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Stanke F.,Hannover Medical School | Stanke F.,Biomedical Research in Endstage and Obstructive Lung Disease Hanover BREATH
Mediators of Inflammation | Year: 2015

In the context of cystic fibrosis, the epithelial cell has been characterized in terms of its ion transport capabilities. The ability of an epithelial cell to initiate CFTR-mediated chloride and bicarbonate transport has been recognized early as a means to regulate the thickness of the epithelial lining fluid and recently as a means to regulate the pH, thereby determining critically whether or not host defense proteins such as mucins are able to fold appropriately. This review describes how the epithelial cell senses the presence of pathogens and inflammatory conditions, which, in turn, facilitates the activation of CFTR and thus directly promotes pathogens clearance and innate immune defense on the surface of the epithelial cell. This paper summarizes functional data that describes the effect of cytokines, chemokines, infectious agents, and inflammatory conditions on the ion transport properties of the epithelial cell and relates these key properties to the molecular pathology of cystic fibrosis. Recent findings on the role of cystic fibrosis modifier genes that underscore the role of the epithelial ion transport in host defense and inflammation are discussed. © 2015 Frauke Stanke.


Ochs M.,Hannover Medical School | Ochs M.,Biomedical Research in Endstage and Obstructive Lung Disease Hanover BREATH
Annals of Anatomy | Year: 2014

Chronic obstructive pulmonary disease (COPD) is one of the most common lung diseases. The major component of COPD, which affects the gas-exchanging parenchyma of the lung, emphysema, is characterized by destruction of alveolar septae leading to loss of functional surface, loss of alveoli and enlargement of remaining distal airspaces. These microstructural alterations can be modeled in animals and can be measured using stereological methods applied to imaging datasets. Many animal models of emphysema exist, but most of them are insufficiently characterized with respect to the underlying nature (e.g. destructive or developmental) and the degree of the structural alterations. The most popular parameter for assessment of emphysematous alterations, mean linear intercept length, has severe limitations. It can, therefore, not be recommended. Better design-based stereological alternatives exist but are less often applied, such as total volumes of parenchymal compartments (alveolar airspace, alveolar duct airspace, alveolar septum), total alveolar surface area, total alveolar number and mean alveolar size and its size variation. A prerequisite is the use of appropriate fixation, sampling, and specimen processing protocols. This article reviews the challenges of stereologic assessment of emphysematous alterations in the lung and illustrates possible strategies. © 2013 Elsevier GmbH.


Schneider J.P.,Hannover Medical School | Ochs M.,Hannover Medical School | Ochs M.,Biomedical Research in Endstage and Obstructive Lung Disease Hanover BREATH
American Journal of Physiology - Lung Cellular and Molecular Physiology | Year: 2014

Preservation of original tissue dimensions is an essential prerequisite for morphometric studies. Shrinkage occurring during tissue processing for histology may severely influence the appearance of structures seen under the microscope and stereological calculations. Therefore, shrinkage has to be avoided so that estimates obtained by application of unbiased stereology are indeed unbiased. The present study investigates the alterations of tissue dimensions of mouse lung samples during processing for histology. Different fixatives as well as embedding protocols are considered. Mouse lungs were fixed by instillation of either 4% formalin or a mixture of 1.5% glutaraldehyde/1.5% formaldehyde. Tissue blocks were sampled according to principles of stereology for embedding in paraffin, glycol methacrylate without treatment with osmium tetroxide and uranyl acetate, and glycol methacrylate including treatment with osmium tetroxide and uranyl acetate before dehydration. Shrinkage was investigated by stereological measurements of dimensional changes of tissue cut faces. Results show a shrinkage of the cut face areas of roughly 40% per lung during paraffin embedding, 30% during "simple" glycol methacrylate embedding, and <3% during osmium tetroxide/uranyl acetate/glycol methacrylate embedding. Furthermore, the superiority of the glutaraldehyde-containing fixative regarding shrinkage is demonstrated. In conclusion, the use of a glutaraldehyde-containing fixative and embedding in glycol methacrylate with previous treatment of the samples with osmium tetroxide and uranyl acetate before dehydration is recommended for stereological studies of the mouse lung. © 2014 the American Physiological Society.


Cramer N.,Clinical Research Group | Wiehlmann L.,Clinical Research Group | Ciofu O.,Copenhagen University | Tamm S.,Clinical Research Group | And 3 more authors.
PLoS ONE | Year: 2012

Background/Methods: The molecular epidemiology of the chronic airway infections with Pseudomonas aeruginosa in individuals with cystic fibrosis (CF) was investigated by cross-sectional analysis of bacterial isolates from 51 CF centers and by longitudinal analysis of serial isolates which had been collected at the CF centers Hanover and Copenhagen since the onset of airway colonization over 30 years. Results: Genotyping revealed that the P. aeruginosa population in CF is dominated by a few ubiquitous clones. The five most common clones retrieved from the CF host also belonged to the twenty most frequent clones in the environment and in other human disease habitats. Turnover of clones in CF airways was rare. At the Hanover clinic more than half of the patient cohort was still harbouring the initially acquired clone after twenty years of airway colonization. At the Copenhagen clinic, however, two rare clones replaced the initially acquired individual clones in all but one patient. Conclusion: The divergent epidemiology at the two sites is explained by their differential management of hygiene and antipseudomonal chemotherapy. Hygienic measures to prohibit patient-to-patient transmission and the modalities of antipseudomonal chemotherapy modify the epidemiology of the chronic P. aeruginosa infections in CF. © 2012 Cramer et al.


Muhlfeld C.,Hannover Medical School | Muhlfeld C.,Biomedical Research in Endstage and Obstructive Lung Disease Hanover BREATH | Ochs M.,Hannover Medical School | Ochs M.,Biomedical Research in Endstage and Obstructive Lung Disease Hanover BREATH
American Journal of Physiology - Lung Cellular and Molecular Physiology | Year: 2013

Design-based stereology provides efficient methods to obtain valuable quantitative information of the respiratory tract in various diseases. However, the choice of the most relevant parameters in a specific disease setting has to be deduced from the present pathobiological knowledge. Often it is difficult to express the pathological alterations by interpretable parameters in terms of volume, surface area, length, or number. In the second part of this companion review article, we analyze the present pathophysiological knowledge about acute lung injury, diffuse parenchymal lung diseases, emphysema, pulmonary hypertension, and asthma to come up with recommendations for the disease-specific application of stereological principles for obtaining relevant parameters. Worked examples with illustrative images are used to demonstrate the work flow, estimation procedure, and calculation and to facilitate the practical performance of equivalent analyses. © 2013 the American Physiological Society.

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