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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  42. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 24. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR); 20140917-20140920; Düsseldorf; DOCER.25 /20140912/
    Publication Date: 2014-09-13
    Keywords: Rheumatoid arthritis ; synovial fibroblasts ; T lymphocytes ; tryptophan metabolism ; ddc: 610
    Language: English
    Type: conferenceObject
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  • 2
  • 3
    ISSN: 1420-9071
    Keywords: Freund's complete adjuvant ; diurnal rhythms ; ornithine decarboxylase ; prolactin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The aim of this study was to investigate the effects of Freund's complete adjuvant (FCA) on the diurnal rhythms of hormonal parameters in serum and ornithine decarboxylase (ODC) activity in various tissues of male rats. On days 1–2 after FCA, increase of ODC activity (used to evaluate the level of activation) was observed in the hypothalamus, pituitary gland, adrenal medulla, adrenal cortex, liver and lymphoid tissues, while the ODC activity in the kidney was reduced. This was accompanied by an increase in serum corticosterone. On days 3–4 after FCA, ODC activity remained elevated in the pituitary gland, liver and lymphoid tissues, while the ODC activity in the testes and panceas was reduced; kidney ODC activity returned to baseline. This was associated with increased serum levels of prolactin (Prl) and luteinizing hormone, but decreased growth hormone, testosterone and insulin. The increase in ODC activity in the thymus, as well as the reduced ODC activity in the testes and kidney, can be obtained with paraffin. Furthermore, bromocryptine microcapsules (CBLA) reduced the FCA-induced increase of ODC activity in the pituitary gland, liver and lymphoid tissues (days 3–4) but did not affect the changes in other tissues. The increase in ODC activity in the pituitary gland, liver and lymphoid tissues is specific for FCA. A role for Prl in the induction of ODC in liver and lymphoid tissues is suggested by the fact that CBLA suppresses this enhancement.
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  • 4
    ISSN: 1432-0584
    Keywords: Key words CD4+ T lymphocytes ; CD45 isoforms ; Interleukin-1β ; Luteinizing hormone ; Prolactin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The expected association between age and the CD45 isoforms expression on CD4+ T-PBL is much more obvious in men than in women. We investigated whether or not circulating factors influence the differentiation of CD4+ T-PBL. Peripheral blood samples were obtained from 56 healthy age-matched subjects (28 men and 28 women, 21–55 years old). Mononuclear leukocytes were analyzed by three-color flow cytometry. The serum concentrations of interleukin-1β (IL-1β), interleukin-6, tumor necrosis factor-α (TNF-α), GM colony-stimulating factor, prolactin (Prl), and luteinizing hormone (LH) were determined by ELISA. The expected age-related decrease of naive (CD45RA+,RO–) cells and increase of memory (CD45RA–,RO+) cells among CD4+ T-PBL were observed in men only (p〈0.001 and 0.005). In women, these correlations were not significant. On the other hand, in women only, elevated IL-1β was associated with fewer naive and more memory cells among CD4+ T-PBL (p〈0.001). In both sexes, IL-1β correlated with the expression of CD25 on CD4+ T-PBL (on either naive or memory cells, p〈0.001). Other cytokines or the CD8+ T-PBL showed no significant correlation. In women, the elevation of LH at mid-cycle inversely correlated with the proportion of naive CD4+ T-PBL (p〈0.01). Elevated LH was associated with more CD25 on memory CD4+ T-PBL (p〈0.01). A significant correlation exists between IL-1β and LH (p〈0.001). Furthermore, in both sexes, Prl correlated with the proportion of CD4+ cells among T-PBL. In men, elevated Prl was associated with more naive CD4+ T-PBL (p〈0.005), while in women, Prl correlated with more transient CD45RA+, RO+ cells among CD4+ T-PBL and increased TNF-α (p〈0.05 for both). Thus, circulating IL-1β could be involved in the expression of CD25 on CD4+ T-PBL and favors the generation of memory CD4+ T-PBL. In women, the IL-1β- and/or mid-cycle-dependent processes seem to overwhelm the age-related changes. Elevated Prl might exert a dual influence: it favors the development of naive CD4+ T lymphocytes and possibly acts in, synergy with other cytokines during immune stimulation.
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  • 5
    ISSN: 1420-9071
    Keywords: Adjuvant arthritis ; experimental allergic uveitis ; periarteritis nodosa ; diabetes mellitus ; prolactin ; bromocryptine ; cyclosporine A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Pre-treatment of male Sprague-Dawley rats with long-acting bromocryptine microcapsules (CBLA) significantly inhibited the arthritic response to Freund's complete adjuvant and reduced weight loss, thymolysis, splenomegaly and leukocytosis. In the prevention of adjuvant arthritis (AA), the combination of CBLA plus sub-optimal doses of cyclosporine A (CsA) was more efficient than either of the drugs alone. Sub-optimal doses of CsA were 0.1 and 1.0 mg/kg/day s.c. for 5 days. Furthermore, CBLA alone did not decrease the incidence of experimental allergic uveitis (EAU) in the male Lewis rats. Low-dose CsA reduced the incidence of uveitis by 50%, and with the addition of CBLA, 100% of rats were protected. Low-dose CsA was 2 mg/kg/day i.m. for 14 days. Long-term treatment of male Sprague-Dawley rats with CBLA alone reduced the incidence and severity of spontaneous autoimmune periateritis nodosa (PN) in a dose-dependent manner; CsA was less potent than CBLA, and only additive effects were obtained. Finally, for the prevention of spontaneous autoimmune insulin-dependent diabetes (DM), the administration of CBLA did not improve the effect of a low-dose CsA in male BB rats. Nevertheless, a delay in onset of DM could be achieved. A sequential therapy using CsA plus CBLA clearly showed beneficial effects. The dose of CsA was 10 mg/kg p.o. 6 days/week for 21 weeks. Compared with Sprague-Dawley or Lewis male rats, BB male rats showed only weak prolactin suppression after the same doses of CBLA. It is suggested that the use of CBLA may be particularly beneficial in autoimmune disorders. The effectiveness of the combination therapy CBLA plus CsA, however, was dependent on the model considered. Various factors could play a role: (1) the different ways of administering CsA (s.c. in AA, i.m. in EAU and PN, oral in DM); (2) strain-dependency in the capacity of CBLA to suppress Prl secretion; and(3) at least in the BB rats, the transient increase of CsA bioavailibility which was possibly induced by CBLA.
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  • 6
    ISSN: 0340-1855
    Keywords: Schlüsselwörter Knorpelmarker ; COMP ; Rheumatoide Arthritis ; Arthrose ; Key words Marker of cartilage ; COMP ; rheumatoid arthritis ; osteoarthritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Today, we can assess criteria to predict the tissue destruction and progression of Rheumatoid Arthritis (RA) and Osteoarthritis (OA) only in a late stage of the disease. It would be an advantage to have biochemical markers of disease activity and joint destruction to optimize therapy. Patients and Methods: In this cross-sectional study with 37 RA and 20 OA patients (disease duration 119±130 months for RA and 41±73 months for OA), ESR, CRP, disease activity score (DAS), the functional status of RA (American College of Rheumatology), and the radiological scoring systems of Larsen and Kellgren/Lawrence, respectively, were used as parameters for disease activity and joint destruction. Cartilage oligomeric matrix protein (COMP) was measured with an enzyme-linked immunosorbent assay (ELISA) in serum and synovial fluid, COMP fragments with immunoblot in the synovial fluid. Results: The mean COMP value in synovial fluid was 38ug/ml (RA) and 46ug/ml (OA); 6.5ug/ml (RA) and 3.4ug/ml (OA) in serum. RA patients had a higher amount of small COMP fragments in synovial fluid than OA patients. In RA patients, there was a significant positive correlation between disease activity (DAS) and COMP in synovial fluid and serum, a negative correlation between functional status of RA and serum COMP and between radiologic joint destruction of the knee and serum COMP. In OA patients, there was a significant correlation of joint space width and synovial fluid COMP. Discussion: A high clinical disease activity (DAS) correlated with high COMP values in serum and synovial fluid and with increasing proteolytic activity (higher amount of small COMP fragments especially in RA). An increased turnover of cartilage matrix in joint inflammation might explain this correlation. The correlation of decreased COMP with decreased functional status in RA and increased joint destruction is compatible with a loss of cartilage and less turnover. The correlation between joint space width and increased COMP in OA patients with short disease duration might be explained with a higher turnover of the cartilage matrix in the early stage of the disease
    Notes: Zusammenfassung Alle bis heute verwendeten Kriterien zur Messung der Gewebedestruktion bei rheumatoider Arthritis (RA) und Arthrose (OA) zeigen erst ein relativ spätes Stadium des Krankheitsprozesses an. Die Verfügbarkeit von biochemischen Markern, mit denen die Krankheitsaktivität oder die Gelenkzerstörung im Sinne einer Risikoabschätzung vorausgesagt und deren Verlaufswerte zur Erfolgskontrolle bei Therapie eingesetzt werden könnten, wäre ein wichtiger Fortschritt. Patienten und Methoden: In dieser Querschnittsstudie wurden 37 RA- und 20 OA-Patienten mit einer Krankheitsdauer von 119±130 rsp.41±73 Monaten untersucht. Als Parameter der Krankheitsaktivität bzw. der Gewebezerstörung wurden BSR, CRP, Disease Activity Score (DAS), der funktionelle Status der RA gemäß American College of Rheumatology sowie zwei radiologische Scoring Systeme (Larsen Score bei RA- und die Kellgren-Lawrence Kriterien bei OA-Patienten) bestimmt. Mittels enzyme-linked immunosorbent assay (ELISA) wurde cartilage oligomeric matrix protein (COMP) im Serum und in der Synovialflüssigkeit dieser Patienten gemessen. Zusätzlich wurden mittels Gel-Elektrophorese und Immunoblot die COMP-Fragmente in der Synovialflüssigkeit ermittelt. Resultate und Diskussion: Der mittlere COMP-Wert in der Synovialflüssigkeit betrug bei RA-Patienten 38ug/ml, bei OA-Patienten 46ug/ml, im Serum 6,5ug/ml rsp. 3,4ug/ml. Bei RA-Patienten korrelierte eine zunehmende Krankheitsaktivität (DAS) mit einem erhöhten COMP-Wert, sowohl in der Synovialflüssigkeit als auch im Serum. Eine erhöhte Freisetzung von kleinen COMP-Fragmenten in der Synovialflüssigkeit, wies auf eine vermehrte proteolytische Aktivität hin. Diese Ergebnisse beruhen wahrscheinlich auf einem erhöhten Umsatz von Knorpelmatrix im entzündeten Gelenk bei RA. Die RA-Patienten in dieser Querschnittsstudie wiesen außerdem eine Korrelation von abnehmendem COMP-Spiegel mit Abnahme der körperlichen Funktion bzw. zunehmender Gelenkzerstörung, auf. Dies deutet auf einen Verlust an Gelenkknorpel mit verminderter Gesamtmenge und Umsatz von COMP hin. Bei OA-Patienten mit kurzer Krankheitsdauer wurde eine signifikante Korrelation zwischen zunehmend (aber insgesamt wenig) reduzierter Gelenkspaltweite und einem erhöhtem COMP-Wert in der Synovialflüssigkeit gefunden. Dieser Zusammenhang legt nahe, daß im kurz- bis mittelfristigen Verlauf des Krankheitsprozesses ein erhöhter Umsatz an Knorpelmolekülen beobachtet werden kann.
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  • 7
    ISSN: 1437-160X
    Keywords: Rheumatoid arthritis ; Peripheral blood T-lymphocytes ; CD45 isoforms ; IgM rheumatoid factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated whether, in rheumatoid arthritis (RA), the CD45 isoform expression of peripheral blood T-lymphocytes (T-PBL) is related to auto-immune processes (e.g. IgM rheumatoid factors) and to clinical manifestations. By three-colour flow cytometry, we quantified three subsets of CD4+ or CD8+ T-PBL: “naive” CD45RA+,RO−, “transient” CD45RA+,RO+, and “memory” CD45RA−,RO+ cells, in 102 patients with RA and in 41 age- and sex-matched controls. The serum levels of rheumatoid factors (RF) were determined — besides conventional agglutination tests — by ELISA (IgM-RF). Extensive clinical examination was performed at the time of blood sampling. In RA, age, sex and drug therapy did not constitute major influences on the CD45RA/RO patterns. In “healthy” men, higher age significantly correlated with fewer naive and more memory CD4+ T-PBL (P〈0.01). In RA, distinct correlations between the T-PBL subsets, autoimmune and clinical manifestations became obvious when patients with low and high levels of RF against human IgG Fc fragments, as determined by ELISA, were analysed separately. RA patients with high IgM-RF had elevated proportions of CD45RO+ T-PBL (P〈0.05), that correlated with clinical parameters of disease activity (tender joint count, Ritchie index, P〈0.05) and outcome (Health Assessment Questionnaire, Larsen radiographic scores, P〈0.05). The proportions of memory CD4+ and CD8+ T-PBL correlated strongly (P〈0.001) with the IgM-RF levels. Within 1 year, only three of 34 patients (disease duration of 5–9 years) showed seroconversion from low to high levels of IgM-RF (and positive agglutination tests); this was paralleled by reductions in naive and increases in transient T-PBL (P〈0.02). Thus, in RA, the proportions of memory CD4+ and CD8+ T-PBL correlate with the level of IgM-RF and, together with transient T-PBL, with clinical parameters of disease activity and outcome.
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  • 8
    ISSN: 1437-160X
    Keywords: Key words Cartilage oligomeric protein ; Knee joint injury ; Osteoarthritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The objective was to assess whether changes of cartilage oligomeric matrix protein (COMP) serum levels can predict the development of osteoarthritis following traumatic knee injury. Sera and synovial fluids were acquired at surgery (T0) and postoperatively during the first (T1) and second (T2) year from 30 knee-injured patients. COMP levels and anti-COMP autoantibodies were quantified by ELISA. Radiographs and patient questionnaires were used to assess outcomes. At T0, compared with controls (1.6±1.6 μg/ml), the serum COMP concentration was significantly elevated (6.5±2.8 μg/ml) with a tendency to further increase (T0 vs. T1, P=0.076) and subsequently decrease (T1 vs. T2, P=0.074). However, individual variations are observed, e.g. persistently high (8/30) or increasing (T0 to T2, 8/30) serum COMP. Ten of these patients have elevated COMP at T2 that increased from T0. COMP levels in serum and synovial fluid correlated significantly (P=0.012). Interestingly, some patients who revealed increasing serum levels of COMP from T0 to T2 displayed anti-COMP autoantibodies. These data suggest that local immune response could contribute to further joint damage. The subgroup of 10 patients (33%) with elevated and increasing serum COMP levels and in particular the patients with antibodies against cartilage matrix molecules appear at increased risk for developing posttraumatic osteoarthritis.
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  • 9
    ISSN: 1437-160X
    Keywords: Rheumatoid arthritis ; Peripheral blood T-lymphocytes ; CD45 isoforms ; CD29
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to quantify and characterise the CD4+ and CD8+, CD45RA+, CD45RO- T-lymphocytes that paradoxically expressed the CD29 bright+ phenotype in health and in rheumatoid arthritis. We further evaluated their clinical implications. Blood samples were obtained from 100 patients with rheumatoid arthritis and 40 age- and sex-matched controls. Cell surface antigens and interleukin-2 (IL-2) binding were detected on CD4+ and CD8+ peripheral blood T-lymphocytes (T-PBL) by three-colour flow cytometry. One-third of the patients were clinically evaluated at the time of blood sampling. In healthy donors, we found 16 ± 14% of CD29 bright+cells among CD4+, CD45RA+, RO-T-PBL. These “false naive” CD4+ T-PBL were Leu-8+, and a majority expressed the CD25/p55 receptor (IL-2Rα chain), while a minority showed the CDlla bright+, CD69+ and/or CD 122/p75+ (IL-2Rβ chain) phenotype, and few cells were CD31 bright+ and HLA-DR+. In rheumatoid arthritis, their proportion among CD4+, CD45RA+, RO- cells increased to 25 ± 15% (P 〈 0.001, compared with controls). In patients, the reductions in CD31 and CD38 expression (P 〈 0.05 for both), as well as the enhanced CD25 expression (P 〈 0.001) on CD4+, CD45RA+, RO- T-PBL reflected a more differentiated phenotype. The occurrences of CD25 and CD122 were increased on false naive CD4+ T-PBL (0.01 〈P〈0.001); however, the binding of IL-2 remained very low (in contrast to the binding of IL-2 on CD45RO+ T-PBL). Furthermore, a major subset of CD8+, CD45RA+, RO- T-PBL (45 ± 17% in controls) expressed the CD29 bright+ phenotype. These “false naive” CD8+ T-PBL included a great many of CID 1lb+, CD28- cells, while a minority showed the HLA-DR+, CD69+ and/orCD122+ phenotypes. Patients with low levels of IgM rheumatoid factors (IgM-RF; but with active disease) had an elevated proportion of CD45RA+, RO-cells among the CD8+ T-PBL, in part due to an increased proportion of false naive cells (P 〈 0.05). In patients, the false naive CD8+ T-PBL showed down-regulated CD1lb and an increased expression of IL-2 receptor chains (CD25 and CD 122; 0.05 〈P 〈 0.01), but without a significant increase in IL-2 binding. More CD69 on false naive CD8+ T-PBL was found in patients with high levels of IgM-RF (P 〈 0.005 compared to patients with low 19M-RF). Finally, both false naive CD4+ and CD8+ T-PBL correlated with the clinical process and outcome variables (0.05 〈P 〈0.01). The levels of activated false naive CD4+ T-PBL (CD25+ and/or CD122+) or CD8+ T-PBL (CD69+ and/or CD122+) were associated with clinical parameters of disease activity (0.05 〈P 〈 0.01). Thus, in rheumatoid arthritis, false naive T-PBL showed important qualitative differences. The levels of activated false naive T-PBL could be particularly interesting for monitoring disease evolution.
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