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ID PMID Title PublicationDate abstract
10976081 Effect of IL15 on T cell clonality in vitro and in the synovial fluid of patients with rhe 2000 Sep OBJECTIVE: Recent studies have suggested that interleukin (IL) 15 induces T cell accumulation in synovial lesions of rheumatoid arthritis (RA). This study aimed at determining whether this cytokine could explain in vivo T cell clonality in RA. METHODS: Peripheral blood mononuclear cells (PBMC) from patients with RA were stimulated in vitro with IL15 or IL2. After isolation of mRNA from stimulated cells and synovial T cells, genes coding the V-D(N)-J (CDR3) region of T cell receptor beta chains were amplified by a reverse transcriptase polymerase chain reaction. A single strand conformation polymorphism analysis was used to detect the clonotype(s) of accumulating T cells. Nucleotide and amino acid sequencing was also performed. RESULTS: Stimulation of PBMC with IL15 resulted in oligoclonal expansion of T cells. However, IL15 induced clones from PBMC were mostly different from the dominantly expanding T cell clones in synovial fluid. Furthermore, IL15 and IL2 responding clones were only partially identical. CONCLUSIONS: Although IL15 results in clonal accumulation of T cells, T cell clonality in rheumatoid joints could not be explained by the effect of IL15 alone. The results indicated the requirement of other factor(s), in addition to IL15, in the pathological process affecting RA joints. The results also suggested different responses by each T cell clone to IL15 or IL2.
9709803 [Dental aspects of the treatment of temporomandibular joint disorders]. 1997 Over the last years, aetiological concepts have changed drastically. The role of occlusal factors in the aetiology has been overestimated in the past. The role of occlusal therapy should be aimed at restoring function. In the initial phase of treatment an occlusal splint, counseling, physiotherapy and occasionally NSAID's, leads to relieve pain and reduction of dysfunction in most patients. A repositioning splint in cases of anterior disc dislocation is not longer recommended. Selective grinding can be done in "occlusally sensitive" patients with pain or dysfunction of muscular origin. The adjustment should have a limited character, and is not indicated as preventive measure. Occlusal prosthetic reconstruction is in most patients not indicated for reasons linked to TMD because the aetiologic relationships between TMD and loss of molars has not been established. In cases of rheumatoid arthritis, osteo-arthrosis and spondylitis ankylosans, occlusal changes can occur due to the degeneration of the joint components. After the initial phase of treatment replacing the lost molars by prostheses in these particular patients, results in unloading of the joints and in decreasing recurrence of symptoms.
9536114 Synovial fibroblasts as target cells for staphylococcal enterotoxin-induced T-cell cytotox 1998 Jan Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown aetiology. Recently, superantigens have been implied in the pathogenesis of RA. Superantigens activate a large fraction of T cells leading to the production of cytokines and proliferation. In addition, superantigens direct cellular cytotoxicity towards major histocompatibility complex (MHC) class II-expressing cells. There is now increasing evidence that cytotoxic T cells may be involved in the pathogenesis of RA. In the inflamed synovia class II-positive synovial fibroblasts (SFC) are found. In the present study it was tested whether MHC class II-positive SFC serve as target cells for superantigen-induced cellular cytotoxicity. SFC were stimulated with interferon-gamma to express class II antigens, then they were cultivated in the presence of CD4-positive T cells with or without staphylococcal enterotoxins (SE). Cytotoxicity of T cells was measured as release of lactate dehydrogenase from SFC. Specific cytotoxicity was only found in the presence of class II-positive SFC depending on the dose of SE. Maximum lysis was seen after 20 hr. T-cell cytotoxicity was inhibited by antibodies to MHC class II antigens. The data suggest that class II-positive SFC not only function as accessory cells for SE-mediated T-cell proliferation and interleukin-2 production but may also be the targets of superantigen-mediated cellular cytotoxicity.
9287250 MHC-derived peptides and the CD4+ T-cell repertoire: implications for autoimmune disease. 1997 Jun The receptor repertoire of peripheral CD4+ cells is primarily determined by selection processes in the thymus. These result in the positive selection of T cells whose receptors weakly recognize self-peptides restricted by class II self-MHC heterodimers. A majority of such self-peptide partial agonists are likely to be derived from self-MHC molecules. It is suggested that these thymically selected, weakly autoreactive T cells may subsequently be stimulated by peripheral exposure to microbially derived agonists that 'mimic' corresponding self-MHC peptides. In turn, 'molecular mimicry' between microbial agonists and tissue-specific self-peptides may lead to T-cell-mediated autoimmune disease. Hence such disease may reflect 'three-way mimicry' between peptides of respectively target tissue, pathogen and self-MHC (or other self-peptide dominantly presented in the thymus). This hypothesis accounts for the role of MHC haplotype in determining susceptibility to (or protection from) autoimmune disease. Direct evidence is presented in favour of the model as applied to diseases such as rheumatoid arthritis, autoimmune uveitus and autoimmune diabetes. Strong circumstantial evidence, based primarily on sequence similarities, is also presented for other autoimmune diseases. However, it is noted that the statistics of database searches, and the lack of predictable correlation between sequence similarity and T-cell cross-reactivity, require that such evidence be substantiated by further direct experiment.
10602665 Human retroviral sequences associated with extracellular particles in autoimmune diseases: 1999 Apr Publications describing retroviral sequences associated with extracellular particles in Sjögren's syndrome or systemic lupus erythematosus, multiple sclerosis, and type I diabetes present novel arguments and raise complex questions about eventual relationships between retroviruses and autoimmunity. They are presented and discussed in the present review, preceded by an overview of the biology of retroviral elements.
9093794 Elastase from polymorphonuclear leukocyte in articular cartilage and synovial fluids of pa 1997 Mar Objective was to study the significance and the mechanism of action of elastase from polymorphonuclear leukocyte (PMN elastase) in patients with rheumatoid arthritis (RA). The experiments conducted consisted of two phases. Firstly, articular cartilage and synovia from 8 patients with RA undergoing total knee replacement were obtained, and the gelatinolytic enzyme activity was extracted with 2M guanidine hydrochloride. The gelatinolytic activity of each tissue was measured to confirm that the activity was due to PMN elastase by using an antihuman leukocyte elastase antibody. Secondly, the levels of PMN elastase-alpha 1 proteinase inhibitor complex (EIC) in the blood and synovial fluid of 170 patients with RA were measured by immunoassay. The results were as follows: 1. Gelatinolytic activity was shown to be mainly due to PMN elastase, and found to be highest in cartilage and synovia in RA joints. 2. The EIC levels in plasma of RA patients were significantly higher than those in gout and osteoarthritis (OA), and the EIC levels increased according to the stage of articular cartilage destruction. Moreover, the EIC levels in synovial fluid of RA patients were higher compared to those of OA patients. The activity of PMN elastase was elevated in destructive joints of RA. With the progression of articular cartilage destruction, EIC levels in plasma of RA patients increased as well. We suggest that PMN elastase may play a significant role in RA disease.
9195815 The Rotaflex total knee replacement--a 5 year review. 1997 Jun We report the results of a retrospective analysis of 43 patients who received 56 Rotaflex total knee arthroplasties, with a mean follow-up of 55.7 months. The British Orthopaedic Association (BOA) knee assessment protocol was used in evaluating the clinical results. Two patients could not receive post-operative scores. In the remaining 54 knees, the mean pre-operative score was 25.6, improving to 30.8 post-operatively. Ten knees showed a decrease in knee score, two were unchanged and 42 improved. The greatest improvements were in pain relief and maximum flexion. Wound infection and dehiscences were common, the latter requiring further surgery in five cases. Later, there were eight fractures involving the prosthesis, seven dislocated or subluxed patellae, two deep infections and three cases of severe aseptic loosening. A common feature was severe patellar wear, due to the design fault of an absent femoral groove. The high rate of complications and poor functional result of the Rotaflex knee preclude its use in current practice.
9558401 Raised neutrophil phospholipase A2 activity and defective priming of NADPH oxidase and pho 1998 May 1 Intermittent painful crises due to vasoocclusion are the major clinical manifestation of sickle cell disease (SCD), but subclinical episodes may also occur. There is sparse evidence for the involvement of neutrophils in the pathophysiology of SCD, but production of cytokines by the damaged endothelium might influence neutrophil function and modulate responses to subsequent cytokine exposure. In addition, the activation of neutrophils in the microcirculation could itself exacerbate vasoocclusion. To test whether neutrophil inflammatory responses were altered in SCD, neutrophil phospholipase A2 and NADPH oxidase activity in response to in vitro priming by granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha) were measured both during and between painful crises. Resting levels of neutrophil phospholipase A2 activity in steady-state SCD (4.0% +/- 0. 5% of total cell radioactivity) were raised relative to control values (2.0% +/- 0.2%, n = 10, P = .008). There was no defect of agonist-stimulated phospholipase A2 or NADPH oxidase activity in steady-state SCD; however, the ability of phospholipase A2 to respond to priming with GM-CSF was attenuated to 63% +/- 17% of control values (n = 10, P = .04). Similarly, neutrophil NADPH oxidase activity after priming with GM-CSF and TNF-alpha was, respectively, 65% +/- 11% (n = 7, P = .03) and 57% +/- 7% of control (n = 10, P = .007) in steady-state disease, and was further reduced during painful vasoocclusive crises to 34% +/- 9% and 25% +/- 3% of control for GM-CSF and TNF-alpha, respectively. These data were not explained by poor splenic function or any racial factor, as normal cytokine responses were seen in splenectomized patients in remission from Hodgkin's disease and in healthy Afro-Caribbean subjects. Abnormal neutrophil cytokine priming responses were not observed in either patients with rheumatoid arthritis or iron-deficiency anemia. Our findings are indicative of an ongoing inflammatory state in SCD between painful crises involving neutrophil activation and an abnormality of cytokine-regulated neutrophil function, which may compromise the host defenses against certain microorganisms.
9497784 Genetic susceptibility to the development of autoimmune disease. 1997 Dec 1. Autoimmune diseases are common conditions which appear to develop in genetically susceptible individuals, with expression of disease being modified by permissive and protective environments. Familial clustering and data from twin studies provided the impetus for the search for putative loci. Both the candidate gene approach in population-based case-control studies and entire genome screening in families have helped identify susceptibility genes in a number of autoimmune diseases. 2. After the first genome screen in type 1 (insulin-dependent) diabetes mellitus it seems likely that most autoimmune diseases are polygenic with no single gene being either necessary or sufficient for disease development. Of the organ-specific autoimmune diseases, genome screens have now been completed in insulin-dependent diabetes mellitus and multiple sclerosis. Furthermore, the clustering of autoimmune diseases within the same individuals suggests that the same genes may be involved in the different diseases. This is supported by data showing that both HLA (human leucocyte antigen) and CTLA-4 (cytotoxic T-lymphocyte-associated-4) appear to be involved in the development of insulin-dependent diabetes mellitus and Graves' disease. 3. Genome screens have also been completed in some of the non-organ-specific autoimmune diseases including rheumatoid arthritis, inflammatory bowel disease and psoriasis. Many candidate genes have also been investigated although these are predominantly in population-based case-control studies. 4. Substantial progress has been made in recent years towards the identification of susceptibility loci in autoimmune diseases. The inconsistencies seen between case-control studies may largely be due to genetic mismatching between cases and controls in small datasets. Family-based association studies are being increasingly used to confirm genetic linkages and help with fine mapping strategies. It will, however, require a combination of biology and genetics, as has been necessary with the major histocompatibility complex in insulin-dependent diabetes mellitus, to identify primary aetiological mutations.
11244314 Reversible nephrotic syndrome in a patient with amyloid A amyloidosis of the kidney follow 2001 Feb A common form of methicillin-resistant Staphylococcus aureus (MRSA) associated glomerulonephritis is either an endocapillary proliferative glomerulonephritis or a crescentic glomerulonephritis. This report describes the development of reversible nephrotic syndrome following MRSA infection in a patient with amyloid A amyloidosis. The patient had been diagnosed as having rheumatoid arthritis for 50 years. Suppurative arthritis due to MRSA became complicated 2 years prior to admission to our hospital. In the meantime, a nonnephrotic-range proteinuria developed. Two weeks before admission, nephrotic syndrome developed. The serum creatinine level remained unchanged throughout the course, but common features characteristic of MRSA-associated glomerulonephritis were observed in this patient, such as elevated serum IgG and IgA levels. A renal biopsy specimen showed glomerular amyloid A amyloidosis of a nodular type, infiltrated mononuclear cells in the mesangium, deposition of IgG, IgA, and C3, and swelling of glomerular endothelial cells. There were no crescentic glomeruli. Following surgical eradication of the MRSA focus in the right knee joint, nephrotic syndrome disappeared. Hence, it was highly possible that MRSA infection induced a reversible nephrotic syndrome by causing reversible injuries to glomerular endothelial cells. The description of this case serves to illustrate the range of MRSA infections that may cause various forms of glomerulonephritides.
9893194 Expression of soluble human signaling lymphocytic activation molecule in vivo. 1999 Jan BACKGROUND: Signaling lymphocytic activation molecule (SLAM) is a novel glycoprotein expressed on activated T and B cells. Ligation of cell surface SLAM, either by anti-SLAM mAbs or the recombinant soluble form of SLAM (sSLAM), enhanced the proliferation of T and B cells in vitro. In addition, the engagement of SLAM on T cells preferentially induced IFN-gamma production even by allergen-specific TH2 clones. OBJECTIVE: In this study we investigated the expression of sSLAM in vivo in healthy individuals and in disease conditions that are associated with increased TH1 - or TH2 -cell responses. METHODS: The expression of mRNA encoding sSLAM in peripheral blood and synovial fluid (SF) lymphocytes was studied by using reverse transcriptase-PCR, and the presence of sSLAM protein in serum and SF samples was investigated by using a specific ELISA. RESULTS: Lymphocytes from patients with rheumatoid arthritis (RA) and healthy individuals consistently expressed mRNA encoding sSLAM. In addition, sSLAM protein was present in 38% of serum and 54% of SF samples from patients with RA and in 47% of serum samples from healthy individuals. The levels of sSLAM in positive serum and SF samples from patients with RA and in positive serum samples from healthy individuals were not significantly different. In contrast, the levels of sSLAM were significantly lower in patients with reactive arthritis or in patients with elevated IgE levels than in patients with RA. Similarly, the frequency of positive SF samples was significantly lower in reactive arthritis (28%) than in RA (54%). CONCLUSION: These results indicate that sSLAM is present in serum and SF, further suggesting that sSLAM regulates T- and B-cell function in vivo. Moreover, these data suggest an association between low sSLAM production and the occurrence of TH2 responses in vivo.
11326478 Longitudinal study of rheumatoid arthritis patients discloses sustained elevated serum lev 2001 Mar OBJECTIVE: To appreciate the evolution of serum angiogenic and/or adhesion molecules levels during a long term follow-up of rheumatoid arthritis (RA) patients. METHODS: Serum levels of 5 soluble adhesion/angiogenesis glycoproteins (VEGF, CD31, CD54, CD62E, CD106) were measured in Elisa in samples collected over 6 years in a cohort of 43 RA patients with monitored clinical parameters of disease activity and severity. RESULTS: RA patients had significantly higher levels (p < 0.0001) of sCD106 (VCAM-1) than control subjects. Conversely, the levels of soluble VEGF, CD31, CD54 and CD62E were normal or lower than normal. No statistically significant time effect was noted. No effect either was noted as related to the therapeutic agents taken by the patients. CONCLUSION: The sustained elevated serum levels of sCD106 observed here imply that this molecule might be related to the chronicity and progression of RA.
9462175 Cytokine production in whole blood cell cultures of patients with rheumatoid arthritis. 1997 Nov OBJECTIVE: The measurement of cytokine production of activated lymphocytes and monocytes in the whole blood cell (WBC) culture system may provide a sensitive tool for evaluating the actual ongoing immune response of patients with rheumatoid arthritis (RA). METHODS: Lipopolysaccharide (LPS) up to 250 pg/ml was used for the stimulation of monocytes for measuring the production of tumour necrosis factor alpha (TNF alpha), interleukin 6 (IL6) and IL12, while the anti-CD3 (1 microgram/ml) and anti-CD28 (5 micrograms/ml) combination was used for T cell stimulation with the measuring of IL4 and interferon gamma (INF gamma) production. Twenty seven patients with RA and 23 healthy controls were studied. RESULTS: The results showed a decreased IL6 (LPS stimulus 4-6 pg/ml) and IL-12 (LPS stimulus 16-62 pg/ml) production in the RA patients. The maximal production of both cytokines was comparable with the normal controls. T cell stimulation showed a significant decreased INF gamma production in the RA patients. CONCLUSIONS: These findings obtained in the WBC culture system are highly suggestive for a decreased TH-1 derived cytokine production by a diminished IL12 production in RA patients. Another possibility is that both IL12 and INF gamma production in WBCs are inhibited by eventual circulating serum factors.
10761533 Six-month prospective study to monitor the treatment of rheumatic diseases with sustained- 2000 Nonsteroidal antiinflammatory drugs (NSAIDs) are used in the therapy of both inflammatory and degenerative diseases of the locomotor system. Due to the relatively high occurrence of adverse effects, mainly on the gastrointestinal tract, NSAID therapy often has to be discontinued. Studies focusing on long-term NSAID therapy end points are rare. Two hundred patients presenting with classic rheumatic diseases (osteoarthritis, n = 50; rheumatoid arthritis, n = 130; ankylosing spondylitis, n = 20) were given a daily dose of 200 mg sustained-release flurbiprofen (flurbiprofen SR). The aim of the study was to assess the results of a 6-month treatment. This open therapeutic study was carried out in 10 rheumatological outpatient departments in the Slovak Republic with 20 patients from each department. The patients were monitored monthly during the 6 months of treatment. The group comprised 71% females with an average age of 52.7 years (range 22-72 years). The degree of the disease activity was assessed at the start of the study as moderate (68%) for all groups. Average disease duration was 10.4 years (0.4-35 years). Most patients had previously been treated with other NSAIDs. A total of 151 patients (75.5%) successfully completed the 6-month therapy with flurbiprofen; 49 patients (24.5%) withdrew from the treatment prematurely, most of them at an early stage (23 during the first month, 11 during the second month, five during the third and fourth months each, three during the fifth month and two during the sixth month). The reasons were lack of efficacy in 10 patients and adverse effects (mostly mild to moderate gastrointestinal intolerance) in 26. The remaining 13 patients gave other reasons for withdrawal. No predictive factors could be identified on comparing the basic demographic data of patients who completed the course of treatment with those who withdrew from therapy. In conclusion, flurbiprofen SR given in a single daily dose of 200 mg is an effective and relatively well tolerated NSAID, which is suitable for the long-term treatment of most patients with chronic arthritic conditions.
9348142 The moderate intestinal side effects of auranofin do not require prophylactic therapy with 1997 Sep Incidences of diarrhoea and loose stools are reported up to 50% in patients starting treatment with auranofin. Moreover, +/-4% of patients discontinue treatment because of severe diarrhoea. We investigated whether a water binding agent would diminish the incidence of loose stools and diarrhoea. Endpoints were the patient's general impression of the quality of stools and a daily assessment of stool's frequency/consistency and adverse events. Secondly, some disease activity parameters were used to evaluate whether the bulkforming agent influences the efficacy of auranofin. In this study 269 patients suffering from Rheumatoid Arthritis (RA) were treated with auranofin 6 mgr daily for a period of six months. Simultaneously the patients were randomly treated with either a bulkforming agent (Volcolon: psyllium fibres) or placebo. Results show a 15% incidence of loose stools and diarrhoea during treatment with auranofin. During the treatment period the patients' general impression of defecation consistency showed a shift to softer types. The changes in defecation consistency was not significantly different between groups (Intention-to-treat analysis: C2=4.01; p=0.13). Also, the percentage of patients experiencing episodes of diarrhoea (reported as an adverse experience) was not different (14% of the patients treated with bulkformer versus 15% with placebo). During the first month 7% (n=5) of placebo treated patients reported short episodes of watery stools versus none in the bulkformer treated group. The percentage of days with loose or watery stools, reported on the diary cards, was consistently lower in bulkformer treated patients. Both groups improved equally with respect to disease activity parameters. Sixty-eight percent of patients continued auranofin treatment after the study period. In conclusion, these data do not support adjuvant therapy with a bulkforming agent on initiation of auranofin therapy. The overall low incidence of loose stools and diarrhoea suggests that a dose increase to 9 mgr daily is an option to enhance the efficacy of auranofin treatment.
9234243 Degradation of C1-inhibitor by plasmin: implications for the control of inflammatory proce 1997 Jun BACKGROUND: A correct balance between protease and inhibitor activity is critical in the maintenance of homoeostasis; excessive activation of enzyme pathways is frequently associated with inflammatory disorders. Plasmin is an enzyme ubiquitously activated in inflammatory disorder, and C1-inhibitor (C1-Inh) is a pivotal inhibitor of protease activity, which is particularly important in the regulation of enzyme cascades generated in plasma. The nature of the interaction between plasmin and C1-Inh is poorly understood. MATERIALS AND METHODS: C1-Inh was immunoadsorbed from the plasma of normal individuals (n = 21), from that of patients with systemic lupus erythematosus (n = 18) or adult respiratory distress syndrome (n = 9), and from the plasma and synovial fluid of patients with rheumatoid arthritis (n = 18). As plasmin is a putative enzyme responsible for C1-Inh was examined using SDS-PAGE. In addition, peptides cleaved from C1-Inh by plasmin were isolated and sequenced and the precise cleavage sites determined from the known primary sequence of C1-Inh. Homology models of C1-Inh were then constructed. RESULTS: Increased levels of cleaved and inactivated C1-Inh were found in each of the inflammatory disorders examined. Through SDS-PAGE analysis it was shown that plasmin rapidly degraded C1-Inh in vitro. The pattern of C1-Inh cleavage seen in vivo in patients with inflammatory disorders and that produced in vitro following incubation with plasmin were very similar. Homology models of C1-Inh indicate that the majority of the plasmin cleavage sites are adjacent to the reactive site of the inhibitor. CONCLUSIONS: This study suggests that local C1-Inh degradation by plasmin may be a central and critical event in the loss of protease inhibition during inflammation. These findings have important implications for our understanding of pathogenic mechanisms in inflammation and for the development of more effectively targeted therapeutic regimes. These findings may also explain the efficacy of anti-plasmin agents in the treatment of C1-Inh deficiency states, as they may diminish plasmin-mediated C1-Inh degradation.
11006493 An Epstein-Barr virus-associated pulmonary lymphoproliferative disorder as complication of 2000 Oct Inherited or acquired immunodeficiencies as well as autoimmune diseases treated with cytotoxic drugs are associated with an increased incidence of lymphoma. Non-Hodgkin's lymphomas that occur in the context of drug-induced immunosuppression, acquired or congenital immunodeficiency, are frequently associated with Epstein-Barr virus infection. This report describes the occurrence of an Epstein-Barr virus associated pulmonary B cell lymphoma in a patient with longstanding rheumatoid arthritis treated with methotrexate.
10367040 Polymorphism of the vitamin D receptor gene and corticosteroid-related osteoporosis. 1999 Corticosteroid therapy (CST) is associated with reduced intestinal calcium absorption, bone loss and increased fracture risk. As polymorphisms of the vitamin D receptor (VDR) gene may be associated with bone mineral density (BMD) and intestinal calcium absorption, we asked whether patients with a given VDR genotype receiving CST may be at increased or decreased risk for corticosteroid-related bone loss and osteoporosis. We measured areal BMD (g/cm2) by dual-energy X-ray absorptiometry in 193 women (50 premenopausal, 143 postmenopausal) and 70 men with rheumatoid arthritis (n = 44), obstructive airway diseases (n = 128) and other corticosteroid-treated diseases (n = 91). All patients received a cumulative dose greater than 1.8 g per year or a minimum of 5 mg daily of prednisolone or equivalent for at least 1 year. VDR alleles were typed by polymerase chain reaction assay based on the polymorphic BsmI and TaqI restriction sites. BMD in patients was expressed as a Z-score (mean +/- SEM) derived from age- and gender-matched controls. BMD was reduced in patients at the lumbar spine (bb, -0.52 +/- 0.12; Bb, -0.47 +/- 0.11; BB, -0.65 +/- 0.18 SD; p < 0.01), femoral neck (bb, -0.46 +/- 0.10; Bb, -0.34 +/- 0.10; BB, -0.54 +/- 0.14 SD; p < 0.01), Ward's triangle (bb, -0.44 +/- 0.10; Bb, -0.31 +/- 0.10; BB, -0.45 +/- 0.13 SD; p < 0.01), and trochanter (bb, -0.50 +/- 0.10; Bb, -0.30 +/- 0.10; BB, -0.44 +/- 0.14 SD; p < 0.01). However, there was no significant difference in the deficit in BMD in any of the genotypes, either before or after adjusting for age, sex, body mass index, disease type, age at onset of disease, disease duration, cumulative steroid dosage, smoking status and dietary calcium intake. Similarly, there were no detectable differences between the BsmI genotypes and the rate of bone loss in 79 patients with repeated BMD measurements at an interval of 4-48 months. The data suggest that the VDR genotypes may not be a means of identifying patients at greater risk of corticosteroid-related bone loss.
10332972 A platelet activating factor receptor antagonist prevents the development of chronic arthr 1999 May OBJECTIVE: To examine the effect of treatment with the platelet activating factor (PAF) receptor antagonist BN 50730 on the clinical and morphological evolution of collagen induced arthritis in mice. METHODS: Mice with collagen induced arthritis were treated with BN 50730 (0.3, 1, 3 mg/kg) or vehicle (0.1% Tween-20 in saline) once a day, from 3 days before the induction of the arthritis to 70 days after. Disease evolution was followed daily by inspection of inflammatory signs and measurement of the knee joint diameter on Days 0, 40, and 70. At the end of the treatment period, the morphological evaluation of the synovial membrane, the immunodetection of fibronectin, and the content of cartilage proteoglycans were studied. RESULTS: On Day 40, mice receiving the highest dose of BN 50730 (3 mg/kg) showed a reduction in the knee joint diameter in comparison with untreated (2.1 +/- 0.2 vs 2.8 +/- 0.4 mm, p < 0.01). On Day 70, animals receiving 1 and 3 mg/kg had a normal knee diameter, while it remained enlarged in the untreated ones. In BN 50730 treated mice (3 mg/kg) we also observed a significant reduction of the inflammation score (0.1 +/- 0.1 vs 2.5 +/- 0.2 in the untreated) and deposition of fibronectin. Depletion of cartilage proteoglycans was also reversed with BN 50730. CONCLUSION: The beneficial effects in this model of joint injury after administration of the PAF antagonist BN 50730 suggest that PAF could be implicated in the pathogenesis of chronic arthritis.
10343777 Production of cartilage oligomeric matrix protein (COMP) by cultured human dermal and syno 1998 Nov OBJECTIVE: Cartilage oligomeric matrix protein (COMP) is a large disulfide-linked pentameric protein. Each of its five subunits is approximately 100,000 Da in molecular weight. COMP was originally identified and characterized in cartilage and it has been considered a marker of cartilage metabolism because it is currently thought not to be present in other joint tissues, except for tendon. To confirm the tissue specificity of COMP expression we examined cultured human dermal fibroblasts, human foreskin fibroblasts, and normal human synovial cells for the synthesis of COMP in culture. METHOD: Normal synovial cells and normal human dermal foreskin fibroblasts were isolated from the corresponding tissues by sequential enzymatic digestions and cultured in media containing 10% fetal bovine serum until confluent. During the final 24 h of culture, the cells were labeled with 35S-methionine and 35S-cysteine in serum- and cysteine/methionine-free medium. The newly synthesized COMP molecules were immunoprecipitated from the culture media with a COMP-specific polyclonal antiserum, or with monoclonal antibodies or affinity-purified COMP antibodies. The immunoprecipitated COMP was analyzed by electrophoresis in 5.5% polyacrylamide gels. For other experiments, synovial cells cultured from the synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were similarly examined. RESULTS: A comparison of the amounts of COMP produced by each cell type (corrected for the DNA content) revealed that synovial cells produced > or = 9 times more COMP than chondrocytes or dermal fibroblasts. COMP could be easily detected by immunoprecipitation in all cell types. Electrophoretic analysis revealed a distinct band with an apparent MW of 115-120 kDa in samples from each of the three cell types, regardless of the antibody used. COMP expression in cultures of synoviocytes derived from OA and RA patients showed that OA and RA synovial cells produced similar amounts of monomeric COMP of identical size to those COMP monomers produced by normal synovial cells. The addition of TGF-beta to these cultures resulted in an increase in COMP production in normal, OA and RA synovial cells (45, 116 and 115% respectively). CONCLUSION: These studies demonstrate that substantial amounts of COMP are produced by several mesenchymal cells including synoviocytes and dermal fibroblasts. These findings raise important concerns regarding the utility of measurements of COMP levels in serum or in synovial fluid as markers of articular cartilage degradation because of the likelihood that a substantial proportion of COMP or COMP fragments present in serum or synovial fluid may be produced by cells other than articular chondrocytes.