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Biomedical subjects

Mary F Ward

Publications and source records attributed to Mary F Ward.

5 recordsLinked to original sources
PubMed2006

Potential role of high mobility group box 1 in viral infectious diseases.

A nuclear protein, high mobility group box 1 (HMGB1), is released passively by necrotic cells and actively by macrophages/monocytes in response to exogenous and endogenous inflammatory stimuli. After binding to the receptor for advanced glycation end products (RAGE), or Toll-like receptor 4 (TLR4), HMGB1 activates macrophages/monocytes to express proinflammatory cytokines, chemokines, and adhesion molecules. Pharmacological suppression of its activities or release is protective against lethal endotoxemia and sepsis, establishing HMGB1 as a critical mediator of lethal systemic inflammation. In light of observations that many viruses (e.g., West Nile virus, Salmon anemia virus) can induce passive HMGB1 release, we propose a potential pathogenic role of HMGB1 in viral infectious diseases.

HMGB1 Protein↗
PubMed2004

Extracellular HMGB1 as a proinflammatory cytokine.

High mobility group box-1 protein (HMGB1, formerly known as HMG-1), a highly conserved ubiquitous protein, has been for a long time described as a nuclear DNA-binding protein involved in nucleosome stabilization and gene transcription. Recent discoveries indicate that HMGB1 is released from activated innate immune cells or necrotic cells and functions as an important mediator of endotoxemia, sepsis, arthritis, and local inflammation. Therapeutic agents that inhibit HMGB1 release or action confer significant protection against endotoxemia, sepsis, and arthritis in animal models and thus hold potential for the clinical management of various inflammatory diseases.

Animals↗
PubMed2004

Bench to bedside: HMGB1-a novel proinflammatory cytokine and potential therapeutic target for septic patients in the emergency department.

Overwhelming gram-negative bacterial infection and life-threatening systemic inflammation are widespread problems in critically ill emergency department patients. Currently, the treatment of these patients is largely supportive, focusing on antibiotics, fluids, hemodynamic and ventilatory support, and intensive monitoring. The only Food and Drug Administration-approved pharmaceutical agent for the treatment of sepsis is activated protein C, with its use largely relegated to the intensive care unit. The subject thus remains an active area of exploration for emergency medicine research. During sepsis and inflammation, innate immune cells release excessive amounts of proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1beta. If delivered early enough, anti-TNF antibodies can be an effective therapy in experimental models of septic shock. Anti-TNF antibodies have been developed for clinical use in rheumatoid arthritis and Crohn's disease. However, anti-TNF treatment for sepsis has been difficult to achieve in the clinical setting, perhaps because TNF's early release and transient appearance in the serum create a narrow therapeutic window. An alternative strategy would be to identify "late" mediators that may be clinically more accessible. High mobility group box 1 (HMGB1), a protein previously known only as a nuclear transcription factor, is now implicated as a late mediator of sepsis. Targeting late mediators of lethal systemic inflammation represents a novel approach that may widen the therapeutic window and lead to new strategies for inhibiting the deleterious effects of the inflammatory cascade. Here the authors review the studies that led to the discovery of HMGB1 as a late mediator of systemic inflammation and discuss the possibility of HMGB1 as a therapeutic target for septic patients in the emergency department.

Animals↗
PubMed2003

A survey of the emergency department population and their interest in preventive health education.

OBJECTIVE: To determine which preventive health information the emergency department (ED) population (patients and visitors) would be most interested in having available to them while they spend time in the waiting area. METHODS: This was a prospective survey of consecutive adults seated in the ED waiting area during a representative week on predetermined shifts. The survey asked them to indicate whether they would be interested in obtaining information about the following preventive health issues: breast cancer, prostate cancer, smoking, obesity, stress reduction, exercise programs, alcohol/drugs, HIV, blood pressure screening, immunizations, referrals to primary care physicians, Pap smears, car safety, smoke detectors, domestic and youth violence, depression, gun safety, and safe sex. RESULTS: Of the 1284 subjects approached, 878 (68%) made up the study group (56% female, mean age = 44 years, 60% white); 406 refused. The information people were most interested in obtaining was the following: 52% of the respondents were interested in referral to stress reduction programs, 51% in information about exercise programs, 42% in blood pressure screening, 40% in information about breast cancer screening, 33% in depression information/screening, 33% in prostate cancer screening, 26% in immunization against pneumococcus, 24% in immunization against tetanus, 26% in smoking cessation programs, and 26% in safe driving information. Women were most interested in breast cancer screening (64%); and men, in prostate cancer screening (55%). CONCLUSIONS: Of the 878 subjects in the study group, 96% were interested in obtaining information about one or more preventive health issues. An opportunity exists to respond to this interest by providing material for public health education in the waiting area of EDs.

Adult↗