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Biomedical subjects

J E Bennett

Publications and source records attributed to J E Bennett.

At least 163 records · Page 9Linked to original sources
PubMed1974

Polyene-resistant mutants of Aspergillus fennelliae: identification of sterols.

Four mutants strains of Aspergillus fennelliae resistant to various polyene antibiotics have been analyzed for their sterol content. The mutant strains contained Delta(7,22,24(28))-ergostatrien-3beta-o1 and Delta(7,22)-ergostadien-3beta-o1 as the major sterols, whereas the wild types contained ergosterol, indicating that the mutants contain metabolic blocks for C(5)-C(6) dehydrogenation and C(24)-C(28) reduction in the biosynthesis of ergosterol. Revertant sectors arising from the mutant colonies contained either more Delta(7,22)-ergostadien-3beta-o1 than the parent mutant strain or showed the reappearance of ergosterol. The revertant sectors also showed lower resistance to amphotericin B and a higher rate of sporulation than the parent mutant strain. These results confirm our previous observations that the presence of ergosterol is directly related to the drug susceptibility and the normal rate of sporulation in this species.

Anti-Bacterial Agents↗
PubMed1973

Experimental therapy of cladosporiosis and sporotrichosis with 5-fluorocytosine.

Cladosporium trichoides and Sporothrix schenckii are fungi known to be pathogenic for man. No effective chemotherapy is available for cladosporiosis, and systemic sporotrichosis can be very resistant to antifungal chemotherapy. Experimental infections of mice with these fungi resembled their respective infections in man and provided a model for evaluating a new antifungal agent, 5-fluorocytosine (5-FC). Our results with four isolates of C. trichoides demonstrated a statistically significant dose-related therapeutic effect with 5-FC. Mortality was significantly reduced in all treatment groups, and survivors showed no clinical sign of disease despite positive brain cultures. Results with a single isolate of S. schenckii were less encouraging. Fatality rate was significantly decreased in all treatment groups, but no trend was noted with increasing 5-FC dosage. Survivors manifested the signs of active disease, and all liver and spleen cultures were positive for S. schenckii. These results indicated that (i) 5-FC may be the first drug useful in the treatment of cladosporiosis, and (ii) 5-FC may have only limited therapeutic benefit in systemic sporotrichosis.

Animals↗
PubMed1973

5-fluorocytosine resistance in Cryptococcus neoformans.

Isolates of Cryptococcus neoformans from six patients were obtained before and after unsuccessful therapy with 5-fluorocytosine (5-FC). Post-therapy isolates exhibited massive and stable 5-FC resistance. The frequency of drug-resistant mutants in susceptible isolates of C. neoformans was <0.001% (70.4 +/- 17.9 per 10(7) cryptococci), whereas mutant frequencies in resistant isolates approached 100%. Non-drug-induced, spontaneously appearing 5-FC resistant mutants were documented in four susceptible isolates of C. neoformans by use of the statistical method of fluctuation analysis. Mutation rates on these same four isolates ranged from 1.2 x 10(-7) to 4.8 x 10(-7). Total intracellular uptake and incorporation of cytosine-5-(3)H (CyH(3)) and 5-fluorocytosine-2-(14)C (5-FC(14)) into a trichloroacetic acid-insoluble fraction were markedly reduced in six isolates with in vivo-acquired resistance when compared with susceptible pretreatment strains from the same patients. Five of these six isolates also had acquired massive resistance to 5-fluorouracil (5-FU), suggesting that a mutation in the uridine-5'-monophosphate pyrophosphorylase was responsible for drug resistance. The sixth isolate, which remained susceptible to 5-FU, appeared to have a defect in a cytosine-specific permease accounting for 5-FC resistance. A single isolate with in vitro-acquired 5-FC and 5-FU resistance had no reduction in uptake or incorporation of CyH(3) or 5-FC(14). The mechanism of resistance in this isolate is discussed.

Antifungal Agents↗
PubMed1973

Variables influencing susceptibility testing of Cryptococcus neoformans to 5-fluorocytosine.

The minimum inhibitory concentration (MIC) of 5-fluorocytosine (5-FC) was determined for 65 isolates of Cryptococcus neoformans by using a twofold serial tube dilution method. The MIC was profoundly influenced by incubation temperature, inoculum size, and duration of incubation. By using a standard set of test conditions, 100% of 49 pretreatment isolates of C. neoformans were susceptible to 10 mug of 5-FC per ml or less, and 9 (56%) of 16 isolates recovered during or after 5-FC therapy were massively drug resistant (MIC > 320 mug/ml). With the standard test conditions recommended here, the tube dilution method was found to be both accurate and reproducible, and the results correlated with the treatment status of patients.

Antifungal Agents↗