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Biomedical subjects

M Wegmann

Publications and source records attributed to M Wegmann.

14 recordsLinked to original sources
PubMed2005

A new approach to an influenza live vaccine: modification of the cleavage site of hemagglutinin.

A promising approach to reduce the impact of influenza is the use of an attenuated, live virus as a vaccine. Using reverse genetics, we generated a mutant of strain A/WSN/33 with a modified cleavage site within its hemagglutinin, which depends on proteolytic activation by elastase. Unlike the wild-type, which requires trypsin, this mutant is strictly dependent on elastase. Both viruses grow equally well in cell culture. In contrast to the lethal wild-type virus, the mutant is entirely attenuated in mice. At a dose of 10(5) plaque-forming units, it induced complete protection against lethal challenge. This approach allows the conversion of any epidemic strain into a genetically homologous attenuated virus.

Animals↗
PubMed2005

Prenatal lipopolysaccharide-exposure prevents allergic sensitization and airway inflammation, but not airway responsiveness in a murine model of experimental asthma.

BACKGROUND: Epidemiological evidence underlines the impact of prenatal environmental factors on the development of postnatal allergies. In this regard an inverse correlation between lipopolysaccharide (LPS) exposure and development of childhood allergy has been found. OBJECTIVE: To assess the impact of prenatal LPS exposure on the development of postnatal respiratory allergies in a mouse model of experimental asthma. METHODS: Female BALB/c mice were exposed to LPS before conception and during pregnancy. Several weeks after birth offspring were sensitized to ovalbumin (OVA) followed by aerosol allergen challenges. RESULTS: Prenatal, maternal LPS-exposure enhanced neonatal IFN-gamma, but not IL-4 and IL-2 production. OVA sensitization of prenatally LPS-exposed mice was accompanied by a marked suppression in anti-OVA IgG1 and IgE as well as unchanged IgG2a antibody responses, paralleled by a significant reduction in IL-5 and IL-13 levels following mitogenic stimulation of splenic leucocytes. Assessment of bronchoalveolar lavage fluids following allergen challenges revealed a marked reduction in eosinophils and macrophages in these mice. Surprisingly, development of airway hyper-responsiveness, a hallmark of bronchial asthma, was not affected. CONCLUSION: This study provides first experimental evidence that LPS may already operate in prenatal life in order to modulate the development of allergies in the offspring.

Animals↗
PubMed2005

Involvement of distal airways in a chronic model of experimental asthma.

BACKGROUND: Bronchial asthma is characterized by chronic airway inflammation and airway remodelling which occurs in both proximal and distal airways. These changes are associated with development of airway hyper-responsiveness and airflow limitation. OBJECTIVE: This study was aimed to analyse whether chronic inhalative allergen challenges in mice lead to morphological and physiological changes comparable with this phenotype. METHODS: For this purpose, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed by aerosol allergen challenges on 2 consecutive days per week for 12 weeks. RESULTS: In chronically challenged mice, tissue inflammation in proximal as well as distal airways was observed with a predominance of lymphocytes within the cellular infiltrate. In contrast, inflammation in the airway lumen decreased over time. These changes were associated by a shift in bronchoalveolar lavage-cytokine levels from IL-4, IL-5 and TNF-alpha production (during the acute phase) towards markedly increased levels of TGF-beta during the chronic phase. Goblet cell hyperplasia and subepithelial fibrosis occurred throughout the airway tree. In terms of lung function, chronically challenged mice developed persistent bronchial hyper-responsiveness and progressive airflow limitation. Six weeks after OVA aerosol discontinuation, airway inflammation still persisted although lung function was normalized. CONCLUSION: These data indicate that our model of chronic aerosol allergen challenges leads to a phenotype of experimental asthma with participation of distal airways and persistence of inflammation thereby resembling many morphological and physiological aspects of human bronchial asthma.

Administration, Inhalation↗
PubMed2004

Three-dimensional analysis of porous BaTiO3 ceramics using FIB nanotomography.

Three-dimensional (3D) data represent the basis for reliable quantification of complex microstructures. Therefore, the development of high-resolution tomography techniques is of major importance for many materials science disciplines. In this paper, we present a novel serial sectioning procedure for 3D analysis using a dual-beam FIB (focused ion beam). A very narrow and reproducible spacing between the individual imaging planes is achieved by using drift correction algorithms in the automated slicing procedure. The spacing between the planes is nearly of the same magnitude as the pixel resolution on scanning electron microscopy images. Consequently, the acquired stack of images can be transformed directly into a 3D data volume with a voxel resolution of 6 x 7 x 17 nm. To demonstrate the capabilities of FIB nanotomography, a BaTiO3 ceramic with a high volume fraction of fine porosity was investigated using the method as a basis for computational microstructure analysis and the results compared with conventional physical measurements. Significant differences between the particle size distributions as measured by nanotomography and laser granulometry indicate that the latter analysis is skewed by particle agglomeration/aggregation in the raw powder and by uncertainties related to calculation assumptions. Significant differences are also observed between the results from mercury intrusion porosimetry (MIP) and 3D pore space analysis. There is strong evidence that the ink-bottle effect leads to an overestimation of the frequency of small pores in MIP. FIB nanotomography thus reveals quantitative information of structural features smaller than 100 nm in size which cannot be acquired easily by other methods.

Journal Article↗
PubMed2004

Characterisation of post-pneumonectomy lung growth in adult mice.

A model of inducible expansion of the gas exchange area in adult mice would be ideal for the investigation of molecular determinants of airspace regeneration in vivo. Therefore, the post-pneumonectomy (post-PNX) compensatory lung growth in adult C57BL/6 mice was characterised in this study. Mice underwent left-sided PNX. Right lung volume was assessed on days 1, 3, 5, 7, 10 and 21 after PNX, and total DNA and cellular proliferation of the right lung were determined. Lung histology was studied using immunohistochemistry and quantitatively characterised by detailed stereological investigations. Pulmonary function was assessed using a mouse body-plethysmograph. Following PNX, right-lung volume rapidly restored the initial volume of left and right lung. Total DNA increased significantly over 21 days and equalled the total DNA amount of both lungs in the control mice. Septal cell proliferation significantly increased after PNX, and included endothelial cells, epithelial cells, smooth muscle cells and fibroblasts. Stereological investigations of left and right control lungs versus right lungs 21 days after PNX indicated complete restoration of body mass-specific alveolar surface area. Pulmonary function testing showed marked alteration at 3 days and normalisation at 21 days post-PNX. In conclusion, well reproducible reconstitution of alveolar gas-exchange surface based on septal tissue expansion may be provoked by pneumonectomy in adult mice.

Animals↗
PubMed2003

Prostaglandin E2 stimulates sodium reabsorption in MDCK C7 cells, a renal collecting duct principal cell model.

We examined the direct epithelial effects of the major product of arachidonic acid metabolism in the kidney, prostaglandin E(2) (PGE(2)), on ion transport and signal transduction in the hormone-sensitive Madin-Darby canine kidney (MDCK) C7 subclone as a model of renal collecting duct principal cells. MDCK C7 cells were grown on microporous permeable filter supports and mounted in Ussing-type chambers. Reverse transcriptase (RT)-PCR and sequencing were used to determine E-prostanoid (EP) receptor expression. Basolateral and, about 14-fold less potent, apical addition of PGE(2) increased short-circuit current (I(sc)) in a concentration-dependent manner. This ion transport was biphasic with a rapid peak not detectable under chloride-free conditions. The remaining, stably elevated current was unaffected by furosemide, hydrochlorothiazide, ethylisopropanol amiloride, and 5-nitro-2-(3-phenyl-propyl-amino)benzoic acid (NPPB). In contrast, apical amiloride (10 microM) significantly decreased I(sc), indicating sodium reabsorption. The effect of PGE(2) was attenuated in the presence of vasopressin. Agonists acting by cAMP elevation like dibutyryl-cAMP and theophylline also induced an amiloride-sensitive ion transport with similar kinetics as PGE(2). Moreover, PGE(2) rapidly increased intracellular cAMP levels. RT-PCR demonstrated mRNA expression of the epithelial sodium channel (ENaC), and of the EP2 receptor in MDCK C7 cells. Accordingly, EP2 receptor agonist butaprost mimicked PGE(2) epithelial action. In conclusion, PGE(2) induces amiloride-sensitive sodium reabsorption in MDCK C7 monolayers. This ion transport is most likely mediated by EP2 receptor activation leading to increased intracellular cAMP levels. Therefore, PGE(2) might also contribute to Na(+) reabsorption in the mammalian collecting duct.

Alprostadil↗
PubMed2000

Effect of hydroxyeicosatetraenoic acids on furosemide-sensitive chloride secretion in rat distal colon.

Arachidonic acid metabolites such as prostaglandins, thromboxanes, and leukotrienes are well known modulators of intestinal vascular perfusion, motility, and electrogenic ion transport. We investigated the effect of different hydroxyeicosatetraenoic acids (HETEs) from cytochrome P450- and lipoxygenase-dependent arachidonate metabolism on electrogenic chloride secretion in rat distal colon. Using conventional Ussing techniques, basolateral 12-HETE significantly decreased basal short-circuit current (I(sc)) and inhibited furosemide-sensitive Cl(-) secretion stimulated by either dibutyryl cAMP, prostaglandin E(2), or theophylline in a concentration-dependent manner (IC(50) = 1.5 nM). These data were underlined by significant inhibition of J(net)(Cl) in unidirectional (36)Cl flux measurements. Direct regulation of the basolateral Na(+)-K(+)-2Cl(-) cotransporter or the Na-K-ATPase could be excluded because 12-HETE had no effect on furosemide-sensitive K(+) secretion induced by epinephrine, or ouabain-sensitive Na(+) reabsorption stimulated by aldosterone. Inhibitors of Ca(2+)-activated and voltage-gated K(+) channels such as apamin, charybdotoxin, and dendrotoxin did not affect secretagogue-dependent I(sc) and its regulation by 12-HETE. In contrast, glibenclamide significantly attenuated the effect of 12-HETE on secretagogue-induced I(sc), whereas chromanol 293B, an inhibitor of cAMP-dependent K(+) conductance, had an additive effect. We speculate that 12-HETE, like glibenclamide, affects intestinal Cl(-) secretion by inhibiting basolateral K(+)(ATP) channels. In contrast to these findings, neither 5-HETE nor 20-HETE had any effect on basal I(sc) or cAMP-dependent Cl(-) secretion.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1991

Perceived depth scales with disparity gradient.

Perceived difference in depth between two adjacent stimuli decreases with increasing disparity gradient even if the disparity stays constant, ie when the stimuli approach each other along paths within fronto-parallel planes. This depth scaling effect is more pronounced with line stimuli than with two isolated points or two small symbols and is insignificant for easily discriminable symbols. The decrease in perceived depth is more pronounced for horizontal orientation than for oblique or vertical orientation. The ratio of perceived depth difference to displayed disparity difference also decreases when the distance between the stimuli increases at a constant gradient in depth. This is to say that we are more correct in our depth estimates for steep gradients in depth when the euclidean distance between the stimuli is short.

Attention↗
PubMed1986

Brain-stem auditory response in Ondine's syndrome.

Brain-stem auditory evoked responses were measured during sleep in four infants with congenital central alveolar hypoventilation syndrome (Ondine's syndrome) and four controls matched for age and sex. Delays in peak latencies p III and interpeak latencies p I-III were consistently seen in these patients but not in the control children. These abnormalities were reproducible and suggested disruption in the normal auditory pathways at the level of the mid to upper brain stem through which fibers pass close to the area of respiratory control. These abnormalities, both electrophysiologic and metabolic, imply a functional disturbance of brain-stem control of ventilation during sleep in infants and children suffering from Ondine's syndrome.

Audiometry, Evoked Response↗
PubMedDate not supplied

Long-term NO2 exposure induces pulmonary inflammation and progressive development of airflow obstruction in C57BL/6 mice: a mouse model for chronic obstructive pulmonary disease?

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways, development of emphysema and irreversible airway obstruction. Macrophages, neutrophils and CD8+ T cells and their products have been shown to play an important role in the initiation and maintenance of these processes. In contrast, the mechanisms underlying COPD pathogenesis still remain uncertain. This article focuses on the generation of an animal model that mirrors some features of human COPD in association with a progredient airflow limitation.

Animals↗