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Biomedical subjects

G Medoff

Publications and source records attributed to G Medoff.

At least 109 records · Page 6Linked to original sources

Growth and rejection of leukemia cells in individual mice after combined treatment with amphotericin B and 1,3-bis(2-chloroethyl)-1-nitrosourea.

We assayed the femoral marrows of individual AKR mice for leukemia colony-units (LCFU) after treatment with amphotericin B (AmB) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or with BCNU alone. No differences between the groups were noted in the first 7 days after treatment. All the mice treated with BCNU alone were dead by day 8, and all the survivors among the animals receiving AmB and BCNU retained high levels of LCFU for 2 more days; these LCFU were subsequently rejected by the host. By day 12, LCFU were undetectable. Histologic examination of organs from the same mice on day 5 showed fewer leukemia cells in the mice treated with the combination of agents. In all treatment groups, mice dying of leukemia early (by day 9) had systemic leukemia and most had central nervous system (CNS) involvement. All animals dying between days 10 and 14 had CNS leukemia, but few had systemic leukemia; at later times, though few animals died, they invariably had CNS leukemia without systemic involvement.

Amphotericin B↗

Mechanism of the inhibition by RNA of the RNA polymerases of Histoplasma capsulatum.

4 S RNA isolated from the dimorphic fungus Histoplasma capsulatum inhibited the DNA-dependent RNA polymerase activity of the yeast phase of this fungus. Inhibition was specific for initiation, and resulted from binding of the RNA to the enzyme. Among a variety of synthetic polynucleotides tested, only poly(G) and oligo(dG) were effective inhibitors, suggesting a role for guanines or guanine-rich sequences of RNA in the inhibition reaction.

DNA-Directed RNA Polymerases↗

Response of transplanted AKR leukemia to combination therapy with amphotericin B and 1,3-bis(2-chloroethyl)-1-nitrosourea: dose and schedule dependency.

A number of different amphotericin B (AmB)-1,3-bis(2 chloroethyl)-1-nitrosourea (BCNU) treatment regimens were evaluated with our model of transplantable AKR leukemia. We found that dose levels and treatment schedules were critical in determining the number of survivors. A 4-day treatment regimen of 0.5 mg AmB/mouse on days 1, 2, 3, and 4 and 0.2 mg BCNU/mouse on day 4 was found to be the most effective and has been chosen as our standard regimen. The efficacy of the treatment regimen depended on the presence of a large tumor burden, and the response was abolished when the mice were preirradiated or treated with the immunosuppressive agent, cyclophosphamide. These results, as well as others which we discuss, supported our notion that AmB affected host immune response to the tumor.

Amphotericin B↗

Effects of amphotericin B on macrophages and their precursor cells.

The effect of amphotericin B (AmB) treatment on the mononuclear phagocyte system of mice was investigated. Peritoneal macrophages from mice that received AmB treatment showed a higher phagocytic and antibacterial activity than those from normal untreated mice. When the levels of macrophage precursor cells in bone marrow and spleen were followed in mice after AmB treatment, an eightfold increase in the splenic content of limited stem cells for both macrophages and granulocytes (colony-forming units in culture) and a threefold increase in the number of pluripotent hemopoietic stem cells (colony-forming units in spleen) were observed on day 4. These were also accompanied by a slight increase in the colony-forming units in spleen and in culture in femoral marrows. AmB was capable of inducing a large number of peritoneal colony-forming cells in the peritoneum, and caused a significant rise in the serum level of colony-stimulating factor. No significant change in the level of blood monocytes was noted, although a transient increase in the proportion of neutrophils was observed within 24 h after AmB treatment.

Amphotericin B↗

Therapy of murine aspergillosis with amphotericin B in combination with rifampin of 5-fluorocytosine.

Suboptimal doses of amphotericin B in combination with either rifampin or 5-fluorocytosine were better than single-drug therapy in the treatment of disseminated Aspergillus fumigatus infection in mice. Despite the increased effectiveness of combination therapy, none of the therapeutic regimens we used completely eradicated infections in the mice when evaluated by mycological culture, even in long-term survivors.

Amphotericin B↗

Amphotericin B and filipin effects on L and HeLa cells: dose response.

Amphotericin B (AmB) and filipin effects on L and HeLa cells were compared by monitoring drug-induced potassium leakage from cells, changes in radioactive uridine incorporation into cellular ribonucleic acid, protein leakage from cells, and cell viability. L cells were much more susceptible to both AmB and filipin than were HeLa cells, but the overall dose response was similar. For AmB, the various effects were easily separable. Potassium leakage occurred at the lowest concentrations of AmB and was reversible. Inhibition of uridine incorporation and loss of viability occurred at intermediate levels, and protein loss occurred at higher levels. In contrast, filipin was much more potent; its effects on potassium leakage were only minimally reversible, and the separation of the permeabilizing effects from complete cell lysis was possible only over a limited concentration range and for a short time.

Amphotericin B↗

A rapid radiometric method for determining the sensitivity of clinical isolates of Mycobacterium tuberculosis to several chemotherapeutic agents.

Current methods of performing antibiotic susceptibility tests on M. tuberculosis require 4 to 6 weeks for completion and in some cases have a poor correlation with clinical results. We have developed a rapid radiometric method of sensitivity testing which utilizes the incorporation of 3H-uracil into ribonucleic acid (RNA) as a measure of mycobacterial growth. The radiometric method is sensitive and reproducible and the results are completed in 48 hours. An excellent correlation was found between the radiometric method of sensitivity testing and the traditional agar plate technique when the two were compared with respect to isoniazid, streptomycin, and rifampicin sensitivities. There was no correlation between the two methods when ethambutol was tested. These results have confirmed our previous experiments on the usefulness of the radiometric method for the rapid determination of antibiotic susceptibilities of mycobacteria.

Ethambutol↗

Inhibition of isolated yeast and mycelial phase RNA polymerases of Histoplasma capsulatum by rifamycin derivatives.

Various derivatives of rifamycin were shown to inhibit the RNA polymerases of the yeast and mycelial phases of Histoplasma capsulatum. The relative potency of each of the derivatives against the isolated polymerases was the same as the potency of each against the viable organism. RNA polymerase PC III from the yeast phase was more susceptible to the rifamycin derivatives than yeast phase polymerases PC I and PC II and the biggest differences in susceptibility were seen with the derivative AF/ABDP (2,6-dimethyl-4-benzyl-4-demethyl-rifamycin). The susceptibility pattern of the mycelial polymerase activity was identical to the yeast polymerase PC III.

Cell Differentiation↗

Cutaneous protothecosis. Successful treatment with amphotericin B.

A patient had cutaneous protothecosis because of the alga-like organism, Prototheca wickerhamii. In vitro sensitivity tests showed that the organism was sensitive to amphotericin B, and was treated successfully with this polyene antibiotic. As with treatment of some fungal infections, a clinical response was achieved when therapy with low doses of amphotericin B was given during a short period of time. The basis of the amphotericin B response may have been due to a combination of its immunostimulatory and antibiotic properties.

Adult↗

Antibiotic sensitivity of the yeast and mycelial phases of Histoplasma capsulatum.

Cycloheximide and chloramphenicol in combination have a greater effect on yeast cells of Histoplasma capsulatum than on the mycelial phase of this fungus. In contrast, clotrimazole was found to be more effective against mycelia. Miconazole produced a pronounced effect against both phases wheras tolnaftate was only slightly active. Sulfadiazine and griseofulvin were completely inactive against both phases. The differential sensitivities of the 2 phases of H. capsulatum to various antibiotics can be useful in studying the transition of the dimorphic fungus from 1 phase to the other.

Anti-Bacterial Agents↗

Protective effects of amphotericin B against spontaneous and transplantable murine tumors.

Two tumor systems were used to test prophylactic effects of amphotericin B (AmB). When 0.5 mg AmB was given ip every 2 weeks to AKR mice beginning at 8 weeks of age, the 50% tumor incidence for spontaneous lymphoma development was delayed 2-3 months. In the second tumor system, BALB/c mice received injections of either 20 or 50 mug AmB before receiving MOPC-315-C cells sc. The mice given the low dose of AmB demonstrated a decreased tumor incidence and a reduced tumor growth rate, when compared with controls. Opposite effects were found for the group administered the high dose; tumor incidence and rate of growth were increased.

Adjuvants, Immunologic↗