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  • 1
    Electronic Resource
    Electronic Resource
    The BAFF/APRIL System in Systemic Autoimmune Diseases with a Special Emphasis on Sjögren's Syndrome (2005)
    Oxford, UK; Malden, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 62 (2005), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Systemic autoimmune diseases, such as Sjögren's syndrome (SS), are characterized by a complex aetiology with multiple pathogenic factors. In SS, disturbed B-cell biology and humoral immunity including B-cell-activating factor (BAFF)-mediated processes have been described. Dysregulated BAFF expression has been described to lead to disease progression and perpetuation of humoral autoimmunity. Moreover, BAFF has been proposed to contribute to the development of B-cell malignancies. In this review, we summarize the current knowledge on BAFF with regard to SS pathology and discuss special features such as germinal centre (GC) formation and lymphomagenesis. Locally, in SS salivary glands, the reduced level of apoptosis among BAFF-expressing cells might lead to longer-existing BAFF expression and thereby maintain signalling for tissue-infiltrating B cells to proliferate and supposedly to become autoantibody-producing plasma cells. We assume that prolonged BAFF signalization may contribute to GC formation and/or lymphoma development in the disease. Finally, we discuss possibilities of novel treatments targeting the BAFF-system in SS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.2005.01688.x
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  • 2
    Electronic Resource
    Electronic Resource
    Apoptotic Effect of Rituximab on Peripheral Blood B Cells in Rheumatoid Arthritis (2004)
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc.
    Scandinavian journal of immunology 60 (2004), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Rituximab (RTX) has proven efficacious in the treatment of rheumatoid arthritis (RA). Herein, we assessed the apoptosis-inducing capability of RTX in vitro on RA peripheral blood B-cell subsets and also compared the effects of RTX on B cells from rheumatoid factor-positive (RF+) and RF– patients. The likely relevance of B cells in disease was assessed by measuring B-cell-modulating serum cytokines. Peripheral blood B cells were isolated and cultured with the presence or absence of RTX. The levels of apoptosis within the naïve, memory and IgD+CD27+ B-cell subpopulations were determined by cytofluorometric analysis and caspase 3/7 assays. Levels of serum cytokines were measured with a multiplex cytokine array system. RTX induced significant apoptosis in all B-cell subsets in both RA and controls. In naïve and memory B cells from RA patients, RTX induced significantly higher levels of apoptosis than in controls. RTX induced apoptosis of B cells in RF+ and RF– patients. Serum levels of interleukin-1β (IL-1β), IL-4, IL-10 and IL-13 were profoundly increased in RF+ patients compared to RF− patients and controls. Although our cohort was small (10 RA patients), the data suggest that RTX induces apoptosis in all investigated subsets of B cells from RA patients. Interestingly, memory B cells from RA patients were more sensitive to RTX than memory cells from normal controls, suggesting that the delay in treatment response to RTX observed in clinical trials may be due in part to memory cell depletion. The apoptotic effects of RTX were similar in RF+ and RF– patients, but serum levels of B-cell-activating cytokine levels were only elevated in RF+ but not RF– patients. These data suggest that RTX is less effective in RF– RA because B cells play a less significant role in RA pathogenesis in RF– patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0300-9475.2004.01441.x
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  • 3
    Electronic Resource
    Electronic Resource
    Circulating Cytokines in Primary Sjögren's Syndrome Determined by a Multiplex Cytokine Array System (2004)
    Oxford, UK; Malden, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 59 (2004), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Plasma cytokines play an important role in the pathogenesis of Sjögren's syndrome (SS) by initiating and perpetuating various cellular and humoural autoimmune processes. The aim of the present study was to describe a broad spectrum of T-cell and B-cell cytokines, growth factors, chemokines and molecules that could contribute to cell death in SS. A novel protein array system was utilized to measure simultaneously the levels of 25 plasma cytokines of patients with primary SS and healthy individuals. Furthermore, we correlated these plasma cytokine levels with potential laboratory and clinical parameters related to disease activity in SS. A subset of plasma cytokines [e.g. interleukin-1β (IL-1β), IL-6, CXCL8 (IL-8), IL-12 p40, IL-15, tumour necrosis factor-α (TNF-α), epidermal growth factor, CCL4 (MIP-1β), CCL2 (MCP-1), CCL11 (Eotaxin), CCL5 (RANTES), TNF-RI and TNF-RII] was found to significantly differ between patients and controls. Also, distinct populations of cytokines were found to differentiate between patients with normal versus elevated ESR or IgG levels and patients with the presence or absence of extra-glandular manifestations (EGMs). Our results support the assumption that the multiplex cytokine array system can be successfully utilized in the diagnosis and disease management of SS. Furthermore, it may provide a powerful tool in the design of individualized anticytokine therapies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0300-9475.2004.01432.x
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  • 4
    Electronic Resource
    Electronic Resource
    Do Autoantibodies Predict Autoimmune Liver Disease in Primary Sjögren's Syndrome? Data of 180 Patients upon a 5 Year Follow-Up (2002)
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 56 (2002), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Objective: To evaluate the clinical value of autoantibodies as serological markers to predict autoimmune liver diseases in primary Sjögren's syndrome (SS). Materials and methods: 180 patients who met the European diagnostic criteria for SS but without a history of liver disease were studied upon a 5 year follow-up. Sera taken at enrolment were evaluated by immunofluorescence analysis (IF-AMA) on rat liver, stomach and kidney sections, enzyme-linked immunosorbent assay using rat mitochondrial, microsomal and soluble liver antigens and Western blot (WB) analysis using rat mitochondrial antigens. Results: At presentation, 152 (84%) sera had autoantibodies. Antinuclear antibodies (ANA) were expressed in 58% of patients and displayed three distinct patterns (speckled, homogenous and anticentromere). Smooth muscle autoantibodies (SMAs) and parietal cell autoantibodies were found in 39 and 4.5% of patients, respectively. Three patients presented antimitochondrial antibodies by IF-AMA, and two of them developed symptomatic primary biliary cirrhosis (PBC). Two patients without IF-AMA and without evidence of cholestasis had PBC-specific AMA (anti-PDC–E2 and anti-BCKADC–E2). However, these two patients and the third IF-AMA-positive woman remained free from symptoms and biochemical signs of PBC. Autoimmune hepatitis (AIH) (n = 2), ‘overlap syndrome’ of AIH and chronic hepatitis C (n = 1) and autoimmune cholangiopathy (AIC) (n = 1) were diagnosed in four patients. Conclusions: Patients with IF-AMA usually develop symptomatic PBC upon a 5 year follow-up. Our findings support the idea that patients without IF-AMA, who express PBC-specific AMA, are in early, asymptomatic stage of the disease. High-titre SMA and IF-AMA are the most specific indicators for AIH and PBC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.2002.01165.x
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  • 5
    Electronic Resource
    Electronic Resource
    CD40, CD154, Bax and Bcl-2 Expression in Sjögren's Syndrome Salivary Glands: a Putative Anti-Apoptotic Role During its Effector Phases (2002)
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 56 (2002), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Sjögren's syndrome (SS) is an autoimmune rheumatic disorder characterized by chronic lymphocytic infiltration and decreased secretion in the salivary glands (SGs). For some time, apoptosis has been suggested to constitute the major mechanism for acinar epithelial destruction during the effector phases; however, this is still controversial. We have recently demonstrated that despite the expression of Fas and FasL, the incidence of apoptosis is not increased in SS patients compared with control individuals. Our aim was therefore to further evaluate the expression of the pro- and anti-apoptotic Bax and Bcl-2 proteins. CD40 and CD154 expression was also investigated, as CD40 ligation has been suggested to protect cells from Fas-mediated apoptosis. Immunohistochemical staining was performed on SG tissue from primary and secondary SS patients, a group of patients with non-SS-related degenerative changes as well as on healthy control individuals. The frequency of stained cells in the foci of infiltrating mononuclear cells (IMCs) and in the acinar and ductal epithelium was determined. We found the expression of Bcl-2 but rarely Bax in SS SG IMCs. Bcl-2 in epithelial cells was sparse, while Bax expression occurred frequently and with no significant difference between the patient groups. CD40 and CD154 expression was high among SS IMCs, while CD40 levels were slightly decreased in SS epithelium compared with controls. Elevated CD154 expression was found in SS epithelium, being significantly increased in the ducts. In conclusion, our study further supports the hypothesis about apoptosis resistance among SS focal IMCs and suggests a putative protective role of CD40 ligation in SS SG epithelium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.2002.01168.x
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  • 6
    Electronic Resource
    Electronic Resource
    Physiological role of coronary constriction in the tortoise (Emys orbicularis L.) (1964)
    Springer
    Cellular and molecular life sciences 20 (1964), S. 313-314 
    Details
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Konstriktion der Herzkranzgefässe nach epicardialer Anwendung von Catecholaminen vermindert den O2-Verbrauch des Schildkrötenherzens. Das Konstriktorsystem dieser Gefässe sichert eine rasche Anpassung des Herzstoffwechsels an den O2-Mangel.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02171065
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