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Biomedical subjects

M Omata

Publications and source records attributed to M Omata.

At least 361 records · Page 20Linked to original sources
PubMed1995

Increased nitric oxide in the exhaled air of patients with decompensated liver cirrhosis.

OBJECTIVE: To determine if nitric oxide output in exhaled air is increased in patients with liver cirrhosis. DESIGN: Cross-sectional study. SETTING: A university hospital. PATIENTS: 50 patients with liver cirrhosis, 6 patients with chronic hepatitis, and 15 healthy controls. MEASUREMENTS: Nitric oxide in exhaled air was measured using a chemiluminescence analyzer. Cardiac index was determined using echocardiography. RESULTS: Patients with decompensated liver cirrhosis had higher levels of exhaled nitric oxide output (Child C patients, 190 +/- 11 nL/min per m2 body surface area) than controls (97 +/- 8 nL/min per m2 body surface area; P < 0.001), whereas patients with compensated liver cirrhosis or chronic hepatitis had levels of nitric oxide output similar to those found in controls. Cardiac index was greater in patients with liver cirrhosis (Child C patients, 4.3 +/- 0.3 L/min per m2 body surface area) than in controls (2.9 +/- 0.2 L/min per m2 body surface area; P < 0.001). Cardiac index correlated with nitric oxide levels (r = 0.621; P < 0.001). CONCLUSIONS: Increased nitric oxide output in exhaled air is associated with systemic circulatory disturbances in patients with liver cirrhosis.

Aged↗
PubMed1995

Modulation of the levels of ouabain-like compound by central catecholamine neurons in rats.

Catecholamine regulates the Na+,K(+)-ATPase activity in the central nervous system and the Na+,K(+)-ATPase has been shown to have endogenous ligands (ouabain-like compound; OLC). To examine the relationship between OLC and central adrenergic neurons, we evaluated the effects of central sympathectomies with intracerebroventricular (i.c.v.) injection of 6-hydroxydopamine (6-OHDA; 250 micrograms) on brain and plasma OLC levels and brain catecholamine levels. In centrally sympathectomized rats, hypothalamic OLC content and plasma OLC level were significantly decreased by 90% (P < 0.01) and 70% (P < 0.01), respectively, in accordance with reduced brain norepinephrine content compared with control rats pretreated by i.c.v. injection of vehicle (ascorbic acid). On the other hand, peripheral sympathectomy with a similar manner did not affect plasma OLC level at all. These findings suggest that central adrenergic neurons may be involved in the synthesis and/or release of circulating OLC.

Animals↗
PubMed1995

Sensitive assay for detection of hepatocellular carcinoma associated gene transcription (alpha-fetoprotein mRNA) in blood.

The sensitivity of RT-PCR and nested RT-PCR for detection of circulating hepatocellular carcinoma was assessed by demonstrating the tumor cell-associated gene transcription, alpha-fetoprotein mRNA, in the nuclear cells of peripheral blood. When HepG2 cells were mixed in blood, 100-1000 tumor cells/5ml of blood could be detected by RT-PCR, in contrast to 1-10 tumor cells/5ml of blood by nested RT-PCR. In addition, 2 x 10(4) copies of AFP mRNA were found in one HepG2 cell when analyzed by the quantitative nested RT-PCR assay. Thus, the nested RT-PCR assay could provide a useful tool for detecting a tiny amount of circulating tumor cells in patients with hepatocellular carcinoma presenting extra-hepatic metastasis.

Base Sequence↗
PubMed1995

Direct measurements of endothelium-derived nitric oxide release by stimulation of endothelin receptors in rat kidney and its alteration in salt-induced hypertension.

BACKGROUND: Stimulation of endothelin subtype B (ETB) receptors has been proposed to induce release of endothelium-derived nitric oxide (EDNO). METHODS AND RESULTS: To obtain direct evidence of its release and its alteration in deoxycorticosterone acetate (DOCA)-salt hypertension, EDNO released from renal vessels by ET stimulation was assayed by a highly sensitive chemiluminescence method. Kidneys were isolated from DOCA-salt and control rats, and renal perfusion pressure (RPP) and EDNO (by hydrogen peroxide-luminol chemiluminescence) in the perfusate were monitored simultaneously during perfusion of ET-1, ET-3, an ETA receptor antagonist (BQ-123), and an ETB receptor agonist (BQ-3020). In control rats, ET-1 and ET-3 dose-dependently increased both RPP and NO release. Although the vasoconstricting effects of ET-1 were greater, their NO-releasing effects were comparable. The increase in NO release by ETs was inhibited by NG-monomethyl-L-arginine. After 10(-6) mol/L BQ-123 treatment, ET-1 decreased RPP and increased NO release in control kidneys. DOCA-salt rats responded to these agents with much less NO release. BQ-3020 at up to 10(-10) mol/L caused vasodilation (RPP, 10(-11) mol/L, -5.4 +/- 1.7%, P < .01) associated with increased NO release in control kidneys (+9.0 +/- 2.7 fmol.min-1.g-1 kidney wt, P < .01). However, in DOCA-salt kidneys, BQ-3020 caused renal vasoconstriction (RPP, +5.4 +/- 2.4%, P < .01 versus control) and a much smaller NO release (+1.1 +/- 0.4 fmol.min-1.g-1 kidney wt, P < .01 versus control). Northern blot analysis revealed that renal ETB mRNA was significantly decreased in DOCA-salt rat kidneys compared with controls (0.36 +/- 0.13 versus 1.00 +/- 0.23, P < .05). CONCLUSIONS: These results suggest that ET-1 and ET-3 release EDNO via ETB receptors in renal vessels. ETB-mediated NO release was reduced in DOCA-salt rats, which may modulate renal function and thus blood pressure regulation in DOCA-salt hypertensive rats.

Animals↗
PubMed1995

Ionic basis of neurokinin-A-induced depolarization in single smooth muscle cells isolated from guinea-pig trachea.

Neurokinin A (NKA) caused single tracheal smooth muscle cells (TSMCs) to contract. The effects of NKA on the electrical activity of guinea-pig TSMCs were examined using the tight-seal whole-cell patch-clamp technique. Under current-clamp conditions at rest, the membrane potential of TSMCs spontaneously oscillated at about -40 mV and NKA rapidly depolarized the membrane potential to nearly 0 mV, which then gradually repolarized to about -20 mV in the presence of NKA. The oscillations in potential disappeared transiently during the rapid phase of depolarization in response to NKA and reappeared during the sustained phase of depolarization. Under voltage-clamp conditions, NKA evoked an inward current which faded quickly. Subsequently, the cell conductance in the presence of NKA at potentials greater than -40 mV decreased gradually. The reversal potential of the NKA-induced inward current was about 0 mV, and shifted with changes in the Cl- equilibrium potential. The Cl- current was not elicited by NKA when using a pipette solution containing 10 mM ethylenebis(oxonitrilo)tetraacetic acid (EGTA). During the sustained phase, K+ currents evoked by depolarizing voltage steps were inhibited by NKA. The present results indicate that NKA causes rapid and sustained depolarization of TSMCs by two distinct mechanisms: (1) initial transient activation of the Ca(2+)-dependent Cl- current, and (2) sustained inhibition of K+ currents.

Animals↗
PubMed1995

Chemotactic factors released from hepatocytes exposed to acetaminophen.

To clarify the mechanism of neutrophil infiltration in the liver of acetaminophen-induced hepatic injury, chemotactic factor released from hepatocytes exposed to acetaminophen has been investigated. Hepatocytes exposed to acetaminophen release nondialyzable chemotactic factor, although acetaminophen in itself inhibits chemotaxis of neutrophils. Chemotactic activity of the nondialyzable chemotactic factor was reduced after treatment with heat (56 degrees C, 30 min) or trypsin. Chemotactic activity was demonstrated at the molecular weights of around 25 and 55 kDa. Chemotactic activity of the conditioned medium was not significantly reduced in the presence of antibody against rat KC/gro protein (interleukin-8-related cytokine in rodent). Chemotactic activity of a 25-kDa factor was reduced by the antibody against the antibody against KC/gro protein, but that of a 55-kDa factor was not reduced. Immunoblot analysis revealed that the peptide reacted with antibody against rat KC/gro protein was demonstrated at a molecular weight of around 20-25 kDa, but not around 55kDa, when the conditioned medium of acetaminophen-treated hepatocytes was electrophoresed. These results suggest that hepatocytes exposed to acetaminophen release two types of chemotactic factors for neutrophils and that a major part of the chemotactic factor could be different from a member of interleukin-8 family.

Acetaminophen↗
PubMed1995

Endothelium-derived relaxing factors in the kidney of spontaneously hypertensive rats.

Acetylcholine (ACh)-induced vasodilation is mainly due to endothelium-derived nitric oxide (EDNO) and hyperpolarizing factor (EDHF). To explore the mechanisms underlying attenuated endothelium-dependent vasodilation in hypertensive arteries, we measured the EDNO released from isolated kidneys of spontaneously hypertensive rats (SHR) using a sensitive chemiluminescence assay system of NO. ACh-induced renal vasodilation was significantly smaller in SHR than in the normotensive control, Wistar-Kyoto rats (WKY). However, ACh-induced NO release did not differ between SHR and WKY (10(-7) M: SHR +37 +/- 2 [SE] vs. WKY +32 +/- 4 fmol/min/g kidney). Perfusion with a 20 mEq/L high-K+ buffer, which is reported to inhibit action of EDHF, significantly reduced ACh-induced vasorelaxation in WKY but not in SHR, resulting in identical renal perfusion pressure in SHR and wKY under these conditions. These results indicate that attenuated ACh-induced vasorelaxation in the SHR kidney may be attributed to a decrease in EDHF rather than that in EDNO.

Acetylcholine↗
PubMed1995

A new adenosine subtype-1 receptor antagonist, FK-838, attenuates salt-induced hypertension in Dahl salt-sensitive rats.

We investigated the effects of the adenosine type-1 receptor antagonist FK-838 on salt-induced hypertension in Dahl-Sea salt-sensitive (Dahl S) rats. Dahl S rats fed a high-salt (4% NaCl) diet for 4 weeks were treated with FK-838 or hydrochlorothiazide for 4 weeks and alterations in kidney function and morphologic changes were assessed. FK-838 attenuated the development of hypertension in Dahl S rats, and caused a decrease in aortic weight in a dose dependent fashion. The adenosine antagonist did not produce any detectable metabolic disturbance. The blood pressure reduction by FK-838 was associated with attenuation of glomerular and arterial injury in the kidney. The renal protective effect of FK-838 treatment was associated with a reduction of plasma renin activity and plasma aldosterone concentration. In contrast, the thiazide diuretic, which produced almost the same blood pressure reduction as FK-838, did not attenuate renal damage. These data indicate that adenosine A1 receptor antagonism reduces salt-induced hypertension and the consequent renal injuries.

Animals↗
PubMed1995

Participation of endogenous atrial natriuretic peptide in the regulation of urinary protein excretion in experimental diabetic rats.

1. In order to determine whether atrial natriuretic peptide might play a role in the development of glomerular hyperfiltration in diabetes mellitus, we examined the effects of administration of glucose, albumin, atrial natriuretic peptide and an atrial natriuretic peptide receptor antagonist on renal function in rats with streptozotocin-induced diabetes mellitus and vehicle-treated control rats. 2. Four weeks after treatment, rats with diabetes mellitus had a higher mean plasma atrial natriuretic peptide concentration than controls [152 +/- 5 (SE) versus 115 +/- 6 pg/ml, P < 0.01] and a higher glomerular filtration rate (3.3 +/- 0.1 versus 2.7 +/- 0.2 ml min-1 kg-1, P < 0.05). 3. Infusion of albumin or glucose caused significant increases in atrial pressure, plasma atrial natriuretic peptide concentration and urinary excretion of sodium and protein in both groups of rats. 4. Increasing plasma atrial natriuretic peptide concentration by 60% via atrial natriuretic peptide infusion increased urinary excretion of sodium and protein in both control rats and rats with diabetic mellitus. 5. Administration of the atrial natriuretic peptide receptor antagonist HS-142-1 to diabetic rats resulted in diminished urinary excretion of both sodium (-61 +/- 14%, P < 0.02) and protein (-51 +/- 17%, P < 0.05). These changes were associated with a significant reduction in glomerular filtration rate (-32 +/- 11%, P < 0.05) and urinary cGMP excretion (-40 +/- 14%, P < 0.05). No significant effects of HS-42-1 on renal function were observed in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Involvement of alpha 1 and alpha 4 integrins in gut mucosal injury of graft-versus-host disease.

We have investigated the involvement of adhesion molecules in the lymphocyte infiltration associated with acute intestinal graft-versus-host disease (GVHD) induced by injection of C3H lymph node cells into irradiated (C3H x DBA/2)F1 mice. First we analyzed the expression profile of adhesion molecules including alpha 1, alpha 2, alpha 4, alpha 5, alpha 6, alpha L and beta 7 integrins, CD44 and L-selectin of lymphocytes from lymph nodes and gut mucosa in normal mice. In normal mice, intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL) uniquely showed increased expression of alpha 1, alpha 2 and beta 7 integrins, and decreased expression of L-selectin compared with that of lymphocytes of the lymph nodes and Peyer's patches. In mice with GVHD, IEL and LPL of donor lymph node cells origin underwent phenotypic changes characterized by the increased expression of alpha 1, alpha L and beta 7 integrins, and the loss of L-selectin. The expression profile of adhesion molecules on IEL and LPL of GVHD mice resembled that of normal mice except for the lack of alpha 2 integrin. Treatment of GVHD mice with anti-alpha 1, -alpha 4 or -beta 7 integrin antibody alone partially prevented the mucosal pathology of intestinal GVHD, whereas only mice treated with anti-alpha 1 showed reduced donor lymphocytic infiltration into the intestinal mucosa. In contrast, treatment with anti-alpha L or anti-CD44 antibody did not affect the intestinal GVHD. Furthermore, dual blockade of both alpha 1 and alpha 4 integrins completely inhibited the mucosal pathology and donor lymphocyte infiltration of intestinal GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Lipid peroxidation as an indicator of biocompatibility in haemodialysis.

Peroxidation of cell membrane (phosphatidylcholine hydroperoxide, PCOOH) was quantitatively assessed using a chemiluminescence-HPLC system to clarify whether haemodialysis patients are damaged by oxidative stress. Patients were divided into two groups, one dialysed with conventional cellulose membranes, and the other with cellulose triacetate for 3 months, subsequently followed by a crossover study of each membrane for 3 more months. The mean value of PCOOH in haemodialysis patients was 508.5 +/- 208.7 pmol/ml (P < 0.01 vs normal controls), which showed a statistically insignificant tendency to increase during each haemodialysis session of 4 h. Two years after commencing haemodialysis, PCOOH was maintained within almost the same range, but significantly greater than normal. There was no significant tendency between an index of aortic sclerosis and plasma PCOOH. However, three patients using conventional cellulose membranes died of myocardial infarction. Plasma PCOOH increased after the commencement of haemodialysis. This tendency was more notable in patients using conventional cellulose membrane compared to the cellulose triacetate. Cellulose triacetate, which we thought to be more biocompatible, did not necessarily produce lipid peroxide. We conclude that it is very important to check production of oxygen radicals when developing new membranes.

Biocompatible Materials↗
PubMed1995

Effect of isoproterenol on facilitation of electrical defibrillation by E-4031.

To determine whether isoproterenol could reverse enhancement of electrical defibrillation effectiveness by class III antiarrhythmic agents, we measured the internal defibrillation threshold (DFT) in 12 anesthetized dogs during infusion of (a) saline (baseline), (b) isoproterenol, (c) isoproterenol + E4031 (a new class III antiarrhythmic agent), and (d) E4031 alone. The isoproterenol infusion was adjusted so that heart rate (HR) was at least 30 beats/min greater than baseline. E4031 was given as a 40-micrograms/kg bolus at the beginning of the third stage of the study, followed by constant infusion at 2 micrograms/kg/min. Eight dogs completed the study. Although the energy-based DFT was not affected by isoproterenol (from 6.1 +/- 1.5 to 6.0 +/- 1.7 J), it was decreased to 3.7 +/- 1.6 J in the third stage by infusion of E4031 and isoproterenol (p < 0.01 vs. baseline and vs. isoproterenol). After the discontinuation of isoproterenol in the fourth stage, i.e., during infusion of E4031 alone, DFT was 3.4 +/- 1.6 J (p < 0.01 vs. baseline and vs. isoproterenol). Therefore, isoproterenol did not antagonize the effect of E4031 on the DFT, suggesting the possible clinical usefulness of class III agents for facilitating defibrillation even in the presence of augmented sympathetic activity.

Animals↗
PubMed1995

Endotoxin induced cellular communication in the liver: murine models for clarification of the role of LPS-responsive macrophages in the pathogenesis of liver diseases.

In several experimental models, lipopolysaccharide (LPS) plays an important role in the pathogenesis of liver diseases. Murine models of C3H/HeN and C3H/HeJ mice have been used to elucidate the role of LPS and its responsive-macrophages in vivo, as C3H/HeN strain mice are known to be LPS-responsive, while C3H/HeJ strain mice are LPS-resistant. Furthermore, release of several kinds of biologically active mediators such as interleukin-1, tumour necrosis factor-alpha, colony stimulating factor and reactive oxygen radical is not enhanced in C3H/HeJ mice even after stimulation with LPS. Thus, these murine models could be suitable for clarification of endotoxin induced cellular communication in the liver.

Animals↗
PubMed1995

Detection of hepatitis C virus RNA by a combined reverse transcription PCR assay: comparison with nested amplification and antibody testing.

Many of the current reverse transcription (RT)-PCR assays for the detection of hepatitis C virus (HCV) RNA are multistep processes which use multiple enzymes and buffers. The assays are also often suboptimal, requiring nested amplification to achieve the desired levels of sensitivity. As a result, these assays are cumbersome and prone to false-positive results. The susceptibility to contamination is further aggravated by the lack of carryover controls. We have previously reported the development of a combined RT-PCR assay for HCV RNA detection which is sensitive and simple to perform. We have since successfully integrated dUTP-uracil-N-glycosylase carryover prevention into the combined assay. Restriction of as much as 0.5 microliter of deoxyuridine-containing amplification products has been achieved. The performance of the improved combined assay was compared directly with conventional nested RT-PCR and antibody detection. The combined assay was found to have sensitivity similar to that of nested RT-PCR in detecting HCV RNA from HCV antibody-positive specimens. In an analysis of hepatitis B virus antibody-positive specimens, nested amplification had false-positive rates ranging from 8 to 31%, while no false-positive results were seen with the combined assay. In comparison with serological methods, the combined assay had specificity and sensitivity of 100 and 95%, respectively.

Base Sequence↗
PubMed1995

Efficacy of longterm interferon treatment in chronic liver disease evaluated by sensitive polymerase chain reaction assay for hepatitis C virus RNA.

Effects of interferon treatment on hepatitis C virus were examined by investigating the presence of hepatitis C virus ribonucleic acid and anti-hepatitis C virus antibody in 70 patients with non-A, non-B chronic liver diseases. Twenty one patients were treated with three million units of interferon alfa 2a three times a week for 52 weeks, 24 patients were treated similarly for eight weeks, and 25 patients were given a placebo for eight weeks and served as control. Sixty six of 70 patients (94%) were positive for both hepatitis C virus RNA and second generation anti-hepatitis C virus antibody. Fourteen of 21 (67%) receiving the longterm treatment had a normalised alanine aminotransferase (ALT) activity, and in 12 of these hepatitis C virus ribonucleic acid became undetectable by the end of treatment and remained so during the three year follow up after the treatment. Anti-hepatitis C virus antibody determined by first generation assay became negative in one case at the end of the 52 week treatment, and in four cases at the end of the one year follow up. In contrast, only one of 24 (4%) who received the eight week treatment and only one of 25 (4%) who received the placebo had normalised ALT activities. Hepatitis C virus ribonucleic acid became negative in two patients undergoing short-term treatment and in none receiving the placebo. Thus, longterm interferon treatment seems effective in clearing hepatitis C virus from serum of patients with chronic liver disease.

Adult↗
PubMed1995

Stress-induced elevation of ouabainlike compound in rat plasma and adrenal.

Recent observations demonstrate the presence of neurosteroids and their rapid increase in response to acute stress. In view of a steroidal nature of ouabainlike compound, we tested the hypothesis that ouabainlike compound may participate in a homeostatic response to acute stress. Male Wistar rats were subjected to acute stress by swimming in water (22 degrees C) for 10 minutes. The levels of ouabainlike compound in plasma, hypothalamus, pituitary, and adrenal at 10, 40, and 70 minutes (n = 8 for each) after the end of swim stress were compared with nonstressed control levels (n = 10). Ouabainlike compound was measured by a radioimmunoassay for ouabain. Plasma levels of corticosterone and catecholamines were also measured. Plasma corticosterone concentrations increased rapidly at 10 minutes (P < .01) and then declined. A trend for a rise in plasma catecholamines was found at 10 minutes. Adrenal levels of ouabainlike compound concomitantly increased at 10 minutes (P < .01, control: 58.9 +/- 5.9 pmol ouabain equivalents per gram; 10 minutes: 92.5 +/- 4.8; 40 minutes: 47.3 +/- 9.6; 70 minutes: 45.1 +/- 6.3). In contrast, the response of plasma ouabainlike compound was slow and doubled at 40 minutes (P < .01, control: 115 +/- 12 pmol ouabain equivalents per liter; 10 minutes: 132 +/- 23; 40 minutes: 226 +/- 53; 70 minutes: 117 +/- 16). Ouabainlike compound levels in hypothalamus and pituitary remained unaltered. These findings suggest that ouabainlike compound may function as a stress hormone.

Acute Disease↗