Joan M. Fisher

Toso, a Cell Surface, Specific Regulator of Fas-Induced Apoptosis in T Cells

Fas is a surface receptor that can transmit signals for apoptosis. Using retroviral cDNA library-based functional cloning we identified a gene, toso, that blocks Fas-mediated apoptosis. Toso expression was confined to lymphoid cells and was enhanced after cell-specific activation processes in T cells. Toso appeared limited to inhibition of apoptosis mediated by members of the TNF receptor family and was capable of inhibiting T cell self-killing induced by TCR activation processes that up-regulate Fas ligand. We mapped the effect of Toso to inhibition of caspase-8 processing, the most upstream caspase activity in Fas-mediated signaling, potentially through activation of cFLIP. Toso therefore serves as a novel regulator of Fas-mediated apoptosis and may act as a regulator of cell fate in T cells and other hematopoietic lineages.

Moral Distress Among Healthcare Professionals: Report of an Institution‐Wide Survey

PURPOSE Moral distress is a phenomenon affecting many professionals across healthcare settings. Few studies have used a standard measure of moral distress to assess and compare differences among professions and settings. DESIGN A descriptive, comparative design was used to study moral distress among all healthcare professionals and all settings at one large healthcare system in January 2011. METHODS Data were gathered via a web-based survey of demographics, the Moral Distress Scale-Revised (MDS-R), and a shortened version of Olsons Hospital Ethical Climate Scale (HECS-S). FINDINGS Five hundred ninety-two (592) clinicians completed usable surveys (22%). Moral distress was present in all professional groups. Nurses and other professionals involved in direct patient care had significantly higher moral distress than physicians (p = .001) and other indirect care professionals (p < .001). Moral distress was negatively correlated with ethical workplace climate (r = -0.516; p < .001). Watching patient care suffer due to lack of continuity and poor communication were the highest-ranked sources of moral distress for all professional groups, but the groups varied in other identified sources. Providers working in adult or intensive care unit (ICU) settings had higher levels of moral distress than did clinicians in pediatric or non-ICU settings (p < .001). Providers who left or considered leaving a position had significantly higher moral distress levels than those who never considered leaving (p < .001). Providers who had training in end-of-life care had higher average levels of moral distress than those without this training (p = .005). CONCLUSIONS Although there may be differences in perspectives and experiences, moral distress is a common experience for clinicians, regardless of profession. CLINICAL RELEVANCE Moral distress is associated with burnout and intention to leave a position. By understanding its root causes, interventions can be tailored to minimize moral distress with the ultimate goal of enhancing patient care, staff satisfaction, and retention.

Intracellular Combinatorial Chemistry with Peptides in Selection of Caspase-like Inhibitors

Fas is a cell surface receptor that can transmit signals for programmed cell death. Using a retroviral expression system, we have demonstrated that a short peptide derived from the cleavage site in a cellular target of a pro-apoptotic cysteine protease can be expressed within intact cells with sufficient activity to inhibit Fas-mediated apoptosis. In vitro analysis demonstrates that this retrovirally-expressed peptide is as potent as 150uM levels of the chemically synthesized peptide. Furthermore, using retroviral peptide library-based functional cloning we identified variants of this peptide with apparent anti-apoptotic activity. This approach is likely to lead to the identification of peptide variants with activity against a variety of signaling processes, both normal and pathological.