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J P Edmonds

Publications and source records attributed to J P Edmonds.

At least 37 records · Page 2Linked to original sources
PubMed1984

Persistence of HLA-B27 cross-reactive bacteria in bowel flora of patients with ankylosing spondylitis.

Previous studies have shown that antisera raised in rabbits to certain enteric bacteria (cross-reactive bacteria) are capable of specifically lysing in a 51chromium-release lymphocytotoxicity test the lymphocytes of HLA-B27-positive (B27+) patients with ankylosing spondylitis (AS). This study investigated the clinical relevance of this finding by ascertaining whether Escherichia coli isolated from the rectal swabs of 20 B27+ AS patients (B27+ AS+) and 46 controls (35 B27- AS- and 11 B27+ AS-) were able to absorb the lymphocytotoxic activity of these antisera. All isolates from B27+ AS+ patients and one from a B27- AS- individual were capable of removing this activity. These organisms persisted in the bowel flora of five selected patients for at least 9 months. Cross-reactive bacteria were also found in a range of gram-positive organisms, including streptococcal, staphylococcal, and clostridial species. The relevance of these findings is discussed in terms of a pathogenetic concept relating the persistence of cross-reactive bacteria in the bowel flora of B27+ individuals to an early event in the development of AS.

Antibodies, Bacterial↗
PubMed1984

Immunoregulation in juvenile chronic arthritis.

The presence of hyperimmunoglobulinaemia and antinuclear antibodies in patients with juvenile chronic arthritis (JCA) suggests a possible role for immunoregulatory abnormalities in the pathogenesis of the disease. This is further supported by the demonstration in the sera of such patients of an autoantibody active against a suppressor inducer T cell subset. To identify immunoregulatory defects in JCA, a method of measuring concanavalin A (Con A)-inducible lymphocyte suppression of IgG production in vitro has been established. Peripheral blood mononuclear cells were cultured in the presence of either medium alone, pokeweed mitogen (PWM), Con A, or PWM together with Con A. IgG present in culture supernates at 8 days was measured by a double-antibody radioimmunoassay. Spontaneous IgG synthesis by lymphocytes by both patients and child controls was found to be more than double that of lymphocytes from adult control subjects. However, lymphocytes of children (patients or controls) did not show stimulation of IgG production in the presence of PWM. Con A-induced suppression of spontaneous IgG synthesis was reduced compared to adult controls in both patients (p less than 0.02) and child controls (p less than 0.05). Con A-induced suppression of IgG synthesis in the presence of PWM was also reduced compared to adult controls in both patients (p less than 0.01) and child controls (p less than 0.01) but was also reduced in the patient group compared to the child controls (p less than 0.01). Thus, spontaneous IgG synthesis in children is increased compared to adults, and IgG-producing cells appear less subject to regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Ewing's sarcoma presenting as monoarthritis.

A 22-year-old woman presented with a monoarthritis which mimicked septic arthritis. Synovial biopsy showed chronic synovitis. The synovial fluid was macroscopically purulent but was subsequently shown to contain malignant cells arising from a Ewing's sarcoma of the distal femur. This case indicates that malignancy should be considered in the differential diagnosis of an unexplained monoarthritis, and documents a monoarthritis as the presenting feature of Ewing's sarcoma.

Adult↗
PubMed1984

A factor in the culture filtrate of some Klebsiella isolates specifically modifies the fibroblasts of HLA-B27-positive normal individuals.

Cultured skin fibroblasts of HLA-B27-positive clinically normal individuals specifically bind, and are modified by, a factor in the culture filtrate of some Klebsiella isolates. These modified fibroblasts are serologically similar to the cells (lymphocytes and fibroblasts) of B27-positive patients with ankylosing spondylitis (B27+AS+). By contrast, B27+AS+ cells fail to bind the factor, presumably because a receptor present on B27+AS- cells has already been blocked or modified by a Klebsiella antigen in vivo.

Cells, Cultured↗
PubMed1983

Possible role of enteric organisms in the pathogenesis of ankylosing spondylitis and other seronegative arthropathies.

One-hundred eighty-five clinical isolates of Salmonella sp., Shigella sp., Escherichia coli, and Campylobacter sp. were tested for their ability to absorb the lymphocytotoxic activity of an antiserum (anti-Klebsiella sp. K43) directed against a specific HLA-B27-associated cell surface determinant on the lymphocytes of patients with ankylosing spondylitis (AS). Seven of these isolates (three Salmonella sp., two Shigella sp., one E. coli, and one Campylobacter sp.) were found to cross-react with the B27-positive cells of AS patients (B27+ AS+); an E. coli organism isolated from the rectal swab of an HLA-B27-negative clinically normal individual also cross-reacted with B27+ AS+ cells. These cross-reactive enteric organisms elaborate a factor (modifying factor) which specifically modifies the B27-positive lymphocytes of normal individuals; this factor is structurally and antigenically related to a functionally similar factor secreted by certain isolates of Klebsiella sp. These data suggest that certain enteric organisms share a common determinant which cross-reacts with B27+ AS+ cells. It is suggested that this cross-reactivity is somehow related to an early event in the pathogenesis of AS and possibly of other seronegative arthropathies.

Chromatography, Gel↗
PubMed1982

Immunochemical characterization of Klebsiella antigens which specifically modify an HLA-B27-associated cell-surface component.

Culture filtrates of some Klebsiella isolates contain a factor(s) capable of specifically modifying the HLA-B27-positive lymphocytes of normal individuals, resulting in a phenotypic change similar to that seen on lymphocytes from patients with ankylosing spondylitis (AS). To further delineate the nature of the interaction between HLA-B27 and some Klebsiella products we have undertaken a chemical characterization of B27+AS+-cross-reactive Klebsiella antigens from the culture filtrate and the bacterial cell-membrane. Biogel P-100 chromatography of the Klebsiella K43-derived modifying factor from the culture filtrate and from an NP-40-solubilized membrane extract gave a molecular weight of 26,000-30,000. Isoelectric focusing revealed that the modifying factor had an isoelectric point of approximately 5.4. Membrane-associated modifying factor activity was found only in outer-membrane preparations indicating that the cross-reactivity between Klebsiella K43 and B27+AS+ cells is defined, at least in part, by outer-membrane antigens. These studies demonstrate that membrane components of Klebsiella K43 share antigenic determinants with a modifying factor, which is released into the culture medium, and that these components are capable of specifically altering the HLA-B27 antigen or an associated cell-surface structure. Such a modification occurring in vivo following exposure to Klebsiella, or to antigenically related organisms, could explain the triggering of the B27-associated arthropathies such as AS.

Antigens, Bacterial↗
PubMed1981

The distribution of a specific HLA-B27-associated cell surface component on the tissues of patients with ankylosing spondylitis.

In this paper, we report the presence on Epstein-Barr virus-transformed lymphoblastoid cell lines on platelets and on fibroblasts of an HLA-B27-associated cell surface complex (antigenically related to some antigens of Klebsiella K43 and K21) which is identical to or cross-reactive with the determinant present on the peripheral blood lymphocytes (PBL) of B27-positive patients with ankylosing spondylitis (AS). By contrast, no Klebsiella K43 markers could be demonstrated on the spermatozoa of B27+ AS+ individuals even though these cells expressed the HLA-B27 alloantigen. No B27-associated K43 antigen was detected on the erythrocytes of patients or of normal controls. The B27-associated membrane marker is still detectable on lymphoblastoid cell lines after 20 generations and on fibroblasts after about 10 generations. This finding implies that the continued expression of Klebsiella-modified B27 structure is generally determined and does not require the repeated exposure of the cell surface to Klebsiella antigen. These data suggest that certain non-lymphoid as well as lymphoid cells may be involved in the complex sequence of events leading to the clinical manifestation of AS.

Blood Platelets↗
PubMed1980

Characterization of a factor(s) present in Klebsiella culture filtrates that specifically modifies an HLA-B27-associated cell-surface component.

It has been shown that HLA-B27 lymphocytes from healthy individuals (B27+ ankylosing spondylitis [AS]-), which are not lysed by an antiserum against Klebsiella K43, can be rendered susceptible to lysis after incubation in the culture filtrate of Klebsiella K43. This finding is compatible with a specific modification by a Klebsiella K43-derived soluble factor of a B27-associated lymphoid cell component. Preliminary characterization of the factor has indicated that it is nondialyzable, but it is heat labile at 56 degrees C for 30 min and has a 35,000-50,000 mol wt. The modifying factor activity of the filtrate is destroyed by neuraminidase but not by trypsin and alpha-chymotrypsin. Furthermore, the ability of the factor to convert B27+AS- lymphocytes can be specifically absorbed by B27+AS- lymphocytes, but not by B27+AS+, B27-AS+, or by B27-AS- lymphocytes, which suggests that B27+AS- cells carry a hypothetical receptor which can specifically bind a Klebsiella K43 antigenic determinant. These results imply that the modification by environmental agents of specific major histocompatibility complex-associated gene products may be an important element in the pathogenesis of the HLA-B27-linked seronegative arthropathies.

Antigens, Bacterial↗
PubMed1977

Diaphragm function and lung involvement in systemic lupus erythematosus.

Lung involvement was assessed in 30 consecutive patients with systemic lupus erythematosus (SLE), not selected by respiratory symptoms. Pulmonary function tests revealed a higher rate of abnormality than either clinical history or radiography. The single breath carbon monoxide diffusing capacity was below 80 per cent of the predicted value in 24 patients (80 per cent), and a reduced total lung capacity was present in 13 (43 per cent). There was a weak correlation between the severity of the functional defect and disease activity, assessed antinuclear factor and DNA binding. No correlation was found with serum complement of Clq precipitation. Since pulmonary fibrosis in SLE is uncommon it cannot account for the high frequency of abnormal findings, and the pathogenesis of the functional changes is probably multifactorial. In seven of the patients with the smallest lung volumes, measurements of static pressure volume curves and of maximum respiratory pressures indicated extrapulmonary volume restriction. In five of these patients, diaphragm function was specifically assessed and found to be grossly abnormal in four. The inability of the diaphragm to generate normal pressure may be due to either severe weakness or immobility following extensive pleural adhesions. The well recognized syndrome of "shrinking lungs" and high "sluggish" diaphragms with clear lung fields on radiography is probably due to dysfunction of the diaphragm rather than to primary intrapulmonary pathology.

Adolescent↗
PubMed1977

Detection and characterization of DNA-anti-DNA complexes in a patient with systemic lupus erythematosus.

DNase digestion of SLE serum, with consequent release of bound DNA antibody has been proposed as a method for the direct demonstration of circulating DNA-anti-DNA complexes. In the present studies on the serum of a girl with active SLE nephritis, circulating DNA-anti-DNA complexes were demonstrated at the precise time of relapse of SLE nephritis. Ultracentrifugation showed that these complexes were of low molecular weight.

Antibodies, Antinuclear↗