Analysis of detergent-free lipid rafts isolated from CD4+ T cell line: interaction with antigen presenting cells promotes coalescing of lipid rafts

<p>Abstract</p> <p>Background</p> <p>Lipid rafts present on the plasma membrane play an important role in spatiotemporal regulation of cell signaling. Physical and chemical characterization of lipid raft size and assessment of their composition before, and after cell stimulation will aid in developing a clear understanding of their regulatory role in cell signaling. We have used visual and biochemical methods and approaches for examining individual and lipid raft sub-populations isolated from a mouse CD4⁺T cell line in the absence of detergents.</p> <p>Results</p> <p>Detergent-free rafts were analyzed before and after their interaction with antigen presenting cells. We provide evidence that the average diameter of lipid rafts isolated from un-stimulated T cells, in the absence of detergents, is less than 100 nm. Lipid rafts on CD4⁺T cell membranes coalesce to form larger structures, after interacting with antigen presenting cells even in the absence of a foreign antigen.</p> <p>Conclusions</p> <p>Findings presented here indicate that lipid raft coalescence occurs during cellular interactions prior to sensing a foreign antigen.</p

Downregulated Expression of Ly-6-ThB on Developing T Cells Marks CD4+CD8+ Subset Undergoing Selection in the Thymus

Interaction of TCRs on CD4+CD8+ immature T cell with MHC-peptide complexes on stromal cells is required for positive and negative selection in the thymus. Identification and characterization of a subpopulation of CD4+CD8+ thymocytes undergoing selection in the thymus will aid in understanding the mechanisms underlying lineage commitment and thymic selection. Herein, we describe the expression of Ly-6 ThB on developing thymocytes. The majority of CD4+CD8+ thymocytes express Ly-6 ThB at high levels. Its expression is downregulated in a subset of CD4+CD8+ thymocytes as well as in mature CD4+CD8- and CD4-CD8+ T cells. More importantly, interaction of TCR/coreceptor with the self-MHC-peptide contributes to the downregulation of ThB expression on developing thymocytes. These findings indicate that downregulation of ThB on CD4+CD8+ thymocytes identifies a unique subset (CD4+CD8+ThBneg–low) of thymocytes that has received the initial signals for thymic selection but have not yet downregulated the CD4 and CD8 cell surface expression. In addition, these results also indicate that a high frequency (Ÿ20–40%) of CD4+CD8+ immature thymocytes receive these initial signals during thymic selection

Hospital competition, resource allocation and quality of care

BACKGROUND: A variety of approaches have been used to contain escalating hospital costs. One approach is intensifying price competition. The increase in price based competition, which changes the incentives hospitals face, coupled with the fact that consumers can more easily evaluate the quality of hotel services compared with the quality of clinical care, may lead hospitals to allocate more resources into hotel rather than clinical services. METHODS: To test this hypothesis we studied hospitals in California in 1982 and 1989, comparing resource allocations prior to and following selective contracting, a period during which the focus of competition changed from quality to price. We estimated the relationship between clinical outcomes, measured as risk-adjusted-mortality rates, and resources. RESULTS: In 1989, higher competition was associated with lower clinical expenditures levels compared with 1982. The trend was stronger for non-profit hospitals. Lower clinical resource use was associated with worse risk adjusted mortality outcomes. CONCLUSIONS: This study raises concerns that cost reductions may be associated with increased mortality

The relationship between safety net activities and hospital financial performance

<p>Abstract</p> <p>Background</p> <p>During the 1990's hospitals in the U.S were faced with cost containment charges, which may have disproportionately impacted hospitals that serve poor patients. The purposes of this paper are to study the impact of safety net activities on total profit margins and operating expenditures, and to trace these relationships over the 1990s for all U.S urban hospitals, controlling for hospital and market characteristics.</p> <p>Methods</p> <p>The primary data source used for this analysis is the Annual Survey of Hospitals from the American Hospital Association and Medicare Hospital Cost Reports for years 1990-1999. Ordinary least square, hospital fixed effects, and two-stage least square analyses were performed for years 1990-1999. Logged total profit margin and operating expenditure were the dependent variables. The safety net activities are the socioeconomic status of the population in the hospital serving area, and Medicaid intensity. In some specifications, we also included uncompensated care burden.</p> <p>Results</p> <p>We found little evidence of negative effects of safety net activities on total margin. However, hospitals serving a low socioeconomic population had lower expenditure raising concerns for the quality of the services provided.</p> <p>Conclusions</p> <p>Despite potentially negative policy and market changes during the 1990s, safety net activities do not appear to have imperiled the survival of hospitals. There may, however, be concerns about the long-term quality of the services for hospitals serving low socioeconomic population.</p

Hospital competition, resource allocation and quality of care.

BackgroundA variety of approaches have been used to contain escalating hospital costs. One approach is intensifying price competition. The increase in price based competition, which changes the incentives hospitals face, coupled with the fact that consumers can more easily evaluate the quality of hotel services compared with the quality of clinical care, may lead hospitals to allocate more resources into hotel rather than clinical services.MethodsTo test this hypothesis we studied hospitals in California in 1982 and 1989, comparing resource allocations prior to and following selective contracting, a period during which the focus of competition changed from quality to price. We estimated the relationship between clinical outcomes, measured as risk-adjusted-mortality rates, and resources.ResultsIn 1989, higher competition was associated with lower clinical expenditures levels compared with 1982. The trend was stronger for non-profit hospitals. Lower clinical resource use was associated with worse risk adjusted mortality outcomes.ConclusionsThis study raises concerns that cost reductions may be associated with increased mortality

Revenue instability induced by conservation rate structures : an empirical investigation of coping strategies

Water suppliers have been adopting new rate structures to promote conservation. The shift away from rates based on historical average cost toward rates based on marginal cost has been motivated by the desire to send consumers the "right" price signal about the need to conserve drinking water. The shift toward conservation rate structures, though perhaps providing better incentives to use scarce water resources wisely, has predictable effects-it changes who pays what and it increases the variability of future revenue streams to the water agency. Though the definition of the "correct" rate structure can rightfully vary in different communities-depending on the marginal cost of new supplies or avoided demand and on the community's understanding of equity-the managerial strategies necessary to cope with the uncertainty brought about by conservation rate structures are universal. Revenue instability creates direct costs for water suppliers in the form of increased costs for borrowing, to say nothing of the indirect but very real costs of more complicated planning to provide for a reliable supply of water in the future. This study empirically examines the experience of water agencies that have adopted conservation rate structures and proposes ways for using quantitative tools to: 1) measure and cope with the added uncertainty; and 2) make explicit the magnitude of tradeoffs between revenue stability, equity, and the provision of incentives for efficient use of water resources