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Biomedical subjects

A Hara

Publications and source records attributed to A Hara.

At least 523 records · Page 29Linked to original sources
PubMed1985

Reductases for carbonyl compounds in human liver.

Two aldehyde reductases with mol. wt 78,000 and 32,000 and one carbonyl reductase with mol. wt 31,000 were purified to homogeneity from human liver cytosol. The high molecular weight aldehyde reductase exhibited properties similar to alcohol dehydrogenase; it had a single subunit of mol. wt 41,000 and a pI value of 10 to 10.5, and showed preference for NADH over NADPH as cofactor and sensitivity to SH-reagents, pyrazole, o-phenanthroline and isobutyramide. The enzyme reduced aliphatic and aromatic aldehydes, alicyclic ketones and alpha-diketones and an optimal pH of 6.0, and oxidized various alcohols with NAD as a cofactor at an optimal pH of 8.8. The identity of the enzyme with alcohol dehydrogenase was established by starch gel electrophoresis and co-purification of the two enzymes. The other enzymes were NADPH-dependent and monomeric reductases; the aldehyde reductase reduced aldehydes, hexonates and alpha-diketones and was sensitive to barbiturates, diphenylhydantoin and valproate, while the carbonyl reductase showed a broad substrate specificity for aldehydes, ketones and quinones and was inhibited by SH-reagent, quercitrin and benzoic acid. The latter enzyme appeared in three multiforms with different charges which occurred in differing ratios in liver specimens. Comparison of kinetic constants for aldehydes among the enzymes indicated that alcohol dehydrogenase is the best reductase with the highest affinity and Kcat values. The enzyme also catalyzed oxidation and reduction of aromatic aldehydes in the presence of NAD at physiological pH of 7.2. Tissue distribution of the three enzymes and variation of their specific activities in human livers were examined.

Adult↗
PubMed1985

Guinea-pig liver testosterone 17 beta-dehydrogenase (NADP+) and aldehyde reductase exhibit benzene dihydrodiol dehydrogenase activity.

We have kinetically and immunologically demonstrated that testosterone 17 beta-dehydrogenase (NADP+) isoenzymes (EC 1.1.1.64) and aldehyde reductase (EC 1.1.1.2) from guinea-pig liver catalyse the oxidation of benzene dihydrodiol (trans-1,2-dihydroxycyclohexa-3,5-diene) to catechol. One isoenzyme of testosterone 17 beta-dehydrogenase, which has specificity for 5 beta-androstanes, oxidized benzene dihydrodiol at a 3-fold higher rate than 5 beta-dihydrotestosterone, and showed a more than 4-fold higher affinity for benzene dihydrodiol and Vmax. value than did another isoenzyme, which exhibits specificity for 5 alpha-androstanes, and aldehyde reductase. Immunoprecipitation of guinea-pig liver cytosol with antisera against the testosterone 17 beta-dehydrogenase isoenzymes and aldehyde reductase indicated that most of the benzene dihydrodiol dehydrogenase activity in the tissue is due to testosterone 17 beta-dehydrogenase.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

Intrathecal substance P analogue causes motor dysfunction in the rat.

(D-Pro2, Trp7,9)-substance P injected into the subarachnoid space produced a severe faccid extension of hindlimb in a dose-related manner in the rat. This motor dysfunction was neither reversed by naloxone, an opioid receptor antagonist nor by intrathecal SP. SP levels in the lumbar cord were markedly depleted in rats with hindlimb paralysis, though there was not significant changes in rats without paraplegia. These results suggest that DPDT-SP produces motor dysfunction which dose not appear to be mediated by opioid and SP receptors.

Animals↗
PubMed1985

Characterization of the hyperalgesic effect induced by intrathecal injection of substance P.

Substance P (SP) was administered to awake rats by injection into the lumbar subarachnoid space via an indwelling cannula. Intrathecal (i.t.) injection of substance P produced a dose-related hyperalgesic response in the tail-pressure assay. This hyperalgesic effect peaked at 1 min and returned to control level within 15 min. Tachyphylaxis to the action of substance P was not observed by successive intrathecal injections. The hyperalgesic effect induced by substance P was increased by pretreatment with naloxone and blocked by a large dose of morphine. A synthetic analogue (D-Pro2, D-Trp7,9)-substance P, was not found to block the action of substance P on mechanical responses. These results suggest that substance P apparently produces a direct action on spinal substance P receptors and the antagonistic effect of morphine on the hyperalgesia induced by substance P may be mediated through a postsynaptic mechanism in the spinal cord.

Animals↗
PubMed1985

Characterization of Fe2+-activated acid phosphatase in rat epidermis.

A particulate acid phosphatase (EC 3.1.3.2, orthophosphoric monoester phosphohydrolase (acid optimum)) was extracted in 1 M KCl, from 2-day rat epidermis. The enzyme has a Mr of 32,000, but two forms, F1 and F2 with pI values of 8.6 and 8.3, respectively, were identified while the pI values of other acid phosphatases soluble in sucrose and Triton X-100 were all acidic. F1 and F2 also differed from other epidermal acid phosphatases because they were (a) activated by Fe2+ and reducing agents, (b) showed immunological cross-reactivity with purple acid phosphatase of rat spleen and (c) dephosphorylated phosvitin and alpha-casein even though they had rather high Km values.

Acid Phosphatase↗
PubMed1985

Neuropathological study and chemico-pathological correlation in sibling cases of Sanfilippo syndrome type B.

Pathological and biochemical studies of two sibling cases (18-year-old girl and 16-year-old boy) with Sanfilippo syndrome type B are presented. Pathological study revealed distended neurons and neuronal processes with inclusions throughout the CNS and the visceral organs, and neuronal loss and corresponding gliosis. The authors paid particular attention to atrophic changes in the thalamus and to "dissociation gliomyélinique" in the cerebral white matter. Histochemistry and electron microscopy revealed regional differences in stored materials. Biochemical studies revealed an accumulation of glycosaminoglycans in the CNS and abnormalities in the lipid metabolism in the brain and visceral organs. A protein assay of the cerebrum showed increased glial fibrillary acidic protein and low levels of myelin basic protein in the white matter.

Adolescent↗
PubMed1985

Kinetic and structural properties of diacetyl reductase from hamster liver.

Kinetic and physicochemical properties of hamster liver diacetyl reductase have been examined. The results of kinetic studies on the reduction of diacetyl and NADPH to acetoin and NADP+ suggest that the reaction follows an Ordered Bi Bi mechanism in which NADPH binds first before diacetyl. The enzyme is a tetrameric glycoprotein of single subunits of a molecular weight of 23,500 with a sedimentation coefficient of 6.0S. The enzyme does not contain Zn, Cu, or Fe. The amino acid composition revealed an unusually low proportion of proline residues (0.9%). p-Chloromercuriphenylsulfonate and phenylglyoxal inactivated the enzyme, but the presence of NADPH prevented the loss of activity due to thiol and arginine modification. The enzyme transferred the pro 4S hydrogen atom of NADPH to the substrate and the binding of the enzyme to NADPH resulted in a red shift of the ultraviolet absorption spectrum of the cofactor.

Acetoin Dehydrogenase↗
PubMed1985

Effect of NCO-700, an inhibitor of protease, on myocardial pH decreased by coronary occlusion in dogs.

During myocardial ischemia in dogs effects of NCO-700, a protease inhibitor on myocardial pH, were investigated. Ischemia was produced for 90 min by partial occlusion of the left anterior descending coronary artery (LAD). Myocardial pH was measured by a micro glass pH electrode inserted in the subendocardium of the LAD area. Before partial occlusion, myocardial pH was 7.50-7.67. It decreased by 0.65 to 0.86 pH units after partial occlusion. NCO-700 was injected intravenously after 30 min partial occlusion. At a dose of 5 or 20 mg/kg NCO-700 increased myocardial pH, which had been decreased by LAD partial occlusion, by 0.26 or 0.31 pH units, respectively. In the nonischemic myocardium pH increased only 0.03 units. Drug-induced restoration of myocardial [H+] was then calculated. At a dose of 5 or 20 mg/kg NCO-700 restored myocardial [H+], which had been increased by partial occlusion. However, NCO-700 did not attenuate the ischemia-induced elevation of ST segment of the surface electrocardiogram. These observations demonstrate that NCO-700 attenuates myocardial pH depressed by partial occlusion of LAD.

Animals↗
PubMed1985

Effects of enalapril maleate (MK-421) on renovascular hypertension.

The effects of enalapril maleate (MK-421), a new angiotensin converting enzyme inhibitor, were studied on 5 patients with renovascular hypertension (RVH) due to unilateral renal artery stenosis. The therapeutic dosage was increased when the blood pressure (BP) was not controlled for more than 3 days. Blood sampling was performed before, and 5 hr and 24 hr after the first administration, and on the 3rd day with each dosage. The BP was normalized on 5 mg/day in 1 case, 10 mg in 1 case, 20 mg in 2 cases, and 40 mg plus mefruside in 1 case. Plasma renin activity (PRA) was significantly increased after 5 hr and recovered after 24 hr with 2.5 mg of the enalapril maleate, when the BP was not affected. This indicates that the increase in PRA is likely due to the reduced negative feedback of angiotensin II. When the blood pressure was lowered, PRA was increased and plasma aldosterone concentration (PAC) was decreased significantly. This rise of PRA may depend not only on the reduced negative feedback but also on the fall of BP. It is also considered that the PAC was decreased through the decrease in plasma angiotensin II. A fall of the glomerular filtration rate in one case and also a fall of the perfusion of the kidney of the stenotic side in another case were observed by radioisotope renograms. MK-421 administration was a useful treatment for RVH, and clearly normalized the BP of all the patients studied. However, there was a risk of a fall of renal function on the stenotic side due to the decrease in perfusion pressure.

Adolescent↗
PubMed1985

Effects of enalapril maleate on plasma level of inactive renin in renovascular hypertension.

Changes in plasma levels of active and inactive renin after the treatment with enalapril maleate (MK-421), a new angiotensin converting enzyme inhibitor, were studied in five patients with renovascular hypertension (RVH) due to unilateral renal artery stenosis. The dosage was increased when the blood pressure (BP) was not normalized for more than 3 days. Blood sampling was performed before, and 5 hours and 24 hours after the first administration, and on the 3rd day with each dosage. Active and inactive renin concentrations (ARC and IRC) showed a reciprocal change in 4 cases, 5 hours after the first dose. In the chronic treatment, ARC and IRC before the morning dose did not change apparently until the BP was normalized, when both ARC and IRC were evidently increased. It was suspected that a conversion from inactive to active renin may occur in the patients with RVH, when the active renin secretion is stimulated suddenly by the first dose of MK-421. The chronically diminished perfusion pressure in the kidney may stimulate the secretion of inactive renin, but the decrease in endogenous angiotensin II may not.

Adolescent↗
PubMed1985

Myoastrocytes in vitreous membrane in nontraumatic giant retinal tear.

Ten cases with giant retinal tear and subsequent tractional retinal detachment were classified into three groups; 6 cases with nontraumatic origin, 2 cases due to blunt trauma and 2 cases due to posterior penetrating trauma. Open sky vitrectomy was performed and a total of 42 specimens of vitreous membranes were removed during surgery. The vitreous membranes of each group were studied by electron microscopy and the cellular elements were compared among these groups. In all three groups, five types of cells were observed, ie, retinal pigment epithelial cells, macrophages, fibroblasts, myofibroblasts and astrocytes. However, only in nontraumatic cases were found cells of another type which contained both glial filaments with the diameter of 9 nm and actin-like filaments with the diameter of 4 nm in their cytoplasm; they were called myoastrocytes from their cytoplasmic characteristics. Other cytoplasmic elements of the myoastrocytes were deeply indented nuclei, endoplasmic reticulum and pseudopodia with large cytoplasm. The myoastrocytes were considered to contribute to the contraction of the proliferative membrane in the eye with nontraumatic retinal tear, as the myofibroblasts do in the eye with traumatic retinal tears.

Adolescent↗