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Biomedical subjects

Y Inouye

Publications and source records attributed to Y Inouye.

At least 37 records · Page 2Linked to original sources

Susceptibility of methicillin-resistant Staphylococcus aureus clinical isolates to various antimicrobial agents. III. Novel, inducible resistance to macrolide-lincosamide-streptogramin B (MLS) antibiotics.

Resistance patterns against 25 antimicrobial agents consisting of beta-lactams, aminoglycosides, tetracyclines, fluoroquinolones, macrolides and etc. were examined for 69 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated at Hiroshima University Hospital from July 1991 to April 1992. Regarding overall resistance (the percentage of highly and moderately resistant strains), the following antimicrobial agents were no more effective chemotherapeutics for MRSA infections (%resistance): methicillin (100), flomoxef (100), kanamycin (100), tobramycin (100), amikacin (100), isepamicin (100), gentamicin (78), dibekacin (100), ofloxacin (99), levofloxacin (99), temafloxacin (99), erythromycin (100), clarithromycin (100), tetracycline (93), minocycline (93) and fosfomycin (100). Further spread of arbekacin-resistant strain, which was isolated in April 1991, into a clinical environment could not be recognized during the period covered in the present study. All the MRSA strains were resistant either constitutively (26 strains) or inducibly (43 strains) to macrolide-lincosamide-streptogramin B (MLS) antibiotics. When expression is constitutive, the strains are resistant to all MLS antibiotics. In contrast, 16-membered macrolide (i.e., jasamycin), lincomycin and mikamycin B escape resistance in the strains with a typical inducible resistance overcome in the presence of 14-membered macrolides by a translational attenuation mechanism. Three of 4 beta-lactamase-positive strains, however, can not be classified in these two resistance groups, being exclusively resistant to mikamycin B. The strains grown in the presence of any inducing MLS antibiotic became susceptible to mikamycin B even in the inducer-free culture.

Anti-Bacterial Agents↗

Suppressive effect of polyoxometalates on the cytopathogenicity of human immunodeficiency virus type 1 (HIV-1) in vitro and their inhibitory activity against HIV-1 reverse transcriptase.

One isopolyoxometalate and 42 heteropolyoxometalates consisting of 3 compounds with the trivacant Keggin structure, 2 with the lacunary Keggin structure, 30 with the Keggin structure, one with the Wells-Dawson structure and 6 with miscellaneous structures were tested for their suppressive effect on the cytopathogenicity of human immunodeficiency virus type 1 (HIV-1) in vitro and inhibitory activity against HIV-1 reverse transcriptase. In contrast to the leading interpretations which attribute the suppressive effect of polyoxometalates on the cytopathogenicity of HIV-1 to the inhibition of HIV-1 reverse transcriptase by these compounds, there was no distinct correlation observed between these two functions of polyoxometalates.

Antimony↗

Molecular cloning and expression of a Streptomyces sarcosine oxidase gene in Streptomyces lividans.

A genomic library of Streptomyces sp. KB210-8SY, prepared in the plasmid vector pACYC184, was screened to obtain the gene encoding sarcosine oxidase with probes based on the amino acid sequence of the protein. A plasmid pSOXS13, which was isolated from a clone identified by hybridization with the probes, contained a 8.4-kb insert of Streptomyces DNA. When the 2.0-kb MIuI/EcoRV DNA fragment of pSOXS13 was inserted into the Streptomyces vector pIJ680 and introduced into S. lividans, the transformants produced 100-fold more sarcosine oxidase intracellularly than KB210-8SY. The nucleotides of the 1.7-kb fragment containing the sarcosine oxidase gene were sequenced. An open reading frame encoded a mature sarcosine oxidase consisting of 388 amino acids, with a calculated molecular mass of 42,107 daltons.

Amino Acid Sequence↗

A new anthracycline antibiotic, cinerubin R. Taxonomy, structural elucidation and biological activity.

A novel anthracycline antibiotic, cinerubin R, was isolated from the fermentation broth of Streptomyces eurythermus strain H1715MY2. The structure of cinerubin R was elucidated to be 4"-aculosyl-4'-rhodinosyl-7-rhodosaminyl-epsilon-py rromycinone. Cinerubin R was active against Gram-positive bacteria and inhibited the growth of divergent multi-drug-resistant cells to the same extent as their parental cells.

Animals↗

Susceptibility of methicillin-resistant Staphylococcus aureus clinical isolates to various antimicrobial agents. II. Isolation of arbekacin-resistant strain.

Resistance patterns against 24 antimicrobial agents were examined for 50 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated at Hiroshima University Hospital during the period October 1990 and July 1991. Overall resistance (the percentage of highly and moderately resistant strains) to the antimicrobial agents is summarized as follows: methicillin 100%, flomoxef 100% (beta-lactams); kanamycin 94%, tobramycin 94%, amikacin 100%, isepamicin 94%, gentamicin 80%, dibekacin 94%, arbekacin 2% (basic oligosaccharide group/aminocyclitols); ofloxacin 96%, temafloxacin 96%, levofloxacin 96% (fluoroquinolones); erythromycin 98%, clarithromycin 98%, josamycin 30% (macrolides); vancomycin 0% (glycopeptide); tetracycline 94%, minocycline 94% (tetracyclines); fosfomycin 100%; mikamycin B 30%, nosiheptide 0% (peptide); rifampicin 2% (ansamycin); streptomycin 2% (basic oligosaccharide group); chloramphenicol 2%. Arbekacin resistance was observed in one case: the cross resistance was complete among the aminocyclitol antibiotics tested in this study and streptomycin, probably due to the ribosomal alteration.

Aminoglycosides↗

Inhibition of proliferation of human immunodeficiency virus type 1 by novel heteropolyoxotungstates in vitro.

Fifteen heteropolyoxotungstates were tested for their effects on the proliferation of human immunodeficiency virus type 1 (HIV-1) using an in vitro system consisting of MT-4 cells and HTLV-IIIb. Eight heteropolyoxotungstates (HPOTs) with the Keggin structure or dimerized deficient Keggin structure proved to be potent inhibitors of HIV-1. In contrast, seven non-Keggin HPOTs including HPA 23 did not have significant effects on HIV-1 proliferation at non-toxic doses. [PTi2W10O40]7- (PM-19) was the most potent inhibitor of HIV-1 among the 15 HPOTs tested. The inhibition of HIV-1 replication by PM-19 presumably results from impaired virus adsorption and/or penetration into target cells. Viral spread of HIV-1 and HIV-2 on cell-to-cell basis was also susceptible to PM-19. In combination, PM-19 and 3'-azido-3'-deoxythymidine were synergistic in inhibiting HIV-1 proliferation.

Adsorption↗

Antiviral activity of polyoxomolybdoeuropate PM-104 against human immunodeficiency virus type 1.

A polyoxomolybdoeuropate PM-104 (NH4)12H2[Eu4(MoO4)(H2O)16(Mo7O24)4].13H2O was found to be a potent inhibitor of the growth of human immunodeficiency virus type 1 (HIV-1), a causative agent of acquired immunodeficiency syndrome (AIDS). On the basis of TI50 [median cytotoxic concentration (CC50)/median effective concentration (EC50)], the in vitro anti-HIV-1 activity of PM-104 is favorably comparable to that of a heteropolyoxotungstate PM-19 K7[PTi2W10O40].6H2O, which is one of the most potent HIV-1 inhibitors among the polyoxometalates so far tested. The heteropolyoxomolybdate with a potent anti-HIV-1 activity is introduced for the first time in this communication.

Antiviral Agents↗

Inhibition of avian myeloblastosis virus reverse transcriptase by heterocyclic quinones: structure-activity correlation.

Synthetic heterocyclic quinones (107 samples) consisting of o- and p-quinoline quinones, o-isoquinoline quinones and p-quinoxaline quinones as well as o- and p-naphthoquinones (3 samples) were tested for their inhibitory activities against avian myeloblastosis virus reverse transcriptase (AMV-RT) and cytotoxic activities against mouse lymphoblastoma L5178Y cells. In general, o-quinoline quinones (i.e., the 5,6-quinolinedione derivatives) are more potent inhibitors of AMV-RT than p-quinoline quinones (the 5,8-quinolinedione derivatives). Furthermore, the growth of L5178/Y cells were significantly refractory to the 8-methoxy-5,6-quinolinedione derivatives whose suppressive effects on AMV-RT function were fairly comparable to those of the other o-quinoline quinones. The longer the chain length of 7-alkyl substituent in o- or p-quinoline quinones, the lower the biological activities.

Avian Myeloblastosis Virus↗

Complete amino acid sequence of phenomycin, an antitumor polypeptide antibiotic.

The primary structure of phenomycin, an antitumor polypeptide antibiotic isolated from the culture broth of Streptomyces fervens var. phenomyceticus, was determined. Sequence analysis has revealed that it consists of 89 amino acid residues (Mr 9,524) and no disulfide bridge is present. The sequence of phenomycin at residues 48-70 was found to be hydrophilic, being surrounded by hydrophobic regions at both sides. Furthermore, clustering of half the lysine residues in this hydrophilic region and marked basicity of phenomycin imply the external disposition of this region. Phenomycin does not show significant sequence homology to any known proteins including antitumor polypeptide antibiotics.

Amino Acid Sequence↗

Susceptibility of methicillin-resistant Staphylococcus aureus clinical isolates to various antimicrobial agents.

Resistance patterns against 23 antimicrobial agents were examined for 42 strains of methicillin-resistant Staphylococcus aureus (MRSA). Thirty-four strains were isolated at Hiroshima University Hospital during 1984-1990 and 8 strains were collected in Tokushima city in 1986. Overall resistance to the antimicrobial agents in clinical use is summarized as follows: methicillin 100%, flomoxef 93% (beta-lactams); kanamycin 98%, tobramycin 88%, amikacin 83%, isepamicin 81%, gentamicin 60%, dibekacin 64%, arbekacin 0% (aminocyclitol aminoglycosides); ofloxacin 31%, TA-167 33% (fluoroquinolones); erythromycin 100%, clarithromycin 100%, josamycin 71% (macrolides); vancomycin 0% (glycopeptide); tetracycline 43%, minocycline 31% (tetracyclines); fosfomycin 93%. The MRSA strains remained susceptible to the non-clinical peptide group of antibiotics except for mikamycin B: mikamycin A 2%, mikamycin B 69%, nosiheptide 0%, bottromycin A2 0%, bottromycin D-1 0%, bottromycin D-2 0%. Since April 1990, the MRSA strains isolated at Hiroshima University Hospital showed a tendency to acquire resistance to tetracyclines and fluoroquinolones and to lose mikamycin B-resistance. As of August 1990, none of the MRSA strains isolated at Hiroshima University Hospital was resistant to vancomycin and arbekacin.

Drug Resistance, Microbial↗

Conformational equilibria of the L-iduronate residue in non-sulphated di-, tetra- and hexa-saccharides and their alditols derived from dermatan sulphate.

The conformation of the L-iduronate residue in non-sulphated di-, tetra- and hexa-saccharides and their alditol derivatives derived from rooster comb dermatan sulphate was investigated by 400 MHz 1H-n.m.r. spectroscopy. The ratio of conformational isomers is obtained by the average spin-spin coupling constants of a mixture of nearly isoenergetic conformers (1C4, 4C1 and 2S0). The non-reducing terminal L-iduronate residue in the tetrasaccharides (I-H-I-H and I-H-G-H) and their alditols (I-H-I-H-ol and I-H-G-H-ol) is in equilibrium with three conformers (1C4, 30%; 4C1, 40%; 2S0, 30%) of nearly equal population. Whereas the internal L-iduronate residue in the tetrasaccharides (I-H-I-H and G-H-I-H) exists as an equilibrium mixture of 1C4 (54%) and 2S0 (42-44%) conformers, that of their alditols (I-H-I-H-ol and G-H-I-H-ol) is in equilibrium between 2S0 conformer (66%) and 1C4 conformer (28%). The conformational population for the internal L-iduronate residue 2I in the hexasaccharide (3I-H-2I-H-1I-H) is also calculated and compared with that for the L-iduronate residue in native dermatan sulphate, which was calculated on the basis of the spin-spin coupling constants reported by Gatti, Casu, Torri & Vercellotti [(1979) Carbohydr. Res. 68, c3-c7].

Animals↗

Comparative studies of the inhibitory properties of antibiotics on human immunodeficiency virus and avian myeloblastosis virus reverse transcriptases and cellular DNA polymerases.

The inhibition of human immunodeficiency virus (HIV) reverse transcriptase by certain antibiotics and related compounds was studied in comparison with that of avian myeloblastosis virus (AMV) reverse transcriptase and cellular DNA polymerases alpha and beta. In general, compounds that inhibited HIV reverse transcriptase also inhibited AMV reverse transcriptase. For example, 10 micrograms/ml of the isoquinoline quinones used in this study inhibited approximately 80% of the activity of reverse transcriptases of HIV and AMV, but did not inhibit the activity of DNA polymerases alpha and beta even at 50 micrograms/ml. AMV enzyme was more sensitive than HIV enzyme to colistin, enduracidins A and B, janiemycin, glysperin A, and thielavins A and B. The streptonigrin alkyl esters, however, inhibited HIV reverse transcriptase only. Sakyomicin A, luzopeptins, ellagic acid and suramine inhibited the activities of reverse transcriptases and cellular DNA polymerases.

Anti-Bacterial Agents↗