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Biomedical subjects

G Medoff

Publications and source records attributed to G Medoff.

At least 127 records · Page 7Linked to original sources
PubMed1976

Variation in the susceptibility of strains of Staphylococcus aureus to oxacillin, cephalothin, and gentamicin.

Three cases of staphylococcal bacteremia caused by organisms that were inhibited by low concentrations of oxacillin, but were resistant to the killing effects of oxacillin, stimulated us to screen 60 clinical isolates of Staphylococcus aureus for their susceptibility to oxacillin, cephalothin, and gentamicin. All 60 strains were inhibited by low concentrations of the antibiotics. The antibiotics were bactericidal against 27 of the 60 strains and only bacteriostatic against the other 33 after 24 h of incubation. However, after 48 h of incubation, the antibiotics were also bactericidal against the latter group.

Adolescent↗
PubMed1976

Antimicrobial susceptibility testing of six clinical isolates of Aspergillus.

Several different methods of performing susceptibility tests on six clinical isolates of Aspergillus are described. Some of the conditions that affected the level of susceptibility to drugs were: the type of media used, temperature and time of incubation, and the initial inoculum size. For amphotericin B susceptibility testing, the effectiveness of the polyene antibiotic as measured by visual growth was equivalent to the effectiveness as measured by inhibition of ribonucleic acid synthesis and dry-weight increase. For 5-fluorocytosine and rifampin, the visual-turbidity method gave minimum inhibitory concentrations that were much higher than those determined by effects on ribonucleic acid synthesis and dry weight. The reason for these discrepancies in susceptibility testing with 5-fluorocytosine and rifampin are unknown. We conclude that the most relevant test of this fungus to antifungal agents will have to be determined by the correlation of in vitro data with animal experiments and clinical results.

Amphotericin B↗
PubMed1976

Activity of amphotericin B, 5-fluorocytosine, and rifampin against six clinical isolates of Aspergillus.

Amphotericin B in combination with 5-fluorocytosine was synergistic against three clinical isolates of Aspergillus fumigatus and one of three clinical isolates of A. flavus. Amphotericin B in combination with rifampin was synergistic against all six clinical isolates of Aspergillus tested. The levels of 5-fluorocytosine and rifampin required for synergism were higher than clinically achievable concentrations when measurements of synergism were based on visual turbidity; but when the effects of the drugs were measured by inhibition of ribonucleic acid synthesis or dry-weight increase, much lower concentrations were effective.

Amphotericin B↗
PubMed1975

A murine model for central nervous system leukemia and its possible relevance to human leukemia.

Treatment of a transplantable leukemia in AKR mice with both amphotericin B and 1,3-Bis(2-chloroethyl)-1-nitrosourea cured a significant percentage of animals with advanced disease. Some long-term survivors developed paralysis, and they invariably demonstrated central nervous system (CNS) leukemia. Some of these animals had a systemic relapse of their leukemia, and the CNS appeared to act as a focus for systemic dissemination. The occurrence patterns and histopathologic features of the CNS leukemia in the long-term survivors were strikingly similar to those observed in humans with acute lymphoblastic leukemia.

Amphotericin B↗
PubMed1975

Marked histoincompatibility between and within sublines of AKR mice used in a syngeneic leukemia model.

Sublines of AKR mice differed significantly in their histoincompatibility to AKR/J mice, as indicated by their ability to reject AKR/J skin grafts and an AKR transplantable leukemia. Further, all sublines tested demonstrated some degree of heterogeneity, because isografts were rejected in 5-97% of the mice, depending on the subline. The presence of excessive heterogeneity among and within sublines poses a serious problem for experimental oncologists using these sublines in their tumor models.

Animals↗
PubMed1975

Stability of amphotericin B in fungal culture media.

We have found that amphotericin B is unstable in two commonly employed fungal culture media. This instability leads to inaccuracies in determining the actual level of susceptibility of slow-growing strains that require prolonged incubation for growth. To help compensate for this problem, we have described two rapid methods of susceptibility testing.

Amphotericin B↗
PubMed1975

Response of yeast and mycelial phases of Histoplasma capsulatum to amphotericin B and actinomycin D.

The dimorphic fungus Histoplasma capsulatum exists in two phases: a unicellular yeast form at 37 C and a mycelium at 25 C. We have found that these two phases have selective drug susceptibilities. The mycelial form of H. capsulatum was much more susceptible to the polyene antibiotic amphotericin B than the yeast form; in contrast, the yeast form was more susceptible to the antibiotic actinomycin D. The changes in susceptibility occurred early in the transition between the two phases and permitted the transitions to be blocked by sublethal concentrations of the appropriate drugs.

Amphotericin B↗
PubMed1975

Characterization of an inhibitor of ribonucleic acid polymerase from the mycelial phase of Histoplasma capsulatum.

An inhibitor of ribonucleic acid polymerases has been obtained from the mycelial phase of Histoplasma capsulatum and partially characterized. The inhibitor, called histin, was purified 200-fold by heat treatment at 100 C and electrophoresis on polyacrylamide gels. Histin moved in electrophoresis as if negatively charged; it was insensitive to treatment with ribonuclease of deoxyribonuclease but was completely digested by Pronase. Sucrose gradient centrifugation suggests a molecular weight of 24,000. The possibility of a regulatory role for histin in the life cycle of H. capsulatum is discussed.

Cell-Free System↗
PubMed1975

Amphotericin B-induced sensitivity to actinomycin D in drug-resistant Hela cells.

HeLa cells, which were selected for resistance to actinomycin D on the basis of decreaded penetration of the antibiotic into the cells, were treated with nontoxic concentrations of the polyene antibiotic amphotericin B. In the presence of amphotericin B, the cells became sensitive to the effects of actinomycin D, as demonstrated by loss of cell viability, typical morphological changes, and effects on the pattern of RNA synthesis. Furthermore, we were able to demonstrate that amphotericin B increased the amount of (3H)actinomycin D incorporated into HeLa cells as determined by both radioactive counts and radioautography. Amphotericin B might be useful in overcoming the resistance is based on decreased entry of the agents into cells.

Amphotericin B↗
PubMed1974

Effects of rifamycin derivatives, alone and in combination with amphotericin B, against Histoplasma capsulatum.

Several derivatives of rifamycin SV inhibited ribonucleic acid synthesis and decreased the viability of Histoplasma capsulatum. Both of these effects were enhanced by low concentrations of amphotericin B. The relative potency of the different rifamycin derivatives against H. capsulatum, when used in combination with amphotericin B or alone, was the same as that reported for the inhibition of the reverse transcriptase of ribonucleic acid tumor viruses.

Amphotericin B↗
PubMed1974

Molecular basis for the selective toxicity of amphotericin B for yeast and filipin for animal cells.

Among the polyene antibiotics, many, like filipin, cannot be used clinically because they are toxic; amphotericin B, however, is useful in therapy of human fungal infections because it is less toxic. Both the toxicity of filipin and the therapeutic value of amphotericin B can be rationalized at the cellular and molecular level by the following observations: (i) these polyene antibiotics showed differential effects on cells; filipin was more potent in lysing human red blood cells, whereas amphotericin B was more potent in inhibiting yeast cell growth; and (ii) the effects of filipin were more efficiently inhibited by added cholesterol, the major membrane sterol in human cells, whereas the effects of amphotericin B were more efficiently inhibited by ergosterol, the major membrane sterol in yeast. The simplest inference is that the toxicity and effectiveness of polyenes are determined by their relative avidities for the predominant sterol in cell membranes.

Amphotericin B↗
PubMed1974

Characterization of the binding of amphotericin B to Saccharomyces cerevisiae and relationship to the antifungal effects.

Based on the enhanced fluorescence of amphotericin B in acid solutions, a quantitative assay for this polyene antibiotic has been developed that is sensitive and linear in the range of 0.1 to 10.0 muM. The binding of amphotericin B to Saccharomyces cerevisiae was assayed under various conditions as the amount bound to cells in a dialysis chamber or after centrifugation. Two types of binding were defined: weak, reversible binding occurred at 0 C or higher temperatures and even in the presence of inhibitors of energy metabolism, whereas strong, irreversible binding did not occur at 0 C and was inhibited when energy metabolism was blocked. Only strong binding was correlated with cell killing. Weak binding probably involves the outer layer of the membrane; strong binding probably requires disruption of hydrophobic regions of the cell membrane.

Amphotericin B↗