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Biomedical subjects

M Okamoto

Publications and source records attributed to M Okamoto.

At least 955 records · Page 53Linked to original sources
PubMed1986

Antihypertensive effects of a new dihydropyridine calcium antagonist.

Methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2 -yl)-1,4-dihydropyridine-3-carboxylate (DHP-218) is a new vasodilatory calcium antagonist with pronounced and long-lasting antihypertensive effects. It produced a significant decrease in blood pressure at doses more than 1 mg/kg in normotensive rats, 0.1 mg/kg in spontaneously hypertensive rats (SHR) and desoxycorticosterone acetate (DOCA)-salt hypertensive rats and 0.3 mg/kg in renal hypertensive rats. In SHR, the antihypertensive effect of DHP-218 was approximately 7 times more potent than nifedipine. The antihypertensive effect of DHP-218 appeared very slowly and persisted even after it was injected i.v. No tolerance to the antihypertensive effects of DHP-218 was observed for 5 weeks at daily doses of 0.3 and 1 mg/kg. The antihypertensive effects of DHP-218 in cats and dogs with normal blood pressure was more than 10 and 30 times more potent than those of nifedipine, respectively. At an equivalent antihypertensive dose, the effect of DHP-218 persisted longer than that of nifedipine in all the animal species used.

Animals↗
PubMed1986

Cardiovascular effects of a new dihydropyridine calcium antagonist.

The effects of methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo- 1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate (DHP-218), a 1,4-dihydropyridine derivative, on the cardiovascular system and myocardial oxygen consumption were investigated. Effects on cardiovascular system: In urethane-alpha-chloralose anesthetized dogs, DHP-218 at a dose of 0.01 mg/kg i.v. decreased blood pressure (BP), and at 0.03 mg/kg i.v., long-lasting BP decrease was accompanied by an increase in heart rate (HR), and an increase in blood flow of the coronary, vertebral and internal carotid arteries. No significant changes in myocardial contractile force (MCF) and blood flow of the common carotid and renal arteries were observed. The duration of action was different for various effects. At doses more than 0.05 mg/kg i.d., blood pressure decreased and HR, MCF and the blood flow of coronary and vertebral arteries increased. The effects of nifedipine on the cardiac and regional blood flow were observed at doses more than 0.001 mg/kg i.v. and 1 mg/kg i.d., but the duration of its action was very short compared to those of DHP-218. Effects on cardiohemodynamics: In urethane-alpha-chloralose anesthetized dogs, DHP-218 at a dose of 0.01 mg/kg i.v. produced a decrease in BP and total peripheral resistance (TPR) and an increase in cardiac output (CO). At a dose of 0.03 mg/kg, a decrease in BP and TPR and increases in HR and CO were observed. The duration of action was different for various parameters. No significant changes in dp/dtmax, stroke volume and cardiac work were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1985

Prolongation of procaine's and procainamide's actions by binding to acryloyl polymers.

Procaine and procainamide were covalently bound to acryloyl monomers and polymers. The dose-response and time-action parameters of the cardiac antiarrhythmic protection afforded by the prototype drugs and their acryloyl derivatives against chloroform-hypoxia-induced cardiac arrhythmias in unanesthetized mice and epinephrine-induced arrhythmias in alpha-chloralose anesthetized cats were determined. Similarly, the pharmacological parameters which characterized their acute toxic responses in unanesthetized male albino mice were also determined. The similar pharmacological spectra of their activity and the parallelism of their lethal dose-response curves indicate that the active constituents of the polymer derivatives are the local anesthetic moieties. Compared to the prototype drugs, the polymer derivatives were more potent on a molar basis and their pharmacological effects were prolonged. The increased potency and duration of action reinforce the idea that the local anesthetic moieties are pharmacologically active while still bound to the polymer backbones.

Acrylic Resins↗
PubMed1985

Immunochemical relatedness between secretory phospholipase A2 and intracellular phospholipase A2.

The immunochemical relationship between rat pancreatic phospholipase A2 and rat splenic phospholipase A2 was examined with the use of anti-rat pancreatic phospholipase A2 antibody as a probe. The immunoelectrophoretic patterns showed that the antibody cross-reacted with the splenic enzyme. The immuno-crossreactivity was also shown by counter immunoelectrophoresis. The splenic phospholipase A2, whether it was purified from the cytosolic fraction or the microsomal fraction, formed an immunoprecipitin band with the anti-pancreatic phospholipase A2 antibody. The antibody was shown to inhibit the activity of the pancreatic phospholipase A2 as well as that of the splenic phospholipase A2.

Animals↗
PubMed1985

Clinical, endocrine and metabolic aspects of the Werner syndrome compared with those of normal aging.

Data on the clinical features of the Werner syndrome in 102 patients in Japan were collected by sending questionnaires to major hospitals and analyzed. The male-to-female ratio was 3 to 2 and the incidences of consanguinity and familial occurrence were 51% and 39.4%, respectively. These patients were divided into 3 subgroups; group 1, 2, and 3 lacked short stature, cataract, and hypogonadism, respectively. Each group had somewhat different clinical features. Endocrine and metabolic abnormalities in the Werner syndrome patients were compared with those in normal aged subjects. Impaired plasma growth-hormone responses to insulin and arginine were more common and impaired plasma thyrotropin responses to TRH were less common in the Werner syndrome patients than in aged subjects. Plasma LH and FSH levels were higher in most patients than those in age- and sex-matched controls; also, their serum testosterone concentrations were lower than those in age-matched controls and testicular biopsy revealed more marked atrophy than in aged subjects. Serum triiodothyronine levels tended to be lower than in age-matched controls. Oral glucose tolerance test revealed diabetic glucose tolerance in 55% and impaired glucose tolerance in 22%, although fasting blood glucose levels were elevated only in 20%. Plasma insulin response to glucose was more exaggerated in those with the Werner syndrome than in normal aged subjects. The euglycemic glucose clamp method revealed lower glucose disposal rates and insulin sensitivity indices in the Werner syndrome than in normal subjects of similar age. The number of erythrocyte insulin-binding sites was normal in the Werner syndrome patients. These results suggest a postreceptor defect in insulin resistance in the Werner syndrome.

Adolescent↗
PubMed1985

Ultrastructural and immunohistochemical studies on non-ciliated cells of the tracheal epithelium of normal, phenobarbital-treated and 3-methylcholanthrene-treated mice.

Non-ciliated SER-rich cells of the tracheal epithelium of normal, phenobarbital-treated and 3-methylcholanthrene-treated mice were studied ultrastructurally and immunohistochemically. The apical portion of these cells protrudes into the tracheal lumen, especially in the mice treated with the two compounds, and the apical cytoplasm is filled with numerous tubular elements of SER. Besides, the non-ciliated cells of 3-methylcholanthrene-treated mice show a strong positive reaction to the antiserum against microsomal cytochrome P-450 of liver. These findings support the concept that the non-ciliated tracheal cell may be involved in the metabolism of endogeneous and exogeneous chemical compounds.

Animals↗
PubMed1985

Ultrastructural and immunohistochemical studies on the zona-reticularis cells of the adrenal cortex of normal and 3-methylcholanthrene-treated mice.

The drug-metabolism activity of adrenocortical cells of normal and 3-methylcholanthrene (MC)-treated ddY mice were examined ultrastructurally and immunohistochemically. Immunoblot analyses performed prior to immunohistochemistry revealed the presence of a protein - possible equivalent to cytochrome P-450 found in the liver microsomes of MC-treated male rats - in the adrenal homogenate of MC-treated female mice. Immunohistochemistry demonstrated the presence of a cytochrome-P-450-like protein in the adrenal-cortical cells (especially in the zona-reticularis cells) of MC-treated female mice; at the same time, a remarkable increase in the amount of SER in these cells was observed by electron microscopy. These findings suggest that cells of the mouse adrenal gland, particularly those of the zona-reticularis, might participate not only in steroid biosynthesis but also in some sort of drug metabolism (detoxication). In addition, there might be a sex-related difference in ddY mice.

Adrenal Cortex↗
PubMed1985

Suppression of amygdala-kindled seizure in cats by enhanced GABAergic transmission in the substantia innominata.

The chronological effect of intracerebral injection of GABAergic drugs, either muscimol or gabaculine, into the substantia innominata, was examined in amygdala-kindled cats. Results obtained indicate: that the substantia innominata may play a significant role in ictal linkage between a nonmotor system such as the amygdala and the motor mechanism responsible for amygdala-kindled convulsion, and that the GABA terminals in the substantia innominata exert a suppressive action toward convulsive seizure generalization of amygdala origin.

Amygdala↗
PubMed1985

19-Hydroxylation of 18-hydroxy-11-deoxycorticosterone by adrenal mitochondria prepared from various animal species.

We have recently reported that bovine adrenocortical cytochrome P-45011 beta catalyzes 19-hydroxylation of 18-hydroxy-11-deoxycorticosterone (18(OH)DOC) in addition to 11 beta-hydroxylation of the steroid. In this report, we examine the presence of these two activities in 18(OH)DOC and 11 beta- and 18-hydroxylation activities on deoxycorticosterone (DOC) among the adrenal mitochondria prepared from man, ox, pig, rabbit, guinea-pig and rat. The results indicate that these animals could be classified into three groups with respect of these hydroxylation activities. Mitochondria of the first group comprising ox and pig showed rather high 19- and 11 beta-hydroxylation activities on 18(OH)DOC compared to the hydroxylation activities on DOC. Mitochondria prepared from the second group which comprised rabbit, guinea-pig and man showed low 19-hydroxylation activity on 18(OH)DOC, whereas the 11 beta-hydroxylation of 18(OH)DOC well occurred in these species. The last group comprising rat had very low activity both of 11 beta- and 19-hydroxylations when 18(OH)DOC was used as the substrate, whereas both 11 beta- and 18-hydroxylations of DOC were high in rat adrenal mitochondria. No significant difference of these activities could be found between zona glomerulosa cells and zonae fasciculata-reticularis cells of bovine adrenal cortex, and between adrenal mitochondria from spontaneously hypertensive rat and those from WKY normotensive rat.

18-Hydroxydesoxycorticosterone↗
PubMed1985

Hydrolytic activities of human pancreatic phospholipase A2 and endotoxin-stimulated endogenous phospholipase A2 toward membrane phospholipids of erythrocytes.

The problem of whether human pancreatic phospholipase A2 (PLA2) can really hydrolyze membrane phospholipids in vitro was studied to understand pathophysiology of acute pancreatitis. Total amount of lysophospholipids generated in erythrocytes by exogenously added human pancreatic PLA2 (2 micrograms/ml) was only 12% of the amount of sphingomyelin, which was not decomposed by the enzyme. About fivefold the amount of lysophospholipids was generated in ghost membranes during one-sixth of the incubation time compared to that in intact erythrocyte membranes. Escherichia coli lipopolysaccharide (LPS) (10 micrograms/ml) was able to stimulate membrane-associated PLA2 of erythrocytes, the amount of lysophospholipids generated being 12.5% of that of sphingomyelin without adding the exogenous PLA2. The stimulation of membrane-associated PLA2 in erythrocytes was inhibited by pretreatment of lipopolysaccharide with polymyxin-B sulfate. When intact erythrocytes were incubated with human pancreatic PLA2 and LPS, the amount of generated lysophospholipids was 24% of that of sphingomyelin. These results suggested that the exogenously added human pancreatic PLA2 cannot degrade phospholipids of intact erythrocytes so extensively under physiological conditions, and, in acute pancreatitis, unknown factors may be involved in the hydrolysis of phospholipids. LPS, which activates membrane-associated PLA2, may be one of the factors, and thus membrane phospholipids are hydrolyzed in the disease.

Endotoxins↗
PubMed1985

Dose-response relationship of gamma-ray-induced reciprocal translocations at low doses in spermatogonia of the crab-eating monkey (Macaca fascicularis).

The yield of translocations induced by acute gamma-irradiation at low doses (0.25 and 0.50 Gy) in the crab-eating monkey's (Macaca fascicularis) spermatogonia was examined. The frequencies of translocations per cell were 0.53% at 0.25 Gy and 1.07% at 0.50 Gy. Over the low dose range from 0 to 1 Gy, the dose-response relationship for translocation yield was a linear one with a regression coefficient of 1.79 X 10(-2). To estimate the sensitivity to the induction of translocations in the crab-eating monkey's spermatogonia, the slope of the regression line was compared with those in other mammalian species. Consequently, over the low dose range below 1 Gy, the sensitivity of the crab-eating monkey's spermatogonia to translocation induction was similar to several mammalian species, the mouse. Chinese hamster, and the rabbit, but significantly higher than that of the rhesus monkey and lower than that of the marmoset.

Animals↗
PubMed1985

Inhibitory effect of gabexate mesilate on pancreatic phospholipase A2-mediated hydrolysis of ghost membranes.

Human erythrocyte ghost membranes were incubated with human pancreatic phospholipase A2 [EC 3.1.1.4] in the presence of gabexate mesilate (FOY, ethyl 4-(6-guanidinohexanoyloxy)-benzoate methanesulfonate) in Tris-buffered saline (10 mM Tris-HCl, 150 mM NaCl, 2 mM CaCl2, pH 7.4). Membrane phospholipids were extracted by chloroform-isopropanol, 7:11 (v/v), and separated by thin-layer chromatography. Gabexate mesilate at a concentration of 400 microM caused a 50% inhibition of the enzyme-mediated hydrolysis of membrane phospholipids. When phosphatidylcholine micelles were incubated with the enzyme in the presence of gabexate mesilate, the mode of inhibition of the enzyme action by the drug appeared to be noncompetitive and Ki of gabexate mesilate for phospholipase A2 was 0.77 mM.

Erythrocyte Membrane↗