Genetic abnormalities in CD-1 mice after dietary restriction.
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Biomedical subjects
Publications and source records attributed to B J Phillips.
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In December 1975 and January and February 1976, an epidemic of cutaneous sporotrichosis occurred in Mississippi among forestry workers and other persons exposed to sphagnum moss used in packing pine seedlings. Seventeen cases were identified, 15 of which were from patients who had been exposed to sphagnum moss from a single source. Attack rates were significantly higher among workers exposed to this moss than among those not exposed. Sporothrix schenckii was cultured from the implicated batch of sphagnum moss but not from other batches. The source of contamination of the sphagnum moss that caused this epidemic and sphagnum moss associated with similar epidemics is unknown. One worker without cutaneous sporotrichosis may have had asymptomatic pulmonary sporotrichosis.
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The primary objective of this study was to determine whether freezing sputa in dry ice had any effect on the recovery of pathogenic fungi. Sputa seeded with each of five fungi (Histoplasma capsulatum, Blastomyces dermatitidis, Cryptococus neoformans, Coccidioides immitis, and Aspergillus fumigatus) were frozen and stored for 24, 48, and 72 hours on dry ice. H. capsulatum was killed, and only a few colonies of B. dermatitidis and C. neoformans were isolated from these sputa. However, A. fumigatus and C. immitis withstood the effects of freezing. A second objective was to compare the recovery of all five fungi from seeded sputa stored at room temperature for 24, 48, and 72 hours, on yeast extract-phosphate agar with NH4OH and on Sabhi agar. The yeast extract-phosphate agar with NH4OH was superior to Sabhi agar, for the isolation of all fungi studied, except A. fumigatus.
The intracellular level of guanosine 3',5'-monophosphate (cGMP) has been measured in Walker carcinoma cells in tissue culture after treatment with various alkylating agents. At concentrations which caused a rise in the level of adenosine 3',5'-monophosphate (cAMP) chlorambucil and 5-(1-aziridinyl)-2,4-dinitrobenzamide (CB 1954) produced only a small (35%) elevation of cGMP, while merophan had no such effect. This suggests that any effect of cAMP will not be outweighed by an equivalent rise in cGMP. Sepcific cytosolic binding of cGMP decreased with increasing resistance of Walker cells to alkylating agents, while the dissociation constant, KD, for binding increased. This was also observed with cAMP binding which suggests that the same protein in responsible for binding both nucleotides.
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The effect of cetylpyridinium chloride (CPC) on pathogenic fungi and Nocardia asteroides was studied. Sputa seeded with each of 11 organisms (Aspergillus flavus; Aspergillus fumigatus, Blastomyces dermatitidis, Candida albicans, Coccidioides immitis, Cryptococcus neoformans, Geotrichum candidum, Histoplasma capsulatum; Nocardia asteroides, Paracoccidioides brasiliensis, and Sporothrix schenckii) were treated with CPC and kept for 2, 5 and 9 days. The CPC reagent used (0.5% CPC and 0.5% sodium chloride) is one the Mycobacteriolgoy Branch at the Center for Disease Control added to sputa before shipping them to laboratories for recovery of mycobacteria. None of the organisms tested survived this treatment, and none was recovered on mycological or mycobacteriological media. Seeded sputa containing these organisms were also tested with a second CPC reagent (0.02% CPC and 0.5% sodium chloride) and held for 2, 5 and 9 days. A few colonies of A. flavus, A. fumigatus, and N. asteroides were recovered from these samples. Neither the morphology of the fungi nor their stainability by the fluorescent antibody method was affected by treatment with the reagent containing 0.5% CPC. However, the background material in smears from the 0.5% CPC-treated samples retained the conjugate, and this made weakly fluorescing organisms more difficult to detect. The 0.5% CPC treatment did not alter the morphology of N. asteroides or its ability to be stained with Kinyoun acid-fast stain.
The hypothesis that selective action of cyclophosphamide, compared to other nitrogen mustards, is due to a balance between enzymatic formation of inactive metabolites and chemical formation of the alkylating product was studied in view of previous observation in our laboratory. Metabolite analysis, inhibition of growth of tumor cells in culture, and kinetic analysis of relevant enzyme activities were used in this investigation. The effect of tissue-soluble enzyme fractions on biochemically prepared aldophosphamide, aldophosphamide analogs, and phosphoramide mustard showed: (a) a range of deactivation abilities with aldophosphamide (liver greater than kidney greater than intestinal mucosa greater than tumor greater than spleen = bovine serum albumin solution); (b) the formation of different amounts of carboxyphosphamide from aldophosphamide; and (c) only comparatively small reductions in the toxicity of phosphoramide mustard and of 4-hydroxy-4methylcyclophosphamide. Correlations were found between NAD+-dependent aldehyde dehydrogenase activity and the deactivation ability of tissue-soluble enzyme fractions. Blockage (by C4 substitution) or inhibition (by disulfiram) of secondary oxidation of aldophosphamide, mediated by aldehyde dehydrogenase, resulted in diminished deactivation ability in vitro and reduced selectivity in vivo.
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