Filtern
Dokumenttyp
Schlagworte
- Beton (2)
- Antigens (1)
- Autoantibodies (1)
- Autoantikörper (1)
- Citrullinated (1)
- Concrete (1)
- Elastic wave propagation (1)
- Elastische Wellenausbreitung (1)
- Grouting defects (1)
- Gruppenstrahler (1)
- Numerical modelling (1)
- Numerische Modellierung (1)
- Phase analysis (1)
- Phasenauswertung (1)
- Polarimetric imaging (1)
- Polimetrische Abbildungsverfahren (1)
- Protein-modification (1)
- Proteinmodifikation (1)
- Rheumatoid arthritis (1)
- Rheumatoide Arthritis (1)
- Spannkanäle (1)
- Tendon ducts (1)
- Verpressfehler (1)
- Wellenausbreitung (1)
- Zitrullin (1)
Organisationseinheit der BAM
Objectives: Porphyromonas gingivalis (P.g.) is discussed to be involved in triggering self-reactive immune responses. The aim of this study was to investigate the autocitrullinated prokaryotic peptidylarginine deiminase (PPAD) from P.g. CH2007 (RACH2007-PPAD) from a rheumatoid arthritis (RA) patient and a synthetic citrullinated PPAD peptide (CPP) containing the main autocitrullination site as potential targets for antibody reactivity in RA and to analyse the possibility of citrullinating native human proteins by PPAD in the context of RA.
Methods: Recombinant RACH2007-PPAD was cloned and expressed in Escherichia coli. Purified RACH2007-PPAD and its enzymatic activity was analysed using two-dimensional electrophoresis, mass spectrometry, immunoblot and ELISA. Autoantibody response to different modified proteins and peptides was recorded and bioinformatically evaluated.
Results: RACH2007-PPAD was capable to citrullinate major RA autoantigens, such as fibrinogen, vimentin, hnRNP-A2/B1, histone H1 and multiple peptides, which identify a common RG/RGG consensus motif. 33% of RA patients (n=30) revealed increased reactivity for α-cit-RACH2007-PPAD before RA onset. 77% of RA patients (n=99) presented α-cit-specific signals to CPP amino acids 57-71 which were positively correlated to α-CCP2 antibody levels. Interestingly, 48% of the α-CPP-positives were rheumatoidfactor IgM/anti-citrullinated peptide/protein antibodies (ACPA)-negative. Anti-CPP and α-RACH2007-PPAD antibody levels increase with age. Protein macroarrays that were citrullinated by RACH2007-PPAD and screened with RA patient sera (n=6) and controls (n=4) uncovered 16 RACH2007-PPAD citrullinated RA autoantigens and 9 autoantigens associated with lung diseases. We showed that the α-CPP response could be an important determinant in parenchymal changes in the lung at the time of RA diagnosis (n=106; p=0.018).
Conclusions: RACH2007-PPAD induced internal citrullination of major RA autoantigens. Anti-RACH2007-PPAD correlates with ACPA levels and interstitial lung disease autoantigen reactivity, supporting an infection-based concept for induction of ACPAs via enzymatic mimicry.
Für die zerstörungsfreie Prüfung großer Betonbauwerke unter dem Aspekt der Analyse von Spannkanälen hat sich die Ultraschalltechnik in den letzten Jahren als geeignete Methode herausgestellt, da sowohl die Messtechnik insbesondere die Ultraschallwandler als auch die numerischen Auswerteverfahren in einem Stadium sind, das es erlaubt, größere Messflächen und damit größere Volumina zu beschallen und abzubilden. Mit Hilfe der Modellierung der Ausbreitung elastischer Wellen in komplexen Medien können praxisrelevante Problemstellungen untersucht werden, auch unter dem Aspekt, Testkörper zu planen oder gar zu ersetzen. Durch die Auswertung der Phase der Rekonstruktion eines Streuvorgangs können Fehlstellen klassifiziert und damit Aussagen über die Bauwerkssicherheit signifikant objektiviert werden. Die Methoden werden, im Hinblick auf eine ganzheitliche Sichtweise von skalaren und polarimetrischen Abbildungsverfahren mit Unterstützung der Modellierung und der anschließenden Klassifizierung durch Phasenanalyse, an ausgewählten Beispielen erläutert.
For nondestructive testing of concrete buildings under the aspect of tendon duct analysis, ultrasonic testing has proven to be a suitable method, as both the measuring technique in particular the acoustic sensors and the numerical methods allow the insonification and imaging of larger surfaces and volumes. With the aid of numerical modelling of elastic wave propagation in complex media real life problems can be examined with the goal to design or even to replace test specimen. By determination of the phase of an imaged scattering event, defects can be classified, and the prediction of the integrity of buildings can be significantly objectified. The methods are explained for selected examples in an integral way with respect to scalar and polarimetric imaging algorithms supported by modelling and subsequent classification through phase analysis.
This paper presents three examples of applied
numerical modeling and inverse profiling in electromagnetic
non-destructive testing. In the first example, we discuss
numerical modeling and optimization of eddy current sensors for
in-line inspection of hot wire steel. To detect longitudinal cracks
a series of new sensors are modelled and optimized by numerical
modeling and is successfully tested. The second example presents
the application of a time-domain technique to reconstruct the
unknown permittivity and electric conductivity profile of a onedimensional
slab of finite length. The inverse scattering problem
is solved by an Invariant Embedding Method which requires a
finite time trace of reflection data and therefore is suitable for
reconstructing the material parameters in real-time. The
implemented method is validated against synthetic and measured
Time Domain Reflectometry data. The third example
demonstrates the application of the Contrast Source Inversion
method to reconstruct the 2-D permittivity profile of a beech
tree. Thus, the discussed applications present an identified need
of numerical modeling and inverse profiling in electromagnetic
non-destructive evaluation.
Background: There is a need for biomarker to identify patients “at risk” for rheumatoid arthritis (risk-RA) and to better predict the therapeutic response and in this study we tested the hypothesis that novel native and citrullinated heterogeneous nuclear ribonucleoprotein (hnRNP)-DL autoantibodies could be possible biomarkers.
Methods: Using protein macroarray and ELISA, epitope recognition against hnRNP-DL was analysed in sera from different developed RA disease and diagnosed SLE patients. Toll-like receptor (TLR) 7/9 and myeloid Differentiation primary response gene 88 (MyD88)-dependency were studied in sera from murine disease models. HnRNP-DL expression in cultivated cells and synovial tissue was analysed by indirect immunofluorescence, immunoblot and immunohistochemistry.