We have constructed strains of Pseudomonas aeruginosa with mutations in the algC gene, previously shown to encode the enzyme phosphomannomutase. The algC mutants of a serotype O5 strain (PAO1) and a serotype O3 strain (PAC1R) did not express lipopolysaccharide (LPS) O side chains or the A-band (common antigen) polysaccharide. The migration of LPS from the algC mutant strains in Tricine-sodium dodecyl sulfate-polyacrylamide gels was similar to that of LPS from a PAO1 LPS-rough mutant, strain AK1012, and from a PAC1R LPS-rough mutant, PAC605, each previously shown to be deficient in the incorporation of glucose onto the LPS core (K. F. Jarrell and A. M. Kropinski, J. Virol. 40:411-420, 1981, and P. S. N. Rowe and P. M. Meadow, Eur. J. Biochem. 132:329-337, 1983). We show that, as expected, the algC mutant strains had no detectable phosphomannomutase activity and that neither algC strain had detectable phosphoglucomutase (PGM) activity. To confirm that the PGM activity was encoded by the algC gene, we transferred the cloned, intact P. aeruginosa algC gene to a pgm mutant of Escherichia coli and observed complementation of the pgm phenotype. Our finding that the algC gene product has PGM activity and that strains with mutations in this gene produce a truncated LPS core suggests that the synthesis of glucose 1-phosphate is necessary in the biosynthesis of the P. aeruginosa LPS core. The data presented here thus demonstrate that the algC gene is required for the synthesis of a complete LPS core in two strains with different LPS core and O side chain structures.
Objective: One of the factors that may promote deterioration in quality of life and body composition in elderly men is the relative decline in serum testosterone levels with aging. In this study, we assessed the effects of modest doses of testosterone and a home-based strengthening program on quality of life and body composition in elderly men with relative testosterone insufficiency. Design: Double-blind, placebo-controlled randomized study (testosterone), and additional randomization to a resistance exercise program or no additional exercise for 12 weeks in men between ages of 65 and 85 years with relative testosterone insufficiency. Methods: Seventy sedentary, community dwelling men were randomized to a 5 mg testoderm transdermal system applied daily vs placebo system, and additionally randomized to a home-based resistance exercise program. Subjects were randomized to Group 1 (testosterone plus exercise), Group 2 (testosterone plus no exercise), Group 3 (placebo plus exercise), and Group 4 (placebo plus no exercise). Endpoints included quality of life (assessed by the short form-36 questionnaire) and body composition (measured by dual x-ray absorptiometry scan). Results: Serum testosterone increased by a mean of 10.0G1.9, 6.6G1.6, 0.52G0.6, and 0.5G 0.6 nmol/l in Groups 1, 2, 3, and 4 respectively. There was a significant interaction of testosterone and exercise on quality of life in the domains of physical functioning (PZ0.03), role physical (PZ0.01), general health (PZ0.049), and social functioning (PZ0.04). There were no effects of testosterone or exercise on quality of life alone, nor in body composition parameters. Conclusions: Modest testosterone supplementation to elderly men with relative testosterone insufficiency improved quality of life when accompanied by an exercise program. The combination of testosterone and exercise may be an important strategy in the elderly, though further studies are necessary to determine the long-term impact on body composition and function and for analysis of risk/benefit ratios as well.European Journal of Endocrinology 155 867-875
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