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See detailEvidence for a role of heat shock factor 1 in inhibition of NF-kB pathway during heat shock response-mediated lung protection
Wirth, D.; Bureau, Fabrice ULg; Melotte, D. et al

in American Journal of Physiology - Lung Cellular and Molecular Physiology (2004), 287

Heat shock transcription factor (HSF)-1 is recognized as a central component of the heat shock response, which protects against various harmful conditions. However, the mechanisms underlying the ... [more ▼]

Heat shock transcription factor (HSF)-1 is recognized as a central component of the heat shock response, which protects against various harmful conditions. However, the mechanisms underlying the protection and the role of HSF-1 in these mechanisms have not yet been clearly elucidated. Using HSF-1 knockout mice (Hsf1_/_), we examined whether heat shock responsemediated lung protection involved an inhibition of the proinflammatory pathway via an interaction between HSF-1 and NF-_B, in response to cadmium insult. The HSF-1-dependent protective effect against intranasal instillation of cadmium (10 and 100 _g/mouse) was demonstrated by the higher protein content (1.2- and 1.4-fold), macrophage (1.6- and 1.9-fold), and neutrophil (2.6- and 1.8-fold) number in bronchoalveolar fluids, higher lung wet-to-dry weight ratio, and more severe lung damage evaluated by histopathology in Hsf1_/_compared with wild-type animals. These responses were associated with higher granulocyte/macrophage colony-stimulating factor (GMCSF; 1.7-fold) but not TNF-_ concentrations in bronchoalveolar fluids of Hsf1_/_ mice compared with those of wild-type animals, indicating that HSF-1 behaved as a repressor of specific cytokine production in our model. To further investigate the mechanism of GM-CSF repression, we analyzed the NF-_B activity and I_B stability. The DNA binding NF-_B activity, in particular p50 homodimer activity, was higher in Hsf1_/_ mice than in wild-type mice after cadmium exposure. These results provide a first line of evidence that mechanisms of lung protection depending on HSF-1 involve specific cytokine repression via inhibition of NF-_B activation in vivo. [less ▲]

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See detailEvidence for a role of microRNA-21 and microRNA-125b in negatively regulating angiogenic processes
Malvaux, Ludovic ULg

Doctoral thesis (2011)

Recently discovered, miRNAs have quickly become strong regulators of biological processes. These small non-coding RNAs of about 22 nucleotides partially base pair to the 3’UTR of the targeted mRNAs and ... [more ▼]

Recently discovered, miRNAs have quickly become strong regulators of biological processes. These small non-coding RNAs of about 22 nucleotides partially base pair to the 3’UTR of the targeted mRNAs and repress them. Due to their wide range effects, microRNAs were extensively studied in various diseases and were rapidly demonstrated to be deregulated in pathologies such as cancer. More recently, they have been shown to be implicated in vascular network formation (angiogenesis) and were proposed to be used in anti-angiogenic therapies. Nowadays about twenty angiomiRs have been discovered including the endothelial specific miR-126. As observed in several miRNA profiling of endothelial cells and confirmed in our laboratory in HUVECs (human umbilical veins endothelial cells), miR-21 and miR- 125b are highly expressed in this cell type suggesting that these miRNAs could play a role in vascular network formation. We then studied the implication of miR-21 and miR-125b in in vitro as well as in vivo angiogenesis. One of the most studied miRNA in cancer progression is miR-21 as it was shown to modify proliferating properties of numerous tumor cells. Our experiments revealed that miR-21 overexpression and inhibition have no direct effect on endothelial cells proliferation rate. However, miR-21 overexpression leads to the inhibition of HUVECs migration and tube formation as demonstrated in in vitro angiogenic assays. Moreover, opposite effects were observed upon miR-21 inhibition. We also confirmed that RhoB, a small Rho-GTPase implicated in stress fibers formation, is involved in these phenomena as RhoB inhibition using siRNA mimics miR-21 overexpression in endothelial cells. Moreover, miR-21 modulation affects RhoB mRNA and protein expressions. We further demonstrated a direct interaction between miR-21 and the RhoB 3’UTR confirming that miR-21 modulates angiogenesis partially through its effect on RhoB expression. A similar approach was used to study the implication of miR-125b in vascular network formation. In vivo, miR-125b expression was modulated in the zebrafish revealing that miR-125b expression needs to be controlled for proper intersomitic blood vessels establishment. In vitro, miR-125b overexpression decreases HUVECs migration and tube formation whereas miR-125b inhibition increases these functions. A transcriptomic analysis suggests that numerous adhesion molecules such as VE-cadherin or MCAM are involved in these processes. Furthermore, other proteins known to regulate angiogenesis such as the transcription factor ETS1 and the VEGFA receptor, VEGFR2 were also shown to be regulated by miR-125b. This observation confirms that miR-125b modulates angiogenic properties of endothelial cells. Finally, we investigated the impact of miR-21 and miR-125b overexpression in an in vivo pathological model of angiogenesis. In a mouse model of choroïdal neovascularization we demonstrated that miR-21 or miR-125b overexpression in the eyes of these mice decreases blood vessel establishment suggesting that these microRNAs could be used as therapeutic antiangiogenic agents. Taken together, the results presented in this thesis show that miR-21 and miR-125b regulate angiogenesis in vitro and in vivo. [less ▲]

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See detailEvidence for a role of prolactin fragments in corpus luteum function
Ricken, A.; Merkwitz, C.; Struman, Ingrid ULg et al

in The society for the study of reproduction Annual meeeting, Quebec 2005 (2005)

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See detailEvidence for a role of sleep in forgetting of irrelevant information
Collette, Fabienne ULg; Rauchs, Géraldine; Landeau, Brigitte et al

in NeuroImage (2009, June), 47(Suppl 1), 328-

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See detailEvidence for a role of the Simian Virus 40 in human breast carcinomas
Hachana, Mohamed Ridha ULg; Trimeche, Mounir; Ziadi, Sonia et al

in Breast Cancer Research and Treatment (2009), 113(1), 43-58

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See detailEvidence for a Second Receptor Binding Site on Human Prolactin
Goffin, Vincent; Struman, Ingrid ULg; Mainfroid, V. et al

in Journal of Biological Chemistry (1994), 269(51), 32598-606

The existence of a second receptor binding site on human prolactin (hPRL) was investigated by site-directed mutagenesis. First, 12 residues of helices 1 and 3 were mutated to alanine. Since none of the ... [more ▼]

The existence of a second receptor binding site on human prolactin (hPRL) was investigated by site-directed mutagenesis. First, 12 residues of helices 1 and 3 were mutated to alanine. Since none of the resulting mutants exhibit reduced bioactivity in the Nb2 cell proliferation bioassay, the mutated residues do not appear to be functionally necessary. Next, small residues surrounding the helix 1-helix 3 interface were replaced with Arg and/or Trp, the aim being to sterically hinder the second binding site. Several of these mutants exhibit only weak agonistic properties, supporting our hypothesis that the channel between helices 1 and 3 is involved in a second receptor binding site. We then analyzed the antagonistic and self-antagonistic properties of native hPRL and of several hPRLs analogs altered at binding site 1 or 2. Even at high concentrations (approximately 10 microM), no self-inhibition was observed with native hPRL; site 2 hPRL mutants self-antagonized while site 1 mutants did not. From these data, we propose a model of hPRL-PRL receptor interaction which slightly differs from that proposed earlier for the homologous human growth hormone (hGH) (Fuh, G., Cunningham, B. C., Fukunaga, R., Nagata, S., and Goeddel, D. V., and Well, J. A. (1992) Science 256, 1677-1680). Like hGH, hPRL would bind sequentially to two receptor molecules, first through site 1, then through site 2, but we would expect the two sites of hPRL to display, unlike the two binding sites of hGH, about the same binding affinity, thus preventing self-antagonism at high concentrations. [less ▲]

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See detailEvidence For a Self-Enrichment Process in Galactic Halo Globular Clusters
Parmentier, G.; Jehin, Emmanuel ULg; Magain, Pierre ULg et al

in Grebel, E.; Bradner, W. (Eds.) Modes of Star Formation and the Origin of Field Populations (2002)

Not Available

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See detailEvidence for a sharp structure variation inside a red-giant star
Miglio, Andrea ULg; Montalban Iglesias, Josefa ULg; Carrier, F. et al

in Astronomy and Astrophysics (2010), 520

Context. The availability of precisely determined frequencies of radial and non-radial oscillation modes in red giants is finally paving the way for detailed studies of the internal structure of these ... [more ▼]

Context. The availability of precisely determined frequencies of radial and non-radial oscillation modes in red giants is finally paving the way for detailed studies of the internal structure of these stars. <BR /> Aims: We look for the seismic signature of regions of sharp structure variation in the internal structure of the CoRoT target HR 7349. <BR /> Methods: We analyse the frequency dependence of the large frequency separation and second frequency differences, as well as the behaviour of the large frequency separation obtained with the envelope auto-correlation function. <BR /> Results: We find evidence for a periodic component in the oscillation frequencies, i.e. the seismic signature of a sharp structure variation in HR 7349. In a comparison with stellar models we interpret this feature as caused by a local depression of the sound speed that occurs in the helium second-ionization region. Using solely seismic constraints this allows us to estimate the mass (M = 1.2[SUB]-0.4[/SUB][SUP]+0.6[/SUP] M_&sun;) and radius (R = 12.2[SUB]-1.8[/SUB][SUP]+2.1[/SUP] R_&sun;) of HR 7349, which agrees with the location of the star in an HR diagram. [less ▲]

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See detailEvidence for a specific impairment of serial order short-term memory in dyslexic children
Martinez Perez, Trecy ULg; Majerus, Steve ULg; Mahot, Aline et al

in Dyslexia : The Journal of the British Dyslexia Association (2012), 18(2), 94-109

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See detailEvidence for an own-age bias in age estimation from voices in older persons
Moyse, Evelyne ULg; Beaufort, Aline ULg; Brédart, Serge ULg

in European Journal of Ageing (2014)

Previous studies have investigated the effect of ageing on age estimation from faces as well as the occur- rence of an own-age bias in such age estimation from faces. To the best of our knowledge, the ... [more ▼]

Previous studies have investigated the effect of ageing on age estimation from faces as well as the occur- rence of an own-age bias in such age estimation from faces. To the best of our knowledge, the occurrence of an own age effect on age estimation from voices has never been examined earlier using an experimental design in which the age of participants (young vs. old) and the age of voice stimuli (young vs. old) were crossed. Results revealed an own-age bias in older adults only. In comparison with younger adults, older participants showed age estimation abilities that are preserved for voices from their own age group and impaired for younger voices. This own age bias was absent in younger participants. [less ▲]

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See detailEvidence for association between the HLA-DQA locus and abdominal aortic aneurysms in the Belgian population: a case control study.
Ogata, Toru; Gregoire, Lucie; Goddard, Katrina A B et al

in BMC Medical Genetics (2006), 7

BACKGROUND: Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the ... [more ▼]

BACKGROUND: Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with HLA polymorphisms. METHODS: HLA-DQA1, -DQB1, -DRB1 and -DRB3-5 alleles were determined in 387 AAA cases (180 Belgian and 207 Canadian) and 426 controls (269 Belgian and 157 Canadian) by a PCR and single-strand oligonucleotide probe hybridization assay. RESULTS: We observed a potential association with the HLA-DQA1 locus among Belgian males (empirical p = 0.027, asymptotic p = 0.071). Specifically, there was a significant difference in the HLA-DQA1*0102 allele frequencies between AAA cases (67/322 alleles, 20.8%) and controls (44/356 alleles, 12.4%) in Belgian males (empirical p = 0.019, asymptotic p = 0.003). In haplotype analyses, marginally significant association was found between AAA and haplotype HLA-DQA1-DRB1 (p = 0.049 with global score statistics and p = 0.002 with haplotype-specific score statistics). CONCLUSION: This study showed potential evidence that the HLA-DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs. [less ▲]

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See detailEvidence for atypical categorical speech perception in Williams syndrome.
Majerus, Steve ULg; Poncelet, Martine ULg; Bérault, Aurélie et al

in Journal of Neurolinguistics (2011), 24

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See detailEvidence for basement membranes in rat tail tendon sheaths.
Guizzardi, S.; Foidart, Jean-Michel ULg; Leonardi, L. et al

in Basic and Applied Histochemistry (1987), 31(2), 177-81

The presence of anti-laminin antibodies and a basement membrane-like thin electrondense lamina has been demonstrated in the peritendineum of the rat tail tendon by indirect immunofluorescence and electron ... [more ▼]

The presence of anti-laminin antibodies and a basement membrane-like thin electrondense lamina has been demonstrated in the peritendineum of the rat tail tendon by indirect immunofluorescence and electron microscopy. [less ▲]

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See detailEvidence for behavioral sensitization to cocaine in preweanling rat pups
Wood, R. D.; Tirelli, Ezio ULg; Snyder, K. J. et al

in Psychopharmacologia (1998), 138(2), 114-123

Sought to determine whether promoting context-dependent sensitization might facilitate expression of sensitization in preweanlings. Sprague-Dawley rats were injected daily from postnatal day 14 to ... [more ▼]

Sought to determine whether promoting context-dependent sensitization might facilitate expression of sensitization in preweanlings. Sprague-Dawley rats were injected daily from postnatal day 14 to postnatal day 20 with 0, 5, 15, or 30 mg/kg cocaine hydrochloride and placed for 30 min in either the experimental chamber or home cage. On postnatal day 21 (test day), Ss were challenged with either 15 mg/kg cocaine or saline prior to placement in the experimental chamber. Significant sensitization of cocaine-induced stereotyped head movements was evident in animals given 15 or 30 mg/kg chronically in the experimental chamber, but not when these same doses were given in the home cage. Less consistent evidence for cocaine-induced sensitization was seen when examining locomotion, although trends for sensitization of this behavior were seen in animals chronically injected in either the test chamber or home cage. Thus, preweanlings can exhibit cocaine sensitization, particularly in terms of stereotypy, when tested shortly after the chronic exposure period, with expression of this sensitization being facilitated by pairing the chronic injections with the test context. ((c) 1998 APA/PsycINFO, all rights reserved) [less ▲]

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See detailEvidence for cooperative effects in the exchange reaction catalysed by the oxoglutarate translocator of rat-heart mitochondria.
Sluse, Francis ULg; Sluse-Goffart, Claudine; Duyckaerts, Claire ULg et al

in European Journal of Biochemistry (1975), 56(1), 1-14

The initial rates of the exchange external oxoglutarate/internal malate through the inner membrane of rat-heart mitochondria, for various concentrations of the two substrates, have been reinvestigated for ... [more ▼]

The initial rates of the exchange external oxoglutarate/internal malate through the inner membrane of rat-heart mitochondria, for various concentrations of the two substrates, have been reinvestigated for an extended range of concentrations of the external oxoglutarate. This has been made possible by use of the inhibitor-stop technique that allows 100 times smaller incubation times than the centrifugation-stop technique used previously. Under the experimental conditions the uptake of the external-labelled oxoglutarate into the mitochondrial-matrix space is mediated by the oxoglutarate translocator performing a ono-to-one exchange of the anions oxoglutarate (external) and malate (internal). Two intermediary-plateau regions are observed in the kinetic saturation curve of the translocator by the external oxoglutarate, revealing a complex rate equation which is found to be the product of two one-substrate functions. Analysing these features it is shown that the model, proposed earlier, of a "double carrier" as catalyst in a rapid-equilibrium random bi-bi mechanism, is still applicable but that several external binding sites have to be considered. As already noticed the external and the internal substrates bind to their respective sites independently of each other. Furthermore, some additional requirements imposed by the observed kinetics suggest that the exchange reaction is performed by only one translocator species made of identical interacting subunits. The anion exchange is tentatively viewed as a rotation of a subunit around an axis situated in the plane of the membrane after two independent local configuration changes induced by the binding of the two substrates on this subunit. [less ▲]

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See detailEvidence for cross-talk between the LH receptor and LH during implantation in mice
Gridelet, Virginie ULg; Tsampalas, Marie; Berndt, Sarah et al

in Reproduction, Fertility and Development (2013), 25

The present study investigated the first interaction that occurs between the blastocyst and endometrium during implantation. Given the ethical objections to studying implantation in humans, a mouse model ... [more ▼]

The present study investigated the first interaction that occurs between the blastocyst and endometrium during implantation. Given the ethical objections to studying implantation in humans, a mouse model was used to study the dialogue between luteinising hormone (LH) and luteinising hormone receptor (LHCGR). Several studies performed on LHCGR-knockout mice have generated controversy regarding the importance of the dialogue between LH and LHCGR during implantation. There has been no demonstration of a bioactive LH-like signal produced by the murine blastocyst. The first aim of the present study was to examine and quantify, using radioimmunoassay, the generation of a bioactive LH signal by the murine blastocyst. We went on to examine and quantify endometrial Lhcgr expression to validate the mouse model. Expression of LHCGR in mouse uteri was demonstrated using immunohistochemistry and western blot analysis. To quantify the expression of Lh in the mouse blastocyst and Lhcgr in the endometrium, reverse transcription–polymerase chain reaction (RT-PCR) and real-time quantitative (q) RT-PCR were performed. The results demonstrate that Lhcgr expression in BALB/c mouse endometrial epithelium is increased at the time of implantation and indicate that LHCGR may contribute to the implantation process. In support of this hypothesis, we identified a bioactive LH signal at the time of murine blastocyst implantation. [less ▲]

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See detailEvidence for decoupling of atmospheric CO2 and global climate during the Phanerozoic eon
Veizer, J.; Godderis, Y.; François, Louis ULg

in Nature (2000), 408(6813), 698-701

Atmospheric carbon dioxide concentrations are believed to drive climate changes from glacial to interglacial modes', although geological(1-3) and astronomical(4-6) mechanisms have been invoked as ultimate ... [more ▼]

Atmospheric carbon dioxide concentrations are believed to drive climate changes from glacial to interglacial modes', although geological(1-3) and astronomical(4-6) mechanisms have been invoked as ultimate causes. Additionally, it is unclear(7,8) whether the changes between cold and warm modes should be regarded as a global phenomenon, affecting tropical and high-latitude temperatures alike(9-13), or if they are better described as an expansion and contraction of the latitudinal climate zones, keeping equatorial temperatures approximately constant(14-16). Here we present a reconstruction of tropical sea surface temperatures throughout the phanerozoic eon (the past similar to 550 Myr) from our database(17) of oxygen isotopes in calcite and aragonite shells. The data indicate large oscillations of tropical sea surface temperatures in phase with the cold-warm cycles, thus favouring the idea of climate variability as a global phenomenon. But our data conflict with a temperature reconstruction using an energy balance model that is forced by reconstructed atmospheric carbon dioxide concentrations(18). The results can be reconciled if atmospheric carbon dioxide concentrations were not the principal driver of climate variability on geological timescales for at least one-third of the Phanerozoic eon, or if the reconstructed carbon dioxide concentrations are not reliable. [less ▲]

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See detailEvidence for distinct roles for basal ganglia and SMA in automatic and unconscious inhibition of voluntary actions
D'Ostilio, Kevin ULg; Garraux, Gaëtan ULg

Poster (2009, June)

Introduction: Although previous research highlighted the importance of automatic and unconscious inhibition in motor control, the neural correlates of such processes remain unclear. Basal ganglia ... [more ▼]

Introduction: Although previous research highlighted the importance of automatic and unconscious inhibition in motor control, the neural correlates of such processes remain unclear. Basal ganglia dysfunctions have long been associated with impairment in automatic motor control. In addition, Sumner & al. (2007) suggested a key role of the medial frontal cortex by administrating a masked priming task (e.g., Eimer & Schlaghecken 2003) to a patient with a small lesion restricted to the supplementary motor area (SMA)., Here, we used fMRI in normal subjects to better delineate the respective roles of SMA and basal ganglia in automatic and unconscious motor inhibition. Methods: We used event-related BOLD fMRI at 3T to record brain activity in 26 healthy volunteers (22 ± 2 years) as they performed the subliminal masked priming task. In this visuomotor task, participants are asked to make speeded button presses with the left or right hand following leftward or rightward pointing arrows, which are preceded by masked prime arrows. Here, two experimental variables were manipulated: the interval between the mask and the target (SOA: 0,100,150,200 or 250 ms) and the prime/target direction (compatible or incompatible). Imaging data processing and analysis were performed using SPM8b. Results: using Repeated Measures ANOVA of behavioral data (global interaction SOA*compatibility, p<0.0000001), we replicated the masked priming effects showing faster reaction times (i.e., motor response facilitation) in compatible than incompatible trials at 0-SOA (positive compatibility effect: diff = 21 ms, linear contrast : p<0.0000001) and the reverse (negative compatibility effect) at 100 (diff = -12 ms, p= 0.01) and 150-SOA (diff= -12 ms, p= 0.008) suggesting motor response inhibition. At 200 & 250 SOA, we no longer found significant compatibility effects (p>0.05) By applying a similar statistical model to imaging data, we observed a stronger activity in the in several regions, the SMA (p<0.001, uncorrected), caudate (p=0.002, uncorrected) and thalamus (p<0.001, uncorrected) showing stronger activity in compatible than incompatible trials at 100 and 150-SOA, as compared with 0-SOA. Moreover, the differential activity in the SMA was correlated with the negative compatibility effect (p= 0.01). When testing for a main effect of SOAs we didn’t find a differential activation of the SMA, but a stronger deactivation of the caudate (p=0.009, uncorrected) and the thalamus (p=0.007, uncorrected) at 100-150 SOA (inhibition conditions) compared to 0-SOA (facilitation condition). In a prime identification task administered after the fMRI experiment, subjects’ performance was at chance levels for primes displayed for 17 ms as in the main study, suggesting that the prime was not consciously perceived. Conclusions: These new findings suggest that automatic and unconscious inhibition of an activated motor response is mediated by the basal ganglia whereas medial frontal regions seem to be more implicated in the control of response conflict related to inhibition. [less ▲]

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See detailEvidence for enhanced inflammatory cell activity, ICAM-1 expression and eosinophil chemotactic activity in the sputum of asthmatics.
Louis, Renaud ULg; Shute, J.; Biaggi, S. et al

in American Journal of Respiratory & Critical Care Medicine (1997), 155(2), 466-472

We have applied the technique of sputum induction by hypertonic saline in asthmatics and nonatopic control subjects to study an array of indices of airway inflammation believed to be relevant to asthma ... [more ▼]

We have applied the technique of sputum induction by hypertonic saline in asthmatics and nonatopic control subjects to study an array of indices of airway inflammation believed to be relevant to asthma pathogenesis. Compatible with a central role for eosinophils and mast cells in asthma, sputum of asthmatic subjects contained increased numbers of eosinophils and levels of eosinophil cationic protein (ECP) and mast cell tryptase. Eosinophil numbers, and ECP and histamine levels correlated with the degree of methacholine airways responsiveness, and ECP, tryptase, and histamine correlated with raised concentrations of albumin. Using the micro-Boyden chamber technique eosinophil chemotactic activity was identified only in the sputum from asthmatics. The correlation between the raised levels of total IgA, IL- 8/IgA complexes, and tryptase and the degree of sputum eosinophilia and ECP levels, suggests possible mechanisms for eosinophil chemotaxis and activation in asthma. Row cytometric analysis of sputum lymphocytes showed an increase in CD4+ T cells and T cells expressing intercellular adhesion molecule-1 (ICAM-1) in asthma which, together with the finding of raised levels of soluble ICAM-1 in the sputum, indicates upregulation of this adhesion molecule. Finally, the proportion of CD16+ natural killer (NK) cells was reduced in the sputum of asthmatics. These observations highlight the importance of the airway inflammation in causing asthma and further confirm the usefulness of sputum induction as a tool in asthma research. [less ▲]

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See detailEvidence for Expansion of Host-derived CMV-specific CD8+ T cells after Allogeneic Transplantation with Non-Myeloablative Conditioning
MENTEN, Catherine ULg; Castermans, E.; Hannon, Muriel ULg et al

in Belgian Journal of Hematology (2012), Abstracts book(Supplement of 27th General Meeting of the Belgian Hematological Society), 16

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