Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3.

Monoclonal antibodies were prepared to anti-HLA-DR cytolytic T lymphocytes (CTLs) and screened for inhibition of CTL-mediated killing. Binding of monoclonal antibodies to four types of molecules, LFA-1, LFA-2, LFA-3, and HLA-DR, inhibited killing, suggesting that these molecules participate in the CTL-target cell interaction. The antigens were characterized by immunoprecipitation, crosslinking, NaDodSO4/polyacrylamide gel electrophoresis, and immunofluorescence flow cytometry. The LFA-1 antigen contains alpha and beta polypeptide chains of Mr 177,000 and 95,000 that are noncovalently associated in an alpha 1 beta 1 structure. It is present on both B and T lymphocytes and marks subpopulations that differ in quantitative expression. Human LFA-1 appears to be the homologue of mouse LFA-1. Human LFA-2 is of Mr 49,000 with a minor component of Mr 36,000. It is expressed on CTL lines but not on a B-cell line and in peripheral blood preferentially on T lymphocytes. Human LFA-3 is of Mr 60,000 and is expressed on both B and T lymphocytes.     

Immunohistologic analysis of the distribution of cell adhesion molecules within the inflammatory synovial microenvironment

Antigen-independent binding of T lymphocytes to a variety of cell types has been shown to be mediated by receptor-ligand pairs of adhesion molecules. In forms of inflammatory synovitis (including rheumatoid arthritis), T cells home to synovium, become activated, and participate in the generation of chronic synovitis. Using indirect immunofluorescence assays on synovial frozen tissue sections and on synovial fibroblast cell lines, we studied the distribution of cell adhesion molecules on components of the synovial microenvironment in inflammatory synovitis. We reasoned that analysis of the cell types within synovium that express adhesion molecules might provide clues to lymphocyte-stromal interactions that occur in inflammatory synovitis. We found that antibodies against the lymphocyte function-associated antigen 3 (LFA-3) molecule and the intercellular adhesion molecule 1 (ICAM-1) both reacted with macrophage-like type A synovial cells and synovial fibroblasts, as well as with tissue macrophages and vessel endothelium. Using flow cytometry, we found that anti-LFA-3 and anti-ICAM-1 (but not antibodies against their ligands CD2 and LFA-1) reacted with synovial fibroblast cells cultured in vitro. Thus, these data demonstrate that the ligands for lymphocyte LFA-1 molecules (ICAM-1) and for T cell CD2 molecules (LFA-3) are widely distributed among cell types of the synovial microenvironment and provide numerous cell types with which lymphocytes can interact via these 2 adhesion pathways during the course of inflammatory synovitis.     

Validation of Reflectance Pulse Oximetry: an Evaluation of a New Sensor in Piglets

Objective. A new reflectance pulse oximetry sensor, developed for intrapartum estimation of arterial oxygen saturation (SaO2), was calibrated and evaluated. The sensor contains two light emitting diodes of 735 and 890 nm, and a photodetector at a distance of 14 mm from both light emitting diodes. Methods. In seven Yorkshire/Hampshire piglets, the reflectance sensor (Nellcor Puritan Bennett Inc.) was calibrated using blood sample SaO2 values. The resulting calibration line was evaluated in four Dutch piglets, by comparing pulse oximetry saturation readings (SpO2) with blood sample and intravascular fiberoptic oximetry SaO2 values. Several reflectance sensors were fixed on each animal. Desaturation levels were obtained by changing the gas mixture of oxygen/nitrous oxide via a tracheal catheter. Results. In the Yorkshire/Hampshire piglets, the standard deviation of difference (SpO2 - SaO2) was 4.7% (n = 364), over an SaO2 range of 17% to 100%. In the Dutch piglets, the mean difference (SpO2 - SaO2) was -1.6% and the standard deviation of difference was 5.4%, over the same SaO2 range (n = 254). Comparisons of continuous recordings of reflectance SpO2 and fiberoptic SaO2 revealed variation in individual regression lines. Conclusions. This new 735/890 nm reflectance sensor demonstrates acceptable accuracy in piglets. A further evaluation during labor should assess its feasibility for fetal surveillance.     

The Chemokine SDF-1 Is a Chemoattractant for Human CD34+ Hematopoietic Progenitor Cells and Provides a New Mechanism to Explain the Mobilization of CD34+ Progenitors to Peripheral Blood

Hematopoietic progenitor cells migrate in vitro and in vivo towards a gradient of the chemotactic factor stromal cell-derived factor-1 (SDF-1) produced by stromal cells. This is the first chemoattractant reported for human CD34⁺ progenitor cells. Concentrations of SDF-1 that elicit chemotaxis also induce a transient elevation of cytoplasmic calcium in CD34⁺ cells. SDF-1-induced chemotaxis is inhibited by pertussis toxin, suggesting that its signaling in CD34⁺ cells is mediated by seven transmembrane receptors coupled to G_i proteins. CD34⁺ cells migrating to SDF-1 include cells with a more primitive (CD34⁺/CD38⁻ or CD34⁺/DR⁻) phenotype as well as CD34⁺ cells phenotypically committed to the erythroid, lymphoid and myeloid lineages, including functional BFU-E, CFU-GM, and CFU-MIX progenitors. Chemotaxis of CD34⁺ cells in response to SDF-1 is increased by IL-3 in vitro and is lower in CD34⁺ progenitors from peripheral blood than in CD34⁺ progenitors from bone marrow, suggesting that an altered response to SDF-1 may be associated with CD34 progenitor mobilization.     

Magnetic field and tissue dependencies of human brain longitudinal 1H2O relaxation in vivo.

Brain water proton (1H2O) longitudinal relaxation time constants (T1) were obtained from three healthy individuals at magnetic field strengths (B0) of 0.2 Tesla (T), 1.0T, 1.5T, 4.0T, and 7.0T. A 5-mm midventricular axial slice was sampled using a modified Look-Locker technique with 1.5 mm in-plane resolution, and 32 time points post-adiabatic inversion. The results confirmed that for most brain tissues, T1 values increased by more than a factor of 3 between 0.2T and 7T, and over this range were well fitted by T1 (s)=0.583(B0)0.382, T1(s)=0.857(B0)0.376, and T1(s)=1.35(B0)0.340 for white matter (WM), internal GM, and blood 1H2O, respectively. The ventricular cerebrospinal fluid (CSF) 1H2O T1 value did not change with B0, and its average value (standard deviation (SD)) across subjects and magnetic fields was 4.3 (+/-0.2) s. The tissue 1/T1 values at each field were well correlated with the macromolecular mass fraction, and to a lesser extent tissue iron content. The field-dependent increases in 1H2O T1 values more than offset the well-known decrease in typical MRI contrast reagent (CR) relaxivity, and simulations predict that this leads to lower CR concentration detection thresholds with increased magnetic field.