TY - JOUR A1 - Jobst, Bertram J. A1 - Wielpütz, Mark O. A1 - Triphan, Simon M.F. A1 - Anjorin, Angela A1 - Ley-Zaporozhan, Julia A1 - Kauczor, Hans-Ulrich A1 - Biederer, Jürgen A1 - Ley, Sebastian A1 - Sedlaczek, Oliver T1 - Morpho-Functional 1H-MRI of the Lung in COPD: Short-Term Test-Retest Reliability JF - PLOS ONE N2 - Purpose Non-invasive end-points for interventional trials and tailored treatment regimes in chronic obstructive pulmonary disease (COPD) for monitoring regionally different manifestations of lung disease instead of global assessment of lung function with spirometry would be valuable. Proton nuclear magnetic resonance imaging (1H-MRI) allows for a radiation-free assessment of regional structure and function. The aim of this study was to evaluate the short-term reproducibility of a comprehensive morpho-functional lungMRI protocol in COPD. Materials and Methods 20 prospectively enrolled COPD patients (GOLD I-IV) underwent 1H-MRI of the lung at 1.5T on two consecutive days, including sequences for morphology, 4D contrast-enhanced perfusion, and respiratory mechanics. Image quality and COPD-related morphological and functional changes were evaluated in consensus by three chest radiologists using a dedicated MRI-based visual scoring system. Test-retest reliability was calculated per each individual lung lobe for the extent of large airway (bronchiectasis, wall thickening, mucus plugging) and small airway abnormalities (tree in bud, peripheral bronchiectasis, mucus plugging), consolidations, nodules, parenchymal defects and perfusion defects. The presence of tracheal narrowing, dystelectasis, pleural effusion, pulmonary trunk ectasia, right ventricular enlargement and, finally, motion patterns of diaphragma and chest wall were addressed. Results Median global scores [10(Q1:8.00; Q3:16.00) vs. 11(Q1:6.00; Q3:15.00)] as well as category subscores were similar between both timepoints, and kappa statistics indicated "almost perfect" global agreement (\(\kappa\)= 0.86, 95%CI = 0.81-0.91). Most subscores showed at least "substantial" agreement of MRI1 and MRI2 (\(\kappa\)= 0.64-1.00), whereas the agreement for the diagnosis of dystelectasis/effusion (\(\kappa\)= 0.42, 95%CI = 0.00-0.93) was "moderate" and of tracheal abnormalities (\(\kappa\)= 0.21, 95%CI = 0.00-0.75) "fair". Most MRI acquisitions showed at least diagnostic quality at MRI1 (276 of 278) and MRI2 (259 of 264). Conclusion Morpho-functional 1H-MRI can be obtained with reproducible image quality and high short-term test-retest reliability for COPD-related morphological and functional changes of the lung. This underlines its potential value for the monitoring of regional lung characteristics in COPD trials. KW - capability KW - obstructive pulmonary disease KW - quantitative computed tomography KW - cystic fibrosis KW - proton MRI KW - perfusion KW - emphysema KW - CT KW - agreement KW - dysfunction Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151365 VL - 10 IS - 9 ER - TY - JOUR A1 - Kunz, Anna Lena A1 - Labes, Antje A1 - Wiese, Jutta A1 - Bruhn, Torsten A1 - Bringmann, Gerhard A1 - Imhoff, Johannes F. T1 - Nature's Lab for Derivatization: New and Revised Structures of a Variety of Streptophenazines Produced by a Sponge-Derived Streptomyces Strain JF - Marine Drugs N2 - Eight streptophenazines (A-H) have been identified so far as products of Streptomyces strain HB202, which was isolated from the sponge Halichondria panicea from the Baltic Sea. The variation of bioactivities based on small structural changes initiated further studies on new derivatives. Three new streptophenazines (I-K) were identified after fermentation in the present study. In addition, revised molecular structures of streptophenazines C, D, F and H are proposed. Streptophenazines G and K exhibited moderate antibacterial activity against the facultative pathogenic bacterium Staphylococcus epidermidis and against Bacillus subtilis. All tested compounds (streptophenazines G, I-K) also showed moderate activities against PDE 4B. KW - marine natural product KW - phenazine KW - Baltic Sea KW - streptomyces KW - halichondria panicea KW - obstructive pulmonary disease KW - phosphodiesterase-4 inhibitor KW - absolute configuration KW - biosynthesis KW - rofumilast Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116816 SN - 1660-3397 VL - 12 IS - 4 ER - TY - JOUR A1 - Roier, Sandro A1 - Leitner, Deborah R. A1 - Iwashkiw, Jeremy A1 - Schild-Prüfert, Kristina A1 - Feldman, Mario F. A1 - Krohne, Georg A1 - Reidl, Joachim A1 - Schild, Stefan T1 - Intranasal Immunization with Nontypeable Haemophilus influenzae Outer Membrane Vesicles Induces Cross-Protective Immunity in Mice JF - PLoS One N2 - Haemophilus influenzae is a Gram-negative human-restricted bacterium that can act as a commensal and a pathogen of the respiratory tract. Especially nontypeable H. influenzae (NTHi) is a major threat to public health and is responsible for several infectious diseases in humans, such as pneumonia, sinusitis, and otitis media. Additionally, NTHi strains are highly associated with exacerbations in patients suffering from chronic obstructive pulmonary disease. Currently, there is no licensed vaccine against NTHi commercially available. Thus, this study investigated the utilization of outer membrane vesicles (OMVs) as a potential vaccine candidate against NTHi infections. We analyzed the immunogenic and protective properties of OMVs derived from various NTHi strains by means of nasopharyngeal immunization and colonization studies with BALB/c mice. The results presented herein demonstrate that an intranasal immunization with NTHi OMVs results in a robust and complex humoral and mucosal immune response. Immunoprecipitation revealed the most important immunogenic proteins, such as the heme utilization protein, protective surface antigen D15, heme binding protein A, and the outer membrane proteins P1, P2, P5 and P6. The induced immune response conferred not only protection against colonization with a homologous NTHi strain, which served as an OMV donor for the immunization mixtures, but also against a heterologous NTHi strain, whose OMVs were not part of the immunization mixtures. These findings indicate that OMVs derived from NTHi strains have a high potential to act as a vaccine against NTHi infections. KW - conjugate KW - obstructive pulmonary disease KW - vaccine KW - vibrio cholerae KW - detoxified lipooligosaccharide KW - nasopharyngeal colonization KW - functional characterization KW - growing escherichia coli KW - DNA-binding vesicles KW - otitis media KW - hemophilus influenzae Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135201 VL - 7 IS - 8 ER -