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Biomedical subjects

T Higuchi

Publications and source records attributed to T Higuchi.

At least 415 records · Page 23Linked to original sources
PubMed1994

Stereoselective inhibition of carbonyl reductase from rabbit kidney by enantiomers of carprofen.

The inhibitory effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the reduction of acetohexamide catalyzed by carbonyl reductase from rabbit kidney were examined. Of NSAIDs tested, only carprofen exhibited a pronounced stereoselectivity for the inhibition of the purified enzyme; (-)-carprofen inhibited more strongly the enzyme than three fold of its (+)-form. (-)-Carprofen was found to inhibit the enzyme noncompetitively with respect to acetohexamide and competitively with respect to NADPH. Similar modes were observed for the inhibition of the enzyme by (+)-carprofen. The treatment of the apoenzyme with (-)-carprofen led to a time- and concentration-dependent loss of the catalytic activity. Furthermore, NADP+ afforded a significant protection against inactivation of the enzyme by (-)-carprofen. These results suggest that enantiomers of carprofen bind to coenzyme-binding domain of the enzyme and cause the stereoselective inhibition of acetohexamide reduction by competing with NADPH.

Alcohol Oxidoreductases↗
PubMed1994

[Cytological features and prognosis of megakaryoblastic leukemia].

Nine patients with acute leukemia showing 10% or more positive blast cells with platelet peroxidase (PPO) or CD41b were diagnosed as megakaryoblastic leukemia. Three patients transformed from myelodysplastic syndromes or myeloproliferative disorders. The PPO positivity ranged from 7 to 55% (median 45%), and that for CD41b was 1.6 to 67.0% (median 16.4%). Because electron microscopic myeloperoxidase or glycophorin A were also positive in some patients, and also because CD41b positivity was often discordantly lower than PPO positivity, a possibility of mixed leukemia demonstrating myeloid or erythroid differentiation was suggested in 6 of these cases. As for the treatment results, all 3 pediatric cases who received combination chemotherapy achieved complete remission (CR). Among 6 adult cases CR was obtained in only one patient to whom low-dose cytosine arabinoside was administered. The remaining adult patients who received combination chemotherapy died relatively early.

Adult↗
PubMed1993

Kinetic studies on the reduction of acetohexamide catalyzed by carbonyl reductase from rabbit kidney.

The kinetic mechanism for the reduction of acetohexamide catalyzed by carbonyl reductase from rabbit kidney was investigated. The initial velocity and product inhibition studies indicated that the enzymatic reaction follows an ordered Bi Bi mechanism, in which NADPH binds to the enzyme first and NADP leaves last. This kinetic mechanism was confirmed on the basis of the dead-end inhibition by Cibacron Blue and the binding of NADPH and NADP to the free enzyme. However, whether or not coenzyme-induced isomerization is involved in the enzymatic reaction remains to be clarified. In kinetic studies of inhibition of the enzyme by therapeutically active drugs, indomethacin and befunolol were found to be noncompetitive and competitive inhibitors, respectively, with respect to acetohexamide.

Acetohexamide↗
PubMed1993

[Breath hold MR cholangio-pancreatography (MRCP) using long echo train length fast spin echo sequence in combination with surface coil].

To test the feasibility of MR cholangio-pancreatography (MRCP) using long echo train length (32) fast spin echo sequence in combination with shoulder surface coil, 20 patients who had had ERCP were examined. Good correlations were acquired between the findings obtained by two modalities in terms of ductal strictures, dilatations and intraductal lesions. MRCP was considered to be an examination of choice in various kinds of pathologies affecting biliary duct as well as pancreatic duct for its non-invasiveness and reasonable image quality.

Adult↗
PubMed1993

Unusual substituent effects in the hydroxylation of phenols by a Cu(2+)-ascorbic acid-O2 system, gamma-radiolysis, and microsomes.

Aromatic ring hydroxylation of phenolic compounds proceeded selectively in a Cu(2+)-ascorbic acid-O2 system. In contrast to usual oxidation systems, unusual substituent effects were observed: electron-withdrawing groups accelerate and electron-donating groups retard the hydroxylation. Hydroxyl radicals generated by gamma-radiolysis also converted phenols into catechols and hydroquinones. The close resemblance of these two systems led us to presume that the active intermediate in the Cu(2+)-ascorbic acid-O2 system is hydroxyl radical or an equivalent species. The unusual substituent effects were also observed in the hydroxylation of p-substituted phenol by microsomes, a cytochrome P-450-dependent reaction. These results imply that the Cu(2+)-ascorbic acid-O2 system is an effective biomimetic oxidation system.

Animals↗
PubMed1993

Purification and properties of carbonyl reductase from rabbit kidney.

An enzyme catalyzing the metabolic reduction of acetohexamide, an oral antidiabetic drug, has been purified from the cytosolic fraction of rabbit kidney to apparent homogeneity by various chromatographic techniques. The purified enzyme consists of a single polypeptide chain with a molecular weight of 28,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme requires NADPH as a cofactor and has an optimal pH of 6.0. A variety of xenobiotic carbonyl compounds including acetohexamide are effectively reduced by the enzyme. Flavonoids (quercetin and quercitrin) are potent inhibitors for the enzyme, but pyrazole or barbiturates have little effect on the enzyme activity. These findings clearly indicate that the enzyme can be classified as one of the carbonyl reductases. The enzyme also shows both prostaglandin 9-ketoreductase and 3 alpha-hydroxysteroid dehydrogenase activities. Judging from the Kcat/Km values of the enzyme for 4-pyridylketones with a straight-chain alkyl group, a hydrophobic pocket that binds most strongly to a straight-chain alkyl group of five carbon atoms in length appears to be located in the substrate-binding region of the enzyme.

Alcohol Oxidoreductases↗
PubMed1993

CCK-8 excites oxytocin-secreting neurons in the paraventricular nucleus in rats--possible involvement of noradrenergic pathway.

Systemic administration of CCK-8 increased plasma oxytocin (OXT) level in rats anesthetized with a mixture of urethane and alpha-chloralose. Extracellular recordings were made from magnocellular neurosecretory neurons in the paraventricular nucleus (PVN) of the hypothalamus in anesthetized rats to examine the effects of CCK-8 on the firing of PVN neurons. Thirteen out of 16 nonphasic neurons (putative OXT-secreting neurons) were excited by intravenous and/or intraperitoneal administration of CCK-8. By contrast, 8 out of 10 phasic cells, vasopressin(AVP)-secreting cells, were inhibited by systemic administration of CCK-8. Four out of five nonneurosecretory neurons in the PVN were excited by the administration of CCK-8. Moreover, microiontophoretically applied phentolamine blocked the excitatory responses induced by CCK-8 in nonphasic neurons. We measured extracellular noradrenaline (NA) level in the PVN, using in vivo microdialysis. Intravenous administration of CCK-8 induced NA release in the PVN. These results suggest that CCK-8 activates the excitatory afferent pathway to putative OXT-secreting neurons in the PVN which may, at least in part, be involved in the central noradrenergic projection.

Adrenergic Antagonists↗
PubMed1993

Purification and partial sequences of Aralia cordata cinnamyl alcohol dehydrogenase.

Cinnamyl alcohol dehydrogenase (CAD) (EC 1.1.1.195) from a dicot, Aralia cordata, was purified to homogeneity and its properties were characterized. The enzyme shows a preference for cinnamyl alcohols and cinnamyl aldehydes as substrates. The M(r) is estimated at 72,000. The enzyme is composed of two heterogeneous subunits of slightly different sizes, and it differs from the bean enzyme in the size of subunits. Partial amino acid sequencing of the purified enzyme was carried out both from the N-terminus and using selected peptides obtained by cyanogen bromide cleavage.

Alcohol Oxidoreductases↗
PubMed1993

An autopsy case of suicide by hanging with multiple stab wounds of the neck and chest.

We report, from the aspect of 'acting' capability, an autopsy case of suicide by hanging in which multiple deep stab wounds were observed in the neck and chest. A 49-year-old man was found dead in a state typical of hanging. His car was found about 100m away with a blood-stained climber's knife on the seat. Multiple incised and stab wounds were in the neck, with a lesion of the right inner jugular vein. Three penetrating stab wounds of the chest punctured the lungs, with pooling of about 500ml of blood in the left thorax and about 100ml in the right. Two other shallow stab wounds were in the chest. All the above wounds were explainable as self-inflicted. From the autopsy findings and the circumstantial evidence, it was concluded that he walked approximately 100m after stabbing his neck and chest and finally committed suicide by hanging.

Airway Obstruction↗
PubMed1993

Ring fracture of the base of the skull and atlanto-occipital avulsion due to anteroflexion on motorcycle riders in a head-on collision accident.

This report concerns a head-on collision accident of a motorcycle at a very high speed (c. 80-100 Km/h) against a bonnet-type automobile, in which both the motorcyclist and pillion rider were injured at the base of the skull by violent anteroflexion of the head due to the force of inertia. A difference in their injuries was: the motorcyclist sustained a 'ring' fracture and the pillion rider an atlanto-occipital avulsion; dural tear. Anteroflexion without impact on the occiput such as described above seems to be a rare causal mechanism of the 'ring' fracture. In addition, the mode of action of the accelerating forces to the heads of the victims along with their physiques may explain the mechanism which caused the different injuries in this accident.

Accidents, Traffic↗
PubMed1993

Antibody responses of Japanese horses to influenza viruses in the past few years.

A total of 305 horse sera collected in the Hidaka district of Hokkaido in the years 1988-90 were tested for the presence of hemagglutination-inhibition (HI) antibodies to A/equine/Newmarket/1/77 (H7N7), A/equine/Tokyo/2/71 (H3N8) and A/equine/Kentucky/1/81 (H3N8, Kentucky) strains of equine influenza (EI) virus. Antibodies to the 3 strains were detected in hardly of the 45 sera from 2-years-old horses which were collected before vaccination. Many of the 51 horses, after vaccination with inactivated EI virus, had HI antibodies to the 3 strains in 37 to 88 per cent. However, the number of positive reactors among the horses aged 3 to 23 years gradually decreased with the advance in age. In particular, no antibody response was found in the 60 horses over 9 years of age, except for 3 cases with HI antibody of low titer, with the Kentucky strain which has recently been prevalent among the horse populations in many countries. In a complement-fixing test, antibodies to the soluble antigen of type A influenza virus were detected in the sera collected from the horses which were exposed to an outbreak of EI virus infection, but not in the sera from the vaccinated horses examined.

Age Factors↗
PubMed1993

Evaluation of exercise intensity indicated by serum lactate dehydrogenase activity in healthy adults.

Noting relationship between exercise and serum LDH and alpha-HBD activities, we prescribed 3 exercise regimens of various intensities for 22 healthy adult subjects over predetermined periods. Variations in the serum enzyme activities were determined in relation to these exercise programs. We studied whether these enzyme levels may serve as new indices to evaluate the amount of exercise. The test subjects were divided into 3 groups to perform 3 types of exercise (30%, 50%, 70% of VO2max) for 6 weeks. The serum enzyme activities at the start and completion of the experiment were determined and compared. The results obtained were as follows: A rise in the serum LDH activity was noted in association with exercise. The mean increases for these groups were 10.2%, 7.5% and 23.5%. A statistically significant decrease in the serum alpha-HBD activity was noted in association with exercise. It has been suggested that by observing variations in these enzyme levels in normal individuals for an extended period, change in the intensity of physical exertion within the range of daily activities can be estimated.

Adult↗
PubMed1993

Chemical modification of histidine residue in substrate-binding domain of carbonyl reductase from rabbit kidney.

Carbonyl reductase from rabbit kidney was rapidly inactivated by diethylpyrocarbonate (DEPC). A similar inactivation was observed in photooxidation of the enzyme by methylene blue. The inactivation by DEPC was time- and concentration-dependent and followed pseudo-first-order kinetics. The results obtained from the inactivation kinetics and the protective effect of 4-acetylpyridine (4-AP) with NADP+ against the inactivation led to the idea that one essential amino acid is located in substrate-binding domain of the enzyme. The treatment of the enzyme with DEPC formed N-carbethoxyhistidine. Judging from the effect of 4-AP with NADP+ on the formation of N-carbethoxyhistidine, it is concluded that one histidine residue is located in substrate-binding domain of the enzyme. Furthermore, whether one essential amino acid inactivated by DEPC corresponds to one histidine residue modified with DEPC is discussed.

Alcohol Oxidoreductases↗
PubMed1993

Cuproproteins of hepatocyte lysosomes in normal and fatty liver.

The pathophysiological significance of cuproproteins in hepatocyte lysosomes was studied in 7 patients with structurally normal livers and 13 patients with fatty livers by energy-dispersion X-ray microanalysis. In most patients, in both groups, copper and sulfur coexisted in hepatocyte lysosomes. The correlation between copper and sulfur indicated that copper transfer between the cytosol and lysosomes was mediated by a cuproprotein. The copper indices of the lysosomal proteins and transfer proteins were high in some fatty livers. These observations suggest that cuproproteins in hepatocytes are not necessarily pathological, but are present in greater amounts in some fatty livers, probably because of impaired bile drainage.

Adult↗
PubMed1993

[RAEB transformed into AML (M0) showing Ph1 chromosome and rearrangement of major cluster region].

A 78 year old female was found to have pancytopenia in February 1991. Bone marrow was normocellular with 11.7% blasts and showed dysmegakaryopoietic changes. A diagnosis of MDS (RAEB) was made and she was treated with transfusions and ubenimex. Leukemic transformation was noted in July. On Admission in October 1991, her laboratory examinations revealed the following: WBC 38,900/microliters with 93% blast, Hb 8.0 g/dl, Plt 2.1 x 10(4)/microliters, a hypercellular bone marrow with 74% blasts which were negative for myeloperoxidase (MPO) by light microscopy, but were positive by electron microscopy. Surface marker for CD13 was positive. These findings corresponded to M0 of the FAB subtype. Chromosome analysis revealed Ph1 chromosome with 46XX, t (9;22) (q34;q11) in 3 of 3 cells examined, Southern analysis showed the rearrangement of the break point cluster region (bcr). Reverse transcriptase polymerase chain reaction technique demonstrated the presence of major bcr/abl mRNA. She was treated with transfusions and methyl-prednisolone. Her blast counts declined and Ph1 chromosome was only positive in 1 of 12 metaphases examined. She died of pneumonia in December 1991. Eleven cases with MDS showing Ph1 chromosome have previously been reported. The observations indicate that Ph1 chromosome positive acute leukemias were heterogenous in nature.

Aged↗