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See detailL'implication dans la recherche clinique : un chemin vers la psychanalyse
Naziri, Despina ULg

in Revue Belge de Psychanalyse (2002), 40

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See detailImplication de la clusterine dans la survie des cellules prostatiques lors de l'apoptose
Ammar, Hayet ULg

Doctoral thesis (2014)

Prostate cancer is the second leading cause of cancer death in men. Although androgen ablation remains the most effective management option, most patients with advanced disease progress to castration ... [more ▼]

Prostate cancer is the second leading cause of cancer death in men. Although androgen ablation remains the most effective management option, most patients with advanced disease progress to castration resistant prostate cancer (CRPC), within two years of treatment. This results, in part, from the increase in the anti-apoptotic molecules expression following androgen withdrawal. Among the proteins involved in this phenomenon, clusterin, also known as testosterone repressed message-2 (TRPM- 2), which exists in two forms: a pro-apoptotic nuclear form (nClU) and a secreted survival factor (sClU). In our study we investigated the role of the secreted form of clusterin in preventing cells from TNFα-induced apoptosis. For this, we first generated a sCLU inducible stable prostatic cancer MLL rat cell line by using the Tet-On gene expression system. With this model we revealed a new mechanism by which sCLU promotes survival in androgenindependent prostate cancer cells, implicating its receptor megalin and the Akt survival pathway. By applying a comparative proteomic analysis in the androgen-independent epithelial cell line MLLTet-sClu induced to overexpress sClu or non induced control-cells, we identified five proteins known to play a role in cancer. These proteins candidates are heat shock proteins Hsp90 and Hsp70, osteopontin (bone sialoprotein, OPN), proliferating cell nuclear antigen (PCNA) and ADP-ribosylation factor 1 (Arf1). Altogether, our data provide new mechanistic insight in sCLU dependent activation of the major survival pathway upregulated in refractory prostate cancer. The identification of the new sCLU protein targets open new avenues for more research to elucidate the significance of clusterin in prostate cancer progression and resistance to therapy. [less ▲]

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See detailImplication de la compétition pour les acides aminés dans le contrôle biologique de la pourriture bleue des pommes en post-récolte
Krimi Bencheqroun, S.; Bajji, M.; Labhilili, M. et al

Conference (2008, April)

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See detailImplication de la dipeptidyl peptidase IV dans l’insuffisance cardiaque expérimentale et clinique
Gomez Malaver, Nelson ULg

Doctoral thesis (2012)

BNP1-32 is a cardiac hormone showing cardiac and renal protection. Paradoxically, in overt congestive heart failure, high levels of plasma BNP seem devoid of biological effectiveness. Moreover, treatments ... [more ▼]

BNP1-32 is a cardiac hormone showing cardiac and renal protection. Paradoxically, in overt congestive heart failure, high levels of plasma BNP seem devoid of biological effectiveness. Moreover, treatments targeting the BNP system are less effective in dogs with severe heart failure than in healthy dogs or dogs in mild heart failure. The origin of this paradox is not yet clear. Dipeptidyl peptidase IV (DPP4) is an ubiquitary exopeptidase that cleaves small peptides having a proline or an alanine in the N-terminal second position. Human BNP1-32 is a known substrate for DPP4, its second amino acid is a proline and this structure is conserved among several species including the pig and the dog. In dogs, BNP3-32, coming from the cleavage of BNP1-32 by DPP4, shows reduced biological activity. We made 2 hypotheses: (1) in canine congestive heart failure, increased DPP4 activity participates in the “resistance to BNP” and (2) in a pig model of tachycardiomyopathy, inhibition of DPP4 reduces cardiorenal dysfunction increases the effectiveness of exogenous BNP1-32 and decreases myocardial molecular alterations. In the first study, we identified physiologic determinants of plasma DPP4 activity and evaluated DPP4 activity in dogs in heart failure. Population included 81 healthy dogs and 47 dogs at different stages of heart failure. Plasma DPP4 activity was higher in healthy growing dogs than in healthy adults. In healthy adults, DPP4 activity was positively correlated with body weight with no effect of age, sex and of circadian rhythm. DPP4 activity was higher in dogs in asymptomatic cardiac insufficiency than in healthy dogs and in dogs in congestive heart failure without any effect of the disease. In the second study, a tachycardiomyopathy was induced in 12 pigs by rapid right ventricular pacing. Sitagliptin, an oral inhibitor of DPP4, was administered in half of the pigs. In this model, inhibition of plasma DPP4 activity improved global cardiac function, maintained glomerular filtration rate and, increased cardiac contractility during BNP perfusion. Functional improvement was associated with a reduction of myocardial gene expression of calmoduline, sodium-calcium exchanger, BNP and interleukin-6 as well as an increase in myocardial SDF-1 protein concentration. In conclusion, the “BNP resistance” observed in congestive heart failure is not due to increased plasma DPP4 activity but DPP4 inhibition reduces cardiorenal alterations in experimental myocardial failure. DPP4 inhibitors have been developed for treatment of type 2 diabetes. It remains to be studied (1) if this treatment, initially targeted to control glycemia, may protect the heart and the kidney in patients with type 2 diabetes with or without metabolic syndrome (2) if this treatment may be used to treat heart failure and the cardiorenal syndrome. [less ▲]

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See detailImplication de la neurohypophyse dans le stress psychique
Scantamburlo, Gabrielle ULg; Ansseau, Marc ULg; Legros, Jean-Jacques ULg

in Encéphale (L') (2001), 27(3, May-Jun), 245-59

Effects of different psychological stimuli on oxytocin (OT) and vasopressin (AVP) secretion are reviewed in animals and in humans. The secretion of neuropituitary hormones is also discussed in various ... [more ▼]

Effects of different psychological stimuli on oxytocin (OT) and vasopressin (AVP) secretion are reviewed in animals and in humans. The secretion of neuropituitary hormones is also discussed in various psychiatric diseases such an anorexia nervosa, bipolar disorder, schizophrenia and obsessive-compulsive disorder. AVP and OT are secreted into the hypophyseal portal circulation by neurons which project from the paraventricular nucleus to the external zone of the median eminence. AVP and OT-containing neurons in the suprachiasmatic and paraventricular nuclei project to limbic areas, including the hippocampus, the subiculum, the ventral nucleus of the amygdala and the nucleus of the diagonal band. Specific AVP receptors which are pharmacologically different from the pressor and antidiuretic AVP receptors have been found in the anterior pituitary. OT receptors have been identified in a variety of forebrain sites. The neurohypophyseal secretion is regulated by the cholinergic muscarinic, histaminergic and beta-adrenergic systems. Stress alters the secretion of one or more of the hypothalamic factors which interact at the pituitary to increase the secretion of ACTH. AVP and OT have been shown to modulate the effect of Corticotropin-Releasing Factor (CRF) on ACTH secretion and appear to play a key role in mediating the ACTH response to stress. Although AVP is a relatively weak secretagogue for ACTH, it markedly potentiates the activity of CRF both in vitro and in vivo. The role of OT is more complex. In vitro, OT stimulates ACTH release at high doses whereas in human it inhibits ACTH secretion at low doses. The type of stressor appear to determine the relative importance of these secretatogues in ACTH response. Several recent studies indicate that psychological stressors display a similar degree of variety of secretagogue release patterns as was found earlier for physical stressors. A bewildering array of technique produces a bewildering array of conclusions. In rats, OT may be an important secretagogue during a novel stimulus, whereas the role for AVP is less clear. Indeed two studies out of ten suggest a stimulating role for AVP. In response to frustration and submission, OT and AVP are secreted. Regarding social isolation, results are difficult to interpret and the role of AVP could be species-dependent. In contrast plasma OT levels do not change. After restraint, ACTH release is primarily mediated by the active increase of OT and AVP does not appear to play a role. When restraint is associated with moderate levels of physical components and during immobilisation, all two secretagogs are involved in the ACTH response. With fear, ACTH response appears to be driven by OT. In humans, one study indicates that high emotionality women increase plasma OT in response to uncontrollable noise. Various neuroendocrine dysregulations have been observed in psychiatric disease. Either an increase or a decrease of the hypothalamic-pituitary-adrenal (HPA) function have been described in several illnesses. Effects of OT appear to be reciprocal to the effects of AVP. OT has been called the "amnestic" neuropeptide due to its capacity to attenuate memory consolidation and retrieval. AVP exhibits a central activating action on mood, memory and selective attention. Underweight patients with anorexia nervosa have abnormally high levels of centrally directed AVP and reduced OT levels. These modifications could enhance the retention of cognitive distortions of aversive consequences of eating. Patients with bipolar disorder show a biphasic secretion of AVP. Depressive episodes are associated with decreased vasopressinergic activity whereas manic episodes involve an increased release. AVP might be responsible for an increased catecholamine activity. In addition, lithium could act as an antagonist to AVP. In schizophrenic patients, studies using the apomorphine stimulation suggest increased oxytoninergic and decreased vasopressinergic functions. These findings are consistent with the beneficial role of AVP on schizophrenic symptoms noted in several trials. The increased OT could be responsible for "positive" symptomatology such as delusions and hallucinations. Obsessive compulsive disorder (OCD) includes a range of cognitive and behavioral disturbances that could be influenced by OT. In animals, several studies have emphasized the role of AVP in promoting repetitive grooming behaviors and maintaining conditioned response to aversive stimuli. In OCD patients, one study have reported that AVP/OT ratio was negatively correlated with symptom severity. However, an independent report found similar AVP concentrations in OC patients without a personal or family history of tic disorder and in normal subjects. Whether these modifications are only a consequence of the central disturbances or whether those peptides could participate in the pathogenesis of these affections remains to be elucidated. [less ▲]

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See detailImplication de la protéine transmembranaire d’enveloppe du virus de la leucémie bovine dans la fusion cellulaire et l’infectivité virale.
GATOT, Jean-Stéphane ULg; Callebaut, Isabelle; Mornon, Jean-Paul et al

in Séminaire de la Recherche Télévie (1999, March 16)

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See detailImplication de la sous-famille Erg des facteurs de transcription Ets dans la régulation de l'épissage chez l'Homme
Vincent, Côme ULg

Master's dissertation (2013)

The human family of Ets proteins and the Erg subfamily composed of 3 members (ERG, FLI1 and FEV) are known as transcription factors, involved in many cellular processes. On the other hand, most protein ... [more ▼]

The human family of Ets proteins and the Erg subfamily composed of 3 members (ERG, FLI1 and FEV) are known as transcription factors, involved in many cellular processes. On the other hand, most protein-coding genes contain intervening sequences (introns) that must be precisely removed from pre-mRNA through the process of pre-mRNA splicing. The first aim of this project was to molecularly characterise the link between these two actors. To achieve this goal, three different approaches were used. Firth, the link between the Erg subfamily and nuclear speckles, subnuclear structures that are enriched in pre-mRNA splicing factors, was studied using immunofluorescence and confocal microscopy, then an MS2-tethering assay was performed and finally, endogenous targets whose splicing would be dependent on this subfamily were identified. The results of these approaches highlighted interconnectivity between gene expression machineries. Moreover, such understanding of molecular basis of cancer-involved proteins provide new possibilities for earlier detection as well as better diagnosis, prevention and novel treatment strategies. [less ▲]

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See detailImplication des cellules Natural Killer (NK) dans le développement des lésions associées à l'infection par les papillomavirus humains (HPV)
Renoux, Virginie ULg

Doctoral thesis (2011)

Persistent infections with high-risk papillomavirus (HPV) are associated with more than 25% of cancers induced by infectious agents. Nevertheless, the two vaccines preventing HPV infection have no ... [more ▼]

Persistent infections with high-risk papillomavirus (HPV) are associated with more than 25% of cancers induced by infectious agents. Nevertheless, the two vaccines preventing HPV infection have no therapeutic efficacy and it has been estimated that there will be no measurable decline of HPV-associated tumours before 2040. The immune system is able to control, at least partially, HPV infection and subsequent tumour development. Around 90% of HPV-infected women will clear the virus within two years, but the immune effectors responsible for this viral clearance are unknown. Hence, the aim of this study was to determine if Natural Killer (NK) cells could play a role in the immune response against HPV infection and related cancers. The first part of this work was focused on the in vitro interaction of NK cells with L1 and L1L2 Virus Like Particles (VLP) of HPV16. We observed that, in the presence of HPV-VLP, NK cells displayed a higher cytotoxic activity against HPV+ cells by increasing the exocytosis of their cytotoxic granules and by secreting TNF-α and IFN-γ. NK cell activation was correlated with a fast entry of HPV-VLP by macropinocytosis and we determined that cell surface CD16 expression was necessary for HPV internalization, but also for degranulation and cytokine production. In the second part, to understand the molecular mechanisms of HPV-VLP stimulation, we investigated the signalling pathways operating in NK cells to trigger their cytotoxic activity in the presence of viral particles. We observed that the MAP kinases ERK and p38 were phosphorylated in the presence of both L1 and L1L2 HPV-VLP. Using specific inhibitors, we demonstrated that phosphorylation of these MAPK was required for degranulation and cytokine secretion by NK cells in the presence of VLP. In conclusion, NK cell activity could be an important player in the immune response contributing to viral clearance and to regression of HPV-induced cervical lesions. [less ▲]

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See detailImplication des hormones de croissance et du système CD95/CD95-ligand dans la tolérance fœto-placentaire
Thellin, Olivier ULg

Doctoral thesis (1999)

We attempted here to contribute to the study of 2 hypothesis concerning mechanisms implicated in the foeto-tolerance phenomenon. The first hypothesis concerned the potential effects of the replacement of ... [more ▼]

We attempted here to contribute to the study of 2 hypothesis concerning mechanisms implicated in the foeto-tolerance phenomenon. The first hypothesis concerned the potential effects of the replacement of the pituitary growth hormone (hGH-N) by the placental growth hormone (hPGH) on the maternal immune system. We mainly performed a preliminary study of these effects in the man and in the non-pregnant woman in order to transpose the obtained results to the pregnant woman. We have also analyzed the expression of the hGH-N receptor, which can be bound by both hGH-N and hPGH, on the surface of a wide variety of cell types and sub-types, activated or not, which had never been done in a single study before. We showed notably that, among the stydied cell types, the expression of hGH-N-R was mainly performed by activated T cells, by activated or non-activated B cells and by monocytes. Lowly differentiated cells could express more hGH-N-R, which is supported by published data suggesting that immature cells (hematopoietic bone marrow and thymus) are particularly sensitive to hGH-N. However, the activation of lymphoid cells, mainly T lymphocytes, by mitogens increases the expression of hGH-N-R. The comparative study of the effects of hGH-N and hPGH on cells from the human immune system had never been performed before. Our tests performed by the introduction of growth hormones at physiological concentrations in the culture medium of lymphoif cells indicates that their effect on the cell proliferation is equivalent. [less ▲]

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See detailImplication des intolérances et allergies alimentaires dans le syndrome du côlon irritable: quelles sont les evidences?
Ausloos, Floriane ULg; Belaiche, Jacques ULg; Louis, Edouard ULg

in Revue Médicale de Liège (2005), 60(9), 744-9

Irritable Bowel Syndrome (IBS) is a complex and heterogeneous entity that concerns about 1/4 of adults and would be responsible for 50% of gastro-enterology medical consultations. IBS etiopathogenesis and ... [more ▼]

Irritable Bowel Syndrome (IBS) is a complex and heterogeneous entity that concerns about 1/4 of adults and would be responsible for 50% of gastro-enterology medical consultations. IBS etiopathogenesis and physiopathology are not yet fully known. [less ▲]

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See detailImplication des mécanismes d’apprentissage de régularités dans l’acquisition du langage chez l’enfant sain et dysphasique
Gabriel, Audrey ULg; Urbain, Charline

in C. Maillart, M.-A. Schelstraete (Ed.) Les dysphasies : de l’évaluation à la rééducation (2012)

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See detailL'implication des médecins généralistes dans la gestion des abus de substances
Ketterer, Frédéric ULg; Symons, Linda; Lambrechts, Marie-Claire et al

Conference (2014, November 28)

Introduction : Les médecins généralistes jouent un rôle majeur dans la détection et la gestion des abus de substances. L'étude présentée ici investiguait les facteurs qui influencent leur implication ... [more ▼]

Introduction : Les médecins généralistes jouent un rôle majeur dans la détection et la gestion des abus de substances. L'étude présentée ici investiguait les facteurs qui influencent leur implication concernant la gestion des abus d'alcool, des drogues illégales, des hypnotiques et des anxiolytiques dans la population belge des 18-65 ans. Méthode : 20 MG ont été interrogés par entretiens semi-directifs. Le I-Change Model de de Vries a été utilisé pour construire le guide d'entretien et analyser les données récoltées. Il s'agit d'un modèle de prédiction du comportement. Résultats : Parmi les principaux résultats de l'étude, il ressortait que les MG étaient fortement influencés dans leur approche par leurs propres représentations de l'abus, qui oscillait leurs responsabilités professionnelles envers ces patients et la responsabilité de ces derniers quant à la gestion de leur santé, avec l'idée de faute morale en substrat. En ce sens, l'abus de substance était perçu sur un continuum entre l'abus comme forme de maladie chronique d'une part, et la faute morale d'autre part. L'alcool et le cannabis étaient néanmoins mieux acceptés socialement que les autres substances. Les propres expériences personnelles des généralistes concernant les abus avaient aussi une incidence sur leur volonté de s'investir avec ces patients. Pour autant, les pratiques multidisciplinaires (notamment au forfait) et l'expérience étaient évoquées comme des facteurs importants quant à l'engagement dans la gestion. Les contraintes temporelles et l'investissement demandé étaient, en revanche, considérés comme des barrières. Discussion : Les facteurs motivationnels apparaissaient centraux dans la décision de s'investir dans la gestion des abus de substances, bien davantage que les connaissances théoriques et les formations qui semblaient plus secondaires. La peur du burnout s'exprimait donc en substrat. La formation des MG devrait tenir compte de ce souhait de se protéger, afin de favoriser simultanément une approche centrée sur le patient. [less ▲]

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See detailImplication des métalloprot́eases matricielles en obśtetrique: De la nidatiòn a l'accouchement
Christiane, Yolande; Emonard, Violaine ULg; Emonard, Herve

in Revue Médicale de Liège (2014), 69(1), 46-50

Matrix metalloproteases, which remodel the extracellular matrix, are involved in all physiological and pathophysiological processes. In particular, they contribute to the success of a pregnancy : from ... [more ▼]

Matrix metalloproteases, which remodel the extracellular matrix, are involved in all physiological and pathophysiological processes. In particular, they contribute to the success of a pregnancy : from embryo implantation in the endometrium to uterine cervical ripening and uterine involution. A misregulation of their expression and/or of their activity is observed in two major diseases in pregnancy such as spontaneous abortion and preeclampsia. [less ▲]

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