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Biomedical subjects

M Kohno

Publications and source records attributed to M Kohno.

At least 433 records · Page 24Linked to original sources

Inactivation of peroxidases of rat bone marrow by repeated administration of propylthiouracil is accompanied by a change in the heme structure.

Myeloperoxidase and eosinophil peroxidase were isolated from the bone marrow cells of rats treated with or without propylthiouracil (PTU) which caused bone marrow depression. PTU treatment decreased the activity of myeloperoxidase but not of eosinophil peroxidase using guaiacol as the electron donor. However, when KI,N-N'-dimethyl-p-phenylenediamine and pyrogallol were used as the electron donor, the activity of only eosinophil peroxidase was inhibited by PTU treatment. EPR spectra indicated that the structure of myeloperoxidase surrounding the heme iron changed from a rhombic form into an axial one by the repeated administration of PTU. Therefore, the inactivation of peroxidases by PTU treatment was accompanied by an alteration of their structures surrounding the heme.

Animals↗

An immunohistochemical study on "neoplastic angioendotheliosis": demonstration of B lymphocyte markers in the neoplastic cells.

Frozen cerebral and renal tissue sections of an autopsied "neoplastic angioendotheliosis (NAE)" case were investigated immunohistochemically using monoclonal and heterologous antibodies to lymphocyte, monocyte, endothelial, epithelial and histiocytic antigens. In both tissues, positive stainings for surface immunoglobulin (sIg) mu and chi, but not lambda, were observed in most of the neoplastic cells. These cells were also positive for other B cell markers (BA-1, Leu-12 and HLA-DR). No distinct staining was observed in the neoplastic cells with antibodies to T lymphocyte (OKT-11 and Leu-1) or monocyte (OKM-1) markers. Positive stainings were observed only in some small round lymphoid cells which were distributed sporadically in and around blood vessels and were considered to be reactive. No positive staining was observed in the neoplastic cells with antibodies to endothelial (factor VIII), epithelial (cytokeratin) or histiocytic (lysozyme) antigens. Thus, our NAE case was shown to be of monoclonal B cell lymphoma in nature.

Antigens, Surface↗

Influence of exercise on plasma atrial natriuretic factor levels in patients with myocardial infarction.

The influence of dynamic exercise on plasma atrial natriuretic factor (ANF) levels was studied in a group of 10 patients with myocardial infarction (MI) and five patients with atypical chest pain (control group). Exercise protocol consisted of three fixed workloads (25, 50, and 75 watts) every 4 minutes with the use of a supine bicycle ergometer. Plasma ANF levels and hemodynamic indices were measured before, during, and 10 minutes after exercise. In the MI group, plasma ANF levels significantly increased at the 75-watt workload and significantly decreased at 10 minutes after exercise, whereas in the control group, the increase in plasma ANP levels after a 75-watt workload, compared with those at rest, was not significant. Significant correlations of pulmonary artery wedge pressure, right atrial pressure, mean arterial pressure, and heart rate to plasma ANF levels were observed at four points obtained before and during each stage of exercise in the MI group. Furthermore, a significant correlation between maximal creatine kinase levels and plasma ANF levels at a 75-watt workload and a significant inverse correlation between left ventricular ejection fraction and plasma ANF levels at a 75-watt workload were observed. These results suggest that the increase in the circulating ANF level during exercise in MI is associated with elevated atrial pressure resulting from left ventricular dysfunction and that measurement of ANF during exercise may be an indication of the severity of MI and associated left ventricular dysfunction.

Adult↗

Effect of long-term treatment with diltiazem on atrial natriuretic peptides in spontaneously hypertensive rats.

The present study was designed to examine the possible effect of long-term treatment with diltiazem on plasma and atrial concentrations of atrial natriuretic peptides (ANP) in spontaneously hypertensive rats (SHR). Diltiazem treatment reduced blood pressure and ventricular weight in SHR. Plasma ANP concentration in untreated SHR was higher than Wistar-Kyoto rats (WKY). Diltiazem treatment decreased plasma ANP concentration in SHR near to the level of WKY; moreover, plasma ANP concentration was correlated with blood pressure and ventricular weight in treated and untreated SHR. Left atrial ANP concentration in untreated SHR was lower than WKY. Diltiazem treatment increased left atrial ANP concentration in SHR, but this effect was not noted in WKY. These results suggest that the ANP release from the left atrium is chronically stimulated in adult SHR, and that the prevention of an increase in plasma ANP by diltiazem treatment may be, in part, attributed to the improvement of cardiac overload induced by reductions in blood pressure and cardiac hypertrophy.

Animals↗

Induction of (2'-5')oligoadenylate synthetase in serum-starved HeLa S3 cells by growth factors and its role in growth regulation.

When serum-starved HeLa S3 cells were stimulated to proliferate by addition of fetal calf serum (FCS), (2'-5')oligoadenylate synthetase (2-5A synthetase) activity was induced. Although no interferon (IFN) activity was detectable in the HeLa S3 cell-conditioned culture medium after growth stimulation, addition of anti-IFN-beta monoclonal antibody inhibited both the expression of the 2-5A synthetase gene and the production of the enzyme, suggesting that endogenous IFN-beta was involved in 2-5A synthetase induction. Purified preparations of three growth factors, epidermal growth factor, platelet-derived growth factor, and insulin, also induced 2-5A synthetase through IFN-beta. When serum-starved HeLa S3 cells were treated with FCS, DNA synthesis was initiated synchronously, with peaks after 12 and 32 h, although the level of 2-5A synthetase reached a maximum after the first peak of DNA synthesis. Inhibition of 2-5A synthetase induction by anti-IFN-beta antibody enhanced the second, but not the first cycle of DNA synthesis. These results suggested that in HeLa S3 cells, after stimulation with growth factors the IFN/2-5A synthetase system played a role in cell growth negative regulatory mechanisms.

2',5'-Oligoadenylate Synthetase↗

Relation between ESR-detectable Cu(II) and superoxide dismutase activity.

The relation between ESR-detectable Cu(II) and Cu,Zn-superoxide dismutase activity was examined. The Cu(II) spin numbers per one unit of SOD were 6.26 X 10(12) (+/- 0.51 X 10(12] spins in several preparations of recombinant human Cu,Zn-SOD, native placental, and erythrocyte SOD. Measurement could be performed over a wide range of pH (4.0-10.0), preferably at temperatures below -40 degrees C. The data obtained by this method correlated well to the results obtained by the method of Fridovich et al. using the xanthine-xanthine oxidase system (correlation coefficient 0.995). The specific activity of SOD was proportional to the Cu(II) content measured by ESR, but not to the total Cu content measured by atomic absorption. This indicates that it is important to measure the Cu(II) content for determining Cu,Zn-SOD activity.

Copper↗

Effect of glucocorticoid on prostaglandin E1 mediated cyclic AMP formation by vascular smooth muscle cells.

The effect of glucocorticoid on the prostaglandin E1 (PGE1)-mediated cyclic AMP (cAMP) formation by vascular smooth muscle cells (VSMC) from renal arteries (RA) was studied in rats. Dexamethasone (DEX) at concentrations ranging from 10(-10) to approximately 10(-8) mol/l dose-dependently potentiates the PGE1-mediated response. This facilitation began at 6 h and reached its maximum after 24 h of DEX administration. Aldosterone (10(-6) mol/l) did not affect the dose-response curve of PGE1. Inhibitors of protein and RNA synthesis blocked this glucocorticoid effect. The basal activity of adenylate cyclase in DEX-treated cells was twice as high as in control cells. Treatment of VSMC with DEX increased cholera toxin- and pertussis toxin-stimulated adenylate cyclase activity. DEX treatment also augments forskolin-stimulated adenylate cyclase activity. These results suggest that DEX increases PGE1-mediated cAMP formation of VSMC from RA through a mechanism that involves the induction of protein synthesis, and that the activation of the catalytic unit may play some role in this facilitating process.

Alprostadil↗

Possible involvement of protein kinase C in the maintenance of hypertension in spontaneously hypertensive rats.

Calcium-activated phospholipid-dependent protein kinase (protein kinase C) and cyclic AMP-dependent protein kinase (protein kinase A) were measured in tissue extracts of aortas from 7-, 14- and 20-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Protein kinase C and protein kinase A activity was significantly higher in 14- and 20-week-old SHR. Furthermore, protein kinase C and protein kinase A activity in the aorta was positively correlated with systolic blood pressure. Since protein kinase A is known to relax vascular smooth muscle, the observed increase in its activity may represent a compensatory mechanism to offset further elevation of blood pressure in SHR. These results suggest that protein kinase C in the aorta may play a role in the maintenance of hypertension in SHR.

Animals↗

Effects of dietary modulations of protein intake on the progression of glomerulosclerosis in unilaterally nephrectomized rats with passive Heymann nephritis.

This study was undertaken to investigate the effects of dietary protein intake on renal function and pathology in unilaterally nephrectomized rats with passive Heymann nephritis (PHN). 60 Lewis rats were unilaterally nephrectomized and half of them were injected with anti-Fx1A antibody to induce PHN. The rats were divided into four groups of 15 rats each as follows: group A-high-protein diet (HPD 30%) and PHN, group B-high-protein diet (HPD 30%) with no PHN, group C-low-protein diet (LPD 6%) and PHN and group D-low-protein diet with no PHN. These rats were observed for a 30-week period. The rats in group A showed persistent massive proteinuria with eventual deterioration of renal functions. Renal pathology revealed severe glomerulosclerosis with interstitial changes. In addition, marked hypertrophy and hyperplasia of tubular cells were noted. The rats in group B showed only mild and segmental glomerulosclerosis without significant proteinuria and decreased renal functions. The rats in group C exhibited moderate proteinuria in the early experiment stages which completely remitted in the stages thereafter. Renal pathological changes included only deposition of immune complexes in the glomerular basement membrane (GBM). The rats in group D did not show any abnormalities both pathologically and functionally. From these results, HPD enhanced the permeability of GBM which had been already damaged immunologically, leading to glomerulosclerosis of high severity with deterioration of renal functions. On the contrary, LPD ameliorated those changes. Although the role of anti-Fx1A antibody in the pathogenesis of human membranous nephropathy has still been the subject of debate, it is possible that ad libitum ingestion of dietary protein will have adverse effects on the clinical course of human membranous nephropathy, especially in the reduced number of functional nephrons.

Animals↗

Physiological significance of atrial natriuretic peptides in essential hypertension.

To investigate the significance of atrial natriuretic peptides (ANP) in essential hypertension, plasma ANP concentrations in 43 essential hypertensives, 16 borderline hypertensives and 17 normotensive controls were measured. Furthermore, effects of high-sodium and low-sodium intakes on plasma ANP concentration were examined in "salt-sensitive" [SS] and "nonsalt-sensitive" [NSS] patients with essential hypertension. Plasma ANP concentration was significantly higher in hypertensives than in borderline hypertensives and in normotensive controls. No significant difference in plasma ANP concentration was observed between borderline hypertensives and normotensive controls. Plasma ANP concentration increased with the high-sodium diet in both the SS and NSS patients, but the mean increment was significantly greater in the SS than the NSS patients. Urinary excretion of sodium was lower in the SS patients taking the high-sodium diet than the corresponding value in the NSS patients. These findings suggest that an increased level of circulating ANP in hypertensive patients represents a compensatory mechanism to offset further elevation of blood pressure and sodium retention.

Atrial Natriuretic Factor↗

Effect of afterload on the left ventricular pressure fall during isovolumic relaxation period in man.

To assess the effect of afterload on the left ventricular pressure (LVP) fall during isovolumic relaxation period (IRP) in man, we examined the peak (-)dP/dt, (-)dP/dt upstroke pattern in IRP, and time constant (T) in 15 patients [normal (N): 5 valvular heart disease (VHD): 5, dilated cardiomyopathy (DCM): 5]. LVP and echocardiographic internal diameter were measured simultaneously at rest and after about 30 mmHg increment of LV peak systolic pressure (PSP) by drip infusion of angiotensin (20 ng/kg/min). After augmentation in afterload, heart rate (HR) increased slightly in VHD. T increased significantly (p less than 0.05) in N (from 32 +/- 3 to 39 +/- 4 ms) and DCM (from 56 +/- 18 to 72 +/- 12 ms), but not in VHD (from 41 +/- 5 to 46 +/- 8 ms) probably due to increased HR. LV end-systolic dimension had the same trend as T. Although there was no significant change in peak (-)dP/dt in N (from 1937 +/- 385 to 1945 +/- 189 mmHg/s), VHD (from 1521 +/- 210 to 1730 +/- 462 mmHg/s), or DCM (from 814 +/- 143 to 814 +/- 131 mmHg/s), the (-)dP/dt upstroke pattern during IRP became nonexponential in N and more downward convex in VHD or DCM. Thus, these changes of T and (-)dP/dt upstroke pattern suggest the afterload dependence of LVP fall during IRP in normal and diseased hearts.

Adult↗

Blood clearance of 99mTc-phytate for evaluation of hepatic dysfunction in dogs.

Organ distribution pattern, and blood clearance were examined by giving 99mTc-phytate (99mTc-P) to the normal dogs. At the same time, the relation between the severity of hepatic function and blood clearance of 99mTc-P was studied by using the dogs with acute hepatic dysfunction experimentally induced by carbon tetrachloride (CCl4) administration. Furthermore, a comparative discussion on blood clearance test of 99mTc-P was made with serum transaminase test. It appeared appropriate to administer 99mTc-P at the dose of 100 micrograms/kg in order to obtain an effective blood clearance curve. A major part of 99mTc-P intravenously administered was taken up into the liver, while the remainder of small amount into the spleen, kidneys, lung, and so on. Little was recognized in the thyroid. The disappearance rate of 99mTc-P from blood decreased with the increase in dose of CCl4 and with the passage of time after the CCl4 administration. The blood clearance test of 99mTc-P in dogs showed a sensitive reaction for the acute hepatic dysfunction induced by CCl4 equally to the serum transaminase test.

Alanine Transaminase↗

Therapeutic benefits and safety of carvedilol in the treatment of renal hypertension. An open, short term study. Carvedilol Renal Hypertension Study Group in Japan.

Carvedilol, a new beta-blocker with vasodilating activity, was given orally to 9 hypertensive inpatients with impaired renal function in a dosage regimen of 5 to 20mg once daily to evaluate its clinical efficacy and safety. Treatment with carvedilol produced a significant decrease in blood pressure from 172/101 to 150/87mm Hg (p less than 0.01), but it did not cause orthostatic hypotension. Heart rate was decreased from 74.3 to 72.8 beats/min, but the decrease was not statistically significant. Serum creatinine and BUN levels were unchanged and other laboratory parameters were within normal limits. There were no side effects in any of the patients during the trial. These results suggest that carvedilol is a useful and safe drug for the treatment of renal hypertension.

Adrenergic beta-Antagonists↗