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ID PMID Title PublicationDate abstract
15789633 [Histogenic characterization of the cells forming RA pannus]. 2005 Jan OBJECTIVE: This work aims to clarify the histogenesis of the cells forming RA pannus: the pannocytes. METHODS: 15 patients with seropositive RA; 5 controls with post-traumatic knee effusion and 5 with OA knee effusion were included in the study. Synovial tissues and fluids, collected during diagnostic arthrocentesis, were used as a source of cells to be cultured. Viable staining and cytocentrifugation were performed. Cell phenotype was investigated by immunofluorescence assays after different culture periods. Cells were also studied by immunohistochemistry to determine the presence of CD5, CD68:KP-1, CD68:PG-M1, vimentin, cytokeratin, a-SM-Actin. RESULTS: Cells derived from RA samples were sub-divided into two population of lymphocyte-like and macrophage-like cells. Phenotypical characteristics of the first one were analysed after 6 days of culture and suggested they were T lymphocytes. The other population could grow in vitro for undefined time resembling the neoplastic-like proliferation previously described for pannocytes. Phenotypic characterization excluded that these cells were lymphocytes, monocyte-macrophages, fibroblasts, myofibroblasts, endothelial cells or keratinocytes. On the contrary, immunohistochemistry demonstrated that 100% of pannocytes were vimentin positive and 75% of these cells expressed also CD68:KP-1. CONCLUSIONS. The results exclude that pannocytes originate from monocyte-macrophages or from fibroblasts, but strongly support the hypothesis that they belong to the family of primitive embryonal connective tissue-forming cells (residue of the primitive mesenchymal tissue).
16463694 [Activity of N-acetylo-beta-hexosamninidase in joint fluid from knee and serum of patients 2005 N-acetyl-beta-hexosoaminidase (Hex) is a lysosomal enzyme which releases N-acetylaminohexose from non reducing end of glycosaminoglycans, glycoproteins and glycolipids, taking part in degradation of these substances. It is not known what role Hex plays in the degradation of joints in rheumatoid arthritis and osteoarthritis. The aim of our work was evaluation of Hex activity in synovial fluid and serum of patients with rheumatoid arthritis and osteoarthritis. The investigation was performed on material taken from 28 patients with rheumatoid arthritis aged 22-74 years with III or IV stage of disease and 26 patients with osteo-arthritis aged 41-75 years. The synovial fluid was collected from the knee joint during puncture. Hex activity was also determined in serum of healthy people at the age 25-40 years which constitute a control group. Hex activity was determined by the method of Chatterjee et al. modified by Zwierz et al. The concentration of Hex activity in synovial fluid of patients with rheumatoid arthritis was 15.2 nmol/ml/min and 3-4 times excedeed the serum value in these patients. In osteoarthrosis patients Hex concentration in synovial fluid was 6.15 nmol/ml/min. In serum of all investigated groups, concentration of Hex activity was 4.0-4.7 nml/ml/min. The specific activity of Hex (calculated as a constant amount of protein) in synovial fluid of patients with rheumatoid arthritis was significantly higher than in serum of these persons (p<0.017 and 0.014 respectively).
17080519 Metabolic syndrome and subclinical atherosclerosis in rheumatoid arthritis. 2006 Dec OBJECTIVE: We assessed whether features of metabolic syndrome (MetSyn) were risk factors for subclinical atherosclerosis independent of previously identified determinants of cardiovascular disease in 74 patients with rheumatoid arthritis (RA). We further evaluated the clinical utility of currently recommended MetSyn definitions in the identification of RA patients with subclinical atherosclerosis. METHODS: We investigated the associations of MetSyn features and MetSyn definitions with ultrasonographically determined common carotid artery intima-media thickness (CCA-IMT) and plaque, with adjustment for age, radiographic scores (cumulative inflammation), polymorphonuclear cell counts (current inflammation), or hypothyroidism. RESULTS: The Quantitative Insulin Sensitivity Check Index (QUICKI) (partial R = -0.24 to -0.26, p = 0.04 to 0.02), log triglycerides (partial R = 0.23 to 0.30, p = 0.05 to 0.01), and systolic blood pressure (partial R = 0.22 to 0.30, p = 0.06 to 0.002) were consistently associated with the log CCA-IMT. Log triglycerides (OR 1.04, 95% CI 1.01-1.08, p = 0.02) and the QUICKI (OR 0.22, 95% CI 0.05-0.91, p = 0.03) were associated with plaque after adjusting for cumulative inflammation. Hypertension (blood pressure > or = 130/85 mm Hg or drug treatment for hypertension) was consistently associated with CCA-IMT (p = 0.05 to 0.0003) and plaque (p = 0.03 to 0.006). The WHO-defined MetSyn was associated with CCA-IMT (p = 0.08 to 0.04) but not with plaque (p > or = 0.1). The National Cholesterol Education Program-defined MetSyn was not associated with CCA-IMT or plaque (p > or = 0.3). CONCLUSION: In this RA cohort, the MetSyn features of hypertension, insulin resistance, and triglycerides were risk factors for subclinical atherosclerosis, independent of previously identified determinants of cardiovascular disease. Individual MetSyn features were more strongly associated with subclinical atherosclerosis than were currently recommended MetSyn definitions.
15836009 The case of tumour necrosis factor-alpha inhibitors in the treatment of rheumatoid arthrit 2005 BACKGROUND: Treatment with tumour necrosis factor (TNF)-alpha inhibitors offers promising new opportunities to improve the health-related QOL of patients with rheumatoid arthritis (RA) in Denmark. As of September 2003, two such compounds -- infliximab and etanercept -- were registered for use by patients with RA. These drugs have shown the ability to reduce disease activity and to slow down or halt the development of new joint damage in otherwise treatment-resistant patients with RA. The acquisition cost of the drugs is high, with 1 year of treatment costing euros 9000-12,000 per patient. OBJECTIVE: The aim of this study was to assess the potential impact on the Danish healthcare budget of prescribing infliximab or etanercept to patients with RA. METHOD: Two treatment implementation scenarios were investigated. In the progressive scenario, all patients newly diagnosed with RA were offered TNFalpha inhibitors as the drug of first choice. In the modest scenario, only patients with insufficient disease suppression by conventional therapy with disease-modifying anti-rheumatic drugs (DMARDs) were offered TNFalpha inhibitor therapy. The budget impact analysis, which was part of a Danish health technology assessment of TNFalpha inhibitors, focused on the number of patients offered treatment during a 5-year period and resource use related to drug and staff costs. Simple sensitivity analyses assessed the consequences of changing the drug dosage, the number of patients offered treatment and the rate of treatment cessation. RESULTS: The results suggested that both implementation strategies would impose additional costs per year on the Danish healthcare service, in the range of euros 67-188 million for the progressive scenario and euros 17-49 million for the modest scenario (price level August 2002). These costs represent between half and up to five times the amount currently used on treating patients with RA. CONCLUSION: This analysis suggests that the introduction of TNFalpha inhibitors into the treatment regimen of patients with RA could pose a considerable financial burden on the Danish healthcare system.
15809947 Precoated femoral component with proximal and distal centralizers: results at 5 to 12 year 2005 Apr One study, confounded by the use of crystalline polyethylene and ceramic heads, reported a high rate of early failure of a precoated femoral component with proximal and distal centralizers. The present study reports the prospective clinical and radiographic results, and 10-year survival data of 166 consecutive hybrid total hip arthroplasties using this femoral component. An A or B cement grade was obtained in 93% of hips. At a mean follow-up time of 7 years (range, 5-12 years), there were only 4 (2.4%) femoral failures. Ten-year survival of this component was 95% (confidence interval, 94%-99%). The rate of radiographic failure and revision of this component implanted with conventional polyethylene and cobalt chrome heads is similar to that reported with other "modern" femoral components.
15899034 Small GTP-binding protein Rho-mediated signaling promotes proliferation of rheumatoid syno 2005 Rho is a major small GTP-binding protein that is involved in the regulation of various cell functions, including proliferation and cell migration, through activation of multiple signaling molecules in various types of cells. We studied its roles in synovial fibroblasts (SFs) in patients with rheumatoid arthritis (RA) and clarified its relevance to RA synovitis, with the following results. 1)We found that the thrombin receptor was overexpressed on RA synovial fibroblasts (RA SFs) and that thrombin induced a marked proliferation and progression of the cell cycle to the S phase in these cells. 2)We also found that thrombin efficiently activated Rho. 3)Rho activation and proliferation and the progression of the cell cycle to the S phase were completely blocked by p115RGS (an N-terminal regulator of the G-protein signaling domain of p115RhoGEF) and by the C-terminal fragments of Galpha13 (an inhibitor of the interaction of receptors with G13). 4)Thrombin induced the secretion of IL-6 by RA SFs, but this action was blocked by p115RGS or Galpha13. Our findings show that the actions of thrombin on the proliferation of RA SFs, cell-cycle progression to the S phase, and IL-6 secretion were mainly mediated by the G13 and RhoGEF pathways. These results suggest that p115RGS and Galpha13 could be potent inhibitors of such functions. A rational design of future therapeutic strategies for RA synovitis could perhaps include the exploitation of the Rho pathway to directly reduce the growth of synovial cells.
17144392 Polymorphism of HLA-DR and HLA-DQ in rheumatoid arthritis patients and clinical response t 2006 Oct OBJECTIVE: To investigate the frequency and distribution of DRB1 and DQB1 alleles in Patients with rheumatoid arthritis (RA) and analyze the relationship between clinical response to methotrexate (MTX) and the HLA-DR and HLA-DQ genotypes in these patients. METHODS: In this case-control study, the HLA-DRB1 and HLA-DQB1 polymorphism in 91 RA patients and 91 healthy controls was done using polymerase chain reaction and sequence specific primers. RESULTS: There was no statistical difference in frequencies of HLA-DRB1*03, DRB1*04, DRB1*07, DRB1*10, DRB1*11, DRB1*12, DRB1*13, DRB1*14, DRB1*15 and DRB1*16 genotypes between patients and controls. However, DRB1*01 was found to be significantly more common (p=0.015) in RA patients compared to controls. HLA-DRB1*15 was more common in patients (43.5%) compared to controls (30.8%) but results were not significant. HLA-DRB1*08 and DRB1*09 were present in negligible number in patients as well as controls while HLA-DRB1*12 was conspicuously absent in controls. Similarly, DQB1*06 was also significantly more common (p = 0.01) among the patients compared to healthy control subjects, while there was no statistical difference in the frequencies of DQB1*02, DQB1*03, DQB1*04 and DQB1*05 among the cases and the controls. RA susceptibility in most patients appeared to be associated with the HLA-DRB1*01/DQB1 *06 genotype. Regarding association between HLA-DR or HLA-DQ genotype and clinical response to methotrexate (MTX), the data showed that with the exception of HLA-DRB1*03, there appears to be no association between the particular subtypes of HLA-DR and HLA-DQ. HLA-DRB1*03 was significantly-more common among non-responders to MTX alluding to the possibility that another genes responsible for MTX metabolism, might be in linkage disequilibrium with HLA-DRB1*03 in the Pakistani population, thereby making such individuals non-responsive to MTX-therapy. CONCLUSION: RA susceptibility in most Pakistani patients is associated with the HLA-DRB1*01/DQB1*06 genotype. HLA-DRB1*03 was found to be significantly more common among non-responders to MTX treatment suggesting that Pakistani patients with this genotype are less likely to benefit from MTX.
15485996 Expression and localisation of the new metalloproteinase inhibitor RECK (reversion inducin 2005 Mar OBJECTIVE: To assess the expression and localisation of the new metalloproteinase inhibitor RECK, an inhibitor of matrix metalloproteinase-14 (MMP-14) secretion and activity, in the synovial membrane of patients with rheumatoid arthritis (RA). METHODS: RECK expression in synovium samples from patients with RA, osteoarthritis (OA), and "trauma" were studied by quantitative real time reverse transcription-polymerase chain reaction (Q-PCR). RECK mRNA levels were compared with those of the enzyme MMP-14. RECK expression on cryostat sections of synovium was disclosed by goat-antihuman RECK monoclonal antibody. RECK protein was detected on synovial cryostat sections and measured by western blotting. RECK expression on macrophages was investigated by double staining of CD68 and RECK on cryostat sections and characterised by confocal microscopy. RECK expression on RA monocytes or normal monocytes was further investigated by FACS analysis. RESULTS: RECK expression in the synovial membrane of patients with RA was significantly lower than in OA and controls. MMP-14 mRNA levels were not significantly different between the three groups. In RA synovium, RECK protein was expressed mainly in the lining layer but also by macrophages around blood vessels. Fibroblasts and about 50% of the CD68 positive macrophages expressed RECK. In CD68 positive macrophages, RECK was only expressed in secretory granules and not on the membrane. The same pattern was found in M-CSF cultured macrophages of patients with RA and controls. In contrast, synovial fibroblasts showed a diffuse membrane expression within the synovium similar to cultured RA fibroblasts. RECK expression was low on the membrane of monocytes according to FACS analysis. CONCLUSION: The new MMP inhibitor RECK is expressed in synovial membranes of RA, OA, and controls. RECK mRNA is lowest in RA synovial membranes. In contrast with fibroblasts, macrophages in the synovium express RECK only cytoplasmically and not on their membrane.
16818155 Arthroscopic-assisted tibiotalocalcaneal arthrodesis using an intramedullary nail with fin 2006 Jul Arthroscopic arthrodesis of the ankle has become popular because of the reduced invasiveness of the procedure and good bony consolidation compared with conventional open techniques. However, arthroscopic arthrodesis of the subtalar joint has not been as universally accepted. Rheumatoid arthritis frequently involves the talocalcaneal joint in addition to the tibiotalar joint. In such cases, simultaneous fixation of both tibiotalar and talocalcaneal joints is desirable. We undertook arthroscopic-assisted arthrodesis of the tibiotalocalcaneal joint using intramedullary nails with fins for a 76-year-old man with rheumatoid arthritis. Although the patient presented with poor skin condition and osteoporotic bone due to long-term use of systemic corticosteroids, weight bearing was allowed 2 weeks after the surgery. Solid fusion of the tibiotalocalcaneal joint occurred without any complications. Given the twin benefits of reduced invasiveness and secure fixation, this method should be considered for patients requiring both tibiotalar and talocalcaneal joint fusion, when a more extensive surgical exposure would be more risky.
16595373 JC virus in the Irish population: significant increase of genotype 2 in immunocompromised 2006 Feb The human polyomavirus JC virus (JCV) is ubiquitous and can be shed in the urine of more than 40% of the healthy population. Amplification and sequencing of JCV from urine has allowed a distinctive map of the distribution of JCV genotypes worldwide. To define the frequency of JCV urinary excretion and genotype distribution in Ireland, urines from 121 healthy individuals and from 94 immunocompromised individuals (human immunodeficiency virus [HIV]-positive patients and rheumatoid arthritis patients) were collected. JCV DNA was detected by polymerase-chain reaction (PCR) with subsequent nucleotide sequencing of a fragment of the major capsid protein (VP1). JCV was detected in 20.7% of healthy individuals and was found significantly more often in the urine of HIV-positive patients (54.2%; P < .001) and rheumatoid arthritis patients (54.4%; P < .001). In healthy Irish individuals genotype 1 was the predominant genotype in 62.5%, followed by genotype 4 in 16.7% and genotype 2 in 12.5%. In contrast, genotype 2 was significantly more often isolated from the urine of both HIV-positive patients (60%) and rheumatoid arthritis patients (54.4%; P < .01). The pattern of genotype distribution among healthy Irish individuals is in agreement with data reported from other European countries, whereas the overall level of JCV urinary excretion is lower. Previous studies have found genotype 2 significantly more often in cerebrospinal (CSF) samples of patients with progressive multifocal leukoencephalopathy (PML). Here the authors report an increased frequency of genotype 2 in urine samples of immunocompromised non-PML patients. This finding further underlines the hypothesis that there could be biologic differences between JCV genotypes.
16465614 Targeted therapy in rheumatoid arthritis. 2006 Jan The approach of targeting cytokines has dramatically improved the success in the treatment of rheumatoid arthritis (RA). The blocking of tumor necrosis factor (TNF)-alpha or interleukin (IL)-1 is well established in clinical practice, but a lack or loss of clinical response still occurs in up to 30% of RA patients. Therefore, enhanced efforts must be made to develop new strategies to disrupt the inflammatory process and to inhibit synovitis and joint destruction. In this respect, the blocking of IL-6 receptor with tocilizumab, the prevention of costimulatory T cell signals by abatacept, or targeting B cells with rituximab look promising in clinical trials. Furthermore, blocking intracellular signal transduction broadens the spectrum of targeted therapy. This article reviews recent clinical aspects of established anti-cytokine therapies and gives an insight into the experimental and clinical development of new specifically acting drugs.
16755245 Aggravation of laryngeal rheumatoid arthritis after use of a laryngeal mask airway. 2006 Jun We report a case of aggravation of laryngeal rheumatoid arthritis (RA) after the use of a laryngeal mask airway (LMA). The patient was a 55-year-old woman with severe RA who underwent wrist arthrodesis under general anesthesia using a size 3 LMA. A few days after the operation, she reported hoarseness. Inflammation of the arytenoid region and vocal cord immobility were observed by fiberoptic nasolaryngoscopy. Vocal function returned to normal by postoperative day 42 in response to prednisolone therapy. In this case, stridor was misdiagnosed preoperatively, and postoperative symptoms and local findings were probably caused by aggravation of laryngeal RA resulting from substantial compression of the arytenoid region by the LMA. For patients with RA referred for surgery, a careful search for cricoarytenoid arthritis is essential, particularly in those with laryngeal stridor, because it may be aggravated after general anesthesia.
15851377 FK506 enhances triptolide-induced down-regulation of cyclooxygenase-2, inducible nitric ox 2005 Mar 29 OBJECTIVE: To explore the effects of FK506 on the inhibition of cell proliferation and the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and their products PGE subset2 and NO in TNF-alpha-stimulated human rheumatoid arthritis synovial fibroblasts (RASF) treated with triptolide (TP), and to study the mechanisms involved when combining FK506 and TP in RA therapy. MATERIALS AND METHODS: RASF used in the experiments were obtained from the synovial tissue of patients with RA before being cultured. RASF were pretreated with FK506 (10 approximately 1000 nM) for 2 hours before being stimulated with TNF-alpha (20 ng/ml) in the presence or absence of TP (10 ng/ml) . RASF proliferation was determined by [3 supersetH]-TdR incorporation. Production of PGE subset2 and NO in culture supernatants of RASF was detected by competitive ELISA and enzymatic reduction of nitrate, respectively. Expressions of COX-2 and iNOS mRNA in RASF were analyzed by semi-quantitative RT-PCR. Expressions of COX-2 and iNOS protein were estimated by Western-blot and a cellular enzyme immunoassay. NFkappaB activity in whole-cell extract of treated RASF was also measured using an ELISA-based method. RESULTS: Neither FK506 nor TP at a lower concentration (10 ng/ml) affected TNF-alpha-induced COX-2 and iNOS expressions or PGE subset2 and NO productions in synovial cells. Combined treatment of FK506 and a lower concentration of TP (10 ng/ml) reduced both COX-2 and iNOS mRNA and protein expression, and correspondingly reduced PGE subset2 and NO produced by synovial fibroblasts. This effect was highly correlated with FK506 concentration (10 approximately 1000 nM). NFkappaB activity in TNF-alpha-stimulated synovial cells was suppressed more profoundly by FK506 plus TP (10 ng/ml) than by TP (10 ng/ml) alone. However, no change was observed regarding the inhibition of synovial cell proliferation after combined treatment of FK506 and TP. CONCLUSION: FK506 enhanced TP-mediated down-regulation of COX-2 and iNOS as well as their products PGE subset2 and NO in human TNF-alpha-stimulated RASF by more profoundly suppressing the activity of NFkappaB.
16519117 [An 80-year-old woman with progressive stroke, who had rheumatoid arthritis and antiphosph 2006 Feb We report an 80-year-old woman who had rheumatoid arthritis and antiphospholipid syndrome. She was treated for rheumatoid arthritis since her thirties. At 76 years of age, she was diagnosed antiphospholipid syndrome serologically. She felt It. limb weakness and dysarthria and was admitted to the hospital on July 18, 2003. The brain MRI showed T2 hyperintensity signal on the rt. pre-central lobe. She was treated by the argatroban, edaravone, glycerol, and aspirin. However, she became bedridden and fed by NG-tube because her symptoms progressed in spite of the therapy. Progression of stroke stopped by adding heparin at last. After that, she repeated pneumonia. She was found dead on the bed August 2, 2003. The patient was discussed in a CPC. The chief discussant arrived at a conclusion that the cause of infarction was angitis due to rheumatoid arthritis. Other possibilities were multiple thrombus due to antiphospholipid syndrome, amyloid angiopathy, and atherosclerotic infarction. Post-mortem study revealed sputum obstruction in her bronchus, string deposition in her organs. The brain showed infarction on the rt. pre-central lobe. There were multiple thrombus in the leptomeningeal artery, but few atherosclerotic changes of the small arteries. Amyloid didn't deposit in the brain artery and the parenchyma. Pathologist concluded that her infarction was induced with multiple thrombus due to antiphospholipid syndrome.
15770481 In vivo expression of inflammatory cytokine receptors in the joint compartments of patient 2006 Feb To test a hypothesis of compartmentalized pathogenesis of different types of arthritis, namely inflammatory arthritis (IA) and osteoarthritis (OA), synovial and cartilage biopsies were examined for the expression of TNF and IL-1 receptors. In cartilage, we found constitutive expression of all receptors in normal tissues, and decreased expression of signal-transducing receptors in pathological chondrocytes. In synovium, there was a lower expression of signal-transducing receptors in cases of OA compared to those of IA. In OA, the three signal-transducing receptors were more abundantly expressed in cartilage, while in IA they were mainly present in synovial tissue (TNFRp75 being expressed more than p55). IL-1 decoy receptor type II was low or absent in synovial tissues, but present in cartilage. The increased expression of TNFRp75 and IL-1RI in OA cartilage, compared to IA, in addition to the abundant local cytokine production, strengthens the hypothesis of autocrine/paracrine action by inflammatory cytokines in the pathogenesis of cartilage damage.
16272275 Hypoxia regulates macrophage functions in inflammation. 2005 Nov 15 The presence of areas of hypoxia is a prominent feature of various inflamed, diseased tissues, including malignant tumors, atherosclerotic plaques, myocardial infarcts, the synovia of joints with rheumatoid arthritis, healing wounds, and sites of bacterial infection. These areas form when the blood supply is occluded and/or unable to keep pace with the growth and/or infiltration of inflammatory cells in a given area. Macrophages are present in all tissues of the body where they normally assist in guarding against invading pathogens and regulate normal cell turnover and tissue remodeling. However, they are also known to accumulate in large numbers in such ischemic/hypoxic sites. Recent studies show that macrophages then respond rapidly to the hypoxia present by altering their expression of a wide array of genes. In the present study, we outline and compare the phenotypic responses of macrophages to hypoxia in different diseased states and the implications of these for their progression and treatment.
16075756 Regular expression of discoidin domain receptor 2 in the improved adjuvant-induced animal 2005 Jun OBJECTIVE: To investigate the expression of discoidin domain receptor 2 (DDR2) of fibroblast-like synovial cells in improved adjuvant-induced animal (AIA) model for rheumatoid arthritis (RA) and to provide evidence for DDR2's antagonist use clinically. METHODS: AIA was modified by administrating 0.1 mL of complete Freund's adjuvant (CFA, mixed with 5 mg Bacillus Calmette-Guerin vaccine/mL) into rats' right hind paws and 0.125 mL tumor necrosis factor-alpha (2 U/mL) into right ankles and subpatellar fatty tissue. The expression of DDR2 in fibroblast-like synovial cells was assessed using immunohistochemistry, immunofluorescence histochemistry, and in situ hybridization methods. Levels of anti-collagen II antibody were measured using enzyme-linked immunosorbent assay. RESULTS: Given the terms mentioned above, we found a more practical rat model, apparently decreasing immunization time (average 3-5 days). DDR2 can be detected upon the 15th day of immunization; expression gradually increased with time going on, and reaching a peak 35 days after immunization before gradually decreasing. Serum anti-collagen II antibody showed similar expression patterns as DDR2, but reached peak later than DDR2, about 40 days after immunization. CONCLUSION: Regular expression of DDR2 in animal models infers its important role in the pathological process of RA.
16200600 Synovial fibroblasts promote osteoclast formation by RANKL in a novel model of spontaneous 2005 Oct OBJECTIVE: Erosion of cartilage and bone is a hallmark of rheumatoid arthritis (RA). This study was undertaken to explore the roles of hyperproliferating synovial fibroblasts and macrophages in abnormal osteoclast formation, using the recently described BXD2 mouse model of RA. METHODS: Cell distribution in the joints was analyzed by immunohistochemistry, using tartrate-resistant acid phosphatase (TRAP) staining to identify osteoclasts. To identify the defective cells in BXD2 mice, mouse synovial fibroblasts (MSFs) were cultured with bone marrow-derived macrophages. Osteoclast formation was assayed by TRAP staining and bone resorption pit assay, and the cytokine profiles of the MSFs and macrophages were determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: In BXD2 mice, TRAP-positive osteoclasts were found at sites of active bone erosion, in close proximity to hyperproliferating synovial fibroblasts. On coculture, MSFs from BXD2 mice, but not C57BL/6 mice, produced high levels of RANKL messenger RNA, induced macrophages to form osteoclasts, and actively eroded bone slices, through a mechanism(s) that could be blocked by pretreatment with osteoprotegerin. Although macrophages from BXD2 mice expressed higher basal levels of tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and IL-6 than those from C57BL/6 mice, abnormal osteoclast formation was not due to enhanced sensitivity of the BXD2 mouse macrophages to RANKL. TNFalpha, produced by both BXD2 MSFs and BXD2 mouse macrophages, had a strong stimulatory effect on RANKL expression. CONCLUSION: BXD2 MSFs produce RANKL and induce the development of osteoclasts from macrophages. The enhanced production of RANKL is possibly due to autocrine stimulation, together with paracrine stimulation by factors produced by macrophages.
16929972 Phenotype of peripheral blood lymphocytes and serum immunoglobulin concentration in patien 2006 Jan We studied the phenotype of peripheral blood lymphocytes and serum immunoglobulin concentration in patients with early rheumatoid arthritis and rheumatoid arthritis of more than 12 months duration. Subpopulations of CDIgM+, CD25+, and HLA-DR+ lymphocytes and IgA concentration differed in these groups of patients with rheumatoid arthritis. The count of lymphocytes carrying CDIgM+ and HLA-DR+ receptors correlated with activity of rheumatoid arthritis.
16161941 [Degenerative valvular and left ventricle structural changes in echocardiography in patien 2005 May The disproportion between absence of clinical manifestations of circulatory system involvement and serious lesions in the heart found on post mortem examinations, more frequently diagnosed congestive circulatory failure and also higher mortality rate of patients with rheumatoid arthritis (RA), encouraged the authors to study the subject. THE AIM OF THE STUDY: Echocardiographic assessment of the effect of rheumatoid process on the heart in patients with RA without clinically overt features of heart disease. MATERIAL AND METHODS: The study was conducted in 50 patients with RA diagnosed on the basis of the American College of Rheumatology (ACR) criteria and in 50 persons matched with the patients with respect to age, gender, body area and body mass index, heart rate and arterial pressure. Persons with manifestations and/or history of cardiovascular diseases were excluded from the study. RESULTS AND CONCLUSION: The authors found that: in rheumatoid arthritis, the involvement of the heart by the pathological process is manifested as degenerative changes of valve leaflets, and these lesions correlate with interventricular septum thickness and the mass and mass index of the left ventricle.