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M Kohno

Publications and source records attributed to M Kohno.

At least 343 records · Page 19Linked to original sources
PubMed1992

Dynamic determinants of left ventricular early diastolic filling in old myocardial infarction.

The determinants of left ventricular early diastolic filling were assessed in 15 patients with old myocardial infarction. The left atrial pressure (LAP) and left ventricular pressure (LVP) were simultaneously measured by a Millar's multisensor micromanometer with the pusled Doppler mitral inflow velocity at baseline and during angiotensin infusion (20 ng/kg/min). Cardiac output was measured by a thermodilution method. LV peak systolic pressure and end-diastolic pressure were significantly (p less than 0.001) increased during angiotensin infusion from 137 +/- 19 to 170 +/- 21 mmHg and from 13.3 +/- 5.9 to 20.4 +/- 6.2 mmHg, respectively. Cardiac index was significantly decreased during angiotensin infusion. Heart rate, diastolic time, and peak positive dP/dt were unchanged. Although the LA-LV peak pressure gradient[(LAP-LVP) max] was unchanged (from 2.8 +/- 1.0 to 3.0 +/- 1.4 mmHg), the pressure gradient interval (the interval between the first and second points of transmitral pressure crossover) was significantly (p less than 0.001) decreased from 154 +/- 38 to 117 +/- 26 msec during angiotensin infusion. Peak early diastolic mitral inflow velocity (peak E) and the time-velocity integral of E wave (Ei) were significantly decreased during angiotensin infusion from 51 +/- 10 to 45 +/- 11 cm/sec (p less than 0.002) and from 7.47 +/- 1.96 to 5.70 +/- 1.66 cm (p less than 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Cloning and sequence analysis of cDNA encoding Rhizopus niveus lipase.

Complementary DNA encoding Rhizopus niveus lipase (RNL) was isolated from the R. niveus IF04759 cDNA library using a synthetic oligonucleotide corresponding to the amino acid sequence of the enzyme. A clone, which had an insert of 1.0 kilobase pairs, was found to contain the coding region of the enzyme. The lipase gene was expressed in Escherichia coli as a lacZ fusion protein. The mature RNL consisted of 297 amino acid residues with a molecular mass of 32 kDa. The RNL sequence showed significant overall homology to Rhizomucor miehei lipase and the putative active site residues were strictly conserved.

Amino Acid Sequence↗
PubMed1992

[Tracer kinetics of amino acid].

In vivo turnover of an amino acid can be determined either by analysing the disappearance curve of a labeled amino acid after a single dose of labeled amino acid or by measuring the dilution of a continuously infused labeled amino acid at a steady state. From ethical concerns stable isotopically labeled amino acids, such as 13C-leucine and 15N-glycine have been routinely used to study amino acid kinetics with subsequent estimation of whole body protein turnover. Recently, instead of these 2 methods, pulse labeling by taking a single oral dose of labeled amino acid is more practical for the study of whole body protein turnover. We observed plasma 15N-glycine kinetics and urinary 15N excretion by a single oral dose of 15N-glycine simultaneously in healthy subjects and cirrhosis patients, and the results are discussed.

Administration, Oral↗
PubMed1992

[Surgical results of two cases of simultaneous surgery of carotid and coronary occlusive disease].

Two cases of symptomatic extracranial carotid artery stenosis associated with ischemic heart disease are reported. The first case was 72-year-old male, who was admitted because of transient ischemic attack due to the stenosis of left internal carotid artery. He had a history of myocardial infarction and coronary angiography revealed three vessel disease. The second case was 74-year-old female with diabetes mellitus. She was admitted because of cerebral infarction. The carotid angiography revealed critical stenosis of bilateral internal carotid arteries. Her coronary angiography revealed three vessel disease. Her chest symptom became unstable after her admission. In both cases, simultaneous carotid endarterectomy and coronary bypass grafting were performed with successful outcome. In the patients with symptomatic extracranial carotid occlusive disease associated with severe ischemic heart diseases, we advocate simultaneous operation both for carotid and coronary artery occlusive disease.

Aged↗
PubMed1992

Metabolic fate of the new angiotensin-converting enzyme inhibitor imidapril in animals. 1st communication: absorption, pharmacokinetics and excretion in rats and dogs.

Imidapril hydrochloride ((-)-(4S)-3-[(2S)-2-[[(1S)-1-ethoxycarbonyl-3- phenylpropyl]amino]propionyl]-1-methyl-2-oxoimidazolidine-4-carboxylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1) is an ester prodrug of the angiotensin-converting enzyme (ACE) inhibitor, 6366 A (CAS 89371-44-8). Absorption, pharmacokinetics and excretion of imidapril were studied in rats and dogs after oral and intravenous administration of [N-methyl-14C]-imidapril and [N-methyl-14C]-6366 A (1 mg/kg). Following oral administration of 14C-labeled imidapril and 6366 A to rats, plasma concentrations of radioactivity were much higher after [N-methyl-14C]-imidapril dosing than after [N-methyl-14C]-6366 A dosing at all time points. Imidapril was relatively rapidly absorbed from the digestive tract and easily metabolized to the pharmacologically active 6366 A after oral dosing in the rats and dogs. Thus, imidapril proved to be an orally usable 6366 A prodrug. More than 62% and 38% of the dose were assumed to be absorbed from the gastrointestinal tract in the rats and dogs, respectively. The in situ absorption study showed that [N-methyl-14C]-imidapril was absorbed from nearly the entire rat small intestine, especially from the jejunum, but hardly absorbed from the stomach. After oral administration, peak levels of radioactivity in the plasma occurred at 1 h in rats and 30 min to 2 h in dogs. The disappearance of unchanged drug from the plasma was much faster in rats than in dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Metabolic fate of the new angiotensin-converting enzyme inhibitor imidapril in animals. 2nd communication: tissue distribution and whole-body autoradiography of imidapril in rats.

Tissue distribution, whole-body autoradiography and metabolic profiles in selected tissues of imidapril hydrochloride ((-)-(4S)-3-[(2S)-2-[[(1S)-1-ethoxycarbonyl-3- phenylpropyl]amino]propionyl]-1-methyl-2-oxoimidazolidine-4-carboxylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1) were studied in male and female rats after oral and intravenous administration of [N-methyl-14C]-imidapril (1 and 5 mg/kg) or [alanine-3-14C]-imidapril (1 mg/kg). After oral administration of [N-methyl-14C]-imidapril, radioactivity was distributed relatively rapidly to all tissues, except for the central nervous system. Maximum concentrations in most tissues were observed at 30 min to 1 h after dosing. Concentrations greater than those in the plasma were found in the liver, kidney and particularly in the lung except for the gastrointestinal contents. The elimination from the lung was relatively slow (t1/2: ca. 28 h). At 96 h after dosing, there was no evidence of remaining radioactivity in any tissues, except for the lung and kidney. No gender-related differences in the tissue distribution profile of radioactivity were observed in the whole-body autoradiogram. After intravenous administration, the distribution pattern of radioactivity was similar to the results of oral administration, except for the gastrointestinal contents. There was no specific binding of drug-related compounds to melanin-containing tissues such as the hair follicles and the uveal tract of the eye in the pigmented rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Metabolic fate of the new angiotensin-converting enzyme inhibitor imidapril in animals. 3rd communication: tissue accumulation after consecutive oral administration of [N-methyl-14C]-imidapril in rats.

Accumulation characteristics of radioactivity in the organs and tissues, metabolism, and excretion of imidapril hydrochloride ((-)-(4S)-3-[(2S)-2-[[(1S)-1-ethoxycarbonyl-3- phenylpropyl]amino]propionyl]-1-methyl-2-oxoimidazolidine-4-carboxylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1), an oral angiotensin-converting enzyme inhibitor, were investigated after consecutive oral administration of [N-methyl-14C]-imidapril at a once-daily dose of 1 mg/kg to male rats for 14 days. During the consecutive oral administration, the plasma radioactivity levels at 1 h after each dose reached steady-state following the 3rd to 4th administered dose; this was about 1.4 times higher than the corresponding plasma levels of the first dose. At 24 h after each administration, the plasma levels attained a steady-state at 3-4 days after the beginning of the consecutive dosing. Examination of the time course of plasma radioactivity after the single and multiple (7 and 14 times) oral administration revealed that the Cmax and AUCO-24 h values slightly, but significantly, increased according to repeated dosing and the beta-phase of the t1/2 of disappearance became longer after consecutive dosing. However, these values were not markedly different among consecutive dosing groups. The extent and rate of excretion of radioactivity in the urine and feces were nearly constant during the periods of consecutive oral administration, and were also similar to those after the single oral administration. Total recovery of radioactivity from urine and feces within 96 h after the final dosing was more than 98% of the total dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Metabolic fate of the new angiotensin-converting enzyme inhibitor imidapril in animals. 4th communication: placental transfer and secretion into milk in rats.

Imidapril hydrochloride ((-)-(4S)-3-[(2S)-2-[[(1S)-1-ethoxycarbonyl-3- phenylproply]amino]propionyl]-1-methyl-2-oxoimidazolidine-4-car box ylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1) labeled with 14C was administered orally or intravenously to pregnant rats on the 13th or 19th day of pregnancy, and lactating rats on the 7th or 13th day after delivery at a dose of 1 or 5 mg/kg. The placental transfer and the secretion into milk were studied using whole-body autoradiographic methods and/or quantitative determination of total radioactivity after autopsy. Irrespective of the stages of pregnancy, the placental transfer of imidapril was low in the rats after oral administration. The transfer of total radioactivity per fetus on the 13th and 19th day of pregnancy was below 0.001 and 0.07%, respectively, of the dose to their dams during the observation periods. This indicates that the substance-associated radioactivity penetrates the placental barrier to a low extent. After oral administration of [N-methyl-14C]-imidapril to lactating rats on the 7th day after delivery, the concentration of radioactivity in the milk attained a peak at 4 h after administration (0.05 microgram equivalents of imidapril/g), which was about 1/3 of Cmax in the blood. The transfer of imidapril and/or its radioactive metabolites to each suckling via milk after oral dosing was only below 0.03% of the dose to the dams on the 13th day after delivery during the observation periods. The present autoradiographic findings confirmed the above results of tissue distribution studies.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Metabolic fate of the new angiotensin-converting enzyme inhibitor imidapril in animals. 6th communication: interspecies comparison of pharmacokinetics and excretion of imidapril metabolites in rats, dogs, and monkeys.

The pharmacokinetics and excretion of the main metabolites of imidapril hydrochloride ((-)-(4S)-3-[(2S)-2-[[(1S)-1-ethoxycarbonyl-3- phenylpropyl]amino]propionyl]-1-methyl-2-oxoimidazolidine-4-carboxylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1) were investigated in rats, dogs, and monkeys after oral or intravenous administration of [N-methyl-14C]-imidapril and [alanine-3-14C]-imidapril. After oral administration of 14C-labeled imidapril to rats and dogs, the plasma concentrations of the pharmacologically active metabolite, 6366 A (M1, CAS 89371-44-8), reached a peak at 1-2 h in rats and at 2-6 h in dogs. The disappearance half-lives of M1 from plasma were much longer in dogs (6.3-9.3 h) than in rats (0.9-2.3 h). At the point of peak plasma radioactivity, the major radioactive metabolites in the plasma were M2, followed by M3, M4 greater than M1 in rats; in dogs, M2 and M3 followed by M1 greater than M4. After intravenous administration of [N-methyl-14C]-imidapril to rats and dogs, plasma levels of M1 reached a peak at the first measuring time of 5 min in rats and at about 2 h in dogs. The half-lives of plasma M1 levels were similar to those after oral dosing. At 1 h after dosing, the major metabolites in plasma were M1 followed by M2 in both rats and dogs. Irrespective of the route of administration, unchanged imidapril disappeared more rapidly from the plasma in rats than in dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Somatic growth in corticosteroid-treated rats with passive Heymann nephritis--effects of recombinant human growth hormone on growth impairment.

We evaluated the efficacy of recombinant human growth hormone (r-hGH) on corticosteroid (CS)-induced growth-impaired rats with proteinuria (passive Heymann nephritis. R-hGH (2 IU twice daily) improved growth in rats treated with 20 mg/kg per day of prednisolone succinate in our 4-week study. Although plasma hGH was significantly increased in rats treated with r-HGH, plasma insulin-like growth factor-1 levels were not different between treated and untreated rats. The food utilization rate was significantly improved by r-hGH. R-hGH did not affect proteinuria, renal function, or calcium and phosphate metabolism. Our results suggest that r-hGH may be effective in improving growth impairment due to CS administration.

Animals↗
PubMed1991

The protective effect of glycyrrhizin against injury of the liver caused by ischemia-reperfusion.

Effects of glycyrrhizin (GR) on an injury of the liver caused by ischemia-reperfusion in rats were determined. In the liver ischemia-reperfusion model, levels of serum AST, ALT and LDH, lipid peroxides in the liver tissue, and blood superoxide dismutase activity were significantly increased. On the contrary, total glutathione content in the liver tissue was decreased. When rats were given GR 100 mg/kg for 10 days, GR suppressed the elevation of the lipid peroxide level, serum AST, ALT, LDH level, and the decrease in glutathione content during the period of reperfusion. The suppressive effect of GR was similar with that of alpha-tocopherol (VE). GR showed neither 1,1-diphenyl-2-picrylhydrazyl (DPPH) nor 5,5-dimethyl-1-pyrroline-N-oxide(DMPO)-OOH radical-trapping ability, but exhibited DMPO-OH radical-trapping action, while, VE exhibited both DPPH and DMPO-OOH radical-trapping ability. These results indicate that the hydroxyl radical trapping action of GR is the likely mechanism suppressing liver injury caused by ischemia-reperfusion.

Alanine Transaminase↗
PubMed1991

Increased plasma immunoreactive endothelin-1 concentration in hypercholesterolemic rats.

This study examined the influence of hypercholesterolemia on the concentration of plasma immunoreactive (ir) endothelin-1 in rats. Plasma ir-endothelin-1, total cholesterol, triglycerides, and lipoprotein fraction concentrations were measured in three groups of rats; ie, fed a standard diet, a high cholesterol diet, or a high cholesterol diet supplemented with the antihypercholesterolemic drug clinofibrate for 4 and 8 weeks. In the rats fed cholesterol for 8 weeks, morphological changes in thoracic and abdominal aortas were examined. Plasma total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL) and ir-endothelin-1 concentrations increased significantly in the cholesterol-fed rats after both 4 and 8 weeks. In the clinofibrate-treated rats, these lipid parameters and plasma ir-endothelin-1 levels after 4 and 8 weeks were significantly lower than in the cholesterol-fed rats. The plasma ir-endothelin-1 concentration was correlated with plasma total cholesterol, LDL, and VLDL concentrations in the three study groups after 4 and 8 weeks. Morphologically, neither foam cells formation nor intimal thickening was observed in rats fed the high cholesterol diet for 8 weeks. These observations indicate that hypercholesterolemia without atherosclerosis elevates the plasma ir-endothelin-1 level in rats. The observed increase in plasma ir-endothelin-1 associated with hypercholesterolemia may play a role in the initiation or development of atherosclerotic vascular lesions.

Animals↗
PubMed1991

Circulating immunoreactive endothelin in patients undergoing percutaneous transluminal coronary angioplasty.

Circulating immunoreactive endothelin (ir-ET) in the coronary sinus (CS) and the femoral artery (Ao) was measured in patients who underwent percutaneous transluminal coronary angioplasty (PTCA). Plasma ir-ET level in the CS was significantly increased from 1.6 +/- 0.8 pg/mL to 2.0 +/- 1.0 pg/mL after PTCA (P less than .05). Plasma ir-ET level in the Ao tended to increase after PTCA, but it was not significant. Plasma ir-ET level in the CS was not related to the plasma thromboglobulin level, plasma thrombin-antithrombin complex level, mean blood pressure, or heart rate. These results suggest that the increase of plasma ir-ET level in the CS may be associated with the coronary endothelial injury by PTCA.

Adult↗