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Biomedical subjects

M Higuchi

Publications and source records attributed to M Higuchi.

At least 217 records · Page 12Linked to original sources
PubMed1992

Effects of ouabain on contractile response to norepinephrine in isolated rat aorta.

1. Inhibition of sodium(Na+), potassium(K+)-ATPase activity was dependent on the concentration of ouabain and inverse to the concentration of potassium ([K+]) in the reaction mixture. 2. Contractility of isolated rat aorta preparation in response to norepinephrine was augmented by ouabain and low [K+]. 3. Results suggest that inhibition of Na+,K(+)-ATPase activity will be correlated with augmentation of vascular contractility maybe through activation of Na(+)-calcium exchange system.

Animals↗
PubMed1992

Enhancement of vascular contractility by plasma substances obtained from pregnancy-induced hypertension.

1. Augmentation of norepinephrine (NE)-induced contraction of isolated dog mesenteric arteries by ouabain was significantly enhanced under 4 mM potassium ([K+]) medium condition compared with usual medium condition at 6 mM [K+]. 2. Vascular contractility to NE was significantly enhanced by plasma substances obtained from pregnancy-induced hypertension (PIH) patients compared with that from normotensive pregnant women under 4 mM [K+] medium condition despite of no difference between them under 6 mM [K+] medium condition. 3. These results suggest the possible involvement of the ouabain-like substance in development of hypertension in PIH patients.

Adult↗
PubMed1992

Damage to mitochondrial respiration chain is related to phospholipase A2 activation caused by tumor necrosis factor.

Tumor necrosis factor (TNF) has been shown to be cytotoxic to tumor cell lines in vitro, but the mechanism by which TNF exerts its cell growth-regulatory effects is not known. In this report, we used various inhibitors to investigate the sequence of events that lead to cytotoxic effects of TNF on L.P3 cells, a highly sensitive, murine fibroblast cell line. Our results indicate that mitochondrial respiration chains are damaged by a hydroxyl radical at an early stage of the cell lysis after TNF treatment. This event is followed by the activation of phospholipase A2, and finally leads to cell lysis.

Animals↗
PubMed1992

Activation of human monocytes by interleukin-2 and various cytokines.

We previously reported that human macrophages cultured with IL-2 for a long period (lymphokine-activated macrophages, LAMs) showed high tumoricidal activity against human and murine leukemic cell lines through a different mechanism from lymphokine-activated killer (LAK) cells. In this report, we investigated the effects of various cytokines on the tumoricidal activity of IL-2-induced LAMs against HeLa cells. CSF-1 and IL-1 were found to enhance the tumoricidal activity of LAM in a dose-dependent manner, whereas IFN-gamma and TNF had inhibitory effects. CSF-1 in combination with a low dose of IL-2 synergistically induced LAMs with highly tumoricidal activity. We also found that monocytes from some donors that did not respond to IL-2 were differentiated to tumoricidal macrophages by treatment with a combination of CSF-1 and IL-2. Furthermore, IL-2-induced LAMs were found to produce cytotoxic factors in the culture medium when they were cocultured with tumor cells, and the cytotoxic activity in the culture supernatant of LAMs was also increased by the incubation of LAMs with CSF-1. The cytotoxicity of the supernatants from macrophages with different tumoricidal activity correlated with their cell-mediated cytotoxicity. It is suggested from these results that the cytotoxicity of LAMs is regulated by CSF-1, IL-1, IFN-gamma, and TNF, and that the production of cytotoxic molecules is involved in cell-mediated killing by LAMs.

Cytokines↗
PubMed1992

Reduced nicotinamide adenine dinucleotide oxidase involvement in defense against oxygen toxicity of Streptococcus mutans.

The growth inhibition of the Streptococcus mutans group, including Streptococcus mutans, Streptococcus cricetus, Streptococcus rattus and Streptococcus sobrinus, on glucose by oxygen and the properties of reduced nicotinamide adenine dinucleotide (NADH) oxidase induced by oxygen, using a representative oxygen-tolerant strain, were examined. The growth response to oxygen varied among strains and correlated with the level of NADH oxidase activity in the cell extract. The induced synthesis of NADH oxidase as well as superoxide dismutase was affected by oxygen tension and energy sources. The induced NADH oxidase involved at least two types, major H2O-forming NADH oxidase and minor H2O2-forming NADH oxidase activity. In the presence of a scavenger of H2O2, pyruvate, the growth inhibition by oxygen in an oxygen-sensitive strain (GS5) was protected but not in another oxygen-sensitive strain (MT8148). The high level of induced H2O-forming NADH oxidase activity protected against oxygen toxicity.

Aerobiosis↗
PubMed1992

Pharmacological actions of "kyushin," a drug containing toad venom: cardiotonic and arrhythmogenic effects, and excitatory effect on respiration.

The cardiotonic and arrhythmogenic effects, and the excitatory effect on respiration of "Kyushin," a drug containing toad venom, were studied in comparison with those of digoxin. In anesthetized rabbits, the maximum rate of rise of left ventricular systolic pressure (max dP/dt) was measured as an index of cardiotonic effect, and the respiratory flow was measured as an index of respiratory function. Intraduodenal (i.d.) administration of 80 mg/kg "Kyushin" produced a cardiotonic effect and an excitatory effect on respiration, but i.d. administration of 16 mg/kg digoxin produced only a cardiotonic effect, and conversely inhibited respiration. In anesthetized open-chest guinea pigs, myocardial contractile force was measured as an index of cardiotonic effect and the arrhythmogenic effect was evaluated from the appearance of arrhythmic myocardial contraction. By i.d. administration of a 20% ethanol suspension or solution, "Kyushin" and digoxin showed a cardiotonic activity with doses higher than 40 mg/kg and 0.25 mg/kg, respectively. The arrhythmogenic doses of "Kyushin" and digoxin by i.d. administration were 2560 mg/kg and 2 mg/kg, respectively, suggesting that the safety margin of "Kyushin" is broader than that of digoxin.

Amphibian Venoms↗
PubMed1992

Effects of daily physical activity on insulin action in the elderly.

The effects of daily physical activity on peripheral insulin action were investigated in aged individuals. Glucose infusion rates (GIR) during the euglycemic insulin clamp procedure in aged bedridden, aged controls, and aged athletes were compared with those in young controls and young athletes at insulin infusion rates of 40 and 400 mU.m-2.min-1 to estimate insulin action at physiological and maximal insulin concentrations, respectively. At both insulin infusion rates, GIR was significantly higher in aged athletes and significantly lower in aged bedridden subjects than in aged controls. Although there was no statistical difference in GIR at 400 mU.m-2 x min-1 between young athletes and young controls, GIR at 40 mU.m-2 x min-1 was higher in young athletes than in young controls. Comparison of the aged and young groups showed that although GIR at 400 mU.m-2 x min-1 was significantly lower in aged controls than in young controls, there was no significant difference between the aged athletes and the young athletes. We conclude that insulin responsiveness (insulin action at the postreceptor binding site) may decrease with the aging process and may be further affected by physical inactivity. Although physical training may improve insulin responsiveness in aged individuals up to levels similar to those in young athletes, physical training in young individuals may improve only insulin sensitivity.

Adult↗
PubMed1992

Effects of denopamine with or without diltiazem on the ischemic heart of anesthetized dogs.

Effects of denopamine with or without diltiazem on the ischemic heart were investigated in anesthetized open-chest dogs. Partial occlusion of the left circumflex coronary artery (LCX) produced significant decreases in LCX flow and regional myocardial segment shortening rate (%SS) in the LCX-perfused area, and a significant increase in left ventricular enddiastolic pressure (LVEDP). Heart rate (HR) and mean aortic pressure (mAoP) were not altered, but aortic flow (AoF), positive first derivative of left ventricular pressure ((+)LVdP/dt), stroke volume (SV), stroke work index (SWI) and double product showed a tendency to decrease. Total peripheral vascular resistance (TPR) tended to increase. During coronary stenosis, saline infusion (vehicle group) did not change any parameter, but diltiazem infusion (diltiazem group) decreased HR, mAoP, TPR and double product and increased SV and SWI. Under these conditions, denopamine infusion produced increases in HR, mAoP, AoF, (+)LVdP/dt and double product and decreases in LVEDP and TPR in both groups. %SS in the left anterior descending coronary artery-perfused area was increased, but %SS in the LCX-perfused area was slightly decreased in both groups. SV and SWI were decreased by denopamine infusion in the vehicle group, while they were increased in the diltiazem group. Differences in changes in SV and SWI between the groups were statistically significant. Results suggest that combined treatment of denopamine and diltiazem may exert an advantage in alleviation of heart failure due to coronary stenosis.

Adrenergic beta-Agonists↗
PubMed1992

Exercise training increases glucose transporter content in skeletal muscles more efficiently from aged obese rats than young lean rats.

Glucose uptake in rat skeletal muscles decreases with age and obesity, but increases with chronic exercise training. The purpose of our study was to determine whether the GLUT4 content in several skeletal muscles from 1-mo-old young, lean rats and 12-mo-old aged, obese rats alters with exercise training. For exercise, a treadmill run of approximately 1 km/day was made for 4 wk by both groups of rats. The concentration of GLUT4 per protein in membrane fraction from several skeletal muscles was measured by immunoblotting. The amount of GLUT4 in the gastrocnemius and white quadriceps from aged rats slightly but significantly decreased to 73% and 78% of that from young rats, respectively. However, no significant difference in GLUT4 amount in the soleus, plantaris, and red quadriceps was observed between young and aged rats. The exercise training resulted in a larger increase in the amount of GLUT4 in each muscle from aged rats than in muscles from young rats. In aged rats, GLUT4 amount increased significantly with exercise training by 30, 33, 41, and 27% in the soleus, plantaris, gastrocnemius, and red quadriceps, respectively, compared with the sedentary controls. However, in young rats, exercise-induced increase of GLUT4 amount was significant only in the plantaris, and the increase was 17%. In exercised aged, obese rats, decreases of body weight, plasma triglyceride levels, and plasma free fatty acid were also observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Emergency cervical cerclage using a metreurynter in patients with bulging membranes.

Emergency cervical cerclage was performed in 26 women between 18 and 32 weeks of gestation who had fetal membranes bulging through a widely dilated cervix. A bulging bag was pushed into the uterine cavity by a new method, using a metreurynter. The average prolongation of pregnancy after the operation in the 26 women was 41 days (ranging from 2 to 115 days). All pregnancies resulted in the live birth of altogether 28 babies. The neonatal survival rates at gestational ages of less than or equal to 26 (including two sets of twins), 27-29, and greater than or equal to 30 weeks at the time of cervical cerclage were 80.0 (12/15), 85.7 (6/7), and 100% (6/6), respectively. Ten (83.3%) of the 12 infants who survived from patients receiving cerclage at a gestational age of less than or equal to 26 weeks are alive and well. The average duration of pregnancy after cerclage was 60 days when cervical dilation was less than or equal to 5 cm at operation, in contrast to 5.4 days in patients with cervical dilation of greater than or equal to 6 cm, suggesting that emergency cervical cerclage could be suitable in the presence of a cervical dilation of 5 cm or less.

Emergencies↗
PubMed1992

Beneficial effect of dibutyryl cyclic AMP (DBcAMP) on ischemic acute renal failure in the rat.

To determine the effect of dibutyryl cyclic AMP (DBcAMP) on ischemic acute renal failure (IARF), that disorder was induced in male Wistar rats. After the animals were anesthetized with sodium pentobarbital (50 mg/kg, i.p.), the right kidney was removed and the left renal pedicle was clamped for 60 min. DBcAMP (5 mg/kg, i.p.) was given each 30 min before and after the renal pedicle clamping in half the dose each. Twenty-four hours after surgery, the levels of serum creatinine, BUN, serum potassium, and FENa% were significantly less elevated; and the total urine volume was significantly less decreased for 24 h in the group of IARF given DBcAMP than in the group of IARF alone. The elevation in Ca2+ content of the renal cortex was also significantly lower in the group of IARF given DBcAMP than in the group of IARF alone. These data indicate that DBcAMP can produce a beneficial effect on experimentally induced IARF. Since the intracellular accumulation of Ca2+ has been reported to be a potentially harmful factor in the development of IARF, it is suggested that the effect of DBcAMP on IARF can be in part due to an inhibition of the intracellular accumulation of Ca2+ in the kidney.

Acute Kidney Injury↗
PubMed1992

Molecular genetics of hypertension.

During the last decades the evidence that a genetic component contributes to the development of primary hypertension has been accumulating. The identification of the genes involved in blood pressure regulation, however, is only starting to emerge. The recent advances in recombinant DNA technology provide new molecular genetic strategies in cardiovascular research. In this review we will discuss the testing of candidate genes in vivo by transgenic techniques. Furthermore, we will describe the possibilities to identify the genes implicated in primary hypertension by genetic linkage analysis using polymorphic DNA markers.

Animals↗
PubMed1992

Down-modulation of cell surface expression of p80 form of the tumor necrosis factor receptor by human immunodeficiency virus-1 tat gene.

Tumor necrosis factor-alpha (TNF-alpha) induces the expression of human immunodeficiency virus type-1 (HIV-1) in vitro in chronically infected cells of T and monocytic origin. The tat protein from the HIV-1 virus has been shown to be essential for HIV replication and in the immunosuppression associated with the virus infection. Previous studies in our laboratory have shown that HIV-1 tat gene induces TNF-beta (lymphotoxin) in human B-lymphoblastoid cells (Sastry et al., 1990, J. Biol. Chem. 265, 20091-20093). In an attempt to characterize further the relationship between the host and HIV-1, we investigated the effect of the functional HIV-1 tat gene on the expression of TNF receptors in a human B lymphoblastoid cell line (Raji). We report here that Raji cells transfected with HIV-1 tat gene express fewer cell surface TNF receptors than control cells. At least a 5-fold decrease in the receptor number without any significant change in receptor affinity was observed. The decrease in TNF receptors in tat-transfected Raji cells (Raji-tat cells) was found not to be due to receptor occupancy by the autocrine production of TNF-beta. The decrease in the cell surface expression of TNF receptors in Raji-tat cells was also found to be not due to a decrease in the gene expression of the receptor. The kinetics, amount of TNF binding and its internalization were temperature dependent, and it was different in Raji-tat cells than in the control cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Line↗
PubMed1992

Effects of the new thromboxane A2 antagonist vapiprost on isolated canine blood vessels.

Effects of the new thromboxane A2 antagonist vapiprost (SN-309, GR-32191B, CAS 85505-64-2) on isolated canine blood vessels were investigated. U46619 ((15S)-hydroxy-11a, 9a-(epoxymethano) prosta-5Z, 13E-dienoic acid) 10(-10)-10(-6) mol/l, a thromboxane A2 analogue, produced concentration-dependent contractions of oblong or ring preparations isolated from basilar, coronary, mesenteric and femoral arteries. Vapiprost 10(-8) and 10(-7) mol/l significantly and concentration-dependently shifted the concentration-contraction curves for U46619 of these arteries to the right. The pA2 values were 8.80 +/- 0.09 in basilar arteries, 8.67 +/- 0.12 in coronary arteries, 8.86 +/- 0.05 in mesenteric arteries and 9.01 +/- 0.07 in femoral arteries. On the other hand, oblong or ring preparations of basilar, coronary, mesenteric and femoral arteries showed sustained contractile responses to KCl 3 x 10(-2) mol/l, U46619 10(-7) mol/l or prostaglandin (PG) F2 alpha 10(-5) mol/l. Norepinephrine (NE) 3 x 10(-5) mol/l also produced sustained contractions in mesenteric and femoral arterial preparations, but not in basilar and coronary arterial preparations. Vapiprost 10(-10)-3 x 10(-6) mol/l relaxed these four arterial preparations constricted with U46619 10(-7) mol/l and PGF 2 alpha 10(-5) mol/l in a concentration-dependent fashion, but hardly affected them constricted with KCl 3 x 10(-2) mol/l. NE 3 x 10(-5) mol/l-induced contractures of mesenteric and femoral arterial preparations were not influenced by any concentrations of vapiprost. Results indicate that vapiprost has an antagonistic action on a so-called TP-receptor and/or a vasoconstrictive prostaglandin(s)-receptor and thus produces vasorelaxation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Effects of pravastatin on serum lipids and apolipoproteins in hyperlipidemia of the nephrotic syndrome.

The nephrotic syndrome is often accompanied by hyperlipidemia associated with an increased risk of accelerated atherosclerosis. The present study was undertaken to evaluate the effects of pravastatin, a novel competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the serum lipids and apolipoproteins in patients with this syndrome and marked hyperlipidemia. Eleven adult patients received 10 mg of pravastatin twice daily for 4 to 8 weeks. The total serum cholesterol decreased from 426 +/- 44 to 309 +/- 18 mg/dl (-27.4%, mean +/- S.E.; p less than 0.01) following administration of pravastatin. The serum triglyceride decreased from 332 +/- 122 to 229 +/- 50 mg/dl (-30.9%), although this change was not significant. Despite the fact that the HDL cholesterol level was barely changed (51 +/- 7 to 51 +/- 6 mg/dl), the LDL cholesterol fell from 313 +/- 30 to 211 +/- 16 mg/dl (-32.5%; p less than 0.005), and the LDL to HDL cholesterol ratio fell from 7.57 +/- 1.59 to 4.94 +/- 0.88 (-34.8%; p less than 0.05). These changes caused the atherogenic index to decline from 9.6 +/- 2.4 to 6.1 +/- 1.2 (-36.5%; p less than 0.05). No significant alterations could be found among apolipoproteins A-1, A-2, B, C-2, C-3, and E. During the present study period, pravastatin was well tolerated and did not affect the serum protein, albumin, serum urea nitrogen, creatinine levels, or urine protein excretion. Also, there were no serious adverse effects. Pravastatin appears to be effective for treating patients with hyperlipidemia of the nephrotic syndrome.

Adult↗
PubMed1992

A case of IgA nephritis showing diffuse podocytic detachment from the glomerular basement membrane.

We report the case of a 15-year-old Japanese female with severe mesangial proliferative IgA glomerulonephritis who showed a dramatic response to cocktail therapy for nephrotic syndrome. She had suddenly developed massive proteinuria and microscopic hematuria. The first renal biopsy at one month after onset revealed severe mesangial hypercellularity and podocytic detachment from the glomerular basement membrane (GBM). The cocktail therapy resulted in a decrease of proteinuria clinically, and a second biopsy demonstrated repair of the podocytic detachment. We suggest that the massive proteinuria in this case was due to destruction of the size barrier by detachment of podocytes from the GBM, and the repair of the podocytic covering on the GBM was accelerated by the cocktail therapy.

Adolescent↗
PubMed1991

Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.

To date it has been difficult to characterize completely a genetic disorder, such as hemophilia A, in which the involved gene is large and unrelated affected individuals have different mutations, most of which are point mutations. Toward this end, we analyzed the DNA of 29 patients with mild-to-moderate hemophilia A in which the causative mutation is likely to be a missense mutation. Using computer analysis, we determined the melting properties of factor VIII gene sequences to design primer sets for PCR amplification and subsequent denaturing gradient gel electrophoresis (DGGE). A total of 45 primer sets was chosen to amplify 99% of the coding region of the gene and 41 of 50 splice junctions. To facilitate detection of point mutations, we mixed DNA from two male patients, and both homoduplexes and heteroduplexes were analyzed. With these 45 primer sets, 26 DNAs containing previously identified point mutations in the factor VIII gene were studied, and all 26 mutations were easily distinguishable from normal. After analyzing the 29 patients with unknown mutations, we identified the disease-producing mutation in 25 (86%). Two polymorphisms and two rare normal variants were also found. Therefore, DGGE after computer analysis is a powerful method for nearly complete characterization of disease-producing mutations and polymorphisms in large genes such as that for factor VIII.

Base Sequence↗