Transformation-defective mutants of avian sarcoma viruses: the genetic relationship between conditional and nonconditional mutants.
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Biomedical subjects
Publications and source records attributed to A Bernstein.
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Induction of erythroid differentiation in ouabain-resistant murine erythroleukemia cells by ouabain is reported. Ouabain induction results in the appearance of hemoglobin-containing cells 12-24 hr earlier than induction of the same clone by dimethyl sulfoxide. The levels of globin mRNA after ouabain induction are similar in amount to the globin mRNA levels observed after induction by dimethyl sulfoxide. The concentration of ouabain required to induce hemoglobin synthesis depends upon the K+ ion levels in the culture medium. Lowering the extracellular K+ ion concentration 2-4 fold reduced by 10-40 fold the ouabain concentration necessary for the induction of hemoglobin synthesis. In low K+ medium (1.8 mM), ouabain is an effective inducer of hemoglobin synthesis at a concentration of 0.02 mM. This K+ effect is specific for ouabain induction, since induction by other inducers, such as dimethyl sulfoxide and dimethyl acetamide, does not exhibit this marked sensitivity to the levels of K+ ions in the culture medium. These results suggest that the binding of ouabain to the plasma membrane enzyme, Na/K ATPase, is required for the induction of erythroid differentiation by ouabain. A small but significant proportion of wild-type, ouabain-sensitive cells also can be induced by ouabain, below ouabain concentrations that are toxic to these cells. The observation that the binding of ouabain to the Na/K ATPase induces hemoglobin synthesis suggests that changes in the intracellular concentration of K+ ions may be involved in the control of erythroid differentiation in Friend erythroleukemic cells.
Four patients exposed to isocyanate vapour developed dyspnoea associated with restriction and reduced gas transfer as well as moderate airways obstruction on lung function testing. In one patient bilateral radiographic shadowing was present and an open lung biopsy was performed. The microscopic appearances ranged from acute inflammation to end-stage fibrosis but the centribular accentuation of disease and the presence of areas resembling bronchopulmonary aspergillosis suggested that the process was a hypersensitivity response to inhaled allergen. Challenge tests with albumin and toluene diisocyanate-albumin were carried out in sensitized and control rabbits. The sensitized animals developed extensive lung damage of the type associated with an Arthus reaction. It is suggested that patients exposed to isocyanates may occasionally develop a hypersensitivity pneumonitis rather than the more usual asthmatic syndrome.
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Clinical details are given of two patients who developed ipsilateral pulmonary oedema following re-expansion of their spontaneous pneumothoraces by intercostal drainage of air. The possible mechanisms underlying the oedema are discussed, and prior literature is analysed. Reference is made particularly to its predictability and to precautions recommended to minimize the frequency of this potentially fatal complication in the management of spontaneous pneumothorax.
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Colicin-tolerant mutants of Escherichia coli K-12, which map near gal at 17 min (tolA, B mutants), have been isolated and characterized. These mutants exhibited a very broad spectrum of phenotypic changes consistent with the interpretation that they are cell surface mutants. In addition to being colicintolerant and sensitive to deoxycholate and ethylenediaminetetraacetic acid, tolA, B mutants are sensitive to vancomycin, bacitracin, and dodecyl sulfate. The tolA, B mutants from most strains also formed mucoid colonies at 30 C on nutrient agar plates and had a greatly increased plating efficiency for lysisdefective S mutants of bacteriophage lambda. Complementation analysis showed that the four phenotypic groups of tol mutants that map near gal fall into three complementation groups: tolP, tolA, and tolB. Recombination analysis by three-factor crosses established the order of the three groups as tolP-tolA-tolB-gal. Because of the wide variety of phenotypic changes that accompanies mutation to colicin tolerance, revertants were isolated to test whether single or multiple mutations were involved. The reversion analysis, as well as other genetic criteria, confirmed that only single mutations were involved, suggesting that these pleiotropic changes are a consequence of a single change in the E. coli cell surface.
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