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Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes

PMID	Title	PublicationDate	abstract
3261592	DQ beta polymorphism and genetic susceptibility to Felty's syndrome.	1988 Aug	We used an oligonucleotide probe specific for a polymorphic sequence in the HLA-DQ beta gene to investigate the role of DQ polymorphism in genetic susceptibility to Felty's syndrome (FS) and rheumatoid arthritis (RA). The sequence of this gene was identified from a complementary DNA library derived from an RA patient's B lymphoblastoid cell line. With this probe, we studied the prevalence of the specific DQ beta allele in DR4 positive FS patients, RA patients, and normal control subjects. Significantly more FS patients (17 of 25) showed hybridization with this oligonucleotide probe, compared with the number of DR4 positive non-FS RA patients (7 of 23) and normal controls (7 of 21). The findings indicate that genes linked to the DQ region are important in determining susceptibility to FS.
2724329	Binding of complement component C5 to model immune complexes and the use of anti-C5 antibo	1989 Jan	When normal human or mouse serum is added to micro ELISA plates coated with monomeric or aggregated IgG, complement component C5 binds to IgG. C5 binding was demonstrated with a specific chicken anti-C5 antibody. Hydrazine treatment of the serum or addition of EDTA to the serum abolished the binding of C5. C5-deficient mouse serum was negative for C5 binding, whereas the same serum supplemented with human C5 restored the binding of C5. Chicken anti-C5-coated plates were used for determination of C5-containing circulating immune complexes (CIC). Increased concentrations of CIC were found in sera from patients with rheumatoid arthritis and Bell's palsy.
3313057	Two calcium-binding proteins in infiltrate macrophages of rheumatoid arthritis.	1987 Nov 5	The aetiology and cellular mechanism of chronic inflammatory processes are poorly understood. Macrophages act prominently in the inflammatory response and we report here that they express two calcium-binding proteins. The expression of these proteins, referred to as MRP-8 and MRP-14, is specific for cells of myeloid origin, namely granulocytes, monocytes and macrophages, and is observed in blood granulocytes and monocytes but not in normal tissue macrophages. In acutely inflamed tissues, macrophages can express MRP-14 but not MRP-8, and in chronic inflammations, such as primary chronic polyarthritis, infiltrate macrophages express both MRP-8 and MRP-14. Characterization of MRP-8 and MRP-14 could therefore be useful to the understanding of cellular processes induced in chronic inflammation.
1895266	Antiinflammatory and antiarthritic properties of a substituted quinoline carboxylic acid:	1991 Jun	CL 306,293, a substituted quinoline carboxylic acid at a daily oral dose between 1.5 and 3.0 mg/kg suppressed the inflammation and joint destruction (radiological criteria) associated with both developing and established adjuvant arthritis. When a weekly oral dosing regimen was used, joint destruction was attenuated when this agent was administered at a dose of 50 to 200 mg/kg. Inflammation associated with a delayed type hypersensitivity reaction in dogs was suppressed at a daily dose of 0.25 mg/kg or a weekly dose of 1 mg/kg. At efficacious doses, CL 306,293 had no effects on cyclooxygenase or lipoxygenase activities nor did it have an effect on carrageenin induced paw edema. In acute tests, the compound was not ulcerogenic. The above observations indicate that the antiinflammatory effects of CL 306,293 are distinct from those observed with nonsteroidal antiinflammatory agents. Mechanistic studies conducted and to be published indicate that CL 306,293 down regulates T cell function and this mechanism may account, at least in part, for the antiinflammatory and antiarthritic properties observed in animal models of inflammation and joint destruction.
1960160	Statistics for clinicians. 5. Interval data (I).	1991 May	Interval data may be discrete or continuous. They are usually summarized by the average (arithmetic mean). Sometimes, for example when the possible values in a series change by a constant multiple, we need to use the geometric mean. To obtain the overall or mean percentage of a series of percentage values, we need to calculate their weighted mean. The variability of observations in a sample is measured by the standard deviation, and the variability of sample means is measured by the standard error of mean. Confidence interval is a range which contains the population mean with a known probability. It is obtained by deducting from the sample mean, and adding to it, "t" times the SEM, the value of "t" depending on the desired confidence level (1-P) and the sample size (N). The significance of difference between the mean of two sets of unpaired interval data (MA-MB) is tested by Student's t-test. If the data are paired, the significance of the mean difference (MD) is tested by paired t-test. Ordinal data, ie, grades and ranks, may be analyzed by means of the t-test which is more sensitive and allows more refined analyses if needed.
2678953	Interleukin-1 mediated signal transduction associated with synovial cell activation.	1989 Jun	The early biochemical events that link interleukin-1 (IL-1) receptor occupancy to neutral proteinase production in synovial cells were studied. Addition of human r-IL-1 to human synovial cells in culture stimulated phospholipase A2 (PLA2) activity, inositol triphosphate production and plasminogen activator (PA) activity in a dose dependent manner with similar EC50 values (0.1-0.5 nM). These results, coupled with time courses and other studies, suggest that the IL-1 modulation of PA involves both products of PLA2 and phospholipase C (PLC) activation. On the other hand, the IL-1 induction of collagenase may primarily involve PLC and protein kinase C activation.
3346291	The St Georg sledge for unicompartmental replacement of the knee. A prospective study of 1	1988 Mar	Since 1974, we have made a prospective study in Bristol of the results of unicompartmental knee replacement using the St Georg sledge prosthesis. A total of 115 knees in 100 patients have been followed up for 2 to 12 years (mean, 4 years 9 months). Results have assessed both by the Bristol knee score and by survivorship studies on the total series of 138 knees. Results were excellent or good in 86% and fair or poor in 14%. The survivorship study (based on a definition of failure which included significant pain or a dissatisfied patient or the need for revision) showed a cumulative success rate of 76.4% at six years, with no further failures after that time. Seven knees have been revised, in most cases for deterioration of the contralateral compartment. The operation is recommended as a satisfactory and durable form of treatment for osteoarthritis affecting a single tibiofemoral compartment.
3730734	Heberden oration 1985. The rheology of joints.	1986 Aug	The value of rheological studies of joint tissues has been illustrated by studies from our department. These have included studies of the stiffness of joints which suggest that subjective stiffness is more likely to be related to limitation of movement of a joint than to increased physical stiffness (either elastic or dissipative torques). A review of goniometry suggests that the diminution of joint movement with advancing age varies with the frequency of use of the joint. A simple goniometer for the hip has been described, and in contrast a sophisticated telemeterized system has been devised. Instruments to measure passive movement of joints, and their application for hypermobility, have been discussed. A knee analyser has been constructed to measure ligamentous and meniscal damage. Ligament replacement has been successfully achieved in the pig and in man by using a woven polyester tube. The load-bearing function of the menisci has been clearly demonstrated, explaining the relationship found in studies of parachutists and physical-education teachers between meniscectomy and osteoarthrosis of the knee. Support for the Leeds biomechanical hypothesis for the development of osteoarthrosis has been described from rheological studies of cartilage at the patellofemoral joint and at the ankle. The intervertebral joint does not appear to be a shock absorber in compression. The spine must bend to function in this way. The relevance to rigid segments of the spondylitic spine and surgical fusion of vertebrae is discussed.
1873477	Inhibition of interleukin 1 synthesis by tenidap: a new drug for arthritis.	1991 Jul	Tenidap is a new antiarthritic drug of novel chemical structure. This study shows the effects of tenidap on the in vitro synthesis of interleukin 1 (IL-1). IL-1 production by murine peritoneal macrophages was induced either by stimulation with lipopolysaccharide (LPS) or by phagocytosis of zymosan. With either stimulus, tenidap inhibited IL-1 production as measured by a quantitative competitive IL-1 receptor binding assay. Approximately 20 ng/mL of IL-1 was produced by 10(6) macrophages in response to LPS and about half that amount was produced in response to zymosan. Fifty percent inhibition of IL-1 production by tenidap was found at 3 microM for both stimuli. Using goat anti-IL-1 alpha and Western blot analysis, the appearance of intracellular 34 kDa pro-IL-1 alpha was inhibited by tenidap down to 3 microM. Tenidap decreased [35S]Met incorporation into cellular protein at 30 microM but not at 10 or 3 microM, indicating selectivity for IL-1 inhibition relative to total protein synthesis. Because tenidap inhibited IL-1 induction by both zymosan and LPS, it must act subsequently to receptor triggering. As the appearance of IL-1 was inhibited both intracellularly and extracellularly, the primary drug effect cannot be on secretion.
2012103	The role of infections in the rheumatic diseases: molecular mimicry between bacterial and	1991 Feb	Infections can cause or exacerbate the rheumatic diseases in several ways, including immune cross-reactivity between bacterial heat shock proteins and similar proteins in normal human tissues. This may lead to autoimmunity in rheumatoid arthritis and systemic lupus. In addition, increased activation of the gene regulating the synthesis of a heat shock protein has been found in scleroderma fibroblasts. As an infection-induced model for other rheumatic diseases, rheumatic fever (RF), with its well-established link to prior group A streptococcal infection, will be revisited. The lessons learned from RF and other rheumatic diseases directly linked to infection will be applied to ankylosing spondylitis, rheumatoid arthritis, Sjogren's syndrome and polymyositis, for which a mounting body of circumstantial evidence suggests a probable infectious cause. The interplay of genetic susceptibility and infection with particular organisms and the implications of this new information for present and future therapy of the rheumatic diseases will also be presented.
2379041	Diversity of antibodies to type II collagen in patients with rheumatoid arthritis: detecti	1990 Aug	Antibodies to denatured type II collagen were detected in the sera of a group of patients with rheumatoid arthritis by ELISA and by immunoblotting. The antibodies were further examined by immunoblotting against cyanogen-bromide derived peptides of type II collagen. The majority of sera reacted against only one or two peptides and antibodies to the CB-10 and CB-11 peptides were those most commonly found. However, some sera reacted with up to eight peptides, indicating that patients had antibodies to differing combinations of epitopes on type II collagen. Examination of sequential serum samples from an individual patient showed that there were changes in the class of antibody produced to type II collagen and that antibodies to different peptides were preferentially produced at different times in the course of the disease. Thus there was a selective response to different peptides of type II collagen not only between patients but also at different times in the course of disease in the same patient.
2678392	[Analysis of distribution of histocompatibility antigens class I and II in children with r	1989 Apr	The authors studied distribution of antigens HLA A, B, C in 115 children and of antigens HLA DR in 102 children of the Russian nationality with classic or diagnosed juvenile rheumatoid arthritis (JRA). A rise in the frequency of antigens B21, B27 and DR3 was noted as compared to the control values. Then distribution of HLA-antigens was analysed in separate groups of patients depending on the nature of the clinical course of JRA. It was characteristic of patients of patients depending on the nature of the clinical course of JRA. It was characteristic of patients with mono-oligoarthritis with an polyarticular form of JRA to exhibit a rise in the frequency of antigens B27 and DRW8, with uveitis--of antigens A2, B27 and DRW8, with a high degree of activity of the inflammatory process--B21, with an allergic variant--B21, with an articulovisceral form--B21, DR3 and DR4, with Still's disease--DR3, rheumatoid nodes--DR2 and DR3. Thus, specificity of associations was determined in most of the cases by the nature of JRA clinical course. The authors confirm the number of associations previously described in the literature abroad.
3616947	[Immune reactions with streptococcal antigens and homologous myocardial tropomyosin in rhe	1987	A humoral and cellular immune response to polysaccharide and protein antigens of the cell wall of streptococci (Groups A, B, C and G) and to homologous myocardial tropomyosin was studied in patients with rheumatoid arthritis (RA) with different clinical variants of disease and in healthy persons. In RA patients humoral and cellular immune reactions to polysaccharide and protein streptococcal antigens were especially marked with the use of the structural components of the cell wall of streptococcus, Group B. Elevated titers of antibodies to homologous myocardial tropomyosin were detected in RA patients as compared to those in a group of healthy persons, an average titer of antibodies to tropomyosin in RA patients with systemic symptoms being much higher than in patients with an articular form of disease. The authors emphasized a possible role of antigens of the cell wall of streptococcus, Group B, in the occurrence and development of immunopathological reactions in RA, and a role of antibodies to myocardial tropomyosin in immunopathogenesis of cardiac disorder in this disease.
3665247	Salvage procedures for complications of total ankle arthroplasty.	1987 Nov	Total ankle arthroplasty (TAA) has been a satisfactory procedure with a low failure rate only when applied to the rheumatoid patient. For the active, posttraumatic patient, ankle joint fusion is superior and avoids the attendant high failure rate. In general, salvage of failed TAA is best solved by ankle fusion. Only in one of five cases (a compliant patient with a clear-cut correctable technical error) was a good result achieved with a revision arthroplasty. To maintain limb length, the authors transplanted iliac crest autogenic bone to fill a large defect. When tightly packed with bone, the joint is slightly distracted and compression enhances fusion. For septic loosening, osteotomy of the malleoli and fusion without grafting is recommended. Persistent pain unassociated with loosening an infection may be treated by removal of impingement of bone overgrowth. Soft tissue release to improve motion is rarely successful. Marginal skin slough was a problem in 8.5% of 71 cases. To facilitate healing, debridement of nonfunctional exposed tendons may be advisable.
3940692	Turbidimetry of rheumatoid factor in serum with a centrifugal analyzer.	1986 Jan	We describe the simple, rapid turbidimetry of IgM rheumatoid factor in human serum by use of the Cobas-Bio centrifugal analyzer. Heat-aggregated human IgG is used as the antigen. The immunoturbidimetric reaction is monitored at 340 nm for 300 s, and the changes in absorbance after the antigen is added are used to prepare the standard curve. Test results are calculated from the stored curve and reported in int. units/mL, based on comparison with the WHO reference serum for rheumatoid factor. There is no interference from bilirubin (up to 340 mumol/L) or hemoglobin (up to 5600 mg/L). Serum samples with a triglyceride concentration greater than 2.20 mmol/L must be cleared of lipids before analysis. The standard curve is linear from 30 to 500 int. units/mL. Precision, accuracy, linearity, and sensitivity are quite acceptable. The CV was generally less than 5% for different concentrations of rheumatoid factor. Results agree well with those by a rate-nephelometric procedure on the Beckman ICS system (rs = 0.932). However, both correlate poorly with a modified classical Waaler-Rose test. Of 47 patients with rheumatoid arthritis, 34 had IgM rheumatoid factor in their serum, but the measured value did not reflect the activity of the disease.
3232034	Interactions between the immune system and connective tissue in arthritis. Possible signif	1988	The synovial inflammation in rheumatoid arthritis (RA) resembles inflammatory reactions in other tissues concerning features such as increased expression of MHC class II antigens and infiltration of large amounts of activated T lymphocytes. The present communication is concerned with how to explain features such as local production of rheumatoid factors that distinguish the synovial inflammation in seropositive RA from other chronic inflammatory reactions; We show here that monomeric IgG and, to an even higher extent, aggregated IgG show a high binding capacity for native collagen type II. This finding is discussed in the light of previous findings that native collagen II structures are readily exposed to the environment in the cartilage of inflamed joints, and the evidence that T-cell reactivity to cartilage-derived molecules among them collagen II appears to be a common feature in seropositive RA. We suggest that an enhanced formation of IgG-collagen II complexes in RA joints, together with activation of T-cells to collagen II or collagen II-associated structures may constitute the basis for local rheumatoid factor production and to disease perpetuation in seropositive RA.
3363280	Significance of rheumatoid factors in an eight-year longitudinal study on arthritis.	1988	A community-based cohort comprising 150 patients with recent-onset seropositive arthritis or seronegative oligoarthritis or polyarthritis was monitored for 8 years. Of the different rheumatoid factor (RF) tests, the initial positivity in the most sensitive assays (latex slide test and IgM-RF by enzyme immunoassay) was the most reliable factor when distinguishing between the erosive and nonerosive cases. The individual RF isotypes fluctuated in four serial specimens, but each patient tended to preserve his or her reactivity pattern. Seroconversion from positive to negative within the 1st year of follow-up did not indicate a particularly good long-term prognosis.
3213269	[Effectiveness and limits of D-penicillamine therapy].	1988	A total of 232 patients with rheumatoid arthritis were treated with DPA. Withdrawal from treatment was mainly due to adverse events in the first year of treatment, while in the subsequent years it was mainly due to loss of efficacy. Of the patients treated, 68 were included in the present study, as they fulfilled the criteria of continuous long-term observation regularly performed. The effects of therapy were graded after 1 year of treatment, at the last examination in the outpatient department or before withdrawal, respectively. It could be seen that a long duration of the disease did not exclude positive effects of therapy; however, early use of DPA led to more favourable results with respect to the number of successfully treated patients and to the extent of the grading of efficacy. In patients who did not respond to DPA therapy, not only was the duration of the disease longer, but also previous therapy with other slow acting antirheumatic agents had been stopped because of inefficacy. This group of patients seems to cover therapy-resistant cases. After 1 year of treatment, improvement was measured in 54 patients. During further treatment, a tendency to return to initial values of clinical and laboratory parameters was noted. In about half the patients with only moderate improvement after 1 year, subsequent treatment was terminated (because of inefficacy) quite soon in most cases, i.e. within 5 years. Optimal improvement after 1 year, however, seems to indicate a long-term positive response to DPA therapy. In cases with no obvious effect of DPA after 1 year a response is not to be expected with ongoing treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
2958193	Origin of defective T lymphocyte-suppressor activating factor interaction in patients with	1987 Jul	We previously examined the generation of T cell released suppressor activity (TRSA) from peripheral blood T cells from patients with rheumatoid arthritis (RA) in response to a soluble suppressor activating factor (SAF) produced by a 6-thioguanine resistant mutant of the human T cell line CEM. We reported (Lau et al., 1985 Clin. exp. Immunol. 61, 481) that T cells from a substantial proportion of RA patients exhibited impaired TRSA release. To delineate further the TRSA abnormality observed in patients with active RA, we evaluated the kinetics of SAF activation, precursor frequency of SAF reactive cells and quantity of activated SAF released on a per cell basis. The results showed that a lower precursor frequency of SAF reactive cells accounted for defective TRSA release in a majority of RA patients, while TRSA release on a per cell basis was normal. The defective TRSA response to SAF could not be explained by abnormal dose kinetics of SAF, time kinetics of TRSA release or prior in vivo lymphocyte activation of the RA T cells.
3941125	Complications of the Attenborough knee replacement.	1986 Jan	Of a consecutive series of 144 Attenborough knee replacements, 107 were re-examined between two and six years after operation and revealed a high incidence of complications. Wound problems were common and led to deep infection in four knees. When a patellar implant was used fracture of the patella followed in 17.5% of knees, but when the patella was not resurfaced 16% of knees developed patellofemoral pain of sufficient severity to require a further operation. In 10% of knees, definite loosening of one or both of the major components occurred.