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Biomedical subjects

D Schlessinger

Publications and source records attributed to D Schlessinger.

At least 217 records · Page 12Linked to original sources

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↗

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↗

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↗

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↗