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Biomedical subjects

A Shinohara

Publications and source records attributed to A Shinohara.

At least 127 records · Page 7Linked to original sources
PubMed1987

Origin of leucine-enkephalin fibers and their two main afferent pathways in the bed nucleus of the stria terminalis in the rat.

The destruction of the central amygdaloid nucleus (Ce), which contains a large group of neurons with leucine-enkephalin (L-ENK)-like immunoreactivity (L-ENKI), resulted in a marked ipsilateral reduction of these fibers in the bed nucleus of the stria terminalis (BST) suggesting that L-ENKI neurons in the Ce project ipsilaterally to the BST. This was supported by the finding that injection of biotin-wheat germ agglutinin into the BST labeled many neurons in the Ce. Simultaneous staining with antiserum showed that some of these neurons are L-ENKI. The L-ENKI fibers from the Ce reach the BST via two pathways; one from the venral amygdalofugal pathway (VA), which terminate in the ventral subdivision of the BST pars lateralis (BSTL), and the other from the stria terminalis (ST), which terminates in the lateral subdivision of the BSTL, because accumulation of L-ENKI structures appeared in the axons of these two systems on the amygdaloid side, transection or destruction of the ST alone caused only a slight reduction of ENKI fibers in the lateral subdivision of the BSTL ipsilaterally and transection or destruction of VA alone markedly reduced the number of L-ENKI fibers in the ventral subdivision of the ipsilateral BSTL. Thus, the VA L-ENKI fiber system is the major source of L-ENKI fibers in the ventral subdivision, while the ST L-ENKI fiber system is a minor source of the L-ENKI fibers in the lateral subdivision. The presence of an intrinsic L-ENKI system in the BST which may innervate the lateral subdivision was also suggested.

Afferent Pathways↗
PubMed1987

Drug oxidation activities of horseradish peroxidase, myoglobin and cytochrome P-450cam reconstituted with synthetic hemes.

Drug oxidations by horseradish peroxidase (HRP), myoglobin (Mb) and cytochrome P-450cam (P-450cam) reconstituted with synthetic hemes were studied in comparison with a form of cytochrome P-450 purified from liver microsomes of polychlorinated biphenyl (PCB)-treated rats. N,N-Dimethylaniline (DMA) and 7-isopropoxycoumarin were hardly dealkylated by the heme-substituted proteins in the presence of NADPH-cytochrome c (P-450) reductase and NADPH, while substantial activity of this kind was observed in the presence of hydrogen peroxide or cumene hydroperoxide as oxygen donors. Specific activity varied, depending on the substrates, oxygen donors, heme derivatives and apoproteins employed. Very high levels of activity were observed in hydrogen peroxide-dependent DMA N-demethylation with HRP substituted with certain hemes. The highest level of activity was about two hundred times as high as that of rat liver cytochrome P-450. The relationship between such activity and the chemical structure of heme derivatives was discussed.

Cytochrome P-450 Enzyme System↗
PubMed1987

[Spontaneous occlusion of a cerebral arteriovenous malformation--report of a case].

The authors report a case of spontaneous occlusion of an arteriovenous malformation (AVM) verified by the second angiography performed 3 days after the initial one. This 65-year-old man had a sudden attack of headache, nausea, and vomiting and was admitted to our hospital next day. On admission, CT scan showed subcortical hemorrhage in the right temporo-parietal area and right CAG showed a small AVM in the same area. The main feeder was a MCA distal branch and the drainer joined Labbe's vein. Repeated angiography 3 days after initial one failed to demonstrate the AVM. Craniotomy was performed and thrombosed AVM was totally removed. Mechanism for disappearance of the malformation is assumed to be acute thrombosis due to intracranial hemorrhage and arteriosclerotic change. The literature is reviewed.

Aged↗
PubMed1986

A new assay for N-hydroxyarylamine O-acetyltransferase: reduction of N-hydroxyarylamines through N-acetoxyarylamines.

A simple fluorometric assay for N-hydroxyarylamine O-acetyltransferase is described and compared with a nucleic acid-binding assay. The assay method is based on the finding that the highly mutagenic 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-OH-Glu-P-1) was reduced to the corresponding amine, 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), through N-acetoxy-Glu-P-1 as the reactive intermediate in the presence of N-hydroxyarylamine O-acetyltransferase, acetyl-CoA, and a sulfhydryl compound. The formation of Glu-P-1 was determined by its characteristic fluorescence intensity at 445 nm with excitation wavelength at 376 nm. The reductive reaction was inhibited by the addition of tRNA, DNA, and poly(G), to which the enzymatic product, N-acetoxy Glu-P-1, bound effectively due to its electrophilic nature. Since the fluorometric assay for the O-acetyltransferase is rapid, simple, and sensitive as compared with the nucleic acid-binding method using radioisotope-labeled N-hydroxyarylamine, this method is applicable to the general assay for the formation of reactive N-acetoxy-Glu-P-1.

Acetyltransferases↗
PubMed1986

Inhibition of acetyl-coenzyme A dependent activation of N-hydroxyarylamines by phenolic compounds, pentachlorophenol and 1-nitro-2-naphthol.

Pentachlorophenol (PCP) and 1-nitro-2-naphthol were found to be potent inhibitors of enzymatic acetyl-CoA dependent activation, which is suggested as proceeding through direct O-acetylation, of N-hydroxyarylamines to tRNA binding by liver cytosolic enzymes from hamsters and rats. IC50 values of PCP for the activation of 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-OH-Glu-P-1), 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (N-OH-Trp-P-2) and N-hydroxy-2-aminofluorene (N-OH-AF) were 20, 25 and 17 microM, respectively, in hamster cytosol system. Similar inhibition was observed with rat liver cytosol (IC50 values of PCP and 1-nitro-2-naphthol were 13 and 12 microM, respectively, for the binding of N-OH-Glu-P-1). PCP is known as an inhibitor of sulfotransferase; however, another potent inhibitor of sulfotransferase, 2,6-dichloro-4-nitrophenol, did not inhibit the acetyl-CoA dependent binding. Antibiotic thiolactomycin, which inhibits bacterial O-acetyltransferase, did not affect the activation by hamster and rat cytosol, indicating the difference in property between bacterial and mammalian enzymes. The kinetic data obtained with hamster cytosol suggested the competitive inhibition of PCP with substrate, N-OH-Glu-P-1, and non-competitive inhibition with acetyl-CoA. In addition to the O-acetylation, PCP and 1-nitro-2-naphthol also inhibited N-acetylation of arylamines and N,O-acetyltransfer reaction of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) by hamster cytosol. IC50 values for these two types of acetyltransfer reactions, however, were slightly higher than those observed for acetyl-CoA dependent activations of N-hydroxyarylamines.

Acetyl Coenzyme A↗
PubMed1986

N-hydroxyarylamine O-acetyltransferase in hamster liver: identity with arylhydroxamic acid N,O-acetyltransferase and arylamine N-acetyltransferase.

N-Hydroxyarylamine O-acetyltransferase, arylhydroxamic acid N,O-acetyltransferase, and arylamine N-acetyltransferase in hamster liver cytosol were co-purified almost to electrophoretical homogeneity by ion exchange chromatography on DEAE-cellulose, gel filtration on Cellulofine GCL-2000-sf and high-performance KB-hydroxyapatite chromatography. The molecular weight of the acetyltransferase was estimated to be 33,000 by gel filtration and SDS-polyacrylamide gel electrophoresis. The three acetyltransferase activities were inhibited by iodoacetamide, pentachlorophenol, and 1-nitro-2-naphthol. Furthermore, 2-aminofluorene, a substrate for arylamine N-acetyltransferase, inhibited the reactions of N-hydroxyarylamine O-acetyl transfer and arylhydroxamic acid N,O-acetyl transfer. These results suggest that the same enzyme catalyzes the three types of acetyl transfer reactions. The acetyltransferase could activate N-hydroxyarylamines, such as 2-hydroxyamino-6-methyldipyrido[1,2-alpha:3',2'-d]imidazole, 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole, and N-hydroxy-2-aminofluorene, to the corresponding N-acetoxyarylamines, which are capable of binding to nucleic acid. Polyguanylic acid was most efficiently modified by the N-acetoxyarylamines formed by the acetyltransferase.

Acetyltransferases↗
PubMed1986

Acetyl coenzyme A dependent activation of N-hydroxy derivatives of carcinogenic arylamines: mechanism of activation, species difference, tissue distribution, and acetyl donor specificity.

Acetyl coenzyme A dependent activation of 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-OH-Glu-P-1) and 3-hydroxyamino-1-methyl-5H-pyrido [4,3-b]indole (N-OH-Trp-P-2) was investigated using cytosols from hepatic and extrahepatic tissues of various animal species in comparison with that of N-hydroxy-2-aminofluorene. N-OH-Glu-P-1 and N-OH-Trp-P-2 were metabolized to the reactive species capable of binding to transfer RNA through a putative O-acetylation process by liver cytosols. Kidney, small intestinal mucosa, lung, and bladder from hamsters and rats also mediated the reaction, although their activities were lower than that in the liver. Marked species differences in the enzymatic activities of livers were observed. Hamsters showed the highest ability in the activation for N-OH-Glu-P-1 and N-OH-Trp-P-2, followed by rats. Rabbits with a rapid acetylator phenotype, which showed a high activity in the N-acetylation of arylamines, activated N-OH-Glu-P-1 but scarcely N-OH-Trp-P-2. A rabbit with a slow acetylator phenotype, mice, guinea pigs, and a dog showed marginal or nondetectable activities with N-OH-Glu-P-1 and N-OH-Trp-P-2. A typical nonheterocyclic N-hydroxyarylamine, N-hydroxy-2-aminofluorene was also activated by the acetyl coenzyme A dependent system to an intermediate which bound to transfer RNA. However, the acetyl-CoA dependent binding of N-hydroxy-2-aminofluorene was markedly different from those observed with N-OH-Glu-P-1 and N-OH-Trp-P-2 concerning the order of activities among animal species used. In addition to short chain acyl coenzyme As, N-hydroxy-2-acetylaminofluorene also served as an acetyl donor for the activation of N-OH-Glu-P-1 and N-OH-Trp-P-2 in liver cytosol systems. The formation of N-acetyl-N-OH-Glu-P-1, however, was not detected in the cytosolic system of N-OH-Glu-P-1 with acetyl-CoA, suggesting the direct O-acetylation at the N-hydroxy group as a major pathway for the activation of N-hydroxyarylamines.

Acetyl Coenzyme A↗
PubMed1985

Metabolic activation of mutagenic N-hydroxyarylamines by O-acetyltransferase in Salmonella typhimurium TA98.

A new enzymatic activation of mutagenic N-hydroxyarylamines is described. An acetyl-CoA dependent enzyme that can activate 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-OH-Glu-P-1) to a reactive species capable of binding to nucleic acid was found in a cell-free extract of Salmonella typhimurium TA98 but not in that of TA98/1,8-DNP6, which shows low sensitivity to the mutagenic activity of N-OH-Glu-P-1. The enzyme was partially purified by streptomycin treatment, ammonium sulfate precipitation, DEAE-cellulose chromatography, and gel filtration chromatography of Sephadex G-150. Its molecular weight was estimated to be approximately 48,000. The directly mutagenic N-hydroxyarylamines, such as N-OH-Glu-P-1, 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (N-OH-Trp-P-2), and N-hydroxy-2-aminofluorene (N-OH-AF), were transformed to reactive derivatives by partially purified enzyme in the presence of acetyl-CoA. The Km value for acetyl-CoA was calculated to be 3.3 microM. No acetyl residue, however, was incorporated into nucleic acid adducts. The enzymatic product of N-OH-Glu-P-1 bound most efficiently to polyguanylic acid among four polynucleotides. The enzyme did not show the N,O-acetyltransfer activity of N-hydroxyacetylaminofluorene (N-OH-AAF). These results indicate that the enzymatic product of N-hydroxyarylamine is N-acetoxyarylamine, and that this enzyme can be called acetyl-CoA:N-hydroxyarylamine O-acetyltransferase. O-Acetyltransferase activity was inhibited by SH-blocking agents, several phenolic compounds, such as pentachlorophenol and 1-nitro-2-naphthol, and an antibiotic thiolactomycin. S. typhimurium mutation studies suggested that the O-acetyltransferase functions as an enzyme activating certain N-hydroxyarylamines within bacterial cells and is involved in the formation of mutants.

Acetyltransferases↗
PubMed1985

Delayed intracerebral hemorrhage after ventriculoperitoneal shunt.

A serious intracerebral hemorrhage occurred as a result of a measurement for grip power performed on the 7th postoperative day of a ventriculoperitoneal shunt. This type of delayed intracerebral hemorrhage after the placement of a ventriculoperitoneal shunt has not been described in the literature. The increased intracranial venous pressure produced by Valsalva's effect induced this complication, which is also considered to be the same mechanism as traumatic delayed intracerebral hemorrhage.

Adolescent↗
PubMed1985

DNA binding of N-hydroxy-Trp-P-2 and N-hydroxy-Glu-P-1 by acetyl-CoA dependent enzyme in mammalian liver cytosol.

3-Hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole and 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole, active metabolites of protein pyrolysate carcinogens, were further activated to DNA-binding species by an acetyl-CoA dependent enzyme in hepatic cytosol. This activity was supported also by N-hydroxy-2-acetylaminofluorene instead of acetyl-CoA, and it was inhibited by iodoacetamide and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) but not by diethyl-p-nitrophenylphosphate. The activity was observed in the cytosols of rats, mice and rapid acetylator rabbits, which possessed N-acetylation activity of 2-aminofluorene and Trp-P-2. On the other hand, the activity could not be detected in the cytosols of a dog and a slow acetylator rabbit.

Acetyl Coenzyme A↗
PubMed1985

Catalysis of the covalent binding of 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole to DNA by a L-proline- and adenosine triphosphate-dependent enzyme in rat hepatic cytosol.

An enzymatic mechanism involved in the activation of 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (N-hydroxy-Trp-P-2), a mutagenic intermediate of a tryptophan pyrolysate, was studied in vitro. In hepatic cytosol supplemented with adenosine triphosphate and L-proline, N-hydroxy-Trp-P-2 was converted to a form which reacts readily with DNA. The enzyme responsible for the activation was partially purified and identified as prolyl transfer RNA synthetase as judged by their cofactor requirements, inhibition by pyrophosphate or adenosine monophosphate, and copurification of their activities. The prolyl transfer RNA-dependent covalent binding of N-hydroxy-Trp-P-2 to DNA of hepatic cytosol was highest in rats, followed by mice, hamsters, rabbits, and guinea pigs in that order. The capacity for the binding of N-hydroxy-Trp-P-2 was largely consistent with their prolyl transfer RNA synthetase activity. With regard to the ultimate form of N-hydroxy-Trp-P-2 for the covalent binding, a possible formation of N,O-prolyl-3-amino-1-methyl-5H-pyrido[4,3-b]indole was proposed.

Adenosine Triphosphate↗