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At least 1,639 records · Page 91Linked 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↗
PubMed1998

Study of pro-inflammatory (TNF-alpha, IL-1alpha, IL-6) and T-cell-derived (IL-2, IL-4) cytokines in plasma and synovial fluid of patients with juvenile chronic arthritis: correlations with clinical and laboratory parameters.

Acute phase proteins, synovial fluid (SF) cellular infiltrates, pro-inflammatory (TNF-alpha, IL-1alpha, IL-6) and Th1 (IL-2) and Th2 (IL-4) derived cytokine levels both in plasma and SF were examined in pauciarticular and polyarticular juvenile chronic arthritis (JCA) patients during the active (n = 22) and inactive (n = 14) period in order to determine pathogenic mechanisms and correlations between cytokines and laboratory parameters showing disease activity. The erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) and IgG concentrations were found to be significantly elevated in the active period of JCA. In pauciarticular JCA patients, when compared with their peripheral blood lymphocyte subpopulations, SF CD3+ cells (73.1%) and HLA-DR+ active T cells (22.5%) were found to be significantly increased. In the active period of JCA, plasma TNF-alpha and IL-6 concentrations were significantly elevated. Plasma IL-2 and IL-4 levels were not elevated and were found to be similar to those in the inactive phase and in healthy controls. SF IL-6, TNF-alpha and IL-1alpha levels were extremely high in all the patients. SF IL-4 and IL-2 levels were all undetectable. There was a significant correlation between ESR values and plasma IL-6 levels and between serum CRP levels and plasma IL-6 and TNF-alpha concentrations. In conclusion, increased local production of pro-inflammatory cytokines appears to account for the articular manifestations of JCA. The impaired production of anti-inflammatory Th2-derived cytokines (IL-4) seems to cause increased production of inflammatory cytokines acting on the balance between them. The deficit in IL-2 production was not suggested to be primarily involved in the pathogenesis. In addition, not only CRP and ESR values, but also plasma IL-6 and TNF-alpha concentrations may be used as markers of disease activity.

Adolescent↗
PubMed2000

Loading-induced changes in synovial fluid affect cartilage metabolism.

The object of this study was to determine whether changes in the synovial fluid (SF) induced by in vivo loading can alter the metabolic activity of chondrocytes in vitro, and, if so, whether insulin-like growth factor-I (IGF-I) is responsible for this effect. Therefore, SF was collected from ponies after a period of box rest and after they had been exercised for a week. Normal, unloaded articular cartilage explants were cultured in 20% solutions of these SFs for 4 days and chondrocyte bioactivity was determined by glycosaminoglycan (GAG) turnover (i.e., the incorporation of 35SO4 into GAG and the release of GAG into the medium). Furthermore, the extent to which the bioactivity is IGF-I-dependent was determined in a cartilage explant culture in 20% SF, in the presence and absence of anti-IGF-I antibodies. In explants cultured in post-exercise SF, GAG synthesis was enhanced and GAG release was diminished when compared to cultures in pre-exercise SF. SF analysis showed that IGF-I and IGFBP-3 levels were increased in post-exercise SF. There was a positive correlation between IGF-I levels and proteoglycan synthesis, but no correlation between IGF-I levels and proteoglycan release. Addition of anti-IGF-I antibodies significantly inhibited stimulation of proteoglycan synthesis in explants cultured in SF with 40%. However, there was no difference in inhibition of proteoglycan synthesis between pre- and post-exercise SF which indicated that the relative contribution of IGF-I in the stimulating effect of SF did not change. Proteoglycan release was not influenced by the presence of anti-IGF-I antibodies. It is concluded that chondrocyte metabolic activity is at least partially regulated by changes in the SF induced by in vivo loading. Exercise altered the SF in a way that it had a favourable effect on cartilage PG content by enhancing the PG synthesis and reducing the PG breakdown. IGF-I is an important contributor to the overall stimulating effect of SF on cartilage metabolism. It is, however, unlikely that IGF-I is the only mediator in the exercise-induced increase in this stimulating effect.

Animals↗
PubMed1978

Gold and penicillamine: a proposed mode of action in rheumatoid arthritis, based on synovial fluid analysis.

Although in common use, there is still controversy as to the way in which gold and penicillamine act in rheumatoid arthritis (RA). In this study, synovial fluids from 4 groups of patients have been compared: (1) RA patients on gold/penicillamine, (2) RA patients on non-steriodal anti-inflammatory drugs (NSAID) only, (3) osteoarthritis patients, and (4) patients with sero-negative arthropathies. The parameters measured were differential agglutination titre (DAT), total haemolytic complement (CH50), total protein, total white cell count, and immunoglobulins. RA patients on gold/penicillamine have lower synovial DAT levels and higher CH50 levels than RA patients on NSAID only, and total and cryoprecipitable IgM levels very close to those found in the sero-negative joint fluids. The non-specific inflammatory parameters, ie, white cell count and total protein are unchanged after good/penicillamine therapy. In a second study, the serum DATs of patients in total remission after gold/penicillamine were compared with similar patients on NSAID only. The DAT falls significantly in the former group (P less than 0.001), but not in the latter suggesting that fall in DAT is a consequence of therapy rather than remission. The parameters altered by gold/penicillamine in the synovial fluid are those that distinguish RA from non-rheumatoid arthropathies suggesting the drug's primary effect is to render the disease sero-negative. The results support the hypothesis that both drugs have a common mode of action based on their active thiol groups, and that the fall in DAT is due to the reduction of the antigenicity of the IgG complexes.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Nerve growth factor in the synovial fluid of patients with chronic arthritis.

Cytokines regulate nerve growth factor (NGF) synthesis during inflammatory processes. Since cytokines are also involved in the inflammatory processes of autoimmune rheumatic diseases, we examined levels of NGF in patients with rheumatoid or other types of chronic arthritis. NGF was present in the synovial fluid and synovium of patients with chronic arthritis, but was undetectable in control fluids. We conclude that NGF might be involved in the pathogenesis of arthritis.

Aged↗
PubMed1980

The role of the synovial fluid and tendon sheath for flexor tendon nutrition. An experimental tracer study on diffusional pathways in dogs.

Radioactive tracers were used to analyse nutritional mechanisms of flexor tendons of dogs during various experimental conditions. The transport and distribution of methyl glucose in the tendon was analysed 15 min after intravenous injection during the following experimental conditions: (1) normal state--rest; (2) passive mobilization of the tendon; (3) active mobilization of the tendon; (4) exclusion of exposure to synovial fluid-preservation of vascular supply; (5) exclusion of vascular supply--preservation of exposure to synovial fluid. The results indicate that active mobilization gives a significant increase in tracer concentration in the volar part of the tendon, while passive mobilization has no such effect. Diffusional pathways from the synovial fluid plays a major role for transport of tracer into the tendon, while the intrinsic vascular system apparently is of no or minor importance in this respect. The main mechanism for solute transport within the tendon is passive diffusion. Transport of sulphate in the volar part follows a similar pattern as in other avascular tissues and the incorporation of sulphate by the cells is low and comparable to that in articular cartilage. The results support our previous hypothesis that the flexor tendon system physiologically corresponds to a joint, and that the synovial fluid plays an important role for flexor tendon nutrition.

Animals↗
PubMed2003

Generation of three-dimensional pannus-like tissues in vitro from single cell suspensions of synovial fluid cells from arthritis patients.

Using single cell suspensions from synovial fluid cells of arthritis patients, we observed differentiation of three-dimensional tissues in vitro. This new model of pannus-like tissue (PLT) might be useful to study pannus tissue formation and differentiation. In the PLT cultures, we observed two cell types, fibroblast-like and macrophage-like cells, defined by their distinct morphology and major histocompatibility complex (MHC) by human leukocyte antigen (HLA) class II expression. We could discriminate several intermediate steps of differentiation which finally led to 3D villi-like structures. Secretion of interferon gamma, interleukin-10, and tumor necrosis factor alpha was measured in the culture supernatants. Using methotrexate at various concentrations, the growth of PLT could be inhibited. We describe definite intermediate steps of differentiation. The present approach could be a suitable model for the in vitro study of pannus tissue formation.

Arthritis, Reactive↗
PubMed1983

Interferon in synovial fluid and serum of patients with rheumatic disease.

Interferon (IFN) was sought in simultaneously obtained samples of synovial fluid (SF) and serum from patients with a variety of rheumatological diseases. IFN was identified in 11 of 84 samples of SF and 10 of 84 specimens of serum. IFN positive specimens were contributed by patients with rheumatoid arthritis (RA), systemic lupus erythematosus, seronegative spondyloarthropathies, pseudogout, coccidioidomycosis and unclassified arthritis. Significantly, IFN was frequently found either in SF or in serum but generally not in both of the simultaneously obtained fluids. The highest titers of IFN found in SF were from patients with RA.

Arthritis↗
PubMed1989

Synovial fluid glycosaminoglycan (acid mucopolysaccharide) analysis in assessment of temporomandibular joint dysfunction. A pilot study.

Temporomandibular joint (TMJ) synovial fluid was aspirated from normal control subjects and patients undergoing surgery for TMJ dysfunction. The glycosaminoglycan (GAG) composition of this fluid was analysed and compared with the clinical diagnosis and histological appearance of the condylar tissues. Changes in GAG composition were observed where a histologically hyperplastic response was seen in joint tissues, but these findings did not necessarily correlate with the initial clinical diagnosis. It is suggested that the fluid composition reflects the current metabolic activities of the tissues and may provide a useful marker of such processes.

Adult↗
PubMed2000

Synovial fluid glycosaminoglycan concentration does not correlate with severity of chondropathy or predict progression of osteoarthritis in a canine cruciate deficiency model.

OBJECTIVE: Considerable interest exists today in biochemical or immunochemical tests for monitoring the progression of osteoarthritis (OA). It has been suggested that measurements made on synovial fluid (SF) will more accurately reflect the magnitude of cartilage destruction in an index joint than those performed on serum. However, we have shown that the synovitis that occurs in OA affects the rate of protein clearance from the joint. We tested the hypothesis that if adjusted for clearance rate, the SF concentration of cartilage proteoglycans (PG) estimates severity of chondropathy and predicts progression of cartilage damage more accurately than if clearance is not taken into account. METHODS: Clearance of radioiodinated serum albumin (RISA), a surrogate for the clearance of PG, was measured in 19 adult dogs at baseline and again 16 weeks and 32 weeks after anterior cruciate ligament transection (ACLT). Severity of chondropathy was determined arthroscopically after 16 weeks of instability and at postmortem 32 weeks after ACLT. RESULTS: Adjustment for the RISA clearance rate showed that the SF PG concentration markedly underestimated the quantity of PG released from the OA cartilage. Regardless of whether the concentration was adjusted for clearance, no correlation existed between the SF PG level and the severity of chondropathy. Further, the SF concentration of PG 16 weeks after ACLT failed to predict severity of cartilage damage at postmortem. CONCLUSION: SF concentration of a cartilage derived molecule is unlikely to predict the course of cartilage damage in an OA joint over time or in response to treatment with a potential disease modifying OA drug.

Animals↗
PubMed1988

Lipid microspherules in synovial fluid of patients with pigmented villonodular synovitis.

We describe 2 patients with pigmented villonodular synovitis. In both patients, synovial fluids (SF) were characterized by the presence of abundant, strongly birefringent lipid microspherules, which appeared as Maltese crosses and were found both inside foam cells and free in the SF. Histologically, the synovial membranes showed pigmented villonodular synovitis, with aggregation of foam cells containing abundant lipid microspherules in their cytoplasm. Observation of numerous birefringent lipid microspherules and foam cells in SF may be a clue to the diagnosis of pigmented villonodular synovitis.

Adult↗
PubMedDate not supplied

The hydrolysis of cortisol 21-esters by a homogenate of inflamed rabbit synovium and by rheumatoid synovial fluid.

Long chain esters of cortisol have shown prolonged anti-inflammatory activity in both clinical and animal studies. This effect has been ascribed to the decreased water-solubility of the higher esters, but an alternative explanation is that the higher esters are hydrolysed more slowly to free steroid by the synovial tissue enzymes. In order to investigate the influence of chain length on hydrolysis rate we synthesized a series of cortisol 21-esters. When incubated in a 0.1% (w/v) homogenate of inflamed rabbit synovial tissue the esters with chain lengths of 4, 6, 8 and 10 carbon atoms were hydrolysed much faster than those with 2, 12, 14 and 16 carbon atoms. At tissue concentrations of 10% (w/v), however, the breakdown of cortisol acetate was greatly accelerated, whereas cortisol palmitate remained quite stable. Although cortisol esters were hydrolysed in 50% (v/v) rheumatoid synovial fluid, the rates of hydrolysis were relatively slow. The chain length dependence was similar to that seen with the tissue homogenate.

Animals↗
PubMed1991

The role of serum and synovial fluid components in the promotion of urate crystal formation.

The effect of various components of serum and synovial fluid (SF) on in vitro urate crystal formation was measured. Serum and SF has been shown to promote urate crystal formation. The component(s) responsible for this promotion was found to be a macromolecule, sensitive to heat denaturation. Albumin, alpha and beta globulins and chondroitin sulphate had little effect, whereas gamma globulin markedly promoted crystal formation and insoluble collagen also promoted crystal formation in a dose dependent fashion.

Blood Physiological Phenomena↗
PubMed2002

Synovial fluid from patients with rheumatoid arthritis inhibits neutrophil apoptosis: role of adenosine and proinflammatory cytokines.

OBJECTIVE: In synovial fluid (SF) from patients with rheumatoid arthritis (RA), neutrophils are exposed to proinflammatory mediators endowed with either anti-apoptotic or pro-apoptotic properties. We investigated neutrophil apoptosis in the presence of SF from 11 RA patients. METHODS: SF was obtained from affected knees of 11 patients with RA. Human neutrophil apoptosis was evaluated by light microscopic examination and flow-cytometric analysis of annexin V binding. Immune complex-induced neutrophil activation was evaluated as superoxide anion production. Adenosine levels in SF were detected by chromatographic analysis and cytokine levels were studied by enzyme-linked immunosorbent assay. RESULTS: Spontaneous and immune complex-triggered neutrophil apoptosis was reduced by SF from eight out of 11 patients. Immune complex-induced neutrophil activation was unaffected by SF. The cytokines tested had no role in promoting the anti-apoptotic activity of SF. On the contrary, the anti-apoptotic activity of SF was found to depend on the presence of adenosine. Adenosine levels detected in the various samples of SF correlated significantly with the anti-apoptotic activity of the fluids and with the number of apoptotic neutrophils detected in the articular exudate. CONCLUSION: The microenvironment of rheumatoid SF is a proinflammatory milieu responsible for the in loco persistence of activated and long-surviving neutrophils. Adenosine plays a crucial role in this phenomenon, which is related to anti-apoptotic activity.

Adenosine↗
PubMedDate not supplied

Unusual immunocytochemical and ultrastructural features of synovial fluid cells in multicentric reticulohistiocytosis. A case report.

We present the first report in which cells in synovial fluid from a patient with multicentric reticulohistiocytosis (MRH) were studied by immunocytochemistry for correlation with routine light and electron microscopy. MRH cells stained predominantly for lymphocyte-related surface antigens and not for the monocyte marker LEU M3 (CD14). These findings suggest a lymphocytic origin of MRH cells and not a histiocytic origin, as previously suggested. In addition, large numbers of membrane-bound, electron-dense, secretory-type granules were found ultrastructurally in the cytoplasm of these cells.

Antibodies, Monoclonal↗
PubMed1989

Synovial fluid acidosis correlates with radiological joint destruction in rheumatoid arthritis knee joints.

Metabolic variables in samples of synovial fluid (SF) from 33 rheumatoid arthritis (RA) knees were analyzed. These variables were correlated with radiological destruction and SF proteoglycan concentrations. SF acidosis correlated with radiological involvement (rs = 0.62, p less than 0.002), but not with proteoglycan concentrations. A weak correlation was found between SF acidosis and granulocyte concentrations (rs = 0.37, 0.02 less than p less than 0.05). Metabolic variables covaried as expected. Samples from right and left knees from the same patients correlated regarding cellular and metabolic variables. Our results indicate insufficient nutritional supply in RA joints with increasing radiological involvement.

Acidosis↗
PubMed2000

Longitudinal characterization of synovial fluid biomarkers in the canine meniscectomy model of osteoarthritis.

Damage to the meniscus can lead to posttraumatic osteoarthritis. Early markers of joint injury and tissue disease may be useful in developing and administering clinical treatment. We investigated the effects of total medial meniscectomy on biomarkers measured serially in synovial lavage fluid each month for 3 months. Following meniscectomy in dogs, four biomarkers were evaluated: cartilage oligomeric matrix protein, keratan sulfate epitope (5D4), the 3B3(-) neoepitope of chondroitin-6-sulfate, and the 3B3(+) chondroitinase-generated epitope of chondroitin-6-sulfate. Meniscectomy led to statistically significant elevations of all four biomarkers, with levels peaking at 4 weeks. By 12 weeks, the level of the 5D4 epitope returned to the preoperative baseline level whereas that of cartilage oligomeric matrix protein, 3B3(-), and 3B3(+) remained above the baseline. Concentrations of these biomarkers in the knees not operated on did not change significantly from the baseline. The levels of cartilage oligomeric matrix protein and 3B3(-) relative to 3B3(+) remained constant in all knees. In contrast, the level of 5D4 relative to 3B3(+) declined over time in the knee operated on but remained constant in the knee not operated on. These results demonstrate a quantitative change in the molecular components of synovial fluid after meniscectomy, as well as a qualitative change evinced by an alteration in the relative proportions of these epitopes. Extensive analyses showed a strong correlation between serum levels of 3B3(-) from the femoral and cephalic veins; however, serum 3B3(-) was not correlated with synovial fluid 3B3(-). These findings support the hypothesis that the concentrations of select cartilage biomarkers in synovial fluid are altered following meniscectomy and are promising tools for objectively monitoring the induction of osteoarthritis in this model system.

Animals↗
PubMed1992

Detection of stromelysin and collagenase in synovial fluid from patients with rheumatoid arthritis and posttraumatic knee injury.

OBJECTIVE: To quantify stromelysin and collagenase in synovial fluid (SF) from patients with rheumatoid arthritis (RA) or traumatic knee injury. METHODS: Stromelysin and collagenase were measured in the SF of 33 patients with RA or posttraumatic knee injury, using specific double-antibody sandwich enzyme-linked immunosorbent assays. Stromelysin was fractionated from representative SF, and the molecular form was identified by immunoblot analysis. RESULTS: The stromelysin concentration was approximately 20-fold higher than the collagenase concentration in the fluids from patients with RA and approximately 8-fold higher in the fluids from patients with traumatic injury. For both metalloproteinases, there was a higher enzyme concentration in RA SF than in the SF from patients with trauma (stromelysin 40.1 +/- 26 micrograms/ml [mean +/- SD] in RA SF, 8.5 +/- 15 micrograms/ml in trauma SF; collagenase 2.2 +/- 3.3 micrograms/ml in RA SF, 1.1 +/- 2.3 micrograms/ml in trauma SF). The majority of the stromelysin within the SF bound to reactive red-agarose and was identified as prostromelysin based on electrophoretic mobility and immunoblotting with monospecific antibodies. CONCLUSION: The finding of high levels of stromelysin in SF from patients with RA supports the proposal that this enzyme may play a role in the connective tissue degradation observed in this disease.

Adolescent↗