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Biomedical subjects

K Ogino

Publications and source records attributed to K Ogino.

At least 109 records · Page 6Linked to original sources

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↗

Proliferation of hepatocytes and attenuation from carbon tetrachloride hepatotoxicity by gadolinium chloride in rats.

Intravenous injection of gadolinium chloride (GdCl3) at a dose of 10 mg/kg caused an increase in proliferating cell nuclear antigen labeling index and the grade of pyronin positivity (RNA level) in rat liver. In CCl4-exposed rats, pretreatment with GdCl3 also showed a preventive effect of the liver injury both biochemically and histologically. Moreover, the proliferative action preceded the attenuative effect of the liver injury. Results suggest that GdCl3 induces hepatocyte proliferation, and this action of GdCl3 may modify the development of CCl4-induced liver injury.

Alanine Transaminase↗

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 in lipid peroxide and antioxidant enzyme activities in corpora lutea during pseudopregnancy in rats.

This study investigated the involvement of lipid peroxidation and antioxidant enzymes in the regulation of luteal function in pseudopregnant rats. The activities of superoxide dismutase (SOD), a specific scavenger of superoxide radicals, and glutathione peroxidase, a scavenger of hydrogen peroxide, and lipid peroxide concentrations were measured in the corpus luteum on days 1, 3, 5, 7, 9, 11 and 13 of pseudopregnancy. The activity of SOD in the corpus luteum gradually increased until day 9 of pseudopregnancy and decreased thereafter, in a similar manner to serum progesterone concentration. Glutathione peroxidase activity significantly increased from day 1 to day 3 and remained high until day 11 of pseudopregnancy. The concentrations of lipid peroxides in the corpus luteum increased from day 3 to day 13 of pseudopregnancy. The involvement of prostaglandin F2 alpha (PGF2 alpha) in the production of lipid peroxides in regression of the corpus luteum was investigated by administering PGF2 alpha (3 mg kg-1, s.c.) or saline on days 7, 9 and 12 of pseudopregnancy. Each group of rats was autopsied 2 h later, and SOD activity, glutathione peroxidase activity and the concentration of lipid peroxides in the corpus luteum were determined. PGF2 alpha significantly increased lipid peroxide concentrations in the corpus luteum on days 7, 9 and 12 of pseudopregnancy (approximately twofold increases on days 7 and 9, and a fivefold increase on day 12, compared with the control that received saline). The activity of SOD in the corpus luteum was significantly increased by PGF2 alpha on days 7 and 9, but not on day 12, of pseudopregnancy. PGF2 alpha did not cause any significant changes in glutathione peroxidase activity in the corpus luteum on days 7, 9 and 12 of pseudopregnancy. It is concluded that lipid peroxides play an important role in regulating luteal function in pseudopregnant rats.

Animals↗

Structure and action of MIP (Mytilus inhibitory peptide)-related tetrapeptides synthesized with a multipeptide synthesizer.

Using a multipeptide synthesizer we synthesized 19 peptide libraries, each of which consisted of 19 MIP-related tetrapeptides, and isolated a number of peptides, which have an inhibitory effect on phasic contraction of the ABRM of Mytilus, from the libraries. To the present, the structures of about 30 species of the peptides were determined, and the peptides with the determined structures were synthesized. The structure and action of each synthetic peptide was compared with those of others to explain structure-activity relationship of MIPs.

Amino Acid Sequence↗

Identification of EGF as an angiogenic factor present in conditioned medium from human salivary gland adenocarcinoma cell clones with varying degrees of metastatic potential.

We have previously shown that conditioned medium (CM) from metastasizing human salivary gland adenocarcinoma cell clones contains factor(s) that stimulate the proliferation and migration of bovine aortic endothelial (BAE) cells, and inhibit the production of collagenases by BAE cells (Azuma M. et al. (1993) Cancer Lett., 73, 85-93). To further characterize this, we evaluated the expression level of epidermal growth factor (EGF) secreted by a non-metastasizing cell clone (HSGc) and its metastasizing cell clones, and analysed the effect of EGF on the biologic behaviors of BAE cells. When the secretion of EGF by cell clones was estimated by enzyme-linked immunosorbent assay, metastasizing cell clones released a large amount of EGF as compared with HSGc. However, the number of EGF receptor was detected consistently at a level that was similar in all cell clones. With regard to the effect of EGF on the malignant potential of cell clones such as proteolytic aggressiveness, EGF did not affect the secretion of both collagenases and their inhibitor from cell clones. Alternatively, exogenous EGF stimulated the proliferation and migration of BAE cells, and inhibited the secretion of collagenases from BAE cells. Neutralization with a neutralizing antibody of EGF released into CM abolished the inhibitory effect of CM on the secretion of collagenases from BAE cells. Thus, the CM-contained factor, which is responsible for the induction of biologic behaviors of BAE cells, can be attributed to EGF.

Adenocarcinoma↗

Zinc hydroxide induced respiratory burst in rat neutrophils.

The effects of zinc hydroxide on the respiratory burst and phagocytosis by rat neutrophils were examined. Zinc hydroxide induced an increase in oxygen consumption and O2- production. Electronmicroscopy showed that neutrophils engulfed zinc hydroxide particles by phagocytosis. Pertussis toxin (0.25, 0.5, 1.0 micrograms/ml) and EGTA (1, 2, 5 mM) inhibited zinc hydroxide-induced O2- production in a dose-dependent manner. The inhibitors of protein kinase C, 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide inhibited zinc hydroxide-induced O2- production with IC50 values ranging between 10 microM and 25 microM. The inhibitory study using an inhibitor of myosin light chain kinase, 1-(5-iodo-naphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine, showed IC50 values ranging from 5 microM to 10 microM. These findings indicate that zinc hydroxide induces respiratory burst and phagocytosis by rat neutrophils.

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↗

Perfusion reserve of coronary collateral circulation and its significance in the development of exercise-induced ischemia in patients with multivessel disease.

To assess the perfusion reserve of coronary collateral circulation, we analyzed exercise-stress tomographic thallium-201 myocardial images in 12 patients who had total occlusion in the right coronary artery (RCA) or left circumflex coronary artery (LCX) with well-developed collateral circulation and 90% stenosis in the left anterior descending coronary artery (LAD). In 6 of the 12 patients, the collateral circulation was non-jeopardized (group A). In the remaining 6 patients, the collateral circulation was jeopardized (group B). All 6 of the patients in group A had an exercise-induced decrease in thallium uptake in the segments supplied by the occluded RCA or LCX with collateral circulation, and 3 (50%) of these 6 also showed a decrease in thallium uptake in the segments supplied by the LAD. All 6 of the patients in group B also had an exercise-induced decrease in thallium uptake in the segments supplied by the occluded RCA or LCX with collateral circulation, but none showed a decrease in thallium uptake in the segments supplied by the LAD. In conclusion, the perfusion reserve of collateral circulation is equal to or less than 90% stenosis and myocardial ischemia occurs first in the collateralized segments during exercise in patients with jeopardized collateral circulation.

Adult↗

[Response to a questionnaire on DNR-order from 307 trustee members of Japanese Medical Societies].

A questionnaire on the use of DNR-order was conducted on 427 trustee members of Japan Society of Reanimatology, Intensive Care Medicine and Anesthesiology with responses from 307 or 71.9%. The results of the questionnaire are as follows: DNR-order is unnecessary, 2.9%. Necessary depending on the situation, 96.7%. Here dying in dignity was the main reason for necessity of DNR-order and ethical, legal and technical problems were the reasons cited for objection. Patients' will is indispensable for DNR-order, 11.4%. Patients' will is not indispensable, 84.9%. Quality and quantity of treatment after the decision of DNR-order should not be limited or withdrawn, 21.2%. Should be withdrawn except for respirator, 60.6%. The percentage of those who had carried out a DNR-order was 69.1% (most of them more than once), but half of them did not describe the order on the chart. A guideline for a DNR-order by scientific societies and/or governmental policy for a DNR-order should be made and publicized not only for the benefit of the patients and their families but also for physicians themselves.

Adult↗

Effects of media conditioned by a non-metastasizing human salivary gland adenocarcinoma cell clone and metastasizing clones from salivary gland and various other tissues on the proliferation, migration and protease production of bovine aortic endothelial cells in vitro.

We demonstrate the role in tumor-associated angiogenesis of factors released into conditioned medium (CM) from in vitro human salivary gland cell clones with biological phenotypes ranging from non-metastasizing to metastasizing. A non-metastasizing human salivary gland adenocarcinoma cell clone HSGc and its subclone with metastatic potential (Gc2-100 cl-1) were employed. We also used metastasizing cell clones obtained by explant cultures of organs of Gc2-100 cl-1 tumor-bearing nude mouse. The proliferation and migration of bovine aortic endothelial (BAE) cells were significantly stimulated by the addition of CM obtained from Gc2-100 cl-1 and metastasizing cell clones, while CM from HSGc was ineffective. When the effect on protease secretion by BAE cells was examined, CM from Gc2-100 cl-1 and metastasizing cell clones inhibited the secretion of type IV collagenases by BAE cells much more than did CM from HSGc. These findings, therefore, may imply that Gc2-100 cl-1 and metastasizing cell clones secrete angiogenic factors that stimulate not only the proliferation and migration of endothelial cells but also the formation of basement membrane components necessary for the reconstruction of new blood vessels at migrated sites of endothelial cells by preventing the degradation of basement membrane component, type IV collagen.

Adenocarcinoma↗

Role of plasminogen activators, metalloproteinases and the tissue inhibitor of metalloproteinase-1 in the metastatic process of human salivary-gland adenocarcinoma cells.

An in vitro system has been established in which conversion from non-metastasizing to metastasizing adenocarcinoma cells can be induced, and subsequently subjected to analysis of the expression of proteases and tissue inhibitor of metalloproteinases-1 (TIMP-1). A human salivary-gland adenocarcinoma cell clone HSGc, with no metastatic ability, was exposed to N-methyl-N-nitrosourea (MNU). Following exposure to MNU, cells with altered morphology were cloned. Upon s.c. inoculation into nude mice, MNU-treated HSGc clones formed metastatic foci in various organs, and then 5 metastasizing clones were isolated. Evaluation of expression of tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), metalloproteinases and TIMP-1 was performed by means of enzyme immunoassay, zymogram, or immunoblot. MNU-treated HSGc and metastasizing clones were found to secrete high levels of tPA, while HSGc produced undetectable levels of this enzyme. Expression of uPA was not observed in any of the cell clones. When the secretion of gelatinolytic enzymes was examined, metastasizing clones produced higher levels of 57- and 32-kDa, but not of 92- or 72-kDa gelatinases, as compared to HSGc cells. Although TIMP-1 was detected in all cell clones, metastasizing clones secreted less TIMP-1 than HSGc cells; in addition, one metastasizing clone produced TIMP-1 with a molecular weight distinct from that of 28-kDa TIMP-1. Our results suggest that the acquisition of metastatic ability by human salivary-gland tumor cells is closely associated with increased secretion of several metalloproteinases as well as decreased or altered TIMP-1 expression.

Adenocarcinoma↗

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↗

Renal hypouricemia with both drug-insensitive secretion and defective reabsorption of urate: a novel type of renal hypouricemia.

Renal handling of urate in the hypouricemic patient with increase in both urate clearance (Cur) and Cur/creatinine clearance (Ccr) and normal urinary excretion of urate was studied according to the pharmacological evaluation. In the present case there was no response of urate excretion to either pyrazinamide or probenecid. Both furosemide and prednisolone could not alter Cur and Cur/Ccr. Administration of inosine could have increased Cur, which was greater than Ccr. These results suggest that the present case had the defect of both pre- and postsecretory reabsorption of urate, accompanied by the existence of drug-insensitive secretion of urate, which is different from hitherto known types of renal hypouricemia, i.e. a novel type of renal hypouricemia.

Adult↗

Effects of volume and pressure overloads and myocardial hypertrophy on exercise-induced changes in electrocardiographic QRS amplitude.

To investigate the effects of volume and pressure overloads and myocardial hypertrophy on exercise-induced changes in QRS amplitude, we reviewed treadmill exercise electrocardiograms. In 10 normal young men, Rv5 amplitude decreased and Sv1 amplitude increased at peak exercise, and returned to the resting value in the recovery period. In 10 patients with aortic regurgitation, Rv5 and Sv1 amplitudes increased after 5 min of recovery. In 12 patients with essential hypertension and 10 with idiopathic hypertrophic non-obstructive cardiomyopathy, Rv5 amplitude remained unchanged or higher at peak exercise compared with the resting value, but patterns of serial changes were similar to that of normal subjects. In 9 patients with atrial septal defect, R'v1 amplitude increased with exercise, whereas it remained unchanged in 12 with isolated complete right bundle branch block. In 5 patients with mitral stenosis, Sv1 amplitude decreased at peak exercise. In conclusion, changes in QRS amplitude with exercise are influenced by hemodynamic abnormality and myocardial hypertrophy, and a major determinant of these serial changes seems to be the change in ventricular volume.

Adult↗