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167 results on '"Schett, Georg"'

4. Accuracy and tolerability of self-sampling of capillary blood for analysis of inflammation and autoantibodies in rheumatoid arthritis patients—results from a randomized controlled trial

Author

Knitza, Johannes, Tascilar, Koray, Vuillerme, Nicolas, Eimer, Ekaterina, Matusewicz, Paul, Corte, Giulia, Schuster, Louis, Aubourg, Timothée, Bendzuck, Gerlinde, Korinth, Marianne, Elling-Audersch, Corinna, Kleyer, Arnd, Boeltz, Sebastian, Hueber, Axel J., Krönke, Gerhard, Schett, Georg, and Simon, David

Published
2022
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6. Digitally-supported patient-centered asynchronous outpatient follow-up in rheumatoid arthritis - an explorative qualitative study

Author

Stenzel, Ramona, Hadaschik, Katharina, May, Susann, Grahammer, Manuel, Labinsky, Hannah, Welcker, Martin, Hornig, Johannes, Bendzuck, Gerlinde, Elling-Audersch, Corinna, Erstling, Ulrike, Korbanka, Patricia Steffens, Vuillerme, Nicolas, Heinze, Martin, Krönke, Gerhard, Schett, Georg, Pecher, Ann-Christin, Krusche, Martin, Mucke, Johanna, Knitza, Johannes, and Muehlensiepen, Felix

Published
2022
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11. Accuracy, patient-perceived usability, and acceptance of two symptom checkers (Ada and Rheport) in rheumatology: interim results from a randomized controlled crossover trial

Author

Knitza, Johannes, Mohn, Jacob, Bergmann, Christina, Kampylafka, Eleni, Hagen, Melanie, Bohr, Daniela, Morf, Harriet, Araujo, Elizabeth, Englbrecht, Matthias, Simon, David, Kleyer, Arnd, Meinderink, Timo, Vorbrüggen, Wolfgang, von der Decken, Cay Benedikt, Kleinert, Stefan, Ramming, Andreas, Distler, Jörg H. W., Vuillerme, Nicolas, Fricker, Achim, Bartz-Bazzanella, Peter, Schett, Georg, Hueber, Axel J., and Welcker, Martin

Published
2021
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28. Chromosomal radiosensitivity in oncological and non-oncological patients with rheumatoid arthritis and connective tissue diseases.

Author

Rzepka, Dinah, Schenker, Hannah, Geinitz, Hans, Silberberger, Elisabeth, Kaudewitz, Dorothee, Schuster, Barbara, Kuhlmann, Lukas, Schonath, Miriam, Ayala Gaona, Horacio, Aschacher, Bernhard, Fietkau, Rainer, Schett, Georg, and Distel, Luitpold

Subjects
CONNECTIVE tissue diseases, CANCER patients, RADIATION tolerance, RHEUMATOID arthritis, FLUORESCENCE in situ hybridization, RADIATION injuries
Abstract

Background: The risk of developing late radiotoxicity after radiotherapy in patients with high chromosomal radiosensitivity after radiotherapy could potentially be higher compared to the risk in patients with average radiosensitivity. In case of extremely high radiosensitivity, dose reduction may be appropriate. Some rheumatic diseases (RhD), including connective tissue diseases (CTDs) appear to be associated with higher radiosensitivity. The question arises as to whether patients with rheumatoid arthritis (RA) also generally have a higher radiosensitivity and whether certain parameters could indicate clues to high radiosensitivity in RA patients which would then need to be further assessed before radiotherapy. Methods: Radiosensitivity was determined in 136 oncological patients with RhD, 44 of whom were RA patients, and additionally in 34 non-oncological RA patients by three-colour fluorescence in situ hybridization (FiSH), in which lymphocyte chromosomes isolated from peripheral blood are analysed for their chromosomal aberrations of an unirradiated and an with 2 Gy irradiated blood sample. The chromosomal radiosensitivity was determined by the average number of breaks per metaphase. In addition, correlations between certain RA- or RhD-relevant disease parameters or clinical features such as the disease activity score 28 and radiosensitivity were assessed. Results: Some oncological patients with RhD, especially those with connective tissue diseases have significantly higher radiosensitivity compared with oncology patients without RhD. In contrast, the mean radiosensitivity of the oncological patients with RA and other RhD and the non-oncological RA did not differ. 14 of the 44 examined oncological RA-patients (31.8%) had a high radiosensitivity which is defined as ≥ 0.5 breaks per metaphase. No correlation of laboratory parameters with radiosensitivity could be established. Conclusions: It would be recommended to perform radiosensitivity testing in patients with connective tissue diseases in general. We did not find a higher radiosensitivity in RA patients. In the group of RA patients with an oncological disease, a higher percentage of patients showed higher radiosensitivity, although the average radiosensitivity was not high. [ABSTRACT FROM AUTHOR]

Published
2023
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30. Induction of sustained remission in early inflammatory arthritis with the combination of infliximab plus methotrexate: the DINORA trial

Author

Stamm, Tanja Alexandra, Machold, Klaus Peter, Aletaha, Daniel, Alasti, Farideh, Lipsky, Peter, Pisetsky, David, Landewe, Robert, van der Heijde, Desiree, Sepriano, Alexandre, Aringer, Martin, Boumpas, Dimitri, Burmester, Gerd, Cutolo, Maurizio, Ebner, Wolfgang, Graninger, Winfried, Huizinga, Tom, Schett, Georg, Schulze-Koops, Hendrik, Tak, Paul-Peter, Martin-Mola, Emilio, Breedveld, Ferdinand, and Smolen, Josef

Published
2018
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33. Estrogen induces St6gal1 expression and increases IgG sialylation in mice and patients with rheumatoid arthritis: a potential explanation for the increased risk of rheumatoid arthritis in postmenopausal women

Author

Engdahl, Cecilia, Bondt, Albert, Harre, Ulrike, Raufer, Jasmin, Pfeifle, René, Camponeschi, Alessandro, Wuhrer, Manfred, Seeling, Michaela, Mårtensson, Inga-Lill, Nimmerjahn, Falk, Krönke, Gerhard, Scherer, Hans U., Forsblad-d’Elia, Helena, and Schett, Georg

Published
2018
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38. Tumour necrosis factor activates the mitogen-activated protein kinases p38α and ERK in the synovial membrane in vivo

Author

Görtz, Birgit, Hayer, Silvia, Tuerck, Birgit, Zwerina, Jochen, Smolen, Josef S, and Schett, Georg

Subjects
MAP Kinase Signaling System, Tumor Necrosis Factor-alpha, Macrophages, Synovial Membrane, JNK Mitogen-Activated Protein Kinases, Mice, Transgenic, Fibroblasts, p38 Mitogen-Activated Protein Kinases, Autoimmune Diseases, Arthritis, Rheumatoid, Enzyme Activation, Mice, Antirheumatic Agents, Animals, Humans, Phosphorylation, Extracellular Signal-Regulated MAP Kinases, Protein Processing, Post-Translational, Research Article
Abstract

Tumour necrosis factor (TNF) is considered to be a major factor in chronic synovial inflammation and is an inducer of mitogen-activated protein kinase (MAPK) signalling. In the present study we investigated the ability of TNF to activate MAPKs in the synovial membrane in vivo. We studied human TNF transgenic mice – an in vivo model of TNF-induced arthritis – to examine phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun amino terminal kinase (JNK) and p38MAPKα in the inflamed joints by means of immunoblot and immunohistochemistry. In addition, the effects of systemic blockade of TNF, IL-1 and receptor activator of nuclear factor-κB (RANK) ligand on the activation of MAPKs were assessed. In vivo, overexpression of TNF induced activation of p38MAPKα and ERK in the synovial membrane, whereas activation of JNK was less pronounced and rarely observed on immunohistochemical analysis. Activated p38MAPKα was predominantly found in synovial macrophages, whereas ERK activation was present in both synovial macrophages and fibroblasts. T and B lymphocytes did not exhibit major activation of any of the three MAPKs. Systemic blockade of TNF reduced activation of p38MAPKα and ERK, whereas inhibition of IL-1 only affected p38MAPKα and blockade of RANK ligand did not result in any decrease in MAPK activation in the synovial membrane. These data indicate that TNF preferentially activates p38MAPKα and ERK in synovial membrane exposed to TNF. This not only suggests that targeted inhibition of p38MAPKα and ERK is a feasible strategy for blocking TNF-mediated effects on joints, but it also shows that even currently available methods to block TNF effectively reduce activation of these two MAPKs.

Published
2005

41. JNK1 is not essential for TNF-mediated joint disease

Author

Köller, Marcus, Hayer, Silvia, Redlich, Kurt, Ricci, Romeo, David, Jean-Pierre, Steiner, Günter, Smolen, Josef S., Wagner, Erwin F., and Schett, Georg

Subjects
endocrine system, enzymes and coenzymes (carbohydrates), Arthritis, JNK1, TNF-α transgenic, biological phenomena, cell phenomena, and immunity, environment and public health, hormones, hormone substitutes, and hormone antagonists
Abstract

Tumour necrosis factor (TNF) signalling molecules are considered as promising therapeutic targets of antirheumatic therapy. Among them, mitogen-activated protein kinases are thought to be of central importance. Herein, we investigate the role in vivo of TNF-α signalling through c-Jun N-terminal kinase (JNK)1 in destructive arthritis. Human TNF transgenic (hTNFtg) mice, which develop inflammatory arthritis, were intercrossed with JNK1-deficient (JNK1-/-) mice. Animals (n = 35) of all four genotypes (wild-type, JNK1-/-, hTNFtg, JNK1-/-hTNFtg) were assessed for clinical and histological signs of arthritis. Clinical features of arthritis (swelling and decreased grip strength) developed equally in hTNFtg and JNK1-/-hTNFtg mice. Histological analyses revealed no differences in the quantity of synovial inflammation and bone erosions or in the cellular composition of the synovial infiltrate. Bone destruction and osteoclast formation were observed to a similar degree in hTNFtg and JNK1-/-hTNFtg animals. Moreover, cartilage damage, as indicated by proteoglycan loss in the articular cartilage, was comparable in the two strains. Intact phosphorylation of JNK and c-Jun as well as expression of JNK2 in the synovial tissue of JNK1-/-hTNFtg mice suggests that signalling through JNK2 may compensate for the deficiency in JNK1. Thus, JNK1 activation does not seem to be essential for TNF-mediated arthritis., Arthritis Research & Therapy, 7 (1), ISSN:1465-9905, ISSN:1465-9913, ISSN:1478-6362, ISSN:1478-6354

Published
2004

44. Pasteurella multocida toxin- induced osteoclastogenesis requires mTOR activation.

Author

Kloos, Bianca, Chakraborty, Sushmita, Lindner, Sonja G., Noack, Katrin, Harre, Ulrike, Schett, Georg, Krämer, Oliver H., and Kubatzky, Katharina F.

Subjects
PASTEURELLA multocida, MTOR protein, OSTEOCLASTS, THREONINE, RAPAMYCIN, ACID phosphatase
Abstract

Background: toxin (PMT) is a potent inducer of osteoclast formation. Pigs suffering from an Pasteurella multocida infection with toxigenic strains develop atrophic rhinitis characterised by a loss of turbinate Pasteurella multocida bones and conchae. However, on the molecular level the process of bone loss remains largely uncharacterised. Results: Recently it was found that PMT activates the serine/threonine kinase mammalian target of rapamycin (mTOR) in fibroblasts. Using RAW264.7 macrophages, we investigated the role of the mTOR complex 1 (mTORC1) in PMT-mediated osteoclast formation. PMT induces the differentiation of RAW264.7 macrophages into multinucleated, tartrate resistant acid phosphatase (TRAP) positive osteoclasts that are capable to resorb bone. In the presence of the mTORC1 inhibitor rapamycin, PMT was significantly less able to induce the formation of TRAP-positive osteoclasts. Accordingly, the resulting resorption of bone was strongly reduced. A major target of mTOR is the 70 kDa ribosomal protein S6 kinase 1 (p70 S6K1). Activated p70 S6K1 decreases the expression of programmed cell death protein 4 (PDCD4), a negative transcriptional regulator of osteoclastogenesis, at the protein and gene level. Ultimately this results in the activation of c-Jun, a component of the activator protein 1 (AP-1) complex, which is a major transcription factor for the induction of osteoclast-specific genes. We now demonstrate that c-Jun and its downstream target, the osteoclast-specific bone degrading protease cathepsin K, are upregulated upon PMT treatment in an mTOR-dependent manner. Conclusions: Activation of mTOR signalling plays a central role in the formation of osteoclasts through the bacterial toxin PMT. On the molecular level, PMT-induced activation of mTOR leads to down regulation of PDCD4, a known repressor of AP-1 complex, culminating in the activation of c-Jun, an essential transcription factor for triggering osteoclastogenesis. [ABSTRACT FROM AUTHOR]

Published
2015
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45. Cells of the synovium in rheumatoid arthritis. Osteoclasts

Author

Schett, Georg

Subjects
musculoskeletal diseases, Arthritis, Rheumatoid, Synovial Membrane, Animals, Humans, Osteoclasts, Review
Abstract

Osteoclasts are multinucleated cells of hematopoietic origin and are the primary bone resorbing cells. Numerous osteoclasts are found within the synovial tissue at sites adjacent to bone, creating resorption pits and local bone destruction. They are equipped with specific enzymes and a proton pump that enable them to degrade bone matrix and solubilize calcium, respectively. The synovial tissue of inflamed joints has a particularly high potential to accumulate osteoclasts because it harbors monocytes/macrophages, which function as osteoclast precursors, as well as cells that provide the specific molecular signals that drive osteoclast formation. Osteoclasts thus represent a link between joint inflammation and structural damage since they resorb mineralized tissue adjacent to the joint and destroy the joint architecture.

Published
2007

46. Imbalance of local bone metabolism in inflammatory arthritis and its reversal upon tumor necrosis factor blockade: direct analysis of bone turnover in murine arthritis

Author

Zwerina, Jochen, Tuerk, Birgit, Redlich, Kurt, Smolen, Josef S, and Schett, Georg

Subjects
musculoskeletal diseases, Inflammation, Mice, Inbred C57BL, Mice, Tumor Necrosis Factor-alpha, Animals, Antibodies, Monoclonal, Mice, Transgenic, Arthritis, Experimental, Bone and Bones, Infliximab, Research Article
Abstract

Chronic arthritis typically leads to loss of periarticular bone, which results from an imbalance between bone formation and bone resorption. Recent research has focused on the role of osteoclastogenesis and bone resorption in arthritis. Bone resorption cannot be observed isolated, however, since it is closely linked to bone formation and altered bone formation may also affect inflammatory bone loss. To simultaneously assess bone resorption and bone formation in inflammatory arthritis, we developed a histological technique that allows visualization of osteoblast function by in-situ hybridization for osteocalcin and osteoclast function by histochemistry for tartrate-resistant acid phosphatase. Paw sections from human tumor necrosis factor transgenic mice, which develop an erosive arthritis, were analyzed at three different skeletal sites: subchondral bone erosions, adjacent cortical bone channels, and endosteal regions distant from bone erosions. In subchondral bone erosions, osteoclasts were far more common than osteoblasts. In contrast, cortical bone channels underneath subchondral bone erosions showed an accumulation of osteoclasts but also of functional osteoblasts resembling a status of high bone turnover. In contrast, more distant skeletal sites showed only very low bone turnover with few scattered osteoclasts and osteoblasts. Within subchondral bone erosions, osteoclasts populated the subchondral as well as the inner wall, whereas osteoblasts were almost exclusively found along the cortical surface. Blockade of tumor necrosis factor reversed the negative balance of bone turnover, leading to a reduction of osteoclast numbers and enhanced osteoblast numbers, whereas the blockade of osteoclastogenesis by osteoprotegerin also abrogated the osteoblastic response. These data indicate that bone resorption dominates at skeletal sites close to synovial inflammatory tissue, whereas bone formation is induced at more distant sites attempting to counter-regulate bone resorption.

Published
2005

47. Characterization and quantification of angiogenesis in rheumatoid arthritis in a mouse model using μCT.

Author

Gayetskyy, Svitlana, Museyko, Oleg, Käßer, Johannes, Hess, Andreas, Schett, Georg, and Engelke, Klaus

Abstract

Background: Angiogenesis is an important pathophysiological process of chronic inflammation, especially in inflammatory arthritis. Quantitative measurement of changes in vascularization may improve the diagnosis and monitoring of arthritis. The aim of this work is the development of a 3D imaging and analysis framework for quantification of vascularization in experimental arthritis. Methods: High-resolution micro-computed tomography (μCT) was used to scan knee joints of arthritic human tumor necrosis factor transgenic (hTNFtg) mice and non-arthritic wild-type controls previously perfused with lead-containing contrast agent Microfil MV-122. Vessel segmentation was performed by combination of intensity-based (local adaptive thresholding) and form-based (multi-scale method) segmentation techniques. Four anatomically defined concentric spherical shells centered in the knee joint were used as analysis volumes of interest. Vessel density, density distribution as well as vessel thickness, surface, spacing and number were measured. Simulated digital vessel tree models were used for validation of the algorithms. Results: High-resolution μCT allows the quantitative assessment of the vascular tree in the knee joint during arthritis. Segmentation and analysis were highly automated but occasionally required manual corrections of the vessel segmentation close to the bone surfaces. Vascularization was significantly increased in arthritic hTNFtg mice compared to wild type controls. Precision errors for the morphologic parameters were smaller than 3% and 6% for intra- and interoperator analysis, respectively. Accuracy errors for vessel thickness were around 20% for vessels larger than twice the resolution of the scanner. Conclusions: Arthritis-induced changes of the vascular tree, including detailed and quantitative description of the number of vessel branches, length of vessel segments and the bifurcation angle, can be detected by contrastenhanced high-resolution μCT. [ABSTRACT FROM AUTHOR]

Published
2014
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49. Influence of antiTNF-alpha antibody treatment on fracture healing under chronic inflammation.

Author

Timmen, Melanie, Hidding, Heriburg, Wieskötter, Britta, Baum, Wolfgang, Pap, Thomas, Raschke, Michael J., Schett, Georg, Zwerina, Jochen, and Stange, Richard

Subjects
TUMOR necrosis factors, BONE fractures, CARTILAGE fractures, RHEUMATOID arthritis treatment, LABORATORY mice
Abstract

Background The overexpression of tumor necrosis factor (TNF)-α leads to systemic as well as local loss of bone and cartilage and is also an important regulator during fracture healing. In this study, we investigate how TNF-α inhibition using a targeted monoclonal antibody affects fracture healing in a TNF-α driven animal model of human rheumatoid arthritis (RA) and elucidate the question whether enduring the anti TNF-α therapy after trauma is beneficial or not. Methods A standardized femur fracture was applied to wild type and human TNF-α transgenic mice (hTNFtg mice), which develop an RA-like chronic polyarthritis. hTNFtg animals were treated with anti-TNF antibody (Infliximab) during the fracture repair. Untreated animals served as controls. Fracture healing was evaluated after 14 and 28 days of treatment by clinical assessment, biomechanical testing and histomorphometry. Results High levels of TNF-α influence fracture healing negatively, lead to reduced cartilage and more soft tissue in the callus as well as decreased biomechanical bone stability. Blocking TNF-α in hTNFtg mice lead to similar biomechanical and histomorphometrical properties as in wild type. Conclusions High levels of TNF-α during chronic inflammation have a negative impact on fracture healing. Our data suggest that TNF-α inhibition by an anti-TNF antibody does not interfere with fracture healing. [ABSTRACT FROM AUTHOR]

Published
2014
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