Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When cultivated together with pieces of cartilage biosynthetically labelled with 35S in their proteoglycans, rabbit macrophages, differentiated in vitro from bone-marrow cells, cause the release of soluble 35S-labelled material into the culture medium. This process is inhibited by killing the macrophages or by cycloheximide treatment, and is due to the secretion by the cells of a metal-dependent neutral proteinase capable of degrading cartilage proteoglycan subunits into fragments of high molecular weight. Enzyme activity is optimum at about pH7, and is inhibited by EDTA, o-phenanthroline, cysteine or serum, but not by di-isopropyl phosphorofluoridate nor by 4-hydroxymercuribenzoate. The effect of EDTA is partially reversed by Co2+ or Zn2+ ions. The enzyme is eluted from Sephadex G-150 columns as a single peak of material (apparent mol.wt. 17000) that contains also most of the proteolytic activity exerted by culture media on Azocoll (denatured collagen) or on casein. The possible role of this metalloproteinase in chronic inflammatory processes is discussed, particularly in connection with joint erosions in rheumatoid arthritis.
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PMID:Degradation of cartilage proteoglycans by a neutral proteinase secreted by rabbit bone-marrow macrophages in culture. 66 44

Immunoelectron microscopy for IgG and IgA was combined with plain electron microscopy and light microscopy to study a variety of articular collagenous tissues from 14 cases of classic rheumatoid arthritis. Numerous extensive aggregates of IgG and IgA positive material were found widely spread in locations that coincided with immunofluorescent staining for these immunoglobulins and B1c. This Ig positive material is thought to represent deposits of immune complexes. As great and greater amounts were seen in fibrocartilage menisci as in hyaline cartilage. A single specimen of disease tendon was also positive. Severe pathologic changes of the matrix characterized by loss of normal morphology, alterations in collagen, and overall reduced density were observed in regions of aggregate deposition with a consistent replacement and disappearance of collagen in the locale of the aggregates themselves. Polymorphonuclear cells in regions of degraded hyaline and tendon matrix were seen to have phagocytosed aggregates. These data give some credence to a direct role of immune aggregates in rheumatoid arthritis articular collagenous tissues in disease pathogenesis.
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PMID:Electron microscopic morphology of immunoglobulin aggregates and their interactions in rheumatoid articular collagenous tissues. 66 72

Using an assay to measure antigen-induction of a lymphocyte mediator, LIF, we detected cellular sensitivities to native human types II and III collagens in three-quarters of a group of 50 patients with rheumatoid arthritis. There was no cellular response to type I collagen. Cellular reactivities to collagen were absent in a group of 41 patients who had other kinds of arthritis, such as osteoarthritis, crystalline-induced synovitis, or arthropathies associated with a high prevalence of the HLA-B27 antigen. Lymphocytes, responding to an unknown persistent antigenic stimulus, are thought to play a major role in the pathogenesis of rheumatoid arthritis. It has previously been hypothesized that collagen might function as an autoantigen in this disease. Based on the disease specificity of our findings and the tissue distribution of types II and III collagens, we propose that cellular sensitivities to these structural proteins may be involved in the pathogenesis of rheumatoid arthritis.
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PMID:Cellular sensitivity to collagen in rheumatoid arthritis. 75 87

The number of large circulating hyperbasophilic mononuclear cells - referred to as hyperbasophilic immunoblasts (HBI)- is often increased in collagen disease and rheumatoid arthritis (RA) and grossly reflects the degree of disease activity. In contrast, in psoriatic arthropathy the percentage of (HBI) is within the normal range. HBI are mainly involved in immune reactions and may provide a valuable routine test for the assessment of the latter in disease states and for the predicition of relapse in chronic collagen diseases. Immunofluorescent techniques applied to samples from active autoimmune diseases have shown that a number of HBI are Ig-producing B-blasts. Moreover, in a few cases these intracytoplasmic immunoglobulins exhibited a rheumatoid factor-like activity, a finding which promises to yield additional information on the immunopathogenesis of RA.
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PMID:Hyperbasophilic immunoblasts in circulating blood in chronic inflammatory rheumatic and collagen diseases. 76 8

It is well known that majority of patients with collagen diseases are women and that collagen diseases take turn for the worse or the better when the secretion of sex hormones changes greatly at menarche, pregnancy, delivery or menopause. These facts suggest that sex hormones are involved in the pathophysiology of collagen diseases. In the present study, the responses of plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels following the intravenous injection of 100 mug luteinizing hormone-releasing hormone (LR-RH) were investigated in 34 patients with systemic lupus erythematosus (SLE) and in 15 patients with rheumatoid arthritis (RA). The results obtained were as follows: 1) The magnitude of plasma LH response to LH-RH in 29 mature female patients with SLE was significantly greater than that in normal subjects. 2) On the other hand, the magnitude of plasma FSH response to LH-RH in patients with SLE was comparable to that in control subjects. 3) In patients with RA who have normal menstrual cycles, the magnitude of increase in plasma LH and FSH levels after the injection of LH-RH was the almost same as that in normal subjects. Increased responses in plasma LH and FSH levels to LH-RH were observed in 7 patients with RA who were 3 menopausal females and 4 aged males. These findings suggest that the secretion of LH, but not FSH, in response to LH-RH might augment in patients with SLE. On the other hand, in RA patients the function of the pituitary-gonadal axis might maintain within normal limits. For that reason, I guess the following possibilities: 1) In patients with SLE the pathological changes of the disease reached to the ovary and ovarial function was slightly suppressed and then a hypersecretion of LH was observed, 2) the hypothalamus was attacked with the disease and then an unknown mechanism caused the hypersecretion of LH.
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PMID:[Studies on the secretion of gonadotropins in patients with collagen diseases]. 78 33

Beginning with lesions of the capillary wall, rheumatoid arthritis is morphologically expressed by an aseptic inflammation of the synovia with following necrosis of the cartilage and the underlying bone tissue. Only little is known regarding the pathogenesis but most porbably immune mechansims are involved. There is evidence for the participation of type IV and type III-reactions i.e. sensitized lymphocytes as well as immune complexes. Equally the etiology of RA is totally unknown. Once the inflammatory process has reached some activity, in most cases it shows the character of a selfpertetuation as in other autoimmune diseases. Laboratory examinations include BSR, blood count, measurement of Fe, Cu, RF, complement, streptolysins, staphylolysins, ANA, and in doubtful cases synovial biopsy. Furthermore, effusion fluid of the joint may be examined for RF, ANA, complement, rhagocytes, crystals, protein content etc.--Among the collagen diseases sensu strictori, systemic lupus erythematosus is the most important. The underlying process may be characterized as vasculitis due to immune complexes and local activation of the complement system, the complexes containing native and/or denatured DNA, and antibodies mostly of the IgG class. Laboratory examinations include the demonstration of ANA but should concentrate on the measurement of DNA-antibodies using radioimmunological or at least a sensitive and specific immunofluorescence technique. The value of the various tests is discussed.
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PMID:[Pathophysiology and laboratory diagnosis of collagen diseases (author's transl)]. 79

Sections of the pannus-articular cartilage junction from a patient with rheumatoid arthritis (RA) were prepared for electron microscopy. Cells at this interface contained membrane-bound collagen fibrils, apparently in various stages of digestion. Previous studies have demonstrated intracellular collagen fibrils at sites of very active and rapid collagen resorption. It is suggested that at certain times in certain patients with RA, phagocytosis of cartilage collagen fragments and subsequent intracellular digestion may serve as a supplemental pathway to extracellular collagen degradation.
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PMID:Intracellular collagen fibers at the pannus-cartilage junction in rheumatoid arthritis. 84 60

We have found that intradermal injection of native type II collagen extracted from human, chick or rat cartilage induces an inflammatory arthritis in approximately 40% of rats of several strains whether complete Freund's adjuvant or incomplete Freund's adjuvant is used. Type I or III collagen extracted from skin, cartilage proteoglycans and alpha1(II) chains were incapable of eliciting arthritis, as was type II collagen injected without adjuvant. The disease is a chronic proliferative synovitis, resembling adjuvant arthritis in rats and rheumatoid arthritis in humans. Native type II co-lagen modified by limited pepsin digestion still produces arthritis, suggesting that type-specific determinants residing in the helical region of the molecule are responsible for the induction of disease. Since homologous type II collagen emulsified in oil without bacterial preparations regularly causes the disease, this new animal model of arthritis represents a unique example of experimentally-inducible autoimmunity to a tissue component.
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PMID:Autoimmunity to type II collagen an experimental model of arthritis. 89 90

An arthritis closely resembling rheumatoid arthritis in man can be produced by the intra-articular injection of Fab2 into the knee joint of rabbits. This experimental model was used for the examination of ultrastructural alterations in articular cartilage. The lesion starts at the surface and advances gradually to the deeper zones of the cartilage. Morphologically, the lesion is characterized by progressive necrobiosis of the chondrocytes, as well as by a continually increasing thickening of the collagen fibres. It is suggested that the initial damage to the cartilage is not brought about by the pannus tissue, but is caused by a direct reaction to the pathologically-altered synovial fluid in response to inflammation.
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PMID:[Morphology of articular cartilage in fab2-induced arthritis of the knee-joint in the rabbit (author's transl)]. 91 61

By using the complement fixation test, antibodies against collagen were examined. Pronase-solubilized insouble collagen served as antigen (20 degrees, 24 hours, collagen: enzyme ratio 10:1). Of 79 patients suffering from rheumatoid arthritis, the presence of collagen antibodies was demonstrated in 8 cases. 56 patients with degenerative joint disease served as the control group, in which collagen antibodies were detected in only one single patient.
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PMID:Rheumatoid arthritis and collagen antibodies. 92 25


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