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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Rheumatology international 17 (1997), S. 91-99 
    ISSN: 1437-160X
    Keywords: Key words Autoimmune diseases ; Pathogenesis ; Animal models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Failure of distinction between self and non-self is regarded a critical event in the pathogenesis of several human diseases such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, myasthenia gravis, uveoretinitis or diabetes mellitus. Autoagressive immune reactions driven by activated autoreactive lymphocytes are a characteristic feature of these autoimmune diseases. The mechanisms by which the pathogenic control of autoreactive lymphocytes deviates from physiology can be studied in appropriate animal models under well-defined experimental conditions. Experimental models of autoimmune diseases in rodent inbred strains allow for the genetic mapping of susceptibility loci and might help to identify candidate genes also relevant to the pathogenesis of human diseases. Finally, the experimental models are valuable tools to develop rational immunotherapeutic strategies. Interesting features of some of the models employed for such research will be introduced in this review.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1437-160X
    Keywords: Alpha 1-proteinase inhibitor ; Leucocyte elastase ; Cartilage ; Rheumatoid arthritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Synovial fluids of patients suffering from rheumatoid arthritis contain elevated levels of granulocyte (PMN) elastase in complex with alpha 1-proteinase inhibitor (alpha 1-PI), whereas free-elastase activity is usually not detectable. This absence of free enzymatic activity in joint effusions has cast some doubt on the pathophysiological relevance of PMN elastase in inflammatory joint destruction. Our in vitro experiments using bovine nasal cartilage demonstrate that incubation with elastase and alpha 1-PI in equimolar concentrations to or even in excess of the serum proteinase inhibitor resulted in significant tissue destruction as assessed by histological staining for proteoglycans, release of uronic acid from the matrix and loss of mechanical stability. Though in the supernatants containing alpha 1-PI, free-elastase activity was not detectable, immunofluorescent staining for elastase evidenced penetration of the enzyme into the matrix. Simultaneous measurements of the incubation media employing a sandwich enzyme-linked immunoadsorption assay (ELISA) revealed PMN elastase in complex with alpha 1-PI but without correlation to the parameters of tissue degradation. In comparison with the results obtained using the chromogenic substrate Suc-Ala-Ala-Ala-pNA (SAPA) for titration of alpha 1-PI against elastase, the employment of cartilage matrix showed that a fourfold increase in inhibitor concentration was necessary to achieve 100% enzyme inhibition. Hence, cartilage surface obviously interferes with the interaction between alpha 1-PI and elastase. Measurements of elastase-inhibitor concentrations or free enzymatic activity in synovial fluid seem to have limited value in predicting cartilage destruction.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1437-160X
    Keywords: Biomechanics ; Lysosomal elastase ; Proteoglycans ; Collagen ; Cartilage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rheumatic joint destruction usually starts with the destabilisation of cartilage. Lysosomal elastase is a candidate effector of this process, since this enzyme is found at the site of cartilage erosion by rheumatoid synovial tissue. In order to prove this hypothesis we assessed the mechanical stability of cartilage during treatment by this enzyme in vitro. An indentation apparatus was used for this purpose and biochemical as well as microscopic techniques were used to supplement the results thus obtained. Our findings show that elastase irreversibly impairs the stability of cartilage by lysis of matrix proteoglycans without the help of additive enzymes. Collagen fragmentation played no significant role during elastase-induced destabilisation, while specific collagenase attacked the collagen network within the matrix only subsequent to the removal of proteoglycans. These findings suggest that elastase is a leading enzyme during proteolytic cartilage degradation. In addition polysulfonated glycosaminoglycan was found to reduce the mechanical effect of elastase on normal cartilage. It is therefore concluded that local inhibition of elastase promises therapeutic benefit during rheumatic cartilage degradation. Upon treatment of cartilage with elastase we observed this enzyme not only within the matrix under destruction but also bound to chondrocytes. These findings support the hypothesis that elastase plays a role on the matrix not only by direct degradation, but also by an indirect effect mediated through living chondrocytes.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Rheumatology international 17 (1997), S. 85-90 
    ISSN: 1437-160X
    Keywords: Key words Immunosuppressive drugs ; Autoimmune disease ; Animal models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An unprecedented arsenal of new xenobiotic immunosuppressive agents has been developed recently. Most of the new immunosuppressants have been tested primarily in the treatment of allograft rejection in experimental models of transplantation, and some of the new drugs have already proven their safety and efficiency in extensive clinical trials on transplant patients. Another field for their potential application is the treatment of autoimmune diseases. This review will give an overview of the therapeutic potential of the new xenobiotic drugs in different animal models of rheumatoid arthritis, systemic lupus erythematosus, myasthenia gravis, multiple sclerosis, diabetes mellitus, thyroiditis and uveoretinitis. The new xenobiotics are either inhibitors of the de novo synthesis of nucleotides, for example mycophenolate mofetil, mizoribine, leflunomide, and brequinar, or are immunophilin-binding agents (cyclosporin, FK506 and rapamycin) that inhibit signal transduction and cell cycle progression in lymphocytes. A different mode of action is likely to account for the immunosuppressive effects of deoxyspergualin, which may interfere with intracellular chaperoning by the heat shock protein HSP70 and the activation of transcription factor NF-kappa B.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Zeitschrift für anorganische Chemie 171 (1928), S. 102-125 
    ISSN: 0863-1786
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Zeitschrift für die chemische Industrie 43 (1930), S. 330-333 
    ISSN: 0044-8249
    Keywords: Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 59 (1926), S. 897-900 
    ISSN: 0365-9631
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 59 (1926), S. 2682-2682 
    ISSN: 0365-9631
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 59 (1926), S. 890-896 
    ISSN: 0365-9631
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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