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Biomedical subjects

S Carsons

Publications and source records attributed to S Carsons.

At least 19 recordsLinked to original sources
PubMed2001

Preferential recognition of a fragment species of osteoarthritic synovial fluid fibronectin by antibodies to the alternatively spliced EIIIA segment.

OBJECTIVE: To characterize the species of synovial fluid (SF) fibronectin (FN) bearing the alternatively spliced EIIIA segment. METHODS: SF from patients with osteoarthritis (OA) and rheumatoid arthritis (RA), as well as corresponding affinity isolation products, were subjected to 1-dimensional and 2-dimensional electrophoresis followed by Western blot analysis. RESULTS: Regardless of the clinical type of arthritis, a polyclonal antibody that recognizes antigenic determinants throughout the FN molecule produced staining of predominantly approximately 200+ and approximately 170-kd species in reduced 1-dimensional electrophoresis. Despite the overall prevalence of the larger species, 4 monoclonal antibodies (mAb) reactive with sequences lying near the center of the EIIIA segment exhibited a relative failure to recognize the larger of these 2 species in OA, but not RA, SF. The absence of recognition of EIIIA sequences within the approximately 200+ kd forms of OA SF FN was unrelated to their derivation from dimers, since anti-EIIIA mAb recognized the smaller fragment species in preference to both monomeric and dimeric forms. The approximately 170-kd EIIIA+ fragments were observed to have minimal gelatin-binding capacity and appeared on 2-dimensional electrophoresis to extend from the N-terminus of FN through at least the center of the EIIIA segment. Similar results were obtained for samples obtained by needle aspiration or arthroscopic lavage, suggesting a widespread applicability of these findings. CONCLUSION: The approximately 170-kd EIIIA+ species of FN could potentially constitute a soluble "vehicle" by which chondrocyte-regulating EIIIA sequences, liberated from inhibitory flanking C-terminal sequences, could reach cells in the arthritic joint. Additionally, "FN species-specific" recognition of this segment within OA SF could constitute a marker by which to gauge the activity of the OA disease process.

Alternative Splicing↗
PubMed2001

A review and update of Sjögren's syndrome: manifestations, diagnosis, and treatment.

Sjögren's syndrome is an autoimmune disorder that affects approximately 1% of the population. It is a disease that in recent years has not been studied extensively, but for which much study is needed. Diagnosis of this disease is extremely difficult. Until recently no strong consensus on diagnostic criteria has been published. The disease can cause dry eyes, dry mouth, vasculitis, and neurologic disease, and each symptom may be at times correctly attributed to Sjögren's or incorrectly attributed to another disease. Because it affects many different areas, many specialists (rheumatologists, primary care physicians, ophthalmologists, and dentists) have to be educated about Sjögren's syndrome's pathogenesis, manifestations, diagnosis, and treatments to manage this disease and help improve these patients' quality of life.

Eye↗
PubMed1998

Rheumatologic disorders in women.

This article reviews common rheumatic diseases that most frequently occur in women including fibromyalgia, rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus and the antiphospholipid antibody syndrome. Many of these women are of child bearing potential and special considerations concerning pregnancy often arise. Rheumatic conditions that frequently affect older women such as osteoarthritis and polymyalgia rheumatica are discussed as well. Osteoporosis, which has emerged as a significant women's health issue, is also reviewed.

Antiphospholipid Syndrome↗
PubMed1997

The association of malignancy with rheumatic and connective tissue diseases.

This article reviews the associations of cancer with rheumatic diseases. Recent epidemiologic data linking the autoimmune connective tissue diseases with malignancy will be emphasized. Reports linking the occurrence of malignancy with rheumatoid arthritis, systemic lupus erythematosus, idiopathic inflammatory myopathy, scleroderma, and vasculitis are described. The effect of immunomodulating drugs in the development of malignancy is discussed. Mechanisms potentially responsible for malignant transformation in the lymphoproliferation of Sjogren's syndrome are described. The relationship of gout to cancer as well as direct effects of cancer on the musculoskeletal system is also reviewed.

Autoimmune Diseases↗
PubMed1994

Expression of a developmentally regulated epitope on fibronectins from the synovial fluid of patients with rheumatic disease.

OBJECTIVE: To determine if differential glycosylation of fibronectin (Fn) in inflammatory synovial fluid (SF) included expression of an oncofetal epitope (Onf Fn) heretofore detected only on Fn derived from embryonal or neoplastic tissue. METHODS: Fn were purified from plasma, SF and synoviocyte conditioned medium by affinity chromatography and were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting utilizing a monoclonal antibody (FDC-6) specifically recognizing the Onf Fn. RESULTS: The Onf Fn was not expressed on Fn isolated from normal or RA plasma but was strongly expressed on Fn from rheumatoid arthritis (RA) SF and to a lesser extent osteoarthritis SF. Onf Fn was also detected on Fn secreted by cultured RA synoviocytes. CONCLUSION: Fn present in the SF but not plasma of patients with rheumatic disease contains an epitope previously thought to be restricted to Fn produced by embryonal or malignant tissue.

Antibodies, Monoclonal↗
PubMed1992

Fibronectin mediates anchorage-dependent focus formation in cultured human synoviocytes.

To determine the effect of extracellular matrix proteins on synoviocyte phenotype, a serum-free, defined-medium culture system was established. Rheumatoid synoviocytes maintained on type I collagen appeared monolayered, whereas cells maintained on fibronectin showed focus formation. Focus formation was abrogated by maintaining cells in the presence of antifibronectin. Focus formation was associated with a fibronectin-rich extracellular matrix, whereas monolayer morphology was associated with matrices containing a greater proportion of collagen. The abundant amount of fibronectin present in the synovial microenvironment may be partially responsible for the transformationlike phenotype displayed by rheumatoid synoviocytes.

Arthritis, Rheumatoid↗
PubMed1988

Newer laboratory parameters for the diagnosis of rheumatic disease.

Measurement of serum autoantibodies is a useful adjunct in the diagnosis of connective tissue diseases. Approximately 15 percent of patients with rheumatoid arthritis are seronegative for rheumatoid factor by standard assays. The development of enzyme-linked immunosorbent assays for additional isotypic and idiotypic determinants may expand the diagnostic sensitivity of rheumatoid factor measurements. Although extremely sensitive, the finding of antinuclear antibodies is not highly specific for systemic lupus erythematosus and related disorders; the ability to rapidly screen serum against newly characterized specific nuclear antigens has been helpful in the diagnosis of newly described systemic lupus erythematosus subtypes, overlap syndromes, Sjögren's syndrome, and scleroderma variants. Women with unexplained recurrent fetal loss and patients with unexplained thrombotic episodes should be screened for the presence of the anticardiolipin antibody. Glycoproteins (C-reactive protein, alpha-1-glycoprotein, fibronectin) may prove useful as indicators of rheumatic disease activity and the efficacy of therapeutic intervention.

Antibodies↗
PubMed1988

Plasma fibronectin concentrations in breast fed and formula fed neonates.

Plasma fibronectin concentration was measured in neonates of 2 to 5 days of age. Although breast fed and formula fed infants were similar in demographic characteristics, the mean (SD) plasma concentration of fibronectin in 26 breast fed infants, 237 (117) mg/l, was significantly higher than in 27 formula fed infants (171 (91) mg/l). Fibronectin was detected in five colostrum specimens (mean concentration 13.4 mg/l). Similar bands were detected after gel electrophoresis of purified adult plasma fibronectin and whole plasma from breast fed and formula fed neonates after staining or immunoblotting. Fibronectin isolated from breast milk also appeared similar to purified plasma fibronectin. It is possible, although unlikely, that fibronectin is absorbed intact from ingested colostrum. Alternatively, a factor(s) might be present in colostrum that contributes to the regulation of plasma fibronectin concentration.

Bottle Feeding↗
PubMed1988

Chondronectin in human synovial fluid.

Chondronectin is a cartilage matrix protein that specifically mediates the attachment of chondrocytes to type II collagen. A monoclonal antibody to chondronectin was used in a competitive enzyme linked immunosorbent assay (ELISA) and Western blot assay to detect, measure, and characterise chondronectin in human synovial fluid. Chondronectin was detected in all 18 rheumatoid and 11 osteoarthritic synovial fluids examined. Chondronectin concentrations in synovial fluid were lower than those in plasma and correlated most strongly with concentrations of synovial fluid albumin and fibrinogen. These results suggest that synovial fluid chondronectin is in part derived from plasma. The role of chondronectin as a marker of cartilage destruction and potential mediator of pannus formation is discussed.

Albumins↗
PubMed1987

Carbohydrate heterogeneity of fibronectins. Synovial fluid fibronectin resembles the form secreted by cultured synoviocytes but differs from the plasma form.

Large quantities of fibronectin (Fn) are present in inflammatory synovial fluid. Inflammatory synovial fluid Fn, while indistinguishable from plasma Fn on the basis of reactivity to polyclonal antibodies, displays alterations in molecular size and charge. Since biochemical differences between plasma and synovial fluid fibronectins might be in part due to differences in glycosylation we have compared the carbohydrate composition of plasma Fn, synovial fluid Fn, and Fn from synoviocyte conditioned medium by biochemical assay, glycopeptide analysis, and binding to a series of lectins. Synovial fluid Fn has a greater carbohydrate content but contains less sialic acid when compared with plasma Fn. Glycopeptides formed from synovial fluid Fn are smaller than plasma Fn glycopeptides. These data suggest the presence of an additional N-linked oligosaccharide chain on synovial fluid Fn. In addition, synovial fluid Fn contains N-acetyl galactosamine indicating the presence of O-linked oligosaccharides. Synovial fluid Fn and Fn isolated from rheumatoid synoviocyte-conditioned medium display strong reactivity with the lectins wheat germ agglutinin (WGA) and peanut agglutinin (PNA), whereas normal and rheumatoid plasma Fn react weakly. The PNA reactivity of synovial fluid Fn is mediated by terminal beta-galactose residues on the gelatin-binding domain, whereas the enhanced WGA reactivity of synovial Fn is mediated by a sialic acid containing oligosaccharide located on a 27-kD C-terminal fragment. These data demonstrate domain-specific biochemical differences between plasma and synovial fluid fibronectins. These differences suggest a local origin for synovial fluid Fn and may contribute to functional differences between these forms of the protein.

Acetylgalactosamine↗
PubMed1987

High levels of fibronectin fragments in the plasma of a patient with active systemic lupus erythematosus.

Elevated levels of plasma fibronectin have been described in patients with active systemic lupus erythematosus (SLE). We demonstrated the presence of high levels of fibronectin fragments in the plasma of a patient during the terminal episode of active SLE. The potential consequences of circulating fibronectin fragments on clearance of immune complexes and microorganisms are discussed.

Adult↗
PubMed1985

The immunoreactivity, ligand, and cell binding characteristics of rheumatoid synovial fluid fibronectin.

Fibronectin promotes macrophage adherence and expression of Fc receptors, is chemotactic for fibroblasts, and is an opsonin for fibrin and denatured collagen. These properties suggest a role for fibronectin in the modulation of joint inflammation. Since structural modification of the fibronectin molecule has been shown to result in loss or de novo acquisition of opsonic and chemotactic activity, we determined the functional and immunochemical properties of fibronectin isolated from the inflamed joint. Eighty-six percent of synovial fluids obtained from patients with active rheumatoid arthritis (RA) contained fibronectin fragments, and 39% of the fluids no longer displayed the dimeric form. Compared with native fibronectin, RA peptides were as active in promoting synoviocyte chemotaxis and in glycosaminoglycan binding, but displayed lower affinity for fibrin and gelatin. Although comparable with intact protein in augmenting monocyte attachment to gelatin, the RA synovial fluid peptides did not augment monocyte attachment to fibrin. Analysis of whole synovial fluid and isolated fibronectins by enzyme immunoassay showed that the increased fibronectin immunoreactivity, previously reported in RA synovial fluid, measures intact and nearly intact protein and does not measure extensively degraded fragments.

Animals↗
PubMed1985

Synthesis, secretion, and deposition of fibronectin in cultured human synovium.

We examined fibronectin synthesis, secretion, and deposition in vitro by primary explants of rheumatoid synovium. Primary cultures initiated from tissue with monocytic infiltrates had higher levels of fibronectin synthesis; addition of dexamethasone at concentrations known to stimulate other tissue fibroblasts increased fibronectin synthesis and secretion. Newly synthesized fibronectin recovered from primary rheumatoid culture medium had a higher apparent molecular weight (240-245 kd), on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, compared with fibronectin recovered from passaged normal and rheumatoid cultures (230 kd). Primary rheumatoid explant cultures had a characteristic morphology which correlated with fibronectin deposition. Dense deposits of fibronectin extracellular matrix covered overlapping synoviocytes adjacent to esterase-positive mononuclear cells. Dexamethasone-treated cultures showed little fibronectin deposited as extracellular matrix and did not develop overlapping cellular networks. Characteristic patterns of fibronectin synthesis and deposition in primary rheumatoid cultures appear to result from interaction between fibroblastic and monocytic cells. This culture system may provide a model by which to study interactions between cells and extracellular matrix components that regulate synovial cell function.

Arthritis, Rheumatoid↗
PubMed1985

Plasma fibronectin in systemic lupus erythematosus: relationship to clinical activity, DNA binding and acute phase proteins.

Plasma fibronectin was measured by ELISA in 25 samples from 22 patients with systemic lupus erythematosus (SLE). The mean fibronectin level for the entire patient group (654 micrograms/ml) was greater than that of normal controls (450 micrograms/ml), with highest levels observed in the subgroup of patients with severe disease activity (838 micrograms/ml) followed by those with moderate disease activity (732 micrograms/ml) (p = .04). Fourteen patients with other rheumatic disease had a mean fibronectin level of 407 micrograms/ml. Decreases in fibronectin levels corresponded to clinical improvement and reductions in DNA binding. Although elevated fibronectin levels did not correspond to any specific pattern of organ system involvement, fibronectin levels seem to parallel disease activity in certain patients. Future longitudinal studies of plasma fibronectin in SLE may further define its role as an indicator of disease activity.

Acute-Phase Proteins↗
PubMed1983

Factors influencing the incorporation of fibronectin into synovial fluid cryoprotein.

Methods of synovial fluid collection and processing known to affect cryoprotein formation were examined to investigate the proposed role of fibronectin in synovial fluid cryoprecipitation. Fibronectin, a nonimmunoglobulin, noncomplement synovial fluid protein was present in all resolubilized synovial fluid cryoproteins studied. Radiolabeled fibronectin was precipitated from rheumatoid synovial fluid to a significantly greater extent (10%) than from noninflammatory (osteoarthritic) synovial fluid (2.8%), normal plasma (1.3%), or normal serum (0.5%) (p less than 0.01). Clotting of synovial fluid reduced fibronectin concentration 44% and resulted in a reduction in the amount and percent incorporation of fibronectin into cryoprotein, whereas heparinization and hyaluronidase treatment increased cryoprecipitable fibronectin. Affinity depletion of synovial fluid fibronectin resulted in loss of C1q and reduction in IgG in the cryoprotein; however, fibronectin, C1q, and IgG could not be co-eluted from affinity matrices of gelatin and protein A-Sepharose. Cryoprotein formation from pathologic synovial fluid depends in part on fibronectin and appears to involve interactions between fibronectin and fibrinogen as well as immunoglobulin complexes and complement components.

Arthritis, Rheumatoid↗