CD8 is a surface glycoprotein expressed on most thymocytes and on a subset of mature T cells. The reactivity of mature CD8 + T cells is restricted by polymorphic determinants on class I MHC molecules present on target cells; CD8 itself binds to a monomorphic region of class I MHC proteins and increases the avidity of the interaction between the T cell and the antigen presenting cells (1, 2). Evidence from experiments with inbred transgenic mice supports the hypothesis that the CD8 molecule participates in the intrathymic selection of class I MHC-restricted T cells and in the tolerization to self antigens presented by class I proteins (3-7). No comparable experimental evidence exists in any outbred species. In this article we describe an immune deficient patient with selective depletion ofCD8+ cells. Analysis of this patient reveals the existence of CD8+ cells in the thymic cortex but selective depletion of CD8+ cells in the thymic medulla and peripheral blood. Our results point to a process in the human thymus that targets the CD8+ thymocyte.Flow Cytometry Viable mononuclear cells from thymocytes were isolated using Ficoll/Hypaque. Isolated thymocytes were resuspended at 2 x 106 cells/ml in PBS containing fluorescein-conjugated mAbs and incubated for 30 min at 4°C. After two washes in PBS, labeled cells were analyzed by a Coulter Epics V flow cytometer (Coulter Electronics, Hialeah, FL).Immunohistological Analysis of Cryostat Sections. Thymic biopsies from the patient and from a normal control, undergoing cardiac surgery, were snap frozen in liquid nitrogen and stored at -70°C until use. 4-,um serial cryostat sections were mounted on glass slides and air dried. Tissue sections were immunostained with the specified mAbs using athree-stage biotin-avidinperoxidase staining.Northern Blot Analysis. RNA was extracted from cells in guanidinum isothiocyanate according to the method of Chomezynski and Sacchi (8). Purified RNA (10 ug) was electrophoresed, subsequently transferred to nitrocellulose, blotted and hybridized with labeled probes as previously described (9).Amplification of CD8 cDNA . A 353-bp fragment ofCD8a cDNA was amplified as described
These results raise the possibility of repairing and rebuilding cartilage by resurfacing the cartilage with genetically modified chondrocytes. The ability to infect chondrocytes well after transplant raises the possibility of repeated infections of surface chondrocytes as an alternative to repeated injections of chondrocytes into the joint space.
Climate models may be limited in their inferential use if they cannot be locally validated or do not account for spatial uncertainty. Much of the focus has gone into determining which interpolation method is best suited for creating gridded climate surfaces, which often a covariate such as elevation (Digital Elevation Model, DEM) is used to improve the interpolation accuracy. One key area where little research has addressed is in determining which covariate best improves the accuracy in the interpolation. In this study, a comprehensive evaluation was carried out in determining which covariates were most suitable for interpolating climatic variables (e.g. precipitation, mean temperature, minimum temperature, and maximum temperature). We compiled data for each climate variable from 1950 to 1999 from approximately 500 weather stations across the Western United States (32 • to 49 • latitude and −124.7 • to −112.9 • longitude). In addition, we examined the uncertainty of the interpolated climate surface. Specifically, Thin Plate Spline (TPS) was used as the interpolation method since it is one of the most popular interpolation techniques to generate climate surfaces. We considered several covariates, including DEM, slope, distance to coast (Euclidean distance), aspect, solar potential, radar, and two Normalized Difference Vegetation Index (NDVI) products derived from Advanced Very High Resolution Radiometer (AVHRR) and Moderate Resolution Imaging Spectroradiometer (MODIS). A tenfold cross-validation was applied to determine the uncertainty of the interpolation based on each covariate. In general, the leading covariate for precipitation was radar, while DEM was the leading covariate for maximum, mean, and minimum temperatures. A comparison to other products such as PRISM and WorldClim showed strong agreement across large geographic areas but climate surfaces generated in this study (ClimSurf) had greater variability at high elevation regions, such as in the Sierra Nevada Mountains.
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