Biomedical subjects
G Rhodes
Publications and source records attributed to G Rhodes.
Altered immune response to glycine-rich sequences of Epstein-Barr nuclear antigen-1 in patients with rheumatoid arthritis and systemic lupus erythematosus.
Prior studies have shown that patients with rheumatoid arthritis (RA) have an increased number of circulating Epstein-Barr virus-infected B lymphocytes and elevated titers of antibody to Epstein-Barr nuclear antigen-1 (EBNA-1), the major nuclear antigen expressed in latently infected B cells. However, it is not known whether antibodies from RA patients recognize the same epitopes as antibodies from normal subjects. are directed at the glycine-alanine repeating region of the molecule. Antibodies specific for this region are also somewhat more prevalent in RA patients than in normal subjects. A panel of synthetic peptides derived from EBNA-1 was used to analyze the immune response to antigenic epitopes outside the glycine-alanine region, using the peptides as solid-phase antigen. Sera from RA patients and from systemic lupus erythematosus patients contained elevated levels of IgG antibodies to 2 non-glycine-alanine peptide and to 3 non-glycine-alanine peptides, respectively. Two of the 3 peptides are glycine-rich, but antibodies that react with them are distinct from each other, as well as from those that react with the glycine-alanine epitope. Eight other peptides from the C-terminal portion of EBNA-1 either do not react with sera or show no difference between normal subjects and patient groups. The antibodies to the glycine-alanine peptide are enriched with kappa light chains, whereas antibodies to epitopes outside the glycine-alanine region are not so restricted among kappa and lambda light chains. Thus, RA patients and systemic lupus erythematosus patients have different antibody responses than do normal subjects, both quantitatively and qualitatively.
Autoantibody production by severe combined immunodeficient mice reconstituted with synovial cells from rheumatoid arthritis patients.
In an attempt to characterize the heterogeneity of the human autoantibody response, mice with severe combined immunodeficiency were reconstituted with synovial or blood lymphocytes from patients with rheumatoid arthritis (RA). Mononuclear cells extracted from synovial fluid or tissue (SMC) were a greatly enriched source of IgM rheumatoid factor (RF)-producing cells compared to the peripheral blood mononuclear cells (PBMC) of rheumatoid arthritis patients or normal donors. Six to nine weeks after reconstitution of mice with synovial mononuclear cells, 0%-39.3% (mean = 11.4%) of total IgM consisted of IgM RF compared to 0%-0.15% (mean = 0.02%) in mice given RA PBMC and 0%-1.2% (mean = 0.34%) in mice given normal PBMC. Detectable levels of IgM RF were maintained in some mice for as long as 20 weeks after transfer. Mice reconstituted with synovial membrane or synovial fluid lymphocytes produced a heterogeneous mixture of immunoglobulins. These included other autoantibodies, such as anti-nuclear and anti-cytoplasmic antibodies, and antibodies to exogenous antigens such as the Epstein-Barr virus nuclear antigen-1 (EBNA-1). This heterogeneity is further illustrated by the demonstration that the sera from mice given synovial cells also contained IgG antibodies possessing all three major VH families (VH1, VH3 and VH4) and the four major V kappa families (V kappa 1 to V kappa 4). Autoantibody production gradually decreased with time even under circumstances where total immunoglobulin levels increased, and elevated production could not be induced by antigenic stimulation. These findings describe a new model for the analysis of human autoantibody production.
Identical IgM antibodies recognizing a glycine-alanine epitope are induced during acute infection with Epstein-Barr virus and cytomegalovirus.
We studied antibody production in serial serum samples from patients with acute Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. Sera were analyzed both by enzyme-linked immunosorbent assay (ELISA) using a synthetic peptide (P62) derived from the glycine-alanine repeating region of the Epstein-Barr nuclear antigen (EBNA-1) and by immunoblotting. In prior studies, we have shown that patients with acute EBV infection make IgM antibodies that react with this peptide, that recognize a viral-specific protein (EBNA-1), and that bind with a number of proteins present in uninfected cells; however, antibody binding to these autoantigens was inhibited by the peptide. IgG antibodies reactive with the peptide did not appear until months after the disease and were specific for the EBNA-1 protein. We now find that patients with acute CMV infection but not those with acute infections from a variety of other nonherpes organisms also produce IgM antibodies that recognize the EBV-derived peptide P62. These antibodies also appear to recognize the same cellular proteins as the EBV-induced IgM antibodies. The IgM antibodies appeared in all acutely infected CMV patients studied and occurred both in patients with previous EBV infections and in one patient studied who had not previously been exposed to EBV. It appears that infection with EBV or CMV can induce the synthesis of a very similar or identical set of IgM antibodies.
Asymmetries in face perception: component processes, face specificity and expertise effects.
Three experiments were carried out to analyze the component processes contributing to observed asymmetries in face perception, to determine whether these asymmetries occur for complex visuospatial stimuli other than human faces, and to investigate the effects of expertise on the asymmetries. Two component processes contributed to the observed asymmetries: perceptual bias (PB) in the observer and face asymmetries (FA). There was no PB effect for complex visuospatial stimuli other than human faces (landscapes, abstract paintings and animal faces). Expertise effects were investigated by examining the judgments of Chinese and Caucasian subjects for own-race and other-race faces. A PB was found for both Caucasian and Chinese faces, but the size of the effect was not related unequivocally to expertise. Caucasian subjects showed a PB for own-race faces only, but Chinese subjects showed a PB for both Chinese and Caucasian faces. There was no FA effect for Chinese faces, even when the composites were perceived as more dissimilar than the Caucasian composites, for which there was an FA effect. The implications of these results for the theoretical interpretation of perceptual asymmetries are discussed.
Distinctiveness and expertise effects with homogeneous stimuli: towards a model of configural coding.
Recent studies using Brennan's computerized caricature generator have demonstrated distinctiveness effects consistent with the idea that faces are coded in terms of their individual distinctive properties. Based on these findings it is suggested that, for homogeneous classes whose members share a common configuration, distinctive configural information may be coded as metric deviations from a spatial norm. Experiments are described which demonstrate similar distinctiveness effects in bird identification. Transformations that increase distinctiveness (caricatures) produced faster identification and a higher recognition proportion, for both experts and nonexperts, than transformations that reduce distinctiveness (anticaricatures). This distinctiveness advantage is consistent with the norm-based coding idea. Furthermore, within certain limits, increasing distinctiveness did not impair performance relative to that for veridical drawings. For experts there was also a caricature advantage, such that 50% caricatures of birds in a highly homogeneous and familiar class (passerines) were identified more quickly, provided that they were recognized at all, than uncaricatured veridical drawings. The significance of a caricature advantage for the visual coding of configural information is discussed.
Antibodies to synthetic peptides from Epstein-Barr nuclear antigen-1 in sera of patients with early rheumatoid arthritis and in preillness sera.
We studied IgG antibody levels to synthetic peptides (p62, E11 and E3) from Epstein-Barr nuclear antigen-1 (EBNA-1) protein sequence in sera of patients with rheumatoid arthritis (RA), in pre-RA and in rheumatoid factor (RF) positive non-RA sera from Finland. Anti-E11 and anti-E3 antibody levels were significantly elevated in RA sera, compared with both RF negative and RF positive nonrheumatoid controls. The concentrations of anti-E11 and anti-E3 antibodies in the preillness sera were lower than those in RA sera. Eight-year followup samples of patients with RA had slightly decreased levels of anti-E3 and anti-E11 antibodies compared with samples taken within 6 months of the disease onset. Anti-p62 antibody levels did not differ significantly between any of the groups studied. Thus, elevated levels of antibodies to 2 of the glycine containing EBNA-1 peptides were associated with clinical RA.
Human T cell responses to the Epstein-Barr nuclear antigen-1 (EBNA-1) as evaluated by synthetic peptides.
A panel of synthetic peptides derived from Epstein-Barr virus (EBV) nuclear antigen 1 (EB-NA-1) was used to examine human T cell responses to this antigen. In six of seven normal persons with past EBV infection, T cell precursors specific for five peptides (P27, amino acid residues 83-101;P62, 148-166;E31, 353-367;E41, 368-381; and E11, 461-474) were detectable. The precursor frequencies were in the range of 1:20,000 to less than 1:100,000 peripheral blood mononuclear cells as determined by limiting dilution analyses. Only two of these peptides were predicted as alpha-helices; all peptides were glycine-rich. Four other peptides were not reactive in the seven individuals tested. T cell responses were not detectable in donors without prior EBV infection. Infectious mononucleosis patients investigated 4-6 weeks after diagnosis had likewise no detectable peptide-specific T cell precursors. Thus, it appears that T cells recognizing peptides from EBNA-1 arise and persist in people with past EBV infection.
Refined crystal structure of cytoplasmic malate dehydrogenase at 2.5-A resolution.
The molecular structure of cytoplasmic malate dehydrogenase from pig heart has been refined by alternating rounds of restrained least-squares methods and model readjustment on an interactive graphics system. The resulting structure contains 333 amino acids in each of the two subunits, 2 NAD molecules, 471 solvent molecules, and 2 large noncovalently bound molecules that are assumed to be sulfate ions. The crystallographic study was done on one entire dimer without symmetry restraints. Analysis of the relative position of the two subunits shows that the dimer does not obey exact 2-fold rotational symmetry; instead, the subunits are related by a 173 degrees rotation. The structure results in a R factor of 16.7% for diffraction data between 6.0 and 2.5 A, and the rms deviations from ideal bond lengths and angles are 0.017 A and 2.57 degrees, respectively. The bound coenzyme in addition to hydrophobic interactions makes numerous hydrogen bonds that either are directly between NAD and the enzyme or are with solvent molecules, some of which in turn are hydrogen bonded to the enzyme. The carboxamide group of NAD is hydrogen bonded to the side chain of Asn-130 and via a water molecule to the backbone nitrogens of Leu-157 and Asp-158 and to the carbonyl oxygen of Leu-154. Asn-130 is one of the corner residues in a beta-turn that contains the lone cis peptide bond in cytoplasmic malate dehydrogenase, situated between Asn-130 and Pro-131. The active site histidine, His-186, is hydrogen bonded from nitrogen ND1 to the carboxylate of Asp-158 and from its nitrogen NE2 to the sulfate ion bound in the putative substrate binding site. In addition to interacting with the active site histidine, this sulfate ion is also hydrogen bonded to the guanidinium group of Arg-161, to the carboxamide group of Asn-140, and to the hydroxyl group of Ser-241. It is speculated that the substrate, malate or oxaloacetate, is bound in the sulfate binding site with the substrate 1-carboxyl hydrogen bonded to the guanidinium group of Arg-161.
Laterality effects in identification of caricatures and photographs of famous faces.
Recent evidence suggests that memory representations of familiar faces may exaggerate distinctive information as do caricatures (G. Rhodes, S. Brennan, & S. Carey, Cognitive Psychology, 1987). Therefore caricatures should be effective representations of faces and should yield a right hemisphere processing advantage, as do photographs of faces. Photographs and caricatures of famous faces were presented to the left visual (LVF), the right visual field (RVF), and centrally (CVF), in a name-face verification task. There was a LVF (right hemisphere) advantage for both caricatures and photographs on name-face mismatches but no VF difference for matches. These results were true for both accuracy and reaction time. Processing strategy differences that may account for the difference between matches and mismatches are discussed. Performance was generally better for photographs than for caricatures, irrespective of visual field condition.
Comparison of the molecular structures of cytoplasmic and mitochondrial malate dehydrogenase.
Explore the source record for details and available documents.
Antibodies to an Epstein-Barr virus nuclear antigen synthetic peptide in infectious mononucleosis. Report of two cases.
The Epstein-Barr virus nuclear antigen (EBNA-1) contains a region of repeating glycine and alanine amino acids. It has been shown that this region contains a major epitope of EBNA-1. With well-characterized sequential sera from two cases of acute infectious mononucleosis, a specific IgM response was detected to the EBNA-1 synthetic peptide by enzyme-linked immunosorbent assay (ELISA). Conversely, an IgG response was observed in the convalescent phase of the illness with a progressive decline of the IgM antibodies. This response was observed with heterophil-positive and heterophil-negative EBV/IM. The peptide-specific serologic response was confirmed by immunoblotting, the serial serum samples on extracts of EBV transformed B-cells. There was excellent correlation between the antipeptide ELISA and blotting techniques.
Expertise and configural coding in face recognition.
Diamond & Carey (1986) have argued that expertise in face recognition depends on the ability to code configural properties in addition to isolated features. We tested this hypothesis in two experiments by comparing the effect of inversion on recognition of 'own race' (high expertise) and 'other race' (low expertise) faces. Use of configural information should be associated with a larger inversion effect than use of isolated features, and therefore inversion should produce a larger recognition decrement for own race than for other race faces. In Expt 1 there was a larger inversion effect in reaction times for recognition of own race faces than other race faces, for both European and Chinese subjects (ceiling effects made interpretation of accuracy difficult). In Expt 2 a larger own race inversion effect was found for recognition accuracy, when test face pairs were randomly selected, but not when they were matched on isolated features. Our results are largely consistent with the hypothesis that expertise is associated with greater use of configural information in faces.
"A cat burglar": an unusual reason for growth failure despite nocturnal nasogastric feedings in a uremic child.
Explore the source record for details and available documents.
Looking at faces: first-order and second-order features as determinants of facial appearance.
The encoding and relative importance of first-order (discrete) and second-order (configural) features in mental representations of unfamiliar faces have been investigated. Nonmetric multidimensional scaling (KYST) was carried out on similarity judgments of forty-one photographs of faces (homogeneous with respect to sex, race, facial expression, and, to a lesser extent, age). A large set of ratings, measurements, and ratios of measurements of the faces was regressed against the three-dimensional KYST solution in order to determine the first-order and second-order features used to judge similarity. Parameters characterizing both first-order and second-order features emerged as important determinants of facial similarity. First-order feature parameters characterizing the appearance of the eyes, eyebrows, and mouth, and second-order feature parameters characterizing the position of the eyes, spatial relations between the internal features, and chin shape correlated with the dimensions of the KYST solution. There was little difference in the extent to which first-order and second-order features were encoded. Two higher-level parameters, age and weight, were also used to judge similarity. The implications of these results for mental representations of faces are discussed.
The Epstein-Barr virus glycoprotein gp110, a molecular link between HLA DR4, HLA DR1, and rheumatoid arthritis.
Explore the source record for details and available documents.
Autoantibodies in infectious mononucleosis have specificity for the glycine-alanine repeating region of the Epstein-Barr virus nuclear antigen.
Viruses have been postulated to be involved in the induction of autoantibodies by: autoimmunization with tissue proteins released by virally induced tissue damage; immunization with virally encoded antigens bearing molecular similarities to normal tissue proteins; or nonspecific (polyclonal) B cell stimulation by the infection. Infectious mononucleosis (IM) is an experiment of nature that provides the opportunity for examining these possibilities. We show here that IgM antibodies produced in this disease react with at least nine normal tissue proteins, in addition to the virally encoded Epstein-Barr nuclear antigen (EBNA-1). The antibodies are generated to configurations in the glycine-alanine repeat region of EBNA-1 and are crossreactive with the normal tissue proteins through similar configurations, as demonstrated by the effectiveness of a synthetic glycine-alanine peptide in inhibiting the reactions. The antibodies are absent in preillness sera and gradually disappear over a period of months after illness, being replaced by IgG anti-EBNA-1 antibodies that do not crossreact with the normal tissue proteins but that are still inhibited by the glycine-alanine peptide. These findings are most easily explained by either a molecular mimicry model of IgM autoantibody production or by the polyclonal activation of a germline gene for a crossreactive antibody. It also indicates a selection of highly specific, non-crossreactive anti-EBNA-1 antibodies during IgM to IgG isotype switching.
Identification and ratings of caricatures: implications for mental representations of faces.
Explore the source record for details and available documents.