Rapid assay of phospholipase A2 activity in plasma and synovial fluid.
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Biomedical subjects
Publications and source records attributed to P E Prete.
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This prospective unblinded 24-month-study compared the therapeutic value of oral gold with injectable gold to maintain rheumatoid arthritis (RA) patients in clinical remission and prevent the progression of erosive disease. Forty-six patients with definite RA in remission with injectable gold were randomized into two groups: a control group, continued on maintenance injectable gold (Solganal, aurothioglucose, 50-100 mg, intramuscularly, 2 to 4 weeks); and an experimental group, switched to oral gold (6-9 mg auranofin by mouth daily). Only 29% of the original 24 oral gold patients remained on assigned treatment at 24 months compared with 64% of the injectable gold group. By six months, over one-half of the oral gold patients had electively stopped their randomized therapy. Sixty-seven percent of the oral gold patients had adverse reactions, mostly gastrointestinal complaints, compared with one proteinuria in the injectable gold group. The oral gold group experienced significantly more deterioration in all the primary measures of treatment effect over the follow-up period. At the termination of the trial, 88% of the group had increases of 5 or more points in radiographic scores suggesting progression of erosive disease compared with only 29% of the control group. These data suggest that oral gold is not an effective substitute for injectable gold in maintaining remission in rheumatoid arthritis.
Synovial fluid (SF) of patients with rheumatoid arthritis (RA) has been noted to contain cholesterol crystals and increased amounts of cholesterol compared with normal SF. SF, plasma apolipoproteins (apos) A-I and B, and cholesterol in 12 untreated classic RA patients (inflammatory arthritis) and eight untreated degenerative joint disease ([DJD] noninflammatory arthritis) patients were analyzed. Results showed that mean apo A-I, apo B, and cholesterol levels of RA SF were significantly higher than those of DJD SF (apo A-I, P = .004; apo B, P = .0008; cholesterol, P = .0004). Regression analyses of plasma and SF apo A-I and apo B (r = .72, P = .008 and r = .63, P = .02, respectively) suggested an increased permeability for these lipoprotein constituents across RA synovial membrane that was not observed in DJD synovial membrane. These data suggest that RA synovium but not DJD synovium is more permeable to major apoproteins of low- and high-density lipoproteins (LDL and HDL). These apolipoproteins have been shown to influence the immune response and may therefore be involved in the pathogenesis of RA.
Recent developments in plasma lipoprotein and apolipoprotein research have been striking, but few studies have focused on the analysis of lipoproteins in synovial fluid (SF). SF contains small amounts of lipoproteins and apolipoproteins. The lipid concentration of normal human SF is extremely low and is in sharp contrast to the concentrations found in plasma. Little is known about the lipids in pathological SF, but studies have noted increased cholesterol and lipoprotein content in rheumatoid arthritis (RA) SF ranging from 40% to 60% of the total plasma lipoproteins. Recently apolipoproteins AI, B and E have also been found to be in increased amounts in RA SF. Several theories have been proposed to account for the increased presence of SF lipids in RA. Animal and human studies indicate the SF cholesterol, lipoproteins, and apolipoproteins may aggravate the inflammatory reaction within the synovial space. Research suggests an immunologic role for plasma lipoproteins on lymphocyte and monocytes in the blood and lymph. SF lipoproteins and apolipoproteins should be studied to define their actions within the synovial space.
Partitioning cells in a dextran polyethylene glycol aqueous two-phase system (countercurrent distribution, CCD) is a sensitive method for learning about cell surface membrane properties and for subfractionating cell populations. In this study, we subjected lymphocytes from normal DBA/2 mice and autoimmune F1 New Zealand black/New Zealand white [NZB/NZW)F1) mice to countercurrent distribution and found that T cells partition to the right and B cells partition to the left of the CCD curve. We found no difference between the CCD patterns of normal and autoimmune mice. When the murine lymphocytes were exposed to a cationic dietary amino acid (L-canavanine) in vitro, L-canavanine selectively affected the CCD pattern of autoimmune B cells, reflecting an alteration in surface membrane properties. We separated these lymphocytes with altered surface membrane properties by CCD. Impaired B-cell immune responses associated with L-canavanine were isolated to this lymphocyte fraction. This study provides the first evidence that alterations in the charged surface membrane properties are associated with abnormal (auto) immune response.
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Paraneoplastic syndromes affect a variety of organ systems and often suggest occult malignancy. Recently, a distinct syndrome of palmar fasciitis and arthritis has been associated with ovarian carcinomas. The two cases presented illustrate the fasciitis-arthritis association with other non-ovarian malignancies and suggest an immunologic cause for this disorder.
A modified version of the McGill Pain Questionnaire in visual analogue format was used to evaluate the sensory, affective and evaluative intensities of pain experienced by 40 patients with rheumatoid arthritis and 20 patients with degenerative arthritis. The affective component of the pain was found to be more intense than the sensory component in all patients indicating the importance of emotional factors in the pain experience. The sensory aspects of the pain were more complex than the affective ones reflecting the varied sources and combinations of somatic pathology. There were no significant differences found in the overall pain experience between rheumatoid and degenerative arthritis. No differences were noted in the evaluative category of pain. Overall pain intensity increased with disease duration in both rheumatoid and degenerative arthritis. The relationship of affective and sensory components of the pain experience did not alter with duration of disease.
This study reports the effects in vitro and in vivo of L-canavanine (LCN), an amino acid found in commonly consumed legumes, on immune function in normal and autoimmune mice. L-Canavanine in high doses effectively blocks all DNA synthesis in vitro within 24 h. At lower doses, LCN affects B-cell function of autoimmune New Zealand Black/New Zealand White (NZB/NZW)F1 mice, inhibiting [3H]thymidine incorporation in response to B-cell mitogens, and pokeweed-induced intracytoplasmic immunoglobulin synthesis. LCN stimulates intracytoplasmic immunoglobulin (IgG greater than IgM). T-cell functions such as lymphoproliferation in response to concanavalin A or phytohemagglutinin and T-cell cytotoxicity are not affected. Suppression of the lipopolysaccharide response by LCN is removed by the addition of fresh B cells. Addition of the amino acid to mouse diet resulted in a decrease in the life-span of the autoimmune NZB and (NZB X NZW)F1 mice and abolished the protective effect of male sex on their survival. The decrease in survival in LCN-treated autoimmune mice correlated with an increase in spontaneous immunoglobulin-secreting cells (IgG greater than IgM) and antinuclear and double-stranded DNA antibodies. The histopathological analyses revealed increased glomerular damage and immunoglobulin deposition in the kidneys of the LCN-treated autoimmune and normal (DBA/2) mice. Ten percent of normal mice developed high titers of autoantibodies after 24 weeks of the diet. These data suggest a dietary amino acid, L-canavanine, affects B-cell function resulting in autoimmune phenomena and providing a new animal model of autoimmunity, a diet-induced systemic lupus erythematosus.
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Normal human synovial fluid contains extremely low concentrations of lipoproteins and apolipoproteins, in sharp contrast to those found in plasma. Increased amounts of cholesterol and other lipids have been found in the synovial fluid of a chronic inflammatory joint disorder, rheumatoid arthritis (RA). More recently, apolipoproteins AI, B and E have also been found in increased amounts in RA synovial fluid. Theories have been proposed to account for this increase in the amount of apolipoproteins and for the source of lipids and lipoproteins in normal synovial fluid; however, the mechanisms have not yet been established. Lipoproteins may play dual roles in synovial fluid: A functional one in normal synovial fluid and, as some suggest, a pathologic one in the abnormal synovial fluid of certain arthritic diseases. The recent data prompt the need to define synovial fluid lipids, lipoprotein particle subfractions and their constituent apolipoproteins, as well as their respective roles in synovial fluid.