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Biomedical subjects

J Highton

Publications and source records attributed to J Highton.

At least 55 records · Page 3Linked to original sources
PubMed1987

Macrophage migration and maturation within rheumatoid nodules.

In long-established rheumatoid nodules, monocytes continue to be recruited and to migrate from the outer vascular zone toward the palisade and central necrotic area. Maturation of these cells is shown to take place during tissue migration. We found that the great majority of palisade cells express exclusive mononuclear phagocyte phenotypes. Among this mononuclear phagocyte population are many cells that bear the receptor for iC3b (CR3), but few that bear the receptor for C3b (CR1). HLA-D region molecule expression is intense and widespread.

Aged↗
PubMed1987

Comparison of phenotype expression by mononuclear phagocytes within subcutaneous gouty tophi and rheumatoid nodules.

The mononuclear phagocyte infiltrate which occupies the gout tophus has been compared with that of the subcutaneous rheumatoid nodule. In the gout tophus, macrophage migration appears to be at a relatively low level and effectively terminates once these cells have been recruited into the corona. In the nodule the evidence suggests that both macrophage and granulocyte populations continuously migrate towards, and are progressively incorporated into, the necrotic centres. These observations indicate that chemotactic activity in rheumatoid nodules is at a higher level than in gout tophi, or that the rheumatoid mononuclear phagocyte is more responsive to such stimuli.

Aged↗
PubMed1987

A mononuclear phagocyte subset associated with cell necrosis in rheumatoid nodules: identification with monoclonal antibody 5.5.

A subset of mononuclear phagocytes identified by mAb 5.5 has been found within rheumatoid subcutaneous nodules. These cells appear to be derived directly from blood-borne monocytes. They form a variable proportion of the mononuclear phagocyte population within the nodule and are intimately associated with the tissue necrosis which characterizes these lesions. Necrosis appears within small aggregates of mAb 5.5-positive cells. Similar cells are also associated with localized extensions of necrosis through the palisade zone. Centrifugal extension of the necrotic centers through incorporation of the inner cells of the palisade layer appears to be an independent phenomenon.

Aged↗
PubMed1986

Development of an enzyme immunoassay for the quantitation of cellular antigen expression.

An enzyme immunoassay is described which can be used to quantitate the cellular expression of antigens recognised by mouse monoclonal antibodies (mAb). To provide the sensitivity required, complexes of alkaline phosphatase and mouse monoclonal anti-alkaline phosphatase (APAAP) have been used. The speed and reproducibility of the assay was improved with the aid of immunofiltration methodology. Quantitative measurement of HLA-DR antigen expression by ELISA did not correlate directly with the number of mononuclear cells scored positive following immunohistochemical staining of cytocentrifuged preparations. In patients with rheumatoid arthritis, more HLA-DR was expressed on synovial fluid mononuclear cells than on the corresponding cells obtained from peripheral blood.

Alkaline Phosphatase↗
PubMed1986

Clinical advantages from measurement of IgM-rheumatoid factor by enzyme immunoassay.

Two enzyme immunoassays for rheumatoid factor (RF) were compared with the traditional latex agglutination test. Preference is expressed for an ELISA specific for IgM-RF because it yields specific, quantitative results. Variability of this assay was least in sera containing moderate levels of RF and it was less precise at low concentrations. Survey of a random selection from the local population showed a similar prevalence of IgM-RF positivity as revealed by previous surveys using agglutination techniques. We conclude that measurement by ELISA yields no great increase in the discriminative ability of RF testing.

Adult↗
PubMed1986

Changes in anti-DNA antibody affinity during exacerbations of systemic lupus erythematosus.

The level and average functional affinity of anti-DNA antibody were measured retrospectively in successive serum samples from 5 patients with systemic lupus erythematosus. In 2 patients, severe flares of disease activity were associated with an increase in the level and average functional affinity of anti-DNA antibodies. Three patients who did not experience significant flares in disease activity exhibited more constant levels of antibody of lower average functional affinity. The appearance of antibody of high functional affinity during disease exacerbations suggests that such antibodies may be pathogenic.

Adolescent↗
PubMed1985

The diagnostic value of synovial biopsy in patients with arthritis of unknown cause.

Synovial biopsy of a knee joint was performed in 59 patients with arthritis of unknown cause. Light microscopy revealed a diagnosis in three. A cause became apparent in only a further 23 over a prolonged period of follow-up. Neither light microscopy, immunofluorescence nor electron microscopy discriminated between te principal diagnostic groups. Synovial fluid analysis was better than synovial biopsy at predicting osteoarthritis. Five men with giant effusions developed osteoarthritis and these might represent an entity. Synovial inflammatory changes were less pronounced in those with longer histories. Disease duration and activity may have more influence on synovial characteristics than the nature of the disorder.

Adolescent↗
PubMed1985

HLA-B27 and ankylosing spondylitis: an anti-idiotypic model.

Ankylosing spondylitis (AS) is strongly associated with possession of the HLA (Human Leucocyte Antigen)-B27 histocompatibility alloantigen. It is proposed that immunological tolerance to HLA-B27 allows the emergence of a lymphocyte clone with specificity for connective tissue antigens. Such a pathogenic clone would possess idiotypic determinants cross-reactive with determinants on HLA-B27. This hypothesis was investigated using immunoglobulins from HLA-B27 subjects with active definite AS. Immunoglobulin fractions were assayed for HLA-B27-like idiotopes by inhibition of the cytotoxicity of an anti-HLA-B27 antiserum, and by an ELISA technique. The postulated HLA-B27-like idiotope was not detected using these methods.

Adult↗
PubMed1985

The presence and possible significance of C-reactive protein in rheumatoid inflammation.

C-reactive protein (CRP) is capable of binding to a variety of ligands with subsequent complement fixation in vitro. By this means CRP may contribute to the inflammatory process in some diseases. Elevated levels of CRP were demonstrated in synovial fluids (SF) from patients with a variety of inflammatory arthritides. The contribution of CRP to inflammation in SF was investigated. Sera and SF from patients with rheumatoid and other forms of arthritis were examined for the presence of ligand bound CRP. We were unable to demonstrate significant amounts of bound CRP, either as increased molecular weight using gel filtration, or in the form of CRP-ligand-immunoglobulin complexes using a modified enzyme linked immunosorbent assay. CRP was found associated with the pellet after centrifugation of SF samples. Preliminary studies showed CRP detectable on the surface of cells in some inflammatory SF. The presence of this cell associated CRP suggests that ligand bound CRP may not be demonstrable in the sera and SF examined due to interaction with cells.

Arthritis↗
PubMed1985

An assessment of the diagnostic value of quantitative measurements of IgA rheumatoid factor.

IgA rheumatoid factor (RF) was found in a significant number of the normal population. As a consequence, the presence of IgA RF was not more specific for a diagnosis of rheumatoid arthritis than IgM RF. However, further investigation of IgA RF as a prognostic indicator is important. Our results, which show an association between the presence of IgA RF and higher levels of IgM RF, suggest that careful differentiation between the predictive values of the presence of IgA RF and a high level of IgM RF will be necessary.

Arthritis, Rheumatoid↗
PubMed1984

Concurrent polyarteritis nodosa and temporal arteritis.

A patient is described in which features of both giant cell arteritis and polyarteritis nodosa were present simultaneously. The case emphasises our lack of an aetiologic classification for arteritis and that on occasions typical clinical presentations may be misleading.

Aged↗
PubMed1984

A solid-phase enzyme immunoassay for C-reactive protein: clinical value and the effect of rheumatoid factor.

Measurement of serum C-reactive protein (CRP) concentration is useful in monitoring the progress of chronic inflammatory diseases. Rheumatoid factor, by its interaction with the Fc portion of IgG, has the potential to interfere with solid-phase immunoassays for CRP and other serum proteins. To determine the effect of RF on a solid-phase enzyme immunoassay for CRP we compared assays employing whole antisera or F(ab')2 fragments. In 92 sera with RF latex titres ranging from 1/80 to 1/81,920, no correlation was found between RF concentrations and CRP measurements. CRP concentrations measured by use of whole antisera (mean +/- standard error of the mean, 59.7 +/- 5.7 mg/l, n = 92) were lower than those measured with F(ab')2 fragments (62.5 +/- 5 mg/l), indicating that exaggeration of CRP measurements did not occur in RF containing sera under the conditions of the assay. Our results show that in the CRP-ELISA, interference from RF was precluded by the high serum dilutions employed. At lower serum dilutions RF binding was detected. Consequently, in solid-phase enzyme immunoassays at lower serum dilutions the presence of RF may lead to false positive results and exaggerated measurements.

Arthritis, Rheumatoid↗
PubMed1982

Effect of sera from patients with rheumatoid arthritis on normal lymphocytes: a possible immunoregulatory role for immune complexes.

The ability of rheumatoid sera to support concanavalin-A transformation of normal lymphocytes was inversely related to serum C1q binding activity. When C1q binding activity of the sera was removed by absorption with staphylococcal protein A, subsequent lymphocyte response increased to the level found in immune-complex negative sera. Gel filtration of a small number of sera suggested that the suppressive material had a molecular weight in the range 1.8-4.9 x 10(5) daltons. Aggregated human gammaglobulin suppressed con-A transformation of normal lymphocytes in a dose-dependent fashion. These results suggest that immune complexes present in rheumatoid sera can suppress lymphocyte responsiveness. The relevance of this observation to be clinical features of rheumatoid arthritis is discussed.

Adult↗
PubMed1981

Changes in immune function in patients with rheumatoid arthritis following treatment with sodium aurothiomalate.

The mitogenic response of peripheral blood lymphocytes from 21 patients with rheumatoid arthritis to concanavalin-A (con--A), phytohaemagglutinin (PHA), and pokeweed mitogen (PWM) was significantly lower than in 30 normal subjects. After 15--24 weeks' treatment with sodium aurothiomalate (GST) the response to these mitogens rose to within the normal range. Improvement over pretreatment values was significant for con-A and PWM measured as area under the dose response curve but only for con--A if response at optimal mitogen concentration is the sole criterion. The improvement in PHA response was not significant with either method of measurement. There was an improvement in disease activity by 15--24 weeks as measured by a fall in serum C-reactive protein (CRP), IgM rheumatoid factor (RF), Clq binding activity (ClqBA), and Ritchie articular index. Con--A lymphocyte responsiveness was inversely related to serum CRP levels, but measurements of disease activity were otherwise unrelated to lymphocyte mitogen responsiveness. The observed improvement in peripheral blood lymphocyte responsiveness during gold treatment contrasts with the suppressive effect of gold in vitro. We suggest that the improvement in lymphocyte function is due to the lessening of rheumatoid disease activity during gold treatment, and that the low serum gold levels in our patients were insufficient to mask this effect. Sera from some of our patients were capable of suppressing the function of normal lymphocytes, and this was less apparent after treatment. The suppressive effect of sera correlated with ClqBA. Suppressive factors in serum, including possibly immune complexes, may be one factor leading to suppression of lymphocyte function during rheumatoid arthritis. Such an inverse relationship between humoral and cellular immune mechanisms might influence the clinical expression of rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1981

Synovial histopathology of behçet's syndrome.

Synovial tissue obtained from 7 patients with Behçet's syndrome and 7 patients with early rheumatoid arthritis could not be distinguished under ordinary light microscopy when examined blind. A wide spectrum of features was seen in both diseases, and it is suggested that these may reflect severity and duration as much as the nature of the arthritis. Electron microscopy also failed to illustrate any distinct features of Behçet's syndrome, but immunofluorescent studies indicated consistent deposition of IgG.

Adult↗