Biomedical subjects

K Fujimaki

Publications and source records attributed to K Fujimaki.

40 records · Page 3Linked to original sources

PubMed1988

Purification of Citrobacter freundii DNA gyrase and inhibition by quinolones.

DNA gyrase is a bacterial enzyme which catalyzes the ATP-dependent negative supercoiling of DNA. It is the accepted target of quinolones. The enzyme from Citrobacter freundii IID976 was purified by affinity chromatography on novobiocin-Sepharose and heparin-Sepharose. It had two subunits, designated A and B, which closely resembled those of the enzyme from Escherichia coli and Micrococcus luteus in enzymatic requirements. The inhibitory effects of the quinolones on the supercoiling activities of the enzyme correlated with their antibacterial activities. New quinolones were better inhibitors of DNA gyrase than nalidixic acid and pipemidic acid. We also purified DNA gyrase from a spontaneous nalidixic acid-resistant mutant (M2-5). The gyrases from IID976 and M2-5 were defined as mixtures of subunits As+Bs (s, susceptible) and Ar+Br (r, resistant), respectively. The supercoiling activities of reconstituted Ar+Br and Ar+Bs were more resistant to quinolones than As+Bs and As+Br. These findings indicate that one mechanism of C. freundii resistance against quinolones is resistance modification of the A subunit protein.

Anti-Bacterial Agents↗

PubMed1988

In vitro and in vivo antibacterial activities of T-3262, a new fluoroquinolone.

T-3262, a new fluoroquinolone, showed a broad spectrum of activity against gram-positive and gram-negative bacteria. T-3262 had most potent activity against gram-positive cocci, such as Staphylococcus, Streptococcus, and Enterococcus spp. The MICs of T-3262 for 90% of strains tested were between 0.05 and 1.56 micrograms/ml. Against members of the family Enterobacteriaceae and Pseudomonas aeruginosa, the activities of T-3262 were almost equal to those of ciprofloxacin. Obligate anaerobes were also susceptible to T-3262. T-3262 was bactericidal for one strain each of Staphylococcus aureus, Escherichia coli, and P. aeruginosa at concentrations near its MIC; and fluoroquinolones, including T-3262, inhibited DNA gyrase activity at low concentrations. The 50% effective dose of T-3262 after oral administration against systemic infections with S. aureus in mice was about 6 times lower than that of ofloxacin and about 20 times lower than that of norfloxacin.

Animals↗

PubMed1988

Clinical isolate of Citrobacter freundii highly resistant to new quinolones.

About 30% of 150 recent clinical isolates of Citrobacter freundii were resistant to greater than or equal to 3.13 micrograms of norfloxacin and ofloxacin per ml. Study of one quinolone-resistant strain for which the norfloxacin MIC was 100 micrograms/ml suggested that resistance was associated with both an altered A subunit of DNA gyrase and reduction in drug uptake accompanied by a decrease in an outer membrane protein.

Bacterial Outer Membrane Proteins↗

PubMedDate not supplied

Regulation of phosphorylation of cyclic AMP response element-binding protein by paroxetine treatments.

The present study was undertaken to examine the effect of paroxetine, a selective serotonin reuptake inhibitor, on the phosphorylation of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) in the rat brain. Single administration of paroxetine significantly induces the phosphorylation of CREB in the rat frontal cortex and hippocampus in a time-dependent manner. Repeated administration of paroxetine attenuates CREB phosphorylation in response to acute paroxetine challenge. These findings suggest that the enhancement of intracellular signal transduction after the activation of serotonin receptors may be attenuated after chronic paroxetine treatment, and this attenuation may be, at least in part, involved in the therapeutic efficacy of paroxetine.

Animals↗