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Biomedical subjects

M Omata

Publications and source records attributed to M Omata.

At least 379 records · Page 21Linked to original sources

Effects of intracerebroventricular infusion of Fab fragments of digoxin antibody (Digibind) on development of reduced renal mass-saline hypertension in rats.

To clarify the role of brain ouabain-like compound in reduced renal mass-saline hypertension, we examined the effects of intracerebroventricular infusion of the Fab fragments of antidigoxin antibody (Digibind) on the change in blood pressure of saline-drinking subtotally nephrectomized rats. Twenty male Wistar rats weighing 250 g each underwent subtotal nephrectomy. Two groups of 10 rats received intracerebroventricular infusion of Digibind (20 mg/ml) or normal sheep IgG (20 mg/ml) at a rate of 0.5 microliters/h for 11 days. All rats began to drink 1% NaCl solution after two days of infusion. Systolic blood pressure was measured by the tail-cuff method on days 2, 6 and 9 of infusion. Two groups of saline-drinking rats with reduced renal mass developed hypertension. However, systolic blood pressure was significantly higher in Digibind-infused rats than in IgG-infused rats (day 2, 144 +/- 3(SEM) vs. 133 +/- 1 mmHg, p < 0.05; day 6, 161 +/- 4 vs. 151 +/- 2 mmHg, 0.05 < p < 0.1, day 9, 181 +/- 8 vs. 155 +/- 2 mmHg, p < 0.05). In spite of similar renal dysfunction, plasma aldosterone concentrations, and plasma OLC levels, the accelerated increase in blood pressure was accompanied by a significantly impaired pressure-natriuresis relationship (0.089 +/- 0.013 vs. 0.131 +/- 0.013 mmol/day/mmHg, p < 0.05). These results indicate that chronic intracerebroventricular infusion of Digibind augmented reduced renal mass-saline hypertension in rats and suggest that brain ouabain-like compound may play a protective role against the elevation of blood pressure, at least in this model of hypertension.

Animals↗

Possible linkage between renal injury and cardiac remodeling in Dahl salt-sensitive rats treated with the calcium channel antagonist benidipine.

Interest in cardiovascular protection by calcium channel antagonists has grown over the past decade. We investigated the prevention of cardiac remodeling and renal injury by the long-acting calcium channel antagonist benidipine using 12 week-old Dahl salt-sensitive (Dahl S) rats fed a high-salt (4% NaCl) diet. Six-week benidipine treatment (10 mg/kg chow) decreased systolic blood pressure by 22% in Dahl S rats. This blood pressure reduction was associated with decreases in cardiac mass and weight of the aortic wall. Collagen content in the left ventricle tended to decline with benidipine treatment. In addition, glomerular filtration rate increased by 33% and arterial and glomerular lesions improved morphologically with this treatment. Regression of cardiac mass and collagen content in the left ventricle was due mainly to blood pressure reduction; however, collagen content in the low-pressure right ventricle was not only related to systemic blood pressure but to the severity of renal lesions. These data suggest that the calcium channel antagonist benidipine attenuates cardiac and renal injury in hypertensive Dahl S rats, and that part of the cardiac hypertrophy is due to a non-hemodynamic mechanism that might be responsible for, or be a consequence of, the lesions in the kidney.

Animals↗

Local delivery of heparin inhibits neointimal hyperplasia in injured rabbit artery.

The efficacy of local delivery of an antithrombotic drug on neointimal hyperplasia was investigated in 17 rabbits. One rabbit iliac artery was injured by a balloon catheter as a control injured artery. The other iliac artery was also injured and treated by local delivery of 25 U/kg of heparin. One hour after the balloon injury, angioscopy demonstrated an occlusive or mural thrombus in all the controls, but few in the locally-treated arteries. Four weeks after balloon injury, the percent stenosis was 34 +/- 31% in the heparin treated group (n = 7, p < 0.005) vs control side 73 +/- 17%). Accumulation of FITC-labeled heparin at the injured site was confirmed by microscopy. The activated partial thromboplastin time and fibrinogen level did not change significantly. PDGF-B chain was prominent at the neointimal layer in all the controls, whereas it was less in the locally treated arteries. Thus local delivery of heparin can inhibit neointimal hyperplasia after balloon injury by reducing thrombus-related growth stimulation.

Angioscopy↗

Clonality in hepatocellular carcinoma: analysis of methylation pattern of polymorphic X-chromosome-linked phosphoglycerate kinase gene in females.

Analysis of X-chromosome inactivation patterns in women has been used to assess the clonality of various tumors. In this report, we analyzed 27 liver tumors in women, including 18 samples obtained by the performance of ultrasonically guided thin-needle biopsies. By analysis of the heterogeneity of phosphoglycerate kinase gene, 11 of 27 (41%) cases were found to be heterozygous at the gene. Of these informative 11 cases with liver tumors, 7 cases were "large" tumors (> 25 mm in diameter) and 4 cases were "small" tumors (< 25 mm in diameter). All 7 large tumors showed monoclonal patterns by the phosphoglycerate kinase gene analysis. Of the 4 small tumors, 2 showed monoclonal, and 2 showed polyclonal patterns. The 2 with monoclonal patterns were pathologically diagnosed as hepatocellular carcinoma despite their small sizes (20 mm and 23 mm). Of the two with polyclonal patterns, the smallest one (15 mm) was diagnosed as benign adenomatous hyperplasia, and the other as hepatocellular carcinoma heavily infiltrated by lymphocytes. These data suggest that analysis of the methylation pattern of the phosphoglycerate kinase gene may be helpful on rare occasions in elucidating the nature of liver tumors but must in fact be used in conjunction with histological appearances to avoid errors secondary to inflammatory infiltrates.

Base Sequence↗

Flecainide inhibits the transient outward current in atrial myocytes isolated from the rabbit heart.

We examined the effects of flecainide, a class Ic antiarrhythmic agent, on membrane currents in single rabbit atrial myocytes, using the tight-seal whole cell voltage-clamp technique. Under the current-clamp condition, flecainide (1-100 microM) prolonged the action potential duration at both the early and the late phases of repolarization in a concentration-dependent manner without affecting the resting membrane potential. In the presence of 4-aminopyridine, however, the drug affected the atrial action potential duration differently than it did in the absence of 4-aminopyridine: it shortened the early phase and only slightly lengthened the late phase of the atrial action potential. Under the voltage-clamp condition, flecainide suppressed the 4-amino-pyridine-sensitive, Ca(++)-insensitive transient outward current in a concentration-dependent fashion (the concentration for the half-maximal effect was approximately 17 microM). The drug also slightly inhibited the voltage-dependent L-type Ca++ current and delayed outward K+ current. Flecainide apparently accelerated the inactivation time course of the transient outward current but did not affect the voltage-dependence of its steady-state inactivation. These actions of flecainide on the transient outward current could be described by a voltage-dependent first-order interaction of the drug with the channel.

4-Aminopyridine↗

Incidence of hepatocellular carcinoma in chronic hepatitis B and C: a prospective study of 251 patients.

The incidence of hepatocellular carcinoma (HCC) was prospectively studied in 251 chronic hepatitis patients, and was compared between the 127 cases of hepatitis B and 124 cases of hepatitis C. All patients were diagnosed by needle biopsy on entering the study, and the cases consisted of chronic persistent hepatitis (CPH), chronic active hepatitis (CAH)2a, and CAH2b (cirrhosis was not included). Of the cases of chronic hepatitis B, 5 cases of HCC (3.9%) were detected; among the chronic hepatitis C cases, 13 cases (10.4%) were detected. Thus, although the mean follow-up periods were in the same range, the incidence of hepatocellular carcinoma was 2.7 times higher in hepatitis C than in hepatitis B (chi 2 = 3.116, P < .05). Using the Kaplan-Meier method, the incidence of HCC was significantly higher in chronic hepatitis C (P = .0194, generalized Wilcoxon test). In hepatitis C, the incubation period until HCC was detected was shorter when the liver disease was more advanced. Such a tendency was not observed in hepatitis B. In the 13 cases of HCC occurring in chronic hepatitis C, noncirrhotic liver was seen in only 1 case (7.7%), whereas 2 of the 5 cases of HCC (40%) in chronic hepatitis B were noncirrhotic. The prevalence of hepatitis C virus (HCV) genotypes II and III was the same in the total followed cases and HCC cases.

Adult↗

Effects of azelastine on membrane currents in tracheal smooth muscle cells isolated from the guinea-pig.

Azelastine [4-(p-chlorobenzyl)-2-(hexahydro-1-methyl -1H-azepin-4-yl)-1-(2H)-phthalazinone hydrochloride], an anti-allergic agent, inhibited the high K(+)-induced contraction in tracheal smooth muscle cells isolated from the guinea-pig. In order to investigate the ionic mechanisms, we examined the effects of azelastine on membrane currents, using the tight-seal whole cell voltage clamp technique. Azelastine (1-100 microM) caused an inhibition of the Ba2+ inward current (IBa) through the voltage-dependent L-type Ca2+ channel in a concentration-dependent manner. The inhibitory effect of azelastine on IBa was fully reversible. The IC50 value for azelastine-induced inhibition of IBa was approximately 8 microM, and 100 microM azelastine completely suppressed IBa. Azelastine exerted mainly a tonic block of IBa but did not show use dependence. Azelastine (10 microM) shifted the quasi-steady-state inactivation curve of IBa to more negative membrane potentials by approximately -20 mV, suggesting that the inhibitory effect of azelastine on IBa was voltage-dependent. In addition, azelastine produced inhibitory actions on other membrane currents (i.e. the voltage-dependent transient outward K+ current and the Ca(2+)-activated oscillatory K+ current) at doses higher than 10 microM. These results suggest that azelastine inhibits the voltage-dependent L-type Ca2+ current in single tracheal smooth muscle cells, which may contribute to the anti-allergic actions of azelastine in airways.

Animals↗

Coinfection study of precore mutant and wild-type hepatitis B-like virus in ducklings.

The precore mutant hepatitis B virus often emerges from a mixed infection with combined wild-type and precore mutant viruses. Nevertheless, the precore mutant does not seem to be an evolutionarily favored strain. To investigate the interaction between wild-type and precore mutant hepadnaviruses in an animal model of perinatal transmission, we used an e antigen-defective mutant duck hepatitis B virus with mutations inside the stem-loop structure of precore messenger RNA for this coinfection study. Thirty 1-day-old ducklings were infected with wild-type duck hepatitis B virus, precore mutant virus or both viruses. The amounts of viremia and the distribution of viruses were analyzed by spot hybridization, polymerase chain reaction, restriction fragment length polymorphism, cloning and sequencing. We found that all the ducklings became chronic carriers of duck hepatitis B virus. The precore mutant replicate was less active than wild-type duck hepatitis B virus, and it could be overgrown by wild-type virus during the course of coinfection. These results demonstrated that wild-type duck hepatitis B virus might become the predominant species in a situation similar to the perinatal cotransmission in human beings. This might at least in part explain why the prototype virus could prevail for years.

Animals↗