Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In situ hybridization was used to demonstrate serum amyloid A (SAA) gene expression in arthritic joint tissue from lentivirus-infected sheep and goats. SAA gene transcription occurs in isolated individual synovial cells and occasional giant cells but not in uninfected or uninflamed synovial tissue. These findings support the notion (derived from in vitro observations) that at least one member of the SAA gene/protein family may function as an autocrine collagenase inducer in inflammatory arthritis. Since we used heterologous DNA probes derived from human clones, our findings also support the growing evidence for interspecies conservation of SAA genes.
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PMID:Serum amyloid A gene transcription in synovial cells during retroviral arthritis. 151 61

Acute response after traumatic events was studied in serial serum samples of 21 patients over a period of 13 days. Among the various biochemical and hematologic parameters, serum amyloid A (SAA) exhibited the most striking changes, with a pattern similar to that of the tissue marker creatine-P kinase (CPK). Maximal SAA level was detected 3-4 days after onset of the event, and reached 216 +/- 41 SEM gm/ml (normal range less than 2 gm/ml), while maximal CPK level was detected on the same day and reached 530 +/- 242 SEM IU/L (normal range 24-195 IU/L). Fibrinogen, leucocytes, platelets, albumin, alkaline phosphatase (AP), and calcium (Ca) each showed its own typical pattern of change. Fever did not develop. Comparison of SAA levels after various acute events suggests that damage to the myocardium is the most powerful stimulus for SAA induction, followed by traumatic events, arthritis, viral infections, and malignant diseases. It seems therefore that although acute response is considered a generalized reaction, it is not completely independent of the localized events which induce it. Among the known parameters, SAA is the most sensitive marker for monitoring the intensity of events.
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PMID:Serum amyloid A: an extremely sensitive marker for intensity of tissue damage in trauma patients and indicator of acute response in various diseases. 246 72

Serum and synovial fluid (SF) levels of serum amyloid A (SAA) and C-reactive protein (CRP) were measured in 46 cases of various inflammatory arthritis (Group 1), and in 40 cases of noninflammatory arthritis: 18 cases of osteoarthritis (Group 2) and 22 cases of traumatic arthritis (Group 3). Serum and SF SAA levels were markedly elevated in Group 1: 126.4 micrograms/ml +/- 19.2 SEM and 46.4 micrograms/ml +/- 10.5 SEM, respectively; moderately elevated in Group 2: 10.1 micrograms/ml +/- 2.9 SEM, 4.0 micrograms/ml +/- 1.1 SEM and moderately elevated in Group 3: 10.4 micrograms/ml +/- 1.2 SEM, 4.0 micrograms/ml +/- 1.2 SEM, respectively. Serum/SF SAA ratios were similar in all 3 groups and ranged between 2.52-2.72. In comparison to SAA, the increment of serum and SF CRP above normal levels was moderate. A positive strong correlation was found between serum SAA and serum CRP: r = 0.64 (p less than 0.001) and between SF SAA and SF CRP: r = 0.59 (p less than 0.0001). SF SAA did not correlate with the number of SF white blood cells but did correlate with the percent of SF polymorphonuclear cells: r = 0.23 (p less than 0.05).
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PMID:Serum and synovial fluid levels of serum amyloid A protein and C-reactive protein in inflammatory and noninflammatory arthritis. 341 44

Tenidap is a novel anti-rheumatic drug that combines cytokine modulation with cyclo-oxygenase inhibition. This 24-week, multicentre, double-blind, randomized study compared the clinical efficacy, biochemical effects and safety of tenidap 120 mg/day (once daily) with diclofenac 150 mg/day (50 mg t.i.d) in the treatment of 384 patients with active rheumatoid arthritis. After 24 weeks, improvement with tenidap was significantly greater than with diclofenac for all five primary efficacy parameters, two of the four secondary efficacy parameters and 11 of the 13 Arthritis Impact Measurement Scales assessments. The superior efficacy of tenidap was apparent after 4 weeks of treatment with further improvements observed by 24 weeks. The probability of discontinuation due to lack of efficacy was significantly greater in the diclofenac group. Tenidap but not diclofenac was associated with significant, rapid and sustained reductions in C-reactive protein and serum amyloid A levels and with a significant reduction in plasma interleukin-6. The nature and frequency of side-effects were similar in the two groups as was the discontinuation rate for treatment-related safety reasons. Tenidap was associated with an equal incidence of elevated transaminases, but a higher incidence of mild (> or = 500 mg/24 h < 1500 mg/24 h) non-progressive, proteinuria of proximal tubular origin compared with diclofenac.
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PMID:A comparative study of tenidap, a cytokine-modulating anti-rheumatic drug, and diclofenac in rheumatoid arthritis: a 24-week analysis of a 1-year clinical trial. 867 63

Reactive amyloidosis is a disease occurring in patients suffering from chronic infections, inflammation, and certain malignant conditions that are characterized by a considerable elevation of the acute phase reactant serum amyloid A (SAA). It is defined by the presence of extracellular deposits of fibrillar material containing amyloid A (AA) as its main component. AA is an 8.5-kd protein structurally identical to the NH2-terminal of the acute phase reactant SAA. SAA consists of a group of evolutionally conserved amphipathic proteins, encoded by a large number of genes and produced abundantly during inflammation, all suggesting an important role, probably of a neutralizing (anti-inflammatory) nature. An analysis of various aspects of SAA provides no clues to the mechanism of amyloid production, its occurrence in only selected individuals, and its preferential relationship to one isotype of SAA. Until more data is available, the present view on AA amyloidogenesis remains hypothetical.
Semin Arthritis Rheum 1995 Feb
PMID:The molecular basis of reactive amyloidosis. 774 Mar 5

The joint destruction of osteoarthritis (OA) comprises loss of articular cartilage resulting from an imbalance of enzyme-catalized cartilage breakdown and regeneration. OA is thought to derive from defective chondrocyte metabolism and thus to inherently lack the large-scale systemic response that is the hallmark of rheumatoid arthritis (RA). Because of the apparent absence of systemic inflammation in OA, acute-phase response proteins have not been as extensively studied in OA as they have been in RA. The diagnosis of OA almost always involves radiographic assessment of joint damage, which is useful only after the disease process has been underway for several months. Radiographic evaluation cannot give a good assessment of current disease activity and is a relatively insensitive indicator of prognosis. Cartilage breakdown products can potentially serve as direct surrogate markers of OA disease activity, but have not been extensively used because of their limited sensitivity and the technical difficulties associated with their measurement. Markers of disease activity in RA are indirect and are derived from the acute-phase response, a cycle of temporal changes in cellular and metabolic function. The early part of the acute-phase response involves the local action and production of cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF-alpha) and IL-6. In the late acute-phase response, these cytokines can effect many systemic changes, including increased production of acute-phase proteins (APP). Three valuable surrogate markers of disease activity in RA are provided by the acute-phase response: the time-honored erythrocyte sedimentation rate (ESR) and the newer APPs C-reactive protein (CRP) and serum amyloid A (SAA). As in RA, the joint destruction of OA involves IL-1, TNF-alpha, and IL-6; however, OA can be viewed as an indolent stimulus of the later (systemic) acute-phase response. Recent studies of the acute-phase response in OA suggest that the concentrations of CRP and SAA are elevated in OA, but to a lesser extent than in RA. In the future, long-term monitoring of CRP concentrations in the blood may permit the earlier detection and more effective treatment of OA.
Semin Arthritis Rheum 1995 Oct
PMID:Acute-phase proteins in osteoarthritis. 857 14

Rheumatoid arthritis (RA) has no firm etiologic basis. It progresses as an autoimmune disease and evolves into a chronic inflammatory joint disease complicated by recurrent episodes of systemic acute-phase reactions, which sometimes result in amyloidosis. Cytokines play a pivotol role in inflammation and the immune response. Proinflammatory cytokines such as interleukin-1, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 are present at high levels in arthritic joints, and their blood concentration correlates with the severity of the RA. Some of the activities of the proinflammatory cytokines, such as stimulation of leukocyte infiltration and release of their proteolytic enzymes, may be mediated by acute phase proteins (APPs), such as C-reactive protein and serum amyloid A, and by chemokines such as interleukin-8. Cytokines, chemokines, and APPs reciprocally regulate each others' expression and activities, constituting a communication network between fibroblasts, macrophages, lymphocytes, and hepatocytes. Activation of the network results in inflammation and the progressive destruction of joints and systemic symptoms characteristic of RA.
Semin Arthritis Rheum 1996 Oct
PMID:Role of cytokines, acute-phase proteins, and chemokines in the progression of rheumatoid arthritis. 891 97

Juvenile chronic arthritis (JCA) is the commonest chronic rheumatic disorder of childhood. Although conventional therapy of JCA continues to improve, many patients experience long-term ill health as a result of their disease or treatment. In adult rheumatoid arthritis (RA), similar concerns have led to the development of therapies designed to interfere in key disease processes. One such therapy is cA2, a chimeric neutralizing monoclonal antibody to the inflammatory cytokine, tumour necrosis factor-alpha (TNF-alpha). The administration of cA2 in adult RA has led to impressive short-term suppression of disease, with a good safety profile. Here, we report the first use of cA2 in childhood arthritis, choosing a patient with severe systemic-onset JCA, resistant to conventional therapies. The patient received two i.v. infusions of cA2, each at a dose of 10 mg/kg, separated by 1 week. The treatment was well tolerated and induced rapid control of fever, anorexia and serositis, together with downregulation of interleukin (IL)-6, soluble TNF receptors (sTNFR) and IL-1ra, and the acute-phase proteins C-reactive protein (CRP) and serum amyloid A (SAA). In contrast, we saw no significant improvement in joint pain or tenderness. Our findings suggest that TNF-alpha is a mediator of fever and other systemic aspects of disease in systemic JCA. TNF-alpha blockade as a treatment modality in JCA deserves further study.
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PMID:Suppression of fever and the acute-phase response in a patient with juvenile chronic arthritis treated with monoclonal antibody to tumour necrosis factor-alpha (cA2). 918 62

The serum amyloid A (SAA) protein has been implicated in the progression and pathogenesis of rheumatoid arthritis through induction of collagenase activity in synovial fibroblast cells that line the joint tissues. We demonstrate that SAA is synergistically induced in synovial cells by interleukin (IL)-1 and IL-6 that are present at significantly high level in the synovial fluid of arthritis patients. These cytokines induced phenotypic changes in synovial cells, promoting protrusion and increased cellular contact. Induction of SAA under this condition is mediated by promoter elements located between -254 and -226, which contains binding sites for transcription factors Sp1 and SAA activating sequence binding factor (SAF). Mutation of these sequences abolishes SAA promoter response to IL-1 and IL-6. The role of Sp1 in SAA induction was demonstrated by increased DNA binding activity, phosphorylation, and increased protein content of Sp1 during cytokine treatment. Sp1 interacts with the SAA promoter in association with SAF as an SAF. Sp1 heteromeric complex. Furthermore, using a phosphatase inhibitor, we demonstrated increased transactivation potential of both Sp1 and SAF as a consequence of a phosphorylation event. These results provide first evidence for cytokine-mediated activation of Sp1 in synovial fibroblast cells and its participation in regulating SAA expression by acting in conjunction with SAF.
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PMID:Activation of Sp1 and its functional co-operation with serum amyloid A-activating sequence binding factor in synoviocyte cells trigger synergistic action of interleukin-1 and interleukin-6 in serum amyloid A gene expression. 993 31

Oncostatin M (OM) is a member of the interleukin-6 (IL-6) cytokine subfamily. The binding of OM to its receptor initiates signal transduction through JAK-signal transducers and activators of transcription (STAT) pathways and activates transcription activators through mitogen-activated protein (MAP) kinases. Results of in vitro assays documented that OM modulates cytokine expression and alters the production of proteases that down-regulate inflammation. Administration of OM to lipopolysaccharide (LPS)-challenged mice lowered serum tumor necrosis factor-alpha (TNF-alpha) levels and decreased the lethal effects of LPS administration. OM also reduced inflammation in animal models of human disease, including inflammatory bowel disease, antibody-induced arthritis, and experimental autoimmune encephalomyelitis. Preclinical safety studies have been conducted in the mouse and monkey. Mice were administered OM (subcutaneously) at 72, 360, or 1,560 micrograms/kg/day in a 2-wk toxicity study. Decreased body weights occurred at 1,560 micrograms/kg. Drug-related changes at 360 and 1,560 micrograms/kg consisted of dermal irritation at the injection site, leukopenia, and thymic lymphoid depletion; all changes were reversible following a 2-wk recovery period. In a 2-wk subcutaneous study in monkeys, OM was administered at 1, 5, 15, 45, or 150 micrograms/kg/day. At all doses there was reversible, transient inappetence and dermal irritation at the injection site. Drug-related changes at 5, 15, 45, and 150 micrograms/kg consisted of reversible elevations in both serum amyloid A and IL-6, and reversible thymic lymphoid depletion. Transient increases in body temperature occurred at 15, 45, and 150 micrograms/kg. The observed spectrum of immunomodulatory effects suggests that OM may have therapeutic utility in treating chronic inflammatory diseases.
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PMID:Oncostatin M: development of a pleiotropic cytokine. 1020 78


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