Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 7086182 | The role of collagen autoimmunity in animal models and human diseases. | 1982 Jul | Although immune reactions to collagen have been described in several diseases, the pathophysiologic consequences of collagen autoimmunity remain obscure. We have recently described an animal model of polyarthritis which can be induced in susceptible rats or mice by immunization with native type II collagen. Arthritis develops in animals which have high levels of both cellular and humoral immunity to collagen. In rats, arthritis can be passively transferred with purified IgG antinative type II collagen antibodies. There is circumstantial evidence that antibodies are also important for the initiation of arthritis in susceptible mice. Circulating immune complexes do not appear to be involved and we believe the arthritis is caused by binding of antibodies to autologous collagen. There are a number of similarities between collagen-induced arthritis and human rheumatoid arthritis (RA). Many histopathologic changes are similar including synovitis which progresses to pannus formation, development of marginal erosions and eventual cartilage destruction. Both diseases are associated with collagen autoimmunity which appears to be genetically linked to the major histocompatibility locus. However, there are also significant differences. In particular, the antibody reactivity usually found in RA is primarily directed against covalent structural determinants on collagen and not against the conformation-dependent determinants on type II collagen critical to the development of collagen-induced arthritis. Immunity to collagen has also been described in other animal models of disease and in other human diseases but its relevance to their pathophysiology is unknown. By further characterizing the specific reactions involved including the nature of the immune response, its specificity and the genetic factors important in the host; insight may be gained into the role of collagen autoimmunity in human disease. While significant progress has been made in all of these areas during the last several years, much remains to be learned before the relevance of collagen autoimmunity to any human disease is established. | |
| 6398173 | Methotrexate: its use in the rheumatic diseases. | 1984 Apr | Methotrexate in a low dose intermittent regimen has become popular as a therapeutic choice for refractory psoriatic arthritis, polymyositis, Reiter's disease and more recently rheumatoid arthritis. As a folate analogue, it inhibits the formation of reduced folate cofactors which participate in a host of important reactions including DNA synthesis. It has been shown to have both immunosuppressive and anti-inflammatory properties although its precise mechanism of action in these diseases is not known. It may be variably absorbed especially in psoriatics and its action may be antagonized by folate supplements. Its major route of metabolism appears to be via the enterohepatic circulation. Numerous drugs, including salicylates, may increase serum levels by displacing the drug from protein binding sites and by competing for renal excretion. It has fewer short term side effects than the other immunosuppressives used in rheumatic disease. Its major long term toxicity is liver fibrosis or cirrhosis which appears to increase with greater cumulative dosage and treatment duration. Several recent reports of hypersensitivity pneumonitis reinforce the previous literature on this topic. Pulmonary toxicity may be more common than suggested as more patients are treated with methotrexate for rheumatic diseases. Clinical studies in general have been uncontrolled and lacking in scope and size. Nevertheless, the literature to date appears to show this to be an excellent drug for use in the diseases mentioned. Prospective double blind controlled studies on psoriatic arthritis and rheumatoid arthritis should help establish this drug as the immunosuppressive of choice in these diseases. | |
| 7075085 | Protein binding of some non-steroidal anti-inflammatory drugs in rheumatoid arthritis. | 1982 Jan | The protein binding of 4 non-steroidal anti-inflammatory drugs and warfarin was investigated in 10 patients with rheumatoid arthritis and in a matched control group of patients with osteoarthritis. There were no differences between the groups in the free fractions of the 5 drugs studied. Fluorescent probe studies also showed only minor differences between groups. The results do not support previous suggestions that drug protein binding is altered in rheumatoid arthritis. Albumin concentration was positively correlated with the binding of salicylate, but not with binding of the other 4 drugs. Fatty acid concentration was directly correlated with the binding of warfarin and indomethacin. Correlations between drugs with respect to protein binding were investigated, but only that between salicylate and ibuprofen was significant. | |
| 6440857 | Reactions of infectious mononucleosis sera with glutaraldehyde-treated human erythrocytes. | 1984 | Infectious mononucleosis sera gave positive results in enzymoimmunoassay with glutaraldehyde-treated human erythrocytes. This unexpected reaction appeared to be caused by the interaction of Paul-Bunnell (P-B) antibodies with a partial P-B antigen that apparently appears on human red blood cells in a hidden form and becomes exposed by the treatment with glutaraldehyde. | |
| 3967557 | Low incidence of hepatotoxicity associated with long-term, low-dose oral methotrexate in t | 1985 Feb | Thirty patients with psoriasis or other nonmalignant diseases had liver biopsies done before treatment with low-dose methotrexate, 15 mg/week, and then at one- to two-year intervals as long as they continued the methotrexate. All patients were symptomatically improved on this regimen. The 15 patients who had normal liver biopsies at the start of the study had normal biopsies after methotrexate. Fifteen others had minor hepatic histologic abnormalities before treatment. Eleven patients had fatty infiltration. Ten showed no significant change after treatment while one had increased fat and portal fibrosis on a fourth liver biopsy done seven years after MTX was begun. This last patient, a former alcohol abuser, continued methotrexate and showed no further worsening at 8 years. The remaining four had portal fibrosis before treatment. One patient had less fibrosis after methotrexate, two patients slightly more fibrosis, and one a marked increase in portal fibrosis. No patient developed cirrhosis or clinical liver disease. Our results suggest that in the absence of alcohol consumption, low-dose weekly methotrexate treatment rarely causes clinically significant liver damage. | |
| 7316044 | Successful creation of arteriovenous fistulas in nonuremic patients with heparin and aspir | 1981 Dec | From November 1977 through June 1979, 26 of 28 nonuremic patients had forearm arteriovenous fistulas successfully created for dialysis, lymphapheresis or vascular access. To improve patency, aspirin and heparin therapy was begun the night before operation and continued postoperatively in all except one patient. No major change in coagulation parameters resulted from this treatment. Twenty-five radial artery to cephalic vein fistulas were created in 23 patients, brachial artery to basilic vein fistulas in 3 patients, and 8 mm polytetrafluoroethylene brachial artery to basilic vein loop grafts in two patients. Early fistula failures (within 11 days) required thrombectomy once in four patients and twice in another patient. A sixth patient was not given heparin or aspirin and required multiple thrombectomies before the graft was removed because of infection. One other patient refused further surgery after two unsuccessful attempts to create an arteriovenous fistula. In the remaining 26 patients, the fistulas have been successfully maintained, and in 18 patients more than 214 dialysis or lymphapheresis treatments have been performed without problems. The successful establishment of arteriovenous fistulas in nonuremic patients has been achieved by giving aspirin and low dose heparin therapy, which appears to be an integral step in maintaining patency. | |
| 6896227 | Autoimmune associations in primary biliary cirrhosis. | 1982 Jun | The prevalence of autoimmune associations was determined in 113 patients with primary biliary cirrhosis who participated in a therapeutic trial of D-penicillamine. Eighty-four percent of the patients had at least one associated autoimmune disease and 41% had two or more such diseases in addition to primary biliary cirrhosis. Keratoconjunctivitis sicca, which was present in 66% of the patients, was the most commonly associated autoimmune disease. In most of the patients the autoimmune disease was recognized after the diagnosis of primary biliary cirrhosis had been made. The prevalence of autoantibodies in selected subgroups of patients ranged from 70% (rheumatoid factor) to 22% (anti-native DNA). Polyclonal elevation of serum immunoglobulins was a consistent finding, and frequently all three major isotypes were simultaneously increased. Only IgA elevations correlated with histologic progression of primary biliary cirrhosis. The prominent involvement of epithelial tissues in the autoimmune disease of primary biliary cirrhosis suggests that an autoimmune syndrome affecting the secretory immune system is associated with the pathogenesis of primary biliary cirrhosis and the coexisting autoimmune diseases. | |
| 38536 | Destructive corneal disease in the connective tissue disorders. Comparison with an experim | 1978 Sep | The corneo-scleral changes described are highly characteristic and may be the first signs of an underlying systemic disorder so that otherwise healthy patients who present with limbal guttering and scleral disease must be continuously monitored with this association in mind. The clinical and histological features of limbal guttering in connective tissue disorders strongly suggest that a local antigen-antibody reaction triggers off a number of biochemical and cellular responses which combine to produce lysis of scleral and corneal collagen, although immune complexes have not so far been demonstrated in these eyes. Modes of therapy aimed at one particular chain of events have varying degrees of success, as indeed does more blunderbuss treatment with steroids, anti-inflammatory drugs, or cytotoxic agents. The early stages of the ocular lesion in the rabbit are now being studied, as is the immunological basis for its production. It is hoped that further work with the animal model will lead to a deeper understanding of the pathogenesis of these conditions, which will turn provide both ophthalmologists and rheumatologists with more scientific guidelines for treatment. | |
| 98835 | Pharmacological properties of diclofenac sodium and its metabolites. | 1978 | Diclofenac sodium (Voltaren) is a non-steroid anti-inflammatory agent of a new chemical structure, which is animal experiments shows a high degree of anti inflammatory, analgesic, and antipyretic activity in various pharmacological models. It inhibits prostaglandin biosynthesis in vitro and in vivo, and this inhibitory effect at least partly explains the mechanism of action of the preparation. In animal experiments diclofenac sodium is characterised by a broad therapeutic range. Also, its gastrointestinal tolerability is better than that of other highly effective non-steroid anti-inflammatory agents. Two of the metabolites produced during the biotransformation of diclofenac sodium in man are also biologically active. The activity of these two metabolites, however, is very much weaker than that of unchanged diclofenac sodium and is comparable to that of phenylbutazone. | |
| 6436936 | Lung function tests in connective tissue diseases associated with Raynaud's phenomenon. | 1984 | 13 patients with various connective tissue diseases associated with Raynaud's phenomenon were studied with pulmonary physiologic techniques to see the alterations of lung functions and also whether spasm of pulmonary circulation occurs in these patients. We found that an increase in the dead space ventilation was common and associated with normal tidal volume. We interpreted this finding as evidence of redistribution of blood flow in the lung by spasm of blood vessels going to well-ventilated lung units generating a high dead space ventilation. We also found commonly that the distribution of inspired air in the lung was uneven, the diffusing capacity was reduced and the dynamic compliance decreased with increasing frequency of breathing suggestive of disease in small airways. The restrictive defect, the obstructive defect, the reduction of lung compliance and the arterial hypoxemia were relatively uncommon and probably occurred when the diseases were more advanced. | |
| 14456 | [Gamma-glutamyltranspeptidase in chronic polyarthritis. II. Influence of drugs]. | 1977 Jan | Thirty outpatients with active RA were treated with Sudoxicam, a nonsteroidal antirheumatic drug, for periods of 6-10 months. Gamma-GT, alkaline phosphatase and transaminase were estimated at 2 week intervals. During treatment, the frequently elevated values showed a significant tendency towards normality (time trend analysis). During a second drug trial with Piroxicam in 32 RA outpatients over a period of 18 months, the mean value of gamma-GT and alkaline phosphatase did not decrease significantly. With regards to liver function tests, there was no significant difference between 19 patients receiving and 13 patients not receiving simultaneous gold therapy. During gold treatment periods of 26 patients with a total dose of 3.8 g Fosfocrisolo (0.8 g Au) the mean value of gamma-GT decreased from 26 to IU/l. Cyclophosphamide treatment of 13 patients, with daily doses of 50-150 mg to a total dose auf 48 g, had no significant influence on gamma-GT and alkaline phosphatase. Our results indicate that the very frequent elevations of gamma-GT and of other liver data in RA are caused by the rheumatoid process itself and not induced by drugs. | |
| 239752 | Purification of granulocyte neutral protease from human blood and rheumatoid synovial flui | 1975 Aug 26 | The neutral protease activity of human synovial fluid cells, like that of peripheral blood leucocytes, is located in a granule fraction. It can be solubilised by various agents but only 1 M neutral salts do so without inactivation. Salt-solubilised neutral protease has been purified (300 X) from synovial fluid cells; like preparations obtained in the same way (600 X purified) from peripheral blood leucocytes, it has a broad pH profile of activity (pH 7--10.5) and in this, as well as in substrate specificity and sensitivity to activators and inhibitors, it behaves as a serine-histidine type protease similar to elastase (EC 3.4.21.11). The product showed two major components on polyacrylamide gel electrophoresis. Collagenase or chymotrypsin-like activity were not detected. | |
| 1275584 | Single daily dose corticosteroid treatment. | 1976 Feb | Thirteen patients with rheumatoid or psoriatic arthritis who had not previously received corticosteroids were treated with prednisolone in a single-dose each morning. Insulin-hypoglycaemia tests were performed before starting steroids in each patient, and again at the conclusion of the study in twelve of the thirteen (duration of steroid treatment 8-40 m). There was no difference in the mean basal or peak levels of corticosteroids, or the mean peak of growth hormone (GH) in the tests done before or during treatment, although one patient lost GH responsiveness. There was thus no evidence of hypothalamo-pituitary-adrenal (HPA) suppression in any of the twelve patients, and there was a good therapeutic response in twelve out of thirteen. One patient was dropped from the trial because treatment failed. In contrast, of seven patients who had received a similar total dose of prednisolone twice daily, three showed HPA suppression and two had lost GH responsiveness. | |
| 6745911 | Renal amyloidosis with crescents. | 1984 Jul | An unusual case of renal amyloidosis associated with extensive crescents is reported. Light and electron microscopic examination revealed that deposits of amyloid were almost invariably involved in the locations in which proliferations of epithelial cells in the capsular spaces had merged with the glomerular tufts. Gaps or fractures of the capillary walls were present at such sites, in which amyloid fibrils were mingled with thrombic material containing fibrin. It is highly conceivable that the gaps apparently induced by amyloid deposition, with leakage of fibrin-fibrinogen into the capsular space, play a crucial role in the development of the extracapillary proliferation. | |
| 7019786 | Cefoxitin-associated renal failure. | 1981 May 27 | Two elderly women suffered an acute deterioration of renal function after treatment with cefoxitin sodium. One with stable chronic renal failure due to reflux nephropathy underwent a rapid deterioration of renal function which proved fatal. The other woman had rheumatoid arthritis and developed acute tubular necrosis after treatment with gentamicin and cefoxitin. All the data suggested that the antibiotic was responsible for the deterioration in renal function. The dose of cefoxitin should be reduced in patients with renal functional impairment. Cefoxitin should either be used with great caution or not prescribed in combination with aminoglycoside antibiotics. | |
| 846686 | [Desferrioxamine in the diagnosis of hypo-, normo-, and hypersiderotic hyposideremia]. | 1977 Feb 25 | Evaluation of stored iron by means of DFOX-induced sideruria in 101 subjects with various degree of hyposideraemia with or without anaemia, is reported. Three groups were examined: 49 patients with chronic loss of blood and malabsorption and urinary iron values up to 1 mg/24hr; 43 with non-bleeding neoplasia, collagen disease, lymphoma, cirrhosis of the liver etc. and values of 1-2mg/24 hr; 9 with rheumatoid arthritis and cirrhosis of the liver and values over 2 mg/24 hr. The reasons why hyposideraemia may accompany incipient of frank tissue hypo-, normo- or hypersiderosis are discussed. | |
| 6424638 | Amino acid transport in human tonsillar lymphocytes with regard to patient's age and tonsi | 1984 | Amino acid transport in human tonsillar lymphocytes was investigated in 32 patients of various ages and with different tonsillar diseases. Tonsillar lymphocytes appeared to possess at least four different transport systems for neutral amino acids including the activated Na+-dependent A system transport. The transport activity of neutral amino acid was significantly higher in child cases than in adult cases. In adult cases with focal tonsillitis, tonsillar lymphocytes were taken from patients with rheumatoid arthritis (RA) and skin diseases as secondary lesions who showed good improvement of the skin lesions after tonsillectomy. These lymphocytes were revealed to have more activated Na+-dependent transport than those from patients with skin diseases who showed poor improvement of the skin lesions after the tonsillectomy, and those from patients with recurrent tonsillitis. The characteristics of amino acid transport in human tonsillar lymphocytes and changes influenced by age and tonsillar diseases are discussed. | |
| 1271387 | Bleeding, salicylates, and prolonged prothrombin time: three case reports and a review of | 1976 Mar | Fourteen cases of ASA induced hypoprothrombinemic bleeding, including three patients reported by the authors, are reviewed. Predisposing factors toward bleeding include malnutrition and malabsorption syndrome. Although the bleeding is usually benign, it may be serious on occasion. The importance of this rarely considered cause of ASA associated bleeding lies in the fact that it is readily corrected with Vitamin K. | |
| 1270467 | Review and analysis of silicone-rubber metacarpophalangeal implants. | 1976 Jun | A series of 530 consecutive arthroplasties using silicone-rubber implants in 119 patients was reviewed. Clinical and roentgenographic evaluations were completed on sixty patients and 254 implants, with an average follow-up of two and a half years; the remaining fifty-nine patients were evaluated by questionnaire. All but three patients had rheumatoid disease, usually with severe deformity, and many of the patients underwent other procedures on the upper extremity; these procedures often precluded early motion after the arthroplasties. Three prostheses (0.6 per cent) were removed because of infection, and reoperation was required in 2.4 per cent of the joints. Detailed clinical follow-up of 254 prostheses revealed the following: for Swanson prosthesis-average motion 38 degrees, fracture rate 26.2 per cent, and recurrence of clinical deformity 11.3 per cent; for Neibauer prostheses-average motion 35 degrees, fracture rate 38.2 per cent, and recurrence of clinical deformity 44.1 per cent. It should be noted that use of early implant types and some variations from the designer's recommended rehabilitation protocols were features of this series. | |
| 3878005 | [Correction of immunoregulatory disorders in seronegative and seropositive rheumatoid arth | 1985 | A study was made of the effect of the drugs with an immunostimulant (T-activin, levamisole) and immunosuppressant (prospidin) activity on the synthesis of IgA, IgM and IgG in vitro in lymphoid cultures of 7 healthy donors, 16 patients with seropositive and 9 patients with seronegative rheumatoid arthritis (RA). It was shown that the model of the synthesis of immunoglobulins in vitro demonstrates the impairment of T-B-cell cooperation of lymphocytes in RA patients. It was establised that the effect of immunologically active drugs on the synthesis of immunoglobulins depends on the character of the drug immunotropic action and initial functional activity of the immunoregulatory T-lymphocytes. Like polyclonal mitogens, levamisole and, to a greater extent, T-activin stimulating the initially low activity of T helpers increase spontaneous synthesis of immunoglobulins in lymphoid cultures of patients with seronegative RA, whereas in seropositive RA, these drugs stimulating the initially low activity of T suppressors carrying Fc gamma-receptors inhibit this process. Prospidin inhibit the synthesis of immunoglobulins equally in both RA patterns. Indications and contraindications for administration of he immunologically active drugs on a clinical bases are discussed. |