Biomedical subjects

M H Tsuhako

Publications and source records attributed to M H Tsuhako.

3 recordsLinked to original sources

PubMed1998

Relationship between spontaneous aminoglycoside resistance in Escherichia coli and a decrease in oligopeptide binding protein.

Changes in the amount of oligopeptide binding protein (OppA) in spontaneous kanamycin-resistant mutants of Escherichia coli were investigated. Among 20 colonies obtained from 10(8) cells cultured in the presence of 20 microgram of kanamycin/ml, 1 colony had no detectable OppA and 7 colonies were mutants with reduced amounts of OppA. Sensitivity of wild-type cells to kanamycin increased slightly by transformation of the oppA gene, but the sensitivity of the mutants increased greatly by the transformation. A mutant with no OppA was found to be a nonsense mutant of the oppA gene at amino acid position 166. In a mutant having a reduced level of OppA, the reduction was due to the decrease in OppA synthesis at the translational level. These mutants were also resistant to other aminoglycoside antibiotics, including streptomycin, neomycin, and isepamicin. Isepamicin uptake activities decreased greatly in these two kinds of mutants. The results support the proposition that aminoglycoside antibiotics are transported into cells by the oligopeptide transport system, and that transport is an important factor for spontaneous resistance to aminoglycoside antibiotics.

Amino Acids↗

PubMed1991

Comparative studies of nifurtimox uptake and metabolism by drug-resistant and susceptible strains of Trypanosoma cruzi.

1. Nifurtimox uptake and metabolism by epimastigote forms of three strains of Trypanosoma cruzi (Basileu, Y, YuYu) with different drug responsiveness in mice experimental infections were compared. 2. Statistical analysis of the results demonstrated no correlation between the ability of the strains to catalyze nifurtimox redox-cycling (Basileu = Y = YuYu) nor nifurtimox multiple electron reduction (Basileu = Y greater than Y) and drug susceptibility (Basileu greater than Y greater than YuYu). 3. A partial correlation however, was observed between drug responsiveness and nifurtimox uptake (Basileu greater than Y = YuYu). 4. The results suggest that drug uptake may be more important than drug metabolism in modulating resistance to nifurtimox in T. cruzi strains.

Animals↗

PubMed1989

Restricted bioreductive metabolism of a nitroimidazole-thiadiazole derivative with curative action in experimental Trypanosoma cruzi infections.

The bioreductive activation of megazol [2-amino-5(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole] promoted by ferredoxin: NADP+ oxidoreductase, rat liver microsomes and cellular fractions of Trypanosoma cruzi, Y strain, was investigated. Direct ESR detection and characterization by computer simulation of the megazol nitro anion radical were possible in the presence of NADPH and ferredoxin: NADP+ oxidoreductase under anaerobic conditions. By contrast, the megazol nitro anion radical was not detected in the presence of either rat liver microsomes or cellular fractions of T. cruzi under conditions where the corresponding nifurtimox anion radical was observed. The inefficiency of rat liver microsomes in catalyzing megazol reduction was also attested by visible light absorption spectroscopy. In the presence of cellular fractions of T. cruzi supplemented with NAD(P)H, megazol marginally affected oxygen consumption and decreased the yield of oxyradicals that can be spin-trapped with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Our results indicate a restricted bioreductive metabolism of megazol and suggest that its trypanocidal activity is unrelated to a redox-cycling process.

Animals↗