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

ID PMID Title PublicationDate abstract
3307875 Protein fluorescence and its relationship to free radical activity. 1987 Jun Evidence for free radical involvement in pathological processes is often indirect and frequently depends upon the detection of characteristic changes in tissue constituents, particularly polyunsaturated lipids. Free radical attack on protein leads to specific oxidative changes in their constituent amino acids, principally cysteine, tryptophan and tyrosine. This is associated with the induction of characteristic fluorescence (excitation 360 nm, emission 454 nm) and protein aggregation. This observation leads to a suitable assay for studying protein oxidation, and such fluorescent proteins may be relevant in the pathogenesis of diabetic microangiopathy and rheumatoid arthritis.
3585824 The role of psychological influences in rheumatoid arthritis. 1987 Patients with rheumatoid arthritis were tested on a number of psychological variables, including locus of control, cognitive style, general psychopathology and problem solving. Demographic data were also noted, including social supports and life events. Those people whose serum was positive for rheumatoid factor showed a negative style of thinking, particularly in relation to their illness, and they were more likely to believe in powerful external forces. There were no differences between these patients and those who did not have rheumatoid factor on the general measure of psychopathology, except that the positive group experience more phobias. This latter result is in contradiction to previous findings, and a number of possible reasons are discussed.
3124860 Folate status of rheumatoid arthritis patients receiving long-term, low-dose methotrexate 1987 Dec The folate status of 29 healthy control subjects, 16 rheumatoid arthritis (RA) patients taking methotrexate (MTX), and 20 RA patients who were not being treated with MTX was estimated by an assay of the folate-dependent enzymatic synthesis of serine from formate and glycine, which is termed the C1 index. Analysis of variance demonstrated that the specific activity of the enzyme system in lymphocytes was significantly lower in the MTX-treated group, with an activity approximately one-half that of the control and the non-MTX-treated groups. Since the C1 index is one of the first biochemical parameters found to be different between MTX-treated and non-MTX-treated groups, alterations in folate-mediated amino acid metabolism may be involved in the mechanism of response to MTX therapy. Use of the C1 index may assist in the development of protocols which preserve the efficacy of MTX therapy while minimizing toxicity.
1826649 Elevation of a gamma delta T cell subset in peripheral blood and synovial fluid of patient 1991 Apr We examined the levels of TcR delta 1+ T cells (total gamma delta T cell) and delta TCS1+ (gamma delta T cell subset) T cells in the peripheral blood (PB) and synovial fluid (SF) of 16 patients with rheumatoid arthritis (RA) and compared them to the levels in PB of patients with Felty's syndrome (FS) and 21 healthy control subjects (NML). Synovial fluid from eight patients with seronegative spondyloarthropathies (SSA) was also examined. The results demonstrated elevated levels of the delta TCS1+ subset in the PB of RA and FS patients relative to NML (P less than 0.05). No such differences were observed in the levels of PB TcR delta 1+ T cells. The results did not appear to reflect a non-specific inflammatory response since delta TCS1 T cells were elevated in the SF of RA patients relative to SSA SF and NML PB. delta TCS1 T cells in SSA PB and SSA SF were comparable to NML PB. TcR delta 1+ T cells levels in RA SF were higher than SSA SF levels but were comparable to those of NML PB. Taken together, the results support a pathogenic role for delta TCS1+ T cells in RA.
1791339 [Herpes zoster in connective tissue diseases: II. Rheumatoid arthritis and mixed connectiv 1991 Nov We investigated the incidence of herpes zoster (HZ) and the immunological state to HZ in patients with rheumatoid arthritis (RA) and mixed connective tissue disease (MCTD) in comparison with systemic lupus erythematosus (SLE). HZ occurred in 6 (25%) out of 24 patients with RA and 4 (22%) out of 18 patients with MCTD. One patient had had HZ before the diagnosis of RA. On the other hand, all 4 patients with MCTD had had HZ before the diagnosis of MCTD. The patients with RA and MCTD showed normal or higher antibody titers to varicella zoster virus (VZV) than normal subjects as assayed by both complement fixation technique and neutralization test. However, the antibody levels were not very high compared to those in patients with SLE. On the other hand, only 7 (50%) of 14 patients with RA and 4 (40%) of 10 patients with MCTD showed positive skin reactions to VZV antigen, whereas all 15 normal subjects had positive reactions. Thus, cellular immunity to VZV was thought to be impaired in these diseases. In the patients who were receiving less than 10 mg/day of prednisolone, 7 (64%) of 11 had positive skin reactions in RA patients and 3 (60%) out of 5 patients with MCTD, whereas none (0%) out of 3 patients with RA and 1 (20%) out of 5 patients with MCTD who were receiving 10 mg/day or more prednisolone showed positive skin reactions. These results suggest that the high incidence of HZ in patients with RA and MCTD is probably due to an impaired cellular immunity as in the case of SLE.
3478451 Functional disturbances of the masticatory system related to temporomandibular joint invol 1987 Sep Several theories have been proposed concerning the aetiology of dysfunction of the temporomandibular joint (TMJ). To analyse the relationship of radiographic changes to clinical signs and symptoms of TMJ dysfunction, the present study was conducted in subjects highly predisposed to TMJ involvement, i.e. in patients with rheumatoid arthritis (RA). The aim of the study was to estimate the frequency of disturbances in the masticatory system of RA patients. In addition, the relationship between TMJ abnormalities and the signs and symptoms of dysfunction was investigated. The study consisted of sixty patients with RA and forty control subjects. Asymptomatic subjects were more frequent in the RA group than in the controls. Muscle pain during palpation was recorded in 53.3%, clicking in 53.3%, crepitation in 21.7%, reduced movement capacity of the TMJ in 41.7%, and restricted mouth opening in 31.7% of the RA patients examined. In the control group the most common symptoms and signs were clicking (57.5%), muscle pain during palpation (57.5%) and restricted opening (25.0%). Normal radiographic appearance of the TMJ in RA patients was found in 31.7%. Minor changes comprised 31.7%, moderate changes 21.6%, and severe changes or total loss of the condyle 15.0%. In the control group a normal joint was detected in 87.5%, while minor changes were encountered in 7.5%, and moderate or severe changes only in 5.0%. No relationship was found between Helkimo's anamnestic, clinical or occlusal indices and the severity of the disease graded according the criteria outlined by the American Rheumatism association (ARA). In the ARA group the frequency of signs and symptoms of dysfunction increased with the destructive changes in the TMJ area. In the controls, muscle pain during palpation and clicking sounds in the TMJ were most commonly connected with normal radiographic appearance of the TMJ. In the discriminant analysis the most discriminating factors were crepitation, tenderness to palpation of muscles and movement of TMJ.
2947308 Second-line drug treatment in rheumatoid arthritis associated with depressed autologous mi 1986 The AMLR (autologous mixed lymphocyte reaction) was performed in 24 control subjects, 41 patients with rheumatoid arthritis (RA), 19 patients with ankylosing spondylitis (AS), and 7 patients with psoriatic arthritis (PSA). It was found to be depressed in 21 of the RA subjects and this was linked to medication with sodium aurothiomalate or D-penicillamine. Addition of ultrapure interleukin 1 (IL-1), indomethacin, or catalase did not cause any improvement in the AMLR but some improvement was noted in those RA patients with subnormal AMLR when pure, recombinant interleukin 2 (IL-2) was added to the cultures. Since autoreactive T-cells are generated during the AMLR which are capable of providing help for immunoglobulin production, it is proposed that the defective AMLR seen after second-line drug treatment may be the mechanism whereby rheumatoid factor (RF) production is down-regulated during such treatment.
3402176 Evidence for similarity in testosterone levels in haplotype identical brothers. 1988 Jun An analysis of 89 male sibling pairs from multicase rheumatoid arthritis families demonstrated an association between HLA and serum testosterone levels. In sibling pairs that were haplotype identical, the mean inter-pair difference in testosterone level expressed as a log ratio was significantly less than sibling pairs sharing neither haplotype (p = 0.03). This difference was independent of the RA status of the pairs. These results suggest the presence of a gene(s) controlling testosterone levels linked to the Major Histocompatibility Complex (MHC) on chromosome 6. These findings may aid understanding of the roles of HLA antigens and sex hormones in the susceptibility to RA and other autoimmune disease.
3064525 [Relation of neopterin and beta 2 microglobulin to disease activity in chronic polyarthrit 1988 The correlations of the serum levels of neopterin and beta-2-microglobulin with the disease activity-measured by a clinical index-were investigated in 41 patients suffering from rheumatoid arthritis. Both parameters correlated significantly with the sum of the used disease activity index. There was a closer correlation between the serum levels of beta-2-microglobulin and the sum of the index and most of the particular parameters of the index than it was seen for the neopterin serum levels.
2590603 Salicylate pharmacokinetics in patients with rheumatoid arthritis. 1989 Oct 1. The pharmacokinetics of salicylic acid (SA) and its major metabolite salicyluric acid (SU) were studied in nine patients with rheumatoid arthritis following a 900 mg oral dose of acetylsalicylic acid and during 6 weeks of chronic administration of enteric coated aspirin (3,900 mg day). Response to therapy was also monitored. 2. The various pharmacokinetic parameters determined in the study were similar to those observed in other single dose salicylate studies amongst healthy volunteers but were not predictive of salicylate concentration in the chronic dose study. 3. Plasma concentrations of SA (total and unbound) were found to decline significantly over the 6 weeks and plasma SU concentrations increased. 4. During the chronic dosing study, there was a significant increase in the Vmax (total and unbound) for the formation of SU, whilst the Km and SU clearance remained constant. Also, the elimination rate constant (k) for salicylate was not significantly affected. 5. Therapeutic response to salicylate therapy was not significantly affected by the decline in SA concentrations.
2612748 Campylobacter-like organisms, nonsteroidal anti-inflammatory drugs and gastric lesions in 1989 A histological study was performed in order to evaluate the prevalence of Campylobacter-like organisms (CLO) and gastric antral lesions in 85 rheumatoid arthritis (RA) patients using NSAIDs, and in 100 nonrheumatoid outpatients comparable in terms of sex and age, not using NSAIDs. Histological evidence of gastritis was a common finding both in RA patients (88.2%) and in nonrheumatoid outpatients (89.0%). On the other hand, CLO were detected in a significantly lower proportion (p less than 0.001) of RA patients than outpatients (30.6 and 59.0%, respectively). Considering each NSAID used separately (aspirin, diclofenac sodium and ketoprofen), no significant difference in the presence of CLO in the three groups was found; in the small group of patients treated with aspirin, however, bacteria were never detected. MICs of each NSAID used against 15 isolates of Campylobacter pylori were also determined.
3261054 HLA-DR4 genotype frequency and gender effect in familial rheumatoid arthritis. 1988 May We have studied HLA-A, B, C, and DR antigens in 75 unrelated white families, each with multiple cases of adult-onset definite or classical rheumatoid arthritis (RA) (by ARA criteria). There was no difference in age of onset or serological features of RA between males and females. HLA-DR4 phenotype frequency among female (68%) and male (71%) patients also did not differ significantly. The observed frequencies of HLA-DR4 genotypes (homozygous, heterozygous, and those lacking it) differed significantly (p less than 0.005) between affected and unaffected individuals. However, the observed genotype distribution did not differ from what is expected given the Hardy-Weinburg equilibrium. There is a direct correlation between the number of DR4 allele(s) carried (two, one, or zero) and the percent affected (p less than 0.026 for females and p less than 0.052 for males). These findings highlight the importance of discerning the additional genetic determinants, including those that are gender-associated, which influence susceptibility to RA.
2378171 Migration of the femur head in rheumatoid coxitis. 1990 May The direction of penetration of the destroyed femoral head into the acetabulum in rheumatoid coxitis has been determined by means of the method of geometrical analysis in 81 affected hip joints. Of 48 patients, the duration of coxitis was 1-17 years (mean 4 years). Displacement of the femur head, destroyed by rheumatoid inflammation, was expressed in millimeters by means of a geometrical parameter called "transposition of the center of the femur head". The direction of transposition of the femur head into the deepened acetabulum has been expressed quantitatively by authors making use of the new geometrical parameter "the angle of transposition of the center of the femur head" which is referred to as angle delta. The angle delta is an angle between the line of transposition of the femur head center (tC) and its vertical component. The mean value of the delta angle for the entire group investigated measured 27.6 degrees and ranged from -5 degrees to +54 degrees, whereby an angle of 0 degrees marked the cranial direction of transposition, positive values marked the craniomedial transposition direction of the femur head. The angle delta varied from 21 degrees to 40 degrees in the majority of affected hip joints. The values of the delta angle were constant in every hip joint, thus indicating that the direction of transposition of the femur head did not change in the course of the progression of rheumatoid coxitis. It was found and statistically confirmed that no reciprocal dependence existed between the rate of progression of coxitis and the direction of displacement of the femur head into the acetabulum.(ABSTRACT TRUNCATED AT 250 WORDS)
3006611 Rheumatoid arthritis, juvenile arthritis, iridocyclitis and the Epstein-Barr virus. 1986 Jan In order to examine the relation of Epstein-Barry virus (EBV) infection to chronic arthritis in children antibodies to EB virus capsid antigen (EBVCA) and rheumatoid arthritis nuclear antigen (RANA) were analysed in sera from 133 patients classified as juvenile rheumatoid arthritis (JRA) or pauciarticular, polyarticular, or systemic juvenile chronic arthritis. Except for an increased frequency in the systemic subgroup, the prevalence of antibodies to EBVCA and titres of anti-RANA antibodies was similar in patients and controls. These data do not support an aetiological role for EBV in chronic arthritis in children, including JRA, and suggest that the mechanisms which may account for the higher titres of anti-RANA antibodies in adult RA do not occur in children.
1910687 MHC class-II molecules and autoimmunity. 1991 Molecular and genetic studies of HLA class-II genes provide new insights into the basis for MHC associations with autoimmunity. Polymorphisms among class-II genes identify specific haplotypes associated with autoimmune diseases such as type-I diabetes, rheumatoid arthritis, celiac disease, and pemphigus vulgaris. In some cases, single genes within those haplotypes are themselves implicated in disease susceptibility. Interactions, both cis and trans, between candidate susceptibility genes suggest a number of possible mechanisms critical for autoimmune triggering events involving class-II molecules. Amino acid sequence comparisons between products of candidate susceptibility genes and other class-II genes pinpoint a limited number of critical sites within HLA molecules which appear to be responsible for pathogenic events.
2788150 Interleukin-1 and interleukin-2 production by peripheral blood mononuclear cells of patien 1989 Jul Contradictory results have been reported concerning the secretion of interleukin-1 (IL-1) and interleukin-2 (IL-2) by mononuclear cells of rheumatoid arthritis (RA) patients. In the present study, peripheral blood mononuclear cells from 18 RA patients were stimulated in vitro to produce IL-1 and IL-2 and compared with monocytes of age-matched healthy control subjects. Endotoxin-stimulated monocytes of RA patients produced normal amounts of IL-1 compared with healthy controls (P = 0.5), whereas T-lymphocytes from the same patients produced decreased amounts of IL-2 compared with control T-lymphocytes (P less than 0.01). There was no difference in IL-1 or IL-2 production by mononuclear cells from patients with active or inactive disease. These findings could not be explained by concurrent therapy, and support the notion that defective immunoregulatory T-cell functions are involved in the pathogenesis of RA.
3351840 Effects of rifampicin with and without isoniazid in rheumatoid arthritis. 1988 Jan A patient with rheumatoid arthritis (RA) experienced great improvement in her RA when given antituberculous treatment for pulmonary tuberculosis (TB). Two of the drugs used in TB, rifampicin and isoniazid, include immunomodulatory effects among their properties. To investigate whether these drugs have any effect in RA, we studied 20 patients who were given either rifampicin 600 mg daily (10 patients) or rifampicin 600 mg with isoniazid 300 mg daily (10 patients). Eighteen patients completed at least 3 months' treatment. Six of the 7 patients with early RA (less than 3 years) improved; their median erythrocyte sedimentation rate fell from 43.5-10 mm/h (p = 0.036) and median serum C-reactive protein from 40-0 mg/l (p = 0.036). Eleven patients with longer histories of RA did not improve. Our results suggest rifampicin with or without isoniazid may be effective in RA.
1925260 [Approach to evaluation of the indicators of Yersinia infections in reactive and rheumatoi 1991 Apr A total of 140 patients with reactive arthritis due to Yersinia infection were under observation for 2-10 years. A group of 104 patients with erosive rheumatoid arthritis served as control for analysis of the results of bacteriological and serological studies. The bacteriological analysis of the feces, urine, smears of the feces and blood were made repeatedly. As established the articular syndrome in reactive arthrosis has its specific features depending on the nature of the pathological process: primary, recurrent and chronic. Patients with primary reactive arthritis exhibited recovery without residual phenomena and relapses in 35.8% of the cases; in 86% the disease relapsed; in 36% it was chronic, persisting for a number of years as a non-erosive seronegative arthritis; in 25.3% arthralgia persisted; in 6.2% the clinical picture of secondary osteoarthrosis developed; in 17.3% the disease changed into spondyloarthritis and in 1.2% of the cases it changed into RA. Since in reactive arthritis Yersinia infection was confirmed in 48.5% of the cases and in RA in 14-21%, laboratory diagnosis cannot serve as an absolute criterion for reactive arthritis. It is necessary to take into consideration the anamnesis and the peculiarities of the clinical picture and the course of the articular syndrome.
3467690 Nailfold capillaroscopy: a blinded study of its discriminatory value in scleroderma, syste 1986 Aug The appearances of the nailfold capillaries can be used to distinguish between various connective tissue diseases. In a study of 30 patients (10 with scleroderma, nine with systemic lupus erythematosus, and 11 with rheumatoid arthritis), photographs were taken of the eight nailfolds of each patient (thumbs excluded) and then coded. Each of the photographs was later analysed by a rheumatology registrar and an attempt was made to predict the patient's diagnosis using only the appearance of the nailfold. The diagnostic specificity and sensitivity were 89% and 80%, respectively. The results indicate that nailfold capillaroscopy, performed by a relatively inexperienced observer, can accurately distinguish between patients with scleroderma and those with systemic lupus erythematosus or rheumatoid arthritis.
1866108 Quantitative 99Tcm-HMPAO white blood cells and 67Ga scanning in rheumatoid arthritis. 1991 Jun This investigation assessed 99Tcm-HMPAO white blood cell (Tc-WBC) and 67Ga knee uptake indices before and after 90Y treatment in patients with intractable rheumatoid arthritis (RA) and correlated the uptake indices with the clinical score. Sixteen knee joints with RA were treated with intra-articular injection of 185 MBq of 90Y-silicate colloid (Amersham) flushed with 50 mg of hydrocortisone. Clinical score, quantitative 67Ga and Tc-WBC knee uptake indices were obtained before and three weeks after treatment. Our results showed that 9/16 (56%) had a good response and 7/16 (44%) had a poor response to 90Y injection. There was poor correlation between clinical improvement and changes in 67Ga and Tc-WBC knee uptake indices (r = 0.46 and 0.14, respectively). The correlation coefficient between changes in 67Ga and Tc-WBC knee uptake indices was 0.29.