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Search Results: 1 - 10 of 10610 matches for " Andreas Rembert Koczulla "
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Does Augmentation with Alpha1-Antitrypsin Affect Neutrophil Extracellular Traps Formation?
Eileen Frenzel, Elena Korenbaum, Jan Hegermann, Matthias Ochs, Janine Koepke, Andreas Rembert Koczulla, Tobias Welte, Thomas K?hnlein, Sabina Janciauskiene
International Journal of Biological Sciences , 2012,
Comparison of Two Devices and Two Breathing Patterns for Exhaled Breath Condensate Sampling
Eva-Maria Hüttmann, Timm Greulich, Akira Hattesohl, Severin Schmid, Sarah Noeske, Christian Herr, Gerrit John, Rudolf A. J?rres, Bernd Müller, Claus Vogelmeier, Andreas Rembert Koczulla
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027467
Abstract: Introduction Analysis of exhaled breath condensate (EBC) is a noninvasive method to access the epithelial lining fluid of the lungs. Due to standardization problems the method has not entered clinical practice. The aim of the study was to assess the comparability for two commercially available devices in healthy controls. In addition, we assessed different breathing patterns in healthy controls with protein markers to analyze the source of the EBC. Methods EBC was collected from ten subjects using the RTube and ECoScreen Turbo in a randomized crossover design, twice with every device - once in tidal breathing and once in hyperventilation. EBC conductivity, pH, surfactant protein A, Clara cell secretory protein and total protein were assessed. Bland-Altman plots were constructed to display the influence of different devices or breathing patterns and the intra-class correlation coefficient (ICC) was calculated. The volatile organic compound profile was measured using the electronic nose Cyranose 320. For the analysis of these data, the linear discriminant analysis, the Mahalanobis distances and the cross-validation values (CVV) were calculated. Results Neither the device nor the breathing pattern significantly altered EBC pH or conductivity. ICCs ranged from 0.61 to 0.92 demonstrating moderate to very good agreement. Protein measurements were greatly influenced by breathing pattern, the device used, and the way in which the results were reported. The electronic nose could distinguish between different breathing patterns and devices, resulting in Mahalanobis distances greater than 2 and CVVs ranging from 64% to 87%. Conclusion EBC pH and (to a lesser extent) EBC conductivity are stable parameters that are not influenced by either the device or the breathing patterns. Protein measurements remain uncertain due to problems of standardization. We conclude that the influence of the breathing maneuver translates into the necessity to keep the volume of ventilated air constant in further studies.
The role of vitamin D in pulmonary disease: COPD, asthma, infection, and cancer
Christian Herr, Timm Greulich, Rembert A Koczulla, Silke Meyer, Tetyana Zakharkina, Meret Branscheidt, Rebecca Eschmann, Robert Bals
Respiratory Research , 2011, DOI: 10.1186/1465-9921-12-31
Abstract: VitD supplementation appears to be correlated with decreased total mortality [1]. In the early 1920s a group of scientists independently discovered that irradiating of certain foods with ultraviolet light renders them antirachitic [2,3] and in 1922 Elmer V. McCollum identified an antirachitic substance in cod liver oil and called it "vitamin D" [4]. While the role of VitD in calcium and bone homeostasis has been well described, its activities on other physiological and pathophysiological processes have been recognized only in the last years. Epidemiological data suggest that several lung diseases, all inflammatory in nature, may be related to activities of VitD. VitD deficiency might have a role in the development of these diseases. The underlying mechanisms how VitD metabolisms could be linked to the pathophysiology of these diseases are often complex and not fully understood. This review summarizes the role of VitD in lung diseases.VitD and its receptors are found throughout the animal kingdom and are often linked to bone and calcium metabolisms. The fact that precursors of VitD are found in ancient organisms like krill and phytoplankton that existed unchanged for at least 750 million years [5] highlights its importance in physiologic and homeostatic processes.Variants of VitD and its receptors have been identified in higher terrestrial vertebrates like humans [6], rodents [7], birds [8], amphibia [9], reptiles [10], as well as in zebrafish [11]. These animals possess a calcified skeleton and depend on a functional VitD hormone system for calcium and phosphorus homeostasis. Surprisingly, functional VitD receptors (VDRs) have also been found in lampreys, an ancient vertebrate that lacks a calcified skeleton [12]. VDRs were also identified in animals with a naturally impoverished VitD status like the subterranean mole rat [13] and a frugivorous nocturnal mammal, the Egyptian fruit bat Cavaleros [14]. VitD precursors have been found in ancient organisms like phytopla
Comparison of exhaled breath condensate pH using two commercially available devices in healthy controls, asthma and COPD patients
Rembert Koczulla, Silvano Dragonieri, Robert Schot, Robert Bals, Stefanie A Gauw, Claus Vogelmeier, Klaus F Rabe, Peter J Sterk, Pieter S Hiemstra
Respiratory Research , 2009, DOI: 10.1186/1465-9921-10-78
Abstract: To assess the reproducibility of EBC pH for two commercially available devices (portable RTube and non-portable ECoScreen) in healthy controls, patients with asthma or COPD, and subjects suffering from an acute cold with lower-airway symptoms. In addition, we assessed the repeatability in healthy controls.EBC was collected from 40 subjects (n = 10 in each of the above groups) using RTube and ECoScreen. EBC was collected from controls on two separate occasions within 5 days. pH in EBC was assessed after degasification with argon for 20 min.In controls, pH-measurements in EBC collected by RTube or ECoScreen showed no significant difference between devices (p = 0.754) or between days (repeatability coefficient RTube: 0.47; ECoScreen: 0.42) of collection. A comparison between EBC pH collected by the two devices in asthma, COPD and cold patients also showed good reproducibility. No differences in pH values were observed between controls (mean pH 8.27; RTube) and patients with COPD (pH 7.97) or asthma (pH 8.20), but lower values were found using both devices in patients with a cold (pH 7.56; RTube, p < 0.01; ECoScreen, p < 0.05).We conclude that pH measurements in EBC collected by RTube and ECoScreen are repeatable and reproducible in healthy controls, and are reproducible and comparable in healthy controls, COPD and asthma patients, and subjects with a common cold.The accessibility of the respiratory system compared with the internal organs provides a unique opportunity for non-invasive assessment of inflammation present in most respiratory diseases. Non-invasive techniques for analyzing inflammatory mediators present in lower airway secretions include the collection of induced sputum (IS) and exhaled breath condensate (EBC). EBC is a technique first described by Russian researchers in the early Eighties [1,2]. The use of EBC collection and analysis has several advantages: It is non-invasive, easy to use, allows repeated sampling, and is suitable for analysis of children
Krüppel-like zinc finger proteins in end-stage COPD lungs with and without severe alpha1-antitrypsin deficiency
Rembert Koczulla, Danny Jonigk, Thomas Wolf, Christian Herr, Sarah Noeske, Walter Klepetko, Claus Vogelmeier, Nils von Neuhoff, Johanna Rische, Sabine Wrenger, Heiko Golpon, Robert Voswinckel, Maurizio Luisetti, Ilaria Ferrarotti, Tobias Welte, Sabina Janciauskiene
Orphanet Journal of Rare Diseases , 2012, DOI: 10.1186/1750-1172-7-29
Abstract: Explanted lungs of end-stage ZZ AATD-related (treated and non-treated with AAT augmentation therapy) and “normal” MM COPD, and liver biopsies from patients suffering from liver cirrhosis with and without ZZ AATD were used for gene expression analysis by Affymetrix microarrays or RT-PCR.A total of 162 genes were found to be differentially expressed (p-value?≤?0.05 and |FC|?≥?2) between MM and ZZ COPD patients. Of those, 134 gene sets were up-regulated and 28 were down-regulated in ZZ relative to MM lung tissue. A subgroup of genes, zinc finger protein 165, snail homolog 1 (Drosophila) (SNAI1), and Krüppel-like transcription factors (KLFs) 4 (gut), 9 and 10, perfectly segregated ZZ and MM COPD patients. The higher expression of KLF 9 and KLF10 has been verified in the replication cohort with AATD-related end-stage lung emphysema and liver cirrhosis. Furthermore, higher expression of KLF9, SNAI1 and DEFA1 was found in ZZ COPD lungs without augmentation therapy relative to MM COPD or ZZ COPD with augmentation therapy.These results reveal the involvement of transcriptional regulators of the zinc-finger family in COPD pathogenesis and provide deeper insight into the pathophysiological mechanisms of COPD with and without AATD.
Analysis of the Airway Microbiota of Healthy Individuals and Patients with Chronic Obstructive Pulmonary Disease by T-RFLP and Clone Sequencing
Tetyana Zakharkina, Elke Heinzel, Rembert A. Koczulla, Timm Greulich, Katharina Rentz, Josch K. Pauling, Jan Baumbach, Mathias Herrmann, Christiane Grünewald, Hendrik Dienemann, Lutz von Müller, Robert Bals
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0068302
Abstract: Chronic obstructive pulmonary disease (COPD) is a progressive, inflammatory lung disease that affects a large number of patients and has significant impact. One hallmark of the disease is the presence of bacteria in the lower airways. Objective: The aim of this study was to analyze the detailed structure of microbial communities found in the lungs of healthy individuals and patients with COPD. Nine COPD patients as compared and 9 healthy individuals underwent flexible bronchoscopy and BAL was performed. Bacterial nucleic acids were subjected to terminal restriction fragment (TRF) length polymorphism and clone library analysis. Overall, we identified 326 T-RFLP band, 159 in patients and 167 in healthy controls. The results of the TRF analysis correlated partly with the data obtained from clone sequencing. Although the results of the sequencing showed high diversity, the genera Prevotella, Sphingomonas, Pseudomonas, Acinetobacter, Fusobacterium, Megasphaera, Veillonella, Staphylococcus, and Streptococcus constituted the major part of the core microbiome found in both groups. A TRF band possibly representing Pseudomonas sp. monoinfection was associated with a reduction of the microbial diversity. Non-cultural methods reveal the complexity of the pulmonary microbiome in healthy individuals and in patients with COPD. Alterations of the microbiome in pulmonary diseases are correlated with disease.
A Real-World Observational Study of Patients with Advanced Melanoma Receiving First-Line Ipilimumab in a Community Practice Setting  [PDF]
Debra A. Patt, Debra Rembert, Menaka Bhor, Debajyoti Bhowmik, Sumati A. Rao
Journal of Cancer Therapy (JCT) , 2014, DOI: 10.4236/jct.2014.512110
Abstract: Background: Following approval of ipilimumab, this observational cohort study (CA184-332) was initiated to describe patient and disease characteristics, patterns of care, survival, and adverse events (AEs) in advanced melanoma (AM) patients treated with first-line ipilimumab in realworld US community practice. Methods: Adult patients with treatment-naive AM who received ≥1 dose of ipilimumab 3 mg/kg between April 2011 and September 2012 were retrospectively identified at US Oncology sites. Clinical data were abstracted from patient medical records. Results: Median age of the 157 patient cohorts was 66 years (range 21 - 91). 68.2% were male, and 90.5% had a cutaneous primary site. At ipilimumab initiation, 80.9% of patients had an ECOG performance status of 0 or 1; 54.1% were stage M1c; 34.4% had brain metastases; 24.8% had elevated lactate dehydrogenase, and 13.4% were positive for BRAF mutation. All 4 cycles of ipilimumab were completed by 55.8% of patients. At a median follow-up of 8.5 months (range 2.9 - 15.0), median overall survival was 11.5 months (95% CI: 8.9 - 16.6) and 1-year survival was 46.7% (95% CI: 38.1 - 54.9). During ipilimumab treatment, AEs were experienced by 63.7% of patients. The most frequent AEs were gastrointestinal (41.4%; diarrhea in 19.1%) and skin-related (28.0%; rash in 17.8%); 17.8% of patients had an AE that led to ipilimumab discontinuation. Conclusions: These real-world results are consistent with those from clinical trials and provide evidence supporting the effectiveness and safety of first-line ipilimumab 3 mg/kg monotherapy in patients with AM treated in a community practice setting.
Reactive Arthritis due to Shigella Infection after a Visit to Egypt: A Late Complication of an Intestinal Infection
Alwin Tilanus,Rembert Mertens,Lucie Seyler,Patrick Lacor,Brigitte Velkeniers
Case Reports in Gastrointestinal Medicine , 2012, DOI: 10.1155/2012/972517
Abstract: We describe a case of reactive arthritis following Shigella infection after a trip to Egypt. The diagnostic challenge and treatment of this acute medical condition are discussed.
A proteogenomic update to Yersinia: enhancing genome annotation
Samuel H Payne, Shih-Ting Huang, Rembert Pieper
BMC Genomics , 2010, DOI: 10.1186/1471-2164-11-460
Abstract: The application of experimental proteomics data to genome annotation, called proteogenomics, can quickly and efficiently discover misannotations, yielding a more accurate and complete genome annotation. We present a comprehensive proteogenomic analysis of the plague bacterium, Yersinia pestis KIM. We discover non-annotated genes, correct protein boundaries, remove spuriously annotated ORFs, and make major advances towards accurate identification of signal peptides. Finally, we apply our data to 21 other Yersinia genomes, correcting and enhancing their annotations.In total, 141 gene models were altered and have been updated in RefSeq and Genbank, which can be accessed seamlessly through any NCBI tool (e.g. blast) or downloaded directly. Along with the improved gene models we discover new, more accurate means of identifying signal peptides in proteomics data.Yersinia pestis, a Gram-negative bacterium, is the causative agent of the bubonic and pneumonic plague. The pathogenic lifestyle of this microbe involves two distinct life stages, one in the flea vector, the other in mammalian hosts, primarily rodents [1]. Y. pestis recently speciated from Y. pseudotuberculosis, acquiring two pathogenic plasmids and a chromosomal pathogenicity island. Seven Y. pestis genomes have been sequenced to completion, along with five other Yersinia sequences. Numerous other Yersinia have been sequenced to draft quality.Genome annotation is often divided into two sequential phases, finding genes and assigning function. Most prokaryotic genome annotation pipelines consist of automated gene finding, corroborated by limited homology comparisons. As such they lack any experimental validation of primary structure. Fundamentally, an accurate primary structure implies finding the correct start/stop of the gene, which may be erroneously predicted for 20% of genes in some bacterial and archaeal genomes [2,3]. But it also includes recognizing any true frame-shifting events, which must be delineated f
Integrated next-generation sequencing of 16S rDNA and metaproteomics differentiate the healthy urine microbiome from asymptomatic bacteriuria in neuropathic bladder associated with spinal cord injury
Fouts Derrick E,Pieper Rembert,Szpakowski Sebastian,Pohl Hans
Journal of Translational Medicine , 2012, DOI: 10.1186/1479-5876-10-174
Abstract: Background Clinical dogma is that healthy urine is sterile and the presence of bacteria with an inflammatory response is indicative of urinary tract infection (UTI). Asymptomatic bacteriuria (ABU) represents the state in which bacteria are present but the inflammatory response is negligible. Differentiating ABU from UTI is diagnostically challenging, but critical because overtreatment of ABU can perpetuate antimicrobial resistance while undertreatment of UTI can result in increased morbidity and mortality. In this study, we describe key characteristics of the healthy and ABU urine microbiomes utilizing 16S rRNA gene (16S rDNA) sequencing and metaproteomics, with the future goal of utilizing this information to personalize the treatment of UTI based on key individual characteristics. Methods A cross-sectional study of 26 healthy controls and 27 healthy subjects at risk for ABU due to spinal cord injury-related neuropathic bladder (NB) was conducted. Of the 27 subjects with NB, 8 voided normally, 8 utilized intermittent catheterization, and 11 utilized indwelling Foley urethral catheterization for bladder drainage. Urine was obtained by clean catch in voiders, or directly from the catheter in subjects utilizing catheters. Urinalysis, urine culture and 16S rDNA sequencing were performed on all samples, with metaproteomic analysis performed on a subsample. Results A total of 589454 quality-filtered 16S rDNA sequence reads were processed through a NextGen 16S rDNA analysis pipeline. Urine microbiomes differ by normal bladder function vs. NB, gender, type of bladder catheter utilized, and duration of NB. The top ten bacterial taxa showing the most relative abundance and change among samples were Lactobacillales, Enterobacteriales, Actinomycetales, Bacillales, Clostridiales, Bacteroidales, Burkholderiales, Pseudomonadales, Bifidobacteriales and Coriobacteriales. Metaproteomics confirmed the 16S rDNA results, and functional human protein-pathogen interactions were noted in subjects where host defenses were initiated. Conclusions Counter to clinical belief, healthy urine is not sterile. The healthy urine microbiome is characterized by a preponderance of Lactobacillales in women and Corynebacterium in men. The presence and duration of NB and method of urinary catheterization alter the healthy urine microbiome. An integrated approach of 16S rDNA sequencing with metaproteomics improves our understanding of healthy urine and facilitates a more personalized approach to prevention and treatment of infection.
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