Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1865418 | Rheumatic manifestations in myelodysplastic syndromes. | 1991 May | The myelodysplastic syndromes are characterized by ineffective hematopoiesis with possible transformation to acute nonlymphocytic leukemia. We describe a patient with refractory anemia with excess blasts with unusual rheumatic manifestations of vasculitis, migratory synovitis, arthralgias, and myalgias. A retrospective review over a 6-month period of 162 patients with myelodysplastic syndromes found 16 patients (10%) with several rheumatic manifestations. We divided these manifestations into 4 different categories: cutaneous vasculitis, "lupus-like syndrome," neuropathy, and patients with both a rheumatic disease and a myelodysplastic syndrome. There were 7 with cutaneous vasculitis including leukocytoclastic vasculitis and other individual cases of urticarial vasculitis and panniculitis; 3 with lupus-like manifestations with histological evidence of an inflammatory process; 3 with neuropathic manifestations including peripheral neuropathy, mononeuritis with foot drop, and chronic inflammatory demyelinating polyneuropathy; and 3 patients in which their myelodysplastic syndrome was diagnosed after their rheumatic disease was known, including rheumatoid arthritis. Sjögren's syndrome and mixed connective tissue disease. The class with refractory anemia with excess blasts had 9 patients with rheumatic manifestations but also had the largest number of patients in the study (46/162 or 29%). Three of the 16 patients died, all from the refractory anemia with excess blasts class, reflecting the known mortality in this group of patients. We believe there is a significant association between myelodysplastic syndromes and rheumatic manifestations. | |
| 3496934 | Upper gastrointestinal findings and faecal occult blood in patients with rheumatic disease | 1987 Aug | An upper gastrointestinal endoscopic examination was performed, following a test for faecal occult blood, on a group of 108 patients with rheumatic complaints. The majority of the group studied had rheumatoid arthritis (RA) and 50% of the total group were anaemic. Every patient was taking a single nonsteroidal anti-inflammatory drug (NSAID). When the finding of blood in the faeces was compared with findings in the upper gastrointestinal tract, approximately half the subjects with ulcerative and inflammatory lesions had a positive test for blood. However, 50% of the subjects with an apparently normal upper gastrointestinal tract had a positive test for blood in the stool and these comprised the largest group of those examined. It was concluded that the finding of a positive faecal occult blood in such subjects is a poor indicator of ulcerative or inflammatory lesions of the upper gastrointestinal tract. The possible reasons for a finding of blood in the stool of patients taking NSAID who apparently have a normal upper gastrointestinal tract is discussed. | |
| 3962779 | Animal models for the study of atypical anti-inflammatory agents. | 1986 Jan | In contrast to the approach focusing on aspirin and cortisone as models for research, a physiopathologically-oriented approach provides the rationale for developing animal models suitable for detecting anti-inflammatory agents with a profile of therapeutic and side effects unlike that of currently used drugs. The so-called 'primary' anti-inflammatory agents have a marked efficacy in animal models of acute inflammation and lack significant anti-PG effects. Clinically, they relieve the symptoms of acute inflammatory conditions, both topically and systemically, are practically inactive in rheumatic disorders and have a profile of side-effects different from that of aspirin or cortisone. Available data suggest that their characteristic profile of side and therapeutic effects reflect qualitative, rather than quantitative differences, from aspirin and cortisone. The so-called 'secondary' anti-inflammatory agents affect the conditioning factors for some inflammatory diseases, including rheumatoid arthritis, rather than the inflammatory process itself. Besides the derangement of the immune system and the consequent development of immunomodulators, the role of specific protein changes as a conditioning factor is discussed and animal models are illustrated focusing on this phenomenon. The possibility is also discussed that protein denaturation is not only responsible for the formation of new antigenic determinants, but also for necrotic lesions accompanying some inflammatory disorders. Results obtained with animal models of conditioned inflammation with marked necrotic lesions are presented. The interest for this approach is that conditioning factors for inflammation appear a more specific target for drug treatment, rather than inflammation itself. | |
| 2218905 | [Kidney involvement in patients with rheumatoid arthritis]. | 1990 | Renal pathology was revealed in 284 out of 498 patients with rheumatoid arthritis (RA) subjected to the 15 years' prospective controlled follow-up and given individualized pharmacotherapy. Biopsy specimens of the kidney were examined in 90 cases. Of these, in 14 patients, they were examined repeatedly. On morphology the following alterations were detected in renal tissue: minimum morphological alterations (18 cases), glomerulonephritis (32 cases), amyloidosis (53 cases), interstitial nephritis (4 cases), and arteriosclerotic nephrosclerosis (1 case). In patients with nephropathy, no pathology nas revealed on morphology (5 cases). Chronic pyelonephritis was diagnosed in 137, nephroptosis in 47, nephrolithiasis in 17, papillary necrosis in 3, and drug nephropathy in 33 patients. Many patients had concomitant renal pathology. Repeated morphological examinations of renal tissue point to dynamic morphological alterations occurring during treatment and disease. Chlorbutin was found to exert a beneficial effect not only on the manifestations of arthritis but also on renal tissue. It could be seen in patients with a primary morphological diagnosis of mesangioproliferative nephritis and minimum morphological alterations in renal tissue. In some cases the clinical and morphological data did not agree, which provides evidence in favour of making renal biopsy in RA patients with a purpose of early diagnosis and specification of renal pathology, choice of the treatment policy. | |
| 2180403 | Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis. | 1990 Mar | This review has summarized some of the evidence suggesting that cytokines may play an important role in mediating pathophysiologic events in RA. However, these proteins are capable of mediating both stimulatory (agonist) and inhibitory (antagonist) effects in the rheumatoid synovium. GM-CSF, IL-1, TNF alpha, and PDGF are all produced in the rheumatoid synovium and may function to induce inflammation, enzyme release, fibroblast proliferation, and tissue destruction. Local release of IL-6 may alter the effects of IL-1 and TNF alpha, as well as induce Ig production and hepatic synthesis of acute-phase proteins. However, specific inhibitors of IL-1 and TNF alpha exist, which, if also released into the synovium, may antagonize the proinflammatory effects of these cytokines. In addition, IL-1 may have antiinflammatory effects, such as the induction of the synthesis of collagen and enzyme inhibitors by chondrocytes and synovial fibroblasts. Stimulation of these latter cells by TGF beta also may result in decreased matrix degradation and increased formation of scar tissue. The developing scenario is one of cell-cell interactions that are influenced in positive and negative manners by the local release of various mediators. A further understanding of cytokines and cytokine inhibitors in the rheumatoid synovium may lead to the development of more specific and effective therapeutic agents. | |
| 2159392 | Superoxide anion production by circulating polymorphonuclear leucocytes in rheumatoid arth | 1990 Mar | In twelve rheumatoid arthritis (RA) patients, receiving only nonsteroid anti-inflammatory therapy, superoxide anion (02-) generation by polymorphonuclear leucocytes (PMNs) was assessed by Cytochrome C reduction. The 02- production by non-activated PMNs in RA patients was significantly higher than in healthy controls. The 02- production by PMNs activated by zymosan and phorbol myristate acetate was significantly lower than in controls. PMNs from controls preincubated with rheumatoid sera generated higher 02- levels than the same PMNs incubated in normal sera. | |
| 2822924 | Deferoxamine induced decreases of lipid peroxides in rheumatoid arthritis. | 1987 Aug | Eleven patients with rheumatoid arthritis (RA) were treated with intraarticular deferoxamine or placebo to test the hypothesis that iron chelation decreased hydroxyl radical mediated lipid peroxidation in RA. Intraarticular administration of deferoxamine 100 mg resulted in predominantly systemic effects with decreased serum ferritin and decreased serum levels of lipid peroxidation products. Similar changes were not detected in synovial fluid at this dose. Iron chelation with deferoxamine may provide a novel approach to preventing tissue injury in RA by inhibiting hydroxyl radical production and lipid peroxidation. | |
| 2556792 | The efficacy of tenoxicam in patients suffering from rheumatoid arthritis (including asses | 1989 | Every doctor faced with the task of testing a drug is well aware of the difficulty of making his or her results objective. In designing test procedures, methods need to be found which are unaffected by the subjective views of either the testing doctor or the patients undergoing the treatment. This study was designed taking this into account, using scintigraphic joint measurements in patients with chronic rheumatoid arthritis (RA) to record comparable data. Even this method, however, despite its indisputable scientific accuracy, requires clinical interpretation. | |
| 3262473 | Effect of aggregated immunoglobulins on mononuclear cell protein production in rheumatoid | 1988 Nov | The synthesis and secretion of proteins, especially interleukin 1 (IL-1), by mononuclear cells from patients with rheumatoid arthritis (RA) in response to heat-aggregated IgG (HAGG) has been investigated. Mononuclear cells were labeled with 35S-methionine during 1 hr of HAGG stimulation, and the intracellular and extracellular protein content was measured and compared by fluorography. HAGG dramatically accelerated protein release into the medium. This was observed in both normal and RA mononuclear cells but was much more marked with the latter. The phenomenon was correlated with the release of a IL-1 activity measurable in the thymocyte proliferation assay with a more pronounced labeling in the extracellular medium of a 14-kDa band not detectable in the intracellular pattern. Partially purified proteins between 14-20 kDa recovered by transblotting also stimulated thymocyte proliferation. These results therefore suggest a particular sensitivity of RA mononuclear cells to HAGG, resulting in a very rapid de novo synthesis and an accelerated secretion rate of IL-1. | |
| 2649022 | Evening primrose oil in rheumatoid arthritis: changes in serum lipids and fatty acids. | 1989 Feb | The serum concentration of lipids and composition of fatty acids after overnight fasting were studied in 18 patients with rheumatoid arthritis treated for 12 weeks with either 20 ml of evening primrose oil containing 9% of gamma-linolenic acid or olive oil. The serum concentrations of oleic acid, eicosapentaenoic acid, and apolipoprotein B decreased and those of linoleic acid, gamma-linolenic acid, dihomo-gamma-linolenic acid, and arachidonic acid increased during treatment with evening primrose oil. During olive oil treatment the serum concentration of eicosapentaenoic acid decreased and those of high density lipoprotein-cholesterol and apolipoprotein A-I increased slightly. The decrease in serum eicosapentaenoic acid and the increase in arachidonic acid concentrations induced by evening primrose oil may not be favourable effects in patients with rheumatoid arthritis in the light of the roles of these fatty acids as precursors of eicosanoids. | |
| 1837260 | Double-blind comparison of etodolac and piroxicam in patients with rheumatoid arthritis. | 1991 | A study was carried out to compare the efficacy and tolerability of etodolac and piroxicam in patients with rheumatoid arthritis. Sixty patients entered this double-blind, parallel study and after a wash-out period of up to 2 weeks were randomly assigned to receive 200 mg etodolac twice daily or 20 mg piroxicam once daily for 12 weeks. Efficacy and tolerability assessments were made after 2, 4, 6, 8 and 12 weeks. Patients in the etodolac group demonstrated statistically significant improvement in the number of tender joints and the duration of morning stiffness after 12 weeks, as did the piroxicam-treated patients. In addition, the etodolac-treated patients had significant improvement according to the patients' and physician's global evaluations, pain intensity, number of swollen joints, and grip strength. There were significant differences between therapies favouring etodolac for the assessments of the number of tender joints and the physician's global evaluation by the end of the study. Forty-seven percent (47%) of 15 etodolac-treated patients compared with 7% of 15 piroxicam-treated patients showed improvement according to the physician's global evaluation at Week 12. Similarly, the patients' global evaluation showed that 40% of etodolac-treated patients and 19% of piroxicam-treated patients had improved by the end of therapy. Both therapies were well tolerated. There were no significant differences between groups in the incidence of any adverse reactions or the frequency of withdrawals. | |
| 1895590 | [Cellular interstitial pneumonia and follicular bronchiolitis diagnosed by open lung biops | 1991 Jun | A 54-year-old woman under treatment for rheumatoid arthritis was admitted because of aggravation of dyspnea on effort and restrictive pulmonary dysfunction. Although chest X-ray revealed no marked change, the symptoms progressively worsened, necessitating open lung biopsy for diagnosis and treatment. Based on the histopathological findings of the biopsied tissue, the patient was diagnosed as having active rheumatoid lung complicated with cellular interstitial pneumonia and follicular bronchiolitis. The patient responded well to adrenocorticosteroid and immunosuppressor therapy, and is now being followed up as an outpatient. Rheumatoid arthritis can be complicated by diverse lung diseases. Among them one important disease is interstitial pneumonia, which serves as a prognostic factor. When cellular interstitial pneumonia is treated with adrenocorticosteroid therapy, it responds well and its prognosis is good. Therefore, its early detection and appropriate adrenocortical therapy are essential. Patients with rheumatoid arthritis presenting with dyspnea on effort and pulmonary dysfunction should be examined for cellular interstitial pneumonia, follicular bronchiolitis and other lung diseases, even when no marked change is visible on chest X-ray films. | |
| 1700425 | Structural requirements for recognition of the HLA-Dw14 class II epitope: a key HLA determ | 1990 Oct | Although HLA genes have been shown to be associated with certain diseases, the basis for this association is unknown. Recent studies, however, have documented patterns of nucleotide sequence variation among some HLA genes associated with a particular disease. For rheumatoid arthritis, HLA genes in most patients have a shared nucleotide sequence encoding a key structural element of an HLA class II polypeptide; this sequence element is critical for the interaction of the HLA molecule with antigenic peptides and with responding T cells, suggestive of a direct role for this sequence element in disease susceptibility. We describe the serological and cellular immunologic characteristics encoded by this rheumatoid arthritis-associated sequence element. Site-directed mutagenesis of the DRB1 gene was used to define amino acids critical for antibody and T-cell recognition of this structural element, focusing on residues that distinguish the rheumatoid arthritis-associated alleles Dw4 and Dw14 from a closely related allele, Dw10, not associated with disease. Both the gain and loss of rheumatoid arthritis-associated epitopes were highly dependent on three residues within a discrete domain of the HLA-DR molecule. Recognition was most strongly influenced by the following amino acids (in order): 70 greater than 71 greater than 67. Some alloreactive T-cell clones were also influenced by amino acid variation in portions of the DR molecule lying outside the shared sequence element. | |
| 2892049 | Reduced B-cell galactosyltransferase activity in rheumatoid arthritis. | 1987 Dec 26 | Autosensitisation to IgG may be important in the pathogenesis of rheumatoid arthritis and could be related to reduced glycosylation of the oligosaccharides in the C gamma 2 region of serum IgG. The activity of galactosyltransferase, the enzyme that catalyses the addition of galactose to the oligosaccharide chains, was measured in the circulating B cells of seventeen patients with classic rheumatoid arthritis. It was significantly lower than that of a group of eleven controls (p less than 0.001) or of nine age-matched controls (p less than 0.001). In contrast, the enzyme activity of the T cells was within the range of that in nine age-matched controls, and enzyme activity in monocyte-rich mononuclear-cell populations was higher than in controls, possibly reflecting stimulation of the monocytes in rheumatoid arthritis. These findings suggest that galactosyltransferase may regulate the degree of glycosylation during IgG synthesis and could therefore be implicated in the rheumatoid inflammatory process. | |
| 3396252 | Cardiac performance in collagen diseases estimated by non-invasive methods. | 1988 Jan | The myocardial performance was studied in 3 collagen diseases, i.e. rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS). Sixteen patients with SLE, 12 with RA and 11 with PSS were examined, measuring the systolic time intervals from the first derivative of the carotid pulse in all cases. The ejection fraction (EF), was evaluated in 33 patients using radionuclide left ventricular angiography. The systolic time intervals were compared to those of 103 normal persons and the EF to that of 22 normal controls. In the SLE group the pre-ejection period was significantly shorter, while the ejection period was longer than normally expected. In the same group, the EF was significantly higher that the EF of the control group. These differences could not be related to age, blood pressure, disease duration, coronary risk factors, heart rate or blood values. Most findings in the RA group tended to be opposite to those of SLE. It is concluded that in SLE before any direct involvement of the heart the systolic time intervals and the EF present features similar to those of increased cardiac performance. | |
| 3401648 | Prevalence of familial occurrence in patients with rheumatoid arthritis. | 1988 | We studied 985 consecutive patients with definite or classical rheumatoid arthritis (RA) at an arthritis clinic, between April 1976 and August 1986, to investigate the prevalence of familial disease. We have demonstrated that at least 10.9% of unrelated patients with definite or classical RA have one or more first-degree relative(s) affected with definite or classical RA. Moreover, familial RA is not more severe than the more prevalent non-familial, i.e. sporadic, form of the disease. | |
| 3299682 | Efficacy of auranofin as demonstrated by improvement in clinical parameters and decrease i | 1986 | An open, noncomparative study at 8 rheumatology centers in Brazil assessed the efficacy and safety of auranofin (AF) when given for up to 24 months. The study enrolled 80 patients with classic or definite rheumatoid arthritis (RA); disease was severe in 20 (25%), moderate in 55 (69%), and mild in 5 (6%). Patients received auranofin, 3 mg twice daily, and varying doses of anti-inflammatory drugs (aspirin, nonsteroidal anti-inflammatory drugs, and corticosteroids). Sixty patients (75%) completed the full 24 months of therapy. No patients were withdrawn from therapy because of insufficient therapeutic effect. There was statistically significant improvement (p less than 0.001) in 9 clinical parameters of disease activity, evident as early as 3 months after beginning AF therapy, increasing steadily over 12 months, and remaining at improved levels for another 12 months. Improvements in some parameters were particularly striking. By 24 months, assessment of well-being had increased by 150%, intensity of pain had decreased by 66%, and duration of morning stiffness had decreased by 78%. The average daily dose of anti-inflammatory drugs also decreased over time. The safety profile of AF was similar to that found in comparable trials. Ten patients (12.5%) were withdrawn because of adverse events: 6 for diarrhea (7.5%), 2 for proteinuria (2.5%), and 1 each for pruritus and anemia (1.25%). Adverse events occurred in 24 of 80 patients; some reported more than one adverse event. The most common adverse events were loose stools (20 patients) or diarrhea (11 patients).(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2472003 | Hypotheses on the molecular basis of susceptibility to rheumatoid arthritis. | 1988 | An interpretive summary of recent immunologic and molecular biologic data concerning the molecular basis of susceptibility of rheumatoid arthritis will be presented. The central point of view is taken that the MHC class II molecules encoding disease susceptibility function in a specific immune recognition event. This could involve an antigen "X" that currently eludes characterization or be directed to polymorphic determinants on the MHC molecule itself. The problem of understanding the meaning of the association of susceptibility to rheumatoid arthritis with diverse MHC alleles such as DR4 (Dw4 and Dw14) and DR1 is approached by detailed biochemical analysis that led to the identification of common stretches of amino acid sequence, presumably encoding conformationally equivalent structures. The sequence shared by the otherwise unrelated DR1 and DR4 haplotypes from residue 67 in the DR a chain that appears to confer susceptibility is Leu-X-X-Gln-Arg/Lys. Non-classic MHC polymorphisms related to disease susceptibility but not associated with particular alleles such as identified by Ab109d6 prove especially valuable in suggesting new directions for attempting to understand the significance of these associations. Consideration is given to the possibility that a family of either slightly different or identical conformations encoded in either cis or trans cumulatively confer the liability to develop rheumatoid arthritis. This implies a highly non-classic mode of inheritance. It seems reasonable to consider the pathogenesis of rheumatoid arthritis as evolving from a typical immune response based on a simple immune recognition event directed to a single antigen. | |
| 2916885 | Recurrent massive alveolar hemorrhage, crescentic glomerulonephritis, and necrotizing vasc | 1989 Feb | A middle-aged man presented with recurrent alveolar hemorrhage, rheumatoid arthritis, and crescentic immune complex-mediated glomerulonephritis. Nail bed hemorrhages and necrotizing vasculitis were documented concomitantly with the clinical picture of Goodpasture's syndrome. Perusal of the literature disclosed two additional similar cases. It is suggested that Goodpasture's syndrome may evolve in the framework of rheumatoid vasculitis. While immunosuppressive therapy resulted in short-term remission, two of the three patients involved developed late-stage renal failure. | |
| 3946490 | Constrictive pericarditis and pregnancy. | 1986 Jan | A case discussing the medical management of a 30-year-old gravid patient with recurrent pericarditis and pericardial constriction secondary to juvenile rheumatoid arthritis is presented. |