Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2584984 | Treatment of major wound necrosis following total knee arthroplasty. | 1989 | Following total knee arthoplasty, seven patients developed significant wound necrosis and dehiscence, requiring wound coverage with soft tissue flaps. Three patients had rheumatoid arthritis, three had degenerative arthritis, and one had osteosarcoma of the distal femur. Five different prostheses were used and the wound problems were discovered on average 21 days after arthroplasty. The average wound size was 6.0 cm2. Five were infected, four with Staphylococcus epidermidis and one with Staphylococcus aureus. All patients were treated with antibiotics and local debridement for an average of 10 days prior to the flap procedure. Medical gastrocnemius muscle flaps were used in two patients, unipedicle flaps transposed from the lateral thigh in three, and bipedicle flaps shifted from the medial thigh in two. Flaps were done an average of 56 days after arthroplasty, and knee rehabilitation was delayed an average of 76 days after arthroplasty. Patients were followed an average of 48 months after the flap procedure. Six patients had mild or no knee pain and one who remained infected had moderate constant pain. Three of the patients had greater than 90 degrees of knee motion and one had 75 degrees of motion. The remaining three had only 35 degrees of motion, due in part to significant preoperative contractures, infection, local radiation, and chemotherapy. Late infection developed in two patients at 20 and 45 months following the flap procedure. There was one excellent, three good, two fair, and one poor result using the Hospital for Special Surgery knee rating system at final follow-up examination. | |
| 3495570 | Cryoglobulinemia induced by monoclonal immunoglobulin G rheumatoid factors derived from au | 1987 Jun 1 | A MRL strain bearing the autosomal recessive mutant gene, lpr (lymphoproliferation), spontaneously develops, in addition to a lupus-like syndrome, unique serological and pathological manifestations. Production of high titers of IgG rheumatoid factors (RF) may be related to the formation of extremely large amounts of cryoglobulins and the development of tissue lesions such as necrotizing polyarteritis, arthritis, and glomerulonephritis. To analyze more directly the relationship of IgG RF to the development of cryoglobulins and tissue injuries, we have established four monoclonal IgG RF secreting hybridomas from unimmunized MRL-lpr/lpr mice and determined their pathogenic effects in normal strains of mice. All the monoclonal IgG RF obtained in this study were of the IgG3 subclass and generated cryoglobulins. However, the fact that not only IgG3 Rf monoclonals but also four of five non-RF IgG3 monoclonals were able to form cryoglobulins, which were composed exclusively of each IgG3 monoclonal, indicates that the IgG3 molecule has a unique physicochemical property to self-associate via nonimmunological interaction and the ability to form cryoglobulins. When the in vivo pathogenic activities of these IgG3 RF and non-RF monoclonals were examined, three of IgG3 RF monoclonals with the specificity to IgG2a were able to induce extensive pathologic manifestations including peripheral vasculitis and glomerulonephritis characteristic of patients with cryoglobulinemia. Our results indicate that the IgG3 itself, independently of its specificity, could be a potential source of cryoglobulins and IgG3 RF, combined with its activity of cryoglobulin formation, may play a significant role in the development of glomerulonephritis and cutaneous vascular lesions of ears and foot pads observed frequently in aged MRL-lpr/lpr mice. | |
| 2242058 | The American College of Rheumatology criteria for the classification and reporting of oste | 1990 Nov | Clinical criteria for the classification of symptomatic idiopathic (primary) osteoarthritis (OA) of the hands were developed from data collected in a multicenter study. Patients with OA were compared with a group of patients who had hand symptoms from other causes, such as rheumatoid arthritis and the spondylarthropathies. Variables from the medical history, physical examination, laboratory tests, and radiographs were analyzed. All patients had pain, aching, or stiffness in the hands. Patients were classified as having clinical OA if on examination there was hard tissue enlargement involving at least 2 of 10 selected joints, swelling of fewer than 3 metacarpophalangeal joints, and hard tissue enlargement of at least 2 distal interphalangeal (DIP) joints. If the patient had fewer than 2 enlarged DIP joints, then deformity of at least 1 of the 10 selected joints was necessary in order to classify the symptoms as being due to OA. The 10 selected joints were the second and third DIP, the second and third proximal interphalangeal, and the trapeziometacarpal (base of the thumb) joints of both hands. Criteria derived using the "classification tree" method were 92% sensitive and 98% specific. The "traditional format" classification method required that at least 3 of these 4 criteria be present to classify a patient as having OA of the hand. The latter sensitivity was 94% and the specificity was 87%. Radiography was of less value than clinical examination in the classification of symptomatic OA of the hands. | |
| 2386108 | Inhibition of interleukin-1 release by IX 207-887. | 1990 Jun | Compound IX 207-887 is a novel antiarthritic agent which inhibits the release of interleukin-1 (IL-1) from human monocytes and mouse peritoneal macrophages in vitro at concentrations which are achieved therapeutically in human rheumatoid arthritis and in animal models of arthritis. In the present studies IL-1 activity in conditioned media, homogenates or lysates was monitored using four independent assay systems. Biologically active IL-1 was determined by, a) the induction of latent metalloproteinase-release from rabbit articular chondrocytes, which is relatively specific for IL-1 and b) by a sensitive thymocyte proliferation assay. Immunoreactive IL-1-beta was assayed by RIA and ELISA. In all test systems IX 207-887 significantly reduced both biologically active and immunoreactive IL-1 in culture media, whereas the levels of IL-1 in homogenates or lysates were either unaffected or only marginally reduced. The release of other monokines tested, such as interleukin-6 and tumour necrosis factor-alpha, and the secretion of lysozyme were only marginally influenced. IX 207-887 neither affected the adherence of human monocytes nor markedly inhibited IL-1 or IL-2-induced thymocyte proliferation. In the chondrocyte test no IL-1 antagonistic activity of IX 207-887 could be observed. All of these data indicate that IX 207-887 has the novel property of being an inhibitor of IL-1 release. | |
| 2440453 | The immunologic relationship of human neutrophil and skin collagenases. | 1987 Jun | An understanding of the immunologic relationships between collagenases of various cellular origins is necessary to define the roles of various cell types in the pathologic tissue destruction seen in chronic inflammatory diseases, such as rheumatoid arthritis. We compared the immunologic cross-reactivity of human neutrophil and skin fibroblast collagenases, utilizing polyclonal antisera prepared to purified enzymes. Polyclonal antisera from rabbits immunized with neutrophil collagenase recognized fibroblast collagenase, as well as the neutrophil enzyme, when analyzed by immunoblot techniques. The cross-reactive epitopes constituted a major proportion of the antibody population, as shown by competitive inhibition enzyme-linked immunosorbent assay; 50% of the antibody to neutrophil collagenase was inhibited by skin collagenase. Paradoxically, antisera to fibroblast collagenase failed to recognize the neutrophil enzyme, either by immunoblot techniques or competitive inhibition enzyme-linked immunosorbent assay, an observation which supports the notion that there are unique immunodominant epitopes. The cross-reactivity with skin fibroblast collagenase shown by the neutrophil antibody suggests a conservation of epitopes between collagenases of different cellular origins. The presence of epitopes unique for each enzyme, however, could lead to a feasible approach for investigating the differential contribution of various cell types to collagenolytic activity in inflamed tissues. | |
| 1835269 | Effect of etodolac, a new nonsteroidal anti-inflammatory drug, in MRL/lpr mice with articu | 1991 Jul | Etodolac, a new nonsteroidal anti-inflammatory drug, was administered orally at doses of 1 and 5 mg/kg to MRL/MpJ-lpr/lpr (MRL/lpr) mice, and its effect on articular lesions was compared with that of indomethacin. Both etodolac and indomethacin significantly reduced swelling of the hind paw. Histopathological examination showed that etodolac significantly reduced cartilage and bone damage, whereas indomethacin treatment did not achieve a statistically significant effect. Rheumatoid factors were not affected by either etodolac or indomethacin. These results indicate that etodolac delays the development of arthritis in MRL/lpr mice, and reduces cartilage and bone damage. | |
| 1859234 | [Compliance in adolescents with chronic disease]. | 1991 May | This study was undertaken with the aim of improving the understanding of the phenomenon of compliance in adolescents presenting with chronic diseases. In 192 subjects aged 12 to 20 years presenting with diabetes, asthma, cystic fibrosis, systemic lupus erythematosus or juvenile rheumatoid arthritis, appointment keeping, compliance with prescribed medical regimens or general instructions and the filling up of a calendar describing the daily levels of fatigue were studied. Correlations (Pearson) between these various types of measurements were weak: from 0.04 to 0.26. Appointment keeping was about 90%. Overall compliance either with treatments or with general instructions was 50% only (without clearcut changes according to diseases); however only 11% of subjects presented with a good compliance with all the treatment components. Various factors (familial environment, perception of the disease and of the patient-physician relationships) were significantly associated with compliance (p less than 0.005). These results emphasize the necessity of taking care of all aspects of compliance, which is difficult to predict at this age, due to the multiple factors involved. | |
| 2052510 | Giant cell vasculitis with extravascular granulomas in an adolescent. | 1991 Mar | We describe an 18-year-old white male who developed lower extremity ischemia requiring amputation. He presented at 14 with pulmonary infiltrates, hepatosplenomegaly, fever, rash, adenopathy, uveitis, and arthralgias; clinical and laboratory findings were consistent with Mycoplasma pneumoniae infection. Despite adequate treatment with antibiotics, he developed chronic arthralgias and fevers, with rash and pericardial effusion. Criteria for the diagnosis of systemic lupus erythematosus were not met; juvenile rheumatoid arthritis was diagnosed presumptively. Over the subsequent 4 years he developed lymphadenopathy with biopsy-proven nonnecrotizing granulomas, chronic leg ulceration with granulomatous histology, and acute-onset impending gangrene of the left foot. A biopsy of the posterior tibial artery demonstrated giant cell arteritis. Although the histologic features were consistent with Takayasu's arteritis, complete aortic arteriography was normal. Examination of the amputated leg showed multifocal segmental giant cell arteritis. Clinicopathologic features suggested, but were not fully consistent with, juvenile systemic granulomatosis. His disease may represent a separate sarcoid-like entity in the broad spectrum of vasculitis. | |
| 1824833 | Lack of binding between cryoimmunoglobulins, immunoglobulins and fibronectin: implications | 1991 Jan | Immune-complex-mediated vasculitis is a frequent complication of rheumatoid arthritis and systemic lupus erythematosus. The mechanism of deposition of immune complexes within the vessel wall in these diseases remains unknown, but probably involves other proteins. Fibronectin is a likely candidate since it possesses the ability to bind to collagen, endothelial cells, and possibly immunoglobulins and immune complexes. In this study, the binding of fibronectin to IgG and IgM cryoglobulins, cold soluble IgM, IgG, IgG subclasses and IgG fragments was investigated in the solution phase. Static light scattering, fluorescence anisotropy, fluorescence intensity, and PEG precipitation studies were used to investigate binding under different conditions of temperature and ionic strength. These studies failed to demonstrate significant binding between fibronectin and IgM, IgG, IgG subclasses and IgG fragments under the conditions studied. These findings argue against solution phase binding of fibronectin and immunoglobulins contributing to immune complex vasculitis. The possibility of important surface interactions between these proteins has not been ruled out. | |
| 2085145 | Modulatory effect of bucillamine (SA96) on interleukin-1-and/or -2-induced proliferation o | 1990 Nov | Bucillamine [SA96:N-(2-mercapto-2-methylpropanoyl)-L-cysteine], a synthetic SH compound, has recently been developed as remission-inducing agent for rheumatoid arthritis (RA), and its clinical usefulness for RA has been proved in Japan. Bucillamine suppressed the mitogen-induced proliferation of murine lymphocytes in vitro. The present study was undertaken to clarify the effect of bucillamine primarily on the release of interleukin (IL)-1 from monocytes and on the proliferation of T cells. Bucillamine significantly inhibited IL-1-induced thymocyte proliferation in a dose-dependent manner. And, bucillamine also inhibited IL-2-induced proliferation at the concentration of 1 x 10(-4) M, but augmented proliferation at the concentration of 1 x 10(-5) M. In contrast, D-penicillamine (an analogous SH compound to bucillamine) did not show any significant effect at similar concentrations. | |
| 2220394 | Hashimoto's thyroiditis as a risk factor of thyroid lymphoma. | 1990 Jul | Hashimoto's thyroiditis (struma lymphomatosa), first described by Hashimoto in 1912, is an autoimmune inflammation of the thyroid commonly affecting middle-aged women. Histologic features of Hashimoto's thyroiditis (HT) include diffuse infiltration of lymphoid cells usually with formation of lymphoid follicles, varying degrees of fibrosis, oxyphilic change or squamous metaplasia in the epithelial cells. When the presence of focal lymphocytic infiltration is assumed to be an adequate criterion for diagnosis of autoimmune thyroiditis, the incidence appears to be as high as 16-23% in elderly females. An etiologically important role of HT in the development of thyroid lymphoma had been postulated, and recently, this was confirmed by epidemiological studies. In this article, a brief review of HT is given, together with results of our studies on thyroid lymphoma, and a discussion in the light of the pertinent literature. Immunologic and immunohistologic studies revealed that all of the thyroid lymphomas were of the B-cell type. Malignant lymphomas developing in patients with other autoimmune diseases such as Sjögren syndrome and rheumatoid arthritis have also been reported to be B-cell derived. Therefore it is suggested that immune deficiency is a causal factor for B-cell lymphoma. | |
| 2388205 | The effect of human interleukin 1 on proteoglycan metabolism in human and porcine cartilag | 1990 Jun | Human interleukin 1 (IL-1), up to 100 pg/ml, causes a decrease of the proteoglycan content of human (old and young) as well as porcine cartilage explants, without stimulating the proteoglycan release from the cartilage. The proteoglycan depletion is stronger in young than in old human cartilage and stronger in human than in porcine cartilage. The proteoglycan synthesis is considerably more inhibited by IL-1 in young than in old human cartilage. Our data suggest that an IL-1 induced inhibition of the proteoglycan synthesis, rather than a stimulation of proteoglycan breakdown causes the proteoglycan depletion of the cartilage. The data furthermore suggest a clear difference between young and old human cartilage, with respect to their sensitivity for IL-1. IL-1 in a concentration of 500 pg/ml causes in all 3 kinds of cartilage explants chondrocyte damage that might be relevant in the cartilage destruction during rheumatoid arthritis. | |
| 2317934 | A sensitive and specific assay for granulocyte elastase in inflammatory tissue fluid using | 1990 Feb 28 | Granulocyte elastase (GE, EC 3.4.21.37) is a key enzyme in tissue injury. To elucidate the role of GE in tissue injury, a new method of measuring GE activity in various inflammatory tissue fluids was developed using diazotization and the chromogenic synthetic substrate, L-pyroglutamyl-L-prolyl-L-valine-p-nitroanilide (S-2482). GE activity demonstrated first order kinetics in the range from 1.9 to 30 U/l. Other proteases, such as pancreatic elastase, trypsin, and chymotrypsin did not hydrolyze S-2484. This assay permits the determination of GE activity with a coefficient of variance less than 7.8% and 95.6 to 105.4% recovery. With this method, hydrolytic GE activity was found to be increased in bronchoalveolar lavage fluid from patients with ARDS or pneumonia, synovial fluid from patients with rheumatoid arthritis, and blister fluid from burn patients. | |
| 2533001 | Discrepancy between 3H-thymidine uptake and cell cycle studies in stimulated lymphocyte cu | 1989 Nov | The mode of action of methotrexate (MTX) in rheumatoid arthritis (RA) is unknown. The hypothesis that its cytostatic effect may be involved has been questioned based on the evidence of several negative results, the most intriguing being its lack of effect on the Lymphoblastic Transformation Test (LTT) and other lymphoproliferations in cultures from patients' samples. Our study demonstrates that LTT evaluation by 3H-thymidine uptake, a standard method, is misleading when applied to MTX-treated cells. At in-vitro concentrations similar to those present in the red blood cells of RA patients, MTX produced an early block in the cell cycle without reducing the cellular uptake of 3H-thymidine. While the explanation of this discrepancy is still open to discussion, it is clear that future studies on the immunological status of RA patients on MTX should not use thymidine uptake for the measurement of the lymphocyte response to mitogens and various stimuli, but must rely on other methods for evaluating DNA synthesis. | |
| 2573586 | Some disease-associated ancestral haplotypes carry a polymorphism of TNF. | 1989 Oct | We describe here an Nco I restriction fragment length polymorphism of tumor necrosis factor carried by the 8.1 (HLA-A1,B8,BfS,C4AQ0,C4B1,DR3) and the 44.1 (HLA-B44,BfS,C4A3,C4BQ0,DR4) ancestral haplotypes associated with complications of rheumatoid arthritis. By examining multiple examples of these and other ancestral haplotypes it was seen that 8.1 and 44.1 ancestral haplotypes yield fragments of approximately 5.5 kb while many other ancestral haplotypes carry fragments of approximately 10.5 kb. The polymorphism is associated with the ancestral haplotype rather than the HLA-B or -DR allele defined by conventional serology. | |
| 2479743 | Substance P activates and modulates neutrophil oxidative metabolism and aggregation. | 1989 Aug | The substance P (SP) fragment SP(7-11) induced chemiluminescence (CL) and aggregation in human neutrophils at high concentrations (greater than or equal to 10 microM), whereas the entire molecule SP(1-11) was less potent and the SP(1-4) fragment was inactive. At these concentrations SP and its fragments also inhibited CL and aggregation evoked by subsequent addition of formyl-methionyl-leucyl-phenylalanine (fMLP), an effect that may depend on desensitization. However, at lower concentrations (1-10 nM) SP was able to prime human neutrophils to enhanced CL and enzyme release stimulated by fMLP. These findings indicate that, in addition to direct activation of CL and aggregation, SP also modulates neutrophil function and can thus amplify the release of potentially cytotoxic substances, a possible mechanism for nervous system involvement in rheumatoid arthritis. | |
| 2801317 | Inhibitory effects of E-5110 on interleukin-1 generation from human monocytes. | 1989 Jun | Effects of E-5110, a novel non-steroidal antiinflammatory drug, on interleukin-1 (IL-1) generation from human monocytes were studied in vitro. E-5110 reduced the amounts of extra- and intracellular IL-1 activity induced by lipopolysaccharide (LPS, 1 micrograms/ml) in a dose-dependent manner (1-10 microM). E-5110 also inhibited the IL-1 generation induced by antigen-antibody complexes, opsonized zymosan and silica particles. It was suggested that the inhibition of IL-1 generation by E-5110 was independent of the inhibitory effects on arachidonate cyclooxygenase and/or lipoxygenase because indomethacin, piroxicam, BW755C and AA861 had no effects on IL-1 generation. Hydrocortisone (IC50:0.084 microM), aurothioglucose (11.5 microM) and lobenzarit (75.0 microM), which are clinically effective antirheumatic drugs, also inhibited IL-1 generation, like E-5110 (1.21 microM). It is expected that E-5110 will be superior to classical non-steroidal antiinflammatory drugs in medical treatment of rheumatoid arthritis. | |
| 2649948 | [Analysis of adenosine deaminase and its subfractions as a diagnostic parameter in tubercu | 1989 Jan | In this paper we present the results of a study about the diagnostic utility of Adenosine Deaminase (ADA) determination for diagnosing the tuberculous pleural effusion. We carried out this study in 71 patients who came to our Hospital and were diagnosed for pleural effusion. The ADA determination was made in sera and pleural effusion of all these patients. Also we determined how much of this ADA activity was linked to microsomes or not (soluble ADA), by ultracentrifugation as a separative method. Taking as a base the data obtained and using 43 U/l as cutoff point, the Diagnostic Sensitivity of ADA determined in pleural liquid calculated was 1. This means that all patients with tuberculous pleural effusions had ADA activities higher than 43 U/l in their pleural liquid. On the other hand, Diagnostic Specificity was of 0.83. This was due to the existence of 10 false positives: 2 malignancies, 3 empyemas, 1 postpneumonia, 1 secondary to thromboembolic pulmonary disease, 1 secondary to rheumatoid arthritis and 2 of unknown origin. Results obtained show the utility, with some limitations, of ADA determination in pleural liquid in order to diagnose tuberculous pleural effusions. Neither ADA determination in sera nor quantity of ADA linked to microsomes or solubles ADA in pleural liquid seem to have great clinical interest. | |
| 3051283 | Effects of D-penicillamine on mononuclear cells in vitro. | 1988 | D-penicillamine (D-pen) inhibited pokeweed mitogen-induced plaque-forming cell (PFC) response in a dose-dependent manner. This inhibition was irreversible as preincubation for a few hours with the drug followed by washes still caused suppression of the PFC response. Pretreatment of the different mononuclear cell populations with D-pen for short periods (2-24 h) showed that both macrophages (Mo) and B lymphocytes were affected by the drug. By contrast T cells were resistant. Mo appears to be more susceptible to D-pen than B cells, and in the case of drug-treated Mo, the response was restored completely with the addition of 20% fresh Mo. Our results show that D-pen, without exogenous Cu2+, inhibits the polyclonal immunoglobulin secretion by human mononuclear cells in vitro due to a strong effect on both Mo and B cells. This may explain the decrease in serum immunoglobulin levels seen in patients with rheumatoid arthritis undergoing this therapy. | |
| 3664371 | Acetylcholine receptor antibodies in myasthenia gravis: use of a qualitative assay for dia | 1987 Aug | We have modified the techniques of Lindstrom and of Tindall to measure serum acetylcholine receptor antibody using human antigen bound to 125I-alpha Bungarotoxin. By using 10 microliters of serum and precipitating antigen-antibody complexes with an excess of staph A, we found that only one out of 43 patients with clinically diagnosed active generalized Myasthenia Gravis had no antibodies. In pooling these results with the results of tests done for diagnostic purposes we found positive results in 54/55 generalized active MG, 8/21 MG in remission, 16/37 ocular MG and 0/55 healthy controls. Two out of 38 non MG were also positive and their clinical diagnosis of botulism and penicillamine treated rheumatoid arthritis have been confirmed by a one year follow-up. Most of these sera were also tested for reactivity with fetal calf AchR. Six out of 49 samples positive with the human receptor were negative with calf receptor. We conclude that our technique is extremely useful for the diagnosis of Myasthenia Gravis and that fetal calf antigen cannot replace human antigen in the assay. |