PubMed Health⌕ Search

Biomedical subjects

S Iguchi

Publications and source records attributed to S Iguchi.

At least 55 records · Page 3Linked to original sources

Effect of a prostacyclin analog OP-2507 on acute ischemic cerebral edema in cats.

We evaluated the inhibitory activity of a novel prostacyclin analog, OP-2507 (15-cis-(4-n-propylcyclohexyl)-16,17,18,19,20-pentanor-9-deo xy-6,9 alpha- nitriloprostaglandin F1 methyl ester) on the brain edema induced by occlusion of the middle cerebral artery in cats. Middle cerebral artery occlusion for 4h caused a decrease of regional cerebral blood flow. The specific gravity of the cerebral cortex measured 4h after the middle cerebral artery occlusion as an index of cerebral edema showed a significant reduction. Intravenous infusion of OP-2507 at infusion rates of 10 and 50 ng/kg per min was started 30 min before the middle cerebral artery occlusion and was continued for 4.5 h. While OP-2507 did not affect the blood pressure, heart rate and regional cerebral blood flow before and after the middle cerebral artery occlusion, the reduction of the specific gravity of cerebral cortex was significantly prevented by OP-2507 treatment at both doses. Prostacyclin prevented the reduction of the specific gravity only at the higher dose of 50 ng/kg per min. The present results indicate the potential usefulness of OP-2507 in acute ischemic cerebral disorders.

Animals↗

A murine monoclonal anti-metallothionein autoantibody recognizes a chemically synthesized amino-terminal heptapeptide common to various animal metallothioneins.

A murine hybridoma clone (MT 189-14-7) producing an IgM-class monoclonal antibody specific for metallothionein (MT) was produced with rat Zn-MT 2-keyhole limpet hemocyanin conjugate as an immunogen. The reactivity of the monoclonal antibody with MTs obtained from various animal species was determined by the competitive radioimmunoassay. The MT 189-14-7 antibody bound equally to various MTs 1 and 2 including mouse MTs 1 and 2. This indicates that the antibody is a murine autoantibody reactive with various animal MTs and recognizes a common structure of the various MTs. Subsequently, the location of the antigenic determinant recognized by the MT 189-14-7 antibody was determined by using various synthetic human MT 2 peptides. Among the synthetic peptides examined, both the amino-terminal beta-domain, Ac-(hMT 2 1-29)-OH, and an amino-terminal heptapeptide, Ac-(hMT 2 1-7)-OH, but not the carboxy-terminal alpha-domain peptides, H-(hMT 2 29-35)-OH and H-(hMT 2 30-61)-OH, showed inhibitory activities slightly higher than the native MTs in the competitive radioimmunoassay. These results demonstrate that the MT 189-14-7 autoantibody recognizes the epitope located within the amino-terminal heptapeptide common to various MTs.

Animals↗

High concentration of pancreatic metallothionein in normal mice.

An elution profile of supernatant of normal mouse pancreas on a Sephadex G-75 column showed a high peak of zinc in the metallothionein fraction. Cd was added to the supernatant of the mouse pancreas, and 2 cadmium binding proteins were purified by gel filtration and DEAE chromatography. Absorption spectrum and amino acid compositions of the purified proteins agreed with those of MT-I and -II. The concentration of metallothionein in the mouse pancreas was high (227 +/- 11 micrograms/g on 36th day after the birth). The metallothionein concentration in the mouse pancreas was increased by injections of zinc, alloxan or streptozotocin. The results indicate that metallothionein is one of the main zinc-binding components in mouse pancreas.

Alloxan↗

Amino acids and peptides. XVIII. Dipeptide formation during the synthesis of Z-Asp(OBzl)-OH.

During the benzyloxycarbonylation of H-Asp(OBzl)-OH by the Schotten-Bauman reaction with benzyloxycarbonyl chloride in the presence of NaHCO3 or Na2CO3, besides Z-Asp(OBzl)-OH, Z-Asp(OBzl)-Asp(OBzl)-OH was formed as side product, although the extent of the dipeptide formation differed depending on the base used (10% and 20% respectively). It was found that melting point, rotation value and Rf values upon thin-layer chromatography of Z-Asp(OBzl)-Asp(OBzl)-OH were quite similar to those of Z-Asp(OBzl)-OH.

Amino Acids↗

Carbocyclic inosine as a potent anti-leishmanial agent: the metabolism and selective cytotoxic effects of carbocyclic inosine in promastigotes of Leishmania tropica and Leishmania donovani.

Carbocyclic inosine is a potent inhibitor for the growth of the promastigote form of Leishmania tropica and Leishmania donovani. In culture, the EC50 values of carbocyclic inosine are 8.3 X 10(-8) and 1.3 X 10(-7) M for the promastigotes of L. tropica and L. donovani, respectively. On the other hand, it is less toxic towards mouse mammary tumor FM3A cells: the EC50 value is 2.7 X 10(-4) M. Carbocyclic inosine is metabolized by Leishmania promastigotes to give carbocyclic adenosine-5'-triphosphate (aristeromycin-5'-triphosphate) and carbocyclic guanosine-5'-triphosphate. This metabolic conversion provides a mechanism for the parasite-selective toxicity of carbocyclic inosine.

Adenosine↗

Stereospecific conversion of prostaglandin D2 to (5Z,13E)-(15S)-9 alpha-11 beta,15-trihydroxyprosta-5,13-dien-1-oic acid (9 alpha,11 beta-prostaglandin F2) and of prostaglandin H2 to prostaglandin F2 alpha by bovine lung prostaglandin F synthase.

A prostaglandin F (PGF) synthase was recently purified from bovine lung that catalyzed the reduction of both PGH2 and PGD2 but at different active sites on the enzyme. In view of the recent finding that PGD2 is stereospecifically reduced to a unique biologically active compound, (5Z, 13E)-(15S)-9 alpha, 11 beta, 15-trihydroxyprosta-5,13-dien-1-oic acid (9 alpha,11 beta-PGF2 or 11-epi-PGF2 alpha), by a human liver cytosolic enzyme, detailed characterization of the products formed from PGH2 and PGD2 by the bovine lung PGF synthase was carried out. Chromatographic characteristics of the products formed and stereochemical analysis procedures using mass spectrometry indicated that the enzyme stereospecifically reduces PGH2 to PGF2 alpha, whereas PGD2 is stereospecifically converted to 9 alpha,11 beta-PGF2. The finding that this enzyme catalyzes the formation of both C-11 hydroxy epimers of PGF2, albeit from different substrates, is of interest in that these two compounds may exert different biological actions.

Animals↗

Product inhibition of aminopyrine N-demethylation in isolated hepatocytes.

The product inhibition of aminopyrine (AM) N-demethylation by 4-monomethylaminoantipyrine (MAA) was examined in vitro in preparations of isolated rat hepatocytes using gas chromatograph-mass spectrometer (GC-MS). The kinetic study for AM N-demethylation, which was determined by MAA formation, was studied at concentrations from 0.2 to 4.0 mM with or without various concentrations of D3-MAA. D3-MAA inhibited AM N-demethylation non-competitively at concentrations of 0.2 to 1.0 mM of AM (Ki = 0.81 mM), though it did competitively at concentrations of 1.0 to 4.0 mM of AM (Ki = 0.81 mM). From the present observation, it was suggested that the inhibition type of AM N-demethylation by D3-MAA was dependent on the substrate (AM) concentration.

Aminopyrine↗

Tissue distribution of hydrazine and its metabolites in rats.

The tissue distribution and the urinary excretion of hydrazines, hydrazine, acetylhydrazine and 1,2-diacetylhydrazine, were determined by mass fragmentography using a gas chromatography-mass spectrometer equipped with a multiple ion detector-peak matcher. Using the compounds labeled with a stable isotope as an internal standard, namely the isotope dilution method, made it possible to estimate trace amounts of hydrazine and its metabolites in the tissues. Significantly high levels of all hydrazines were detected in the kidney. Especially, acetylhydrazine, a metabolite of hydrazine, accumulated to a great extent in the kidney. Free hydrazine which was liberated from acetylhydrazine was detected both in the tissues and in the urine after the administration of acetylhydrazine. This demonstrates clearly that the metabolic pathway between hydrazine and acetylhydrazine is reversible.

Acetylation↗

Biohydroxylation of aminopyrine: quantitative studies of 3-hydroxymethyl metabolite in rats.

Significance of the formation of 4-dimethylamino-3-hydroxymethyl-2-methyl-1-phenyl-3-pyrazolin-5-on e (AM-3-CH2OH) for the metabolism of AM was examined quantitatively in rats. Although urinary excretion of AM-3-CH2OH accounted for only 0.7% to the dose, incubation of AM in the isolated hepatocyte system resulted in the formation of 9% of AM-3-CH2OH. Furthermore, metabolic disappearance of AM-3-CH2OH in the same system was fast, indicating the properties of an intermediate metabolite. These results suggested that the metabolic pathways via AM-3-CH2OH are very important in the metabolism of AM.

Aminopyrine↗