Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 10765919 | Tumor necrosis factor alpha 5'-flanking region, tumor necrosis factor receptor II, and HLA | 2000 Apr | OBJECTIVE: New polymorphisms affecting transcriptional activity were recently reported within the 5'-flanking region of the tumor necrosis factor alpha gene (TNFalpha). In addition, genome-wide linkage screening indicated 1p36 as one of the candidate chromosomal regions where the TNF receptor II gene (TNFR2) is located. In the present study, HLA-DRB1, TNFalpha promoter, and TNFR2 genotypes were determined to examine whether these polymorphisms are associated with rheumatoid arthritis (RA), either independently or in combination. METHODS: Genotypes of HLA-DRB1, TNFalpha upstream promoter, and TNFR2 codon 196 were determined in 545 Japanese patients with RA and 265 healthy controls. Association of these genes with susceptibility to RA was analyzed both independently and after stratification by one of the genotypes. RESULTS: As expected, the HLA-DRB1 shared epitope was strongly associated with RA. In addition, a significant negative association of DRB1*1405 and 1302 was observed. Furthermore, DRB1*1405 was suggested to possess a protective role for the development of RA in DRB1*0405-positive individuals. A significant increase in TNFalpha-U02 in RA was detected, which was not independent of DRB1*0405. A significant association was not observed between TNFR2-196M/R polymorphism and RA. CONCLUSION: Among the 3 genes examined in this study, HLA-DRB1 was considered to be most strongly associated with RA. | |
| 9972959 | Hypothalamic-pituitary-adrenocortical axis function in premenopausal women with rheumatoid | 1999 Feb | OBJECTIVE: To assess hypothalamic-pituitary-adrenocortical axis function in patients with rheumatoid arthritis (RA) not previously treated with glucocorticoids in relation to their inflammatory condition and in comparison to healthy controls. METHODS: We evaluated, in 10 premenopausal patients with RA and 7 age matched controls, plasma dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and cortisol concentrations, together with inflammatory cytokine levels [interleukin 6 (IL-6) and IL-12], both in basal conditions and after stimulation with ovine corticotropin releasing hormone (oCRH) and with low dose intravenous (5 microg) adrenocorticotropic hormone (ACTH). RESULTS: DHEA and DHEAS basal concentrations were found to be significantly lower (p<0.05) in premenopausal patients with RA than in controls. As expected, significantly higher basal levels of IL-6 and IL-12 (p<0.05) were found in patients with RA. After the low dose ACTH testing, the DHEA area under the curve value was found to be significantly lower (p<0.01) in patients than controls. Similar results, but without statistical significance, were observed after oCRH stimulation. DHEA levels at basal time showed a significant negative correlation with the erythrocyte sedimentation rate and platelet count, as well as with the Steinbrocker class of the disease (p<0.05). Normal plasma cortisol levels during oCRH and ACTH testing were found in patients with RA in spite of their inflammatory condition. After ACTH testing, IL-6 levels decreased significantly (p<0.05), whereas IL-12 levels were unchanged. No significant changes in IL-6 and IL-12 levels were found after oCRH testing. CONCLUSION: The abnormal androgen concentrations observed during testing in patients with RA might support the implication of adrenal androgens in the immune/inflammatory cytokine mediated mechanisms involved in the pathophysiology and clinical aspects of RA. | |
| 9558160 | Infrequent detection of cytomegalovirus and Epstein-Barr virus DNA in synovial membrane of | 1998 Apr | OBJECTIVE: To study the role of the cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus types 1 and 2 (HSV-1 and 2), varicella zoster virus (VZV), and human herpes virus 6 (HHV-6) in the etiology of rheumatoid arthritis (RA). METHODS: Polymerase chain reaction (PCR) was used to detect DNA of the different herpes viruses in synovial membranes from 31 patients with chronic RA and 14 control patients. Specific antibodies were determined by indirect immunofluorescence and ELISA. RESULTS: Out of 31 patients with RA, CMV DNA was detected in synovial membranes from 2 patients and EBV DNA was detected in synovial membranes from 2 other patients. All samples from the patients with RA were negative for DNA from HSV-1 and 2, VZV, and HHV-6. All samples from the 14 control patients were negative in all PCR assays. No statistically significant differences in IgG antibodies were found for CMV, HSV-1, VZV, and HHV-6 in patients with RA compared to controls. Higher titers of IgG antibodies against EBV viral capsid antigen were found in patients with RA, with a significance of p < 0.05. CONCLUSION: Both CMV and EBV DNA were detected in synovial membranes from 6% of the patients with RA. We cannot exclude the possibility that these viruses were associated with disease development in a minority of patients with RA. | |
| 11263783 | Invasiveness of synovial fibroblasts is regulated by p53 in the SCID mouse in vivo model o | 2001 Mar | OBJECTIVE: In vitro data suggest that the tumor suppressor p53 is critically involved in the regulation of proliferation and apoptosis in fibroblast-like synoviocytes (FLS). Based on evidence that abnormalities in p53 expression and function are found in rheumatoid arthritis (RA), we analyzed whether inhibition of p53 using gene transfer with the human papilloma virus type 18 (HPV-18) E6 protein results in an increased cellularity and invasiveness of synovial fibroblasts in vivo. METHODS: RA and normal FLS were transduced with a pLXSN-based construct encoding for the HPV-18 E6 protein or with the pLXSN vector alone. After selection with G418, FLS were coimplanted with normal human cartilage under the renal capsule of SCID mice. Parental, nontransduced cells were used as additional controls. After 60 days, the implants were removed, and FLS invasion into the cartilage, perichondrocytic degradation, and cellularity were assessed. RESULTS: Nontransduced and mock-transduced RA FLS exhibited characteristic invasion into the cartilage (mean +/- SEM scores 2.2 +/- 0.3 and 2.4 +/- 0.2, respectively). Invasion was increased significantly in the E6-transduced RA FLS (mean score 3.1 +/- 0.3; P < 0.05). Inhibition of p53 also resulted in an increase in cellularity. Parental and mock-transduced normal FLS did not exhibit significant invasion (mean score 1.5 +/- 0.1 and 1.4 +/- 0.3, respectively), but transduction with E6 resulted in clear invasiveness (mean score 2.4 +/- 0.4) as well as increased cellularity. CONCLUSIONS: The data suggest that inhibition of endogenous p53 leads to increased invasiveness and cellularity of RA FLS and may also transform normal FLS to cells that display an aggressive, RA FLS-like behavior. Therefore, abnormalities such as somatic mutations in the p53 tumor suppressor may contribute to synovial hyperplasia and invasion in RA. | |
| 10513803 | Lower prevalence of Chlamydia pneumoniae DNA compared with Chlamydia trachomatis DNA in sy | 1999 Sep | OBJECTIVE: To assess the presence of Chlamydia pneumoniae DNA in the joints of patients with reactive arthritis (ReA) and other arthritides. METHODS: DNA was prepared from synovial tissue (ST) and several synovial fluid (SF) samples from 188 patients with either ReA, undifferentiated oligoarthritis, or other forms of arthritis, and from 24 normal (non-arthritis) individuals. Preparations were screened using polymerase chain reaction (PCR) assays that independently targeted the C. pneumoniae 16S ribosomal RNA and major outer membrane protein genes. RESULTS: Twenty-seven of 212 ST samples (12.7%) were PCR positive for C. pneumoniae DNA; 10 SF samples from these 27 patients were similarly positive. Among the PCR-positive patients, 3 had ReA, 2 had Reiter's syndrome, 7 had undifferentiated oligoarthritis, 4 had undifferentiated monarthritis, 6 had rheumatoid arthritis, and 5 had other forms of arthritis. No samples from normal control individuals were PCR positive. CONCLUSION: DNA of C pneumoniae is present in synovial specimens from some arthritis patients. The prevalence of this organism in the joints was lower than that of C trachomatis, and synovial presence of the organism was not associated with any distinct clinical syndrome. Widely disseminated nucleic acids such as those of C. pneumoniae might have some role in the pathogenesis of several arthritides, since the organism was not found in the ST from normal control individuals. | |
| 9805922 | [Beneficial effect of salazosulfapyridine (SASP) in a patient with secondary renal amyloid | 1998 Sep | A 55-year old female with rheumatoid arthritis (RA) had presented with proteinuria since July 1996. She was referred to us for persistent edema on her face and legs in November 1996. On admission, her 24-hour urinary protein excretion was 4.4 g/day, total serum protein level was 5.3 g/dl, and serum level of amyloid A protein (SAA) was elevated to 45.8 mg/ml. A percutaneous renal biopsy was performed, and light microscopy revealed varying degrees of amyloid deposits in the mesangial areas and arteriolar walls. The diagnosis of secondary amyloidosis (AA amyloidosis) was based on immunohistochemical staining for amyloid A protein using monoclonal antibody against SAA. Four weeks after treatment with salazosulfapyridine (SASP) and dipyridamole, proteinuria began to decrease and the edema had disappeared. Finally she recovered from nephrotic syndrome. AA amyloidosis has been thought to have a poor prognosis, with progression to renal failure. Since there is no specific effective therapy for the disease, it is very important to reduce the activity of the underlying cause. In our patient with renal amyloidosis following RA, SASP was evidently effective for arthritis and improvement of renal function. SASP might have a beneficial effect on AA amyloidosis by suppressing inflammatory cytokines. | |
| 10493682 | Chemokine production by human chondrocytes. | 1999 Sep | OBJECTIVE: To evaluate the role of chondrocytes in producing CXC chemokines [interleukin 8 (IL-8), growth related gene product (GRO-alpha)] and CC chemokines [monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP-1alpha), RANTES] in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and subjects after traumatic injury (PT). METHODS: Articular cartilage specimens were obtained from 38 patients with OA and 18 with RA undergoing joint replacement surgery. Healthy human cartilage was obtained from femoral condyles removed after trauma in 11 subjects with no history of joint pathology (PT cases). Chondrocytes were isolated from articular cartilage by sequential enzymatic digestion and cultured in vitro. Chemokine production was investigated in unstimulated condition and after 72 h incubation with proinflammatory [IL-1beta, tumor necrosis factor-alpha (TNF-alpha)] and antiinflammatory [transforming growth factor-beta1 (TGF-beta1), IL-10] mediators. Chemokine concentrations in cell supernatants were evaluated by ELISA. RESULTS: Chondrocytes produce all these chemokines to a different extent. IL-1beta was a more potent stimulus than TNF-alpha in inducing production of all chemokines except MCP-1. We found no statistical differences among chondrocytes isolated from OA, RA, and PT for chemokine production in either basal conditions or after cytokine stimulation. IL-1beta induced chemokine production can be modulated by TGF-beta1 in different ways according to the various chemokines, while IL-10 does not affect IL-1beta induced chemokine production. CONCLUSION: Chondrocytes produce IL-8, GRO-alpha, MCP-1, MIP-1alpha, and RANTES. Proinflammatory factors (IL-1beta, TNF-alpha) effectively upregulate chemokine production, but production is scarcely modulated by the antiinflammatory mediators TGF-beta and IL-10. Chondrocyte derived chemokines may play a role in triggering the mechanisms involved in pathogenesis and persistence of joint diseases. | |
| 9388467 | A new mechanism of bone destruction in rheumatoid arthritis: synovial fibroblasts induce o | 1997 Nov 17 | Bone-resorbing multinucleated cells were efficiently formed in primary culture of cells isolated from synovial tissues of patients with rheumatoid arthritis in 2-3 weeks in the presence of 1,25(OH)2vitaminD3 without any additional stromal cells, and that formation was further facilitated by macrophage-colony stimulating factor. Furthermore, we show that osteoclast-like cells are formed in co-culture of peripheral blood mononuclear cells and rheumatoid synovial fibroblasts obtained by continued sub-cultures. The multinucleated cells showed all the phenotypical and functional characteristics of osteoclasts including the expression of tartrate resistant acid phosphatase, vitronectin receptors, receptors for human calcitonin and the ability to resorb bone. These results indicate that synovial macrophages are capable of differentiating into osteoclasts in the presence of rheumatoid synovial fibroblasts which can support differentiation of monocytes/ macrophages, implicating that osteoclasts generated within the synovial membrane are probably involved in bone destruction in rheumatoid arthritis. | |
| 9182912 | Enhancement of cartilage matrix protein synthesis in arthritic cartilage. | 1997 Jun | OBJECTIVE: To investigate whether the synthesis of cartilage matrix protein (CMP) is enhanced in arthritic cartilage. METHODS: The content of CMP in human and pig cartilage was determined by immunoblotting, and CMP-producing chondrocytes in osteoarthritic (OA) and rheumatoid arthritic (RA) joints were immunostained. RESULTS: CMP was undetectable in the condylar cartilage and disc of pigs, whereas it was abundant in the rib and tracheal cartilage of the same animals. By immunohistochemical analysis, CMP was localized in only a few chondrocytes (5%) in normal human joints, whereas numerous chondrocytes (>60%) were immunostained in RA joints. The number of CMP-producing cells was also increased in OA cartilage (>40%). Immunoblotting analyses confirmed that the CMP content in the cartilage from OA and RA patients was much higher than that in normal cartilage. CONCLUSION: These findings demonstrate that articular chondrocytes can synthesize CMP, although it is suppressed under physiologic conditions. The results also suggest that articular chondrocytes express CMP in response to arthritic stimuli. | |
| 9566100 | [Is H15 (resin extract of Boswellia serrata, "incense") a useful supplement to established | 1998 Feb | BACKGROUND: Leukotrienes and prostaglandines are important mediators of inflammation. While prostaglandine synthesis can be influenced by NSAIDs therapeutical approaches to the 5-lipoxygenase pathway are rare. Resinous extracts of Boswellia serrata (H15, indish incense), known from traditional ayurvedic medicine, decrease leukotriene synthesis in vitro. Case reports suggest a clinical role for that drug. METHODS: Outpatients with active RA have been enrolled into a multicenter controlled trial. Patients received 9 tablets of active drug (3600 mg) or placebo daily in addition to their previous therapy. Doses of NSAIDs could be adjusted on demand. Efficacy parameters, Ritchies Index for swelling and pain, ESR, CRP, pain on VAS and NSAID dose were documented at baseline and 6 and 12 weeks after initiation. Mean values and medians were calculated to compare the groups for significant or clinically relevant change from baseline or difference between both groups at any time point of observation. RESULTS: A total of 78 patients were recruited in 4 centers, the data have been published in abstract form. Only 37 patients (verum 18, placebo 19), enrolled in Ratingen were available for detailed efficacy and safety analysis. All evaluations in these patients were performed by one investigator (G.H.). There was no subjective, clinical or laboratory parameter showing a significant or clinically relevant change from baseline or difference between both groups at any time point of observation. The mean NSAID dose reduction reached levels of 5.8% (H15) and 3.1% (placebo). One patient in each group showed a good response in all parameters but 4 patients in each group worsened. The others showed no alteration of their disease. CONCLUSION: Treatment with H15 showed no measurable efficacy. Controlled studies including a greater patient population are necessary to confirm or reject our results. | |
| 10622295 | Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo | 1999 Dec 4 | BACKGROUND: Not all patients with rheumatoid arthritis can tolerate or respond to methotrexate, a standard treatment for this disease. There is evidence that antitumour necrosis factor alpha (TNFalpha) is efficacious in relief of signs and symptoms. We therefore investigated whether infliximab, a chimeric human-mouse anti-TNFalpha monoclonal antibody would provide additional clinical benefit to patients who had active rheumatoid arthritis despite receiving methotrexate. METHODS: In an international double-blind placebo-controlled phase III clinical trial, 428 patients who had active rheumatoid arthritis, who had received continuous methotrexate for at least 3 months and at a stable dose for at least 4 weeks, were randomised to placebo (n=88) or one of four regimens of infliximab at weeks 0, 2, and 6. Additional infusions of the same dose were given every 4 or 8 weeks thereafter on a background of a stable dose of methotrexate (median 15 mg/week for > or =6 months, range 10-35 mg/wk). Patients were assessed every 4 weeks for 30 weeks. FINDINGS: At 30 weeks, the American College of Rheumatology (20) response criteria, representing a 20% improvement from baseline, were achieved in 53, 50, 58, and 52% of patients receiving 3 mg/kg every 4 or 8 weeks or 10 mg/kg every 4 or 8 weeks, respectively, compared with 20% of patients receiving placebo plus methotrexate (p<0.001 for each of the four infliximab regimens vs placebo). A 50% improvement was achieved in 29, 27, 26, and 31% of infliximab plus methotrexate in the same treatment groups, compared with 5% of patients on placebo plus methotrexate (p<0.001). Infliximab was well-tolerated; withdrawals for adverse events as well as the occurrence of serious adverse events or serious infections did not exceed those in the placebo group. INTERPRETATION: During 30 weeks, treatment with infliximab plus methotrexate was more efficacious than methotrexate alone in patients with active rheumatoid arthritis not previously responding to methotrexate. | |
| 9832413 | Active and inhibitory components of the insulin-like growth factor binding protein-3 prote | 1998 Dec | Circulating insulin-like growth factor binding protein-3 (IGFBP-3) proteolytic activity is normally low but increases in serum from pregnant women and from patients with various pathologies. In contrast, we have recently reported that outside the circulation, such activity is normally high but decreases in various pathologies. We have now compared components of the IGFBP-3 proteolytic system revealed after size fractionation of serum and extravascular fluids with different intrinsic levels of such activity. Normal serum, serum from pregnant women, and synovial fluid from patients with rheumatoid arthritis revealed high and low molecular weight (MW) areas of activity. However, only the low MW activity was apparent in interstitial fluid from normal skin (N Inst F) or psoriatic lesions (P Inst F) and in synovial fluid from normal volunteers (N Syn F) or patients with osteoarthritis (OA Syn F). Addition of inhibitors revealed both areas to comprise more than one enzyme, including serine proteases and metalloproteinases; both could also be inhibited by P Inst F, NS, RA Syn F, and inhibitory fractions from the separation of the latter two. These findings demonstrate low and high MW regions of proteolytic activity, which may contribute to the IGFBP-3 protease system, the former always present, whereas the latter seems to be retained within the circulation apart from inflammatory conditions. The variations apparent in IGFBP-3 protease activity in the intact samples related to the presence of an inhibitor, which may protect IGFBP-3 from proteolysis, rather than to changes in the component proteases. | |
| 11602475 | The burden of musculoskeletal diseases in the general population of Spain: results from a | 2001 Nov | OBJECTIVE: The objective of the EPISER study was to estimate the prevalence of rheumatoid arthritis (RA), low back pain, hand and knee osteoarthritis (OA), and fibromyalgia in the adult Spanish population, and to assess the impact of these diseases on function and quality of life, and use of health and social resources. METHODS: 2998 subjects aged 20 years or above were randomly selected by stratified multistage cluster sampling from the censuses of 20 municipalities. Trained rheumatologists carried out structured visits at which subjects were asked about rheumatic symptoms and sociodemographic characteristics, completed validated instruments for measuring function (HAQ) and quality of life (SF-12), and underwent a standardised physical examination. Cases were defined by previously validated criteria. RESULTS: The estimated prevalences with 95% confidence intervals were as follows: RA lifetime cumulative: 0.5% (0.3 to 0.9); low back pain: 14.8% (12.2 to 17.4); symptomatic knee OA: 10.2% (8.5 to 11.9); hand OA: 6.2% (5.9 to 6.5); fibromyalgia: 2.4% (1.5 to 3.2). Most conditions significantly impaired function and quality of life. CONCLUSIONS: The EPISER study has internal and external validity for application of the results to the adult Spanish population. The diseases studied affect a significant proportion of the population, with various degrees of impact on disability and quality of life resulting in a significant number of physician visits, work disability, and medication use. | |
| 10589358 | Combination DMARD therapy with hydroxychloroquine, sulfasalazine, and methotrexate. | 1999 Nov | Triple combination therapy with hydroxychloroquine, sulfasalazine, and methotrexate (MTX) has been shown in double-blind, placebo-controlled studies to be significantly superior to MTX alone (Paulus 50% responses of 77% versus 33%). In long-term follow-up studies, this therapy has now been shown to be well-tolerated with continued efficacy in the majority of patients. | |
| 10546358 | Femoral bone grafting in primary and revision total knee arthroplasty. | 1999 Sep | The purpose of this study was to evaluate the clinical and radiographic results of TKA's with morsellized and solid femoral bone grafting. From April 1989 to February 1996, 6 primary and 18 revision TKA's with femoral bone grafting were performed in 22 patients with an average age of 62 years. Eleven knees were affected by rheumatoid arthritis, 10 by osteoarthritis, 2 by osteonecrosis and one by hemophiliac arthropathy. The femoral bone defects were large in 12, medium in 9, small in 3, contained in 10 and uncontained in 14 cases. Reconstruction was done with impacted morsellized fresh frozen trabecular bone grafts in 13 knees, with solid bone grafts in 7 knees and with combined grafts in 4 knees. Twenty-one cases were clinically evaluated at an average of 38 months (range: 9-89 months). The average Knee Society knee score increased by 39 points to 85 points at follow-up. The average functional score increased by 22 points to 48 points. Two cases with solid femoral bone grafts failed due to aseptic loosening. There were no infections. Radiographic follow-up revealed osteopenia around the femoral component in 10 knees. Two knees showed circumferential radiolucency around the femoral stem, and 5 knees had minor radiolucency at the anterior part of the femoral component. Radiographic incorporation was present in 5 of the 6 cases that could be evaluated. Histologic analysis of two biopsies revealed incorporation of the morsellized bone graft. The authors advocate impacted morsellized bone grafting for contained and small-to-medium uncontained femoral bone defects in combination with cemented TKA. | |
| 9333669 | [Chloroquine-induced bull's eye maculopathy without electrophysiologic changes]. | 1997 Jun | BACKGROUND: Electrophysiologic findings are usually pathologic in patients with chloroquine-induced bull's-eye maculopathy. To avoid maculopathy the daily dosage of chloroquine is estimated not from the actual but from the ideal body weight and should not exceed 3.5 mg/kg/day. PATIENT AND METHODS: A 59-year-old housewife took a daily dosage of 250 mg chloroquine for her rheumatoid arthritis over a period of 5 years up to a total dose of 450 g. With the height of 160 cm she weighed 68 kg. In 1990, two years after cessation of treatment she complained about blurred vision. Her visual acuity then was 0.8 and fell to 0.3 (right eye) and 0.4 (left eye) in 1996. No vortex keratopathy was observed. A central scotoma was present and fundus-examination showed a typical bull's-eye maculopathy. The mid hypopigmented ring correlated with an increased background fluorescence in the fluorescence-angiogram. Color vision and the retinal nerve fiber photo were normal. In spite of the prominent fundoscopic changes the electrophysiologic examination of this patient (ERG, EOG and pattern-ERG) was normal. The relative smallness of affected retina might explain the normal electrophysiology. CONCLUSION: This case of a patient with typical chloroquine-induced bull's-eye maculopathy with normal electrophysiology points to the importance of ophthalmoscopic and visual fields examination in patients under long-term chloroquine treatment. The correct daily dosage of chloroquine below 3.5 mg/kg/day should be given to avoid maculopathy. | |
| 11477102 | A novel role for interleukin-18 in adhesion molecule induction through NF kappa B and phos | 2001 Oct 5 | Interleukin-18 (IL-18) is a novel proinflammatory cytokine found in serum and joints of patients with rheumatoid arthritis (RA). We studied a novel role for IL-18 in mediating cell adhesion, a vital component of the inflammation found in RA and other inflammatory diseases. We examined the expression of cellular cell adhesion molecules E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) on endothelial cells and RA synovial fibroblasts using flow cytometry. Adhesion of the monocyte-like cell line HL-60 to endothelial cells was determined by immunofluorescence. IL-18 significantly enhanced ICAM-1 and VCAM-1 expression on endothelial cells and RA synovial fibroblasts. In addition, IL-18 induced E-selectin expression on endothelial cells and promoted the adhesion of HL-60 cells to IL-18-stimulated endothelial cells. Neutralizing anti-VCAM-1 and anti-E-selectin could completely inhibit HL-60 adherence to endothelial cells. IL-18-induced adhesion molecule expression appears to be mediated through nuclear factor kappa B (NF kappa B) and phosphatidyl-inositol 3 kinase (PI 3-kinase) since addition of inhibitors to either NF kappa B (pyrrolidine dithiocarbamate and N-acetyl-l-cysteine) or PI 3-kinase (LY294002) inhibited RA synovial fibroblast VCAM-1 expression by 50 to 60%. Addition of both inhibitors resulted in inhibition of VCAM-1 expression by 85%. In conclusion, the ability of IL-18 to induce adhesion molecule expression on endothelial cells and RA synovial fibroblasts indicates that IL-18 may contribute to RA joint inflammation by enhancing the recruitment of leukocytes into the joint. IL-18 requires NF kappa B as well as PI 3-kinase to induce VCAM-1 on RA synovial fibroblasts, suggesting that there may be two distinct pathways in IL-18-induced adhesion molecule expression. | |
| 10476018 | Patients teach students: partners in arthritis education. | 1999 Sep | CONTEXT: A large metropolitan teaching hospital within The Northern Clinical School, University of Sydney. OBJECTIVE: To assess whether students taught by trained patients (Patient Partners) acquire the same levels of competence in musculoskeletal examination skills for arthritis as students taught by Consultant Rheumatologists. SUBJECTS: Year four medical students in a six-year Undergraduate Medical Programme. METHOD: Students randomized to eight tutorial groups were taught musculoskeletal examination skills in a 75-90 minute tutorial. Four groups were taught by Consultants with an untrained patient present and four groups were taught by Patient Partners. RESULTS: Students' mean self-ratings of skill before and after their tutorial were summed. For both groups, self-ratings before the tutorial were similar. After the tutorial both groups showed substantial gains in levels of skill. Patient Partners' ratings of students' taught by either Consultants or Partners were comparable. CONCLUSIONS: Patient Partners are at least equal to Consultant Rheumatologists in the teaching of musculoskeletal examination techniques for arthritis. | |
| 11188854 | [Collagenase production increases in rheumatoid arthritis and osteoarthritis synoviocytes | 2000 | Cartilage is a specialized connective tissue. It contains few cells into an extracell matrix. The matrix mainly constituents are collagen and proteoglycans. Its degradation depends on synoviocytes activity, that secrete metalloproteases, agents to proteoglycans catabolism. There are two types of synoviocytes: macrophagics (type "A:') and fibroblastics (type "B"). The proteoglycan destruction can be LT-dependent or LT-independent. The aim of this work is synoviocytes function ex vÃvo study, free immune system influence. In order to do it, heparinized synovial fluid samples were obtained from 6 osteoarthritic (OA) and 6 arthritic (RA) both sex untreated patients, diagnosed according ACR criteria, which disease duration was longer than 6 months. Patients average age was 70 +/- 2 years. Control samples were synovial fluid from traumatic arthritis or non inflammatory bone-muscle pathology. Synovial fluid was centifugated at 1500 g for 30 minutes to isolate synoviocytes. Sediment containing cells was 6 hs incubed with Dulbecco-Eagles media, that has HEPES Gibco (26 mM); NaHCO3 (0.5 g/I); glutamine (2 mM), streptomicine (100 mg/l), G-penicillin (1 U/ml); anphotericine B (2.5 mg/l). Cells calification and viability were cytopathologically determined. Before and after incubation, collagenase activity was measured by ELISA-double-sandwich, using 10 micrograms/ml monoclonal anti-MMPs in phosphate-buffer-saline. The antigen-antibody complex production with inespecific proteins was blocked by bovine seric albumine. Streptavidin peroxidase was added and washed with 2,2,azin,di(3-ethyl-benztazoilinsuiphonic) acid to develop color. The link of labeled antibody by absorbance at 410 nm was determined in ELISA-spectrophothometer. RA patients earlier MMPs synoviocytes production was 1373 +/- 115 ng/ml. Then 6 hs incubation 2143 +/- 132 ng/ml was reached. The increase (56%) had high significance (p < 0.0001). OA earlier MMPs cells production was 276 +/- 23 ng/ml, but after incubation it reached 542 +/- 47 ng/ml. (96% increased with highly significativa difference too: p < 0.0001). Microscopic study was carried out before and after incubation, and shows a lot of synoviocytes with plenty of cytopiasme when the collagenase leveis were highest. On the contrary, when low MMPs production by synovial fluid, as no incubated osteoarthritic material, a few cells containing picnotics nucleous were observed. Significant quantitative differences in AR and OA enzymatic secretion were observed. Although in rheumatoid arthritic MMPs leveis synoviocytes production were 4.6 times than OA levels, after 6 hs incubation percentage of increase in OA cells secretion was highest. Described results confirm MMP-1 synthesis by synoviocytes, and these levels correlate with inflammation, more pronounced in acute (RA) than chronic pathology (OA). Synoviocyte incubation let us to test disease changes in synovial fluid according to cells number and phagocytic activity. Authors agree to assert that synovial fluid may reflect what is happening in an articular cartilago, because SF provides markers of joint disease. MMPs are giving information about pathways involved in OA and RA cartilage degradation. | |
| 9175930 | Synovial fluid chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluron | 1997 May | OBJECTIVES: To determine concentrations of chondroitin sulphate (CS) and keratan sulphate (KS) epitopes, glycosaminoglycans (GAGs) and hyaluronan (HA) in knee synovial fluid (SF) from normal subjects and patients with osteoarthritis (OA) or rheumatoid arthritis (RA), to test whether these variables may be used as markers of the OA process. METHODS: OA was subdivided into large joint OA (LJOA), nodal generalised OA (NGOA), and OA with calcium pyrophosphate crystal deposition (CPA). Clinical assessment of inflammation (0-6) was undertaken on OA and RA knees. Knee SF was examined by enzyme linked immunosorbent assay for: CS epitopes, using monoclonal antibodies 3-B-3 and 7-D-4; KS epitope using monoclonal antibody 5-D-4; and HA, using biotinylated HA binding region of cartilage proteoglycan. Total sulphated GAGs were measured by dye binding with 1:9 dimethylmethylene blue. RESULTS: Increased SF 3-B-3 concentrations and 3-B-3/GAG ratio were found in OA, compared with RA or normal knees, with higher 3-B-3 and 3-B-3/GAG in LJOA and NGOA than in CPA. SF 7-D-4 and 7-D-4/GAG were reduced in RA, compared with normal and OA; SF 5-D-4 was reduced in OA compared with normal. GAG and HA concentrations were decreased in both OA and RA. No correlations with radiographic scores were observed, but SF 7-D-4 was lower in 'inflamed' compared with 'non-inflamed' RA and OA knees. In patients with bilateral samples there were strong correlations between right and left knees for all SF variables. CONCLUSIONS: Changed concentrations of SF CS and KS can be detected in OA with a profile that differs from that seen in RA. Clinical subgrouping and local joint inflammation may influence these measures, supporting different pathogenesis within OA subgroups and requirement for careful patient characterisation in SF studies. |