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Biomedical subjects

K W Walton

Publications and source records attributed to K W Walton.

At least 19 recordsLinked to original sources
PubMed1990

Diagnostic relevance of fibronectin in cryoprecipitates.

Fibronectin is a known component of plasma cryoprecipitates. It is seen in cryoglobulins from patients with monoclonal gammopathies and also from rheumatoid arthritis, and patients with systemic lupus erythematosus and other connective tissue diseases. We evaluated the clinical relevance of measures of cryoprecipitable fibronectin from the sera of 88 patients with rheumatic diseases and 27 healthy controls. There were 28 patients with rheumatoid arthritis, 19 with systemic vasculitis, 5 with cutaneous vasculitis, and 36 with a systemic connective tissue disorder. We measured total and cryoprecipitable fibronectin and for comparison immunoglobulins G, A, and M and complement C3 and C4. Cryoprecipitable fibronectin was detected in 33% control sera and 42% patient sera. The mean levels were higher in the sera of patients in all diagnostic groups. The highest levels were seen in rheumatoid patients with systemic disease, systemic vasculitis, and connective tissue diseases. The presence of cryoprecipitable fibronectin was related to the clinical activity of systemic vasculitis; none of the 6 patients with clinically inactive vasculitis had detectable fibronectin in their cryoprecipitates; but it was seen in 7 to 13 cases with active vasculitis. There were only weak relationships between cryoprecipitable fibronectin and immunoglobulin and complement levels in cryoprecipitates. We conclude that routinely measuring fibronectin levels in cryoprecipitates is generally of doubtful diagnostic value. However, it appears to be a useful marker of the clinical activity of systemic vasculitis and we recommend its use in the laboratory assessment of vasculitis.

Adult↗
PubMed1989

What proteins are present in polyethylene glycol precipitates from rheumatic sera?

The proteins present in 4% polyethylene glycol (PEG) precipitates of 10 normal sera and 60 samples from patients with rheumatic diseases were studied. A variety of immunochemical methods were used, including estimation of the percentages of total serum proteins precipitated by PEG, gel filtration analyses of the precipitates, and affinity chromatography with protein A and anti-immunoglobulin columns. Substantial amounts of protein were precipitated from normal sera. Many non-immunoglobulin proteins were precipitated from patients' sera, including fibronectin, haptoglobin, albumin, transferrin, and alpha 1-antitrypsin. Affinity chromatography with anti-immunoglobulin columns bound non-immunoglobulin proteins from PEG precipitates, but the protein A affinity column did not do so. The view that circulating antibody-antigen complexes alone are precipitated by 4% PEG is too simplistic; many non-immunoglobulin proteins are involved. They may either bind to immune complexes or be coprecipitated owing to non-specific protein aggregation.

Adolescent↗
PubMed1986

Atherosclerotic lesions from the reduction of pulmonary emboli.

Seventy-five intimal arterial thickenings (from 58 subjects) related to pulmonary emboli were examined. Many showed residua derived from the emboli (fibrin, platelets, haemosiderin) and proliferation of elastica and smooth muscle cells. Features resembling those of atherosclerosis were the frequent presence of extracellular lipid and apolipoprotein-B containing lipoproteins (LpB) which corresponded closely in distribution; and (in about 40% of the thickenings) collections of fat-filled (foam) cells. Platelet antigens were often detected within foam cells in some cases, in company with LpB. The results indicate that at least some intimal thickenings originating from pulmonary emboli undergo transformation to atherosclerotic plaques. The role of pulmonary hypertension in the process was investigated. Mechanisms relevant to this transformation and to theories of atherogenesis are discussed.

Adolescent↗
PubMed1986

Atherosclerosis in vascular grafts for peripheral vascular disease. Part 2. Synthetic arterial prostheses.

Thirty-nine synthetic (32 Dacron and 7 Teflon) arterial prostheses (from 38 patients with peripheral arterial disease) removed after periods between 2 months and 18 years, were examined by histology and immuno-histology. The grafts were initially permeated by thrombus containing platelet antigens and this became organised and converted to granulation, and then to fibrous, tissue. The newly-formed tissue contained 'foreign-body' giant-cells in contact with the plastic prosthesis and showed evidence of permeation by plasma proteins. In grafts of over 2 years duration, this reactive tissue no longer contained platelet antigens but invariably revealed bound lipid, identifiable as apolipoprotein-B-containing lipoproteins (LpB), and fibrinogen-related antigens (FRA), in a distribution resembling that seen in atherosclerotic arteries. LpB and FRA were also seen in organised, or partially organised, mural thrombi in older grafts. The oldest grafts additionally showed stenosis, calcification or aneurysm formation. Lipid deposition increases with the age of grafts; is independent of the nature of the plastic fibre used or its mode of fabrication; and sometimes contributes to graft failure. Immuno-histology indicates that this is an insudative process indistinguishable from 'true' atherosclerosis which occurs in graft-linings of prostheses of long duration and in old mural thrombi in grafts and that the lipid in these lesions derives from plasma LpB rather than from platelets. This source for the lipid suggests that the insudative and thrombogenic theories of atherogenesis can be reconciled.

Adult↗
PubMed1986

Takayasu's arteritis: a pathogenetic role for cytotoxic T lymphocytes?

Takayasu's arteritis is an inflammatory panarteritis of unknown aetiology affecting large elastic arteries. We examined a segment of abnormal common carotid artery removed at by-pass surgery from a 23-year-old man with typical angiographic features of Takayasu's arteritis. Using monoclonal antibodies we were able to demonstrate marked infiltration of the arterial wall with OKT8 positive lymphocytes (suppressor/cytotoxic cells) but not with OKT4 positive lymphocytes (helper cells). Studies of circulating lymphocytes showed increased numbers of "activated" cells and increased in vitro cytotoxicity against cultured human umbilical cord endothelial cells, compared to normal lymphocytes. Cellular immunological mechanisms may play an important role in the pathogenesis of Takayasu's arteritis, possibly through the direct action of cytotoxic T cells on large elastic arteries.

Adult↗
PubMed1985

Differences between plasma and synovial fluid fibronectin.

Fibronectin is a high molecular weight glycoprotein of plasma and tissue fluids, and one of its functions is to opsonise particulate material. Chromatographic and electrophoretic analyses showed that the main components of fibronectin are biochemically similar in rheumatoid patients' plasma and synovial fluid. But synovial fluid fibronectin also contains a slow-moving component seen on two-dimensional immunoelectrophoresis, suggesting the presence of fibronectin complexes. Affinity chromatography provided evidence that these involved IgG, and in vitro studies showed that fibronectin influenced the reaction between IgG and anti-IgG. Synovial fluid fibronectin is functionally active in binding to gelatin in an haemagglutination assay, and it gave a relatively higher degree of haemagglutination than did plasma fibronectin, supporting the concept of multivalent fibronectin complexes in synovial fluid. These results suggest synovial fluid fibronectin may be involved in the opsonic removal of IgG-containing complexes from synovial fluid.

Arthritis, Rheumatoid↗
PubMed1985

Atherosclerosis in vascular grafts for peripheral vascular disease. Part 1. Autogenous vein grafts.

29 autogenous vein grafts, from 26 patients with peripheral arterial disease, were studied. 4 grafts of Group I (less than 3 months duration) were patent and removed for reasons other than graft failure. These showed 'arterialisation' only; 4 grafts of Group II (duration 5-18 months) showed thrombotic occlusion; 21 grafts of Group III (duration greater than 2 years) showed impaired graft patency and lipid identifiable as apolipoprotein B-containing-lipoproteins (LpB), and fibrinogen-related antigens (FRA) were seen as intramural deposits in the thickened grafts. LpB was also seen in a perifibrous distribution on the collagen of organised thrombi. Complicated lesions in some Group III grafts showed stenosis or occlusion, ulceration, calcification or aneurysm formation. These features suggest that a process indistinguishable from 'true' atherosclerosis affects vein grafts of long duration. The ways in which such changes may: contribute to graft failure; and improve our understanding of the basic processes involved in atherogenesis, are discussed.

Adult↗
PubMed1985

Ultrastructural changes in the rectal mucosa of patients with rheumatoid arthritis.

The rectal mucosa from patients with severe rheumatoid arthritis has been examined by electron microscopy. Initially the patients were biopsied for investigation into the diagnosis of amyloidosis or vasculitis, which proved to be negative. A range of ultrastructural abnormalities was found which included proliferation of the rough endoplasmic reticulum, mitochondrial inclusions, association of the mitochondria with cytoplasmic filaments, and marked increase in the number of iron containing siderosomes. Most of these abnormalities have already been reported in rheumatoid synovial tissue, and attention is drawn to the similarity in findings between these two sites.

Adult↗
PubMed1985

Transferrin receptor expression by stimulated cells in mixed lymphocyte culture.

Transferrin receptor (TRFr) expression by cells in mixed lymphocyte culture increases steadily for the first 5 days, but then reaches a plateau. By the sixth day in culture, about 20% of viable cells express TRFr in two-way mixed lymphocyte reactions. This subpopulation of TRFr-positive cells represents the proliferating population; it is heterogeneous, containing T-cell blasts and smaller cells which are a mixture of T and non-T cells. A small group of non-T cells have phenotypic similarity to natural killer (NK) cells. T cells appear to divide earlier in the course of the response than non-T cells. The biphasic nature of this response and the slower non-T reactivity may be due to a secondary stimulation of non-T cells by factors released from activated T cells (such as interleukin-2).

Antigens, Surface↗
PubMed1984

The use of cytocentrifuge preparations for the demonstration of T cell surface antigens.

Cytocentrifuged cell preparations have been evaluated as substrates for the demonstration by immunofluorescence of T cell surface antigens. Results obtained by a 2-stage method with fluorescent conjugate specific for the isotype of the first stage monoclonal antibody, and by a 3-stage procedure employing an intermediate antiserum to mouse IgG as amplifying agent, showed good correlation with those obtained by a standard technique performed on cells in suspension. These methods have the advantages of requiring fewer cells and less antibody and the cytocentrifuge preparations may be stored for batch assay.

Animals↗
PubMed1984

The binding of acetic anhydride- and citraconic anhydride-modified human low-density lipoprotein to mouse peritoneal macrophages. The evidence for separate binding sites.

Human plasma low-density lipoprotein (LDL) was modified chemically with either the monocarboxylic acid derivative, acetic anhydride, or the dicarboxylic acid derivative, citraconic anhydride, reagents which react principally with the lysine residues of protein. The modifications increased the net negative charge on the LDL particles, with citraconyl-LDL displaying a greater negative charge than acetylated LDL. Neither the antigenic reactivity nor the overall gross protein/lipid composition of the LDL were affected by the modification procedures, although a small reduction in the total cholesterol content was observed. The altered LDL species lost the ability to bind to the high-affinity cell surface B/E receptor but both bound to mouse peritoneal macrophages with saturable high-affinity kinetics. At 4 degrees C, the macrophages bound 125I-labelled citraconyl-LDL more avidly (K = 21 X 10(-3) ml/ng) than they bound labelled acetyl-LDL (K = 2 X 10(-3) ml/ng). Competitive inhibition studies indicated that acetyl-LDL and citraconyl-LDL were bound to non-identical sites on the macrophage monolayer surface and that the binding site for citraconyl-LDL was also different from that recognized by hypercholesterolaemic rabbit plasma VLDL (beta VLDL).

Acetic Anhydrides↗
PubMed1984

Reticulin and its related structural connective tissue proteins in the rheumatoid synovium.

Argyrophilic reticulin fibres are an important component of the rheumatoid synovium and their distribution and that of their individual protein constituents have been studied in synovial biopsies from a series of 29 cases of rheumatoid arthritis. In acutely inflamed synovia they are predominantly found underneath the hyperplastic synovial lining layer and related to the inflammatory cell infiltrate. With developing chronicity the reticulin network is gradually replaced by mature collagen. This histological pattern is mirrored by changes in the individual components of reticulin fibres-fibronectin, the non-collagenous reticulin component of Pras and Glynn (NCRC) and collagen type III.

Adult↗
PubMed1984

Whipple's disease diagnosed at hip arthroplasty.

A patient is reported with a six-year history of seronegative inflammatory arthritis, lymphadenopathy, and a rash. Many investigations, including repeat jejunal and synovial needle biopsies, failed to establish the diagnosis. Eventually right hip destruction led to arthroplasty. Synovial membrane obtained at operation was examined by electron microscopy and organisms were found with the morphological characteristics of those in patients where the diagnosis was firmly established as Whipple's disease. We propose that Whipple's disease should be seriously considered as a rare but distinct and treatable possibility in the differential diagnosis of seronegative inflammatory arthritis.

Adult↗
PubMed1984

Laminin and vascular proliferation in rheumatoid arthritis.

Laminin is a high molecular weight basement membrane structural glycoprotein. In rheumatoid arthritis and other arthropathies immunoreactive laminin was prominent in synovial blood vessel basement membranes and acted as a marker for them. It codistributed with collagen type IV. Immunohistological reactivity to laminin showed extensive vascular proliferation in rheumatoid arthritis together with basement membrane reduplication, which was confirmed ultrastructurally. Parallel histological studies showed vascular proliferation was predominantly in the subintimal rheumatoid synovium, where it was related to connective tissue proliferation but not to the inflammatory cell infiltrate. Vascular proliferation was also seen in relation to connective tissue changes in biopsies from cases of haemophilic arthritis, osteoarthritis, and meniscal tears. We suggest connective tissue activation is non-specific reaction associated with vascular proliferation. This involves laminin and other structural proteins. It occurs in rheumatoid arthritis and other arthropathies but is distinct from inflammatory cell infiltration.

Adolescent↗
PubMed1984

An experimental model for the study of the opsonic activity of fibronectin in the clearance of intravascular complexes.

An experimental model is described which provides direct evidence of endocytosis of complexes of a charged colloid (dextran sulphate or DS) and of plasma fibronectin (FN) by reticulo-endothelial (RE) cells. This supports previous suggestions that plasma FN acts as a non-immunologically mediated opsonin which effects the clearance of various kinds of circulating colloids and particles by RE cells. DS of molecular weight 500 000 forms FN-containing complexes in rat plasma in vitro and lowers plasma FN levels acutely and in a dose-related fashion when given parenterally to rats. The plasma changes are accompanied by deposition of DS (shown histochemically as metachromatic material) and of FN (shown by specific immunofluorescence) in an identical distribution within RE cells in rat liver and spleen. The protein and polysaccharide components of the complex are disposed of by RE cells at markedly different rates. The model thus also offers a means of studying the dynamics of catabolism of plasma FN by this 'scavenger' pathway. Possible further extensions of the model for other purposes are also discussed.

Animals↗
PubMed1984

A model of persistent antigen-induced chronic inflammation in the rat air pouch.

Continuing antigen-induced inflammation was established in a subcutaneous air pouch in rats by recurrent local challenge. The animals were sensitized using bovine serum albumin in Freund's complete adjuvant and were challenged 14 days later by injection of the antigen in a solution containing sodium carboxymethylcellulose into the air pouch to produce allergic inflammation. A single antigenic challenge induced acute inflammation with a predominantly polymorph infiltration in the first 48 h. Later samples showed a low-grade mononuclear response which persisted for 4-5 days. Repeated challenge produced chronic inflammation with an accentuated mononuclear response. Connective tissue activation involving fibronectin and collagen was seen as the inflammation progressed, and this was associated with production of ferritin by mononuclear cells. Discontinuation of challenge injections resulted in resolution of the granuloma. We suggest this model can be used to investigate the mechanisms involved in chronic inflammatory diseases with an immunological component and to evaluate the effects of therapeutic intervention upon chronic allergic inflammation.

Animals↗
PubMed1984

Failure of R1 type anti-reticulin antibody to react with fibronectin, collagen type III or the non-collagenous reticulin component (NCRC).

The precise specificity of the R1 anti-reticulin antibody (ARA) associated with untreated gluten sensitive enteropathy (GSE) is unknown. Collagen type III, fibronectin and the non-collagenous reticulin component (NCRC) of Pras & Glynn (1973) co-distribute in tissues in a manner consistent with their being components of reticulin. We therefore used purified preparations of these connective tissue components in studies of the specificity of the ARA. Our results show that the ARA found in GSE does not react with collagen type III, fibronectin or NCRC.

Antibodies↗