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ID PMID Title PublicationDate abstract
11285370 Expression of proteinases and inflammatory cytokines in subchondral bone regions in the de 2001 Mar OBJECTIVE: We previously described abnormalities in the bone marrow of patients with rheumatoid arthritis (RA), but were able to shed little light on the pathogenic roles of inflammatory cytokines and proteinases in joint destruction in the subchondral region in RA. This is the first report to describe the co-localization of cytokines and proteinases in this area. METHODS: Decalcified paraffin-embedded sections from 10 patients with RA and five patients with osteoarthritis (OA) were examined for the immunolocalization of cathepsins B, K and L and the localization of messenger RNAs for interleukin 1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha) and matrix metalloproteinase 9 (MMP-9). The cells were double-stained with anti-CD68 or anti-prolyl 4-hydroxylase (PH) antibody. RESULTS: An immunohistochemical study confirmed the expression of cathepsins B and L by CD68-positive mononuclear cells at the sites of significant cartilage and bone erosion from the subchondral region in all RA specimens. Osteoclast-like cells showed intense staining for cathepsin K and MMP-9. Osteoblast-like cells strongly expressed MMP-9. Analysis of serial sections revealed that expression of the IL-1beta and TNF-alpha genes occurred near that of the cathepsins and MMP-9 in the subchondral region. CONCLUSION: We conclude that inflammatory cytokines and tissue-damaging proteinases play important roles in joint destruction in the subchondral region in RA.
9313385 Nutrient intake patterns, body mass index, and vitamin levels in patients with rheumatoid 1997 Feb OBJECTIVE: To assess nutrient intakes and vitamin levels in 79 patients with rheumatoid arthritis participating in a trial and to determine whether changes in body mass index were associated with changes in disease activity. METHODS: This study evaluated baseline vitamin levels, 1-day dietary intakes, and weight every 3 months for 1 year. Linear regression analysis was used to evaluate the relationship of time to body mass index. Analysis of covariance was used to determine if body mass index, time, or treatment had an effect on disease activity. RESULTS: Deficient vitamin levels and poor nutrient intake patterns were prevalent in the study population. Changes in body mass index over time did not correlate with changes in disease activity. CONCLUSIONS: Rheumatoid arthritis patients are at high risk of obesity, abnormal vitamin levels, and poor nutrient intakes. Changes in body mass index failed to correlate with changes in disease activity.
10666168 Angiotensin converting enzyme in human synovium: increased stromal [(125)I]351A binding in 2000 Feb OBJECTIVE: To determine whether tissue angiotensin converting enzyme (ACE) is increased in synovia from patients with rheumatoid arthritis, osteoarthritis or chondromalacia patellae. METHODS: Sections of synovia from patients with rheumatoid arthritis (n = 7), osteoarthritis (n = 7) or chondromalacia patellae (n = 6) were tested for immunoreactivity for ACE, and for binding of the ACE inhibitor [(125)I]351A. The amount of ACE was measured with computer assisted image analysis as the proportion of synovial section area occupied by ACE-immunoreactive cells, and the density of [(125)I]351A binding. RESULTS: [(125)I]351A binding sites had characteristics of ACE and colocalised with ACE-like immunoreactivity to microvascular endothelium and fibroblast-like stromal cells in inflamed and non-inflamed human synovium. Stromal [(125)I]351A binding densities (B(eq)) and the fraction of synovial section area occupied by ACE-immunoreactivity (fractional area) were higher in synovia from patients with rheumatoid arthritis (B(eq) 28 amol/mm(2), fractional area 0.21) than from those with osteoarthritis (B(eq) 9 amol/mm(2), fractional area 0.10) or chondromalacia patellae (B(eq) 9 amol/mm(2), fractional area 0.09)(p < 0.05). Density of [(125)I]351A binding to stroma was similar to that to blood vessels in rheumatoid arthritis, but less dense than vascular binding in chondromalacia patellae and osteoarthritis. Increases in [(125)I]351A binding densities were attributable to increases in the numbers of binding sites, and were consistent with an increase in the density of ACE bearing stromal cells. CONCLUSION: ACE is upregulated in synovial stroma in rheumatoid arthritis. Increased tissue ACE may result in increased local generation of the vasoconstrictor and mitogenic peptide angiotensin II and thereby potentiate synovial hypoxia and proliferation in rheumatoid arthritis.
11406524 Quantitative ultrasonography in rheumatoid arthritis: evaluation of inflammation by Dopple 2001 Jul OBJECTIVE: To evaluate ultrasonographic methods, including the Doppler technique, as measures of synovial inflammation in finger joints of patients with rheumatoid arthritis. METHODS: Ultrasonography was performed with a high frequency transducer (13 MHz). Evaluation of the sonographic data was conducted by two independent observers and included measurement of synovial area and thickness (grey tone ultrasound), vascularisation (power/colour Doppler), and indices of the intra- and extrasynovial arterial flow (spectral Doppler). The flow pattern was estimated by the indices of pulsatility (PI) and resistance (RI). RESULTS: The sonographic measurements of joint space were reproducible with intraobserver, intraclass correlation coefficients (ICC) 0.82-0.97 (p<0.0001) and interobserver ICC 0.81 (p<0.0001). The mean (SD) fraction of the synovium vascularised in the patients was 0.15 (0.15). The synovial blood flow was characterised by a diastolic flow-that is, the flow persisting during the diastole. The mean (SD) PI was 1.92 (1.18) and RI 0.70 (0.13). The estimated vascular fraction correlated with the erythrocyte sedimentation rate (ESR) (r(s)=0.53, p=0.03). The relative Pi (rPi), an estimate of an abnormally low resistance to vascularisation, correlated with both ESR (r(s)=-0.557, p<0.05) and Health Assessment Questionnaire score (r(s)=-0.584, p<0.05). After an injection of contrast Levovist the vascular fraction increased, while no difference in PI and RI was observed. CONCLUSION: Ultrasonography is a reliable tool for estimating the size of the joint space and the synovial activity measured by the degree of vascularisation and pattern of flow. Ultrasonography may be useful in monitoring the synovial inflammation in rheumatoid arthritis.
10555021 Autologous hematopoietic stem cell transplantation in refractory rheumatoid arthritis: sus 1999 Nov OBJECTIVE: To investigate the safety and efficacy of immune ablation with subsequent autologous hematopoietic stem cell transplantation (HSCT) in severe rheumatoid arthritis (RA). METHODS: Four patients with refractory RA and poor prognostic indicators were treated. Stem cells were collected and lymphocytes were depleted by 2.3-4.0 logs. The conditioning regimen included cyclophosphamide (200 mg/kg), antithymocyte globulin (90 mg/kg), and, for 1 patient, total body irradiation (TBI) with 400 cGy. Improvement was evaluated according to the American College of Rheumatology (ACR) preliminary definition of improvement in RA (ACR 20), and also according to the ACR 50 and ACR 70 criteria. RESULTS: HSCT was well tolerated. Three patients fulfilled the ACR 70 criteria at 1 month and 3 months post-HSCT. One patient did not fulfill the ACR 20 criteria because of persistent joint tenderness, despite improvement of the joint swelling. At 6 months post-HSCT, 1 patient fulfilled the ACR 70 criteria and 1 fulfilled the ACR 50 criteria, and these 2 patients fulfilled the ACR 70 criteria at 9 months post-HSCT. The other 2 patients (including the patient who received TBI) did not meet the ACR 20 criteria at 6 months and 9 months post-HSCT. The only patient with followup of >9 months fulfilled the ACR 70 criteria at 20 months post-HSCT. CONCLUSION: In this series, autologous HSCT was safe and effective in inducing major clinical response and maintained significant benefit for 2 patients at 9 months and 20 months posttreatment, respectively. Sustained response did not occur for 2 of 4 patients. A regimen dose-response effect may exist, but the addition of TBI did not prevent disease relapse for 1 of the patients. More aggressive T cell depletion of the autograft, use of a myeloablative regimen, or use of an allograft may be necessary to decrease relapse rates.
9101496 Development of an instrument to measure knowledge in individuals with rheumatoid arthritis 1997 Apr OBJECTIVE: Education is an important component of community based rehabilitation programs for people with rheumatoid arthritis (RA). This study describes the development of a questionnaire to measure knowledge in this context. METHODS: Items were generated using focus group methodology and covered the domains of prognosis, pain management, medications, joint protection, energy conservation, exercise, and coping strategies. RESULTS: After extensive pretesting, the questionnaire was administered to 252 people with RA. The final 31 item questionnaire had acceptable internal consistency (Cronbach's alpha: 0.76, n = 185), test-retest reliability (r = 0.91, p < or = 0.001), content and construct validity. Sensitivity to change was confirmed in the context of a 6 week home based physiotherapy educational intervention. CONCLUSION: The RA knowledge questionnaire is a reliable, valid, and sensitive instrument for measuring the effect of a RA educational intervention.
10828838 Alterations in insulin-like growth factor binding protein-3 proteolysis and complex format 2000 Jun Increased concentrations of insulin-like growth factor (IGF) system components have previously been observed in rheumatoid arthritis (RA) and osteoarthritis (OA); however, disruption of the IGF axis and the implications for the disease process remain largely unaddressed. This study was undertaken to characterise the IGF binding protein (IGFBP)-3 proteolysis and complex formation systems in synovial fluid and to investigate changes in these systems in arthritic disease, and their impact on the availability of IGF. Western blotting or autoradiography of SDS gels was used to visualise IGFBP-3 or its proteolysis. IGF-I and IGFBP-3 concentrations were determined by radioimmunoassays and acid-labile subunit (ALS) was measured by ELISA. A shift in distribution of IGFBP-3 and IGF-I in RA and OA synovial fluids (RASynF, OASynF) and an associated increase in ALS suggested the presence of 150 kDa ternary complexes. IGFBP-3 proteolysis was decreased in RASynF and OASynF, but was apparent in size-fractionated fluid and resembled serum activity. The presence of serum-like inhibitors of IGFBP-3 proteolysis in RASynF was also demonstrated by the ability of this fluid, and 150 kDa fractions from its size fractionation, to inhibit IGFBP-3 proteolysis in the other synovial fluid. A marked disruption in the IGF system was observed, as considerably more IGF-I was retained in ternary complexes. We also classified the IGFBP-3 proteolysis system in synovial fluid and found it to be disturbed in RASynF and OASynF. These changes may be caused by an increased flux of circulatory proteins into synovial fluid, resulting from an inflammation-induced increase in vascular permeability. The net result in RA and OA would be a decrease in IGF availability in arthritic joints, and therefore loss of a potential anabolic stimulus. This disruption to the IGF axis would influence disease progression in RA and OA.
11206348 Distribution of double-negative (CD4- CD8-, DN) T subsets in blood and synovial fluid from 1999 Double-negative (CD4- CD8-) T (DNT) cells have been postulated to be potentially autoreactive. However, the role of DNT cells in rheumatoid arthritis (RA) has received limited attention. We investigated the distribution of DNT subsets in peripheral blood (PB) and synovial fluid (SF) from patients with active RA to determine whether these cells have relevance to RA. Two-colour flow cytometric analysis was performed to detect DNT cells in PB from 35 RA patients, 26 healthy controls and in SF aspirated from 19 inflamed rheumatoid joints. The subsets of DNT cells, i.e those expressing T cell receptor alphabeta (alphabeta DNT) or gammadelta (gammadelta DNT) were simultaneously examined. Our results showed that DNT cells constituted a very minor subset of PB lymphocytes. When expressed as a percentage of total lymphocytes, alphabeta DNT levels in normal individuals ranged from 0.27 to 2.08% (average 0.76%), while those of gammadelta DNT ranged from 1.02 to 11.42% (average 3.23%). Compared with normal individuals, RA patients had a similar distribution of alphabeta DNT cells in both PB and SF. However, RA patients had significantly lower levels of gammadelta DNT cells in PB than control subjects (1.38 +/- 1.08% vs 3.23 +/- 2.12%, p<0.05), while the levels of gammadelta DNT cells in SF of RA patients were higher than those in PB from RA patients and normal controls. The difference between PB and SF in RA was statistically significant (3.90 +/- 1.88% vs 1.38 +/- 1.08%, p<0.05). A higher level of gammadelta DNT in SF than their paired PB was consistently noted from nine available paired samples. Our findings suggest that gammadelta NT cells, but not alphabeta DNT cells, are probably relevant to RA. The lower percentage of circulating gammadelta DNT cells might have resulted from migration from the circulation into the synovium, suggesting a role for gammadelta DNT cells in the pathogenesis of rheumatoid synovitis.
11361208 A proposal for developing a large patient population cohort for longterm safety monitoring 2001 May This paper proposes the creation of an objectively acquired reference database to more accurately characterize the incidence and longterm risk of relatively infrequent, but serious, adverse events. Such a database would be maintained longitudinally to provide for ongoing comparison with new rheumatologic drug safety databases collecting the occurrences and treatments of rare events. We propose the establishment of product-specific registries to prospectively follow a cohort of patients with rheumatoid arthritis (RA) who receive newly approved therapies. In addition, a database is required of a much larger cohort of RA patients treated with multiple second line agents of sufficient size to enable case-controlled determinations of the relative incidence of rare but serious events in the treated (registry) versus the larger disease population. The number of patients necessary for agent-specific registries and a larger patient population adequate to supply a matched case-control cohort will depend upon estimates of the detectability of an increased incidence over background. We suggest a system to carry out this proposal that will involve an umbrella organization, responsible for establishment of this large patient cohort, envisioned to be drawn from around the world.
9235811 [RA-specific autoantibodies against a 68k antigen]. 1997 Mar Despite commonly applied clinical criteria, the early diagnosis of rheumatoid arthritis (RA) often remains difficult, thus delaying on suitable early treatment. In search for a test furthering the early and reliable diagnosis of RA, we have screened for novel disease specific autoantibodies. To this end proteins were isolated from synovial membranes and other tissues following a special protein purification protocol, and these were separated electrophoretically. Western blots were then used to screen sera of RA patients and of individuals suffering from other rheumatic diseases for antibodies to any of these proteins. The most prominent RA specific immunoreaction was with a 68k antigen, occurring in 110 of 167 RA patients (sensitivity is 66%). The antibody could also be identified in seronegative RA patients but not in healthy individuals (55 tested), in only 1 SLE patient of a group of 98 patients with other rheumatic diseases and in 1 out of 22 HIV patients, resulting in a specificity of 99%. Moreover, the anti-68k antibody could be correlated with a more severe course of RA. 13 out of 20 anti-68k positive RA patients (58%) had subcutaneous nodules, while only 2 out of 11 anti-68k negative (20%) did. The mean sedimentation rate of these antibody positive patients was 51 mm/h and 26 mm/h for the negative respectively. The 68k antigen was shown to be present in all human tissues investigated and is probably ubiquitously expressed. It is either located in the endoplasmatic reticulum or cytoplasm or both. Its isoelectric point is 5.1. It proved to be O-glycosylated and contains only one or a few sugar residues as the untreated and the deglycosylated antigen identical electrophoretical mobilities. The patient derived anti-68k antibodies were directed against the sugar residue: deglycosylation of the antigen completely abolished its immunoreactivity. N-acetylglucosamine competes with the antibody for binding the 68k antigen. The antigen physicochemical data of the 68k antigen argue against identity with one of the autoantigens in this molecular mass range already known to be associated with RA or other autoimmune diseases. It is neither identical to the 62k human antigen (EBNA-1) nor to RA33 (A2hnRNP), the 50k Sa antigen or the Hsp70 class of heats-hock proteins. It is argued that the particular method of protein purification applied in combination with separation via SDS-PAGE in the presence of urea, made it possible to detect a hitherto unidentified antigen. Considering the striking disease specificity of the anti-68k antibody it is now worthwhile to look for corresponding autoreactive T cells in order to analyse its role in the pathogenesis of RA.
11036828 Expression of the precursor of secretoneurin, secretogranin II, in the synovium of patient 2000 Oct OBJECTIVE: Secretoneurin (SN) is a neuropeptide that is chemotactic for mononuclear cells and it has been suggested to be involved in the mediation of pain; there is also evidence that SN is involved in the inflammation process. As secretogranin II (SGII) is the precursor of SN, we investigated expression of SGII mRNA and SN protein in the synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Snap frozen synovial tissue specimens from 12 patients with RA and 11 patients with OA were examined. RNA was isolated and cDNA copied by reverse transcription. The expression of SGII was determined by polymerase chain reaction and in situ hybridization (ISH). SGII expressing cells were compared with CD68 positive cells stained by immunohistochemistry. SN protein was also detected by immunohistochemistry. RESULTS: A 524 bp SGII-specific fragment could be amplified by PCR from the cDNA of all specimens. ISH showed scattered expression of SGII in both RA and OA synovial tissue; its expression pattern was characterized by positive staining for SGII in both the lining and the sublining layer. Immunohistochemical double labeling with anti-CD68 antibodies revealed expression of SGII in CD68 negative, fibroblast-like cells, whereas CD68 positive macrophages did not. In RA and OA, the SGII staining by ISH was positive with a diffuse staining throughout the entire synovial tissue. SN protein expression was scattered in RA but more intense in OA synovium. CONCLUSION: The expression of SGII mRNA in RA and OA synovial fibroblasts clearly supports the hypothesis that SN is involved in the synovial tissue inflammation in both diseases. The significant lower SN expression in RA could be due to an inhibitory mechanism with respect to the SN levels in synovial fluid. SN might be involved in the modulation of afferent nerve transmission and therefore might play a role in the sensation of pain, especially in patients with OA.
9676755 Is there an optimal time to administer methotrexate in the treatment of rheumatoid arthrit 1998 Jul OBJECTIVE: To determine the optimal time to administer methotrexate (MTX) in rheumatoid arthritis (RA). METHODS: In a crossover study 23 patients were administered MTX intramuscularly at either 10 AM or 6 PM. A 2 week interval separated the 2 injections. MTX concentrations were measured using a fluorescence polarization immunoassay. Pharmacokinetic variables were estimated using a Bayesian approach. The morning and evening schedules were compared using analysis of variance to determine the optimal time of injection. RESULTS: No statistical difference was found in the pharmacokinetics of MTX according to hour of injection. A difference in the creatinine clearance, however, was observed in the samples obtained at noon and 8 PM, but clearance of MTX was unchanged. CONCLUSION: Pharmacokinetic variables suggest that MTX can be administered either in the morning (10 AM) or evening (6 PM) in the treatment of RA.
10583116 Hypersensitivity to gold in gold sodium thiomalate-induced dermatosis. 1999 Oct Gold compounds are widely used in the treatment of rheumatoid arthritis. Mucocutaneous side-effects leading to the discontinuation of medication are common with these drugs. We investigated whether allergic mechanisms are involved in dermatosis induced by gold sodium thiomalate (GSTM). Thirteen gold dermatosis patients, 15 arthritis patients without any side-effects from GSTM and 11 healthy controls participated in the study. Venous blood lymphocytes from these subjects were cultured with GSTM and gold sodium thiosulphate (GSTS) in the lymphocyte proliferation test (LPT). In some cases, interferon-gamma-producing cells were enumerated in vitro (T-cell ELISpot). The subjects were also patch-tested with GSTM and GSTS. The LPT to either GSTM, GSTS or both was positive in 12 of 13 patients with gold dermatosis. In the arthritis patient group without side-effects from gold, the LPT gave two false-positive results and in the healthy control group the LPT was falsely positive with one subject. T-cell ELISpot was positive in four of six gold dermatosis patients and negative in the arthritis and healthy control groups. Only one patient who also developed contact dermatitis from gold jewellery was positive to gold in the patch test. These results indicate that gold dermatosis is mediated, at least in part, by allergic mechanisms and that the LPT is of value in the diagnosis of gold dermatosis.
11222499 A potential role for protein tyrosine kinase p56(lck) in rheumatoid arthritis synovial flu 2001 Mar Rheumatoid arthritis (RA) synovial fluid (SF)-T lymphocytes appear relatively inactive in situ and respond only weakly to diverse stimuli ex vivo. To characterize the molecular defects underlying this hyporesponsiveness we analyzed the expression level of several proteins involved in TCR-proximal signal transduction. As compared to peripheral blood (PB)-T lymphocytes, SF-T cells from some (but not all) of the patients analyzed expressed lower levels of TCRalphabeta, CD3epsilon, TCRzeta, p56(lck) and LAT, while p59(fyn), phospholipase C-gamma1 and ZAP-70 expression was unaltered. Semi-quantitative analysis of T cells from several patients revealed that the degree of TCRzeta chain and p56(lck) modulation correlated statistically significantly with the level of SF-T cell hyporesponsiveness. The differential reactivity of p56(lck) specific monoclonal and polyclonal antibodies in SF-T but not PB-T lymphocytes indicated that p56(lck) modulation consists of a conformational change rather than loss of expression. Our results indicate that multiple signaling molecules can be modulated in RA SF-T cells and show for the first time a direct quantitative correlation between T cell hyporesponsiveness and modulation of TCRzeta and of p56(lck), a critical protein tyrosine kinase required for T cell activation.
10769420 Corticotropin releasing hormone (CRH) promoter polymorphisms in various ethnic groups of p 2000 Feb The regulatory region of the corticotropin releasing hormone (CRH) is highly conserved and plays a crucial role in the response of the organism to stress. Release of CRH initiates a cascade of events leading to the release of cortisone and the regulation of inflammatory and immune events. OBJECTIVE: Since it has been postulated that the impaired corticotropin releasing hormone (CRH) response to stress in patients with rheumatoid arthritis (RA) has a genetic basis, we investigated the distribution of CRH alleles in a cohort of UK patients as well as in South African RA patients. METHODS: Restriction fragment length polymorphism of PCR amplified DNA products of the CRH promoter. We compared the allele frequencies in the RA patients with the respective healthy control population described previously. RESULTS: As in the control populations we found two biallelic polymorphic sequences (named A1 and A2 and B1 and B2, respectively) in the CRH promoter which could be assigned to compound alleles. The A2B1 compound allele was protective against development of RA in a large group of UK Caucasoid patients (p = 0.03; odds ratio 0.43, 95% confidence interval 0.21-0.88). In contrast, A1B1 was positively associated with RA in a cohort of black South African RA patients (p = 0.05; odds ratio 1.78, 95% confidence interval 1.01-3.15). CONCLUSION: Taken together, these findings support the hypothesis that CRH promoter polymorphism represents a new genetic marker for RA susceptibility and may prove useful for the prediction of RA risk in the future when further genetic and environmental risk factors are determined.
9338928 Magnetic resonance imaging and axial involvement in spondylarthropathies. Delineation of t 1997 Jul We used magnetic resonance imaging in a prospective cross-sectional study to evaluate the components of axial involvement in spondylarthropathies, to determine whether the entire intervertebral disk is an enthesis and to gauge how useful this imaging technique is in detecting enthesitis of the spine. Thirty-one patients with spondylarthropathies and 14 controls with mechanical spinal disease were included. Images of the thoracic and lumbar spine were obtained using plain radiography, radionuclide bone scanning, and magnetic resonance imaging (sagittal sections, T1-weighted sequences before and after gadolinium injection and fat saturation and T2-weighted sequences). Magnetic resonance imaging signal abnormalities reflected inflammation and hypervascularization of the subchondral bone underlying the affected entheses (low signal enhancing after gadolinium and fat saturation on T1 images, high signal on T2 images). These abnormalities were often visible early in the disease process, at a time when there were not yet any clinical manifestations or radiographic or bone scan changes. In addition to showing involvement of the classic spinal entheses, magnetic resonance imaging also demonstrated evidence of inflammation and hypervascularization of the central part of the vertebral endplates and intervertebral disks, confirming that the center of the disk is an enthesis and that inflammatory enthesitis is the mechanism underlying at least some cases of discitis seen in patients with spondylarthropathies.
9182883 Restricted expression of Fc gammaRIII (CD16) in synovium and dermis: implications for tiss 1997 Jun Interactions between immune complexes and immunoglobulin Fc receptors may contribute to inflammation in RA. Previous studies suggested that Fc gammaRIII (CD16) may be preferentially expressed in diseased synovial intima. The distribution of immunoreactive Fc gammaRIII was examined in normal fetal limb tissues, and both normal and selected abnormal samples of adult synovium and skin. In fetal limbs at 10-14 weeks gestation Fc gammaRIII was restricted to synovial intima. In normal adult synovium Fc gammaRIII was restricted to intimal cells. In inflamed synovia differential expression of Fc gammaRIII in the intima was less consistent. In both fetal and adult synovium Fc gammaRIII was largely restricted to cells expressing CD45 (leucocyte common antigen). Staining for Fc gammaRIII was, however, occasionally associated with CD45 intimal cells in fetal synovium. In both fetal and adult tissues cell membrane Fc gammaRIII was frequently closely associated with complement decay-accelerating factor (DAF), which is present on intimal fibroblasts and extracellular matrix. Fc gammaRIII expression was minimal in normal forearm dermis, but widespread on CD45+ cells in skin exposed to mechanical stress. In skin containing rheumatoid nodules, Fc-gammaRIII was preferentially expressed on palisading macrophages. These observations indicate that expression of Fc gammaRIII on macrophages may be involved in the susceptibility of connective tissues to immune complex-induced damage in RA. Colocalization of Fc gammaRIII and DAF in synovium may indicate an unrecognized functional interrelationship.
9297067 [Pathogenesis of rheumatoid arthritis]. 1997 Jun 15 BACKGROUND: Despite ongoing intensive research using sophisticated new molecular tools and methods, the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) is still not completely understood. HYPOTHESES: In this paper the two favorite hypotheses of the pathogenesis of rheumatoid arthritis currently discussed are introduced and compared. Hypothesis 1 is focussing on the central role of the T cells and T cell dependent phenomena in the pathogenetic scenario of RA. In contrast, hypothesis 2 stresses the role of altered synovial fibroblasts and their specific features critical for the destruction of inflamed joints. Both hypotheses are thoroughly discussed and suggestions for further research activities are made. CONCLUSION: Insights in the pathogenesis of RA provide options to develop new therapeutic strategies aimed at the inhibition of pathogenetic relevant processes.
9627010 Progressive polyarthritis induced in BALB/c mice by aggrecan from normal and osteoarthriti 1998 Jun OBJECTIVE: To find an "unlimited" source of antigenic material (aggrecan) for arthritis induction in BALB/c mice; to analyze the specificities of immune reactions to aggrecan and type II collagen in 2 arthritis-susceptible murine strains, BALB/c mice for proteoglycan (aggrecan)-induced arthritis and DBA/1j mice for collagen-induced arthritis; to compare the histopathologic features of arthritis induced by purified aggrecans or total extracts of osteoarthritic (OA) cartilage; and to determine arthritis susceptibility in various BALB/c colonies. METHODS: Aggrecans from total extracts of human fetal, normal adult, OA, and rheumatoid cartilage samples and from osteophytes were isolated, purified by gradient centrifugation, deglycosylated, characterized, and tested for arthritis induction. Purified type II collagen and salt-soluble collagens from OA cartilage were denatured, stromelysin treated, and used for immunization and arthritis induction in arthritis-susceptible (DBA/1j and BALB/c) murine strains. RESULTS: Chondrocytes from OA cartilage synthesize predominantly fetal-type aggrecan, which is the most efficient antigenic material for arthritis induction in BALB/c mice. The critical autoimmune/arthritogenic T cell epitopes of aggrecan are located in the G1 domain. Although most of the aggrecan molecules are heavily degraded and lost from OA cartilage, the G1 domain-containing fragments accumulate in OA cartilage. The amount of G1-containing fragments is approximately twice as much in OA than in normal adult articular cartilage, and the arthritogenic epitope(s) remains intact in G1-containing fragments retained in cartilage. Thus, total extracts of OA cartilage (without additional purification), if deglycosylated appropriately, can be used as arthritogenic material in BALB/c mice. CONCLUSION: Predominantly G1 domain-containing fragments of aggrecan accumulate in OA cartilage, and these are the fragments which induce arthritis in BALB/c mice. Arthritis induction is highly specific for aggrecan epitopes and dictated by the genetic background of the BALB/c strain.
10483693 [Therapy of degenerative diseases of the musculoskeletal system with South African devil's 1999 Extracts of the secondary tubers of Devil's Claw (Harpagophytum procumbens) are recommended for the supportive treatment of degenerative painful rheumatism. There was observed an improvement of motility and a reduction of pain sensation in several clinical studies. Pharmacological experiments have shown analgesic, antiphlogistic and antiinflammatory actions. Most important constituents are iridoid glycosides, which are supposed to contribute mainly to the observed effects. However, the entire extract has to be considered as active ingredient.