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See detailFunctional characterization of glycolytic enzymes from Arabidopsis: do they only have a metabolic function?
Ros, Ros; Muñoz-Bertomeu, Jesús; Cascales - Miñana, Borja ULg et al

Conference (2009, November)

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See detailFunctional characterization of new allelic polymorphisms identified in the promoter region of the human MxA gene.
Tran Thi Duc, Tam; Desmecht, Daniel ULg; Cornet, Anne

in International Journal of Immunogenetics (2013), 40

The Mx proteins are high-molecular-weight dynamin-like proteins whose expression depends strictly on type-I and -III interferons (IFN). Some isoforms are able to inhibit the life cycle of one or several ... [more ▼]

The Mx proteins are high-molecular-weight dynamin-like proteins whose expression depends strictly on type-I and -III interferons (IFN). Some isoforms are able to inhibit the life cycle of one or several viruses and are thus components of innate immune response. The human MxA protein displays the broadest antiviral spectrum which makes it appear as a key antiviral effector of innate immunity. Allelic polymorphisms located in the MxA gene promoter can be expected to affect the magnitude of MxA mRNA transcription in response to IFNs and therefore to alter the severity of viral diseases in humans. Here, three single nucleotide polymorphism sites (-309, -101 and +20) were examined for their ability to alter MxA gene promoter-driven reporter expression. We show that, besides the previously reported role of 123A and -88T, the presence of -101G is equally important. Moreover, when a promoter construct carries these three critical nucleotides, a first additional positive effect is conferred by a C at position -309 and, in this latter case, a second additional effect is produced by a A at position +20. This finding is clinically useful to improve prediction of IFN-responsiveness in patients not only with viral diseases for which type-I IFN therapy is used. [less ▲]

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See detailFunctional Characterization of Snail2 Mediated E-Cadherin repression
Molina Ortiz, Patricia ULg; MacPherson, Matthew; Cano, Amparo et al

Poster (2007, December 02)

Snail2, also called Slug, is a member of the Snail-family of zinc-finger transcription factors that plays a significant role both during development and carcinogenesis, by controlling epithelial ... [more ▼]

Snail2, also called Slug, is a member of the Snail-family of zinc-finger transcription factors that plays a significant role both during development and carcinogenesis, by controlling epithelial-mesenchymal transition (EMT) processes. Snail2 has been also described as a direct transcriptional repression of E-cadherin during EMT being implicated as a prosurvival factor during tumorogenesis. Snail1 and Snail2 are highly homologous factors, containing a common N-terminal transrepressor domain (SNAG), a C-terminus DNA binding domain of four (Snail1) or five (Snail2) zinc fingers, and a divergent central region, which in Snail2 is formed by a unique domain called `Slug domain´ whose function remains to be elucidated. Snail1 repressor activity has been shown to be dependent on SNAG-mediated interaction with a repression complex formed by the corepressor mSin3a and histone deacetylases 1/2 (HDAC1/2). Importantly Snail1 transcription factor is further regulated through phosphorylation by various kinases. However, at date little is known about the control of Snail2 repressor activity. Here, we present interesting data shedding light into the regulation and function of Snail2 as a E-cadherin repressor. For this purpose we have performed ectopic expression of several Snail2 deletion mutants and examined the contribution of the specific domains to protein stability, localization and E-cadherin repressor activity. These data reveal a key role for the `Slug domain´ to repress E-cadherin expression. Furthermore, in vivo phosphorylation analysis revealed that specific phosphorylation on Snail2 protein is implicated in Snail2 function as a transcriptional repressor whose functional significance is currently being investigated. [less ▲]

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See detailFunctional Characterization of Snail2 repression complex
Molina Ortiz, Patricia ULg; MacPherson, Matthew; Cano, Amparo et al

Poster (2007, September 10)

Snail2, also called Slug, is a member of the Snail-family of zinc-finger transcription factors that plays a significant role both during development and carcinogenesis, by controlling epithelial ... [more ▼]

Snail2, also called Slug, is a member of the Snail-family of zinc-finger transcription factors that plays a significant role both during development and carcinogenesis, by controlling epithelial-mesenchymal transition (EMT) processes. Snail2 has been also described as a direct transcriptional repression of E-cadherin during EMT being implicated as a prosurvival factor during tumorogenesis. Snail1 and Snail2 are highly homologous factors, containing a common N-terminal transrepressor domain (SNAG), a C-terminus DNA binding domain of four (Snail1) or five (Snail2) zinc fingers, and a divergent central region, which in Snail2 is formed by a unique domain called `Slug domain´ whose function remains to be elucidated. Snail1 repressor activity has been shown to be dependent on SNAG-mediated interaction with a repression complex formed by the corepressor mSin3a and histone deacetylases 1/2 (HDAC1/2). Importantly Snail1 transcription factor is further regulated through phosphorylation by various kinases. However, at date little is known about the control of Snail2 repressor activity. Here, we present interesting data shedding light into the regulation and function of Snail2 as a E-cadherin repressor. For this purpose we have performed ectopic expression of several Snail2 deletion mutants and examined the contribution of the specific domains to protein stability, localization and E-cadherin repressor activity. These data reveal a key role for the `Slug domain´ to repress E-cadherin expression. Furthermore, in vivo phosphorylation analysis revealed that specific phosphorylation on Snail2 protein is implicated in Snail2 function as a transcriptional repressor whose functional significance is currently being investigated. [less ▲]

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See detailFunctional connectivity and dynamic causal modeling
Phillips, Christophe ULg

Scientific conference (2010, May 03)

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See detailFunctional connectivity and recognition of familiar faces in Alzheimer’s disease
Kurth, Sophie ULg; Bahri, Mohamed Ali ULg; Moyse, Evelyne ULg et al

in Frontiers in Human Neuroscience (2014)

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See detailFunctional connectivity in the default network during resting state is preserved in a vegetative but not in a brain dead patient.
Boly, Mélanie ULg; Tshibanda, Luaba ULg; Vanhaudenhuyse, Audrey ULg et al

in Human Brain Mapping (2009), 30(8), 2393-400

Recent studies on spontaneous fluctuations in the functional MRI blood oxygen level-dependent (BOLD) signal in awake healthy subjects showed the presence of coherent fluctuations among functionally ... [more ▼]

Recent studies on spontaneous fluctuations in the functional MRI blood oxygen level-dependent (BOLD) signal in awake healthy subjects showed the presence of coherent fluctuations among functionally defined neuroanatomical networks. However, the functional significance of these spontaneous BOLD fluctuations remains poorly understood. By means of 3 T functional MRI, we demonstrate absent cortico-thalamic BOLD functional connectivity (i.e. between posterior cingulate/precuneal cortex and medial thalamus), but preserved cortico-cortical connectivity within the default network in a case of vegetative state (VS) studied 2.5 years following cardio-respiratory arrest, as documented by extensive behavioral and paraclinical assessments. In the VS patient, as in age-matched controls, anticorrelations could also be observed between posterior cingulate/precuneus and a previously identified task-positive cortical network. Both correlations and anticorrelations were significantly reduced in VS as compared to controls. A similar approach in a brain dead patient did not show any such long-distance functional connectivity. We conclude that some slow coherent BOLD fluctuations previously identified in healthy awake human brain can be found in alive but unaware patients, and are thus unlikely to be uniquely due to ongoing modifications of conscious thoughts. Future studies are needed to give a full characterization of default network connectivity in the VS patients population. [less ▲]

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See detailFunctional degradable polymers for advanced drug delivery systems
Cajot, Sébastien; Riva, Raphaël ULg; Jérôme, Christine ULg

Conference (2012, September)

Nowadays, polymer micelles have attracted an increasing interest in pharmaceutical research because they could be used as efficient drug delivery systems. Micelles of amphiphilic block copolymers are ... [more ▼]

Nowadays, polymer micelles have attracted an increasing interest in pharmaceutical research because they could be used as efficient drug delivery systems. Micelles of amphiphilic block copolymers are supramolecular core-shell type assemblies of several tens of nanometers in diameter. In principle, the micelle core is usually constructed with biodegradable hydrophobic polymers such as aliphatic polyesters, e.g. poly(ε-caprolactone) (PCL), which serves as a reservoir for the incorporation of various lipophilic drugs. Water soluble poly(ethylene oxide) (PEO) is most frequently used to build the micelle corona because it is very efficient in preventing protein adsorption at surfaces and in stabilizing micelles in the blood compartment, making particles invisible to the body defense system. Even if micelles get a high stability in aqueous media thanks to their low critical micellar concentration, micelle dissociation is not always preserved when they are injected in the blood compartment. A way to provide the micelle stability during their administration is to cross-link them. Different kinds of cross-linked micelles can be investigated depending on the localization of the cross-linking. Shell cross-linked micelles or nanocage structures with a degradable core have the great advantage to reach drug encapsulation with a high loading rate. However, cross-linking the hydrophilic shell may affect the stealthiness of the carrier. Thus, we have designed reversibly cross-linked micelles by introducing the cross-linking bridges in the hydrophobic segment of the block copolymer, rather than in the hydrophilic one, leading so to more internal cross-linking and thus preserving the mobility of the hydrophilic segment. Three different localizations of the cross-linking has been targeted; (i) loose core cross-linking of a core-corona system, (ii) tight core cross-linking of a core-shell-corona system (the shell and the core being both hydrophobic and the corona hydrophilic) and (iii) tight shell cross-linking of a similar core-shell-corona system. To reach this goal, three types of amphiphilic copolymers have been used bearing pendent azide groups in the hydrophobic segment. These copolymers have been obtained by starting the ring-opening polymerization of ε-CL and a functional CL, either as a mixture or sequentially from a poly(ethylene oxide) macroinitiator leading to the three targeted architectures. The azide groups located along the PCL backbone have then been used to cross-link the micelles by the Huisgens cycloaddition with a bis-alkyne cross-linker. The choice of this cross-linker has also taken into account the requirement to make the cross-linking reversible. For that purpose, disulfide bridges have been selected in order to impart reversibility to the cross-linking by intracellular reduction. Indeed, the marked concentration difference of glutathione between extra- and intra-cellular environments has already been used to trigger drug release by intracellular disulfide bond cleavage. Accordingly, a bis-alkyne disulfide molecule has been chosen as cross-linker. The micellization and cross-linking of these amphiphilic azido macromolecules have been studied. The reversibility of the cross-linking in reductive environment and the cross-linked micelles stealthiness have been tested. [less ▲]

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See detailFunctional degradable polymers for advanced drug delivery systems
Jérôme, Christine ULg

Conference (2012, July 05)

Nowadays, polymer micelles have attracted an increasing interest in pharmaceutical research because they could be used as efficient drug delivery systems. Micelles of amphiphilic block copolymers are ... [more ▼]

Nowadays, polymer micelles have attracted an increasing interest in pharmaceutical research because they could be used as efficient drug delivery systems. Micelles of amphiphilic block copolymers are supramolecular core-shell type assemblies of several tens of nanometers in diameter. In principle, the micelle core is usually constructed with biodegradable hydrophobic polymers such as aliphatic polyesters, e.g. poly(ε-caprolactone) (PCL), which serves as a reservoir for the incorporation of various lipophilic drugs. Water soluble poly(ethylene oxide) (PEO) is most frequently used to build the micelle corona because it is very efficient in preventing protein adsorption at surfaces and in stabilizing micelles in the blood compartment, making particles invisible to the body defence system. Even if micelles get a high stability in aqueous media thanks to their low critical micellar concentration, micelle dissociation is not always preserved when they are injected in the blood compartment. A way to provide the micelle stability during their administration is to cross-link them. Different kinds of cross-linked micelles can be investigated depending on the localisation of the cross-linking. Shell cross-linked micelles or nanocage structures with a degradable core have the great advantage to reach drug encapsulation with a high loading rate. However, cross-linking the hydrophilic shell may affect the stealthiness of the carrier. Thus, we have designed reversibly cross-linked micelles by introducing the cross-linking bridges in the hydrophobic segment of the block copolymer, rather than in the hydrophilic one, leading so to more internal cross-linking and thus preserving the mobility of the hydrophilic segment. Three different localizations of the cross-linking has been targeted; (i) loose core cross-linking of a core-corona system, (ii) tight core cross-linking of a core-shell-corona system (the shell and the core being both hydrophobic and the corona hydrophilic) and (iii) tight shell cross-linking of a similar core-shell-corona system. To reach this goal, three types of amphiphilic copolymers have been used bearing pendent azide groups in the hydrophobic segment. These copolymers have been obtained by starting the ring-opening polymerization of ε-CL and a functional CL, either as a mixture or sequentially from a poly(ethylene oxide) macroinitiator leading to the three targeted architectures. The azide groups located along the PCL backbone have then been used to cross-link the micelles by the Huisgens cycloaddition with a bis-alkyne cross-linker. The choice of this cross-linker has also taken into account the requirement to make the cross-linking reversible. For that purpose, disulfide bridges have been selected in order to impart reversibility to the cross-linking by intracellular reduction. Indeed, the marked concentration difference of glutathione between extra- and intra-cellular environments has already been used to trigger drug release by intracellular disulfide bond cleavage. Accordingly, a bis-alkyne disulfide molecule has been chosen as cross-linker. The micellization and cross-linking of these amphiphilic azido macromolecules have been studied. The reversibility of the cross-linking in reductive environment and the cross-linked micelles stealthiness have been tested. [less ▲]

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See detailFunctional Development of Advanced Driver Assistance Systems by means of Driving Simulators
Christen, Fréderic ULg; Benmimoun, A.; Deutschle, S.

Poster (2008, April 16)

Der Beitrag beschreibt die Funktionsentwicklung von Fahrerassistenzsystemen an der Forschungsgesellschaft Kraftfahrwesen mbH Aachen (fka) und am Institut für Kraftfahrwesen (ika) der RWTH Aachen mittels ... [more ▼]

Der Beitrag beschreibt die Funktionsentwicklung von Fahrerassistenzsystemen an der Forschungsgesellschaft Kraftfahrwesen mbH Aachen (fka) und am Institut für Kraftfahrwesen (ika) der RWTH Aachen mittels Fahrsimulatoren. Dabei wird konkret auf die Entwicklung eines Kreuzungsassistenten sowie eines sogenannten KONVOI-Systems eingegangen. Beide Systeme wurden u.a. unter Verwendung des statischen Fahrsimulators InDriveS entwickelt. Der in diesem Beitrag vorgestellte Ansatz eines Kreuzungsassistenten basiert auf Kommunikation: Fahrzeug-Fahrzeug-Kommunikation (C2C) und Infrastruktur-Fahrzeug- Kommunikation (I2C). Hierfür wurden in der Verkehrsfluss- und Fahrsimulation verschiedene Systemvarianten betrachtet, um unterschiedliche Stufen der Systemkomplexität und unter- schiedliche Zeitrahmen für die Realisierung eines solchen Assistenten zu berücksichtigen. Jede dieser Systemvarianten wurde hinsichtlich deren Wirkung auf die Verkehrssicherheit bewertet. Daneben wurde auch die Benutzerakzeptanz unter Berücksichtigung verschiedener Mensch-Maschine-Schnittstellen betrachtet. Die Ergebnisse zeigen, dass die Kommunikationsreichweite der wichtigste Parameter für die Systemauslegung und -spezifikation darstellt. Für die Wirkung des Kreuzungsassistenten auf die Verkehrssicherheit ist in erster Linie der Ausrüstungsgrad entscheidend. Für die Benutzerakzeptanz ist die Detektionsrate von möglichen Konfliktsituationen und die Vermeidung von kritischen Situationen entscheidend. Das dargestellte KONVOI-System ermöglicht die Automatisierung von Nutzfahrzeugkolonnen auf Autobahnen. Neben der Funktionsentwicklung zur automatischen Abstandsregelung und Querführung werden in dem Projekt die Auswirkungen von KONVOIs auf den übrigen Verkehr analysiert und die bei den Fahrern auftretenden Belastungen und die Akzeptanz des Systems untersucht. Begleitend werden rechtliche Aspekte der kommerziellen Nutzung von Lkw-KONVOIs in Deutschland weiterentwickelt. Um die Komplexität der zu entwickelnden Lösungen zur Funktionserweiterung der Fahrzeuge zu bewältigen und eine hohe Zuverlässigkeit der Systeme zu gewährleisten, erfolgt die Systementwicklung mit Hilfe von Simulationswerkzeugen (MATLAB/Simulink, Stateflow, Verkehrsflusssimulation PELOPS und Lkw- Fahrsimulator InDriveS). Abschließend geht der Beitrag auf den neuen dynamischen Fahrsimulator der RWTH Aachen ein. [less ▲]

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See detailA Functional Diachronic Approach to Prolepsis: The Complementation of PCU Verbs in Ancient Egyptian
Grossman, Eitan; Polis, Stéphane ULg

Conference (2010, June 01)

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See detailFunctional distribution and dynamics of Arabidopsis SR splicing factors in living plant cells
Tillemans, Vinciane ULg; Dispa, Laurence ULg; Remacle, Claire ULg et al

in Plant Journal (The) (2005), 41(4), 567-582

Serine/arginine-rich (SR) proteins constitute an important class of splicing regulators in higher eukaryotes that share a modular structure consisting of one or two N-terminal RNA recognition motif (RRM ... [more ▼]

Serine/arginine-rich (SR) proteins constitute an important class of splicing regulators in higher eukaryotes that share a modular structure consisting of one or two N-terminal RNA recognition motif (RRM) domains and a C-terminal RS-rich domain. Herein, we have investigated the in vivo functional distribution of Arabidopsis SR factors. Agrobacterium-mediated transient transformation revealed nuclear speckled distribution and the overall colocalization of fluorescent protein (FP)-tagged SR factors in both tobacco and Arabidopsis cells. Their overall colocalization in larger nucleoplasmic domains was further observed after transcriptional and phosphorylation/dephosphorylation inhibition, indicating a close functional association between SR factors, independent of their phosphorylation state. Furthermore, we demonstrated in vivo the conserved role of the RS and RRM domains in the efficient targeting of Arabidopsis SR proteins to nuclear speckles by using a series of structural domain-deleted mutants of atRSp31 and atRSZp22. We suggest additional roles of RS domain such as the shuttling of atRSZp22 between nucleoplasm and nucleolus through its phosphorylation level. The coexpression of deletion mutants with wild-type SR proteins revealed potential complex associations between them. Fluorescence recovery after photobleaching demonstrated similar dynamic properties of SR factors in both tobacco transiently expressing cells and Arabidopsis transgenics. Cell cycle phase-dependent organization of FP-tagged SR proteins was observed in living tobacco BY-2 cells. We showed that atRSp31 is degraded at metaphase by fluorescence quantification. SR proteins also localized within small foci at anaphase. These results demonstrate interesting related features as well as potentially important differences between plant and animal SR proteins. [less ▲]

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See detailFunctional diversity of microbial communities associated to the mucus of scleractinians around Moorea (French Polynesia)
Ladrière, Ophélie ULg; Theunis, Laetitia; Wilmotte, Annick et al

Poster (2008, July 07)

Mucus production by scleractinians appears as an antifouling mechanism which prevents settlement of other organisms and accumulation of sediments on their surface. This Surface Muccopolysaccharide Layer ... [more ▼]

Mucus production by scleractinians appears as an antifouling mechanism which prevents settlement of other organisms and accumulation of sediments on their surface. This Surface Muccopolysaccharide Layer (SML) harbours dense populations of bacteria which play a paramount role in scleractinians nutrition, metabolism and good health maintenance. However, environmental disturbances can alter these microbiocenoses. Characterization of bacterial communities was carried out using a set of simple techniques that enable us to describe the state and functions of whole microbial communities associated with different hard coral species. Multi-comparisons have been performed on bacterial communities from open water, interstitial water, sedimentary interface and macro algae as well as between healthy and bleached colonies, and patches associated or not with Pomacentridae fishes. The functional study included measurements of bacterial biomass, respiration, oxydative and hydrolytic metabolisms. Non-Fungiidae corals and sedimentary interface have a quite similar bacterial biomass but open water, interstitial water and macro-algae are characterized by higher bacterial biomass. Bacterial respiration potential is similar on corals and at the sedimentary interface, but it is higher in interstitial water and lower in open water and for bacterial community associated with macro-algae. Hydrolytic activities are highest in SML. Bleached corals and patches associated with Pomacentridae fishes show more abundant bacteria, with higher respiration rate and higher hydrolytic activity than corals without fishes and healthy ones. In addition, bacteria of bleached corals display a higher division percentage, a higher growth rate and a lower turn-over time We confirmed that bleaching events or the presence of sedentary fishes modify the bacterial communities structure and affect relationships between coral, endosymbiotic algae, SML-associated microbial community and associated organisms. Such results highlight that SML-bacterial communities are modified by bleaching and raise the question of a potential protection of fishes against pathogens. [less ▲]

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See detailFunctional domains of the 67-kDa laminin receptor precursor.
Castronovo, Vincenzo ULg; Taraboletti, G.; Sobel, M. E.

in Journal of Biological Chemistry (1991), 266(30), 20440-6

We report the characterization of two functional domains of the metastasis-associated 67-kDa laminin receptor (67-LR). Using synthetic peptides deduced from the cDNA sequence of the 37-kDa precursor of ... [more ▼]

We report the characterization of two functional domains of the metastasis-associated 67-kDa laminin receptor (67-LR). Using synthetic peptides deduced from the cDNA sequence of the 37-kDa precursor of the laminin receptor (37-LRP) as well as their corresponding affinity-purified polyclonal antibodies, we identified a unique laminin binding site as well as a membrane-associated domain of the receptor. In laminin dot blot and solid phase radioligand assays, a 20 amino acid synthetic peptide (IPCNNKGAHSVGLMWWMLAR, amino acid residues 161-180, designated peptide G) specifically bound to laminin with high affinity (Kd = 5 x 10(-8) M). Peptide G also specifically eluted the 67-LR from a laminin affinity column. Peptide G and laminin reacted with a 1:1 stoichiometry, suggesting that there is one recognition site on laminin for the peptide G domain. Immunofluorescence studies, performed on permeabilized and nonpermeabilized human A2058 melanoma cells using 10 different affinity-purified antibodies to distinct regions of the 37-LRP, identified an unusually short membrane-associated domain that was consistent with a computer predicted transmembrane domain (residues 86-101). Our data demonstrate for the first time that the 37-LRP has two functional domains consistent with the characteristics of the mature 67-LR. Furthermore, we propose peptide G as a potential inhibitor of tumor cell interactions with laminin. [less ▲]

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See detailFunctional effects of a muscarinic receptor blockade during acute respiratory distress syndrome in double-muscled calves
Genicot, Bruno; Mouligneau, Frédéric; Close, Roland et al

in Veterinary Record : Journal of the British Veterinary Association (1994), 134(5), 110-113

Eighteen Belgian white and blue double-muscled calves suffering from the acute respiratory distress syndrome were studied. Fifteen of the calves inhaled ipratropium bromide (0.6 mg) four times a day for ... [more ▼]

Eighteen Belgian white and blue double-muscled calves suffering from the acute respiratory distress syndrome were studied. Fifteen of the calves inhaled ipratropium bromide (0.6 mg) four times a day for three to four days whereas the other three control calves inhaled sterile 0.9 per cent saline. All the animals were injected with ceftiofur sodium (1 mg/kg/day) for five days, the first injection being given one hour after the first inhalation of ipratropium bromide or saline. Arterial oxygen tension, alveolar arterial oxygen difference, carbon dioxide tension and arterial pH, respiratory and heart rates, oscillatory resistance and phase angle, measured by the mono-frequency forced oscillation technique, were recorded both before and one hour and 168 hours after the first inhalation. The measurement of oscillatory resistance and phase angle made it possible to resolve the impedance of the respiratory system into its real and imaginary components. The oscillatory compliance (Cosc) was determined from the imaginary component (Im). By one hour after the first inhalation of ipratropium bromide the oscillatory resistance was already significantly reduced and Im and Cosc had significantly increased, but the other parameters showed no significant improvement. However, between one hour and 168 hours after the first inhalation all the parameters reached physiological values. The control calves did not show any change. It was concluded that the pulmonary dysfunction associated with the acute respiratory distress syndrome in these calves was at least partly due to a severe bronchoconstriction. [less ▲]

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