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Biomedical subjects

K Hosono

Publications and source records attributed to K Hosono.

At least 55 records · Page 3Linked to original sources

Enantiotopic differentiation in horse-liver alcohol-dehydrogenase-catalyzed oxidoreduction studied with novel substrates having organometallic moieties.

Horse-liver alcohol-dehydrogenase-catalyzed oxidation of 1,2-bis(hydroxymethyl)ferrocene (1) gave (1R)-(+)-1-formyl-2-hydroxymethylferrocene (3) (86 +/- 2% enantiomeric excess, e.e.), while the reduction of the corresponding dialdehyde 1,2-diformylferrocene (2) gave the antipode (1S)-(-)-3 (94 +/- 2% e.e.). This fact indicates that the pro-R group in both 1 and 2 was preferentially converted by the enzyme. When one of two substituents on the substrate was replaced by a methyl group or moved to the beta-site, the stereoselectivity in the reaction decreased as evidenced by the enantiomeric purity of the products (5-64% e.e.). Treatment of racemic 1-hydroxyethylferrocene (14) with horse-liver alcohol dehydrogenase (HLADH) gave optically pure (R)-(-)-14 together with acetylferrocene. The reduction of 2 with HLADH, NAD and (2H6)ethanol gave (-)-(1S,2R)-1-formyl-2-[(R)-hydroxy(2H1)methyl]ferrocene and that of 1,2-di[(2H)formyl]ferrocene with HLADH, NAD and ethanol gave (-)-(1S,2R)-1-(2H)formyl-2-[(S)-hydroxy(2H1)methyl]ferrocene. These configurations indicate that the enzymic reduction occurred on the re-face of pro-R formyl group. The re-face selectivity was also found in the enzymic reduction of (eta 6-benzaldehyde)tricarbonylchromium and its (2H)formyl analogue. Docking of 2 into the active site of HLADH was examined using computer graphics. It has been suggested that the enantioselectivity to the pro-R side in the oxidoreduction of 1 and 2 by HLADH is a natural consequence of the re-face selectivity, which is caused by a steric interaction between the ligand and the side chain of Phe-93 or the Zn complex and strengthened by an interaction between the unreactive polar alpha-substituent and the protein, probably by hydrogen bond formation.

Alcohol Dehydrogenase↗

Induction of bronchial hyperresponsiveness by Bordetella bronchiseptica infection in dogs.

Six beagles were examined for time-related changes of bronchial responsiveness to methacholine, plasma histamine and thromboxane B2, and biopsy of bronchial tissues after intratracheal injection of Bordetella bronchiseptica. A progressive increase in bronchial responsiveness was induced after injection. The mediators, however, did not elevate and tissue neutrophil counts did not correlate with increased airway hyperresponsiveness. Intratracheal injection of heat-killed Bordetella bronchiseptica produced no alteration in these parameters. Thus, it is speculated that airway epithelial damage and effects on ciliostatic function induced by the organism are primarily involved in the pathogenesis.

Animals↗

Effects of treadmill and pacing stress testing on peripheral arterial thromboxane, platelet function and catecholamine activities in patients with chronic coronary artery disease.

Two different methods of causing myocardial oxygen demand and supply imbalance; symptom limited treadmill exercise and right atrial pacing stimulation, were used to examine the alteration of hemodynamics and the effects upon sympathetic nerve activities, platelet functions and prostaglandin synthesis in patients with coronary artery disease (CAD). Age and sex distributions, the cardiothoracic ratio, left ventricular end-diastolic pressure, ejection fraction and coronary artery obstructions of the patients did not differ significantly between the two tests. Arterial blood samples were obtained to assay for plasma catecholamine, beta-thromboglobulin (beta TG), platelet factor 4 (PF4), TXB2 (thromboxane B2) and 6 keto-PGF1-alpha (6 ketoprostaglandin F1-alpha) without any difficulties before and immediately after testing. The arterial systolic pressure and pressure rate product (PRP) were changed more significantly by treadmill exercise than pacing, while the DPTI/TTI (diastolic pressure time index/tension time index) ratio and ST segment deviations showed similar changes with both tests. The plasma NE (norepinephrine) level, beta TG, PF4, and TXB2/6 keto-PGF1-alpha were significantly elevated by treadmill exercise, but not by pacing. 6 keto-PGF1-alpha was not markedly affected by either tests. There were no significant differences between the patients with and without anginal pain either in hemodynamics or metabolites. Significant relationships were observed between changes in plasma NE levels and the PRP (r = 0.76, n = 26, p less than 0.01) and also changes in the arterial systolic pressure (r = 0.64, n = 26, p less than 0.01), but there were no significant correlations between any other hemodynamic parameters with plasma NE, platelet function, prostaglandin activity, or between each metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Effect of nicorandil on exercise performance in patients with effort angina: a multicenter trial using a treadmill exercise test.

The effects of a single oral dose (20 mg) of a new vasodilator, nicorandil, on exercise performance were assessed in 29 patients with stable effort angina using a symptom-limited treadmill exercise test. A single-blind, placebo-controlled, randomized, crossover design was employed. Compared with placebo, 20 mg of nicorandil significantly increased maximal exercise duration and time to 1 mm of ST-segment depression at 1, 3, and 6 h after administration. Systolic blood pressure was reduced both at rest and during exercise. Heart rate increase during exercise did not differ significantly compared with control, though resting heart rate was increased. The maximal pressure-rate product at peak exercise was increased in association with increased exercise time in about half of the patients, while it was unchanged or decreased in the others. It was suggested that nicorandil may act by either reducing myocardial oxygen demand and/or increasing myocardial oxygen supply.

Adult↗

[Radionuclide ventriculographic evaluation of left ventricular systolic function in acute myocardial infarction].

Within 18 hours of acute myocardial infarction, global left ventricular (LV) function was evaluated by radionuclide ventriculography for 127 patients. Ejection fraction (EF) was calculated using a variable region of interest counts method. LV end-diastolic volume index (EDVI) was calculated from the LV outlines in the anterior and LAO projections using the area-length method. To validate the determination of EDV by the area-length method, the radionuclide EDV correlated with that derived from direct contrast angiography in 44 other patients who had both studies within two weeks, with an overall correlation coefficient of 0.84. To minimize any potential problems with the geometric ellipsoid model, the end-systolic volume index (ESVI) was calculated from EF and EDVI. Peak systolic blood pressure (PSP) was recorded with a cuff during imaging and the PSP/ESV calculated as a measure of LV contractile function. The regional wall motion of five segments in both the anterior and LAO projections were each scored on a scale, from 4 (= normal) to 0 (= dyskinesis). The wall motion index (WMI) derived from the sum of the 10 segment scores represented an overall index of wall motion (maximum = 40). In addition, the more widely used % abnormally contracting segments (%ACS) was calculated. The severity of wall motion abnormalities were associated with significant increases in heart rate and ESVI, whereas EDVI began to increase under more severe damage to the myocardium. Our data are consistent with those of Klein who found that the LV enlarges only when 20 to 25% of the surface area is rendered akinetic. There were significant decreases in EF and PSP/ESV with moderate reduction in wall motion, and the relation between EF and PSP/ESV was curvilinear. Information about ventricular volume and systolic blood pressure might be of additional value to EF for a more complete understanding of the changes in the functional state of the LV. Global LV function was compared between anterior and inferior myocardial infarcts. The size of %ACS was larger in anterior than in inferior infarction and a greater decrease in WMI in the former suggested larger infarct size in anterior infarction. As a result, ESVI was significantly larger in anterior infraction than in anterior infraction. However, an increase in EDVI was not significantly different between the two groups. EF was reduced to a greater extent in anterior than in inferior infarction. The overall data indicate that patients with anterior infarction have more severe impairment of left ventricular global function than do those with inferior infarction.

Cardiac Volume↗

Morphological transformation of Chinese hamster cells by acylpeptides, inhibitors of cAMP phosphodiesterase, produced by Bacillus subtilis.

Treatment of Chinese hamster ovary cells in vitro with acylpeptide, an inhibitor of adenosine 3':5'-cyclic monophosphate (cAMP) phosphodiesterase, produced by Bacillus subtilis C-756 converts the culture from one of randomly oriented, epithelial-like cells to one of elongated, fibroblast-like cells. This transformation is similar to the effect of N6,O2'-dibutyryl adenosine 3':5'-cyclic monophosphate (dibutyryl cAMP), but is manifested at a lower concentration of the inhibitor than with dibutyryl cAMP. The intracellular level of cAMP in the cells grown with the inhibitor is 3-4-fold higher than the level without the inhibitor. The transformation is reversible and, when reversed, the level of cAMP simultaneously decreases to the level without the inhibitor. The acylpeptide has cytolytic activity as well as inhibitory activity and the former activity is prevented by the addition of serum.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Effects of percutaneous transluminal coronary angioplasty on left ventricular function at rest and during exercise].

The effects of percutaneous transluminal coronary angioplasty (PTCA) on left ventricular function at rest and during stress test were examined. Effect of PTCA at rest We studied 10 patients who fulfilled the following criteria, 1) single vessel disease, 2) high grade stenosis in the left anterior descending artery, 3) successful PTCA, 4) no restenosis, 5) without electrocardiographic evidence of previous myocardial infarction, and 6) technically adequate left ventriculograms in both pre and post PTCA studies. Follow-up studies were done six months after PTCA. Filling fraction as an index of early diastolic function was significantly lower than that of normal controls. There were no significant changes in left ventricular end-diastolic pressure, peak dp/dt, negative peak dp/dt, ejection fraction, left ventricular systolic pressure/end-systolic volume, between pre- and post-PTCA studies. Filling fraction in a jeopardized area, which was supplied by the left anterior descending artery, increased significantly after PTCA. No significant change was observed in the inferior area. Effect of PTCA during stress test A contrast stress test in eight successful cases without restenosis was performed by injecting 0.7 ml per kilogram of contrast material (76% urografin) at a rate of 13 ml/sec into the left ventricle before and six months after PTCA. The left ventricular end-diastolic pressure increased to 20.1 +/- 3.8 mmHg during stress test before PTCA, and only to 14.3 +/- 5.3 mmHg after PTCA (difference highly significant). Before the procedure, negative peak dp/dt during stress test was 1782 +/- 358 mmHg/sec; it increased significantly to 2342 +/- 702 mmHg/sec after PTCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗