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ID PMID Title PublicationDate abstract
10469242 Ability of T cells from patients with rheumatoid arthritis to respond to immunoglobulin G. 1999 Sep The ability of T cells from rheumatoid factor (RF)-positive patients with rheumatoid arthritis (RA) to respond to immunoglobulin G (IgG) was assessed. Peripheral blood mononuclear cells (PBMC) from RA patients and normal individuals were cultured with and without human IgG or Mycobacterium tuberculosis-purified protein derivative (PPD) for 7 days and their proliferative response measured at intervals by their ability to take up tritiated thymidine. PBMC from 14/26 RA patients proliferated in response to IgG (taking a stimulation index of 3 or above as positive). The peak response varied between individuals but usually occurred on day 5, the same day, or 1 day later than the peak response to PPD. By contrast, PBMC from a significantly lower proportion (1/9) of normal individuals and patients with other arthritides (0/6) responded to IgG, although all responded to PPD. PBMC from 9/14 RA patients responded to Fab fragments of IgG but only 3/9 to the Fc fragment. Higher proliferative responses from RA PBMC were elicited by IgG aggregates than the original IgG preparation, but PMBC from 5/5 normal individuals and 5/6 patients with other arthritides failed to respond to the aggregates. The response to IgG was human leucocyte antigen (HLA)-DR restricted and mediated by CD4+ T cells. It is considered that these results advance the hypothesis that IgG-reactive T cells contribute to the initiation or perpetuation of RA.
11213913 IL-12, IL-6 and IFN-gamma production by lymphocytes of pregnant women with rheumatoid arth 2000 BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease with progressive activity. The RA remission was observed in women during pregnancy, but the mechanism responsible for remission is hypothetical only and concerns mechanisms of immune regulation such as lymphocyte subpopulations and interleukin production. AIMS: The lymphocyte subpopulations and interleukin production in vitro in a group of healthy non-pregnant women, healthy pregnant women and pregnant women suffering from RA may help towards a better understanding of regulation of the immune processes. METHODS: The investigations were performed in trimester III--2 days after delivery and 6 weeks after delivery. Peripheral blood lymphocytes were isolated on Gradisol gradient and analysed immediately or after having been cultured for 72 hours in RPMI medium supplemented with 10% FCS. The cultures were terminated after 72 h, supernatants stored at -72 degrees C for interleukin evaluation. The concentrations of IFN-gamma, IL-2, IL-6, IL-12, TNF-alpha and its soluble receptors R-I, R-II were estimated in non-stimulated and PHA (Sigma, 5 microg/ml) stimulated culture supernatants using ELISA Endogen kits according to the manufacturer's instructions. RESULTS: The general pattern of T cell subpopulation distribution was similar in all analysed groups. Decreased IFN-gamma, IL-12 and increased IL-6 production by lymphocytes after PHA stimulation was found in trimester III in pregnant women with RA as compared to healthy pregnant woman. CONCLUSION: The obtained results suggest that in pregnant women with RA the TH1 cell response predominates, contrary to healthy pregnant women with TH2 type functional response. These phenomena were not observed after delivery.
11093593 Rheumatoid arthritis T cells produce Th1 cytokines in response to stimulation with a novel 2000 Rheumatoid arthritis (RA) T cells respond poorly to conventional mitogens. We have examined the proliferative and cytokine responses of T cells to a synthetic trispecific antibody (Tsab) directed against CD2, CD3, and CD28. In 11 subjects RA T cells proliferated more, and secreted significantly more IL-2, in response to Tsab than did control peripheral blood (PB) cells. Very high levels of IL-2 were produced by 2 patients with aggressive disease. Measurement of intracellular IL-2, IFN-gamma, IL-4, and IL-5 by flow cytometry showed a Th1 pattern of cytokine production in 13 RA and 9 control subjects. We conclude that RA T cells are not irreversibly inactivated, and that spatial arrangement of stimulating molecules may be important in eliciting maximal responses.
10452831 Effects of interleukin-6 on proliferation and proteoglycan metabolism in articular chondro 1998 Interleukin-6 (IL-6) levels are markedly increased in the synovial fluid of patients with rheumatoid arthritis or osteoarthritis. However, the effects of IL-6 on proliferation and proteoglycan metabolism in articular cartilage are not known. We demonstrated here the effects of human recombinant (hr) IL-6 on proliferation and proteoglycan metabolism in rabbit articular chondrocyte cultures. In vitro, these cells proliferated and produced abundant extracellular matrices. We found that 1-10 ng/ml of hrIL-6 inhibited proliferation to approximately 65% of control levels and suppressed colony formation induced by bFGF in soft agarose. The same concentration of hrIL-6 depressed proteoglycan synthesis to approximately 60% of control levels. Moreover, hrIL-6 significantly enhanced proteoglycan degradation induced by hrIL-1beta, although hrIL-6 alone did not affect proteoglycan degradation. These findings suggest that IL-6 is a negative regulator for chondrocyte proliferation and articular cartilage metabolism.
9741316 Iron, lactoferrin and iron regulatory protein activity in the synovium; relative importanc 1998 May OBJECTIVES: To determine the ability of lactoferrin in rheumatoid arthritis (RA) synovial fluid to bind "free" iron, and to study the regulatory mechanisms therein that control iron homeostasis. METHODS: "Free" iron was determined by the bleomycin assay and lactoferrin concentrations by enzyme linked immunosorbent assay. The activities of iron regulatory protein (IRP) and NF-kappa B in synovial fluid cells were assayed by mobility shift assay. RESULTS: 30% of synovial fluids contained "free" iron and in these, lactoferrin concentrations were significantly lower than in those with no "free" iron (p < 0.01). Addition of exogenous lactoferrin consistently reduced the amount of "free" iron in positive synovial fluids. IRP activity in synovial cells did not correlate with synovial fluid iron concentrations but did correlate with NF-kappa B activation and with serum C reactive protein. CONCLUSION: Lactoferrin may prevent iron mediated tissue damage in RA by reducing "free" synovial iron concentration when inflammatory stimuli have disregulated IRP mediated iron homeostasis.
11583972 Plasma apolipoprotein(a) co-deposits with fibrin in inflammatory arthritic joints. 2001 Oct Extravascular coagulation and diminished fibrinolysis are processes that contribute to the pathology of both inflammatory arthritis and atherosclerosis. We hypothesized that, given its homology with plasminogen, apolipoprotein (apo) (a), the distinctive glycoprotein of the atherogenic lipoprotein (Lp) (a), may be equally implicated in inflammatory arthritis. We detected the presence of apo(a) as part of Lp(a) in human arthritic synovial fluid. The abundance of apo(a) in synovial fluid rose in proportion to plasma apo(a) levels and was higher in inflammatory arthritides than in osteoarthritis. In addition, apo(a) immunoreactive material, but not apo(a) transcripts, was detected in inflammatory arthritic synovial tissues. These data indicated that synovial fluid apo(a) originates from circulating Lp(a) and that diffusion of Lp(a) through synovial tissue is facilitated in inflammatory types of arthritis. In synovial tissues, apo(a) co-localized with fibrin. These observations could be reproduced in a model of antigen-induced arthritis, using transgenic mice expressing human Lp(a). Although in this mouse model the presence of apo(a) did not change the severity of arthritis, the co-localization of apo(a) with fibrin in synovial tissue suggests that, in humans, apo(a) may modulate locally the fibrinolytic activity and may thus contribute to the persistence of intra-articular fibrin in inflammatory arthritis.
10759780 Down-regulation of the T cell receptor CD3 zeta chain in rheumatoid arthritis (RA) and its 2000 Apr T cells implicated in chronic inflammatory diseases such as RA respond weakly when stimulated in vitro with mitogen or antigen. The mechanism behind this hyporesponsiveness is unclear, but a depressed expression of the T cell receptor (TCR)-associated CD3zeta chain has been suggested. In the present work we describe a low expression of CD3zeta in synovial fluid (SF) T cells from RA patients compared with peripheral blood (PB) T cells, but no difference in CD3zeta expression between RA and healthy control PB T cells. In vitro studies demonstrated that granulocytes but not SF macrophages are able to down-regulate the expression of CD3zeta. Through stimulation with anti-CD3 antibodies we demonstrated that the TCR-dependent proliferative response was decreased in SF T cells compared with PB T cells. Stimulation with phorbol ester and ionomycin also resulted in a low proliferative response of SF T cells, indicating that both signal transduction through the TCR (stimulation with anti-CD3) and events further downstream in the signalling pathways (stimulation with phorbol ester and ionomycin) are affected. A similar depression of T cell activity was observed when induction of IL-2 and IL-4 was measured. However, SF T cells were not defective in the induction of interferon-gamma (IFN-gamma) when stimulated with phorbol myristate acetate (PMA)/ionomycin, in contrast to the diminished IFN-gamma response observed after stimulation with anti-CD3. This indicates that the hyporesponsiveness of SF T cells can not be generalized to all T cell functions. The differential response to external stimuli is likely to be of importance for the capacity of SF T cells to influence inflammatory reactions.
9864836 [Therapy of refractory chronic polyarthritis with tumor necrosis factor alpha receptor fus 1998 Oct AIM OF THE STUDY: To investigate the long-term effect of TNFR55-IgG1 in patients with severe rheumatoid arthritis refractory to multiple previous DMARD treatments. METHODS: Between 1994 and 1995 we recruited 80 patients for two double blind, placebo-controlled multicenter trials. All patients were treated for 2-30 months with a glycosylated fused protein consisting of two human p55 TNF receptors linked to a human IgG1-Fc. The dose range was 2.5-100 mg/month given i.v. with cumulative doses from 40-940 mg. All patients were followed-up prospectively for 24-36 months after initiation of therapy. The evaluations included a 48 swollen and tender joint count, ESR. CRP, RF, ANA, ENA, and safety parameters at 6 month intervals. In addition, pharmacokinetics, TNF, and anti-TNFR55-IgG1 antibody levels were available after the first and third injection. RESULTS: Data from 80 patients are available representing an experience of more than 170 patient years; 11 patients are still being treated. Predominant reasons for treatment withdrawal were restrictions in treatment protocol. Six patients died (1 during treatment, 5 in the post-treatment follow-up). All deaths were related to preexisting cardiovascular disease except one post-surgery septic arthritis 6 months after the last dosing (during vacation in another country). No malignancies were detected. Anti-TNFR55-IgG1 antibodies correlated with a decrease in drug half-time. Shifts in the TNFR55-IgG1 glycosylation pattern affected pharmacokinetics and efficacy. A lupus nephritis occurred 18 months after the last dosing in one patient with erosive RA (ANA and dsDNS positive already before TNFR55-IgG1 initiation). Continued treatment for 3 years in 11 patients resulted in an 81% reduction in swollen joint count, less morning stiffness, less pain, and a reduction in steroids. CONCLUSION: Treatment with TNFR55-IgG1 is safe and efficacious over the long-term in patients with severe refractory RA.
9495380 Development of rheumatoid arthritis after treatment of large granular lymphocyte leukemia 1998 Mar The association of T-cell large granular lymphocyte (LGL) leukemia and rheumatoid arthritis is well described and it is now recognized that these patients and patients with Felty's syndrome represent different aspects of a single disease process. Most patients have rheumatoid arthritis at the time of diagnosis of LGL leukemia. This is the first detailed report of the development of rheumatoid arthritis after the diagnosis and treatment of LGL leukemia as well as the first report of rheumatoid arthritis that occurred in association with deoxycoformycin treatment. It is likely that the beneficial sustained normalization of neutrophil counts as a result of deoxycoformycin treatment played a significant role in the development of this complication. Hematological improvement occurred despite molecular genetic evidence of persistence of the abnormal T-cell clone. The role of the clonally expanded T cells in the pathogenesis of neutropenia and rheumatoid arthritis is discussed.
9751519 Human osteoclasts and osteoclast-like cells synthesize and release high basal and inflamma 1998 Oct Chemokines, including interleukin-8 (IL-8), function as key mediators in diverse inflammatory disorders via promoting the recruitment, proliferation, and activation of vascular and immune cells. IL-8 levels are elevated in inflammatory diseases, such as rheumatoid arthritis, osteoarthritis, osteomyelitis, and periodontal disease, that also exhibit progressive bone loss. Therefore, it is possible that IL-8 contributes to the osteopenia associated with these pathological conditions. Although macrophages, neutrophils, and endothelial cells are considered the primary sources of inflammation-induced IL-8 increases, we report here for the first time that human bone marrow-derived osteoclast-like cells (hOCL) as well as authentic bone-resorbing human osteoclasts (hOC) isolated from osteoporotic femoral heads express messenger RNA (mRNA) for IL-8 and secrete high levels of IL-8 during culture. Basal IL-8 release by cultured hOC or hOCL was orders of magnitude greater than the release of the proinflammatory cytokines IL-1beta, IL-6, and tumor necrosis factor-alpha. At a cellular level, in situ hybridization analysis revealed that IL-8 mRNA was expressed in resorbing hOC of rheumatoid arthritic pannus and was substantially greater than that expressed in hOC of noninflammatory giant cell tumor of bone tissue. Therefore, the potential inflammation-mediated induction of IL-8 was directly assessed using cultured hOCL. IL-8 release was stimulated by proinflammatory signals (IL-1alpha, tumor necrosis factor-alpha, lipopolysaccharide, or phorbol 12-myristate 13-acetate), unaffected by various other osteotropic modulators (transforming growth factor-beta1 and -beta3, IL-6, 17beta-estradiol, or calcitonin) and was decreased by interferon-gamma, vitamin D3, and the antiinflammatory glucocorticoid dexamethasone. Changes in IL-8 secretion were paralleled by corresponding changes in IL-8 mRNA steady state levels. We conclude that hOC and hOCL synthesize and secrete high constitutive and inflammation-stimulated levels of the chemokine IL-8. Consequently, hOC-derived IL-8 could act as an important regulatory signal for bone, vascular, and immune cell recruitment and activation during normal and pathological bone remodeling.
11011144 Autoantibody activity of IgG rheumatoid factor increases with decreasing levels of galacto 2000 Oct The occurrence of N-linked oligosaccharides lacking galactose is significantly higher than normal in serum IgG of patients with rheumatoid arthritis (RA) in whom rheumatoid factor (RF), an autoantibody against autologous IgG, has been detected. In the present study, IgGs with and without RF activity (IgGRF and non-RF IgG, respectively) were prepared from sera of RA patients, and their oligosaccharide structures were characterized in order to investigate the relationship between RF activity and glycosylation. Three IgGRF fractions and a non-RF IgG fraction were obtained based on their ability to bind to an IgG-Sepharose column. The specific RF activity, as measured by immunoassays, was highest in the IgGRF fraction, which bound most avidly to the IgG-Sepharose. When the oligosaccharides were released by hydrazinolysis, and analyzed by MALDI-TOF mass spectrometry and HPLC, in combination with sequential exoglycosidase treatment, all the IgG samples were found to contain a series of biantennary complex-type oligosaccharides. The incidence of galactose-free oligosaccharides was significantly higher in both IgGRFs and non-RF IgG from RA patients compared with IgG from healthy individuals. In all IgGRFs, the levels of sialylation and galactosylation were lower than those in non-RF IgG from RA patients; the sialylation of non-RF IgG was the same as that of IgG from healthy individuals. In addition, the decreases in galactosylation and sialylation of oligosaccharides in IgGRF correlated well with the increase in RF activity. These findings could contribute to our understanding of the mechanisms of IgG-IgG complex formation and the pathogenicity of these complexes in RA patients.
11040429 Distribution of ecto 5'-nucleotidase on Mycoplasma species associated with arthritis. 2000 Nov 1 The enzyme ecto 5'-nucleotidase (5'N) was found to be active on 8/14 strains of Mycoplasma fermentans, K(m) (+/-S.D.) 3.8+/-2.8 microM 5'-AMP, and on the type strain of Mycoplasma pulmonis, K(m) 0.63 microM 5'-AMP. The six M. fermentans strains lacking 5'N activity were related by restriction fragment length polymorphism typing. At pH 8.5, the type strains of Mycoplasma arthritidis, Mycoplasma buccale and Ureaplasma urealyticum showed a relatively non-specific phosphatase activity against 5'-AMP but no activity was shown by the type strains of Mycoplasma genitalium, Mycoplasma hominis, Mycoplasma orale, Mycoplasma penetrans, Mycoplasma pneumoniae and Mycoplasma salivarium at this pH. M. fermentans has been reported from rheumatoid joints, which show a raised 5'N activity on their synovial cells and in their fluid which may be associated directly or indirectly with the mycoplasma.
11491188 The transcription factor Egr-1: a potential drug in wound healing and tissue repair. 2001 Jul In the United States, between 40 and 90 million hospital days are lost per year as a result of trauma and surgical procedures which result in the loss of functional tissue. This is estimated to cost the economy and healthcare providers in excess of US$ 500 billion, a figure that is increasing because of extending population lifespan. Tissue engineering and gene therapies are radical new treatments that are aimed at tissue regeneration ranging from dermal, osteal and occular repair to the replacement of failing tissue with entire biosynthetic organs. Over the last decade, numerous proteins have been identified that are able to direct the synthesis of new tissue. Such proteins include growth factors, cytokines and, more recently, transcription factors.
10796393 Folic acid and folinic acid for reducing side effects in patients receiving methotrexate f 2000 OBJECTIVES: To assess the effects of folic acid and folinic acid in reducing the mucosal and gastrointestinal (GI) and haematologic side effects of low-dose of Methotrexate (MTX) in patients with Rheumatoid Arthritis (RA) and to determine whether or not folate supplementation alters MTX efficacy. SEARCH STRATEGY: We searched the Cochrane Controlled Clinical Trial's Register (CCTR), the Cochrane Musculoskeletal Group Specialized Register and Medline up to and including June 1999, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). We also handsearched the following: (i) bibliographic references; (ii) current contents of the last 6 months; (iii) abstracts of the rheumatology meetings; and (iv) all issues of four journals; Journal of Rheumatology, Arthritis & Rheumatism, Clinical and Experimental Rheumatology, and British Journal of Rheumatology. All languages were included. Principal investigators were also contacted in order to look for unpublished literature. SELECTION CRITERIA: We selected all double-blind, randomized, placebo-controlled, clinical trials (RCTs), in which adult RA patients were treated with a low dose of MTX (<20 mg / week) concurrently with folate supplementation. DATA COLLECTION AND ANALYSIS: Two observers extracted the data and assessed the quality of the trials. (BS, Z0) The overall treatment effect across trials was calculated using a fixed effect model. Disease activity was evaluated using standardized mean differences to ensure comparability across outcome measures. Results are presented with 95% Confidence Inervals (95% CI). Subgroup analyses were conducted evaluating different doses and sensitivity analysis looking at the quality of the trials. Publication bias was assessed with an inverted funnel plot technique. Heterogeneity of the trials was measured using a standard chi square test. Costs per month in different countries were compared. MAIN RESULTS: Of the 12 trials retrieved, 7 met the inclusion criteria. The total sample included 307 patients, of which 147 were treated with folate supplementation, 80 patients with folinic acid and 67 patients with folic acid. A 79% reduction in mucosal and GI side effects was observed for folic acid [OR = 0.21 (95% CI 0.10 to 0.44)]. For folinic acid, a clinically but non-statistically significant reduction of 43% was found [OR = 0. 57 (95% CI 0.28 to 1.15)]. No major differences were observed between low and high doses of folic or folinic acid. Haematologic side effects could not be analyzed, since details of each haematologic side effect by patients were not provided. No consistent differences in disease activity parameters were observed when comparing placebo and folic or folinic acid at low or high doses, although patients on high dose folinic acid had an increase in the number of tender joints, but not swollen joints. Large differences in costs across countries were found, but folinic acid was more expensive in all. REVIEWER'S CONCLUSIONS: The results support the protective effect of folate supplementation in reducing MTX side effects related to the oral and GI systems. We could not determine if folic was different from folinic acid. Therefore, for folinic acid to be considered cost-effective it must be found more effective than folic acid at reducing MTX side effects.
11160344 Il-4 and IL-13, but not IL-10, protect human synoviocytes from apoptosis. 2001 Feb 15 Interleukin-4, which has been contemplated for the treatment of rheumatoid arthritis and/or osteoarthritis because of its anticatabolic properties, has also been shown to modulate apoptosis. Because inadequate apoptosis is thought to contribute to synovial hyperplasia, we have investigated the ability of IL-4 and other Th2 cytokines to protect human synovial cells from apoptosis. Human synoviocytes or synovial explants were pretreated with IL-4, IL-10, and IL-13 before exposure to NO donor sodium-nitro-prusside (SNP). Apoptosis was evaluated by microscopy, annexin V-FITC, 3-(4,5-dimethylthiazol-2-gl)-5-(3-carboxymethoxylphenyl)-2-(4-sulphophenyl-2H: tetrazolium inner salt (MTS) test, pulse field gel electrophoresis, and a method proposed in this study based on (32)P Klenow end labeling of high m.w. DNA. Pretreatment by IL-4 or IL-13, but not IL-10, protected human synoviocytes from apoptosis induced by SNP. Even at doses as high as 2 mM SNP, up to 86% and 56% protection was achieved, after IL-4 and IL-13 treatment, respectively. Cell survival was dependent on IL concentration. IL-4 and IL-13 also had antiapoptotic effects on SNP-treated human synovial explants. Effects of IL-4 and IL-13 varied in the presence of phosphatidylinositol-3 kinase and protein kinase C inhibitors, implying the involvement of these pathways in antiapoptotic signaling. Antiapoptotic effects were dramatically inhibited by LY294002, and partially by the protein kinase C inhibitor Gö 6976, while insulin-like growth factor increased synoviocyte survival. The possibility that IL-4 and IL-13 may enhance synovial expansion in vivo by their antiapoptotic effects is discussed.
10088774 Synovial fluid transforming growth factor beta inhibits dendritic cell-T lymphocyte intera 1999 Mar OBJECTIVE: To examine whether rheumatoid synovial fluid (SF) inhibits dendritic cell (DC) expression of the CD80 and CD86 costimulator molecules and contributes to SF T lymphocyte hyporesponsiveness. METHODS: Cell-free rheumatoid SF was tested for its effect on DC-stimulated autologous/allogeneic mixed lymphocyte reactions and for its effect on DC surface antigen expression, as assessed by flow cytometry. Blocking monoclonal antibodies were used to identify the SF cytokines that inhibited DC-T lymphocyte interactions. RESULTS: Low concentrations of SF (2.5%) could inhibit DC-mediated autologous and allogeneic T lymphocyte proliferation. This inhibitory effect could be reversed by neutralizing transforming growth factor beta (TGFbeta) and interleukin-2 (IL-2), but not by IL-12, in the SF. Hyaluronic acid, IL-6, IL-10, and tumor necrosis factor alpha were not associated with SF inhibition. In vitro culture alone and crosslinking with the CD40 ligand up-regulated DC CD80/CD86 expression and costimulator function, and this was not affected by inclusion of SF. In the presence of SF, DC clustered with autologous T lymphocytes showed decreased CD80 and CD86 expression, and variable CD80/CD86 decreases were observed on DC clustered with allogeneic T lymphocytes. CONCLUSIONS: TGFbeta in SF appears to suppress T lymphocyte function, which may affect both signaling to DC and the induction of DC costimulator function.
11791639 Characterization of human serum dipeptidyl peptidase IV (CD26) and analysis of its autoant 2001 Nov OBJECTIVES: To assess the serum levels, specific activity and other characteristics of dipeptidylpeptidase IV (DPP IV/CD26), an ectoenzyme that plays a critical role in the modulation and expression of autoimmune and inflammatory diseases, from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjögren syndrome (SS) and normal controls. To study the possible underlying molecular basis if significant differences were found. METHODS: Serum DPP IV was purified by ion-exchange and affinity chromatography techniques and its specific activity and sera levels were determined by an enzyme-linked assay (ELISA). The enzyme was further analyzed for its sialic acid content, its adenosine deaminase binding capacity and its electrophoretic mobility. The levels of circulating IgA, IgG, and IgM anti-DPP IV autoantibodies were determined by an ELISA technique. RESULTS: The median serum levels of DPP IV in RA patients was similar to controls (0.85 microg/ml versus 1.03 microg/ml, p = n.s.); in SLE and SS patients the enzyme serum levels were reduced to nearly one half of controls (p < 0.001). DPP IV specific activity was significantly reduced in serafrom RA patients when compared with those of SLE, SS and normal sera (12.24 versus 16.5, 19.69 and 16.34 mol pNA x 10(-4)/min/mol respectively, p < 0.005). Both RA and SLE enzymes were hypersialylated, but only RA DPP IV augmented its specific activity to close to control values after desialylation with V. cholerae neuraminidase. Sera from all patient groups contained anti-DPP IV autoantibodies, but only those of the IgA isotype were significantly higher than those found in normal subjects. CONCLUSION: The specific activity of serum DPP IV was decreased only in RA patients, although its levels were similar to normal controls. While both RA and SLE DPP IV were hypersialylated, desialylation restored the specific activity only of RA DPP IV. This finding suggests that different specific glycosylation sites in the enzyme might be involved as the underlying mechanism of the decreased enzyme specific activity of RA patients. The differences in DPP IV levels observed between RA and SLE patients seem to reflect a different status of T cell activation in both diseases.
9710884 Cyclooxygenases as the principal targets for the actions of NSAIDs. 1998 Aug The recent identification, cloning, and characterization of two cyclooxygenases has provided insight into how nonsteroidal anti-inflammatory drugs can beneficially inhibit prostaglandin production in inflammation but also produce side-effects in the gut and kidney. The subtle differences in the sites in which these drugs bind the enzymes has allowed development of inhibitors that exhibit selectivity for the inflammatory cyclooxygenase and spare the housekeeping enzyme. This selectivity in theory should enhance the therapeutic potential of these new drugs.
9395486 Matrix metalloproteinase-8 is expressed in rheumatoid synovial fibroblasts and endothelial 1997 Dec 12 Neutrophil collagenase (matrix metalloproteinase-8 or MMP-8) is regarded as being synthesized exclusively by polymorphonuclear neutrophils (PMN). However, in vivo MMP-8 expression was observed in mononuclear fibroblast-like cells in the rheumatoid synovial membrane. In addition, we detected MMP-8 mRNA expression in cultured rheumatoid synovial fibroblasts and human endothelial cells. Up-regulation of MMP-8 was observed after treatment of the cells with either tumor necrosis factor-alpha (10 ng/ml) or phorbol 12-myristate 13-acetate (10 nM). Western analysis showed a similar regulation at the protein level. The size of secreted MMP-8 was 50 kDa, which is about 30 kDa smaller than MMP-8 from PMN. Conditioned media from rheumatoid synovial fibroblasts contained both type I and II collagen degrading activity. However, degradation of type II collagen, but not that of type I collagen, was completely inhibited by 50 microM doxycycline, suggesting specific MMP-8 activity. In addition, doxycycline down-regulated MMP-8 induction, at both the mRNA and protein levels. Thus MMP-8 exerts markedly wider expression in human cells than had been thought previously, implying that PMN are not the only source of cartilage degrading activity at arthritic sites. The inhibition of both MMP-8 activity and synthesis by doxycycline provides an incentive for further studies on the clinical effects of doxycycline in the treatment of rheumatoid arthritis.
9442332 Anterior interosseus nerve injury following elbow arthroscopy. 1997 Dec Elbow arthroscopy is becoming an increasingly invaluable tool for both evaluation of and treatment of a variety of interarticular disease processes. Case reports have documented radial and posterior interosseus injuries following anterior capsular release. To date, this is the first report of an anterior interosseus nerve injury following arthroscopic surgery of the elbow. Arthroscopic surgery offers unparalleled visualization of the multiple articulations and facets of the elbow. It has been reported as useful for removal of loose bodies, synovectomy, release of arthrofibrosis, and the treatment of osteochondritis dessicans. However, the technique does require thorough knowledge of neurovascular structures about the elbow as well as appreciation of the protective layers including the capsule, brachialis, and brachioradialis muscles. This report documents direct injury to the anterior interosseus branch of the median nerve during an elbow debridement and synovectomy in a 65-year-old patient with rheumatoid arthritis.