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

ID PMID Title PublicationDate abstract
2229577 MR patterns of dialysis arthropathy. 1990 Nov Ten patients (average age 51 years) on long-term hemodialysis (average duration 13.5 years) were examined by magnetic resonance (MR) (all cases) and CT (five cases) for cystic radiolucencies of the wrist, shoulders, and hips. MR and CT revealed more lesions of smaller size than plain films and both showed a constant communication with the joint space. Synovial hypertrophy was generally absent or very mild even in the case of large osseous erosions. The MR analysis of the content of the lesions in the wrist was quite variable: low signal on T1- and T2-weighted images (12 of 24), low signal on T1- and high signal on T2-weighted images (10 of 24), and high signal on T1- and T2-weighted images (2 of 24). The patterns of transplanted (four cases) or ungrafted (six cases) patients were indistinguishable. These results suggest an articular origin of the lesions, but different from synovial processes such as rheumatoid arthritis, and confirm their probable multifactorial pathogenesis.
2140714 [Disease of the locomotor system in a shoe factory]. 1990 Mar In 24,964 employees of a shoe factory a retrospective analysis of the work incapacity on account of diseases of the locomotor system was made. On account of these diseases in the course of the calendar year 11.7% of the employees were unable to work and these diseases accounted for 19.5% of the sickness days. The largest number of work incapacities was in March and November. The mean period of work incapacity was 21.4 days. The shortest work incapacity was recorded in patients suffering from gout (13.2 days) and the longest one in patients with rheumatoid arthritis (125.4 days). The most frequent cause of work incapacity was back pain (62.2%), extraarticular rheumatism (17.4%) and osteoarthritis of the joints of the extremities (7.2%). Two hundred-sixty-four patients had in-patient treatment (9%). The greatest proportion of patients were hospitalized on account of back pain (54.9%). The mean period of hospitalization was 17.3 days. Between different factory medical officers relatively great differences in the number and length of granted work incapacity were found. The investigation revealed the importance of diseases of the locomotor system in the investigated shoe factory and the need to investigate the influence of the working environment and occupation on clinical manifestations of affections of the locomotor system.
2106909 Cyclosporin A modulation of the acute inflammatory response: an explanation for the effect 1990 Feb Previous studies have shown that the administration of cyclosporin A (CsA) to animals with experimentally induced pyelonephritis resulted in considerable exacerbation of infection. T-lymphocytes are not involved in the host response to pyelonephritis but neutrophils are known to be a key component in the pathogenesis of this infection, so the effect of CsA on this inflammatory component was investigated. CsA administration did not affect the metabolic activity of neutrophils in vitro nor their ability to phagocytose and kill microorganisms. However, the ability of neutrophils to mobilize to a sterile inflammatory focus in vivo was significantly impaired. Further experiments, using models of pyelonephritis and subcutaneous infection, demonstrated that the CsA-induced suppression of neutrophil mobilization was directly related to the observed increase in bacterial numbers and exacerbation of tissue damage. Additionally, the actual effect of CsA on host defences and the outcome of infection was found to be dependent on the level of the initial infectious challenge. The results of this study provide an explanation for the current pattern of infectious disease in patients treated with CsA, in whom infection with extracellular pathogens is still common. It is also clear that the effect of CsA on inflammatory mechanisms may explain the efficacy of the agent in inflammatory diseases such as rheumatoid arthritis. This suggests a wider therapeutic role for CsA than is currently recognized.
2786243 Lymphocyte extracellular matrix interactions. Induction of interferon by connective tissue 1989 May Limiting dilution analysis was performed in the presence of interleukin 2 (IL-2) on lymphocytes isolated from the synovial fluid (SF) and peripheral blood (PB) of patients with rheumatoid arthritis (RA) and PB of normal donors. Clones of these 'spontaneously' IL-2-responsive cells from PB and SF were compared for their reactivity with components of the extracellular matrix (i.e. native or denatured type I or type II collagen and proteoglycan). It was determined that all clones from both PB and SF were activated to produce interferon (IFN) in the presence of any of the connective tissue components (CTC). Clones derived from normal PB behaved in a similar fashion but produced lower IFN-gamma levels. There was a synergy between the CTC and serum or plasma fibronectin, which was more apparent when soluble CTC were used as the stimuli rather than immobilized CTC. The fibronectin alone was unable to induce IFN-gamma production under any of the conditions tested (i.e. soluble or immobilized). These results demonstrate that clones of IL-2-responsive T cells can be activated by interactions with connective tissue components to produce IFN-gamma.
2727420 Salivary gland biopsy in sarcoidosis. 1989 Mar Previous studies have suggested that the simple technique of minor salivary gland biopsy might be a useful method of diagnosing sarcoidosis. We have therefore investigated the success of this technique in 25 consecutive patients who were attending a chest clinic and in whom a diagnosis of sarcoid had been made. The histological appearances of the minor salivary glands were correlated with the degree of gallium uptake by the parotid glands after intravenous injection of gallium citrate. We also compared the histological appearances of the sarcoid patients with 40 patients suffering from a variety of mixed connective tissue disorders (systemic lupus erythematosis, systemic sclerosis, primary Sjogrens syndrome, rheumatoid arthritis and polymyositis). Five out of twenty-five (20%) of the sarcoid patients had classical non-caseating granulomata in their minor salivary glands, four of whom also had hilar lymphadenopathy and one had bone marrow involvement. All the patients with sarcoid histology in their minor salivary glands also had Gallium uptake in parotid tissue. None of the patients with mixed connective tissue disorders had granulomata in their minor salivary gland tissue although a continuum of changes were found, ranging from normal appearances through small foci of lymphocytic infiltrate to extensive inflammation and destruction of glandular tissue with fibrosis. Whilst minor salivary gland biopsy may be a simple and rapid method of diagnosing sarcoidosis it is most likely to be positive in patients with hilar lymphadenopathy.
3372009 Autoimmune diseases other than lupus share common anti-DNA idiotypes. 1988 Mar We examined the sera of 170 patients with various autoimmune diseases other than systemic lupus erythematosus (SLE) for the presence of an anti-DNA antibody idiotype termed 16/6 and known to occur with high frequency in sera of patients with SLE. The idiotype was found in 6/15 sera from patients with polymyositis (49%), 3/18 with multiple sclerosis (17%), 3/18 with primary Sjögren's syndrome (18%), 9/40 with autoimmune thyroid diseases (23%), 2/35 with myasthenia gravis (6%), and 3/42 patients with rheumatoid arthritis (7%). The idiotype was not detected among 12 patients with scleroderma or 77 normal controls. The presence of the 16/6 idiotype was associated with the presence of another anti-DNA idiotype termed 134-Id. Serum samples were also tested for activity against DNA, various synthetic polynucleotides, and cardiolipin. The serum activity against these antigens was found to be polyspecific, though overlap in reaction against the various polynucleotides was not absolute. The 16/6 idiotype is thought to be coded by a germline gene. The presence of this idiotype in various autoimmune diseases points to a pathophysiologic link between the diseases.
3238375 Pharmacologic and non-drug therapies for osteoarthritis. 1988 Many treatments have been shown to relieve symptoms in osteoarthritis but none have been found to influence the course of the disease. In the context of a symposium on cartilage changes in osteoarthritis, the major interest is in the possible action of non-steroidal anti-inflammatory drugs, either favourable or unfavourable, on the progression of cartilage destruction in this disease. On the one hand, there is experimental evidence that some anti-inflammatory drugs like indomethacin can adversely affect cartilage or interfere with repair mechanisms. Others like tiaprofenic acid do not have such effects. There is largely anecdotal evidence that indomethacin therapy can lead to rapid progression of hip disease in osteoarthritis. On the other hand, it is traditionally postulated that the process of inflammation with the release of enzymes and other noxious substances in diseases like rheumatoid arthritis, leads to cartilage damage. Anti-inflammatory drugs might be expected to inhibit such a process as they do in animal models. The long term actions of anti-inflammatory drugs are now being explored in a large scale prospective trial which should provide an answer to the question of whether anti-inflammatory drugs are good or bad for osteoarthritis. Meantime they remain the major symptomatic therapy for the disease.
3034067 Phospholipid base exchange activity in the leukocyte membranes of patients with inflammato 1987 May Phospholipid base exchange and cholinephosphotransferase (CPT) and ethanolaminephosphotransferase (EPT) activities were assessed in the membranes of neutrophils or lymphocytes from patients with various inflammatory disorders. Ethanolamine exchange activity was significantly enhanced in both neutrophils and lymphocytes from patients with active Behçet's disease, active systemic lupus erythematosus (SLE), and severe bacterial infections and slightly enhanced in those from patients with active rheumatoid arthritis (RA), compared with healthy controls. No abnormal findings were found in CPT, EPT, or serine or choline base exchange activities in the leukocytes from any of the diseased groups tested or in the ethanolamine exchange activity of patients with severe viral infections and inactive SLE, RA, and Behçet's disease. The authors have recently demonstrated the enhancement of transmethylation and phospholipase A2 activity in human leukocyte membranes at the height of inflammatory disease states, as well as the activation of leukocyte ethanolamine exchange by bioactive stimulants. These data postulate that phosphatidylethanolamine synthesis by the base exchange reaction may be the precursor of transmethylation and its subsequent activation of phospholipase A2, leading to the induction of arachidonic acid cascade.
3807890 Induction of metallothionein is correlated with resistance to auranofin, a gold compound, 1987 Jan Metallothioneins (MTs) are low molecular weight, thiol-rich, metal-binding proteins. Auranofin (AF) is a gold compound active in the treatment of rheumatoid arthritis. The effects of AF on regulation of MT gene expression in Chinese hamster ovary cells were studied. AF-resistant cells accumulated substantial amounts of MT mRNA and protein, whereas no induction was observed in AF-sensitive cells. Cells capable of inducing MT in the presence of AF were much less sensitive to AF-mediated cytotoxicity. Induction of MT by low concentrations of Cd protected cells from subsequently administered doses of AF. The level of protection correlated with the level of induced MT. These findings indicate that MT plays a central role in the mechanisms underlying cellular resistance to gold compounds.
3497902 Concentration of fibronectin and granulocyte elastase in plasma of patients with systemic 1987 The concentration of granulocyte elastase-alpha-1-protease inhibitor (E-AT) complex in plasma is enhanced in inflammatory processes, e.g. in septicaemia and rheumatoid arthritis, being an expression of granulocyte activation during inflammatory response. In the present study we measured E-AT and fibronectin in the plasma of 46 patients with various connective-tissue diseases in relation to the course of the disease. In about 50% of the cases, E-AT was found to be elevated to 2-3 times the normal concentrations, in relation to increasing serum content of C-reactive protein. In follow-ups over 2 years, an elevation of E-AT and a decreasing fibronectin in plasma was found in patients with activated disease. Without relation to other parameters used in connective-tissue diseases, fibronectin was found to be diminished below the normal range in 7 patients with systemic lupus erythematodes and 1 patient with overlapping syndrome. Our results indicate that the concentration of E-AT and fibronectin in plasma may be helpful parameters for judging the activity of connective-tissue diseases.
3039646 Detection of free radical intermediates in the oxidative metabolism of carcinogenic hydraz 1987 Hydrazine derivatives are widely used in agriculture, in industry, as rocket propellants, and in medicine. Hydrazines also occur naturally in tobacco and mushrooms. Many hydrazines tested in animal studies appear to be carcinogenic and induce tumors in various target tissues in mice, hamsters, and rats. The use of hydrazine derivatives in humans is often complicated by adverse side-effects such as liver injury and rheumatoid arthritis. A number of studies have demonstrated that hydrazine derivatives are activated to reactive intermediates, such as free radicals, through a variety of cellular oxidative metabolic pathways. The aim of this work is to demonstrate the occurrence of free radical intermediates during the metabolic activation of various hydrazine derivatives and to characterize the enzymatic system(s) responsible for the activation to free radical species. The hydrazines studied are acetylhydrazine, isoniazid, isopropylhydrazine, iproniazid, methylhydrazine, 1,1-dimethylhydrazine, and 1,2-dimethylhydrazine. The model systems chosen are those of rat liver microsomes and isolated hepatocytes. Free radical intermediates have been demonstrated by the electron spin resonance spectroscopy coupled to spin trapping technique. The activation mechanism has been characterized using inhibitors of the mixed function oxidase system and of the FAD-dependent oxygenase system. Glutathione was able to scavenge, with high efficiency, the free radicals produced.
2431019 Antinuclear antibodies in primary pulmonary hypertension. 1986 Dec The association of positive antinuclear antibodies with the clinical and hemodynamic features of 43 patients with primary pulmonary hypertension and 16 patients with secondary pulmonary hypertension was investigated. Each patient had determinations of antinuclear antibodies using a KB cell substrate immunofluorescent test. Of the patients with primary pulmonary hypertension, 40% had positive antinuclear antibodies at titers of 1:80 dilutions or greater. There were no differences between patients with primary pulmonary hypertension and positive antinuclear antibodies compared with those with negative antinuclear antibodies in relation to clinical or hemodynamic status. A 6% incidence rate of antinuclear antibodies was found in patients with secondary pulmonary hypertension, similar to that in the normal population. The clinical, hemodynamic, serologic and histologic similarity between patients with primary pulmonary hypertension and those with unexplained pulmonary hypertension associated with collagen vascular disorders suggests that primary pulmonary hypertension in some patients may represent a collagen vascular disease confined to the lungs. The frequency of positive antinuclear antibody tests would place primary pulmonary hypertension between rheumatoid arthritis and scleroderma in the spectrum of collagen vascular diseases. Further studies are necessary, however, before one might expect that immunosuppressive therapy would be beneficial to these patients.
2946958 Identification of a common class of high affinity receptors for both types of porcine inte 1986 Nov 20 Interleukin-1 (IL-1) is the name given to the polypeptides produced by activated mononuclear phagocytes which were originally defined as lymphocyte activating factors (LAF). Administration of IL-1 in vivo causes fever and synthesis of acute phase proteins. In vitro they have been shown to cause cartilage and bone resorption, and to stimulate fibroblasts and chondrocytes to make prostaglandins and latent collagenase. IL-1 has therefore been proposed to be an important inflammatory mediator and may be involved in the destruction of cartilage and bone that is a feature of rheumatoid arthritis and other inflammatory diseases of joints. We therefore looked for IL-1 receptors on connective tissue cells which might be targets for therapeutic intervention. Here we report the iodination, to high specific activity and with retention of full biological potency, of the two types of natural porcine IL-1. These ligands have been used to demonstrate high affinity dissociation constant (approximately 10(-10) M) specific binding sites on pig chondrocytes and synovial fibroblasts, human dermal fibroblasts and murine osteoblasts (3,000-5,000 sites per cell). Most interestingly, the two different Il-1 proteins show a similar affinity for a common class of receptors.
3769266 15-21-year results of the Charnley low-friction arthroplasty. 1986 Oct Ninety-three patients had had 116 Charnley low-friction arthroplasties (LFA) 15 to 21 years (mean, 16.6 years) previously. Their mean age at surgery was 53 years (range, 20-71 years). Fifty-two had osteoarthritis and 19 had rheumatoid arthritis. At follow-up, 85.3% were completely pain-free and 11.2% had occasional discomfort. Seventy-eight percent had near full or full range of movements. Acetabular bone-cement junction was unchanged in 32, and 20 had nonprogressive demarcation of the outer one third measuring less than 1 mm in width. In 36, socket demarcation was complete. Medial femoral cortex was unchanged in 56% and 44% showed loss of definition. Endosteal cavitation of the femur was present in 20.7%. Subsidence of the stem or the stem-cement complex was present in 29%. The diameter of the femoral cortex near the tip of the stem remained unaltered in 83.6%. The rate of socket wear was 0.096 mm/year, and there was a highly significant correlation between time and wear but no correlation between wear and patient's weight. Twenty-two and five-tenths percent of sockets migrated; this was statistically related to the depth of socket wear. The excellent clinical results of a relatively unsophisticated early surgical technique strongly supported the correct concept of the low-frictional torque. Improvements in the surgical technique and component design will further improve the long-term results.
3766135 Pulmonary cytoplasmic hyalin resembling Mallory's alcoholic hyalin in the liver. 1986 Jun Sixty-three consecutive autopsy cases of interstitial fibrosis of the lung, 6 cases of organizing pneumonia, 14 of pneumocystis pneumonia, and 20 of acute bacterial pneumonia complicating as a terminal illness listed in our Department of Pathology during a period from 1978 to 1983 were surveyed for Mallory body-like cytoplasmic hyalins in the alveolar cells. We found the hyalins in 10 of 63 cases (15.9%) with interstitial fibrosis of the lung and one of 6 cases with organizing pneumonia. Seven of the former 10 had an associated malignancy; 3 esophageal cancers, 2 lung cancers, and 2 leukemias. Five of the seven patients received an irradiation for treatment of their malignancies, subsequently developed interstitial fibrosis of the lung. Among the remaining 3 of the 10, one showed diffuse interstitial fibrosis associated with rheumatoid arthritis and two had an idiopathic type of diffuse pulmonary fibrosis. There was only one case in which the pulmonary hyalins were found in the absence of extensive interstitial fibrosis within small organizing foci of peribronchial and subpleural location. Pulmonary hyalins showed the same conventional staining properties and ultrastructural features as Mallory's alcoholic hyalins found in the liver, but did not reveal a simultaneous association with the hepatic hyalins. Pulmonary hyalins frequently stained positively with monoclonal anti-cytokeratin antibodies, more strongly at their periphery. Pulmonary hyalins were considered to be a non-specific reaction of alveolar cells to injuries, mostly in association with the pulmonary fibrosis of any etiology but not the hepatic hyalins.
1859360 Interleukin 1 induces the expression of a heat-shock gene in chondrocytes. 1991 Jul 15 The presence of T cells and antibodies reactive with heat-shock proteins (hsps) in the joints of patients with rheumatoid arthritis may indicate a role of hsps in this disease. In the present study we examined whether increased temperature and interleukin 1 (IL 1), both of which are elevated in arthritic joints, induced the expression of two hsp70 genes in bovine chondrocyte cultures. We found that heat shock resulted in increased expression of constitutive and inducible hsp70 mRNA species. IL 1 and phorbol 12-myristate 13-acetate (PMA) also induced an increase in the constitutive hsp70 mRNA species, but without affecting the expression of the inducible hsp70 gene. The increase induced by IL 1 was observed only after 3 h, whereas increases induced by PMA were observed within 1 h. For all treatments, the hsp70 mRNA decreased by 24 h. Heat treatment of chondrocytes did not affect levels of collagenase and caseinase activity in the medium, nor did it alter proteoglycan synthesis by these cells.
1889221 Scleritis and Streptococcus pneumoniae. 1991 Jul We retrospectively review our experience with four patients with Streptococcus pneumoniae scleritis. Two of the patients had been exposed to beta irradiation after pterygium removal 4 and 13 years previously. One patient had a 3-year history of chronic anterior nodular scleritis, and one patient had severe rheumatoid arthritis. All were treated with intensive i.v. and topical fortified antibiotics. In two of the cases, the infection was controlled and visual acuity returned to 20/30 and 20/60. In one patient, infectious scleritis progressed to endophthalmitis. This eye ultimately became phthisical and required enucleation because of chronic pain. In the remaining patient, infectious scleritis led to perforation, which required a corneal-scleral patch graft. This patient had a final visual acuity of counting fingers. An infectious etiology should be suspected in cases of necrotizing scleritis associated with a purulent discharge, and appropriate smears and cultures should be obtained. Infectious scleritis can be caused by streptococcal organisms. Appropriate topical and intravenous antibiotic treatment is effective in some cases.
1844381 [Standardization of serological tests for Chagas disease: an immunoenzymatic test for bloo 1991 Mar In the serological diagnosis of Chagas disease large divergences may be found even between laboratories with experience, as a consequence of different criteria for the standardization of the tests. To standardize a immunoenzymatic test developed primarily for screening blood donors, serum panels were carefully chosen so as to best represent chagasic and non-chagasic populations. Produced for the highest sensibility and stability, the new reagent (bioELISA cruzi, Biolab Diagnóstica S/A, Brasil), was tested in serum from 1648 patients 219 with Chagas disease and 104 with other diseases, plus a comparison with well standardized immunofluorescence and hemagglutination tests in 1325 sera. In the immunoenzymatic assays, the cut off was indicated by the absorbance value of a chagasic serum showing a minimal reactivity. ELISA sensibility was 0.9954 and specificity 0.9969, as co-negativity. False positive results were absent with sera from syphilis, toxoplasmosis, mononucleosis and high titered sera for antistreptolysin 0 antibodies. However they were seen in 5 to 15 cases of tegumentar leishmaniasis, 1 of 12 Kala-azar 1 of 15 rheumatoid arthritis and 1 of 12 systemic lupus erythematosus. The high sensibility in chagasics and high specificity in the general population indicate the confiability of the immunoenzymatic assay for screening blood donors and even to confirm a clinical diagnosis of Chagas' disease.
2290085 Uncemented press-fit total knee arthroplasty. 1990 Dec Nineteen total knee arthroplasties in 16 patients were performed using a new prosthesis designed specifically for uncemented, press-fit fixation without any provision for tissue ingrowth. This design may be suited for use in patients with juvenile rheumatoid arthritis, postseptic knees, failed total knee arthroplasties with large bone stock deficiencies, and young, active, overweight individuals. Preservation of bone stock is possible because the fixation stems are nails rather than larger cement pegs, removal for revision is easier without cement, sequestration of microbes within cement cannot occur, and bone graft may be continually loaded with this type of prosthesis. Pain relief, discarding crutch support, operative blood loss, and corrective alignment were equivalent to results obtained with cemented arthroplasty. Seventeen of the 18 knees available for review (average follow-up period, 3 years, 7 months; range of follow-up period, 2 years, 10 months to 4 years, 11 months) were pain-free. Range of motion averaged -2 degrees of extension to 101 degrees of flexion. Ambulation was unrestricted and unsupported in the majority of patients. Radiographic evaluation showed the development of increased bone density under the tibial plateau as well as a sclerotic line at the ends of the femoral and tibial stems. This observation gives support to the theory that multiple microtrabecular fractures with healing form a new supportive "subchondral bone plate." There was one incidence of tibial subsidence. Prosthesis migration and loosening were not observed.
2266625 [Clinical study on asbestos pleurisy and review of literature]. 1990 Sep Seven asbestos workers with asbestos pleurisy were investigated in terms of clinical symptoms, findings of pleural biopsies and course of chest roentgenograms. All cases were male and smokers. Duration of asbestos exposure ranged from 3 to 33 years (mean: 20.6 years). Duration between initial exposure and onset of the pleurisy ranged from 22 to 34 years (mean: 28.7 years). Five pleural effusions were aseptic and exudative, and one had sanguineus and eosinophilic effusion. According to the findings of pleural biopsies, our cases were classified into 2 groups. Group A (4 cases) had "basket-weaving formation" on the parietal side and inflammatory changes on the visceral side. No circulating autoantibodies were found in group A. Group B (3 cases) had no "basket-weaving formation" but only intensive inflammatory changes. These 3 cases were respectively complicated with anti-GBM antibody mediated glomerulonephritis, with acute interstitial pneumonia, and with rheumatoid arthritis and acute interstitial pneumonia. They all had circulating autoantibodies. In the course of chest roentgenograms, 6 of the 7 cases finally showed diffuse pleural thickenings which involved obliterations of costo-phrenic angles. Among them, one case developed into progressive pleural fibrosis. It was concluded that asbestos pleurisy can be classified into 2 groups according to the mechanism of occurrence, and immunological changes should be recognized as one of the mechanisms of asbestos pleurisy.