Publications

In the United States, companies that use their own funds to test consumer products on their employees are subject to few regulations. Using previously undisclosed tobacco industry documents, we reviewed the history of that industry's efforts to create internal guidelines on the conditions to be met before employee taste testers could evaluate cigarettes made from tobacco treated with experimental pesticides. This history highlights 2 potential ethical issues raised by unregulated industrial research: conflict of interest and lack of informed consent. To ensure compliance with accepted ethical standards, an independent federal office should be established to oversee industrial research involving humans exposed to experimental or increased quantities of ingested, inhaled, or absorbed chemical agents.

BACKGROUND

Depression leads to adverse outcomes in patients with coronary heart disease (CHD). Medication nonadherence is a potential mechanism for the increased risk of CHD events associated with depression, but it is not known whether depression is associated with medication nonadherence in outpatients with stable CHD.

METHODS

We examined the association between current major depression (assessed using the Diagnostic Interview Schedule) and self-reported medication adherence in a cross-sectional study of 940 outpatients with stable CHD.

RESULTS

A total of 204 participants (22%) had major depression. Twenty-eight (14%) of 204 depressed participants reported not taking their medications as prescribed compared with 40 (5%) of 736 nondepressed participants (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.7-4.7; P<.001). Twice as many depressed participants as nondepressed participants (18% vs 9%) reported forgetting to take their medications (OR, 2.4; 95% CI, 1.6-3.8; P<.001). Nine percent of depressed participants and 4% of nondepressed participants reported deciding to skip their medications (OR, 2.2; 95% CI, 1.2-4.2; P = .01). The relationship between depression and nonadherence persisted after adjustment for potential confounding variables, including age, ethnicity, education, social support, and measures of cardiac disease severity (OR, 2.2; 95% CI, 1.2-3.9; P = .009 for not taking medications as prescribed).

CONCLUSIONS

Depression is associated with medication nonadherence in outpatients with CHD. Medication nonadherence may contribute to adverse cardiovascular outcomes in depressed patients.

The in vivo mechanism of regulatory T cell (T(reg) cell) function in controlling autoimmunity remains controversial. Here we have used two-photon laser-scanning microscopy to analyze lymph node priming of diabetogenic T cells and to delineate the mechanisms of T(reg) cell control of autoimmunity in vivo. Islet antigen-specific CD4(+)CD25(-) T helper cells (T(H) cells) and T(reg) cells swarmed and arrested in the presence of autoantigens. These T(H) cell activities were progressively inhibited in the presence of increasing numbers of T(reg) cells. There were no detectable stable associations between T(reg) and T(H) cells during active suppression. In contrast, T(reg) cells directly interacted with dendritic cells bearing islet antigen. Such persistent T(reg) cell-dendritic cell contacts preceded the inhibition of T(H) cell activation by dendritic cells, supporting the idea that dendritic cells are central to T(reg) cell function in vivo.

Neural progenitor cells (NPCs) have been shown to be a promising therapy for cell replacement and gene transfer in neurological diseases including traumatic brain injury (TBI). However, NPCs often survive poorly after transplantation despite immunosuppression, and the mechanisms of graft cell death are unknown. In this study, we evaluated caspase- and calpain-mediated mechanisms of cell death of neonatal mouse C17.2 progenitor cells, transplanted at 24 h following lateral fluid percussion brain injury (FP) in rats. Adult Male Sprague-Dawley rats (n = 30) were subjected to lateral FP injury (n = 18) or sham surgery (n = 12). C17.2 cells labeled with green fluorescent dye (CMFDA) were engrafted in the perilesional deep cortex, and animals were sacrificed at 24 h, 72 h and 1 week post-transplantation. Pro-apoptotic caspase-mediated cleavage products (Ab246) and calpain-mediated cleavage products (Ab38) were detected in the engrafted cells using immunohistochemistry. Only 2 to 4.5% of grafted NPCs were found to survive at 24 h post-transplantation, regardless of injury status of the host brain, although brain-injured animals had significantly fewer graft cells than sham-injured animals. Limited caspase and calpain-mediated graft cell death was observed in both sham- and brain-injured animals, and caspase-mediated graft cell death was significantly greater than calpain-mediated graft cell death in all animals. Brain-injured animals had significantly increased caspase-mediated graft cell death compared to sham-injured animals. These results suggest that both the caspase and calpain family of proteases are involved in graft cell death, and that caspase-mediated apoptotic graft cell death predominates in the acute post-traumatic period following TBI.