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Biomedical subjects

K W Walton

Publications and source records attributed to K W Walton.

At least 37 records · Page 2Linked to original sources
PubMed1983

The role of fibronectin in the pathogenesis of antigen-induced arthritis in the rabbit.

Fibronectin (FN), a high molecular weight glycoprotein, is present in plasma and is a normal structural component of the synovium in the rabbit, as it is in man. FN is also involved in the sequence of changes seen in synovium in experimental antigen-induced arthritis. Its widespread distribution in inflamed synovia in the initial acute phase of induced arthritis probably merely reflects the presence of FN of plasma origin in serous exudates. In established experimental arthritis, FN co-distributes with fibrin, while in synovia undergoing organisation, FN is present intracellularly in several types of mesenchymal cells (suggesting local synthesis) and is deposited on immature collagen fibrils. However, it is no longer present when mature collagen is formed. The persistence of FN, along with fibrin, in inflamed joints, and its involvement in fibrosis, suggest that it may play a significant part in determining the chronicity of this form of experimental arthritis.

Animals↗
PubMed1983

Ultrastructure of synovial changes in rheumatoid disease and in seronegative inflammatory arthropathies.

Synovial tissue has been examined by electron microscopy from patients suffering from either sero-positive or sero-negative inflammatory arthropathies to allow direct comparison of the ultrastructural changes found in these groups and to confirm and extend observations previously made in a smaller group of sero-negative arthropathies. Both groups have been compared with material from healthy controls. The sero-positive group comprised 13 cases of 'definite' or 'classical' rheumatoid arthritis. The sero-negative group consisted of 9 cases of arthritis secondary to Crohn's disease (3); Reiter's syndrome (2); Whipple's disease (1); Behcet's disease (1); Wegener's granulomatosis (1) and ankylosing spondylitis (1). The control tissue was obtained from 6 non-arthritic subjects undergoing surgery for non-inflammatory conditions. Confirmation was obtained of changes previously reported in subcellular organelles, especially in synovial B cells, in all forms of inflammatory arthritis as compared with controls. Attention is now drawn to other intracellular changes in B cells and intermediate cells which included: a marked increase of intermediate filaments and microfilaments: and proliferation of pinocytotic vesicles and rough endoplasmic reticulum. These changes were often accompanied by the presence, in the immediate environment of these cells, of extracellular microfibrillary masses but little or no accumulation of intermediate filaments. It was confirmed that synovial A cells were reduced in number but showed changes suggestive of increased phagocytic activity and also exhibited proliferation of cytoskeletal elements. Differences in these structural changes between sero-positive and sero-negative arthritis were of degree rather than of kind and no 'specific' or diagnostic differences were observed between the various forms of seronegative athropathies. The possible significance of the structural changes observed is discussed.

Arthritis↗
PubMed1983

Penicillamine-induced myasthenia in rheumatoid arthritis: its clinical and genetic features.

The clinical features and genetic background of 18 patients with rheumatoid arthritis were investigated following the development of penicillamine-induced myasthenia (PIM). The initial myasthenia symptoms in all patients consisted of variable diplopia and/or ptosis with progression to a more generalized involvement in 7 of them. No clinical, humoral, or genetic factor was determined which would allow identification of individuals developing generalized as opposed to ocular myasthenia. Withdrawal of penicillamine was associated over 4-60 weeks with a slow resolution of symptoms, facilitated in 12 patients by the use of anticholinesterase agents. In 2 patients a persistent partial unilateral ptosis remains after 15 and 25 months, while in a further patient diplopia is present 42 months after resolution of the other myasthenic symptoms. The patients with PIM when compared with a healthy 'control' population had a significant increase in HLA Dr1 (p corr less than 0.005) and an absence of HLA Dr 3. A genetic susceptibility to the development of PIM, distinct from that observed in myasthenia gravis of spontaneous onset, is suggested by this abnormal distribution of HLA Dr antigens.

Adult↗
PubMed1983

Musculoskeletal disorders in patients with hyperlipidaemia.

We have assessed the nature and significance of musculoskeletal disorders in 166 patients with the commonly encountered forms of hyperlipidaemia attending a lipid clinic. The incidence of musculoskeletal disorders was determined by questionnaire to the patients, inquiries to general practitioners, and a review of hospital records. To ensure the sensitivity of these methods a series of negatively responding cases were seen and examined; none had identifiable musculoskeletal disease. Eight males with type IV hyperlipidaemia had recurrent acute attacks of gout. The only other musculoskeletal disorder possibly attributable to an association with hyperlipidaemia was a transient polyarthritis in 3 patients. This was inflammatory, recurrent, but nondeforming, and involved the small joints of the hand. It did not require any specific therapy or lead to disability. We suggest that, while we have confirmed the association of type IV hyperlipidaemia and gout, there is little evidence for clinically significant arthritis being associated with other commonly presenting forms of hyperlipidaemia, although we accept that the rarely met homozygous familial hypercholesterolaemia may also be complicated by a crystal arthropathy due to the presence of crystalline cholesterol in joints.

Arthritis↗
PubMed1983

Jejuno-ileal bypass arthropathy: its clinical features and associations.

Postoperative arthropathy has been reported in patients undergoing jejunoileal bypass for morbid obesity. The true frequency of this complication, and its independence from preexisting joint disease and from osteomalacia have not been clearly established. Of 107 patients who had undergone jejunoileal bypass, and in whom osteomalacia had been excluded, 38 developed a distinctive arthropathy. This consisted of episodic polyarthralgia, and occasionally arthritis, affecting both large and small joints. The articular symptom complex was independent of other major postoperative complications and unrelated to metabolic disturbances consequent upon rapid weight reduction. Preoperative joint symptoms had a similar incidence in those who did and in those who did not subsequently develop the postoperative arthropathy. Reversal of the intestinal bypass was always associated with an immediate, complete, and permanent remission of arthropathic symptoms.

Adult↗
PubMed1983

Localisation of collagen types and fibronectin in cartilage by immunofluorescence.

Collagens type I, II, III, IV, and V and the minor cartilage collagens, 1 alpha 2 alpha 3 alpha, C-PS 1, and C-PS 2, were purified, antibodies raised, and then used in immunofluorescence studies on bovine nasal cartilage (BNC). Punctate localisation was seen with the type II antibody. However, pretreatment of sections with hyaluronidase to remove the proteoglycan resulted in diffuse staining over all the section with this antibody. Antibodies to 1 alpha 2 alpha 3 alpha, C-PS 1, and C-PS 2 collagens gave no staining on untreated BNC sections, but after treatment with hyaluronidase all 3 antibodies showed as a diffuse 'halo' round each chondrocyte lacuna. Anti-type I, anti-type III, and anti-type IV collagen antibodies did not stain untreated or enzyme treated BNC. Type V collagen antibodies gave a bright ring in the pericellular region of the lacunae of hyaluronidase-treated BNC. This was unexpected, as we could not detect type V collagen biochemically in the same cartilage. Anti-fibronectin antibodies stained areas distant from the chondrocytes, these areas being distinct from those stained by 1 alpha 2 alpha 3 alpha and C-PS antibodies, suggesting that fibronectin is not associated with these collagens in BNC. These results suggest that different collagen types may have different locations within the cartilage matrix, that proteoglycans may inhibit antibody association with collagen, and that fibronectin is normally not associated with all types of collagen.

Animals↗
PubMed1983

Ultrastructure of the synovial membrane in seronegative inflammatory arthropathies.

The ultrastructure of the synovial membrane has been studied in 6 patients with seronegative inflammatory arthropathies: Reiter's (2), Crohn's (2), Whipple's (1) and Behçet's disease (1). The most striking changes were found in the synovial B cells, many containing abnormally large mitochondria with altered cristae surrounded by fibrillar material. Similar material was present in dilated endoplasmic reticulum which was the probable source of groups of extracellular fibrillar spheroidal bodies. The B cells also contained electron dense granular lysosomes of very variable size which, in common with the abnormal mitochondria, were often associated with bundles of orientated microfilaments and large golgi complexes. Light microscopy of the synovial membrane was consistent with an inflammatory arthritis, as were the high white cell counts in the synovial fluid. Systemic activity in the patients was indicated by raised ESR and C-reactive protein (CRP).

Arthritis↗
PubMed1982

Synovial fluid and plasma fibronectin levels in rheumatoid arthritis.

1. Plasma fibronectin levels were similar in 60 healthy subjects and 88 with the rheumatoid arthritis. 2. In 42 patients with rheumatoid arthritis synovial fluid fibronectin levels were significantly higher than plasma levels (P less than 0.001). Intermediate fibronectin levels were found in synovial fluid from six patients with psoriatic arthritis, eight patients with osteoarthritis and seven with seronegative arthritis. 3. Plasma and synovial fluid fibronectin levels were not related to indices of inflammatory activity such as the erythrocyte sedimentation rate, the Ritchie articular index or synovial fluid cell counts. Nor did fibronectin behave as an acute-phase protein. 4. Immunofluorescent studies showed that fibronectin was adsorbed on fibrinous debris in rheumatoid arthritic joints. 5. These findings suggest that there is local production of fibronectin by the synovium and suggest that measurement of fibronectin levels in the synovial fluid may serve as an indicator of the tissue response to rheumatoid arthritis.

Adolescent↗
PubMed1982

Studies of a variant very-low-density lipoprotein with an acquired deficiency of apolipoprotein C-II.

1. A variant very-low-density lipoprotein was associated with severe hypertriglyceridaemia. Urea-polyacrylamide gel electrophoresis of the tetramethylurea-soluble apolipoproteins of these very-low-density lipoproteins (VLDL) showed that the apolipoprotein C-II content was less than 10% of that in VLDL from hypertriglyceridaemic (3-120 mmol/l) controls. 2. VLDL were incubated with bovine milk lipoprotein lipase (LPL) and a 9,10-3H-labelled triglyceride emulsion. The VLDL deficient in apolipoprotein C-II were a poor activator of LPL, compared with the effect of VLDL with normal content of apolipoprotein C-II obtained from either normal or hypertriglyceridaemic sera. 3. The efficacies of various VLDL as substrates fo activated LPL were examined. Apolipoprotein C-II-deficient VLDL were a poor substrate for the activated enzyme compared with normal or hypertriglyceridaemic VLDL, and compared wtih an artificial triglyceride emulsion. 4. The abnormal VLDL were obtained from a subject with an IgG3 lambda myeloma protein. Intravenous infusion of normal plasma containing apolipoprotein C-II was followed by rapid, complete, but short-lived (5-10 days) clearance of serum triglyceride. The effect was observed on three occasions until treatment of the myeloma was effective. 5. The monoclonal protein behaved as a cryoglobulin, and formed large particle complexes with triglyceride-rich lipoproteins, especially at temperatures below 37 degrees C. The apolipoprotein C-II deficiency, and consequent hypertriglyceridaemia, may be secondary to an autoantibody directed against apolipoprotein C-II. VLDL from relatives with hypertriglyceridaemia, but without myeloma, had normal apolipoprotein content, activated LPL, and were efficient substrates for the enzyme.

Adult↗
PubMed1982

Frequency of occurrence, mode of development, and significance or rice bodies in rheumatoid joints.

The incidence of rice bodies (RB) in synovial effusions has been studied in 36 patients with rheumatoid arthritis (RA) and in 12 patients with seronegative inflammatory arthritis (7 cases of Still's disease, 3 of psoriatic arthritis, and 2 of ankylosing spondylitis). In the RA group 50 joints were aspirated before and after saline lavage with a specially designed wide-bore needle. RB were found in 72% overall of the joints studied in this group, 14% on initial simple aspiration and an additional 58% after lavage. In contrast no rice bodies were found in 31 aspirations with lavage by an identical technique in the 12 patients with seronegative synovitis. The RB in RA synovitis occurred both early and late in the course of the disease and were not related to the severity of clinical or radiological changes. However, removal of rice bodies was accompanied by clinical improvement and reduction of synovitis. Macroscopically RB varied in shape and size, some being so large as to preclude effective removal by needles of the gauge customarily employed for joint aspirations. Microscopically the majority of RB were composed of coarsely reticular material reacting immunologically with antifibrinogen and antifibronectin and containing mononuclear cells. Some showed vacuolation suggestive of fibrinolysis, but many showed organisation like that seen in established connective tissues, with the formation of mature collagen, reticulin, and elastin. These findings are discussed in relation to the origin, development, and significance of rice bodies in rheumatoid synovitis.

Adolescent↗
PubMed1982

Studies on reticulin. I: Serological and immunohistological investigations of the occurrence of collagen type III, fibronectin and the non-collagenous glycoprotein of Pras and Glynn in reticulin.

Collagen Type III, fibronectin and a non-collagenous reticulin component (NCRC) are all secretory products of fibroblasts and other mesenchymal cells. Antisera to human collagen III (isolated from the placenta) human plasma fibronectin, and NCRC (from spleen) have been used to examine possible antigenic relationships between these proteins both by serological studies and by comparison of the distribution of the proteins in various tissues using immunofluorescence. For other comparative purposes, the distribution of collagen and of reticulin in the same tissues was also sought using conventional histological methods. Serologically, the 3 antisera showed distinct specificities. However, when used on sections all 3 antisera gave closely similar staining patterns broadly resembling that of histological "reticulin", although minor differences were noted to be characteristic of the distribution of the respective antigens in certain tissues and in cell monolayers. The results support previous suggestions that histological "reticulin" is not a single entity but is a compound fibrous structure containing collagen Type III, fibronectin and at least 1 additional non-collagenous glycoprotein (NCRC).

Cells, Cultured↗
PubMed1981

The preparation of plasma fibronectin antigen and antiserum.

Affinity chromatography of human plasma, using either gelatin or fibrinogen coupled to Sepharose 4B, depletes the plasma of fibronectin. Other 'contaminant' proteins are also bound by this procedure on the column and elute with the fibronectin, as shown by using the bound and eluted fraction to immunise rabbits. Such antisera can be rendered specific for fibronectin by absorption with fibronectin depleted plasma. Alternatively, purified fibronectin can be obtained by a two-stage chromatographic procedure using a second separation on Sephacryl S300, and immunization with this as antigen produces monospecific antiserum. This reacts both with plasma and tissue fibronectin.

Antigens↗
PubMed1981

Significance of fibronectin in rheumatoid arthritis and osteoarthrosis.

Fibronectin is a glycoprotein secreted by connective tissue cells into their environment and into the blood. Plasma fibronectin has been isolated and used to prepare an antiserum. This has been shown to be specific for fibronectin and unreactive with fibrin(ogen) and collagen, to which fibronectin binds in vitro. The antiserum has been used to examine the distribution of this protein in the synovium in health, in rheumatoid arthritis, and in osteoarthrosis, and to estimate levels in plasma and synovial fluid. The results suggest that fibronectin is synthesised by synovial cells, and the synovial fluid level of fibronectin was found to be about twice the plasma level in rheumatoid arthritis. In long-standing arthritis fibronectin was also found to be codistributed with (presumably by adsorption upon) fibrin and immature collagen in intra-articular structures but was no longer demonstrable in areas where mature collagen had been formed in areas undergoing fibrosis. The possible significance of local fibronectin production within joints in relation to its possible effect on the resolution or continuance of arthritis is discussed.

Adult↗
PubMed1981

Significance of laminar antikeratin antibodies to rat oesophagus in rheumatoid arthritis.

Antikeratin antibodies reacting in a laminar distribution with keratinised rat oesophagus were found in the sera of a proportion of patients with rheumatoid arthritis but not in healthy controls. In rheumatoid arthritis (RA) the proportion of sera exhibiting this reactivity varied with the site tested in the rat's upper alimentary tract. There were 36.4% of 99 patients with RA who gave positive reactivity to the middle third of the rat oesophagus. This antikeratin reactivity was related to the occurrence of other antitissue antibodies (to reticulin, gastric parietal cells, smooth muscle, mitochondria, or nuclear components) in the same patients with rheumatoid arthritis. It was not related to the duration of early morning stiffness, the Ritchie index, the erythrocyte sedimentation rate, certain acute phase proteins (haptoglobin and C-reactive protein) nor to the levels of haemoglobin or immunoglobulins. Antikeratin antibodies were not specific for rheumatoid arthritis and also occurred in 50% of 16 patients with progressive systemic sclerosis.

Adult↗
PubMed1981

Distribution of fibronectin in the rectal mucosa.

Fibronectin is a glycoprotein of high molecular weight present in tissues, plasma, and tissue fluids. Its distribution in the rectal mucosa was studied by immunofluorescent and immunoperoxidase techniques using a monospecific antiserum. Immunofluorescent reactivity for fibronectin was present in the normal rectal mucosa of control subjects in epithelial cells, on basement membranes, and as a loose cribriform network of extracellular reactivity in the lamina propria that codistributed with histochemically demonstrable reticulin. Fibronectin was demonstrated immunoelectromicroscopically on collagen fibres, on smooth muscle cells and within and between columnar epithelial cells. In the rectal mucosa of patients with colitis with marked inflammatory changes, fibronectin appeared thickened and more prominent when present on basement membranes and as sparse strands between inflammatory cells infiltrating the lamina propria. In patients with longstanding colitis and less inflammatory cell infiltration there was a diffuse increase in fibronectin which was densely and uniformly present throughout the lamina propria. Fibronectin is a structural component of the rectal mucosa and changes in its distribution may form an important part of the local reaction to inflammatory bowel disease.

Adolescent↗
PubMed1981

The distribution of fibronectin in the pannus in rheumatoid arthritis.

Fibronectin is an adhesive glycoprotein synthesized by mesenchymal cells. Its distribution in the rheumatoid pannus has been studied by immunofluorescence using a monospecific antiserum. All areas of the pannus contained immunoreactive fibronectin, including its junctions with synovium, ligaments, bone and cartilage. It formed a coarse extracellular meshwork which surrounded the inflammatory cells infiltrating the pannus and which codistributed with reticulin and "immature" collagen. The proliferative cellular areas of the pannus showed marked reactivity for fibronectin. Although fibronectin was present at the pannus-cartilage junction, it was not otherwise found in articular cartilage. Fibronectin in the pannus did not have any relationship to the distribution of immunoglobulins or complement. Fibronectin is a structural component of the rheumatoid pannus and may play a role in the pathogenesis of rheumatoid synovitis.

Aged↗