Differential expression of hla antigen of HLA anigens on human B-cell lines of normal and malignant origin: A consequence of immune surveillance or a phenotypic vestige of the progenitor cells?

Pairs of BL-derived cell lines and in vitro EBV-transformed LCLs, derived from the same patient, were compared for the expression of MHC class-I antigenic determinants as shown both by monoclonal antibody (MAb) binding and by sensitivity to HLA-specific CTL clones. BL lines expressed all polymorphic determinants tested at a lower level than the corresponding LCLs, as indicated by the binding of the MAbs AUF 5.13 (anti-HLA A3,A11), GS 142.1 (anti-HLA A1), GS 114.1 (anti-HLA A24), GSP 35.1 (anti-HLA A2,A28), GSP 55.1 (anti-HLA A25,A32), TER MA32 (anti-HLA A32), GSP 145.2 (anti-HLA B27), B27 M.1 (anti-HLA B27,B7) and GSP 8.1 (anti-HLA B8). The difference was most pronounced for HLA A11 and least for B27,A1 and B8 with intermediate differences for the other specificities. The BL lines were also less sensitive to lysis by HLA-specific CTL clones directed to the same and to additional antigens. The polymorphic determinants detected by the AUF 5.13 and GSP 35.1. MAbs were expressed at a lower level in resting T and B cells compared to mitogen- and EBV-induced blasts. An analogous change in the expression of polymorphic determinants was observed in EBV-converted sublines of originally EBV-negative BLs that have become more "LCL-like" after conversion. The appearance of B-cell activation markers was paralleled by the up-regulation of both the serologically defined and the CTL-target epitopes. The findings suggest that the low expression of HLA determinants on the BL cells is a phenotypic vestige of the normal BL precursor.     

"Weber's law" for position: unconfounding the role of separation and eccentricity

Bisection thresholds are approximately proportional to the separation/eccentricity of the targets. This "Weber's law" for position has been invoked over the past century. It is the separation of the reference targets, or their eccentricity which determines the threshold? In previous studies separation and eccentricity are confounded. In the present report we have pitted separation against eccentricity. Bisection thresholds were measured for stimuli presented on an isoeccentric arc, so that separation could be varied while holding the eccentricity of the test lines constant. We used a 5-fold range of separations from 2-10 deg. In this regime, the present results provide strong evidence against Weber's law. When separation is varied but eccentricity held constant, there is no Weber's law. Rather the thresholds are approximately constant. Our results suggest that the judgement of the separation of widely separated objects is similar to a distance measurement using a ruler on the cortex, in that the error of measurement is independent of the separation between objects. The results imply that when we attempt to gauge the distance between widely separated objects it is unlikely that we do so on the basis of the outputs of large spatial filters; rather it appears that we make such judgements by estimating the cortical distance which separates the targets of interest.     

Validation of computerized three-dimensional reconstruction of intravascular ultrasound: measurements of absolute luminal diameter and cross-sectional area in ex vivo human coronary arteries

Computer based 3-dimensional reconstruction transforms 2-dimensional intravascular ultrasound images into a longitudinal format facilitating analysis of luminal narrowing. To validate the accuracy of current software in measuring coronary artery diameter and cross-sectional area, in arteries with atherosclerosis, we performed 3-dimensional reconstruction in 10 human pathologic coronary arterial segments of 10-25mm length. Images were obtained using a 4.8 French catheter with pullback speed of 1mm/sec acquired at 3 frames/sec onto VHS tape. The data were digitized and intraluminal 3-dimensional reconstruction performed using a voxel-based program. Pathologic sections were obtained every 3mm, and dimensions were measured with a resolution of 0.01 mm. Maximum, minimum, and 3 other representative diameters were recorded by an observer blinded to the ultrasound diameters. Average histo-pathologic diameters were reported, and specimen cross-sectional area was then calculated. Results: In 53 sections, pathological diameters ranged from 1.4-4.5mm (mean 2.7 +/- 0.68mm) while 3-dimensional reconstructed diameters were 1.9 to 3.8mm (mean 2.6 +/- 0.54mm). Pathologic and ultrasound derived 3-dimensional reconstruction diameters had an excellent correlation (r=0.86, SEE=+/-0.36). Pathology and 3-dimensional reconstruction cross-sectional area also correlated closely (r=0.88, SEE=+/-1.50). Diameters less than 2.0mm were systematically overestimated and diameters greater than 3.5mm underestimated by 3-dimensional reconstruction. Most 3 dimensional reconstruction values were within +/- 10% of pathology, but diverged at each diameter extreme, approaching +/- 20%. Thus, computerized 3-dimensional reconstruction of ultrasound images shows excellent quantification of luminal size in the 2.0-3.5mm range, suggesting important investigative and clinical applications.     

Progress in vaccination for histoplasmosis and blastomycosis: coping with cellular immunity.

Human infection with Histoplasma capsulatum or Blastomyces dermatitidis is sufficiently frequent to warrant exploring the development of vaccines. This review examines the advancements that have been accomplished over the last few years. The availability of molecular tools to create recombinant antigens or mutant strains has produced a small number of useful vaccine candidates. More importantly, the studies summarized herein demonstrate that understanding the host response to a protein or mutant fungus is critical to creating a vaccine that may be useful for the immunocompromised patient.     

Cross-reaction to Legionella pneumophila antigen in sera with elevated titers to Pseudomonas pseudomallei.

A significantly greater incidence (P less than 0.005) of Legionella pneumophila microagglutination titers greater than or equal to 32 was found in sera with elevated titers to Pseudomonas pseudomallei as compared with sera with negative titers for P. pseudomallei antibodies. The greater incidence of L. pneumophila titers in these sera suggests that L. pneumophila and P. pseudomallei share an antigen. The incidence of L. pneumophila microagglutination titers of greater than or equal to 32 in sera with elevated titers to Brucella abortus or Francisella tularensis is not statistically significant.     

A technique for the identification of glycoprotein antigens in immune complexes and its application to the detection of a common glycomprotein in sera of patients with burkitt's lymphoma and nasopharyngeal carcinoma

A new technique for the detection of glycoprotein antigens in immune complexes (IC) isolated from serum is described. The technique was developed with a model IC system consisting of ovalbumin (OVA)-rabbit anti-ovalbumin antibodies (aOVA), at 3 times antigen excess. OVA-aOVA IC added to normal human serum (NHS) were purified by absorption onto and elution from tubes coated with rheumatoid factor (RF) and were subjected to electrophoresis in polycrylamide gels. Concanavalin A (Con A) binding proteins were detected by treating the gels with radioiodinated Con A ¹²⁵Con A), followed by autoradiography. IC isolated from sera of patients with Burkitt's lymphoma (BL) and Nasopharyngeal Carcinoma (NPC) were analyzed before and after reduction with dithioreitol. Two closely spaced proteins of about 40 kdalton were identified in the reduced samples in 26 of 30 BL sera (86%) and in 24 of 30 NPC sera (80%) but were not seen in 30 sera of African patients with a variety of unrelated tumors nor in 12 sera of European blood bank donors.     

The essential role of stimulus temporal patterning in enabling perceptual learning

Little is known about how temporal stimulus factors influence perceptual learning. Here we demonstrate an essential role of stimulus temporal patterning in enabling perceptual learning by showing that 'unlearnable' contrast and motion-direction discrimination (resulting from random interleaving of stimuli) can be readily learned when stimuli are practiced in a fixed temporal pattern. This temporal patterning does not facilitate learning by reducing stimulus uncertainty; further, learning enabled by temporal patterning can later generalize to randomly presented stimuli.     

Identification of surface-exposed B-cell epitopes recognized by Haemophilus influenzae type b P1-specific monoclonal antibodies.

A panel of P1 synthetic peptides was synthesized to map the surface-exposed epitopes of Haemophilus influenzae type b outer membrane protein P1 recognized by three murine monoclonal antibodies (MAbs 7C8, 3E12, and 6B1). By using peptide-specific enzyme-linked immunosorbent assays, MAbs 6B1, 7C8, and 3E12 were shown to recognize distinct epitopes localized within residues 60 to 88, 165 to 193, and 400 to 437 of mature P1, respectively. Since MAb 7C8 was shown previously to be protective against certain H. influenzae type b subtypes in the infant rat model of bacteremia, its cognate epitope was further characterized by using truncated peptide analogs. Fine mapping of the 7C8 epitope by competitive inhibition studies revealed that it was localized within residues 184 and 193.     

Serological studies of monoclonal RH1(D) antibodies with RH1(D) variants

In this paper we chose to emphasize three aspects of our work. First we underlined that “low grade and high grade” D weak red blood cells studied at the DNA level could, when monoclonal antibodies were used, give patterns of positive and negative reactions like partial RH1(D) cells. Secondly, we showed the importance of the technical conditions of the study which are essential for establishing a pattern of reactivity defining an epitope. It appears that the use of papain treated cells at room temperature can be misleading for the definition of epitope especially with IgM antibodies. Lastly we pointed out the interest of Rh variant cells, defined at the gene level, to study the expression of RH1(D) epitopes on the external part of the membrane.