Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Volume 27, Issue 2
Displaying 1-50 of 50 articles from this issue
  • NORIKO MOTOHASHI, MINEKO TERAO, ITSUHIKO MORI, YUKIO SUGIURA, NAKAO KO ...
    1979 Volume 27 Issue 2 Pages 279-286
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The organ distribution of new disulfhydryl-compounds, 2, 3-dimercaptopropionyl-glycine (DMPG) and 2-mercaptopropionyl-L-cysteine (MPC), labeled with 113mIn (III) and 67Ga (III) were examined in mice, and the results were compared with those of dimercaptosuccinic acid complex and metal ion without those ligands to evaluate their applicabilities as diagnostic agent in nuclear medicine. The DMPG complex was found to be localized in liver, whereas the MPC complex in kidney. The addition of metal ion carrier varies the distribution patterns of the complex species, on account of the formation of the polymerized products. In the case of indium complexes, the behavior of the ligand was reflected to their distribution patterns more clearly than in the case of gallium complexes. The complex species formed in the labeling reactions were characterized by the electrophoretic and gel-filtration techniques.
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  • HIROYUKI ASAKAWA, MITSUO MATANO, YUTAKA KAWAMATSU
    1979 Volume 27 Issue 2 Pages 287-294
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    Treatment of 2-alkyl-4-oxo-4H-3, 1-benzoxazines (Ia-d, f, i, l) with ethanol gave 2-alkyl-3-(2-carboxyphenyl)-4-quinazolones (VIIa-d, f, i, l) along with the liberation of ethyl alkanoate. This dimeric condensation may be explained in terms of the contribution of the C=N double bond of Ia-d, f, i, l. It was also revealed that the intermediate of the formation of 4-quinazolone (XVIII) in the reaction of Ia with aniline, was the amidine (XVII), which was produced by the addition of aniline to the C=N double bond of Ia.
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  • YOKO KITAGAWA, YUKIO KUROIWA
    1979 Volume 27 Issue 2 Pages 295-300
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    We studied the effect of citrate on 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB)-induced hepatic injury. Examination of the liver of rats receiving a 0.06% 3'-Me-DAB diet with or without simultaneous 1% citrate administration revealed that citrate did not affect the gross findings. In rats receiving a basal diet and 1% citrate solution, no change in the intracellular liver pH (pHi) and blood pH (pHe) was noted. However, in rats on the 3'-Me-DAB diet, simultaneous citrate administration mitigated the 3'-Me-DAB induced decrease of pH. In rats receiving single or continuous 3'-Me-DAB administration, citrate treatment did not recover decreased N-demethylase and azo reductase activities. Time-course examination of protein-bound dyes in the liver revealed that the peak of the amount of bound dyes appeared earlier in rats receiving simultaneous citrate administration than in rats receiving the 3'-Me-DAB diet without simultaneous citrate administration. Fractionation of liver cell sap protein showed that the amount of 3'-Me-DAB bound to each fraction was similar for rats receiving the 3'-Me-DAB diet and citrate and for rats receiving the 3'-Me-DAB diet alone.
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  • SHUNICHI NORO, AKIRA TAKAMURA, MASUMI KOISHI
    1979 Volume 27 Issue 2 Pages 301-308
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    An attempt was made to determine an approximate formula for sedimentation velocity of a solid particle, when a potential difference is applied between two electrodes, from statistical analysis. The powder used was Al-modified rutil type titanium dioxide. Sedimentation velocities of this particle adsorbed by sodium metaphosphate were measured when an electric force affected this suspension. When the strength of electric field, E, affects the powder particle placed between two electrostatic charges, the equation for the sedimentation velocity of a particle can be written as : [chemical formula] where f (E, dp) is the function concerned with an electric field, E, and particle size, dp. This function f(E, dp) is given as, [chemical formula] From the above equation, values of both sedimentation velocity and particle size distribution can be predicted beforehand when a powder particle exists between two electrodes.
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  • SHUNICHI NORO, AKIRA TAKAMURA, MASUMI KOISHI
    1979 Volume 27 Issue 2 Pages 309-316
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    Examinations were made on the effect of Tween group emulsifiers, with combination of Span-20 and Tween-81 among them, to discuss the required HLB in detail, for o/w type emulsions with the use of various measurement methods. Oil-in-water emulsions were prepared containing 45% of dispersed phase. The emulsifiers used were commerical grade nonionic surfactants of four Tweens and Span-20, and the oil used was a mineral oil. Emulsion was formed by agitation, and emulsion stability was measured with four apparatuses, measuring cylinder, Coulter counter, turbidimeter, and rheometer. Following results were obtained, 1) The rate of separation was affected largely by the kind of emulsifiers, which increased in the order of Tween-81, Tween-81+Span-20, Tween-85, Tween-20, and Tween-21. 2) The o/w emulsion showed the maximum value of droplet number at characteristic HLB value equal to 10.0. 3) Viscosity of the emulsion increased with the increase of emulsifier concentration.
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  • TOSHIHIRO HAYASHI, MICHIYO AOYAMA, MINORU FUKUDA, MASAHIKO OHKI, TORAH ...
    1979 Volume 27 Issue 2 Pages 317-325
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The species differences of metabolism of 4-ethoxy-2-methyl-5-morpholino-3 (2H)-pyridazinone (M73101) were studied. The urinary and fecal metabolites in six animals (dog, mouse, rabbit, rat, monkey, and guinea pig) were analyzed qualitatively and quantitatively by thin-layer chromatography and gas-liquid chromatography in addition to gas chromatography-mass spectrum determination. From the results of qualitative analysis, seven to ten metabolites in urine were identified in each animal. From the results of quantitative analysis, total excretion percentage of unchanged M73101 and its metabolites in urine were 50.0, 48.4, 73.8, 56.1, 52.7, and 21.1% of the dose administered in dogs, mice, rabbits, rats, monkeys, and guinea pigs, respectively. The main metabolite excreted in urine was 5-[2-(carboxymethyloxy) ethylamino]-4-ethoxy-2-methyl-3 (2H)-pyridazinone (M-9) in dogs, mice, rabbits, and rats and 5-(N-carboxymethyl-N-2-hydroxy-ethylamino)-4-ethoxy-2-methyl-3 (2H)-pyridazinone (M-8) in monkeys and guinea pigs. For the fecal excretion, 59.4, 19.5, 17.7, and 15.3% of the dose administered were excreted in guinea pigs, mice, dogs, and rats, respectively, and rabbits and monkeys hardly excreted any metabolites. From the results of urinary and fecal excretion, the main excretion route was through liver and bile duct into feces in guinea pigs and was into urine in other five animals. For the effects of the dose administered on metabolism, dose-dependent variations of metabolism characteristic of guinea pigs were observed in biliary excretion, that is, main metabolite was M-8 in low dose (20mg/kg) while M-9 in high dose (500mg/kg) but such phenomenon was not found in rats.
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  • TOSHIHIKO HASHIMOTO, SACHIKO NATSUME, TETSUO MIYADERA
    1979 Volume 27 Issue 2 Pages 326-330
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    Ethyl 2-(1-indanylidene) cyanoacetate (I) was treated with phenylmagnesium bromide and the resultant ambident anion (II) was reacted with a few alkylating agents and aldehydes. Interestingly, the alkylation reactions of the alkylidenecyanoacetate system were accompanied by γ-alkylation to a significant extent together with the preferred α-alkylation. The anion was also formed by the use of sodium hydride and subjected to the alkylation reactions. It seems that the alkylation reactions are dependent upon metal counterions yielding α-and γ-substituted products in a different proportion. Reactions of the anion with aldehydes afforded a diene (VI) and lactone (VII) which were formed as the result of an exclusive reaction at the γ-position.
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  • KOJI YAMAKAWA, ITARU IZUTA, HIROSHI OKA, REIJI SAKAGUCHI, MASATO KOBAY ...
    1979 Volume 27 Issue 2 Pages 331-340
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The total syntheses of (±)-isopetasol (24), (±)-3-epiisopetasol (17), (±)-warburgiadione (23), (±)-petasitol (27a) are described. A key intermediate (11) was synthesized by the Robinson annulation of 2, 3-dimethylcyclohexane-1, 4-dione (6), which was prepared starting from 2, 3-dimethylphenol (2) and methyl vinyl ketone via intermediates 8 and 9. Reduction of 11 with NaBH4 gave epimeric alcohols (13a and 14a) in the 7 : 3 ratio. Stereochemistry of 13a and 14a and the coresponding acetates (13b and 14b) were confirmed by NMR spectrometry. Introduction of the C-7 side chain in 13a was made with CH3Li to give 16 which was treated with HCl-MeOH to afford (±)-17. While, the same procedure applied to 14a was unsucessful. Ketal (19) derived from 11 was converted to isopropyl alcohol (21) by two routes. Treatment of 21 with HCL-MeOH gave (±)-isopetasone (22). (±)-23 and (±)-24 were obtained from 22 by dehydrogenation and reduction, respectively. Dehydrogenation of 21 by 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ) gave a cross dienone (25). Deketalization of 25 followed by reduction afforded (±)-27a and (±)-3-epipetasitol (28).
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  • EIKO OHTSUKA, TETSUO MIYAKE, MORIO IKEHARA
    1979 Volume 27 Issue 2 Pages 341-345
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    A tetranucleotide C-G-C-Gp (cytidylyl-(3'-5')-guanylyl-(3'-5')-cytidylyl-(3'-5')-guanosine 3'-phosphate) was synthesized by condensation of (Bz) bzC (Bz)-ibG (Bz) p (5) with C (Bz)-ibG (Bz) pNHC6H4S (O) CH3 (6) using 2, 4, 6-triisopropylbenzenesulfonyl chloride. This sequence corresponds to the E. coli tRNAMetf 5'-terminus. A base substituted analog U-G-C-Gp was also synthesized by a similar procedure to that used for C-G-C-Gp. These tetranucleotides were characterized by enzymic hydrolysis.
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  • HISASHI ISHII, YASUOKI MURAKAMI, TOKUO FURUSE, KATSUHIRO HOSOYA
    1979 Volume 27 Issue 2 Pages 346-350
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    3, 6'-Biindole (1f), an unsymmetric biindole, was synthesized via the advanced Fischer indolization of ethyl pyruvate 2-[(o-methoxyphenyl) hydrazone] (2a) and ethyl indole-2-carboxylate (8).
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  • HIROTERU SAYO, KOICHI MORI, TAKASHI MICHIDA
    1979 Volume 27 Issue 2 Pages 351-356
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    2-and 4'-Substituted benzenesulfenanilidyl radicals were generated by the oxidations of benzenesulfenanilides (4'-OMe (1a), 4'-Me (1b), 4'-Cl (1c), 4'-H (1d)) and 2-nitrobenzene-sulfenanilides (4'-OMe (3a), 4'-Me (3b), 4'-Cl (3c), 4'-H (3d)) with lead dioxide, and their electron spin resonance (ESR) and visible spectra were investigated. The radicals generated from 1a, 1b, 3a, and 3b in benzene were fairly stable and gave well-resolved ESR spectra, whereas those from 1c, 1d, 3c, and 3d were less stable and decomposed thoroughly in an hour. The oxidations of 1a and 1b in benzene gave the corresponding 2, 7-disubstituted phenazines as the final products, whereas those of 1c, 1d, 3a-d did not. The oxidations of 3a-d in acetonitrile containing 1% CF3COOH and 1% (CF3CO)2O gave the corresponding phenazines and N-(2-nitrophenylthio) acetamide (6). The formation of 6 was interpreted in terms of acetamidation of the sulfenylium ion.
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  • SHIGEKO OZAKI, MASAICHIRO MASUI
    1979 Volume 27 Issue 2 Pages 357-365
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    Anodic oxidation of several N-hydroxycarbamates is studied by cyclic voltammetry and controlled potential electrolysis in acetonitrile with or without amines at a glassycarbon electrode. In the presence of excess amine, the corresponding N, O-dialkoxycarbonyl-and O-alkoxycarbonyl-N-hydroxycarbamates, alcohols and N-alkylacetamides, are produced from ethyl and benzyl N-hydroxycarbamates. N-Methylation of the compound markedly decreases the yields of the corresponding alcohol and N-alkylacetamide, whereas it increases O-alkoxycarbonylation of the starting compound and the demethylated product. O-Alkylated N-hydroxycarbamates yield N, N'-dialkoxycarbonyl-N, N'-dialkoxyhydrazines quantitatively. Plausible oxidation processes for these compounds are proposed.
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  • YURIKO KATO, HISAKO WATANABE, NAOKO MAEYAMA, KAZUKO KIDO
    1979 Volume 27 Issue 2 Pages 366-373
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    Sulfamethizole was pulverized by recrystallization from glycols or their derivatives, and correlation of difference in the degree of pulverization with the solvent was studied. Crystalline properties of the pulverized crystals of sulfamethizole thus obtained were also studied. The degree of pulverization of sulfamethizole by recrystallization from glycols and their derivatives decreased with increase in the number of carbon atoms in the hydrophobic chain of these solvents. When the pulverized sulfamethizole were examined by IR, X-ray diffraction, and DSC-TG, two kinds of hydrate and one kind of anhydride were detected. The form I (anhydride) was transformed into form III (hydrate ; 1 mol H2O) in the artificial gastric juice of 37°, but not in water.
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  • HIROSHI HIRANO, MASANORI TAKAMATSU, KAZUAKI SUGIYAMA, TAKUSHI KURIHARA
    1979 Volume 27 Issue 2 Pages 374-378
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    o-Amino-S-cyanomethylthiophenol (1) obtained by the reaction of o-aminothiophenol with monochloroacetonitrile was converted to 2, 3-dihydro-3-imino-4H-1, 4-benzothiazine (2). Furthermore, the N-methyl derivative (6) was prepared from o-(formyl-methylamino)-S-cyanomethylthiophenol (5) which was obtained by the reaction of benzothiazolium iodide (4) with monochloroacetonitrile under basic conditions. Acetylation of 6 was attempted. The compound 6 (base) was acetylated with acetic anhydride in pyridine at room temperature to give the acetylimino compound (9) by the usual reaction. Unexpectedly, heating under reflux of the hydrochloride of 6 in acetic anhydride afforded a new ring system compound, 8, 15-diazaphenothiazino [8, 7-h] phenothiazine derivative (10) in fair yield. The last reaction gave a small amount of two by-products, which proved to be o-(acetyl-methylamino)-S-acetylcarbamoylmethylthiophenol (11) and 2, 3-dihydro-4-methyl-4H-1, 4-benzothiazin-3-one (12), respectively.
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  • YUKIO MORI, TETSUO YAMAMOTO, KAZUMI TOYOSHI
    1979 Volume 27 Issue 2 Pages 379-385
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    Metabolites of 3'-methyl-4-(methylamino) azobenzene (3'-Me-MAB) in the rat bile and urine were investigated by use of a tracer technique. 3H-3'-Me-MAB in cottonseed oil was administered orally by a stomach tube. The dye metabolites in the bile and urine collected during 24 hr after the administration were hydrolyzed with β-glucuronidase/arylsulfatase. The hydrolyzed metabolites were then extracted with chloroform or separated by chromatography on an Amberlite XAD-2 using methanol as solvent. The metabolites in the chloroform extract or methanol eluate were identified by the reverse isotope dilution analysis, after or before separation by thin-layer chromatography. The N-demethylated, aryl hydroxylated, and their azo-reduced products were detected in the bile, in addition to the products oxidized at the ring methyl group as the new metabolites of 3'-Me-MAB. On the other hand, the metabolites retaining the azo-linkage were hardly excreted in urine. Instead, 3-aminobenzoic acid, 3-amino-6-hydroxytoluene, and their N-acetylated products were major metabolites in urine. The present results indicate that the metabolism for 3'-Me-MAB in the rat involves oxidation at the ring methyl group. Effect of the ring methyl group on the carcinogenic action of aminoazo dyes is also discussed.
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  • TAKASHI ABE
    1979 Volume 27 Issue 2 Pages 386-391
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The effects of some essential vehicles in cosmetics or topical preparations for transepidermal water loss (TWL) and skin surface lipids were investigated on human skin in relation to their physicochemical properties. The test vehicles were isopropyl myristate (IPM), liquid paraffin 70cs (LPC70) and glycerol. The results revealed newer biopharmaceutical aspects concerning the mode of vehicles against skin surface as follows. 1) The degree of occlusive effect for TWL in the closed experimental system was graded in the following order : glycerol>LPC70>IPM. 2) The removal effect for sebaceous squalene and epidermal cholesterol was found to be in the following order : IPM>LPC70>glycerol. 3) The occlusive effect of vehicles on TWL was suggested to be inversely related to the removal effect of vehicles for skin surface lipids. 4) Vehicle viscosity seemed to be one of the physicochemical regulating factors for occlusive nature of vehicles against TWL. 5) The in vitro water loss test seemed to be meaningful for a better understanding of the vehicle effect on TWL. 6) The importance of the removal effect on epidermal cholesterol that reflected TWL increase was suggested in the evaluation of vehicles against human skin surface barrier properties.
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  • HIROSHI TOMISAWA, HIDEKI KATO, REIKO FUJITA, HIROSHI HONGO
    1979 Volume 27 Issue 2 Pages 392-397
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The further studies for synthesis of 6-azabicyclo [3. 2. 1] octane derivatives from 1-alkyl-2 (1H)-pyridones (I) are carried out. Reaction of Ia-e with fumaric acid (II) without solvent gave 6-alkyl-7-oxo-6-azabicyclo [3. 2. 1] oct-2-ene-2, 8-endo-dicarboxylic acid (IIIa-e) and 6-alkyl-7-oxo-6-azabicyclo [3. 2. 1] oct-2-ene-2, 8-exo-dicarboxylic acid (IVa, b, d, e). Reaction of Ia-e with II in water gave IIIa-e. Reaction of Ia with maleic acid in water and without solvent afforded only IIIa.
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  • KANETO UEKAMA, NAOKI MATSUO, FUMITOSHI HIRAYAMA, TATSUYA YAMAGUCHI, YO ...
    1979 Volume 27 Issue 2 Pages 398-402
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    Inclusion complex formation of acetohexamide with β-cyclodextrin in water and in solid state was ascertained by solubility method, circular dichroism spectroscopy, and powder X-ray diffractometry. A solid complex of acetohexamide with β-cyclodextrin in 1 : 2 molar ratio was prepared, and its dissolution behavior in water and hypoglycemic activity in rabbit were examined. Improved dissolution characteristic of acetohexamide by inclusion complexation resulted in potentiation of the reduction in blood glucose levels in rabbit, which may be due to the increase in absorption of the drug.
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  • SHINZO TAMURA, EMIKO TAKEDA
    1979 Volume 27 Issue 2 Pages 403-409
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    Formation of β-arylaminoacrolein from β-ethoxyacrolein (I) and arylamine was studied kinetically. Hammett plot for second order rate constants gave a good linear line with ρ value of-2.63. Neither triethylamine nor acetic acid acted as an effective catalyst for the reaction. In the presence of acetic acid a remarkable amount of malonaldehyde dianil formed as a by-product. Reaction mechanism was discussed.
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  • NORIO SUZUKI, RENZO DOHMORI
    1979 Volume 27 Issue 2 Pages 410-418
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    In order to search for new antimicrobial agents, a number of 2-substituted 8-ethyl-5, 8-dihydro-5-oxothiazolo [5, 4-b] naphthyridine-6-carboxylic acid and their related compounds which consist of a new ring system were prepared. Reactions of the 6-amino-1-ethyl-7-mercapto-1, 4-dihydro-4-oxonaphthyridine-3-carboxylic acid (2) with acid, acid anhydride, acid chloride and ethylxanthate afforded several thiazolo [5, 4-b] naphthyridine derivatives. Refluxing ethyl 7-chloro-1-ethyl-6-nitro-1, 4-dihydro-4-oxonaphthyridine-3-carboxylate (16) with KSCN in acetic acid gave directly the thiazole cyclization product 19. Reaction of 8-ethyl-2-methylthio-5, 8-dihydro-5-oxothiazolo [5, 4-b] naphthyridine-6-carboxylic acid (11) with dimethyl sulfate gave various products (13b, 25 and 26) depending upon its reaction conditions. Some compounds obtained in this work exhibited high activities against gram-negative and gram-positive bacteria in vitro.
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  • TAKAKO YOKOZAWA, NAMIKO KITAHARA, SHOKO OKUDA, HIKOKICHI OURA
    1979 Volume 27 Issue 2 Pages 419-423
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    In comparing the effect of ginseng principle on the activity of pyruvate kinase (EC 2. 7. 1. 40), there was a marked difference among various diet groups. Administration of the extract (fraction 5) from the roots of Panax ginseng C. A. MEYER increased the activity of hepatic pyruvate kinase in rats fed on a laboratory pellet chow. Maximum increase in the enzyme activity was observed 1 hr after the administration of ginseng principle, and it was found that this response depended on the amount of fraction 5 administered to rats. However, rise of the enzyme activity due to ginseng treatment did not seem to involve de novo protein synthesis which requires mRNA production. In contrast, when the diet contained an excess of carbohydrate, ginseng treatment resulted in a decreased enzyme level, and the elimination of food resulted in the loss of the effect of ginseng principle.
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  • TOSHIO AKIMOTO, MASAKO MAEDA, AKIO TSUJI, YOICHI IITAKA
    1979 Volume 27 Issue 2 Pages 424-434
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The crystal structure of (N-sailcylidene ethanolaminato) Zn (II) has been determined by the single crystal X-ray diffraction method. The compound crystallizes in space group P42/n with unit cell dimensions of a=15.004, c=8.125A and Z=8. The complex is tetrameric with 4 symmetry. The core unit of the tetrameric structure has a distorted cubic array of four zinc ions and four oxygen atoms of ethanolamine which occupy the eight vertices alternately.
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  • FUMITOSHI HIRAYAMA, KANETO UEKAMA
    1979 Volume 27 Issue 2 Pages 435-441
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    Base-catalyzed isomerization of prostaglandin A1 (PGA1) to prostaglandin B1 (PGB1) was significantly accelerated by α-and β-cyclodextrins (α-CyD, β-CyD), where catalytic effect of β-CyD was larger than that of α-CyD. Stability constants and rate constants of PGA1-cyclodextrin (CyD) complexes were kinetically determined on the base of 1 : 1 inclusion complex formation. In order to elucidate the catalytic mechanism of CyDs, effects of variables such as pH, ionic strength, cationic and anionic salts, and solvents on the isomerization rate were studied in the absence and in the presence of CyDs. Furthermore, activation parameters for CyD-catalyzed isomerization were determined. The results indicated that the catalytic effect of CyDs was mainly ascribable to conformational changes of PGA1 molecule within the cavity of CyDs and hydrophobic interaction appeared to be predominant as a binding force.
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  • YOSHIO NAKAGAWA, KOGO HIRAGA, TETSUYA SUGA
    1979 Volume 27 Issue 2 Pages 442-446
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The binding of radioactive material (s) to macromolecules in the liver and other tissues was investigated in rats, after oral administration of 14C-BHT. The total radioactivity and the radioactivity bound to macromolecules in the liver reached a maximum in 6 hr and in 6-12 hr, respectively. The rate of decrease of bound radioactivity was slower than that of total radioactivity, and therefore, the binding ratio (bound radioactivity in the term of % of total radioactivity) increased with time. The bound radioactivity in the liver was found in all subcellular fractions, although the radioactivity in the microsomal fraction was higher than that in other fractions. In addition, the pretreatment of animals with phenobarbital further increased the amount of radioactivity bound to the microsomes. The bound radioactivity was also found in other tissues, the binding ratio in the lung and kidneys increased with time and that in the brain and spleen remained at the level of about 50% throughout the experimental period.
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  • MASAHIDE YASUDA, TADASHI FUJITA, YASUHISA MIZUNOYA
    1979 Volume 27 Issue 2 Pages 447-451
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    To investigate metabolic alterations during vitamin E-deficiency, the content of lipid peroxides and lipids in liver and plasma was determined using vitamin E-deficient rats, and its results were as follows : Lipid peroxide in the liver from vitamin E-deficient rats increased about 3 times over the control group, and the value returned to the normal level after intraperitoneal administration of vitamin E in a dose of 50mg/kg/day for 6 days, but that in plasma was almost constant. In vitamin E-deficiency, C16 : 1, C18 : 1, and C20 : 4 increased mainly in triglycerides (TG) in liver lipids. C18 : 2 decreased in the fractions of phospholipids but not in TG fraction. On the other hand, in plasma from vitamin E-deficient rats, C18 : 1 increased and C18 : 2 decreased in all the fractions of lipids. Decrease of C20 : 4 was found in phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in plasma lipids. Free fatty acids of plasma in vitamin E-deficiency increased by approx. 76%, and TG content increased about 73% in the liver and 35% in the plasma. The total cholesterol content of the liver and plasma from vitamin E-deficient rats increased about 55 and 20%, respectively. The content of phospholipids in the liver and plasma showed little change in vitamin E-deficiency.
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  • TOSHIAKI MIURA, HIDETOSHI TAKAGI, KAZUAKI HARITA, MICHIYA KIMURA
    1979 Volume 27 Issue 2 Pages 452-457
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The behavior of testosterone (I) and its related compounds such as 17-methyl-18-norandrosta-4, 13-dien-3-one (II), 17-methyl-18-norandrosta-4, 13 (17)-dien-3-one (III), androst-4-en-3-one (IV), 5α-androstan-17β-ol (VI), 13ξ, 14ξ-epoxy-17-methyl-18-norandrost-4-en-3-one (VIII), and 13ξ, 17ξ-epoxy-17-methyl-18-norandrost-4-en-3-one (IX) in concentrated sulfuric acid was studied, in order to elucidate the mechanism of the early stage in the chromogenic reaction of I with sulfuric acid. When I was dissolved into 97.2% sulfuric acid, the chromophoric species was produced indicating a maximum absorption at about 300nm. From the results of absorption and NMR spectroscopic studies and from the fact that the chromogenic reaction was accelerated by selenic acid as an oxidant, the species was proposed to be the dication (X) which is produced by the protonation, dehydration, angular methyl migration, and oxidation processes and retains the alkenyl as well as hydroxyalkenyl cation chromophores.
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  • TAKASHI ABE, JUNKO MAYUZUMI
    1979 Volume 27 Issue 2 Pages 458-462
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The changing patterns of in vivo human skin barrier functions after irradiation with a single middle-wavelength ultraviolet light (UV-B) were determined with respect to transepidermal water loss (TWL) and skin surface lipid values. Quantitative results were obtained as follows. 1) A significant increase of the TWL value was found 1 week after UV-B exposure at the site irradiated with twice the minimal erythemal dose (MED). 2) Cholesterol value in skin surface lipid was raised significantly 2 or 3 weeks after UV-B exposure at the 2 MED site. On the other hand, total lipid and squalene values showed no significant differences. 3) It was noteworthy that the TWL value recovered after 3 weeks to the initial control level at all UV-B energy doses. Similar tendencies were observed in the cases of total lipid, squalene and cholesterol values. 4) The increase of energy dose was parallel to the increase of the TWL value, i.e. lowering of the barrier efficacy of the stratum corneum.
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  • YORISHIGE IMAMURA, MASANOBU SONODA, KAZUHIKO ARIMORI, HISASHI ICHIBAGA ...
    1979 Volume 27 Issue 2 Pages 463-467
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The binding of carbutamide to rabbit plasma protein in vivo and in vitro was studied by using a new ultrafiltration technique. The binding of carbutamide to rabbit plasma protein in vivo markedly decreased with increasing plasma concentration of carbutamide. On the other hand, the binding of carbutamide to rabbit plasma protein in vitro hardly changed. Over one half of carbutamide in rabbit blood was observed to be as N4-acetyl-carbutamide. N4-Acetylcarbutamide was highly bound to rabbit plasma protein, and caused a marked decrease in the binding of carbutamide to rabbit plasma protein in vitro. These results indicate that the difference of binding of carbutamide to rabbit plasma protein in vivo and in vitro is due to the displacement of carbutamide from plasma protein binding sites by N4-acetylcarbutamide.
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  • MASASHI TOMODA, NORIKO SATOH
    1979 Volume 27 Issue 2 Pages 468-474
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    A mucous polysaccharide, named Lilium-J-glucomannan, has been isolated from the bulbs of Lilium japonicum THUNB. It was homogeneous on glass-fiber paper electrophoresis, by ultracentrifugal analysis, and on gel chromatography. The component sugars of it were D-mannose and D-glucose in the molar ratio of 5 : 2, and its molecular weight was measured to be 318000. The O-acetyl groups in the glucomannan were identified and determined as the content of 5.0%. They were located in positions 2, 3, and 6 of a part of D-mannose units. Methylation, partial acetolysis, and periodate oxidation studies suggested that the glucomannan is mainly composed of β-1→4 linked aldohexopyranose residues and it contains about seventeen aldohexose units per one non-reducing group on the average. D-Mannose units occupy non-reducing terminal positions and branching points linked through positions 2 or 3. A few D-glucose residues are also present as branching points linked through position 3. The comparison of the structure and the property of the glucomannan with those of the other five Lilium-glucomannans was described.
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  • SHENGCHIH CHEN, HIROSHI NAKAMURA, ZENZO TAMURA
    1979 Volume 27 Issue 2 Pages 475-479
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The relationship between the structure and the spectrum of fluorescein in aqueous solution was investigated by mainly comparing the absorption and fluorescence properties of fluorescein with those of monomethylfluorescein, dimethylfluorescein, and fluorescein methyl ester. Fluorescein was proved to be predominantly present in its univalent cation (V), neutral lactonoid (I), univalent anion (III) and bivalent anion (IV) forms at pH<1, pH3, pH 5-6 and pH>8, respectively. All forms except I were fluorescent and IV fluoresced most intensely. The neutral quinonoid form (II) was not detected in aqueous solution against to the results of previous authors.
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  • YOSHIO NAKAGAWA, KOGO HIRAGA, TETSUYA SUGA
    1979 Volume 27 Issue 2 Pages 480-485
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The binding of 14C-labeled butylated hydroxytoluene (14C-BHT) to the liver microsomes was studied in vitro. Binding of 14C-BHT to microsomal macromolecules was linear with time and protein concentration. Oxygen and dihydronicotinamide adenine dinucleotide phosphate (NADPH) were necessary for this binding, while carbon monoxide or SKF-525A inhibited it. It is indicated that a cytochrome P-450-linked monooxygenase system mediated the binding. In addition the binding was more pronounced in the liver microsomes from animals pretreated with inducers (phenobarbital or BHT) of microsomal monooxygenase system. From the effects of pretreatment with these inducers, it is suggested that a cytochrome P-450 with a high BHT oxidase activity is mainly responsible for the metabolic activation of BHT in the liver microsomes. The microsomes in the brain, kidneys and spleen were devoid of BHT-binding capacity, but in the lung microsomes the binding capacity was about 40% of that in the liver microsomes.
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  • TADASHI YASUHARA, OSAMU ISHIKAWA, TERUMI NAKAJIMA, KENGO ARAKI, SHINRO ...
    1979 Volume 27 Issue 2 Pages 486-491
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    Thr6-bradykinin and three kinds of its analogous peptides have been isolated from the methanol extract of the fresh skin of Rana rugosa. The longest bradykinin analogue, Thr6-bradykinyl-Ile-Ala-Pro-Glu-Ile-Val, was named ranakinin-R. Serotonin was also identified in the extract. The new peptide which contracts the rat uterus, guinea pig gall bladder and is hypertensive, was isolated and suggested to be the ranatensin or bombesin analogue by these pharmacological properties and by partial sequence analysis of the peptide.
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  • TADASHI YASUHARA, OSAMU ISHIKAWA, TERUMI NAKAJIMA
    1979 Volume 27 Issue 2 Pages 492-498
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The skin of Rana rugosa contained ranatensin-R, a new analogous peptide to ranatensin. Ranatensin-R is heptadecapeptide amide which is a longest analogue of ranatensin ever isolated from the frog skin. Granuliberin-R, dodecapeptide amide, was obtained from the same ranatensin-R fraction during the separation process. The peptide is a new type of amphibian skin peptide which acts on the rat peritoneal mast cell to liberate granules and histamine from the cells.
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  • KENJI OKAMOTO, KOICHI YASUMURA, SHINICHI SHIMAMURA, MASUHISA NAKAMURA, ...
    1979 Volume 27 Issue 2 Pages 499-507
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The nonatriacontapeptide corresponding to the entrie amino acid sequence of dogfish adrenocorticotropic hormone was synthesized by successive condensations of three peptide fragments ; Z (OMe)-(15-19)-OH, Z (OMe)-(11-14)-NHNH2 and Z-(1-10)-OH, with H-(20-39)-OBzl, a synthetic intermediate of dogfish corticotropin-like intermediate lobe peptide. The synthetic peptide exhibited the in vivo steroidogenetic activity of 21.3 IU/mg.
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  • TARO NOMURA, SACHIKO YAMADA, HIROSHI MITSUHASHI
    1979 Volume 27 Issue 2 Pages 508-514
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The structures of three new polyoxypregnane derivatives, dibenzoylgagaimol, gagaimol-7-methylether, and 7β-methoxysarcostin, all of which were isolated from the root of Metaplexis japonica MAKINO, are shown to be I, II, and III, respectively. These three compounds are the first example of polyoxypregnane derivatives which have been obtained from the Asclepiadaceae plants, and shown to have an oxygen functional group at the 7-position.
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  • TAKETO OGISO, NORIKO OGAWA, TOSHIAKI MIURA
    1979 Volume 27 Issue 2 Pages 515-521
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    Earlier studies showed that high dietary zinc interfered with copper absorption at the intestinal level. The data presented here demonstrated that there was a significant decrease in copper content with a concomitant increase in zinc content of the intestinal segment of the zinc-fed rats. Gel filtration analysis on Sephadex G-75 of the cytosol fraction from the mucosa of the zinc-fed rats demonstrated that major parts of zinc in the cytosol bind to the protein with a molecular weight of about 10000, that is, the zincthionein. The simultaneous administration of copper and zinc to the normal rats also caused an incorporation of copper into this protein. These results suggested that the interference of copper absorption by zinc may be due to the inductive effect of zinc on the synthesis of the zinc-thionein, which sequesters copper available for absorption.
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  • HIROYUKI ASAKAWA, YOSHIYO FUKUSHIMA, EIKO IMAMIYA, YUTAKA KAWAMATSU
    1979 Volume 27 Issue 2 Pages 522-527
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The ester derivatives of salicylic acid and some kinds of anthranilic acid were reduced to corresponding alcohols with sodium borohydride. The reduction behavior of 4-oxo-1, 3-benzodioxanes (IXa-b), 1, 2-dihydro-4-oxo-3, 1-benzoxazines (XIIa-c, e, k) and 4-oxo-3, 1-benzoxazines (XVd-j) were also investigated. These results may be explained in terms of the contribution of the electronic structure of carbonyl group or the neighbouring participation of hydroxyl or amino group.
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  • MISBAHULAIN KHAN, EMELYKAZAN ROCHA
    1979 Volume 27 Issue 2 Pages 528-531
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    1-Phenyl-, and 1-nitrophenylindoles were subjected to the Vilsmeier-Haack reaction to give the corresponding 1-arylindole-3-carboxaldehyde in good yield. These aldehydes were condensed with nitromethane and hydroxylamine. The oximes were dehydrated to afford the 1-arylindole-3-carbonitriles (3b-3d). The Knoevenagal condensation of 1d with ethyl cyanoacetate gave 5d as a 1 : 1 mixture of cis and trans isomers.
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  • MOTOICHI MIYAZAKI, SHIGEKO NISHIMURA, ATSUKO YOSHIDA, NOBORU OKUBO
    1979 Volume 27 Issue 2 Pages 532-535
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    N-Methyl-D-glucosamine (I), D-glucosamine (II), D-galactosamine (III), D-man-nosamine (IV) and D-talosamine (V) were investigated by pH titration method on their complex formations with metal ions. The pKa of these amino sugars were found to be I 7.86, II 7.38, III 7.61, IV 7.50, and V 7.98 respectively. Stability constants, log K1 of seven I-metal complexes were in the order ; Cu 4.5>Pb 3.7>Zn 3.2>Ni 3.1>Cd 2.9»Ca, Mg. Hydrolysis study on I-Cu complex revealed that I-Cu complex was more hydrolyzable to form monohydroxo complex I-Cu (OH), but less dimerized than II-Cu complex. Stability constants, log K1 of the amino sugar-Cu complexes were measured ; II-Cu 4.8, III-Cu 4.6, IV-Cu 5.0 and V-Cu 5.7 respectively. Discussions are given on the complex formation of amino sugar with Cu2+ with conformational considerations.
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  • KAZUYOSHI TAKEDA, TAKANORI KOBAYASHI, HARUO OGURA
    1979 Volume 27 Issue 2 Pages 536-537
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The equimolar reaction of carboxylic acids and amines with halosulfonium chloride afforded the corresponding carboxamides. Mechanism is discussed on the basis of sulfoxide formation.
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  • OSAMU HOSHINO, SHOHEI SAWAKI, BUNSUKE UMEZAWA
    1979 Volume 27 Issue 2 Pages 538-540
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    Photolysis (a 200 W high pressure mercury lamp) under oxygen stream of ethylene dithioacetals of 5, 6-dimethoxy-α-indanone, α-and β-indanone, α-tetralone, 5α-and 5β-cholestan-3-ones, cholest-4-en-3-one, and cyclohexanone in an appropriate solvent (nhexane, ethanol or benzene) was carried out to give the parent ketones. Ethylene dithioacetal of cholest-5-en-3-one on photolysis followed by NaBH4 reduction gave cholest-4-en-3β-o1, showing photo-induced isomerization of the double bond.
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  • EMAKO SUZUKI, MASASHI OKADA
    1979 Volume 27 Issue 2 Pages 541-544
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    Three N-nitrosamino aldehydes, N-butyl-N-(ω-formylalkyl) nitrosamines, which are necessary metabolic intermediates situated between N-butyl-N-(ω-hydroxyalkyl)-nitrosamines and N-butyl-N-(ω-carboxyalkyl) nitrosamines were synthesized for the purpose of investigating their mutagenic effects.
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  • SADAKI FUJIMOTO, TSUTOMU NAKAGAWA, AKIRA OHARA
    1979 Volume 27 Issue 2 Pages 545-548
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The properties of soybean (Glycine max) acid phosphatase, violet-colored and manganese-containing, were further studied. The enzyme was significantly inactivated by the treatment with cysteine in alkaline solution. The enzyme was more inactivated under an aerobic condition than under an anaerobic condition. The inactivation was accompanied by the reduction of the absorbance of the enzyme at 540nm. The mechanisms of the inactivation were also discussed.
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  • ATSUSHI MURAKAMI, YUKIO AKAHORI
    1979 Volume 27 Issue 2 Pages 548-550
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    A conformational energy calculation was carried out on nine prostaglandins / PGE1, 11-epi PGE1, 15-epi PGE1, 11, 15-epi PGE1, PGA1, 15-epi PGA1, PGF, PGF, and PGB1. The number of sterically allowed backbone conformations obtained by the computer experiment is related to the state of prostaglandins. The prostaglandin having a large number of sterically allowed backbone conformations (more than 70) was in an oily state, and the prostaglandin which had a small number of sterically allowed backbone conformations was in a crystalline state. Melting point of prostaglandin is related to conformational energy difference between the mean conformational energy and the lowest conformational energy of all sterically allowed conformations calculated by the computer experiment.
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  • HIDEFUMI YUKIMASA, HIROAKI SAWAI, TAKEO TAKIZAWA
    1979 Volume 27 Issue 2 Pages 551-553
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    Cu2Cl2-pyridine-O2 system oxidize 2-and 3-substituted indole derivatives to form C2-C3 double bond cleaved products. By this reaction, 2-substituted indole (6a), 3-substituted indoles (1a-5a) and 2, 3-disubstituted indole (7a) give N-acetylanthranic acid (6b), 2-acylformanilides (1b-5b) and quinolone derivative (7b), respectively. The reaction could represent a mimic of tryptophan 2, 3-dioxygenase reaction, in which tryptophan undergoes oxidative cleavage to give N-formylkynurenin.
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  • YUKIO MORI, TOSHIRO HORI, KAZUMI TOYOSHI, MASANOBU HORIE
    1979 Volume 27 Issue 2 Pages 554-557
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    Enzymic hydroxylation of 3'-methyl-4-(dimethylamino) azobenzene [4'-2H, 4'-3H, or 5'-3H] or 3'-methyl-4-(methylamino) azobenzene [4'-2H] and the reactions of deuterated aminoazo dyes or 3-acetaminotoluene with several model hydroxylating systems were investigated in order to elucidate the NIH shift in these hydroxylations. The values of retention of isotopic hydrogen (43%) were closely comparable in all hydroxylated metabolites produced from 4'-deuterated aminoazo dyes. Accordingly, it was confirmed that the enzymic hydroxylation of aminoazo dyes or 3-acetaminotoluene showed the characteristic NIH shift in each substrate. The retention values during hydroxylation of these compounds by photolysis of hydrogen peroxide, the Udenfriend or Hamilton system, and m-Cl-perbenzoic acid were lower in any cases than those by photolysis of pyridine-N-oxide. Deuterium retention during these hydroxylations with pyridine-N-oxide was the same level as those obtained with rat in vivo and in vitro. Deuterium retention during all the oxidations of aminoazo dyes with the model systems used was higher than those of 3-acetaminotoluene. These results indicate the close analogy between the NIH shift recognized in the enzyme systems and that in the model hydroxylating systems.
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  • MAKOTO SUGIYAMA, AKIRA MORINO, SHOGO IZUMI
    1979 Volume 27 Issue 2 Pages 557-563
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The amounts of 4'-Chloro-5-methoxy-3-biphenylylacetic acid (DKA-9) and its metabolites (DKA-9G, DKA-24, DKA-24G, DKA-24OG and DKA-24S, see Chart 1) in human urine could be determined separately by measuring the amounts of DKA-9 and DKA-24 generated after hydrolizing under various conditions with gas-liquid chromatography.
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  • TSUYOSHI GOROMARU, KENJI MATSUYAMA, ATSUKO NODA, SADAO IGUCHI
    1979 Volume 27 Issue 2 Pages 563-567
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    The data of urinary excretion of aminopyrine and its metabolites were collected for two years using eight of male healthy volunteers. In conclusion, individual differences among subjects were remarkable. Besides, seasonal variations were demonstrated statistically.
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  • TOSHIO KINOSHITA, YAYOI HIRAGA, NORIKO NAKAMURA, AKIKO KITAJO, FUMIO I ...
    1979 Volume 27 Issue 2 Pages 568-570
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    An equimolar mixture of 8-Hydroxyquinoline and p-anisidine was found to be oxidized with hydrogen peroxide in the presence of peroxidase giving intense blue color. Application of this mixed reagent to the assay of glucose using glucose oxidase and peroxidase provided a sensitive and reproducible method which did not require deproteinization. Ascorbic acid did not interfere with the color development after pre-incubation of the serum for a short period. Satisfactory correlation between the present method and the conventional phenol-4-aminoantipyrine method was observed.
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  • NOBORU MORI, YASUSHI IMAMURA, MICHIYOSHI TAKANASHI, HIDETSUGU WATABE, ...
    1979 Volume 27 Issue 2 Pages 571-572
    Published: February 25, 1979
    Released on J-STAGE: March 31, 2008
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    An attempt was made to detect L-asparaginase activity in adult male human urine and to separate the active principle therefrom. With condensation by salting-out with ammonium sulphate, it was found that original urine contains 0.1-2.1 enzyme units of active principle per 100 litres. Its optimal pH is 8.0 with a stable range of pH 9.0-7.0. The elution pattern as observed, using Sephadex G-100, reveals a mono-peak in enzyme activity, whose molecular weight is about 56000 as against 130000-140000 for E. coli-deriving L-asparaginase. Electrophoretically, its migrative pattern is also different from that of E. coli-deriving L-asparaginase.
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