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Serine protease-like (Spl) proteins produced by Staphylococcus (S.) aureus have been associated with allergic inflammation. However, effects of Spls on the epidermal immune response ...have not been investigated.
To assess the epidermal immune response to SplA, SplD and SplE dependent on differentiation of keratinocytes and a Th2 or Th17 cytokine milieu.
Human keratinocytes of healthy controls and a STAT3-hyper-IgE syndrome (STAT3-HIES) patient were cultured in different calcium concentrations in the presence of Spls and Th2 or Th17 cytokines. Keratinocyte-specific IL-8 production and concomitant migration of neutrophils were assessed.
SplE and more significantly SplA, induced IL-8 in keratinocytes. Suprabasal-like keratinocytes showed a higher Spl-mediated IL-8 production and neutrophil migration compared to basal-like keratinocytes. Th17 cytokines amplified Spl-mediated IL-8 production, which correlated with neutrophil recruitment. Neutrophil recruitment by keratinocytes of the STAT3-HIES patient was similar to healthy control cells.
S. aureus-specific Spl proteases synergized with IL-17A on human keratinocytes with respect to IL-8 release and neutrophil migration, highlighting the importance of keratinocytes and Th17 immunity in barrier function.
Interferon-γ (IFN-γ) and interleukin-4 (IL-4) are key effector cytokines for the differentiation of T helper type 1 and 2 (Th1 and Th2) cells. Both cytokines induce fate-decisive transcription ...factors such as GATA3 and TBX21 that antagonize the polarized development of opposite phenotypes by direct regulation of each other's expression along with many other target genes. Although it is well established that mesenchymal cells directly respond to Th1 and Th2 cytokines, the nature of antagonistic differentiation programs in airway epithelial cells is only partially understood. In this study, primary normal human bronchial epithelial cells (NHBEs) were exposed to IL-4, IFN-γ, or both and genome-wide transcriptome analysis was performed. The study uncovers an antagonistic regulation pattern of IL-4 and IFN-γ in NHBEs, translating the Th1/Th2 antagonism directly in epithelial gene regulation. IL-4- and IFN-γ-induced transcription factor hubs form clusters, present in antagonistically and polarized gene regulation networks. Furthermore, the IL-4-dependent induction of IL-24 observed in rhinitis patients was downregulated by IFN-γ, and therefore IL-24 represents a potential biomarker of allergic inflammation and a Th2 polarized condition of the epithelium.
Background Polymorphous light eruption (PLE) is the most common chronic and idiopathic photodermatosis. PLE is assumed to represent an immunological hypersensitivity reaction to a radiation‐induced ...cutaneous antigen involving reactive oxygen species (ROS) on the basis of a genetic predisposition. Among others, cellular protection against ROS is provided by glutathione S‐transferases (GSTs). Different variants of the GST enzymes may influence the activity and efficiency of detoxification and biotransformation of unknown UV‐induced skin‐antigens and other factors that may play an important role in the pathogenesis of PLE.
Methods In this study the relationship between isoenzymes of the GST genes GSTM1, GSTT1 and GSTP1 and possible protective or predisposing effects on PLE was examined in 29 patients and 144 controls. Diagnosis of PLE was based on the presence of characteristic clinical features.
Results No association between the functional polymorphisms of the GST gene family and PLE was found. Prevalence of certain GST isoenzymes or polymorphisms in patients with PLE did not differ from healthy controls.
Conclusion Our data do not support prevalence of GST isoenzymes or polymorphisms as a protective effect against PLE. Especially a higher carrier frequency of GSTP1 Val105 as a protective factor against PLE which has been published before could not be proved. The GST genotypes GSTM1, GSTT1 and GSTP1 (including SNPs) seem to have no relevant association with PLE.
Interferon-γ (IFN-γ) and interleukin-4 (IL-4) are key effector cytokines for the differentiation of T helper type 1 and 2 (Th1 and Th2) cells. Both cytokines induce fate-decisive transcription ...factors such as GATA3 and TBX21 that antagonize the polarized development of opposite phenotypes by direct regulation of each other's expression along with many other target genes. Although it is well established that mesenchymal cells directly respond to Th1 and Th2 cytokines, the nature of antagonistic differentiation programs in airway epithelial cells is only partially understood. In this study, primary normal human bronchial epithelial cells (NHBEs) were exposed to IL-4, IFN-γ, or both and genome-wide transcriptome analysis was performed. The study uncovers an antagonistic regulation pattern of IL-4 and IFN-γ in NHBEs, translating the Th1/Th2 antagonism directly in epithelial gene regulation. IL-4- and IFN-γ-induced transcription factor hubs form clusters, present in antagonistically and polarized gene regulation networks. Furthermore, the IL-4-dependent induction of IL-24 observed in rhinitis patients was downregulated by IFN-γ, and therefore IL-24 represents a potential biomarker of allergic inflammation and a Th2 polarized condition of the epithelium.
Background IL-22 controls tissue homeostasis by both proinflammatory and anti-inflammatory effects. However, the anti-inflammatory mechanisms of IL-22 remain poorly investigated. Objective We sought ...to investigate the anti-inflammatory role for IL-22 in human asthma. Methods T-cell lines derived from lung biopsy specimens of asthmatic patients were characterized by means of flow cytometry. Human bronchial epithelial cells from healthy and asthmatic subjects were stimulated with IL-22, IFN-γ, or the combination of both cytokines. Effects of cytokine stimulation were investigated by using whole-genome analysis, ELISA, and flow cytometry. The functional consequence of cytokine stimulation was evaluated in an in vitro wound repair model and T cell–mediated cytotoxicity experiments. In vivo cytokine expression was measured by using immunohistochemistry and Luminex assays in bronchoalveolar lavage fluid of healthy and asthmatic patients. Results The current study identifies a tissue-restricted antagonistic interplay of IL-22 and the proinflammatory cytokine IFN-γ. On the one hand, IFN-γ antagonized IL-22–mediated induction of the antimicrobial peptide S100A7 and epithelial cell migration in bronchial epithelial cells. On the other hand, IL-22 decreased epithelial susceptibility to T cell–mediated cytotoxicity by inhibiting the IFN-γ–induced expression of MHC-I, MHC-II, and CD54/intercellular adhesion molecule 1 molecules. Likewise, IL-22 inhibited IFN-γ–induced secretion of the proinflammatory chemokines CCL5/RANTES and CXCL10/interferon-inducible protein 10 in vitro . Consistently, the IL-22 expression in bronchoalveolar lavage fluid of asthmatic patients inversely correlated with the expression of CCL5/RANTES and CXCL10/interferon-inducible protein 10 in vivo. Conclusions IL-22 might control the extent of IFN-γ–mediated lung inflammation and therefore play a tissue-restricted regulatory role.
Im Jahr 2011 hat der Bundestag in Deutschland den Ausstieg aus der Kernenergie beschlossen. Der angefallene Abfall wird mehr als hunderttausend Jahre eine derartig hohe Aktivität besitzen, dass er ...eine erhebliche Gefahr für nachfolgende Generationen darstellen kann. Dieser radioaktive Abfall soll in tiefen geologischen Formationen (z. B. Salz, Ton oder Kristallin) sicher endgelagert werden. Die Endlager werden mittels sogenannter geotechnischer Abdichtbauwerke (Schacht‐ bzw. Streckenverschlüsse) verschlossen, wofür u. a. Zement‐ oder Sorel‐basierte Baustoffe (Betone) in Frage kommen. Die Beschreibung des Dichtvermögens dieser Bauwerke ist unabdingbar. In der Forschungsphase werden verschiedene Werkstoffe untersucht und Methoden für die zerstörungsfreie Untersuchung der Bauwerke als Mittel der Qualitätsprüfung entwickelt. Hierbei ist der Nachweis der Rissfreiheit bzw. die Detektion möglicher Risse ein vorrangiges Thema. In den letzten Jahren konnten bereits umfangreiche Erfahrungen mit der Untersuchung von in‐situ‐Versuchsobjekten in Realmaßstab gesammelt werden. Die Messungen wurden im Endlager für radioaktive Abfälle Morsleben am in‐situ‐Versuch “Abdichtbauwerk im Steinsalz” und in der Grube Teutschenthal am Großversuch GV2 durchgeführt. Es ist gelungen mit einem neu entwickelten Ultraschall‐Messsystem Eindringtiefen bis ca. 9,0 m zu realisieren. Die Messungen mit dem Large Aperture Ultrasonic System in Kombination mit der Rekonstruktion‐Methode Synthetic Aperture Focusing Technique zeigen, dass die zerstörungsfreie Prüfung von Abdichtbauwerken möglich und die Nutzung des Messsystems zur Qualitätssicherung bei der Erstellung der Verschlussbauwerke vielversprechend ist.
Translation
In 2011, the German Bundestag decided to phase out nuclear energy. The resulting waste will remain highly radioactive for many hundreds of thousands of years and represents a considerable danger for future generations. This radioactive waste is to be safely disposed of in deep geological formations (e. g. salt, clay or crystalline). The repositories will be sealed by means of engineered barrier systems. The impermeability of these structures is indispensable. In the current research phase, various materials are being investigated and methods for monitoring the structures are being developed. In this context, the investigation of cracks is a priority topic. In recent years, extensive experience in the investigation of in‐situ test objects in full scale were gained. The measurements were performed in the Morsleben repository for radioactive waste at the test structure for the in‐situ experiment “Sealing structure in rock salt” and in the Teutschenthal mine at the large‐scale GV2 test structure. With a newly developed ultrasonic measuring system it has been possible to achieve penetration depths of up to approx. 9.0 m. Measurements with the Large Aperture Ultrasonic System in combination with the Synthetic Aperture Focusing Technique reconstruction method show that the non‐destructive testing of sealing structures is possible and the use of the measuring system for quality assurance in the construction of sealing structures is promising.
Measurements with the large aperture ultrasonic system in combination with the synthetic aperture focusing technique reconstruction method show that the non‐destructive testing of engineered barrier systems, is possible. Using these techniques, it has been possible to achieve penetration depths of up to approx. 9.0 m. An assessment of the material characteristics of reflectors is possible using phase analysis, with, for instance, a phase angle of 0° corresponding to low density material such as air.
Abstract
Im Jahr 2011 hat der Bundestag in Deutschland den Ausstieg aus der Kernenergie beschlossen. Der angefallene Abfall wird mehr als hunderttausend Jahre eine derartig hohe Aktivität besitzen, ...dass er eine erhebliche Gefahr für nachfolgende Generationen darstellen kann. Dieser radioaktive Abfall soll in tiefen geologischen Formationen (z. B. Salz, Ton oder Kristallin) sicher endgelagert werden. Die Endlager werden mittels sogenannter geotechnischer Abdichtbauwerke (Schacht‐ bzw. Streckenverschlüsse) verschlossen, wofür u. a. Zement‐ oder Sorel‐basierte Baustoffe (Betone) in Frage kommen. Die Beschreibung des Dichtvermögens dieser Bauwerke ist unabdingbar. In der Forschungsphase werden verschiedene Werkstoffe untersucht und Methoden für die zerstörungsfreie Untersuchung der Bauwerke als Mittel der Qualitätsprüfung entwickelt. Hierbei ist der Nachweis der Rissfreiheit bzw. die Detektion möglicher Risse ein vorrangiges Thema. In den letzten Jahren konnten bereits umfangreiche Erfahrungen mit der Untersuchung von in‐situ‐Versuchsobjekten in Realmaßstab gesammelt werden. Die Messungen wurden im Endlager für radioaktive Abfälle Morsleben am in‐situ‐Versuch “Abdichtbauwerk im Steinsalz” und in der Grube Teutschenthal am Großversuch GV2 durchgeführt. Es ist gelungen mit einem neu entwickelten Ultraschall‐Messsystem Eindringtiefen bis ca. 9,0 m zu realisieren. Die Messungen mit dem Large Aperture Ultrasonic System in Kombination mit der Rekonstruktion‐Methode Synthetic Aperture Focusing Technique zeigen, dass die zerstörungsfreie Prüfung von Abdichtbauwerken möglich und die Nutzung des Messsystems zur Qualitätssicherung bei der Erstellung der Verschlussbauwerke vielversprechend ist.
Translation abstract
In 2011, the German Bundestag decided to phase out nuclear energy. The resulting waste will remain highly radioactive for many hundreds of thousands of years and represents a considerable danger for future generations. This radioactive waste is to be safely disposed of in deep geological formations (e. g. salt, clay or crystalline). The repositories will be sealed by means of engineered barrier systems. The impermeability of these structures is indispensable. In the current research phase, various materials are being investigated and methods for monitoring the structures are being developed. In this context, the investigation of cracks is a priority topic. In recent years, extensive experience in the investigation of in‐situ test objects in full scale were gained. The measurements were performed in the Morsleben repository for radioactive waste at the test structure for the in‐situ experiment “Sealing structure in rock salt” and in the Teutschenthal mine at the large‐scale GV2 test structure. With a newly developed ultrasonic measuring system it has been possible to achieve penetration depths of up to approx. 9.0 m. Measurements with the Large Aperture Ultrasonic System in combination with the Synthetic Aperture Focusing Technique reconstruction method show that the non‐destructive testing of sealing structures is possible and the use of the measuring system for quality assurance in the construction of sealing structures is promising.
•Our algorithm for LVAD GIB was associated with a 68% increase in the diagnostic yield and a 113% increase in the therapeutic yield of endoscopy.•Implementation of our endoscopic algorithm decreased ...length of stay by 4 days and cost by 18%.•There was no observed increase in re-bleeding rates after algorithm implementation.
Gastrointestinal bleeding (GIB) is a common complication of left ventricular assist device (LVAD) therapy accounting for frequent hospitalizations and high resource utilization.
We previously developed an endoscopic algorithm emphasizing upfront evaluation of the small bowel and minimizing low-yield procedures in LVAD recipients with GIB. We compared the diagnostic and therapeutic yield of endoscopy, health-care costs, and re-bleeding rates between conventional GIB management and our algorithm using chi-square, Fisher's exact test, Wilcoxon-Mann-Whitney, and Kaplan-Meier analysis.
We identified 33 LVAD patients with GIB. Presentation was consistent with upper GIB in 20 (61%), lower GIB in 5 (15%), and occult GIB in 8 (24%) patients. Forty-one endoscopies localized a source in 23 (56%), resulting in 14 (34%) interventions. Algorithm implementation compared with our conventional cohort was associated with a 68% increase in endoscopic diagnostic yield (P< .01), a 113% increase in therapeutic yield (P= .01), a 27% reduction in the number of procedures per patient (P < .01), a 33% decrease in length of stay (P < .01), and an 18% reduction in estimated costs (P < .01). The same median number of red blood cell transfusions were used in the 2 cohorts, with no increase in re-bleeding events in the algorithm cohort (33.3%) compared with our conventional cohort (43.7%).
Our endoscopic management algorithm for GIB in LVAD patients proved effective in reducing low-yield procedures, improving the diagnostic and therapeutic yield of endoscopy, and decreasing health-care resource utilization and costs, while not increasing the risk of a re-bleeding event.
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