Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3324230 | [Obstructive bronchiolitis]. | 1987 | The term "obstructive bronchiolitis" used in this review covers different clinicopathological aspects. On the one hand, it refers to "small airways disease", where bronchiolar narrowings are widespread, secondary to post inflammatory fibrotic changes linked to tobacco smoke or fibrogenic dust inhalation. These obstructive changes at the level of small airways are responsible for a fixed airflow limitation. The specificity and sensibility of functional tests designed for early detection of such an obstruction (the frequency dependence of compliance, the nitrogen slope and the density dependence of the flow-volume curve) are still controversial. On the other hand, the entity covers a disease described at the beginning of the century under the name "bronchiolitis obliterans". It usually appears as a consequence of various causes: viral infection, toxins acting either inhalation or by systemic route, immunological mechanisms as in connective tissue diseases or in graft versus host reactions. A special emphasis is put on idiopathic bronchiolitis obliterans associated with organizing pneumonia. Some clinicopathologic correlations are of basic interest in relation to etiological factors: bronchiolitis obliterans due to viral infection in children involving mainly membranous bronchioles; by contrast, bronchiolitis obliterans related to other causes seems to extend further down from the terminal bronchioles to the respiratory bronchioles. Lymphoid bronchiolitis appears non specific and is mostly observed in association with systemic connective tissue diseases, such as rheumatoid arthritis. | |
| 3028023 | Expression of tumor cell properties in synovial cells in culture. | 1987 Jan | The tumorigenic properties of human rheumatoid arthritis synovial cells in culture were investigated. The synovial cells developed good colonies and secreted plasminogen activator (PA) and collagenase in the cell cultures, as do Hela cells. Since PA and progesterone receptor (PgR) are considered to be end products of estradiol action in breast cancer cells, the estrogen receptor (ER) and PgR content in these cells was also assayed. Large amounts of ER and PgR were detected in the synovial cells in culture, even though these cells are not targets for sex steroids. Study of the cytomorphologic changes in the synovial cells in culture revealed many characteristics generally observed in neoplastic cells. Whether any or all of these observations have any implication in prognosis or therapy in this disease remains to be studied. | |
| 3780093 | Etiology of osteoarthritis of the hip. | 1986 Dec | More than 90% of patients with so-called primary or idiopathic osteoarthritis of the hips in whom sufficient data were available to make an assessment of the normality of the hip joint at the cessation of growth clearly showed demonstrable abnormalities in the hip joint. The most common are mild acetabular dysplasia and/or pistol grip deformity. This latter deformity is associated with mild slipped capital femoral epiphysis (recognized or unrecognized at the time), Legg-Perthes' disease (recognized or unrecognized at the time), multiple epiphyseal dysplasia, spondyloepiphyseal dysplasia, and/or the presence of an intraacetabular labrum, as well as, in certain instances, acetabular dysplasia. When these abnormalities are taken in conjunction with the detection of other metabolic abnormalities that can lead to osteoarthritis of the hip and which may not be recognized readily, such as hemochromatosis, ochronosis, calcium pyrophosphate disease, and monarticular rheumatoid arthritis, it seems clear that either osteoarthritis of the hip does not exist at all as a primary disease entity or, if it does, is extraordinarily rare. | |
| 3099559 | Immunosuppressive actions of prostaglandins and the possible increase in chronic inflammat | 1986 Oct | A method is described to examine the activity of potential antirheumatic drugs on the release and activity of lymphokines and interleukins in vitro, using human peripheral blood mononuclear cells and synovial cells. The enhancement of lymphocyte-mediated effects brought about by non-steroid anti-inflammatory drugs has been shown to be the result of inhibition of a prostaglandin negative-feedback mechanism. Since the underlying features of rheumatoid arthritis and related diseases are almost certainly brought about by mononuclear cell activation, their enhancement by non-steroid anti-inflammatory drugs might well have serious clinical implications. The possibility is discussed that aspirin-like drugs, administered in large doses to patients suffering slight joint pain, might well exacerbate, perpetuate or even initiate a chronic arthritic condition. We suggest that, as soon as the disease has been diagnosed, patients should be treated with a disease-modifying drug and, if necessary, an analgesic which does not inhibit cyclo-oxygenase. | |
| 3791668 | Characterization of TSH antagonist activity in the serum of patients with thyroid disease. | 1986 Sep | The ability of sera from patients with thyroid disease to block TSH stimulation of cyclic AMP release from isolated porcine thyroid cells has been assessed and the blocking activity characterized. TSH receptor binding activity was also measured. No blocking or receptor binding activity was detectable in patients with primary myxoedema (n = 23), Hashimoto's disease (n = 11), multinodular goitre (n = 6), or rheumatoid arthritis (n = 10). However, analysis of sera from 23 patients (out of an initial screen of 110 patients) with treated Graves' disease which did not stimulate cyclic AMP production in the bioassay showed that two of these sera contained powerful blocking and receptor binding activity. Both these patients had been treated with 131I. Analysis of the two sera by gel filtration on Sephadex G-200 indicated that blocking and TSH receptor binding activity were associated only with the IgG fraction. Digestion of the IgG with pepsin followed by reduction showed that both (Fab)2 and Fab fragments contained high levels of blocking and binding activity. Antibody divalency was not necessary therefore for TSH antagonist activity. However, our studies suggest that autoantibodies of this type with TSH antagonist activity do not occur frequently in patients from the Cardiff region with primary myxoedema, Hashimoto's or treated Graves' disease. | |
| 3009806 | Effects of gold compounds on leukotriene B4, leukotriene C4 and prostaglandin E2 productio | 1986 Feb | The effects of auranofin (AF) and sodium aurothiomalate (GSTM) on the production of specific arachidonic acid metabolites by chemotactic tripeptide activated polymorphonuclear leukocytes has been investigated using radioimmunoassay techniques. AF insignificantly enhanced the production of leukotrienes B4 and C4 at a concentration of 0.5 microgram Au/ml. However, at increasing concentrations, this drug suppressed the production of these metabolites in a dose dependent manner. In contrast, GSTM did not affect the production of either leukotriene at the concentrations tested. Of particular interest, prostaglandin E2 production was not affected by either gold compound. Both leukotrienes and prostaglandins are metabolized from arachidonic acid and are potent mediators of inflammation. The inhibition of leukotriene production may be another mechanism by which AF manifests its antiinflammatory effects in patients with rheumatoid arthritis. | |
| 1797024 | Comparative analysis of murine T lymphocyte responses to cartilage proteoglycans. | 1991 Oct | Cartilage proteoglycans are large molecules consisting of several sub-regions each of which comprises homologous repeating subunits. Comparisons of murine primed popliteal lymph node responses to human cartilage proteoglycans in BALB and B10 congenic mice showed that the major histocompatibility complex (MHC) influences T cell responsiveness to this antigen. H-2k and H-2d were higher responders than H-2b. Responses were MHC class II-restricted, and human cartilage proteoglycans were cross-reactive with mouse cartilage proteoglycans for a BALB/c T cell line. The proportion of proteoglycan-specific T lymphocytes in BALB/c primed popliteal lymph nodes was about 45% lower in females than males. These results show that in mice both MHC haplotype and sex can determine T lymphocyte responsiveness to cartilage proteoglycans. If the same mechanisms apply in humans they could be important in determining the HLA-DR haplotype associations and the predilection of rheumatoid arthritis for females. | |
| 1656898 | In vitro effects of methotrexate on peripheral blood monocytes: modulation by folinic acid | 1991 Sep | The mechanism of action of low dose methotrexate in rheumatoid arthritis has not been established. It has been shown to have an anti-inflammatory effect and to inhibit neutrophil chemotaxis, but the effect on monocytes has not been widely studied. Normal donor peripheral blood monocytes were incubated with methotrexate in vitro and their superoxide production, chemotaxis, and phagocytosis subsequently assessed. Additionally, the influence of different culture media, and of folinic acid, and the methyl donor S-adenosylmethionine, and spermidine on the methotrexate mediated effects were evaluated. It was found that methotrexate in low concentrations inhibited in vitro monocyte chemotaxis and superoxide production but only after prolonged incubation. This inhibition was augmented by incubation in medium containing a low methionine concentration and was abolished by folinic acid and S-adenosylmethionine, suggesting that methotrexate may interfere with specific methylation reactions. | |
| 2023201 | Evaluation of antirheumatic drugs for their effect in vitro on purified human synovial flu | 1991 Jan | Agents used to treat rheumatoid arthritis were examined for their ability to modify synovial fluid phospholipase A2 (SF-PLA2) activity. Nonsteroidal or steroidal antiinflammatory drugs and disease modifying agents exhibited little or no PLA2 modulatory activity. The exceptions include weak inhibition displayed by the cyclooxygenase inhibitors, indomethacin (IC50 = 144.8 microM) and sulindac sulfide (30.2 microM) and a 5-lipoxygenase translocation inhibitor, MK-886 (IC50 = 50 microM). Cyclosporine potentiated acylhydrolysis (EC50 = 1.5 microM) whereas the other immunomodulators examined demonstrated no significant effect on SF-PLA2 activity. Our data show that there are no selective PLA2 inhibitors currently used in the treatment of human arthritic disease and the viability of this novel approach remains to be tested. | |
| 2288818 | Bone loss in prednisone treated sarcoidosis: a two-year follow-up. | 1990 Jul | We followed up 35 sarcoid patients treated with prednisone for two years in order to evaluate bone mineral loss over time. Vertebral cancellous mineral content was detected by quantitative computed tomography and calibration phantom before beginning prednisone therapy and monitored two more times at yearly intervals. The percent mineral loss (ML%) averaged -13.9 +/- 2.1 at the end of the first year and -15.3 +/- 2.6 at the end of second year. We conclude first, that the time course of mineral loss in prednisone treated sarcoidosis is similar to that of other diseases such as asthma and rheumatoid arthritis. In a separate group of 10 early postmenopausal females, we observed a greater ML% averaging -21.9 +/- 16.6 and -26.2 +/- 18.5, at the end of the first and second year respectively. Our second conclusion was thus that the synergic effect of postmenopausal status and prednisone therapy results in an ML% far more significant than expected from the two single conditions. | |
| 2324965 | Structure of amiprilose hydrochloride, a novel anti-inflammatory agent. | 1990 Feb | Amiprilose hydrochloride is a carbohydrate-derived, novel anti-inflammatory with potential application in the treatment of rheumatoid arthritis. A spectroscopy-based approach was undertaken to assign both the relative and absolute configuration of its five chiral centers. The fully assigned 13C and 1H NMR spectra of amiprilose hydrochloride was used to establish the relative stereochemistry of four of its five chiral centers held rigid in its furanose ring system. Parallel synthesis of the enantiomer of amiprilose hydrochloride from L-glucose was followed by CD spectropolarimetry to establish that no inversion of chiral centers had occurred in the synthesis. The hydrobromide salt of amiprilose and its enantiomer were prepared and, together with amiprilose hydrochloride, were crystallized. X-ray crystallographic analysis resulted in the assignment of the absolute configuration of all five chiral centers. | |
| 2801325 | Development of a delayed-type hypersensitivity granuloma model in the mouse for the study | 1989 Jun | A cutaneous model of delayed-type hypersensitivity granuloma (DTH GRA) was developed, using methylated bovine serum albumin (mBSA) which could be easily quantified and represented chronic cellular immune-mediated inflammation characteristic of rheumatoid arthritis (RA). Quantitative kinetics showed maximal DTH GRA "wet" tissue weights at d.5 post-induction, diminishing between d.15-22; DTH GRA "dry" tissue weights peaked between d.8-22. Histological evaluation revealed early extensive fibrin deposition, edema, mixed PMN/mononuclear leucocyte infiltration and angiogenesis (d.2-5), followed by increased macrophage recruitment, lymphocyte infiltration, angiogenesis and vasculitis (d.10-15). Fibrin resorption and replacement by fibrous tissue resulted in resolution by d.35. It is suggested that the DTH GRA reaction represents a relevant model for probing pathogenic mechanisms and potential therapeutics for RA. | |
| 2785792 | Inhibition of the covalent binding reaction of complement component C4 by penicillamine, a | 1989 Apr 15 | D(-)-Penicillamine [D(-)-beta beta-dimethylcysteine] is an anti-arthritic drug, but its use is limited by adverse side effects, which include problems in immune-complex clearance. Complement is important as a source of inflammatory mediators in rheumatoid arthritis and is also involved in immune-complex clearance. Thus inhibition of the complement cascade would be likely to contribute to both the therapeutic and the toxic effects of penicillamine. It is shown that penicillamine and cysteine are potent inhibitors of the covalent binding of activated complement component C4 to immune complexes. [35S]Cysteine itself becomes covalently bound to C4b through the thioester site. Penicillamine and cysteine are more reactive with the C4A isotype than with the C4B isotype of the HLA class III protein C4. The limited amino acid sequence differences between C4A and C4B include a cysteine/serine interchange, and it is suggested that the cysteine residue in C4A contributes to the increased rate of reaction of C4A with the alpha-amino-beta-thiol compounds. | |
| 2568568 | [Clinical and epidemiologic characteristics of hemorrhagic fever with renal syndrome]. | 1989 Mar | Clinical and epidemiological data on 16 patients with HFRS admitted to the University Hospital of Infectious Diseases in Zagreb during the past 10 years (1977-1986) are reported. In 13 of them, the diagnosis was confirmed serologically by indirect fluorescent method. All but two were men between 20 and 45 years of age (80% of patients). The disease appeared sporadically only. According to the domicile, way of living and working all the patients but three mentioned the contact with rodents in the fields or in other places (mill, storehouse). Three patients live in Zagreb and there was no possibility to get infected out of the town. The disease had moderate course, more rarely severe course when shock and acute renal failure developed. General symptoms with fever and algias dominated (febrile stage). Some of the patients had ophthalmic disturbances. Patients with a pronounced gastroenteritis developed shock the most frequently. In some of the patients back and abdominal pains followed by obstipation appeared. HFRS was incriminated disease because of febrile stage followed by the acute renal failure, oliguria, azotemia, polyuria and low urine osmolity. One female patient with active rheumatoid arthritis died after two-week staying in hospital due to irreversible shock followed by cardiopulmonary and renal failure. | |
| 2500316 | [Antiphospholipid antibodies: clinical significance in systemic lupus erythematosus]. | 1989 Feb | A radioimmunoassay using cardiolipin as antigen and labelled SPA, anti-human IgG, anti-human IgM, anti-human IgA as second antibodies in detecting anti-cardiolipin antibody with the sera from 308 patients and 70 normal controls. Among them, 126 patients were of SLE, 27 systemic sclerosis, 40 rheumatoid arthritis, 40 Sjögren syndrome, 26 other connective tissue diseases, 7 syphilis and 32 with obstetric complications. The positive rate of anticardiolipin antibody were 42.9% (SLE), 29.7% (PSS), 20% (RA), 15% (SS), 26.9% (CTD), 85.7% (syphilis), 3.1% (obstetric complication), 0% (NC). In SLE the anticardiolipin antibody were well correlated with thrombocytopenia, cerebral lupus, thrombosis of vein and spontaneous recurrent abortion. Lupus anticoagulant (APTT) was found in 21.3% of SLE and biological false positive of VDRL test in 4.8%. Both of them correlated with the anticardiolipin antibody detected by the radioimmunoassay. The authors concluded that antiphospholipid antibodies is a group of commonly seen antibodies, which may play a rule in the pathogenesis of SLE. Further study is progressing. | |
| 2690856 | Selenium: clinical significance and analytical concepts. | 1989 | Selenium is an essential trace element in humans and animals. Its only established function in humans is the antioxidant activity of glutathione peroxidase, a selenoenzyme. Severe prolonged deficiency may cause a fatal cardiomyopathy. Iatrogenic causes of selenium deficiency include parenteral and enteral nutrition. Low plasma selenium is also found in malabsorption, cystic fibrosis, rheumatoid arthritis, neoplasia, and other varied clinical disorders. Death has resulted from a single massive ingestion of selenium, while chronic excessive intake causes skin, nail, and hair pathology. Extreme geographical variation in population blood and urine selenium levels and a marked age-specific variation in population reference intervals are important factors in understanding selenium nutrition. Nutritional requirements, biological availability, and metabolism are discussed in relation to geographical, age, and method variability. Sampling, processing procedures, and methods for selenium quantitation are reviewed. Selenium content in different biological matrices and reference values for pediatric, adult, and obstetric populations are provided. | |
| 2680924 | Molecular mechanisms involved in human autoimmune diseases: relevance of chronic antigen p | 1989 | The observation that the local site of autoimmune responses over-expressed HLA class II led to the formulation that tissue antigen-presenting capacity contributes significantly to the mechanism of autoimmune disease perpetuation, by continually reactivating auto-antigen-reactive T lymphocytes. These in turn produce mediator molecules which maintain HLA class II expression (and hence antigen-presenting capacity) in the target tissues; and also initiate the immune and inflammatory pathways. The importance of this concept is that it provides a readily testable hypothesis that has been investigated extensively. For the thyroid diseases compelling data to support it have accumulated; in other diseases such as rheumatoid arthritis the evidence is increasing. The concept also relates the human autoimmune diseases to the normal mechanisms of immune induction and immunoregulation. This highlights the areas that we do not yet understand, namely the interplay of genetic susceptibility, extrinsic agents or disorders of immune regulation which permit the autoimmune process to become sufficiently pronounced as to engender a clinical autoimmune disease. Even with our limited understanding of the disease process, it is apparent that there are many opportunities for newer approaches at therapy, based on interfering with the immune cells or their mediators. | |
| 2674558 | The role of cytokines in the immunopathology of tuberculosis, and the regulation of agalac | 1989 Fall | Tuberculosis is characterised by necrosis in the lesions and in skin-test sites, and by fever and weight loss. In contrast, other diseases with chronic T cell mediated responses, such as uncomplicated leprosy and sarcoidosis, have non-necrotising lesions with little systemic upset. Crude sonicates of M. tuberculosis and M. leprae prepare skin sites for TNF-mediated damage via a pathway which unexpectedly appears to involve CD8+ T cells, and both mycobacteria contain potent triggers of TNF release (lipoarabinomannan and peptidoglycan derivatives). These observations can partially explain the pathology of tuberculosis, but fail to explain why similar events do not normally occur in leprosy. It now seems likely that the answer lies in the existence of novel regulatory pathways. A recently recognised correlate (or consequence) of diseases characterised by T cell-dependent tissue-damaging pathology and cytokine release, is an increase in the level of agalactosyl IgG. This behaves like a T cell-dependent acute phase reactant, and is raised in tuberculosis, rheumatoid arthritis, and Crohn's disease, but not in sarcoidosis or uncomplicated leprosy. Thus it may act as a marker for a type of pathology of very broad significance, though its functional role remains obscure. | |
| 3415672 | Inhibition of leucocyte elastase by heparin and its derivatives. | 1988 Jun 1 | Leucocyte proteinases, e.g. leucocyte elastase and cathepsin G, are inhibited by heparin. The activities of pig pancreatic and Pseudomonas aeruginosa elastases are unaffected by this polysaccharide. Heparin derivatives of known Mr and degree of sulphation were isolated. The inhibition of leucocyte elastase by these oligosaccharides can be classified as tight-binding hyperbolic non-competitive. Ki values ranged from 40 nM to 100 microM and were found to be inversely correlated with the chain length of the oligosaccharides. Desulphated compounds lacked inhibitory potential towards leucocyte elastase. Over-O-sulphated di- and tetra-saccharides are more potent inhibitors than their over-N-sulphated counterparts. It is proposed that the therapeutic use of heparin and its derivatives could be extended to disease states such as emphysema and rheumatoid arthritis, where the role of leucocyte elastase has been clearly established. | |
| 3132555 | The effect of longterm treatment with auranofin and gold sodium thiomalate on immune funct | 1988 Mar | Although gold compounds are recognized as effective immunomodulatory agents in the treatment of rheumatoid arthritis (RA), their mechanism of action is controversial. We examined the effect of longterm treatment with 0.6-3.6 mg/kg auranofin (AF) per os q24h, or intramuscular injections of 0.5-2.0 mg/kg gold sodium thiomalate (GSTM) q3d, on 13 variables of immune function in normal dogs. None of the changes in these variables previously attributed to treatment with AF or GSTM could be demonstrated after 6-7 years' dosing. As gold compounds are effective in treating spontaneous RA in dogs, these proposed actions may not be responsible for the remittive effects of chrysotherapy in this disease. |