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Biomedical subjects

M A Brennan

Publications and source records attributed to M A Brennan.

6 recordsLinked to original sources
PubMed2000

Salmonella induces macrophage death by caspase-1-dependent necrosis.

We provide evidence that Salmonella typhimurium kills phagocytes by an unusual proinflammatory mechanism of necrosis that is distinguishable from apoptosis. Infection stimulated a distinctly diffuse pattern of DNA fragmentation in macrophages, which contrasted with the marked nuclear condensation displayed by control cells undergoing chemically induced apoptosis. In apoptotic cells, DNA fragmentation and nuclear condensation result from caspase-3-mediated proteolysis; caspases also subvert necrotic cell death by cleaving and inactivating poly ADP-ribose polymerase (PARP). Caspase-3 was not activated during Salmonella infection, and PARP remained in its active, uncleaved state. Another hallmark of apoptosis is sustained membrane integrity during cell death; yet, infected macrophages rapidly lost membrane integrity, as indicated by simultaneous exposure of phosphatidylserine with the uptake of vital dye and the release of the cytoplasmic enzyme lactate dehydrogenase. During experimentally induced necrosis, lethal ion fluxes through the plasma membrane can be prevented by exogenous glycine; similarly, glycine completely blocked Salmonella-induced cytotoxicity. Finally, inhibition of the interleukin (IL)-1-converting enzyme caspase-1 blocked the death of infected macrophages, but not control cells induced to undergo apoptosis or necrosis. Thus, Salmonella-infected macrophages are killed by an unusual caspase-1-dependent mechanism of necrosis.

Apoptosis↗
PubMed2000

Comparison of service member and military spouse satisfaction with installation fitness facilities and exercise programs.

Satisfaction with fitness facilities has long been accepted as a positive contributing factor to physical activity, readiness, and overall quality of life for military families. Our findings are based on a random sample of military families surveyed at 38 installations worldwide and at remote locations. A total of 8,572 service member and 3,493 spouse (55% and 32% response rate, respectively) questionnaires were completed and returned. Overall, members were satisfied with fitness facilities and programs, but spouses were less satisfied and more unfamiliar with these facilities. Most valued programs were fitness centers and swimming pools. Members reported that elimination of fitness facilities would greatly decrease the quality of life on installations, particularly at sites outside the continental United States, whereas spouses reported that this would not have a dramatic effect. The results of this study could be used to direct funding allocations, improve the health and fitness of military families, and suggest areas for further research.

Adult↗
PubMed1997

A branch in the ToxR regulatory cascade of Vibrio cholerae revealed by characterization of toxT mutant strains.

Co-ordinate expression of genes associated with pathogenicity in Vibrio cholerae requires two transcription activators, ToxR and ToxT. Work carried out to date suggests that ToxR activates transcription of the toxT gene and that ToxT directly activates transcription of several genes whose products play a role in colonization or CT production by V. cholerae. Previous work also suggests that ToxR can directly activate transcription of the CT operon (ctxAB) independently of ToxT, thereby implying a degree of complexity in control of the cixAB operon not found with other genes of the ToxR regulon. We tested the regulatory cascade model of virulence gene expression by constructing strains of classical and El Tor V. cholerae deleted for the coding sequence for the putative DNA-binding domain of toxT. Phenotypic analysis of these strains suggests that V. cholerae has ToxT-dependent and ToxT-independent branches of its virulence regulon. The results also raise questions about the precise role for ToxR in activation of ctxAB transcription.

Adhesins, Bacterial↗
PubMedDate not supplied

Physical activity patterns and body mass index scores among military service members.

Questionnaires on exercise practices, reasons for exercising, factors that would increase exercise, and demographics were mailed to a stratified random sample of 19,510 active duty personnel in all of the United States military services who were stationed at 38 large military installations and a number of remote locations. Responses were returned by 8,572 (55%). Approximately 63% exercised three times a week for 15-20 minutes, and 15% did not exercise at all. Mean BMI was 25.2. The top five reasons for exercising were to improve physical conditioning, have fun, manage weight, improve appearance and manage stress.

Body Mass Index↗