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Biomedical subjects

J E Calvert

Publications and source records attributed to J E Calvert.

At least 19 recordsLinked to original sources
PubMed1994

Influence of Gm allotype on the IgG subclass response to streptococcal M protein and outer membrane proteins of Moraxella catarrhalis.

The IgG antibody response to streptococcal M protein is distributed between the IgG1 and IgG3 subclasses, however individual sera vary with respect to the relative amounts of these two subclasses. The basis of this variation was investigated. Sera were also analysed for IgG subclass antibodies to the outer membrane proteins (OMP) of Moraxella catarrhalis, as these have also been reported to have a major IgG3 component. The mean percentage of IgG3 was higher in the antibody response to OMP and there was less variability between sera for this antigen than was seen for M protein. Non-specific binding of IgG3 in ELISA, which has been reported for some bacterial proteins (including M protein of some serotypes) was excluded as an explanation for the apparent IgG3 bias of these antibodies. The relative amount of IgG3 antibody to the two antigens showed a positive correlation, suggesting that some individuals tended to make a greater IgG3 response to unrelated antigens. Serial bleeds from two individuals maintained a relatively constant subclass profile over several months, suggesting that time since infection did not play a major role in determining the proportion of IgG1 and IgG3. Gm allotypes for the sera were determined, and found to correlate with both total serum IgG3 concentrations and with IgG subclass composition of specific antibodies. Mean serum IgG3 concentrations were highest in sera typed as Gm(fb/fb) homozygous and lowest in sera typed as Gm(ag/ag) homozygous. Similarly, in the M protein-specific antibodies, the mean percentage of IgG3 was much lower in the Gm(ag/ag) sera than in the Gm(fb/fb) homozygous sera. Sera which typed as Gm(fb/ag) heterozygous were not significantly different from the Gm(fb/fb) homozygous sera for either total serum IgG3 or for M protein-specific IgG3. Moreover, both Gm(fb/fb) homozygous and Gm(fb/ag) heterozygous sera included samples in which IgG1 was the predominant antibody subclass and the percentage of IgG3 was very low. In contrast to the M protein-specific antibodies, for the OMP-specific antibodies there was no correlation between Gm phenotype and the proportion of IgG3. The data suggest that Gm allotype may influence the IgG subclass composition of antibody responses to bacterial surface protein, but that other factors are also likely to be involved.

Adult↗
PubMed1992

Processing of spatial contrast in peripheral vision in Parkinson's disease.

Two experiments were carried out to test the hypothesis, based on anatomical evidence, that contrast gain might be reduced in the retinal periphery in Parkinson's disease. In the first experiment, subjects set contrast thresholds before and after adaptation to a vertical grating of 2 cycles per degree (c/deg), either stationary or oscillating sideways through its spatial period at 8 Hz, presented either in central vision or 7 degrees peripherally. Threshold elevations were similar for central viewing in both patients and controls. However, for peripheral viewing, elevations were greater in the controls, but smaller in the patients, than for central viewing. In the second experiment, a staircase procedure was used to find the contrast of a peripherally viewed grating of either 4 or 1.2 c/deg which apparently matched that of a centrally viewed grating of the same spatial frequency. Patients needed more contrast (about 1.6 times, at both spatial frequencies) than controls for a match. These results suggest that contrast gain may be lowered in the peripheral retina in Parkinson's disease, perhaps because of an abnormality of dopamine amacrine cells, whose density peaks in the peripheral retina.

Contrast Sensitivity↗
PubMed1992

Abnormal immunoglobulin G subclass production in response to keyhole limpet haemocyanin in atopic patients.

A proportion of patients with atopic dermatitis have elevated serum levels of IgG4. In order to investigate further this abnormality of IgG subclass production, atopic patients were immunized with the protein antigen keyhole limpet haemocyanin (KLH), and IgG subclass responses following primary and secondary immunization were analysed. In the primary response, titres of IgG1, 2 and 3 antibodies were lower in the atopic patients than in the controls. In contrast, titres of IgG4 were much higher for the patient group. In both patients and controls, the kinetics of IgG4 antibody production following the initial immunization with KLH showed a slow rise reaching a peak at 30 weeks. This time course indicated that the high IgG4 response was unlikely to be due to previous exposure of the patients to a cross-reacting antigen. A higher proportion of IgG4 was also seen in the atopic patients following secondary immunization; indeed, IgG4 was the major subclass in the secondary response in the patient group. In the controls, but not in the patients, titres of IgG4 anti-KLH correlated with total serum levels of IgG4, and some of the highest IgG4 antibody responses were detected in atopic patients whose serum IgG4 concentration was in the normal range. The results suggest that raised serum levels of IgG4 in atopy may reflect abnormal isotype regulation in response to protein antigens.

Adult↗
PubMed1992

Levels of CD5+ B cells are not increased in probands or relatives in a family study of primary Sjögren's syndrome.

Levels of CD5+ B lymphocytes were assayed in a large family study of Primary Sjögren's syndrome. There was no significant difference in CD5 expression by index cases or their relatives when compared to controls. No association between CD5 expression, serological abnormalities or HLA haplotype was found and, furthermore, no evidence of linkage with HLA was observed. There was, however, variation in the expression of CD5+ B cells between the families. Levels in spouses were lower and reached statistical significance. The role for genetic and environmental factors influencing CD5 expression is discussed. Any genetic influence does not appear to involve the HLA region or genes in linkage disequilibrium.

Adult↗
PubMed1991

The effect of improvements in cytometer sensitivity on the detection of CD5-positive B cells with dim fluorescence.

When antigen density on the surface of a cell population is low and variable, the percentage of that population determined to express the antigen (i.e., to be positively stained) depends directly on the sensitivity of the flow cytometer for resolving particles which are dimly fluorescent from those which are unstained. In this study, the sensitivity of a commercial flow cytometer has been improved by changes in the photomultiplier tube, the fluorescence filter, and the amount of stray light entering the fluorescence channel. In a model system with human lymphocytes, modifications to these factors increased the percent of the B-lymphocyte population found to express the CD5 antigen.

Antigens, Differentiation↗
PubMed1991

Tilt aftereffect reveals early visual processing deficits in Parkinson's disease and in chronic schizophrenic patients on depot neuroleptic.

Previous studies suggest that the tilt aftereffect (TAE) may be used to indicate the site of dopaminergic abnormalities in the human visual system. In this study we investigated the TAE in patients with Parkinson's disease, and in chronic schizophrenic patients receiving depot injections of neuroleptic. The results suggest that the retina may be abnormal in both groups of patients, and that schizophrenic patients may also have cortical changes. The results are discussed in terms of the clinical implications of these visual changes.

Adult↗
PubMed1991

Analysis of the IgG subclass production from rheumatoid arthritis synovial cell cultures.

In man there are four subclasses of IgG which differ from each other with respect to their biological properties. Some evidence suggests that the production of IgG3 is unusually high in rheumatoid synovia. In this study secretion of IgG subclasses by synovial lymphocytes in vitro was measured using sensitive subclass-specific ELISAs. It was found that, in both synovial membrane- and synovial fluid-derived cell cultures, the general pattern of IgG subclass secretion was IgG1 greater than 2 greater than 3 greater than or equal to 4, and that, in most cultures, IgG3 was a minor subclass accounting, on average, for only 8% of the total IgG. This was similar to the percentage of this subclass in normal human serum and in culture supernatants from the patients' peripheral blood lymphocytes.

Arthritis, Rheumatoid↗
PubMed1990

Adaptation to peripheral flicker: relationship to contrast detection thresholds.

The time to disappearance of flicker of a temporally modulated uniform 1 degree field, steadily viewed with the temporal retina at an eccentricity of 12 degrees, was measured as a function of temporal frequency and depth of modulation (contrast). As found by others, for a fixed contrast, adaptation time declined as temporal frequency increased. To check whether this effect was genuinely temporal frequency-dependent, or reflected the amount above threshold of the adapting contrast, measurements were also made at contrasts which were multiples of the contrast threshold or matched across temporal frequencies. The results suggest that both temporal frequency and amount of adapting contrast above threshold are important in determining the speed of adaptation.

Adaptation, Ocular↗
PubMed1990

The influence of dopamine on spatial vision.

Contrast thresholds for, and contrast matches between, stationary gratings of three spatial frequencies (0.5, 2, and 8 c/deg) were measured on eight subjects with a history of schizophrenia, just before, and again two to three days after, a therapeutic injection of depot neuroleptic. The drug enhanced sensitivity at the low, and reduced it at the medium and high spatial frequency. After injection, subjects required more contrast to match the apparent contrast of the high, and less contrast to match that of the low, to that of the medium spatial frequency. Pupillary measurements suggested that these effects were not due to drug-induced changes in pupil size. The results are discussed in terms of the functional role of dopamine in the retina, and a possible application in therapy for amblyopia.

Adult↗
PubMed1990

Distinctive development of IgG4 subclass antibodies in the primary and secondary responses to keyhole limpet haemocyanin in man.

The human primary and secondary IgG subclass antibody responses to keyhole limpet haemocyanin (KLH) have been measured by ELISA using IgG subclass-specific monoclonal antibodies. KLH-specific IgG1 and IgG2 antibodies were detected 3 weeks after primary immunization, and IgG1, IgG2 and IgG4 antibodies after secondary immunization. IgG3 antibodies were observed less frequently in both primary and secondary responses. Unlike the other subclasses, IgG4 antibodies developed very slowly during the primary response, with no antibody detected at 3 weeks and often with only low titres 1 year after immunization. In one individual, this IgG4 primary response peaked around 10 months, but there was considerable variation between individuals. Comparing primary and secondary responses, the greatest increase in KLH antibody was for the IgG4 subclass (45-fold rise), followed by IgG1 (7.3-fold rise), whilst IgG2 and IgG3 KLH-specific antibodies did not show a significantly increased secondary response. There was no detectable IgG4 antibody response when secondary immunization was performed 1 month after the primary, even though IgG1, IgG2 and IgG3 antibodies were present. Reasons for the different time-course of IgG4 anti-KLH development and the isotype-related differences in 'memory' responses are discussed.

Adult↗
PubMed1990

Immunoglobulin G subclasses secreted by human B cells in vitro in response to interleukin-2 and polyclonal activators.

The IgG subclasses secreted by human B cells in vitro in response to IL-2 have been analysed. B cells were prepared from tonsil, blood and spleen, and cultured with recombinant IL-2 in the presence or absence of two polyclonal activators: Staphylococcus aureus Cowan 1 (SAC) and bacterial lipopolysaccharide (LPS). Secretion of all four subclasses and of IgM was stimulated by IL-2, but the relative amounts varied according to (i) the tissue source of the B cells, and (ii) which polyclonal activator was used. The amount of IgG1 tended to be higher and IgG2 tended to be lower when SAC was the polyclonal activator (compared to LPS). This difference was most marked for tonsil B cells, and it was found that SAC had a negative effect on secretion of IgM and IgG2 in these cultures, whilst synergizing with IL-2 to stimulate the production of IgG1, 3 and 4. When the degree of stimulation of different pairs of isotypes was analysed, several interesting positive correlations emerged. In tonsil B-cell cultures, stimulation of IgM and IgG2 was linked with each other, but not with IgG1, whilst in blood B-cell cultures all isotypes appeared to be stimulated co-ordinately. Stimulation of IgG1 and IgG3 were positively correlated in cultures of B cells from all tissues. The results emphasize that the effects of a single cytokine on immunoglobulin isotype production can be influenced by the source of the B cells, and by other signals delivered to the cells.

Antigens, Bacterial↗
PubMed1989

Contrast, spatial frequency and test duration effects on the tilt aftereffect: implications for underlying mechanisms.

The tilt aftereffect (TAE) was measured with a forced-choice technique for gratings of different spatial frequencies, contrasts and adapting and test durations. At short test durations, a 2 c/deg grating gave a larger TAE than a 10 c/deg, while at long test durations the opposite occurred. Low contrast gratings tended to give smaller TAEs at short test durations, and larger TAEs at long durations, than high contrast. A longer adapting duration tended to produce larger TAEs at low contrast for any test duration, but larger TAEs at high contrast only at long test durations. We suggest that the spatial frequency effect reflects differential excitation by the test stimuli of transient and sustained channels, and that the contrast effects reflect both a non-linearity in the relationship between excitation and inhibition, and the adapting effects of the test grating.

Adaptation, Ocular↗
PubMed1988

Spatial frequency and duration effects on the tilt illusion and orientation acuity.

The simultaneous tilt illusion and the decline in variance of orientation judgements (Andrews effect) were measured as a function of exposure duration and spatial frequency. The illusions increased in size (to more than 10 deg) with exposure times up to 30-100 msec, then declined. The Andrews effect was largest at the shortest exposure and asymptoted (for a particular spatial frequency) at about the same exposure duration at which the illusion peaked. The exposure duration at which the illusion peaked was longer if the subject was more dark adapted. When the subjects' rating of the perceptual clarity of the gratings was plotted against the size of the Andrews effect (for the same duration and spatial frequency), the data fell on a single function, whether the spatial frequency was 2, 5, or 10 c/deg. The functional significance of these effects is discussed.

Humans↗
PubMed1988

The perception of visual ambiguous figures in schizophrenia and Parkinson's disease.

The frequency of reversal and dominance of aspect of three versions of an ambiguous Schröder staircase were studied in patients with a diagnosis of either schizophrenia or Parkinson's Disease (PD), and in a mixed group of psychiatric patients before and after prolonged neuroleptic therapy. It was found that schizophrenics perceived the staircases from above for significantly less time, and had a (nonsignificant) tendency to have more reversals than controls. PD patients saw the staircases from above for significantly more time, and also had (nonsignificantly) more reversals than controls. In the psychiatric patients, long term neuroleptic therapy had no significant effect on either reversal rate or dominance of aspect. When the contrast and the luminance of the stimulus were manipulated, normal subjects reported significantly less reversals and significantly increased dominance of the superior aspect when the contrast of the stimulus was reduced. Changing the luminance had no significant effect. The implications of these results for visual abnormalities in schizophrenia and Parkinson's Disease are discussed.

Adult↗
PubMed1988

The CD5+ B cell: a B cell lineage with a central role in autoimmune disease?

It is apparent that B cells are heterogeneous with respect to, for example, the antigens they express on their surface, and the stimuli to which they can respond. It is still unclear to what extent these differences relate to the stage of differentiation (eg. virgin B cells differing from activated B cells or memory cells), or whether distinct developmental lineages might exist. It has been proposed by some authors that, in the mouse, B cells expressing the ly-1 antigen constitute a separate lineage. In man also, a minor population of B cells expresses detectable levels of the CD5 antigen, but far less information is available about these cells. Interest in the CD5+ and ly-1+ B cell subpopulations has been further stimulated by the suggestion that these cells might play a special role in autoimmune disease. Although, in mouse, ly-1+ B cells differ in several respects from ly-1- B cells, the main evidence that they form a separate lineage derives from experiments in which ly-1+ B cells could not be reconstituted with adult bone marrow. It should be borne in mind that the situation is quite different in humans where, following bone marrow transplantation, CD5+ B cells are rapidly restored. Moreover, in the irradiated mice, at least in some of the experiments ly-1+ B cells were in fact reconstituted by adult bone marrow. Furthermore, at least in humans, expression of CD5 can sometimes be induced. There is, as yet, no good evidence that human CD5+ B cells form a distinct lineage, and it is possible that CD5 expression depends upon microenvironmental influences acting on the B cell during its differentiation. Several interesting properties have been attributed to ly-1+ B cells, including the ability to provide help to other B cells, and the secretion of autocrine factors. However there is also evidence that these features are not exclusive to B cells expressing ly-1. It has also been suggested that ly-1+ B cells might be long-lived. It is not yet known whether some of the properties of ly-1+ B cells might be a direct result of their expressing this antigen; this may become more clear when the function of CD5 is elucidated. The suggestion that the repertoire of ly-1+ B cells might be biased towards the expression of certain V genes is very interesting. Many of the hybridomas from neonatal mice produce antibodies which are multi-specific, and therefore well suited to form a first line of defence against potential pathogens.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Lymphocytes from patients with primary biliary cirrhosis spontaneously secrete high levels of IgG3 in culture.

The origin of the raised serum IgG3 in primary biliary cirrhosis has been examined. Blood lymphocytes from patients with PBC and from age- and sex-matched controls were cultured, and the culture supernatants were assayed for IgG and IgG3. Lymphocytes from PBC patients spontaneously synthesized a higher percentage IgG3/total IgG than did control lymphocytes, as determined by ELISA. The increased synthesis of IgG3 in culture correlated with serum IgG3 in the patients. This strongly suggests that the raised serum IgG3 in these patients is due to increased synthesis of this isotype. Following PWM stimulation, the proportion of IgG3/IgG synthesized by normal (and most PBC) lymphocytes increased and the difference in IgG3 synthesized by PBC and control lymphocytes became less marked. The kappa/lambda light chain ratio of the IgG3 was assayed by ELISA but no evidence was found for clonally restricted synthesis of IgG3 by PBC blood lymphocytes.

Cells, Cultured↗
PubMed1987

ELISA measurement of IgG subclass production in culture supernatants using monoclonal antibodies.

Specific and sensitive ELISA to quantitate the human IgG subclasses in cell culture supernatants are described. These assays detect a minimum of 5 ng/ml IgG1, 90 ng/ml IgG2, 8 ng/ml IgG3 and 8 ng/ml IgG4 and can generally measure IgG subclasses in lymphocyte cultures containing a minimum of 200 ng/ml of total IgG. The isotype specificity of these ELISA is demonstrated and each individual ELISA shown to react with a number of paraproteins of the relevant subclass independently of their light chain type or their (major Caucasian) allotype. These assays have been used to determine the IgG subclass response of normal human lymphocytes to pokeweed mitogen in vitro.

Antibodies, Monoclonal↗