An ATP-activated channel is involved in mitogenic stimulation of human T lymphocytes

We investigated the effect of pharmacologic modulation of the ATP receptor on intracellular ion changes and proliferative response of human peripheral blood lymphocytes (PBLs) and purified T lymphocytes. Extracellular ATP (ATPe) triggered in these cells an increase in the cytoplasmic Ca2+ concentration ([Ca2+]i) and plasma membrane depolarization. Whereas both Ca2+ release from intracellular stores and influx across the plasma membrane were detected in the whole PBL population, only Ca2+ influx was observed in T cells. In the presence of near physiologic extracellular Na+ concentrations (125 mmol/L), Ca2+ permeability through the ATPe-gated channel was very low, suggesting a higher selectivity for monovalent over divalent cations. The selective P2Z agonist benzoylbenzoic ATP (BzATP) increased [Ca2+]i in the presence but not the absence of extracellular Ca2+ and also caused plasma membrane depolarization. The covalent blocker oxidized ATP (oATP), an inhibitor of P2X and P2Z receptors, prevented Ca2+ influx and plasma membrane depolarization, but had no effect on Ca2+ release from stores. Stimulation with ATPe alone had no significant effects on PBL 3H-thymidine incorporation. On the contrary, ATPe or BzATP had a synergistic effect on DNA synthesis stimulated by selective T-cell mitogens such as phytohemagglutinin, anti-CD3 monoclonal antibody, or allogenic PBLs (mixed lymphocyte cultures). Treatment with oATP inhibited mitogenic stimulation by these receptor-directed agents but not by the combined application of the Ca2+ ionophore ionomycin and phorbol myristate acetate. Interleukin-2 partially relieved inhibition by oATP. These results suggest that human T lymphocytes express a plasma membrane channel gated by ATPe that is involved in mitogenic stimulation.     

Self-report and Cognitive Processing Measures of Depressive Thinking Predict Subsequent Major Depressive Disorder

We examined the utility of two measures of cognitive bias—a self-report questionnaire, the Dysfunctional Attitudes Scale (Weissman and Beck 1978), and a cognitive processing task, the Scrambled Sentences Test (Wenzlaff 1988, 1993), in predicting episodes of depression prospectively in a community-based sample of nondepressed women. When examined separately, each measure contributed significantly to predicting a subsequent diagnosis of MDD, supporting the utility of both types of measures as indicators of depression vulnerability. When examined together, each measure made an independent contribution to the prediction of MDD, raising the possibility that questionnaire and processing tasks may assess separate aspects of cognitive vulnerability to depression.     

Blood donation leads to a decrease in natural killer cell activity: a study in normal blood donors and cancer patients

Transfusion-induced immunosuppression has long been known to be beneficial for organ transplantation patients, but recent retrospective studies suggest that blood transfusions may be detrimental for patients with cancer. If autologous blood is used to avoid immunosuppression, the assumption is that the procedure, involving blood donation, is immunologically neutral. In the present study, this assumption was evaluated by monitoring 33 normal blood donors and 16 colorectal cancer patients before and after donation of 1 (500 mL) and 2 units of blood, respectively. The cancer patients belonged to the autologous arm of a randomized trial in which the effects of allogeneic versus autologous blood on cancer prognosis were studied. The patients donated 2 units of blood with an interval of 3 to 4 days between donations. Flow cytometric analysis revealed that blood donation by normal donors and cancer patients had no effect on the proportion of B, T, and natural killer (NK) cells. Only the total number of lymphocytes was significantly decreased in the normal donors on Day 12 after donation. Blood donation had no significant effect on T-cell function assessed by phytohemagglutinin stimulation in normal donors or in cancer patients donating 2 units of blood. A significant depression of NK cell function (88% and 74% of predonation levels) was observed in normal donors on Days 2 and 5 after donation; on Day 12, the activity was again normal. Colorectal cancer patients had a significantly depressed NK cell activity (54% of predonation activity) on Day 12 after the first donation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Professionalism in medical education: an institutional challenge.

Despite considerable attention to professionalism in medical education nationwide, the majority of attention has focused on training medical students, and less on residents and faculty. Curricular formats are often didactic, removed from the clinical setting, and frequently focus on abstract concepts. As a result of a recent curricular innovation at the University of Washington School of Medicine (UWSOM) in which role-model faculty work with medical students in teaching and modeling clinical skills and professionalism, a new professionalism curriculum was developed for preclinical medical students. Through student feedback, that curriculum has changed over time, and has become more focused on the clinical encounter. This new and evolving curriculum has raised awareness of the existence of an "ecology of professionalism." In this ecological model, changes in the understanding of and attention to professionalism at one institutional level lead to changes at other levels. At the UWSOM, heightened attention to professionalism at the medical student level led to awareness of the need for increased attention to teaching and modeling professionalism among faculty, residents, and staff. This new understanding of professionalism as an institutional responsibility has helped UWSOM teachers and administrators recognize and promote mechanisms that create a "safe" environment for fostering professionalism. In such an institutional culture, students, residents, faculty, staff, and the institution itself are all held accountable for professional behavior, and improvement must be addressed at all levels.