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MITSUO NUMATA, MASAYOSHI YAMAOKA, KATSUTADA MASUDA
1970 Volume 18 Issue 2 Pages
221-227
Published: February 25, 1970
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A novel oxidative acetylation was found in the oxidation of hydroxyalkyl sulfides (IIIa to VIIIa) with 30% H
2O
2-AcOH. Whereby it was concluded that when the hydroxyl can conformationally approach the sulfur atom the sulfide is prone to acetylation during the oxidation. An oxidation-acetylation mechanism has been proposed for the reaction as summarized in Chart 4.
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HISASHI NOGAMI, MANABU HANANO, SHOJI AWAZU, TATSUJI IGA
1970 Volume 18 Issue 2 Pages
228-234
Published: February 25, 1970
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In order to know the kinetic aspects of the enterohepatic circulation, the excretion in bile and the elimination from blood of riboflavin were studied in rat. Three riboflavin derivatives, i. e. free riboflavin (FR), flavin-5'-phosphate (FMN), and flavin adenin dinucleotide (FAD) were used. (1) Biliary Excretion 1) Irrespective of the kinds of administered riboflavin derivatives, FR was the major and FAD was the minor excreted in bile, but no FMN was found. 2) A remarkable dose dependency of biliary excretion was found. When high doses (1-10 μmole) were administered, the rapid excretion occurred instantaneously and excretion was proceeded to 80% within 2 hr, and the excretion time course was described with two rate processes of rate constants k
1 and k
2. On the other hand, when low doses (0.05-0.1 μmole) were administered, the excretion was slow and proceeded to only 50% after 4-5 hr, and the time course was described with one rate process of rate constant k'. It was an interesting result that k' had the similar value to that of k
2. 3) Some kinetic model for the dose dependency were discussed. (2) Elimination from Blood 1) FMN and FAD were found to be dephosphorylyzed very rapidly in blood. 2) The elimination of riboflavin from blood after i. v. administered was very fast and obeyed the two compartmental model. 3) The blood concentration time course of i. v. injected riboflavin was compared between a normal and a cannulated rat. The reabsorption of riboflavin could not be ascertained.
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KENZO SIRAKAWA, OSAMI AKI, TERUAKI TSUJIKAWA, TAKASHI TSUDA
1970 Volume 18 Issue 2 Pages
235-242
Published: February 25, 1970
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S-Alkylthioisothioureas (I) have been synthesized by the reaction of thiols, thiourea and hydrogen peroxide in aqueous solutions at low temperatures. Unsymmetrical disulfides could be obtained by the reaction of I with various thiols.
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TOSHIHIKO OKAMOTO, YO ISOGAI, TORU KOIZUMI, TAKENORI NISHINO, YAEKO SA ...
1970 Volume 18 Issue 2 Pages
243-248
Published: February 25, 1970
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The structure of Crystals E, F, and G were determined as methyl (p-methylcarbamoyloxy) cinnamate, methyl (p-methylcarbamoyloxy) hydrocinnamate, and methyl p-methoxy-cinnamate, respectively. Crystals E and F were confirmed to be the artifacts resulting from the methylation with diazomethane-ether. p-Hydroxycinnamic acid was proved to be a plant-growth retardant existing in Moyashi (etiolated seedlings of a bean, Phaseolus mungo). Several growth retardants were synthesized.
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YASUNOBU SUKETA, MICHIYASU SUGII, TOMOJI SUZUKI
1970 Volume 18 Issue 2 Pages
249-254
Published: February 25, 1970
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Homomethionine was first isolated from nature and some of its biosynthesis was studied by using methionine-
35S, methionine-
14CH
3, and cystine-
35S.
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KAZUO WATANABE, NORIKO ISHIDA, HIDEOMI FUKUDA
1970 Volume 18 Issue 2 Pages
255-260
Published: February 25, 1970
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Mechanism of gastric ammonia formation was studied in mice, and the possibility was examined that the injurious effect of some anti-inflammatory drugs on gastric mucosa was due to the gastric urease inhibition. Ammonia formation in the stomach was remarkably augmented by urea irrigation and was inhibited by benzohydroxamic acid, an urease inhibitor. These results indicate the importance of urease in ammonia formation in stomach. Urease inhibiting-activity in vitro of three anti-inflammatory drugs, aspirin, phenylbutazone and chinophen, and of caffeine were so weak that their injurious effects to gastric mucosa could not be attributed to urease inhibition. Gastric ammonia formation in vivo was found to be accelerated by irrigation of gastric mucosa with above-mentioned drugs, except aspirin. Gastric ammonia formation was also increased by eugenol, a well-known gastric mucosa irritant, and the effect was completely inhibited by benzohydroxamic acid. From these results it is concluded that injury on gastric mucosa by drugs increases gastric ammonia formation by accelerating the enzymatic reaction between urea and urease.
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MASAKO MURAOKA, ATSUSHI TAKADA, TAKEO UEDA
1970 Volume 18 Issue 2 Pages
261-268
Published: February 25, 1970
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In order to find the effective antiviral agents, 5-alkyluracil, 3-alkyluracil, 5-alkylisocytosine, 5-alkyl-6-methylisocytosine, 3-alkyl-6-methyluracil, 5-alkyluracil-1-β-D-glucopyranoside and 5-alkyluracil-1-β-D-ribofuranoside were synthesized and screened as to their antiviral effect on both RNA and DNA containing viruses. For RNA viruses, type-1 Mahoney strain of polio virus and K-2211 strain of ECHO-28 virus were used. For DNA viruses, type-1 and type-12 strains of adeno virus and DV-96 strain of Vaccinia virus were used. Among these tested compounds, 5-butyluracil and 5-butyluracil-1-β-D-ribofuranoside were found to possess effect on both RNA and DNA viruses. Especially, the latter was more effective than the former. Moreover, the latter exerted a broader antiviral spectrum than that of 5-fluorodeoxyuridine.
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MASAKO MURAOKA, YOSHIKO SETO, TAKEO UEDA
1970 Volume 18 Issue 2 Pages
269-274
Published: February 25, 1970
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The site of the inhibition of 5-alkyluracils and 5-alkyluracilnucleosides on intracellular multiplication of Mahoney strain of poliomyelitie virus and type-12 of adeno virus were investigated in Hep. No. 2 cells. Among these compounds 5-ethyuracil (EU), 5-butyluracil (BU), 5-ethyluracil-1-β-D-glucopyranoside (EUG), 5-ethyluracil-1-β-D-ribofuranoside (EUR) and 5-butyluracil-1-β-D-ribofuranoside (BUR) possessed inhibitory effect on the early phase of intracellular multiplication of Mahoney strain. Especially, BUR was more effective than the other compounds. It was suggested from the experimental results, that the site of action of BUR is the inhibition on the early phase of viral reproduction and the inhibition of viral release from host cells is probably the secondary phenomenon.
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KIICHIRO KAKEMI, HITOSHI SEZAKI, RYOJI KONISHI, TOSHIKIRO KIMURA, MASA ...
1970 Volume 18 Issue 2 Pages
275-280
Published: February 25, 1970
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The effects of bile salts, sodium taurocholate and sodium glycocholate, on drug absorption from the rat small intestine were investigated using the in situ perfusion technique. There are three likely mechanisms by which bile salts can effect drug absorption from the rat small intestine ; first, the loss of thermodynamic acitivity of a drug due to the formation of the micellar complex ; second, the local concentration build-up effect such as an accumulation on the absorptive surface ; third, the direct effect on the permeability characteristics of the intestinal mucosa. The absorption of sulfanilamide was not affected, but the absorption of sulfaguanidine and phenol red, poorly absorbable drugs, were enhanced by bile salts above their critical micellar concentration. On the other hand, the absorption of 2-allyloxy-4-chloro-N-(2-diethylaminoethyl) benzamide hydrochloride (A. C. D. B.) was inhibited by bile salts above the critical micellar concentration. Possible mechanisms of these effects are discussed.
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KAZUO OTSUKI, KATSUKO HAGIHARA(OKAMOTO), SHOJI TAKEMURA, YOSHIO UENO
1970 Volume 18 Issue 2 Pages
281-284
Published: February 25, 1970
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The reaction of dihydropyran (I) with N, N-dichlorbenzenesulfonamide (II) and that with N, N-dichlorobenzamide (III) were studied. The reaction of I with II gave trans-2-benzenesulfonamido-3-chlorotetrahydropyran (V) and a minor product which is a cis-isomer of V. In the reaction of I with III, trans-2-benzamido-3-chlorotetrahydropyran (VIII), its cis-isomer (IX), 2-ethoxy-3-chlorotetrahydropyran (X), and benzamide (XI) were obtained. The reactions of N-haloamides, II, III, and N, N-dibromobenzenesulfonamide, with dihydropyran were compared and the mode of them were discussed.
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MITSUO WATANABE, ZENZO TAMURA, MASASHI OKADA
1970 Volume 18 Issue 2 Pages
285-290
Published: February 25, 1970
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A product of fluorescence reaction of 3-hydroxykynurenine with p-toluenesulfonylchloride was separated and its structure was investigated. A reaction product of 2-amino-3-hydroxyacetophenone, which has the same configuration of carbonyl, amino and hydroxyl groups, with p-toluenesulfonylchloride was also studied. It was shown that the product from 3-hydroxykynurenine was p-toluenesulfonylester of the 3-hydroxyl group and p-toluenesulfonylamide of the aliphatic amino group, and that the product from 2-amino-3-hydroxyacetophenone was p-toluenesulfonylester of the 3-hydroxyl group.
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TOKURO OHISHI, HIROSHI KUGITA
1970 Volume 18 Issue 2 Pages
291-298
Published: February 25, 1970
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Hydrolytic cyclization of 3-acetyl-3-(3, 4-dimethoxyphenyl) adiponitrile (V) in 65% sulfuric acid at 140° was found to yield 3a-(3, 4-dimethoxyphenyl)-2, 3, 3a, 4, 5, 6-hexahydroindol-2, 6-dione (VI), whose structure was confirmed by spectral properties and transformation into dl-mesembrane (=3a-(3, 4-dimethoxyphenyl)-1-methylperhydroindol) (XI). Reactions of V in 65% sulfuric acid at room temperature yielded five products, XIII, XIV, XV, XVI and XVII as intermediates of this cyclization reaction, all of which were converted to the final cyclization product (VI) by heating to 140°in the acid. Possible reaction mechanisms of the formation of VI and the intermediates were proposed. An alternate synthesis of VI from 3, 4-dimethoxyphenyl acetone via methyl 3-(2-cyanoethyl)-3-(3, 4-dimethoxyphenyl) levulinate (XIX) was also described.
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TOKURO OHISHI, HIROSHI KUGITA
1970 Volume 18 Issue 2 Pages
299-303
Published: February 25, 1970
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dl-Mesembrine (=3a-(3, 4-dimethoxyphenyl)-1-methyloctahydroindol-6-one) (XIII) and its trans isomer (XIV) were prepared from 3a-(3, 4-dimethoxyphenyl)-1-methyloctahydroindol-2, 6-dione (IV) in 4 steps. Stereochemistry of 3a-(3, 4-dimethoxyphenyl)-1-methyloctahydroindol-2, 6-dione was discussed on the basis of nuclear magnetic resonance (NMR) informations.
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YOSHIO UENO, YOSHIYUKI ISHIKAWA, KAZUE SAITO-AMAKAI, HIROSHI TSUNODA
1970 Volume 18 Issue 2 Pages
304-312
Published: February 25, 1970
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In order to obtain a large amount of fusarenon-X, a cytotoxic mycotoxin of Fusarium nivale Fn 2B, environmental factors influencing the production of the toxin were investigated with the following results. 1) With the stationary culture of F. nivale on Czapek medium, the supplemented peptone or yeast extract increased the lethal toxicity of culture filtrate to mice. 2) Peptone-supplemented Czapek medium (PSC medium) provided all necessary ingredients for the high level production of fusarenon-X. 3) With PSC medium, the maximal yield of fusarenon-X was observed 6-8 days of cultivation at 27°, and the yield decreased at lower temperature. 4) Rice, barley, wheast and corn supported the production of the toxin, and the highest toxicity was observed with rice grains.
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MASAO SHIMIZU, OSAMU NAGASE, SEIZABURO OKADA, YASUHIRO HOSOKAWA
1970 Volume 18 Issue 2 Pages
313-318
Published: February 25, 1970
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Two coenzyme A analogs having purine base different from adenine, such as inosino-(IV) and guano-coenzyme A (IX), have been synthesized by application of the method via the thiazoline intermediate in the same manner as the total synthesis of coenzyme A. Inosino-coenzyme A has been also obtained by deamination with nitrite from the disulfide from of coenzyme A. Synthesis of guano-coenzyme A has been more efficiently effected by a combination of the methods of Moffatt and Khorana, for the formation of pyrophosphate, and of Michelson, for 2', 3'-cyclic phosphate fission, than the thiazoline method.
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TSUNEO KUSAMA, HIKOYA HAYATSU
1970 Volume 18 Issue 2 Pages
319-327
Published: February 25, 1970
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Commercial Merrifield resin was derivatized into a resin bearing acyl chloride groups. The derivatized resin can be linked to the 5'-hydroxyl group of thymidine via an acyl ester linkage. The polymer-supported thymidine gave thymidylylthymidine in a good yield on reaction with 3'-O-acetylthymidine 5'-phosphate in the presence of mesitylene sulfonyl chloride. When the polymer-supported thymidine was reacted with thymidine 5'-phosphate in the presence of dicyclohexylcarbodiimide, polymerization of thymidylic acid took place and polymer-supported oligothymidylic acid was obtained. The oligonucleotides were liberated from the resin by treatment with ammonia. It was found that this oligonucleotide mixture was composed exclusively of oligomers of the type, Tp (Tp)
nT. Oligomers up to the hexamer were purified and identified. This procedure would be convenient for the preparation of oligodeoxyribonucleotides of the general formula, X (pY)
n.
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HISASHI NOGAMI, TSUNEJI NAGAI, HIDEAKI UMEYAMA
1970 Volume 18 Issue 2 Pages
328-334
Published: February 25, 1970
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The effect of 3rd component (additive) on the water structure around tryptophan molecule was discussed on the basis of solubility properties of tryptophan in aqueous urea solution and of the adsorption of tryptophan by carbon black from aqueous EtOH solution. Considering that the iceberg formation around non-polar molecules is an enthalpy effect at room temperature on the basis of Shinoda and Fujihira's new view on the hydrophobic bonding, the following mechanism seemed reasonable for the increase in solubility of tryptophan upon addition of urea : urea comes in contact with hydrophobic moiety of tryptophan to result in a simultaneous structural change (a kind of destruction) of the iceberg around that moiety, accompanying an increase of its affinity to water to result in a predominantly large decrease in enthalpy of mixing. The decrease in adsorption of tryptophan from aqueous solution with the addition of EtOH also might be due to the contact between EtOH and the carbon black surface or the tryptophan molecule containing a simultaneous structural change of iceberg, in the same way as described above. Higher solubility of L-tryptophan than DL-isomer was considered to come from its stronger molecular interaction, as was suggested by a differential scanning calorimetry. Solubility properties of tryptophan in 1, 3-dimethyl urea solution and EtOH solution suggested that the effects of these additive on the hydrophilic moiety were not negligible
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HISASHI NOGAMI, TSUNEJI NAGAI, HIDEAKI UMEYAMA
1970 Volume 18 Issue 2 Pages
335-341
Published: February 25, 1970
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The solubility properties of tryptophan were observed in various solutions of the denaturants for β-lactoglobulin reported by Tanford, et al., and the effects of such 3rd component on the hydrophobic and the hydrophilic moieties of solute molecule was discussed on the basis of the enthalpy of mixing. As a result, it seemed possible to classify the denaturants into three types according to the balance of the effects on hydrophobic and hydrophilic moieties of tryptophan resulting in a change of solubility. In comparison with the existing data, the same classification might be extended to the denaturants according to their effects on the denaturation of β-lactoglobulin, and it was established that the solubility of tryptophan or the denaturation of β-lactoglobulin varies with the effects of additive (or denaturant) on hydrophobic and hydrophilic moieties of molecule, where the decrease in enthalpy of mixing is considered to be a predominant factor to result in the increase in solubility of tryptophan or to result in the denaturation of β-lactoglobulin.
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HISASHI NOGAMI, TSUNEJI NAGAI, SAKAE WADA
1970 Volume 18 Issue 2 Pages
342-347
Published: February 25, 1970
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The adsorption of sulfonamides by carbon black from solution was investigated in detail regarding the hydrophobic interaction. The adsorption isotherms obtained were well described with Langmuir equation. pH and concentration of buffer solution had no distinct effect on the adsorption of sulfonamides near the neutral pH region. From the following results, it was convinced that the adsorption of sulfonamides by carbon black from aqueous solution proceeds by the hydrophobic interaction : (1) adsorption of sulfonamides by carbon black from MeOH solution was correlated to that from aqueous solution ; (2) adsorption of sulfonamides by graphite from aqueous solution was correlated to that by carbon black ; (3) the entropy change of adsorption of sulfonamides by carbon black from aqueous solution was positive.
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HISASHI NOGAMI, TSUNEJI NAGAI, SAKAE WADA
1970 Volume 18 Issue 2 Pages
348-352
Published: February 25, 1970
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As a physico-chemical approach to an understanding of biopharmaceutical phenomena, discussions were given on the basis of the adsorption of sulfonamides by carbon black from aqueous solution. The hydrophobic interaction was considered to be weakened upon addition of urea, resulting in a decrease in adsorption of sulfonamides from aqueous solution. The introduction of Me- or MeO- into the molecular structure of sulfonamide caused the increases in the adsorption by carbon black, in the binding to bovine serum albumin, and in the absorption from rat small intestine. Plotting the adsorption data of sulfonamides against the partition coefficient in butanol-water system reported, a good correlation was given. Then, plotting the same data against the absorption rate from rat small intestine reported, a correlation was observed. It was, therefore, expected that the hydrophobic interaction between the drugs and the intestinal membrane forms an important factor in absorption phenomena.
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KIYOHIKO MASHIMO, YASUHIKO SATO
1970 Volume 18 Issue 2 Pages
353-355
Published: February 25, 1970
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5-Methyl-9β-benzoyloxymethyl-12-benzoyl-6, 7, 8, 9, 10, 11-hexahydro-6, 10-imino-5-H cyclooct [b] indole-8-acetonitrile (8) is a key intermediate in the synthesis of ajmaline (1) by Masamune, et al. We report here an alternate synthesis of this important compound starting from the easily accessible (3), whose preparation has been described in the foregoing paper.
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AKIRA YOKOYAMA, SHOSUKE KAWANISHI, HISASHI TANAKA
1970 Volume 18 Issue 2 Pages
356-362
Published: February 25, 1970
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Four kinds of thio derivatives of β-diketone and their nickel, cobalt, zinc, palladium, copper, lead, rhodium and iron chelates were prepared. The ratio of metal to ligand was 1 : 3 in cobalt, rhodium and iron chelates and 1 : 2 in other metal chelates. Bromination of cobalt chelates by N-bromosuccinimide or bromine were successful in some cases to give tribrominated chelates. Comparison of cobalt thio-β-diketonates with their tribrominated chelates in infrared and nuclear magnetic resonance spectra indicated that the bromination took place at γ-carbon of chelate ring. The success of the bromination can be considered as a kind of support for quasiaromaticity of the chelate to some extent.
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AKIRA YOKOYAMA, SHOSUKE KAWANISHI, HISASHI TANAKA
1970 Volume 18 Issue 2 Pages
363-367
Published: February 25, 1970
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Infrared, electronic and nuclear magnetic resonance spectra of cobalt (III) thio-β-diketonates were studied in comparison with those of cobalt (III) β-diketonates. Quasiaromaticity was more strongly supported in thio-β-diketonates than in β-diketonates by mainly the following observations. In thio-β-diketonates, absorption bands of ν (C-O) and ν (C-C) wereobserved at lower wave number than in corresponding β-diketonates. Chemical shifts of the protons of methine and methyl groups were found in lower field in thio-β-diketonates than those of corresponding β-diketonates. In Co (III) thioacetylacetonate a singlet was observed as a signal of methyl groups in nonpolar solvents. In Co (III) thio-β-diketonates which contain phenyl group, deshielding effect and mesomeric effect of phenyl group were also discussed in nuclear magnetic resonance spectra.
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YUKIO SUGIURA, HISASHI TANAKA
1970 Volume 18 Issue 2 Pages
368-373
Published: February 25, 1970
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Occurance of concurrent redox and complexation reaction between copper (II) and penicillamine, known as an excellent therapeutic agent for Wilson's disease, was investigated by both spectrophotometric and potentiometric methods. Mixing of excess copper (II) with penicillamine was produced a red-violet colored complex. This complex are characterized by much more intense absorption than those oustomarily found in cupric or cuprous complexes, and the complex was presumed as a mixed valence complex. In the presence of excess penicillamine, an yellow copper (I) complex was formed. These complexes were isolated from aqueous solution. It was found that the compounds which have strong excretion activity of copper, such as penicillamine and β-methyl-β-ethyl-cysteine, form stable red-violet complexes, while the compounds which are not effective for the excretion of copper, such as N-acetylpenicillamine and cysteine, do not form stable red-violet complexes.
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HEIHACHIRO TAGUCHI, SHOJI SHIBATA
1970 Volume 18 Issue 2 Pages
374-378
Published: February 25, 1970
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Isousnic acid (IIIb), a structural isomer of usnic acid, was isolated from lichens of Cladonia spp. The so-called "Isodihydrousnic acid" obtained by the thermal rearrangement of dihydrousnic acid has been discussed in comparison with isodihydrousnic acid (XII) prepared by catalytic hydrogenation of isousnic acid.
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SHIGETAKA YOSHINA, ISAMU MAEBA
1970 Volume 18 Issue 2 Pages
379-380
Published: February 25, 1970
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TOHRU HINO, TANAAMI) UOJI(nee, SANYA AKABOSHI
1970 Volume 18 Issue 2 Pages
384-388
Published: February 25, 1970
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TOHRU HINO, KAZUKO TSUNEOKA(YAMADA), SANYA AKABOSHI
1970 Volume 18 Issue 2 Pages
389-391
Published: February 25, 1970
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FUMIHIKO KANZAWA, AKIO HOSHI, TAKAKO NISHIMOTO, KAZUO KURETANI
1970 Volume 18 Issue 2 Pages
392-394
Published: February 25, 1970
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TSUTOMU IRIKURA, HAJIME KAWASAKI, RYOICHI ENTA, YOSHINARI HASEGAWA
1970 Volume 18 Issue 2 Pages
394-396
Published: February 25, 1970
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YUICHI KANAOKA, TAKESHI KUGA, KAZUTAKA TANIZAWA
1970 Volume 18 Issue 2 Pages
397-399
Published: February 25, 1970
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AKIRA HANAKI
1970 Volume 18 Issue 2 Pages
399-401
Published: February 25, 1970
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MASAYUKI KITADANI, AKIRA YOSHIKOSHI, YOSHIO KITAHARA, JAYRDEPAIVA CAMP ...
1970 Volume 18 Issue 2 Pages
402-405
Published: February 25, 1970
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TOKUJI SUZUKI, YUKIYA SAITOH, KAZUYO NISHIHARA
1970 Volume 18 Issue 2 Pages
405-411
Published: February 25, 1970
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TADASHI WATABE, KIMIKO SUZUKI
1970 Volume 18 Issue 2 Pages
414-415
Published: February 25, 1970
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SABURO ISHIWATA, KEIICHI ITAKURA
1970 Volume 18 Issue 2 Pages
416-417
Published: February 25, 1970
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NOBORU YANAIHARA, TADASHI HASHIMOTO, CHIZUKO YANAIHARA, NAOKI SAKURA
1970 Volume 18 Issue 2 Pages
417-420
Published: February 25, 1970
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