Regulation of cell survival during B lymphopoiesis: apoptosis and Bcl-2/Bax content of precursor B cells in bone marrow of mice with altered expression of IL-7 and recombinase-activating gene-2

B cell development in mouse bone marrow depends critically upon IL-7. To examine the possible in vivo trophic role of IL-7, we have quantitated apoptosis and Bcl-2 family proteins in populations of phenotypically defined B lineage cells in IL-7-deficient and IL-7-overexpressing mice. Using immunofluorescence labeling, multiparameter flow cytometry, and a short-term culture assay, we show that the apoptotic rates of precursor B cells, but not of more mature B cells, are enhanced by IL-7 gene deletion, associated with increased intracellular content of Bax and decreased Bcl-2, while, conversely, an IL-7 transgene suppresses precursor B cell apoptosis and produces low Bax and high Bcl-2 levels. During normal B cell development, high Bax/Bcl-2 ratios characterize cells undergoing greatest apoptotic cell death. Pro-B cells in RAG-2-/- mice, all destined to abort, show elevated Bax levels and Bax/Bcl-2 ratios. By comparison with the elevated rate of pro-B cell apoptosis in RAG-2-/- mice, provisional estimates have been made for the fraction of pro-B cells undergoing apoptosis in normal mice (70%), IL-7-/- mice (85%), and IL-7 transgenic mice (35%). The results demonstrate that IL-7 strongly promotes in vivo cell survival and maintains antiapoptotic Bcl-2/Bax ratios during the development of precursor B cells in mouse bone marrow.     

The hot rectus abdominis muscle sign

We report a 2.5-year-old child who presented with an acute abdomen caused by the perforation of a sewing pin through her appendix that had started to penetrate the wall of the bladder.     

Nanoscale Plasticity at Grain Boundaries in Face-centered Cubic Copper Under Shock Loading

We investigate the responses of four representative grain boundaries in face-centered cubic Cu bicrystals to shock compression as a function of the loading direction. Two loading directions are considered, either parallel or perpendicular to the grain boundary plane, representing the extremes that a polycrystalline sample will ordinarily experience under the uniaxial strain conditions of planar shock loading. Using molecular dynamics simulations, we demonstrate that the deformation processes during shock compression of the same boundary are altered measurably by changing the loading direction. The Majority of the differences in the nanoscale deformation processes were related to the activation of varying slip systems in the same boundary under the two loading conditions. This change in deformation processes, and hence the plastic response, might eventually affect the failure stress for a grain boundary.     

The effects of preferred provider organizations on health care use and costs

Preferred provider organizations (PPOs) now account for half the enrollment in managed care plans. There are more than 1,000 PPOs, and over 20% of the insured population in the United States are enrolled in this type of plan. Still, there have been few investigations of use and cost of health services in these plans. This paper presents an analysis of a convenience sample of 1,977 companies, most of them mid-sized, from 1988 to 1990. On average, PPOs were associated with cost savings of 12% per covered life (95% confidence interval, 7.2% to 16.9%) as compared to traditional plans with utilization review. The source of cost savings was primarily through lower utilization rates, including a 9.7% lower rate of physician office visits (5.2% to 14.3%) and a 9.3% lower rate of hospital admissions (4.1% to 14.5%). Cost savings were found in seven individual PPOs and a group of small PPOs in the study. Two PPOs were associated with added costs and results were indeterminate for four others. While PPOs may not achieve the level of savings reported by some health maintenance organizations, they may provide a means to achieve some degree of managed care savings for some employer groups.