RepoMed (Medizinische Hochschule Hannover)
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The multifaceted innate immune evasion strategies of Herpesviruses: novel concepts in host manipulation by murine cytomegalovirus
Get PDFDie modifizierte minimalinvasive ECRL-Tenodese bei skapholunärer Dissoziation: eine prospektive Studie
Get PDFAnalysis of the role of different pattern recognition receptors in murine cytomegalovirus-mediated activation of innate immunity
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Assessment of the Alveolar Capillary Network in the Postnatal Mouse Lung in 3D Using Serial Block-Face Scanning Electron Microscopy.
No full textThe alveolar capillary network (ACN) has a large surface area that provides the basis for an optimized gas exchange in the lung. It needs to adapt to morphological changes during early lung development and alveolarization. Structural alterations of the pulmonary vasculature can lead to pathological functional conditions such as in bronchopulmonary dysplasia and various other lung diseases. To understand the development of the ACN and its impact on the pathogenesis of lung diseases, methods are needed that enable comparative analyses of the complex three-dimensional structure of the ACN at different developmental stages and under pathological conditions. In this study a newborn mouse lung was imaged with serial block-face scanning electron microscopy (SBF-SEM) to investigate the ACN and its surrounding structures before the alveolarization process begins. Most parts but not all of the examined ACN contain two layers of capillaries, which were repeatedly connected with each other. A path from an arteriole to a venule was extracted and straightened to allow cross-sectional visualization of the data along the path within a plane. This allows a qualitative characterization of the structures that erythrocytes pass on their way through the ACN. One way to define regions of the ACN supplied by specific arterioles is presented and used for analyses. Pillars, possibly intussusceptive, were found in the vasculature but no specific pattern was observed in regard to parts of the saccular septa. This study provides 3D information with a resolution of about 150 nm on the microscopic structure of a newborn mouse lung and outlines some of the potentials and challenges of SBF-SEM for 3D analyses of the ACN
In Vivo Cell Fusion between Mesenchymal Stroma/Stem-Like Cells and Breast Cancer Cells
No full textCellular communication within the tumor microenvironment enables important
interactions between cancer cells and recruited adjacent populations including
mesenchymal stroma/stem-like cells (MSC). These interactions were monitored in
vivo following co-injection of GFP-labeled human MSC together with
mcherry-labeled MDA-MB-231 breast cancer cells in NODscid mice. Within 14 days of
tumor development the number of initially co-injected MSC had significantly
declined and spontaneous formation of breast cancer/MSC hybrid cells was observed
by the appearance of double fluorescing cells. This in vivo fusion displayed a
rare event and occurred in less than 0.5% of the tumor cell population. Similar
findings were observed in a parallel in vitro co-culture. Characterization of the
new cell fusion products obtained after two consecutive flow cytometry cell
sorting and single cell cloning revealed two populations, termed MDA-hyb3 and
MDA-hyb4. The breast cancer fusion cells expressed both, GFP and mcherry and
displayed more characteristics of the MDA-MB-231 cells than of the parental MSC.
While little if any differences were determined in the proliferative capacity, a
significant delay of MDA-hyb3 cells in tumor formation was observed when compared
to the parental MDA-MB-231 cells. Moreover, MDA-hyb3 cells developed an altered
pattern of distant organ metastases. These findings demonstrated dynamic tumor
changes by in vivo and in vitro fusion with the development of new breast cancer
hybrid cells carrying altered tumorigenic properties. Consequently, cancer cell
fusion contributes to progressively increasing tumor heterogeneity which
complicates a therapeutic regime
Baseline Dietary Restraint Predicts Negative Treatment Outcomes after 12 Months in Children and Adolescents with Obesity Participating in a Lifestyle Intervention
No full textOBJECTIVE: Current lifestyle interventions for children and adolescents with obesity often exclude patients with an eating pathology, leaving the impact of eating pathologies on treatment outcomes largely unconsidered. We investigated the predictive value of disordered eating symptoms on BMI z-score reduction in a sample of 111 German children and adolescents with overweight (90th percentile 97th percentile) aged 7-15 years in an outpatient lifestyle intervention program. METHODS: We defined a BMI z-score reduction of more than 5% after 12 months as a successful outcome. Disordered eating symptoms (i.e., dietary restraint, emotional eating, external eating, and binge eating) were assessed at baseline with the Eating Pattern Inventory (EPI-C) and the "bulimia" scale of the Eating Disorder Inventory (EDI-2). Covariates were: baseline z-BMI, age, gender, and maternal education level. RESULTS: Multiple regression analysis revealed that dietary restraint significantly predicted change in BMI z-scores between baseline and T1. Higher levels of dietary restraint were associated with a lower BMI z-score reduction between T0 and T1. To compare non-completers with completers on the 4 eating behavior scales, we used MANCOVA. At baseline, children who subsequently dropped out of the program prematurely showed significantly higher dietary restraint scores than children who completed the intervention, irrespectively of their gender, age, and BMI z-score at baseline and their mother's education level. DISCUSSION: Our results provide further evidence that the analysis of treatment processes in lifestyle intervention programs for children and adolescents with overweight and obesity should take into account a broader multidimensional approach including eating and dietary habit
Preeclampsia-Associated Alteration of DNA Methylation in Fetal Endothelial Progenitor Cells
No full textObjective: The pregnancy complication preeclampsia represents an independent risk factor for cardiovascular disease. Our previous research shows a diminished function of fetal endothelial colony-forming cells (ECFC), a proliferative subgroup of endothelial progenitor cells (EPC) in preeclampsia. The aim of this study was to further investigate whether DNA methylation of fetal EPC is affected in preeclampsia. Methods: The genomic methylation pattern of fetal ECFC from uncomplicated and preeclamptic pregnancies was compared for 865918 CpG sites, and genes were classified into gene networks. Low and advanced cell culture passages were compared to explore whether expansion of fetal ECFC in cell culture leads to changes in global methylation status and if methylation characteristics in preeclampsia are maintained with increasing passage. Results: A differential methylation pattern of fetal ECFC from preeclampsia compared to uncomplicated pregnancy was detected for a total of 1266 CpG sites in passage 3, and for 2362 sites in passage 5. Key features of primary networks implicated by methylation differences included cell metabolism, cell cycle and transcription and, more specifically, genes involved in cell-cell interaction and Wnt signaling. We identified an overlap between differentially regulated pathways in preeclampsia and cardiovascular system development and function. Cell culture passages 3 and 5 showed similar gene network profiles, and 1260 out of 1266 preeclampsia-associated methylation changes detected in passage 3 were confirmed in passage 5. Conclusion: Methylation modification caused by preeclampsia is stable and detectable even in higher cell culture passages. An epigenetically modified endothelial precursor may influence both normal morphogenesis and postnatal vascular repair capacity. Further studies on epigenetic modifications in complicated pregnancies are needed to facilitate development of EPC based therapies for cardiovascular alteration
Voluntary Activity Modulates Sugar-Induced Elastic Fiber Remodeling in the Alveolar Region of the Mouse Lung
No full textDiabetes and respiratory diseases are frequently comorbid conditions. However, the mechanistic links between hyperglycemia and lung dysfunction are not entirely understood. This study examined the effects of high sucrose intake on lung mechanics and alveolar septal composition and tested voluntary activity as an intervention strategy. C57BL/6N mice were fed a control diet (CD, 7% sucrose) or a high sucrose diet (HSD, 35% sucrose). Some animals had access to running wheels (voluntary active; CD-A, HSD-A). After 30 weeks, lung mechanics were assessed, left lungs were used for stereological analysis and right lungs for protein expression measurement. HSD resulted in hyperglycemia and higher static compliance compared to CD. Lung and septal volumes were increased and the septal ratio of elastic-to-collagen fibers was decreased despite normal alveolar epithelial volumes. Elastic fibers appeared more loosely arranged accompanied by an increase in elastin protein expression. Voluntary activity prevented hyperglycemia in HSD-fed mice. The parenchymal airspace volume, but not the septal volume, was increased. The septal extracellular matrix (ECM) composition together with the protein expression of ECM components was similar to control levels in the HSD-A-group. In conclusion, HSD was associated with elastic fiber remodeling and reduced pulmonary elasticity. Voluntary activity alleviated HSD-induced ECM alterations, possibly by preventing hyperglycemi