Extracellular calcium sensing promotes human B-cell activation and function.

Calcium is a second messenger for many signaling pathways in B cells, but its role as a receptor ligand has not been well characterized. However, pulses of free calcium were found to cause the rapid release of internal calcium stores in normal human B cells. This response appeared to be mediated by a cell surface protein with receptor properties as it could be blocked by pretreatment with trypsin and with kinase and phospholipase Cgamma inhibitors.

Toll-like receptor-7 tolerizes malignant B cells and enhances killing by cytotoxic agents.

Chronic activation through Toll-like receptors (TLR) occurs in a number of pathologic settings, but has not been studied to the same extent as primary activation. TLR7, expressed by B cells and some dendritic cells, recognizes molecular patterns associated with viruses that can be mimicked by synthetic imidazoquinolines. In response to primary stimulation with the imidazoquinoline, S28690, human mononuclear cells produced tumor necrosis factor-alpha, but were unable to do so upon restimulation with S28690.

Sensitization of IL-2 signaling through TLR-7 enhances B lymphoma cell immunogenicity.

The innate ability of B lymphoma cells to escape control by tumor-reactive T cells must be overcome to develop effective immunotherapies for these diseases. Because signals from both the innate and adaptive immune systems direct the acquisition of strong immunogenicity by professional APCs, the effects of IL-2 and the TLR-7 agonist, S28690, on the immunogenic properties of chronic lymphocytic leukemia (CLL) B cells were studied. IL-2 with S28690 caused CLL cells to proliferate and increased their expression of B7-family members, production of TNF-alpha and IL-10, and levels of tyrosine-phosphorylated STAT-1 and STAT-3 proteins.

Injuries, injury prevention and public health.

Objectives: To introduce the readers to the field of injury prevention and comprehensive public health intervention approaches.

Methods: A review of injury epidemiology, statistics, definitions, intervention approaches, and the importance of health promotion is provided.

Results: Behavioral, environmental, and technological solutions will be necessary to reduce or eliminate the factors that lead to injury.

Risk to self versus risk to others: how do older drivers compare to others on the road?

Background: The objective of this study was to assess the risk of death or nonfatal injury drivers aged >/=65 pose to themselves and to other road users as compared with drivers in younger age groups.

Methods: Crash-related deaths and injuries were separated into two categories: those occurring among the drivers themselves, and those occurring among others, such as passengers, bicyclists, or pedestrians.

Results: The number of deaths among others varied by driver's age, with deaths among others decreasing as the driver's age increased.

Surveillance for traumatic brain injury deaths--United States, 1989-1998.

Problem/condition: Data indicate that approximately 50,000 U.S. residents die as a result of traumatic brain injury (TBI) annually.