The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 20 , Issue 2
Showing 1-12 articles out of 12 articles from the selected issue
Original Articles
Communications to the Editors
  • Setsuzo Nomura, Hiroshi Yamamoto, Iwao Umesawa, Akihiro Matsumae, Toju ...
    1967 Volume 20 Issue 2 Pages 55-61
    Published: 1967
    Released: May 10, 2019
    JOURNALS FREE ACCESS

    Anti-neoplasmic activity against Ehrlich carcinoma and Sarcoma-180 in mice as well as antibacterial effects on Gram positive and negative bacteria has been demonstrated by the culture filtrate of Streptomyces reticuli var. shimofusaensis (Strain No. G-253) originally isolated in 1961 from a Chiba Prefecture soil sample.

    The active portions of the filtrate have been crystallized as reddish or bluish-purple crystals, which have characteristics very similar to those described for the mitomycin group of antibiotics.

    In the preliminary study, two fractions designated as G-253 Band C, were extracted, and B was examined for its antibacterial effect on Gram positive bacteria both in vitro and in vivo.

    Subsequent studies to determine the relationship of products to cultural conditions were performed. The products were extracted and cheked chromatographically. It was thus determined that the product varied in accordance with the cultural conditions and that six substances could be found which possess inhibitory activity by the paper chromatography using water-saturated chloroform as an eluent. Rf values of each component are: 0.40~0.50 (A), 0.27~0.39 (B1), 0.13~0.17 (B2), 0.06~0.10 (B), 0.01~0.06 (C) and 0.00 (C1), respectively.

    Subsequent work proved fractions 4 and 5 were the same components as had been originally isolated and identified as G-253 B and C.

    The isolation procedures, and the physico-chemical and biological properties of the three antibiotics B1, B2 and C1 are described below as well as a comparison of these with the mitomycin group of antibiotics.

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  • Nakao Ishida, Katsuo Kumagai, Tarō Niida, Kazuko Hamamoto, Takashi Sho ...
    1967 Volume 20 Issue 2 Pages 62-65
    Published: 1967
    Released: May 10, 2019
    JOURNALS FREE ACCESS

    In our screening for antibiotics active against R factor-induced drug-resistant Shigella, a weakly basic, water-soluble antibiotic was found in the culture broth of a Streptomyces, which was isolated from a soil sample collected in Nemuro, Hokkaido10). Later, additional two species of Streptomyces were found to produce the same antibiotic in the culture filtrates. As reported in the companion papers, 2,3) this active principle was isolated and designated as nojirimycin. It was found to be active against a limited number of microorganisms such as Xanthomonas oryzae, Sarcina lutea in addition to a drug-resistant strain of Shigella flexneri at 0.6~10 mcg/ml concentrations, while it was neither toxic at 1,000 mg/kg in mice after intraperitoneal injection nor at 100 mcg/ml to HeLa cells. Moreover, the antibiotic was active enough in the pot tests for the prevention of the rice plant disease caused by X. oryzae. This paper is concerned with the taxonomy of the three different orgnisms producing nojirimycin and the fermentation conditions necessary for the production of nojirimycin. Following paper2) will describe the extraction procedure and characterization of nojirimycin as well as its biological activities.

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  • Nakao Ishida, Katsuo Kumagai, Tarō Niida, Takashi Shomura, Hiroshi Yum ...
    1967 Volume 20 Issue 2 Pages 66-71
    Published: 1967
    Released: May 10, 2019
    JOURNALS FREE ACCESS

    This paper describes the isolation of a new antibiotic, nojirimycin, from the fermentation beers of several Streptomyces such as Str. roseochromogenes R-4681), Str. lavendulae SF-425 and Str. nojiriensis n. sp. SF-426. Some chemical, physical and biological properties of the antibiotic are also described. Taxonomy and fermentation study of the antibiotic were already reported.2)

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  • Sadao Miyamura, Naoya Shigeno, Masanao Matsui, Shigetoshi Wakaki, Keiz ...
    1967 Volume 20 Issue 2 Pages 72-76
    Published: 1967
    Released: May 10, 2019
    JOURNALS FREE ACCESS

    Mitomycin is one of the most potent of known antitumor substances. It also has a broad antibacterial spectrum. However, its clinical application is restricted because of its relatively high toxicity. For the purpose of increasing the curative effect, many derivatives of this antibiotic were synthesized.1)

    Mitomycin has a very unique structure as shown in the following formula.2) Quinone, aziridine and carbamoyl groups are known as anticancer active groups. It is very important problem to elucidate the role of these three groups in biological activity. The authors tested the antibacterial action of many derivatives of this compound synthesized by the cooperative research group. 1) This paper deals with antibacterial activities of mitomycin derivatives and the relationship between chemical structure and biological activity.

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  • Takayuki Naito, Susumu Nakagawa, Jun Okumura, Masataka Konishi, Ken-ic ...
    1967 Volume 20 Issue 2 Pages 77-86
    Published: 1967
    Released: May 10, 2019
    JOURNALS FREE ACCESS

    In all of the natural penicillins and most of biologically active semi-synthetic penicillins, 6-aminopenicillanic acid (6-APA) combines with the side chain through an amide linkage. It was interesting to find that an introduction of vinyl group between carbonyl and NH groups of amide linkage still retained the biological activity of penicillin. This paper is to report the preparation and antimicrobial activity of a series of compounds represented by the following general formula:

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  • Hatsuo Aoki, Heiichi Sakai
    1967 Volume 20 Issue 2 Pages 87-92
    Published: 1967
    Released: May 10, 2019
    JOURNALS FREE ACCESS

    Although laboratory animals or tissue culture methods are indispensable for antitumor agents selection, they are rather expensive and laborious for routine or primary works. Therefore many investigators have studied for simple methods which make screening much easier. About 10 years ago Lwoff1) suggested the possible correlation between prophage inducing property and mutagenic and carcinogenic activities. Lein et al.2) showed that

    antitumor antibiotics, azaserine, gancidin A, griseolutein, mitomycin C, phleomycin, porfiromycin, pluramycin and streptonigrin were prophage inducers, and established a screening method for antineoplastic substances. Heinemann et al.,3) on systematic examination of over two hundreds of substance including antibiotics, alkylating agents, thiol derivatives and other miscellaneous compounds, found out that 80 % of the prophage inducing agents had antitumor activity. Endo et al.4) reported a screening method for antineoplastic substances by using prophage induction procedure. However this method is not quite satisfactory, because some antitumor agents such as actinomycin D or chromomycin A3 do not respond to this test. Recently antibiotics which interfere with nucleic acids metabolism have been reported to exert inhibiting effect on vegetative multiplication of bacteriophages. 5, 6) As many antineoplastic drugs disturb nucleic acids metabolism antiphage activity are also supposed to be useful as a screen of antitumor agents.

    In the present investigation, various kinds of antibiotics and synthetic drugs were examined for their prophage inducing and phage inhibiting activities on double layer agar plates. 7)

    The results lead to the conclusion that antiphage act1v1ty gave more useful data for screening of antiphage agents than previous works which laid basis on only prophage inducing activity.

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  • Shinichi Sugawara
    1967 Volume 20 Issue 2 Pages 93-108
    Published: 1967
    Released: May 10, 2019
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    The antibiotic azalomycin F was first obtained1) and characterized2) by Arai of this laboratory in 1960 and it has been found to be effective clinically against vaginal trichomoniasis and candidiasis3, 4). Hagihara et al. 5 , 6) reported that it acts as an uncoupler and enhances ATPase activity in rat liver mitochondrial system; however, little is so far known on the mode of action of the antibiotic on its main target organisms3, 7).

    The present paper describes the mode of action of azalomycin F on Candida albicans.

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  • Kaoru Ohmori
    1967 Volume 20 Issue 2 Pages 109-114
    Published: 1967
    Released: May 10, 2019
    JOURNALS FREE ACCESS

    Rice blast caused by Pyricularia oryzae is the most dreadful disease of nee plant. A new antibiotic, kasugamycin was found by Umezawa et al. in 19651) and was confirmed to be the most promising fungicide for the control of rice blast disease2,3,11).

    A few investigations on P. oryzae made resistant to fungicides have been reported. Yamazaki4) observed the development of resistance to copper sulfate, boric acid, and mercuric chloride, Yosm15l obtained cultures of P. oryzae resistant to a phenylmercuric compound, Suzuki6) obtained phenylmercuric acetate (PMA)-resistant and blasticidin S-resistant cultures of P. oryzae, and Nakamura and Sakurai7,8) obtained a strain of P. oryzae which grew at 4,000 ppm of blasticidin S. All these resistant strains were obtained from the sensitive strains by selecting the cultures growing in media containing the corresponding fungicides. However, there is no report which demonstrated appearance of fungicides resistant strains of P. oryzae on rice plant in the field.

    In cases of drug-resistant Staphylococci, Escherichia coli and Shigella, it has been confirmed that the mechanism of resistance and the transfer of resistance of drug-resistant strains obtained from patients are entirely different from drug-resistant strains made in laboratories9). Therefore, resistant strains made in laboratories can not be considered to be the same as resistant organisms which may occur in nature and the observation on strains made resistant in laboratories can not be utilized to know the future appearance of natural resistant organisms. As in other cases of fungicides, P. oryzae can be made resistant to kasugamycin in the laboratory. In this paper, the characters of resistant cultures thus obtained are presented.

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  • Nobuo Tanaka, Kumiko Sashikata, Hamao Umezawa
    1967 Volume 20 Issue 2 Pages 115-119
    Published: 1967
    Released: May 10, 2019
    JOURNALS FREE ACCESS

    Kanamycin is a basic glycosidic antibiotic and the biological activity is similar to streptomycin. Concerning the mechanism of action of aminoglycosidic antibiotics, such as streptomycin, kanamycin, neomycin, and paromomycin, there proposed a hypothesis that they interfere with binding of aminoacyl-sRNA to the messenger-ribosome complex, cause codon misreading, and result in disturbing protein synthesis1~4). The idea of codon misreading is based on the phenomenon that the aminoglycosides stimulate the incorporation of certain kinds of amino acids into polypeptide in E. coli polynucleotide systems. Spectinomycin and kasugamycin seem to be exceptions and have been reported to exhibit no stimulatory activity on polynucleotide-directed incorporation of amino acids into polypeptide5,6).

    Morikubo described a one-way cross-resistance of microorganisms with streptomycin (SM) and kanamycin (KM): i.e. the SM-resistant mutant is sensitive to KM, but the KM-resistant mutant is resistant to SM7). Tanaka et al. investigated amino acid-incorporating activity of the ribosomes of the antibiotic-resistant mutants of E. coli and the effects of KM and SM on it. They observed the localization of resistant changes on the ribosomes and one-way cross-resistance in the inhibition of protein synthesis, in which native messengers participate, as in the case of antibacterial activity. However, no cross-resistance was demonstrated with poly U-directed polyphenylalanine synthesis. It suggested that the binding site of KM is different from that of SM on the ribosomes or both antibiotics are bound to different ribosomes6).

    The activity of the ribosomes, obtained from SM- and KM-resistant mutants of E. coli has been further investigated in connection with codon misreading caused by the antibiotics, and the results are presented in this publication. Concerning codon misreading, no significant cross-resistance was observed between the ribosomes of KM-resistant mutant and those of SM-resistant one.

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  • Hisao Abe, Sachiko Gotō, Kanji Shinozaki, Shogo Kuwahara
    1967 Volume 20 Issue 2 Pages 120-125
    Published: 1967
    Released: May 10, 2019
    JOURNALS FREE ACCESS

    The transmission of multiple drug-resistance by conjugation was first discovered in 1959 by Akiba1) and Ochiai2) independently, and later, confirmed widely between species belonging to Enterobacteriaceae. The genetic factor responsible for the expression of multiple drug-resistance was named R-factor, the nature of which was extensively studied by Japanese workers.

    In 1963, it was confirmed by Kuwahara and his coworkers3) that the R-factor of Shigella fiexneri was transmitted to freshly isolated strains of Vibrio cholerae and Vibrio eltor by conjugation, although the transmitted resistances were lost rapidly after a few subcultures on drug-free nutrient agar. Thereafter, transmission experiments were also carried out from species of Enterobacteriaceae to other species of Vibrio or related species of bacteria. This report deals chiefly with the experimental results of the transmission of R-factor from resistant Shigella fiexneri to sensitive Aeromonas and non-agglutinablen vibrio.

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  • Saburō Suzuki, Ken-Ichi Asahi, Junsaku Nagatsu, Yoshitsugu Kawashima, ...
    1967 Volume 20 Issue 2 Pages 126
    Published: 1967
    Released: May 10, 2019
    JOURNALS FREE ACCESS
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  • 1967 Volume 20 Issue 2 Pages 128
    Published: 1967
    Released: May 10, 2019
    JOURNALS FREE ACCESS
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