ABSTRACT
Incorporation of glycopeptide, glycolipid and peptidoglycolipid preparations from the culture fluid or organisms of a variety of mycobacterial species in suboptimally stimulated cultures of normal mouse bone marrow cells increased the responsiveness of colony-forming cells to colony-stimulating factor, as measured by enhanced colony formation. Possible mechanisms of action and the significance of enhanced colony growth in relation to the mode of action of mycobacterial adjuvants are discussed.
Subject(s)
Glycolipids/pharmacology , Glycopeptides/pharmacology , Hematopoietic Stem Cells/metabolism , Animals , Cells, Cultured , Colony-Stimulating Factors/biosynthesis , Dose-Response Relationship, Drug , Hematopoietic Stem Cells/drug effects , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , MycobacteriumSubject(s)
Chemotaxis, Leukocyte , Histamine H2 Antagonists/pharmacology , Hypergammaglobulinemia/immunology , Immunoglobulin E , Adult , Cimetidine/pharmacology , Humans , Hypersensitivity, Delayed/diagnosis , Lymphocytes/immunology , Male , Neutrophils , Phytohemagglutinins/pharmacology , Skin TestsABSTRACT
Addition of low concentrations (10 ng/ml) of saponin or Tween 80 to stimulated cultures of normal mouse bone marrow in agar increased the number of granulocyte-macrophage colonies which developed. Addition of cyclic AMP or dibutyryl cyclic AMP in low concentration (10(-8) to 10(-10) M) also enhanced colony numbers although concentrations above 10(-5) M were inhibitory. enhancement was found when marrow cells were pre-treated with these agents and cultured in their absence. The agents did not stimulate colony development in the absence of colony-stimulating factor and enhancement of colony number occurred only in cultures containing a concentration of colony-stimulating factor which was sub-optimal in terms of maximum colony development. There was no indication of increased colony-stimulating factor production by treated marrow cells under the experimental conditions used to show colony enhancement. It was concluded that the agents caused an increased responsiveness of colony-forming cells to colony-stimulating factor.
Subject(s)
Bone Marrow Cells , Bone Marrow/drug effects , Colony-Stimulating Factors/pharmacology , Cyclic AMP/pharmacology , Glycoproteins/pharmacology , Polyethylene Glycols/pharmacology , Polysorbates/pharmacology , Saponins/pharmacology , Adenosine Monophosphate/pharmacology , Adenosine Triphosphate/pharmacology , Animals , Bucladesine/pharmacology , Clone Cells/drug effects , Dose-Response Relationship, Drug , Female , Male , Mice , Mice, Inbred C57BL , Nucleotides, Cyclic/pharmacology , Stimulation, Chemical , TemperatureSubject(s)
Bone Marrow Cells , Bone Marrow/immunology , Hydrocortisone/pharmacology , Leukocytes , Macrophages , Age Factors , Animals , Cell Division/drug effects , Cells, Cultured , Clone Cells , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Mice, Inbred Strains , Sex Factors , Species Specificity , Spleen/cytologySubject(s)
Granulocytes/drug effects , Interferons/pharmacology , Leukocytes/drug effects , Macrophages/drug effects , Animals , Bone Marrow/drug effects , Cell Count , Cell Division/drug effects , Cells, Cultured , Chromatography, Gel , Dose-Response Relationship, Drug , Female , Injections, Intraperitoneal , L Cells , Male , Mice , Mice, Inbred C57BL , UltrafiltrationSubject(s)
Bone Marrow Cells , Bone Marrow/drug effects , Interferons/biosynthesis , Polynucleotides/pharmacology , Animals , Cell Differentiation/drug effects , Cells, Cultured , Chromatography , Cricetinae , Cytosine Nucleotides/pharmacology , Depression, Chemical , Dextrans , Female , Haplorhini , Hematopoiesis , Humans , Injections, Intraperitoneal , Injections, Intravenous , Inosine Nucleotides/pharmacology , Interferons/blood , Male , Poly I-C , Rabbits , Species SpecificityABSTRACT
The antiviral drug methisazone (N-methylisatin beta-thiosemicarbazone) was tested for its effect on immune responses to sheep erythrocytes and on hemopoietic colony-forming cell (granulocyte-macrophage progenitor cell) responses to complete Freund's adjuvant in mice. Suppressive activity was demonstrated in both systems, the immune system being more readily and more consistently susceptible. Evidence is presented which suggests that the insoluble particulate form of the drug has both stimulatory and suppressive effects on the colony-forming cell system, whereas the soluble form is only suppressive. Methisazone increased the mortality from ectromelia in adjuvant-treated animals.
Subject(s)
Antiviral Agents/pharmacology , Hematopoiesis/drug effects , Immunosuppression Therapy , Indoles/pharmacology , Thiosemicarbazones/pharmacology , Animals , Bone Marrow Cells , Cells, Cultured , Erythrocytes/immunology , Female , Mice , Mice, Inbred C57BL , Sheep/immunology , Spleen/cytologySubject(s)
Bone Marrow Cells , Bone Marrow/drug effects , Interferons/blood , Animals , Cell Division/drug effects , Chromatography , Clone Cells , Culture Techniques , Depression, Chemical , Ectromelia virus/drug effects , Encephalomyocarditis virus/drug effects , Hot Temperature , Hydrogen-Ion Concentration , Interferons/pharmacology , Mice , Orthomyxoviridae/drug effectsABSTRACT
Two patients on prolonged steroid therapy developed meningitis due to Cryptococcus neoformans. The first responded satisfactorily to treatment with amphotericin B, both initially and again following relapse. The second died shortly after treatment was begun. Pathogenicity studies suggest that the strain isolated from the fatal case was the more virulent. Cryptococcal meningitis probably occurs more often in Britain than is generally appreciated, and this possibility should be remembered when investigating patients with obscure forms of meningitis; if not, then the correct diagnosis may not be made. Attention is drawn to the increasing number of recently reported cases of this disease which have been associated with long-term steroid therapy.
