups of hearts were studied; in all groups, hearts contracted isovolumically and were perfused with a constant coronary pressure. In the control group, heart rate, coronary flow, peak pressure (LVPmax), peak rate of rise of LV pressure (dP/dtmax), and peak intracellular calcium (measured by aequorin) all increased with PTH and PTHrP in a dose-dependent manner. When heart rate was fixed by pacing in a second group of rats, PTH and PTHrP increased coronary flow, LVPmax, and dP/dtmax significantly, indicating that inotropic actions were not mediated solely by chronotropic effects. However, when heart rate was fixed by pacing and, additionally, coronary flow was held constant (by maximal prevasodilation with nitroprusside) in a third group of rats, there was no significant effect of either PTH or PTHrP on LVPmax, dP/dtmax, or peak intracellular calcium. To demonstrate the responsiveness of this latter preparation to inotropic stimulation, the beta-adrenergic agonist, isoproterenol, increased LVPmax, dP/dtmax, and peak calcium even when heart rate was fixed and vasodilation was maximal. Thus, PTH and PTHrP are inotropic agents by virtue of their influence on coronary flow and heart rate, but not by any direct effect on contractile elements in the heart.

Animals

Changes of QRS axis in transient myocardial ischaemia induced by percutaneous transluminal coronary angioplasty.

The QRS axis of 130 consecutive patients with coronary artery disease undergoing percutaneous transluminal coronary angioplasty (PTCA) were measured before balloon inflation and just before balloon deflation. Patients were divided into two groups. Group A (103) had angina pectoris and/or non-transmural old myocardial infarction with no abnormal Q waves; group B (27) had an old transmural myocardial infarction with abnormal Q waves. In group A, the QRS axis had significantly shifted to the left in patients with left anterior descending artery (LAD) occlusion (from 68.0 +/- 42.7 degrees to 40.2 +/- 44.6 degrees, P < 0.001); however in those patients without involvement of the major septal branch, significant axis changes were not observed (from 53.6 +/- 34.1 degrees to 49.8 +/- 33.1 degrees). When the right coronary artery (RCA) was occluded in group A, the QRS axis shifted to the right significantly (from 63.2 +/- 40.0 degrees to 89.8 +/- 30.1 degrees. P < 0.01); during left circumflex artery (LCX) occlusion, no significant axis shift was observed. In group B, no significant axis shift was observed either in patients with occlusion of the LAD or the RCA. It is concluded that transient left axis deviation reflects an obstructive lesion of the proximal portion of the LAD with involvement of the major septal branch, and transient right axis deviation reflects an obstructive lesion of the RCA.

Angioplasty, Balloon, Coronary

Acute hemodynamic effects of bunazosin in congestive heart failure--differing responses according to degree of cardiac dysfunction.

1. Hemodynamic responses to Bunazosin (BZN) in congestive heart failure (CHF) were evaluated for 6 hours (hr) in 30 patients (A, normal cardiac function; B, mild cardiac dysfunction; C, severe cardiac dysfunction). 2. For 6 hr after BZN, the increments of cardiac index (delta CI) and stroke volume index (delta SVI) with BZN were higher in groups A and B than in group C. 3. A significant positive correlation was observed between ejection fraction and maximum delta CI and SVI, and between % fractional shortening and maximum delta CI and SVI. 4. These data showed that BZN improved the hemodynamics of CHF patients and that patients in groups A and B responded well to this vasodilator, however, patients in group C did not.

Adrenergic alpha-Antagonists

Zinc hydroxide stimulates superoxide production by rat alveolar macrophages.

The effect of zinc hydroxide on superoxide (O2-) production by rat alveolar macrophages was determined by chemiluminescence and by cytochrome c reduction. Zinc ions had no effect on the chemiluminescence of unstimulated alveolar macrophages. By contrast, zinc hydroxide (ZnOH2), a neutralized form of zinc ions, increased the chemiluminescence level and O2- release. Increased O2- release was inhibited by pertussis toxin, isoquinoline sulfonamide and pretreatment with EGTA. These findings indicate that zinc hydroxide formation from zinc compounds can stimulate the O2- production by alveolar macrophages by receptor-mediated and Ca(2+)-dependent process.

Animals

Antiulcer mechanism of action of rebamipide, a novel antiulcer compound, on diethyldithiocarbamate-induced antral gastric ulcers in rats.

The mechanism of the inhibitory action of rebamipide, a new mucosal protective drug, was studied using rats with diethyldithiocarbamate-induced gastric antral ulcers. Rebamipide reduced ulcer formation and inhibited the elevation in lipid peroxide concentration in the gastric mucosa. Rebamipide inhibited both luminol- and lucigenin-dependent chemiluminescence of neutrophils activated by formyl-methionyl-leucyl-phenylalanine. Rebamipide did not alter the reduction of cytochrome c induced by the xanthine-xanthine oxidase system or the NADPH-dependent microsomal lipid peroxidation in the liver. These findings suggest that rebamipide prevents diethyldithiocarbamate-induced gastric ulcer formation by inhibiting neutrophil activation.

Alanine

Suppression of sympathetic nervous system activity by nicorandil during exercise.

1. Treadmill testing was done and plasma epinephrine and norepinephrine were measured during exercise and recovery in 21 patients with coronary artery disease given nicorandil. 2. Epinephrine levels during exercise did not change significantly with nicorandil, but the percent change in epinephrine with nicorandil tended to be lower during exercise. 3. Norepinephrine levels after exercise were suppressed with nicorandil (with, 424 +/- 15 pg/ml; without, 760 +/- 16, P less than 0.05). 4. Also, the percent change in norepinephrine with nicorandil was significantly decreased during exercise and recovery (with, 259 +/- 11%; without, 555 +/- 19, P less than 0.01). 5. Therefore, nicorandil suppressed the sympathetic nervous system hyper-response to exercise.

Adult

Effect of alacepril on blood pressure and neurohumoral factors at rest and during dynamic exercise in patients with essential hypertension.

We assessed blood pressure and neurohumoral factors at rest and during exercise in 10 patients with essential hypertension before and after treatment with the new angiotensin converting enzyme inhibitor, alacepril (25-50 mg day-1). Alacepril significantly lowered mean blood pressure at rest and at the same exercise load as before treatment without affecting heart rate response. The response of plasma renin activity, plasma aldosterone, and plasma adrenaline were not changed by alacepril, but increase of plasma angiotensin II and plasma noradrenaline during exercise were significantly attenuated after alacepril treatment (ANOVA, P = 0.04, both). The change in mean blood pressure during exercise was positively correlated with the decrease in plasma angiotensin II (r = 0.65, P < 0.05). These results demonstrated that alacepril was effective in essential hypertension both at rest and during exercise, suggesting that the antihypertensive effect during exercise might be related to the decrease in pressor hormones, especially in plasma angiotensin II.

Adult

Plasma catecholamine responses to dynamic exercise in patients with coronary artery disease--the relationship between sympathetic activity and systolic blood pressure and exercise-induced ventricular arrhythmias.

In order to investigate the relationship between sympathetic activity and postexercise systolic blood pressure (SBP) and exercise-induced ventricular arrhythmias in patients with coronary artery disease (CAD), we studied 38 patients and 9 normal subjects who underwent treadmill testing. Peak pressure-rate product was similar in the 2 groups. The plasma concentrations of norepinephrine and epinephrine at rest and immediately after exercise were significantly higher in patients with CAD compared with normal subjects (norepinephrine at rest, p < 0.01; norepinephrine immediately after exercise, p < 0.05; epinephrine at rest, p < 0.05; epinephrine immediately after exercise, p < 0.05). The level of norepinephrine immediately after exercise was significantly higher in 15 patients with a postexercise SBP increase than in 23 patients without that SBP change (p < 0.05), whereas the level of epinephrine was similar in the 2 groups. The level of epinephrine immediately after exercise was significantly higher in 10 patients with exercise-induced premature ventricular contractions than in 28 patients without those arrhythmias (p < 0.05), whereas the level of norepinephrine was similar in the 2 groups. We conclude that a postexercise SBP increase is related to the augmentation of sympathoneural activity and that exercise-induced ventricular arrhythmias are related to the augmentation of sympathoadrenal activity.

Arrhythmias, Cardiac

Serum levels of lipids and apolipoproteins in angiographically assessed coronary artery disease in Japanese patients.

Serum total cholesterol (T-CHO), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and apolipoproteins (apo A-I, A-II, B, C-II, C-III and E) values were determined in 143 Japanese subjects undergoing coronary angiography. Among the factors measured, T-CHO, TG, apo B and C-III levels were significantly higher in patients with coronary artery disease (CAD) than in those without CAD. The HDL-C/T-CHO ratio was also significantly lower in patients with CAD. Although no parameters show differences between the group without CAD and the group of single vessel disease, T-CHO and apo B were significantly higher in the groups with double and triple vessel disease, and TG and apo C-III were also higher in the group with triple vessel disease compared with the normal group. Furthermore, the HDL-C/T-CHO ratio was significantly lower in the double and triple vessel groups, and HDL-C was lower only in the triple vessel group. The results indicate that changes in these parameters suggest a high likelihood of multiple vessel disease, and that an increase in TG and apo C-III levels is also one of the important indicators for CAD even in Japanese patients.

Aged

[Cardiac and plasma catecholamine response to dynamic exercise in hyperthyroidism].

To investigate cardiac and sympathoadrenal responses to dynamic exercise, heart rate, systolic blood pressure, serial plasma norepinephrine (NE) and epinephrine (E) concentrations during multistage treadmill exercise were measured in 24 hyperthyroid patients (mean age; 42 +/- 16) and 24 age-sex matched control subjects. Eleven patients were re-examined in the euthyroid state after antithyroid therapy. Exercise duration was shorter in patient with hyperthyroidism. Also, the heart rates and systolic blood pressures at rest and in the early stage of exercise were significantly higher in hyperthyroidism. NE at rest (normal vs hyperthyroid: 124 +/- 10 vs 80 +/- 7 pg/ml, p < 0.01) and NE at peak exercise (475 +/- 38 vs 310 +/- 38 pg/ml, p < 0.01) were lower in hyperthyroidism. E at rest (22 +/- 2 vs 29 +/- 4 pg/ml, n.s.) did not differ, however, E during the first stage of exercise (30 +/- 3 vs 69 +/- 12 pg/ml, p < 0.01) was higher in hyperthyroidism. Re-examination for the euthyroid state revealed the decreases in the heart rates and systolic blood pressures at rest and in the early stage of exercise, and the normalization of the NE and E response. Thus, patients with hyperthyroidism was in the hyperdynamic cardiac state at rest and during dynamic exercise, which was accounted for by decreased sympathetic nervous activity and increased adrenomedullary responses. These modifications of sympathoadrenal response seemed reversible when patients were controlled by antithyroid therapy.

Adolescent

The longest 18S ribosomal RNA ever known. Nucleotide sequence and presumed secondary structure of the 18S rRNA of the pea aphid, Acyrthosiphon pisum.

An EMBL4 recombinant phage which encodes one of the full length of the aphid ribosomal DNA has been isolated from the aphid genomic library. Determination of the complete nucleotide sequence of the aphid 18S rRNA gene revealed that it is 2469 bp with a G + C content of 59%. The aphid 18S rRNA gene studied here is the longest and has the highest G + C content among the 18S rRNA genes examined so far. Evidence provided by the S1 nuclease assay suggests that the aphid 18S rRNA gene examined in this study is not a pseudogene containing an insertion sequence. Based on the nucleotide sequence of the 18S rRNA gene, we constructed a presumed secondary-structure model of the aphid 18S rRNA. In the aphid 18S rRNA, the eucaryote-specific E21 and 41 region are supposed to be longer and more complex than the counterparts of other 18S rRNA.

Animals