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Biomedical subjects

D L Scott

Publications and source records attributed to D L Scott.

At least 199 records · Page 11Linked to original sources
PubMed1987

Fibronectin and immune complexes in rheumatic diseases.

The relation between fibronectin and immune complexes in rheumatic disease was examined in a series of linked studies. Fibronectin was present in immune complexes formed in vitro in the absence of C1q. Gel filtration chromatography showed complexed fibronectin was present in the serum of a patient with rheumatoid vasculitis, but not in normal serum; the complexed fibronectin coeluted with IgA and C3. Two dimensional immunoelectrophoresis showed a single fibronectin component was present in normal serum, but a number of components were present in serum from a rheumatoid patient. Polyacrylamide gel electrophoresis followed by immunoblotting for fibronectin showed that polyethylene glycol precipitates of synovial fluid contained immunoreactive components of a variety of sizes, indicating the presence of fragments of the molecule. An analysis of fibronectin in polyethylene glycol precipitates of paired serum and synovial fluid samples from 17 patients with rheumatoid arthritis and 16 with osteoarthritis showed more fibronectin was present in rheumatoid samples, especially in synovial fluid. More fibronectin was also present in synovial fluid than in serum polyethylene glycol precipitates; there was no direct relationship with C1q levels. All these results suggest that fibronectin is an integral component of immune complexes. This has potential pathogenic significance because it shows that a product of connective tissue cells may influence the functions of the immune system.

Antigen-Antibody Complex↗
PubMed1987

Clinical value of ELISA assays for IgM and IgG rheumatoid factors.

The clinical value of enzyme linked immunosorbent assays (ELISA) assays for IgM and IgG rheumatoid factors was assessed in a series of studies using rabbit IgG as antigen. The tests were reproducible with intra-assay coefficients of variation of 6% and could be simply and rapidly performed. Normal ranges were established using 106 sera from healthy controls. In a cross sectional study of 208 rheumatoid patients these assays were compared with the Rose-Waaler and laser nephelometric assessments of rheumatoid factor. In some patients there were discrepancies between rheumatoid factor positivity determined by one method or another. IgM ELISA and Rose-Waaler titres showed a significant correlation (r = +0.58; p less than 0.001), but there was a low correlation between IgM and IgG ELISA (r = +0.27; p less than 0.001). There was no evidence to show that the measurement of IgM or IgG rheumatoid factor gave significantly more clinical information than traditional tests such as the Rose-Waaler or latex agglutination tests.

Arthritis, Rheumatoid↗
PubMed1987

Long term experience of salazopyrin EN in rheumatoid arthritis (RA).

Our studies have shown that Salazopyrin EN is an effective slow-acting anti-rheumatic drug, improving clinical synovitis, depressing the acute phase response, capable of inducing remissions and possibly influencing the progression of joint damage. It is well-tolerated in the long-term with comparatively few serious side effects. Its mechanism of action, however, is still not entirely clear. We have found that the sulphapyridine moiety penetrates the synovial membrane and also that it can modify immune function. While Salazopyrin undoubtedly has an important role in the therapy of rheumatoid arthritis, it probably also has a place in the treatment of seronegative arthropathies and the spondyloarthritides. Furthermore we suggest that it should be used as an anchor drug in combination therapy to attempt to suppress disease activity further and limit joint damage.

Anti-Inflammatory Agents↗
PubMed1987

An in vitro system for studying cartilage degradation by macrophages.

Cartilage damage in inflammatory arthritis may be mediated by a number of cell types; the macrophage is one of them. To examine their role we developed a new macrophage-cartilage co-culture system on a microscale. This used macrophages derived from the peritoneal cavity of Balb/c mice together with cartilage slices from bovine nasal septa. We examined the effects of macrophages on cartilage proteoglycan loss measured colorimetrically. When chondrocytes were dead, cartilage released proteoglycan; macrophages increase the amount of proteoglycan loss; stimulating macrophages with zymosan further increased proteoglycan loss. With live chondrocytes the situation was different. Macrophages only gave a major increase in cartilage proteoglycan loss when stimulated by zymosan. These results show it is possible to establish a simple model of macrophage-induced cartilage degradation. In this a variety of effects given by macrophages can be demonstrated depending on the presence or absence of live chondrocytes.

Animals↗
PubMed1986

Crystallization and preliminary diffraction studies of the Lys-49 phospholipase A2 from Agkistrodon piscivorus piscivorus.

Previous chemical and structural studies have proposed a major role for Asp-49 in the calcium-mediated activation of phospholipases A2. Recently, a new class of phospholipases A2 has been characterized with a lysine in the place of aspartate at position 49 (Maraganore, J. M., Merutka, G., Cho, W., Welches, W., Kézdy, F. J., and Heinrikson, R. L. (1984) J. Biol. Chem. 259, 13839-13843; Maraganore, J. M., and Heinrikson, R. L. (1986) J. Biol. Chem. 261, 4797-4804). Although both the Lys-49 and Asp-49 phospholipases require calcium for enzymatic activity, the Lys-49 enzymes appear to be unique in their ability to bind phospholipids prior to undergoing calcium-mediated activation. We have successfully crystallized the Lys-49 phospholipase A2 from the venom of the American cottonmouth water moccasin (Agkistrodon piscivorus piscivorus). The crystals are tetragonal, the space group being P4(1)2(1)2 or P4(3)2(1)2 with unit cell dimensions of a = b = 71.05 A, and c = 57.76 A. There is only one molecule in the asymmetric unit and the crystals provide good quality diffraction data to 2.2 A.

Crystallization↗
PubMed1986

Fibronectin in polyethylene glycol precipitates: evidence for a role in immune complexes.

Fibronectin is involved in the opsonic clearance of particulate material. It is present in plasma and synovial fluid and thus might be expected to have a role in the clearance of immune complexes. We have investigated this in a study of polyethylene glycol (PEG) precipitable material from the serum of patients with rheumatoid arthritis, systemic lupus erythematosus, and other connective tissue disorders. Fibronectin is a significant component of PEG precipitates but the amount present is influenced by the method of preparation: more precipitates at 4 degrees C than at 20 degrees C. Fibronectin precipitation by PEG was considered to be related to immune complexes because: there was no direct relationship between serum fibronectin levels and the amount present in PEG precipitates; radiolabelled purified isolated fibronectin did not precipitate in 4% PEG; there was a direct relationship between the amount of fibronectin in PEG precipitates and the amounts of immunoglobulin G, A, and M. These results indicate that fibronectin is involved in immune complexes in rheumatic diseases, though they do not show it has an important biological role in these circumstances.

Antigen-Antibody Complex↗
PubMed1986

Rheumatoid inflammation and joint destruction: cause and effect or parallel phenomena?

Joint damage is a characteristic and important consequence of rheumatoid arthritis; it is usually considered to be a direct result of the inflammatory synovitis. This view implies that by treating actively the synovial inflammation subsequent joint damage will be reduced and the long-term outlook of patients with rheumatoid arthritis thus improved. However, there is relatively little clinical evidence that suppressing inflammation reduces rheumatoid joint damage. An alternative view is that the mechanisms causing inflammation and those leading to joint destruction are parallel processes related only indirectly. Considerable evidence supports such a concept. Clinical studies show radiological progression of the disease occurs despite improvements in measures of joint inflammation and a reduction in the levels of acute phase proteins. Damage can progress in either actively inflamed hot joints or cool swollen joints. Histopathologically the features of rheumatoid synovitis are non-specific, while the radiological pattern of joint damage is very characteristic. There is evidence that lymphocytic infiltration is not a poor prognostic finding, despite it being a typical feature of inflamed joints. Experimental studies also fail to show a close correlation between inflammation and cartilage damage: this is seen in experimental arthritis, coculture in vitro systems, and the air pouch model of cartilage damage. We suggest that attempts to improve the outcome of rheumatoid arthritis should not merely concentrate on controlling inflammation but should also seek to modify the associated connective tissue changes of the disease.

Anti-Inflammatory Agents↗
PubMed1986

Massive eosinophilia in rheumatoid arthritis: report of four cases.

We report four cases of massive eosinophilia (greater than 1.5 X 10(9)/l) a phenomenon uncommon in rheumatoid arthritis. In two patients it preceded therapy with second line anti-rheumatic drugs. The others developed it during therapy with penicillamine and gold, though neither had an adverse reaction. It appears there are two patterns of massive eosinophilia in RA; one is related to the disease process the other to drug therapy. It does not necessarily predict adverse drug reactions nor preclude treatment with anti-rheumatic therapy.

Adult↗
PubMed1986

Factors influencing mortality in rheumatoid arthritis.

The prognosis in rheumatoid arthritis respecting mortality was studied in a consecutive series of 489 hospital patients over a period of 18 years. The relative risk of mortality was raised in both men (2.6; p less than 0.001) and women (3.4; p less than 0.001). In the women the relative risk was also influenced by prior duration of RA and was characterised by a diminution in risk 5-9 years after first presentation. Relative risks for men were more uniformly distributed over time. Annual excess mortality rates were strongly associated with age at first presentation in women, the rate increasing with increasing age in both the group seen within 5 years of onset of disease (chi 2(1) for trend = 30.4; p less than 0.001) and in the later referral group (chi 2(1) = 34.0; p less than 0.001). A similar but much less marked effect was observed in men in the early referral group (chi 2(1) = 13.7; p less than 0.001) only. These results suggest that initially women may have a milder form of disease and that hormonal status may affect prognosis. Future long-term therapeutic studies in RA should take into account the prognostic factors of age, sex and duration of disease.

Adolescent↗
PubMed1986

Fibronectin binding with immunoglobulin aggregates and its association with rheumatic disorders.

Fibronectin was shown to bind heat-aggregated, but not monomeric, human IgG, suggesting that fibronectin may bind directly to IgG immune complexes. The presence of material both binding and already containing fibronectin was demonstrated in polyethylene glycol precipitates of sera and synovial fluids from patients with rheumatoid arthritis (RA) and gout, but not normal sera. By contrast, complement-fixing complexes contained fibronectin in RA synovial fluids and sera, but not in sera and synovial fluids from other rheumatic disorders. It is considered that fibronectin binds to immune complexes in RA synovial fluids and sera but that some other, as yet unidentified material, is effective in binding fibronectin in sera and synovial fluids from patients with osteoarthritis and crystal synovitis.

Antigen-Antibody Complex↗
PubMed1986

Prediction of progressive joint damage in patients with rheumatoid arthritis receiving gold or D-penicillamine therapy.

Seventy two patients with classical or definite rheumatoid arthritis (RA) were randomly allocated to receive gold or D-penicillamine therapy (DPA) in a prospective study designed to evaluate whether it is possible to predict which patients will show radiological progression despite therapy. Forty five patients completed 12 months' treatment. There were no significant demographic or clinical differences between them and the 27 drop outs. Twenty of the 45 patients showed no radiological progression between six and 12 months. These patients had less severe initial radiological damage, lower levels of serum aspartate transaminase (serum AST) and lactic dehydrogenase (LDH), but higher levels of serum cholesterol. Twenty five patients did show progression during the six to 12 month period. This group included all the men with nodules. Of the 43 pretreatment clinical and laboratory variables examined, however, the majority failed to predict whether or not progression would subsequently occur. This included the acute phase response and seropositivity.

Arthritis, Rheumatoid↗
PubMed1986

Long term progression of joint damage in rheumatoid arthritis.

Joint damage in rheumatoid arthritis is assessed radiologically. Previous studies have not examined in detail its long term progression. We evaluated the overall changes of peripheral joint damage radiologically in 50 rheumatoid patients followed up at one rheumatology centre for 10 years. All peripheral joints were scored in 12 groups with Larsen's standard films at 0 and 10 years. In 48 cases the total scored deteriorated (mean increase 13% maximum damage). There was no different pattern of progression in any of the patients, though seropositive patients had more initial damage and a greater rate of progress. The wrist and small joints of the feet were most affected initially. During the 10 years most progression occurred in the wrist, knee, and metacarpophalangeal joints. Progression occurred in both initially normal and abnormal joints. By 10 years only 16.5% joint groups showed no damage. Complete destruction was most common in the wrist, knee, and small joints of the feet. Damage to the hands and wrists have a god indication of overall changes at 0 and 10 years and also the increase in damage (correlation coefficients were from r = 0.74 to r = 0.85). These results show that specific joints are involved in different stages of the disease. Some joints are frequently involved and some less often. The hands and the wrists give a reasonable picture of the overall progression of damage.

Arthritis, Rheumatoid↗
PubMed1986

Susceptibility of cartilage to damage by immunological inflammation.

Injection of ovalbumin into subcutaneous air pouches prepared on the backs of rats previously sensitised to the antigen resulted in the induction of a small and transient accumulation of inflammatory fluid with a predominantly polymorph cell infiltrate. Challenge of pouches of appropriately sensitised rats with Bordetella pertussis vaccine, on the other hand, resulted in a larger and more prolonged accumulation of fluid and cells with a predominantly mononuclear presence. When intact homologous femoral head cartilage was implanted in these inflamed pouches proteoglycan loss was found to be not different from similar implants in non-inflamed pouches. Coating the cartilage with human heat-aggregated immunoglobulin G prior to implantation in air pouches was also found to be without effect on subsequent proteoglycan loss.

Animals↗
PubMed1986

Assessing the progression of joint damage in rheumatoid arthritis.

Joint damage in rheumatoid arthritis can be assessed by plain radiographs of the hands and wrists. There are a number of established methods that give reproducible scores which relate to increasing joint damage by measuring erosions and loss of joint space. Only 3 placebo-controlled trials have shown convincing evidence that gold or cyclophosphamide reduce the rate of progression of joint damage. Most placebo-controlled studies have failed to show a beneficial effect of slow acting antirheumatic drugs on radiological joint damage progression. However, comparative studies or analyses of cohorts of patients taking slow acting antirheumatic drugs show comparable amounts of progression for patients receiving gold and other drugs in this category. In addition, patients who show a clinical response also have less radiological progression after 6 months' therapy. In these circumstances, sulphasalazine produces comparable rates of radiological progression to those produced by gold and penicillamine. There are many problems associated with the use of radiological assessments to determine the progression of rheumatoid arthritis; thus, this method should not be deemed the most important technique by which to measure the success of therapy.

Anti-Inflammatory Agents, Non-Steroidal↗
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↗
PubMed1986

Calculating radiological progression in rheumatoid arthritis.

We examined two methods of calculating radiological progression in rheumatoid arthritis using hand and wrist radiographs scored by Larsen's method. Progression over 12 months was calculated in two ways: absolute change in score; relative change in score. The two methods of scoring progression were investigated in two studies. In the first 173 patients with rheumatoid arthritis treated with a variety of non-steroidal and slow-acting anti-rheumatic drugs were evaluated. There were different results using absolute and relative changes in score. Relative changes gave more meaningful results. The second study looked at 80 rheumatoid patients treated with slow-acting drugs for 6 months; patients with a persistently high ESR had significantly more progression assessed by relative change but not by absolute change. Evaluating the progression of joint damage by methods employing a scoring system must be interpreted with caution. Relative change may provide a more valuable measure than absolute change.

Anti-Inflammatory Agents↗
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↗