Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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12561913 | Study of gamma-interferon in schistosomiasis mansoni, autoimmune diseases and schistosomal | 1999 | IFN-gamma, a Th1 cytokine was quantitatively estimated using EASIA in the sera of patients with different stages of schistosomiasis mansoni autoimmune diseases and schistosomal arthropathy. Level of IFN-gamma was significantly elevated in all the test groups compared to the control group. The highest level of IFN-gamma observed was in RA and SLE, with insignificant statistical difference (P > 0.05) between them. Cases with early S. mansoni infection showed significant higher level (P < 0.05) of IFN-gamma compared to hepatosplenic schistosomiasis with and without ascites. A significant statistical difference (P < 0.05) concerning IFN-gamma level was observed when comparing RA and SLE to different stages of S. mansoni infection and schistosomal arthropathy. This might lead to a conclusion that IFN-gamma estimation in sera of patients having joint complaint could be a good marker for differentiation between autoimmune collagen induced arthritis and schistosomiasis induced arthropathy. | |
11712859 | Effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on the expression | 2001 Nov | This study was performed to investigate whether peroxisome proliterator-activated receptor-gamma (PPAR-gamma) exerted an anti-inflammatory effect on rheumatoid synovial cells and inhibited dysregulated proliferation. The expression of PPAR-gamma mRNA in cultured human synoviocytes and THP-1 cells was analysed by RT-PCR. PPAR-gamma was expressed in normal, osteoarthritis (OA), rheumatoid arthritis (RA) synovial cells as well as a human monocytic cell line, THP-1. In RA and OA synoviocytes, the induction of inflammatory cytokine mRNA expression such as TNF-alpha and IL-1beta was significantly inhibited by the natural PPAR-gamma agonist, 15 deoxy-Delta(12,14)prostaglandin J(2)(15d-PGJ(2)). The effect of PPAR-gamma on the nuclear factor (NF)-kappaB activity was tested by electrophoretic mobility shift assay (EMSA). Both troglitazone and 15d-PGJ(2)markedly inhibited TNF-alpha-induced NF-kappaB activation at 30 microM. However, PPAR-gamma agonist neither reduced proliferation nor induced apoptosis in RA synoviocytes when measured by XTT assay and fluorescence activated cell sorter (FACS) analysis. In contrast, it induced apoptosis in a dose-dependent manner in THP-1 cells and augmented TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis as well. In conclusion, these data demonstrate that PPAR-gamma is expressed in human synoviocytes and THP-1 cells, and the PPAR-gamma activation inhibits expression of inflammatory cytokines in RA synoviocytes. Furthermore, PPAR-gamma activation induces apoptosis by itself and augments TRAIL/Apo2L-induced apoptosis in THP-1 cells. These results suggest that PPAR-gamma agonists may provide a new therapeutic approach for RA. | |
10513812 | Evidence for neurogenic transmission inducing degenerative cartilage damage distant from l | 1999 Sep | OBJECTIVE: To investigate involvement of the nervous system in ipsilateral and contralateral joint inflammation. METHODS: Freund's complete adjuvant (CFA; 1 mg or 1 microg) was injected unilaterally and the messages (a) from the hind paw to the ipsilateral and contralateral knees and (b) from one knee to the contralateral knee were analyzed. The degenerative impact of the local injury on distant cartilage was assessed using patellar proteoglycan synthesis as an indicator. Neurogenic mechanisms were blocked either by spinal cord compression or by injection of neurokinin 1 (NK-1) antagonist, or they were mimicked by intraarticular injection of substance P. The data were compared with those gathered in a model of systemic inflammation, characterized by fever and serum interleukin-6 production. RESULTS: After unilateral subcutaneous injection of CFA, proteoglycan anabolism decreased bilaterally. Spinal cord compression and administration of the NK-1 antagonist inhibited the response in the contralateral limb. Following 1 mg CFA subcutaneous injection, the ipsilateral response implicated both neurogenic and systemic mechanisms, whereas the nervous system alone was implicated after 1 microg subcutaneous CFA injection. The 1 microg CFA intraarticular injection induced a degenerative contralateral signal, which was abolished by spinal cord compression and by pretreatment with the NK-1 antagonist. Intraarticular injection of 1 microg CFA also induced an ipsilateral increase of anabolism, which was enhanced by spinal cord compression. Similar results were obtained after intraarticular injections of substance P. These effects were not reproduced with turpentine treatment, a systemic model, in which spinal cord compression had no effect. CONCLUSION: A unilateral inflammation can induce, by neurogenic mechanisms, distal bilateral degeneration of articular cartilage, implicating involvement of neuropeptides. | |
11435321 | Acquired pure red cell aplasia associated with lymphoproliferative disease of granular T l | 2001 Jul 15 | Acquired pure red cell aplasia (PRCA) can be associated with lymphoproliferative disease of granular T lymphocytes (T-LDGL), also known as T-cell large granular lymphocyte leukemia. Fifteen adult patients with PRCA associated with T-LDGL comprise this study. Neutropenia and rheumatoid arthritis were uncommon. All patients responded to immunosuppressive therapy. The 2 most commonly used treatments were prednisone and cyclophosphamide +/- corticosteroids, producing overall response rates of 50% and 60%, respectively. Treatment with cyclophosphamide was associated with a more durable remission (median, 60 versus 7.5 months). After a median follow-up of 67 months, 2 patients died of treatment-related complications, one from myelodysplasia and another from cyclosporine-induced renal failure. The clinical course and treatment responses of PRCA associated with T-LDGL in this series were similar to the general group of PRCA. Because T-LDGL is frequently underdiagnosed, it is likely that a significant proportion of idiopathic or primary PRCA is in fact secondary to T-LDGL. | |
9217665 | High plasma levels of the soluble form of CD30 activation molecule reflect disease activit | 1997 Jun | PURPOSE: To determine the plasma levels of soluble CD30 (sCD30) in Wegener's granulomatosis (WG) patients, and to investigate the possible correlation of sCD30 with disease extent and activity. PATIENTS AND METHODS: sCD30 was determined by radioimmunoassay in 57 WG patients, 25 patients with rheumatoid arthritis (RA), 23 patients with bacterial infections and 21 healthy controls (HC). The extent and activity of WG disease were assayed according to disease extent index (DEI) and standard laboratory parameters. RESULTS: Plasma sCD30 levels in generalized WG (22.5 +/- 1.5 U/mL), but not in initial phase WG (12.1 +/- 4.0 U/mL), were significantly increased compared with HC (8.8 +/- 0.9 U/mL, P < 0.0001). Furthermore, of 11 generalized WG patients who received long-term follow-up, sCD30 levels declined when the disease activity changed from active disease to remission (29.1 +/- 1.9 U/mL to 15.9 +/- 1.8 U/mL, P = 0.0001). Similar results were observed in the whole group of generalized WG, eg, sCD30 levels in active disease (29.4 +/- 1.4 U/mL) were significantly higher than in partial remission (17.9 +/- 1.9 U/mL, P < 0.001) and in complete remission (13.7 +/- 3.3 U/mL, P < 0.001). No significant difference was noted between complete remission and HC. In addition, sCD30 levels were correlated with other parameters of disease extent and activity such as DEI, plasma levels of sIL-2R, PR3-ANCA, ESR and CRP. The sCD30 levels were increased in RA patients compared with HC (15.2 +/- 2.1 U/mL, P < 0.05), but no correlation was found between disease activity parameters and sCD30 levels. In contrast, in patients with bacterial infections sCD30 levels (6.9 +/- 0.9 U/mL) were not significantly different compared with HC. CONCLUSION: Plasma levels of sCD30 are not only significantly increased but also correlate with disease extent and activity in generalized WG. These findings suggest that sCD30 can act as a useful marker for evaluation of disease extent and activity, and that generalized WG may be associated with Th2-type immune response. | |
10740981 | Cathepsins B and L in synovial fluids from patients with rheumatoid arthritis and the effe | 2000 Feb | To clarify the pathophysiological role of cathepsins in rheumatoid arthritis (RA), we investigated whether cathepsin B or cathepsin L was increased in synovial fluid (SF) of RA joints, and whether the cathepsin isolated from SF of RA patients activated pro-urokinase or not. Thus, we estimated the content of cathepsins in SF of RA patients by measuring their activities by fluorospectrometry, using Z-Phe-Arg-MCA as the substrate. Cathepsin activity was approximately 4-fold higher in the SF of RA patients than in those of patients with osteoarthritis. Cathepsin B and cathepsin L were separated by cation-exchange column chromatography. As a result, a large peak corresponding to cathepsin B and a very small peak corresponding to cathepsin L were detected. Biochemical sequential fractionation of the cathepsin purified from the SF showed that the large peak was mainly composed of cathepsin B. This purified enzyme induced conversion of pro-urokinase to urokinase, and the Km for pro-urokinase was approximately 8.27 microM. These findings indicated that an imbalance between cathepsin B and its inhibitors occurred due to increased concentrations of active cathepsin B in RA articular lesions, and that cathepsin B might be related to the degradation of cartilage in RA by activating the fibrinolytic cascade. | |
9022805 | Analogues of methotrexate in rheumatoid arthritis. 2. Effects of 5-deazaaminopterin, 5,10- | 1997 Jan 31 | Twenty-six compounds derived from the 5-deaza- and 5,10-dideazaaminopterin series of aminopterin analogues were evaluated for antiarthritic activity in the mouse type II collagen model. New compounds in the 5-deaza series were prepared by alkylation of an appropriate N-substituted (4-aminobenzoyl)-L-glutamic acid dialkyl ester or N-(5-amino-2-thenoyl)-L-glutamate diester with a 2,4-diamino-5-alkyl-6-(bromomethyl)-5-deazapteridine. The resultant 5-deazaaminopterin diesters were saponified to provide the target 5-deaza analogues. 5,10-Dideazaaminopterins were synthesized by similar alkylation of the carbanions of appropriate 4-carboxyphenylacetic, (5-carboxy-2-thienyl)acetic, or (5-carboxy-2-pyridyl)acetic acid dimethyl esters. The diesters of the 2,4-diamino-4-deoxy-10-carboxy-5,10-dideazapteroic acid types so obtained were saponified and then readily decarboxylated by heating in Me2SO solution to provide the 2,4-diamino-5,10-dideazapteroic acid-type intermediates. Peptide coupling with diethyl L-glutamate followed by ester hydrolysis at room temperature afforded the new 5,10-dideazaaminopterin analogues. 5-Deazaaminopterins bearing an alkyl substituent at the 5-position were generally quite effective as antiinflammatory agents. Thus 5-propyl-5-deazaaminopterin, 5-methyl-10-propargyl-5-deazaaminopterin, 5-methyl-10-allyl-5-deazaaminopterin, 5-ethyl-5-deazamethotrexate, and 2,5-disubstituted thiophene analogue of 5-methyl-5-deazaaminopterin showed potencies greater than methotrexate by intraperitoneal or oral administration and were active over a considerably broader dose range. Useful activity in the 5,10-dideaza series was only observed for 5,10-dideazaaminopterin and its 10-methyl analogue. Alkyl substitution at C-5 or C-10 was generally detrimental to antiinflammatory activity in this series. | |
11354563 | Serum ferritin as a serologic marker of activity in systemic lupus erythematosus. | 2001 Apr | To investigate the relationship between serum ferritin and disease activity in systemic lupus erythematosus (SLE), we enrolled 128 patients with SLE (18 males and 110 females). Twenty-eight patients (2 males and 26 females) with rheumatoid arthritis (RA) served as controls. The SLE patients were subdivided into three groups according to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores: groups A (0-5), B (6-9), and C (> or =10). We prospectively evaluated 48 SLE patients before and after treatment. Serum ferritin and anti-dsDNA antibody were measured by radioimmunometric assay. C-reactive protein (CRP) was measured quantitatively by immunonephelometry. Complements 3 and 4 (C3 and C4) were measured by nephelometry. Serum levels of ferritin during the more active stage of SLE (group C) exceeded those of RA patients and patients at less active stages of SLE (groups A and B). There were no significant differences between RA patients and groups A and B. Serum ferritin was elevated especially in serositis and hematologic manifestation. In this prospective study, changes in SLEDAI scores before and after treatment correlated significantly with serum ferritin levels and inversely to C3 and C4 levels. We confirm that serum ferritin levels can be a useful marker of disease activity in SLE patients. | |
11317923 | [Treatment of inflammatory diseases: safety of long-term use of infliximab]. | 2001 Mar 31 | INFLIXIMAB: Is a chimeric antitumour necrosis factor-alpha monoclonal antibody that has been studied for the treatment of Crohn's disease and rheumatoid arthritis. A LONG TERM SAFETY: In several placebo controlled, randomized clinical trials and open trials, 771 patients have been given infliximab (a further 192 received placebo). Follow-up for safety has included the time of study (12 weeks after the last infusion), plus 3 additional years. GENERAL TOLERANCE: Acute infusion reactions (headache, fever, chills, urticaria, chest pain) were seen in 17% of patients receiving infliximab compared with 7% of those receiving placebo. While infections were reported more frequently overall in the patients given infliximab (26% over 27 weeks of follow-up versus 16% of placebo-treated patients over 20 weeks of follow-up), there was no increased risk of serious infections. There was no difference in the overall mortality rate between the groups. AT THE POINT OF VIEW IMMUNOLOGIC: While low titres of autoantibodies developed in less than 10% of patients, drug-induced lupus was seen in less than 1%, with these cases resolving upon discontinuation of the drug. Overall, infliximab showed an acceptable safety profile. | |
11503842 | Fractures in adults on systemic steroid therapy: which prophylaxis? | 1999 Oct | (1) Systemic steroid therapy leads to a loss of bone density after a few months. The loss is at least partly reversible on treatment cessation. Together with age, the underlying disease, and reduced mobility, systemic steroid therapy is a risk factor for fractures. (2) There are no treatments with proven efficacy in the prevention of fractures among patients on systemic steroid therapy. Prevention is thus based on restricting steroid therapy to situations where the benefits are likely to outweigh the risks. (3) The first preventive measure is to encourage adequate calcium intake, as for all subjects at risk of osteoporosis. There is no firm evidence that all patients on steroids require medicinal calcium supplementation. (4) Some treatments slow the decline in bone density associated with steroid therapy, but none has a demonstrated preventive effect on symptomatic fractures. This is the case of the calcium + vitamin D combination, which has the best risk-benefit ratio. Two diphosphonates and, in postmenopausal women, hormone replacement therapy, also have a positive effect on bone density. | |
9370881 | Relations between synovial fluid and serum concentrations of osteocalcin and other markers | 1997 Sep | OBJECTIVE: To determine if osteocalcin (OC) is locally produced in the joint and to study the relation between markers of bone, cartilage, and synovial tissue turnover. METHODS: The concentrations of OC, keratan sulphate epitope (5D4), and hyaluronate (HA) were measured in paired serum and synovial fluid in 10 healthy volunteers and 15 patients with osteoarthritis (OA) and 16 with rheumatoid arthritis (RA). OC was measured with a commercial immunoradiometric assay and concentrations of 5D4 and HA were measured using enzyme linked immunosorbent inhibition assays. RESULTS: Synovial fluid OC was found to be significantly lower than serum (p < 0.001) in all patients and controls. Synovial fluid OC concentrations were directly correlated with serum concentrations (r = 0.63, p < 0.001) and with age (r = 0.48, p < 0.01). There were also some relations between OC, HA, and 5D4 in patients with OA and RA. The OC concentrations were directly correlated with HA (r = 0.68, p < 0.01) in OA serum and there was a similar correlation in RA synovial fluid (r = 0.69, p < 0.01). A weak negative correlation was found between OC and 5D4 in OA serum (r = -0.55, p = 0.035) while a weak positive correlation was found in RA serum (r = 0.53, p = 0.034). CONCLUSIONS: These results show that more OC is present in the circulation than in knee joint fluids suggesting that synovial fluid OC may be derived from the blood. | |
10732003 | Rheumatoid arthritis. New disease-modifying and anti-inflammatory drugs. | 2000 Mar | Treatment options for rheumatoid arthritis (RA) are expanding as research has provided a more complete understanding of the pathophysiology of the disease. Three disease-modifying agents approved in the last 18 months for early intervention in RA are etanercept, leflunomide, and infliximab. For the relief of the signs and symptoms of RA, the new selective cyclooxygenase-2 (COX-2) inhibitors are joining the available nonsteroidal anti-inflammatory drugs. One COX-2 inhibitor is approved for use in RA, and another is under investigation for that indication. As a class, the COX-2 inhibitors offer efficacy similar to traditional NSAIDs but with less GI and platelet toxicity. | |
11005747 | Severe anaemia: implications for functional recovery during rehabilitation. | 2000 Aug 15 | PURPOSE: This case report examines the hospital course and functional recovery of a geriatric patient with severe anaemia undergoing rehabilitation following total hip replacement. It serves to highlight the need for further study of the impact of anaemia on recovery in the rehabilitation setting as well as the importance of developing clinical guidelines for the appropriate medical management of anaemia in this patient population. METHODS: Single case report. RESULTS: The course of recovery during rehabilitation in a geriatric patient with severe post-operative anaemia was notably different from other geriatric patients undergoing rehabilitation following total hip replacement. The patient demonstrated a markedly reduced tolerance for therapies and prolonged length of stay, but did not experience cardiopulmonary complications during intensive rehabilitation. Her hematocrit responded nicely to treatment with human recombinant erythropoietin. Despite a prolonged recovery period, the patient ultimately progressed well and achieved a good functional outcome. CONCLUSIONS: The impact of anaemia on functional recovery in the acute inpatient rehabilitation setting as well as the theoretical risk of increased morbidity and mortality during prescribed therapeutic exercise has not been closely examined in the literature. Further study is indicated to examine the implications for anaemia on functional recovery and cardiopulmonary complications during rehabilitation. General guidelines should be developed for the management of anaemia in the rehabilitation setting. | |
9374930 | Neoral--new cyclosporin for old? | 1997 Oct | Cyclosporin A is now well established as an effective second-line drug to treat rheumatoid arthritis. In April 1995, the microemulsion-based formulation of cyclosporin (Neoral) was introduced based on its increased bioavailability at 'no extra cost'. There may have been concerns that with increased bioavailability of Neoral, some patients might experience increased toxicity, particularly if transferring from Sandimmun to Neoral at the same dose. We describe our experience of 51 patients treated with Neoral--39 with rheumatoid arthritis, six with psoriatic arthritis and the remainder with a variety of diseases, including Behçet's, systemic lupus erythematosus and juvenile chronic arthritis. All patients continued their other medication including non-steroidal anti-inflammatory drugs and analgesics. Five continued low dose prednisolone (average 7.5 mg per day) all patients were monitored for safety and efficacy throughout their treatment according to standard protocol. Five patients were enrolled in a study of efficacy and safety where the dose of cyclosporin was reduced to 2.5 mg/kg/day at the time of conversion, i.e. to Neoral 2.5 mg/kg/day; 19 patients were converted dose for dose, cyclosporin A dose range 2.5-4 mg/kg/day converted to Neoral dose range 2.5-4 mg/kg/day and 27 patients started Neoral de novo. We conclude that cyclosporin is a useful disease modifying anti-rheumatic agent, and our experience suggests that the new formulation, Neoral, has a similar safety and efficacy profile to the original preparation (Sandimmun). Neoral was relatively easy to manage and we noted a slight reduction in dose when compared to Sandimmun. With dose adjustments over 18 months the mean dose for patients with RA fell from 3.2 to 2.7 mg/kg/day and of the 27 patients starting Neoral de novo only seven required an increased dose above 2.5 mg/kg/day in order to establish efficacy. | |
9870879 | Cytokine-regulated expression of activated leukocyte cell adhesion molecule (CD166) on mon | 1998 Dec | OBJECTIVE: To determine whether monocyte/macrophage expression of the CD6 ligand, activated leukocyte cell adhesion molecule (ALCAM) (CD166), is regulated by cytokines during inflammation in rheumatoid arthritis (RA). METHODS: We used flow cytometry to test whether cytokines present in rheumatoid synovium could regulate ALCAM cell surface expression on peripheral blood (PB) monocytes and RA synovial fluid (SF) macrophages, and we examined ALCAM expression in situ in RA synovium by immunofluorescence. RESULTS: The monocyte differentiation factors interleukin-3, macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor augmented ALCAM expression on PB monocytes. ALCAM was expressed on monocyte-lineage cells in situ in inflamed synovium from patients with RA (9 of 9), but not in uninflamed synovium from patients with joint trauma (0 of 3). Furthermore, in vitro culture-induced ALCAM expression on PB monocytes and CD14+ RA SF cells was inhibited by an M-CSF neutralizing antibody. CONCLUSION: ALCAM expression on PB and SF monocytes/macrophages is enhanced by M-CSF. | |
9836374 | Joint inflammation and cartilage destruction may occur uncoupled. | 1998 | Chronic arthritis is characterized by a persistent joint inflammation and concomitant joint destruction. Although the joint swelling is a major clinical problem, destruction of bone and cartilage may occur uncoupled to inflammation and it is of utmost importance to fully understand the elements of the destructive process. TNF and IL-1 are considered master cytokines in the process of human RA, with a claimed cascade of TNF inducing most of the IL-1 production. Studies in experimental models revealed that TNF is indeed a pivotal cytokine in joint swelling, yet IL-1 is the dominant cartilage destructive cytokine and its production may occur independent of TNF. This was found with anti-TNF/IL-1 neutralizing antibodies and the observations were recently backed up with similar data in arthritis models in TNF and IL-1 knockout mice. Apart from the absolute level of IL-1, the destructive potential of an arthritis is determined by the balance with regulatory cytokines and anabolic growth factors. IL-4, IL-6, and IL-10 can promote inflammation and tissue fibrosis, yet cartilage destruction is found to be greatly reduced by these cytokines, linked to a range of pathways which can reduce the IL-1 impact on the articular cartilage. Finally, the presence of anabolic growth factors in the inflamed synovium may have a major impact on net destruction. Endogenous transforming growth factor-beta (TGF-beta) is found in inflamed synovia, but local coadministration of TGF-beta further enhanced the degree of synovitis, yet almost fully prevented cartilage damage, providing another example of a major lack of correlation between inflammatory mass and destructive potential. It is suggested that novel therapy in RA patients should not only focus on reduction of outer signs of joint inflammation, but should also include attempts at reduction of cartilage destruction. | |
9513609 | A study of metalloproteinases in fifty joint fluid specimens. | 1997 Jun | OBJECTIVES: To study the activity and concentrations in joint fluid of gelatinases (A or matrix metalloproteinase (MMP)-2 and B or MMP-9), tissue inhibitor of metalloproteinases 1 (TIMP-1), and stromelysin-1 (MMP-3). METHODS: Synovial fluid specimens obtained as part of a diagnostic or therapeutic procedure were studied. Protein levels were determined, cells counted, crystals looked for and microbiological studies done. Gelatinolytic activity was determined quantitatively using computerized zymography. Proteins were identified by electrotransfer and immunorevelation. TIMP-1 and stromelysin-1 were assayed using an ELISA. Results were confronted with laboratory test and clinical findings. RESULTS: Of the 50 specimens studied, 25 were from joints with mechanical disorders and 25 from joints with inflammatory disorders. Activated MMP-2 was found in all the specimens, with no differences between the two groups. MMP-9 was found only in its inactive form. MMP-9, TIMP-1 and MMP-3 were found more often in inflammatory than in mechanical fluids and the levels of MMP-9 and TIMP-1 were correlated with neutrophil counts. In the 16 fluids from rheumatoid arthritis patients, levels of MMP-9 and TIMP-1 were closely correlated with serum C-reactive protein levels. CONCLUSIONS: MMP-9, TIMP-1, and MMP-3 levels show striking differences between inflammatory and mechanical joint fluids. | |
10873487 | Chlamydia pneumoniae present in the human synovium are viable and metabolically active. | 2000 Jul | We demonstrated that chromosomal DNA from Chlamydia pneumoniae is present in synovial tissue in at least some patients with reactive arthritis/Reiter's syndrome and other arthritides. Here, we provide initial molecular evidence that the bacterium is viable and metabolically active when present in the synovium. We used reverse transcription-polymerase chain reaction (RT-PCR) assays targeting primary transcripts from the chlamydial rRNA operons, and mRNA from several C. pneumoniae genes (hsp60, ompA, KDO transferase, Mr=76000 protein), to analyse RNA preparations from synovial tissue of 10 patients with various forms of arthritis; each patient was known to be PCR-positive for C. pneumoniae DNA in synovium prior to RT-PCR assays. Two PCR-negative patients served as controls for RT-PCR assays. In the 10 patients PCR-positive for C. pneumoniae DNA, RT-PCR assays targeting primary transcripts from the rRNA operons of the organism showed that these molecules were present in each sample, as were transcripts from the bacterial hsp60 gene. Assays targeting mRNAs from the Mr=76000 protein and the KDO transferase genes of C. pneumoniae gave positive results for 6/10 preparations. We were unable to identify mRNA from the chlamydial major outer membrane protein gene (ompA) in any preparation. RNA preparations from the two control patients were negative in all RT-PCR assays targeting C. pneumoniae transcripts. These results indicate that in patients infected with the organism, synovial C. pneumoniae are viable and metabolically active, as are C. trachomatis cells in the same context. Such viability is consistent with a role in long-term contribution to pathogenesis in joint disease. | |
9775171 | [Vitiligo in multiple autoimmune syndrome: a retrospective study of 11 cases and a review | 1998 May | PURPOSE: The occurrence in the same patient of three or more autoimmune diseases defines multiple autoimmune disease. Multiple autoimmune disease is an unusual condition in which dermatological autoimmune diseases and especially vitiligo have an important place. METHODS: We examined retrospectively 11 cases of multiple autoimmune diseases associating vitiligo. We studied the clinical characteristics of vitiligo and those of the associated autoimmune disorders. RESULTS: Type III multiple autoimmune disease was diagnosed in all the 11 cases observed. Autoimmune vitiligo was the first autoimmune disorder observed in seven cases and was bilateral, symmetrical and acrofacial in eight cases. Autoimmune thyroid disorder was associated in ten cases. Our data confirms the important association between vitiligo and thyroid autoimmune disorders. CONCLUSION: The predominant female ratio and the acrofacial topography of skin lesions could predict association with others autoimmune disorders in patients with vitiligo. | |
11585004 | Infliximab. | 2001 Jun | Infliximab (Remicade, Centocor, Inc.) is an intravenously administered monoclonal antibody to TNF proven effective in the treatment of moderate to severe Crohn's disease (CD). Its introduction in October 1998 was heralded by some as the most important addition to therapy for this condition in 50 years. Since then, additional indications have been added as efficacy has been proven in fistulising CD and in rheumatoid arthritis. Even though the costs associated with a single dose are several thousand US dollars, more than 150,000 patients have received infusions since its approval. |