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Volume 108, Issue 4
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Kazuo OHUCHI1988 Volume 108 Issue 4 Pages 251-270
Published: April 25, 1988
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSChemical mediators of inflammation, responsible for vascular permeability increasing activity, were analyzed in inflammation models of air pouch type in rats. By use of carrageenin-induced air pouch model, prostaglandin (PG) E2 was found to be an important chemical mediator for vascular permeability response in the acute exudative stage but not in the chronic proliferative stage of inflammation. Vascular permeability response at the chronic proliferative stage was suppressed by the steroidal anti-inflammatory drugs but not by cyclooxygenase inhibitors, suggesting that the steroidal anti-inflammatory drugs are more potent than the cyclooxygenase inhibitors. To get further insight into the mechanism of allergic inflammation, an allergic inflammation model of air pouch type in rats was established by using azobenzene arsonate-conjugated acetyl bovine serum albumin as an antigen. The anaphylactic increase in vascular permeability was found to be substantially mediated by histamine and serotonin although the contents of slow reacting substance (SRS), lyso-form of platelet activating factor (PAF) were high in the pouch fluid in this phase. The possibility of participation of SRS, PG and PAF was found to be remote. β-Agonists were found to suppress the anaphylactic increase of vascular permeability without inhibiting mast cell degranulation. They exert their effects by inhibiting the reactivity of local vasculature to chemical mediators released from mast cells. A model for recurrent allergic inflammation was developed in order to clarify chemical mediators in chronic diseases such as rheumatoid arthritis. Five days after the 1st antigenic challenge, the antigen solution was again injected into a granulation tissue capsule holding around 10 ml of exudate. The role of PGE2 in vascular permeability responses in both types of allergic inflammation was examined to show that there exists a certain phase where PGE2 has no significant role in vascular permeability responses. Characterization of chemical mediators in that phase remains to be elucidated. Tumor promoters in two-stage carcinogenesis model in mouse skin, whether 12-O-tetradecanoylphorbol 13-acetate (TPA) type or non-TPA type, were found to have a very potent stimulating activity on arachidonic acid metabolism in rat peritoneal macrophages. Chemical mediators responsible for the tumor promoter-induced inflammation were identified as histamine, serotonin and PGE2. The role of the inflammatory reactions inducible by these promoters for the tumor promotion process also remains to be elucidated.View full abstractDownload PDF (2068K) -
MASAHITO OCHIAI1988 Volume 108 Issue 4 Pages 271-295
Published: April 25, 1988
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSLewis acid-activated iodosylbenzene reacts readily with a variety of organosilicon and tin compounds to produce hypervalent organoiodine (III) species. Allyl- and vinyliodine (III) compounds act as highly reactive species equivalent to allyl and vinyl cations. Tandem Michael-carbene insertion reaction of alkynyliodine (III) compounds offers an efficient procedure for the synthesis of highly functionalized cyclopentenes. Intramolecular hypervalent Sn-O interaction makes possible the fixation of 6-membered carbocycles to the 1, 3-diaxial conformer and the highly stereoselective osmylation of olefins. Synthesis of functionalized olefins utilizing an oxidative 1, 4-fragmentation of γ-stannyl alcohols and a β-elimination of silyl and stannyl organosulfur compounds is also described.View full abstractDownload PDF (1488K) -
SHIGEYUKI KITAMURA1988 Volume 108 Issue 4 Pages 296-309
Published: April 25, 1988
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSMicrosomes of guinea pig liver exhibited sulfoxide reductase activity in the presence of a small amount of cytosol. The microsomal sulfoxide reductase was composed of microsomal reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase and cytosolic aldehyde oxidase. This reductase system also catalyzed the reduction of N-oxide compounds. Reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase, lipoamide dehydrogenase, xanthine oxidase and xanthine dehydrogenase also exhibited sulfoxide or N-oxide reductase activity when combined with aldehyde oxidase. Liver aldehyde oxidase alone can play an important role in the reduction of sulfoxides, N-oxides, azo dyes, nitrosmaines, nitropolycylic aromatic hydrocarbons and hydroxamic acids in the presence of its own electron donor. On the basis of these facts, a new electron transfer system consisting of aldehyde oxidase and other flavoenzymes is proposed.View full abstractDownload PDF (1317K) -
KEISHIN HONMA, YOSHIO SAITOU, YOUICHI ISHIKAWA1988 Volume 108 Issue 4 Pages 310-316
Published: April 25, 1988
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSIn order to elucidate the antigenicity-producing structure of aspirin and its related compounds, investigation was performed with the enzyme immunoassay (EIA) and multiple regression analysis. For the examination of the antigenic determinant of aspirin, the serum from patients with aspirin allergy was studied with EIA. As for the cross reactivity with salicylic related compounds, multiple regression analysis was made for the electron localization of salicylic acid, obtaining the following results : 1. Among the regional structures of aspirin, the salicyloyl participates in acting as the antigenic determinant, but the antigenicity of the acetyl is not recognized. 2. The antigenicity of hapten-carrier binding site reported by Haukins was not recognized clinically. 3. The cross reactivity between anti-aspirin antibody and salicylic-related compounds is dependent on the frontier electron density in the two lowest unoccupied molecular orbital of carbonyl carbon (fr(N)), and the ratio of superdelocalizability of carbons in ortho-and meta-position (Sr(N)o-c/Sr(N)m-c).View full abstractDownload PDF (760K) -
KAZUMI MORIKAWA, MASAMITSU HONDA, KO-ICHI ENDOH, TOMOKO MATSUMOTO, KEN ...1988 Volume 108 Issue 4 Pages 317-324
Published: April 25, 1988
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSPlatinum complexes of 2-aminoalkylpyridine as a carrier ligand were synthesized and evaluated for antitumor activities against P388 leukemia in mice. Among the analogues, (2-aminomethylpyridine)oxalatoplatinum (II) (X1), (2-aminomethylpyridine)malonatoplatinum (II) (X2), (2-aminomethylpyridine)(1, 1-cyclobutanedicarboxylato)platinum (II) (X3), (2-(1-aminoethyl)pyridine)oxalatoplatinum (II) (X12) and (2-(1-aminopropyl)pyridine)oxalatoplatinum (II) (X17) exhibited excellent activity and were comparable to cis-diamminedichloroplatinum (II) and superior to (1, 1-cyclobutanedicarboxylato)diammineplatinum (II). Structure-activity relationships are discussed.View full abstractDownload PDF (713K) -
MATAICHI SAGI, YOSHIO NAKAGAWA, MICHINAO MIIZUGAKI, HIROSHI YAMANAKA, ...1988 Volume 108 Issue 4 Pages 325-330
Published: April 25, 1988
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSIn order to estimate the generality of the chain elongation reaction observed on the metabolism of fusaric acid (5-butylpyridine-2-carboxylic acid) in rat liver, the metabolism of the following heteroaromatic carboxylic acids, 5-alkylpyrimidine-2-carboxylic acid (3a-d), 2-alkylpyrimidine-5-carboxylic acid (4a-d), 6-pentylpyridazine-3-carboxylic acid (5), and 5-pentylpyrazine-2-carboxylic acid (6), was investigated. Although 4a-d, 5, and 6 did not undergo the chain elongation, in the metabolites of 3a-d collected from the rat urine, pyrimidine-2-propionic acids, pyrimidine-2-acrylic acids, pyrimidine-2-(3-hydroxypropionic)acids, and pyrimidine-2-(3-oxopropionic)acids were detected together with the ω-oxidation products by gas chromatography-mass spectrometry technique. This is a rare example of chain elongation in drug matabolism as well as the case of 5-alkylpyridine-2-carboxylic acids.View full abstractDownload PDF (529K) -
RYOKI TAKAHASHI1988 Volume 108 Issue 4 Pages 331-338
Published: April 25, 1988
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSNew affinity chromatographic solid supports were developed to obtain a high quality of urokinase (UK) preparation. The supports used 6-aminocaproic acid (6-ACA) as a spacer and p-aminobenzamidine (p-AB) as a ligand which were used by Holmberg et al. But the supports were prepared by verying the amount ratio of p-AB/6-ACA were covalently bound to Sepharose CL-6B. The optimum molar ratio of p-AB/6-ACA was found to be approximately 0.3 for the adsorption and desorption of UK. By the single purification step with this affinity chromatographic support, highly purified (116000-85000 IU/mg protein) and pyrogen free UK was successfully obtained from a crude preparation (3300 IU/mg protein) with a recovery of 86%. The activity ratio of high molecular weight UK (HUK)/low molecular weight UK (LUK) was found to be about 4.3.View full abstractDownload PDF (712K) -
WATARU OHTANI, AKIMASA OHMIZU, AKINORI SUMI, TAKAO OHMURA, YAHIRO UEMU ...1988 Volume 108 Issue 4 Pages 339-344
Published: April 25, 1988
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSWe have developed an enzyme-linked immunosorbent assay (ELISA) method for the detection of contaminating yeast components in the hepatitis B surface antigen (HBsAg) which was produced using yeast (Saccharomyces cerevisiae) by gene technology. This method could detect 1 ng/ml of the yeast component mixture. By using this method, we found that average remaining amounts of the yeast component mixture in specimens of recombinant HBsAg manufactured in an industrial real were not more than 0.52%, which was verified by the sodiumdodecylsulfate-polyacrylamide gel electrophoretic method. Next, we have developed an ELISA method for the assay of anti-yeast component antibody and analyzed changes of the antibody level in guinea-pig and human sera after vaccination with recombinant hapatitis B vaccine. Maximum doses given to guinea-pigs and humans were 100 and 20 μg per individual, respectively. As a result, anti-HBs antibody level in guinea-pig and human sera increased after vaccination, but no change was observed in anti-yeast component antibody level.View full abstractDownload PDF (748K) -
YORISHIGE IMAMURA, HIROYUKI MORI, MASAKI OTAGIRI1988 Volume 108 Issue 4 Pages 345-349
Published: April 25, 1988
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSThe effect of probenecid on the plasma concentration and tissue distribution of sulfadimethoxine (SDM) was examined by using fast and slow acetylator rabbits. The intravenously co-administered probenecid significantly increased the tissue distribution of SDM in fast acetylator rabbits, resulting in the reduction of plasma concentration of SDM. On the other hand, the intravenously co-administered probenecid had no effect on the plasma concentration and tissue distribution of SDM in slow acetylator rabbits. Furthermore, the intravenous co-administration of N4-acetylsulfadimethoxine, which is a major metabolite of SDM and strongly displaces SDM from its serum protein binding sites, significantly increased the tissue distribution of SDM in fast acetylator rabbits, resulting in the reduction of plasma concentration of SDM. These findings indicate that the acetylation capacity for SDM is an important factor determining the effect of probenecid on the plasma concentration and tissue distribution of SDM in rabbits.View full abstractDownload PDF (603K) -
MATAICHI SAGI, YOSHIO NAKAGAWA, MICHINAO MIZUGAKI, HIROSHI YAMANAKA, M ...1988 Volume 108 Issue 4 Pages 350-354
Published: April 25, 1988
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSWhen 5-butylthiazole-2-carboxylic acid or 2-butylthiazole-4-carboxylic acid was orally administrated to rats, the corresponding chain elongated products, thiazolepropionic acid and thiazoleacrylic acid accompanied with ω-oxidation, were detected from their urine. Similar results have been already reported on the metabolism of 5-alkylpyridine-2-carboxylic acid and that of 5-alkylpyrimidine-2-carboxylic acid. On the other hand, no metabolite due to the chain elongation was detected on the experiments by using 5-pentylisoxazole-3-carboxylic acid, 3-pentylpyrazole-5-carboxylic acid, 5-pentyloxazole-2-carboxylic acid and 4-pentylimidazole-2-carboxylic acid. The relationship between the chain elongation and the structure of substrates was discussed.View full abstractDownload PDF (464K) -
MASAO KIKUCHI, YOKO YAMAUCHI, YUKA TAKAHASHI, ICHIRO NAGAOKA, MASATAKA ...1988 Volume 108 Issue 4 Pages 355-360
Published: April 25, 1988
Released on J-STAGE: May 30, 2008
JOURNAL FREE ACCESSTwo new secoiridoid glucosides, named syringalactone A and syringalactone B, were isolated together with 8-epikingiside and 7-β-D-glucopyranosyl 11-methyl oleoside from the leaves of Syringa vulgaris LINN. Their structures were elucidated on the basis of nuclear magnetic resonance spectra and other physicohemical evidence.View full abstractDownload PDF (477K)
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