References of "Moutschen, Michel"
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See detailHIV resistance to antiretroviral drugs: Mechanisms, genotypic and phenotypic resistance testing in clinical practice
Blaise, Pierre ULg; Clevenbergh, P.; Vaira, Dolorès ULg et al

in Acta Clinica Belgica (2002), 57(4, Jul-Aug), 191-201

HIV resistance to antiretroviral agents is a major contributory cause of treatment failure. The dynamics of HIV replication, together with patient-, physician-, and drug-related factors, lead to emergence ... [more ▼]

HIV resistance to antiretroviral agents is a major contributory cause of treatment failure. The dynamics of HIV replication, together with patient-, physician-, and drug-related factors, lead to emergence of HIV resistant strains in most of the patients. Phenotypic assays look for an increase in the antiretroviral drug (ARV) concentration that inhibits 50% of the growth of the tested HIV strain (IC50), comparatively with a reference strain cultivated in parallel. Genotypic tests detect resistance mutations in the reverse transcriptase and protease genes by comparing the gene sequences of a resistant virus to those of a wildtype strain that has previously been described. The efficacy of each ARV class and each individual ARV is threatened by specific mutations and resistance mechanisms. In retrospective studies of genotypic or phenotypic resistance testing, baseline resistance tests results were correlated with virological outcomes. There is some evidence from prospective studies that resistance testing may have some benefits when used to choose salvage regimens. However, problems in the areas of test interpretation, patient compliance, availability of active drugs, and technical test performance limit the usefulness of resistance testing in clinical practice. This article reviews the mechanisms underlying HIV resistance, the principles of phenotypic and genotypic tests, and the use of these tests in clinical practice. [less ▲]

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See detailL'image du mois. Malacoplasie pulmonaire a Rhodococcus equi chez un patient atteint du SIDA.
Delbecque, Katty ULg; Radermecker, Maurice ULg; Leonard, Philippe ULg et al

in Revue Médicale de Liège (2002), 57(11), 685-7

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See detailPharma-clinics comment je traite ... une infection par le VIH. IV. Les inhibiteurs de protease
Leonard, Philippe ULg; Nkoghe, D.; Moutschen, Michel ULg et al

in Revue Médicale de Liège (2001), 56(11), 739-44

Protease inhibitors constitute the last class of antiretroviral drugs appeared on the market. They raised an enormous enthusiasm, reinforced by recent studies results. These molecules prevent the ... [more ▼]

Protease inhibitors constitute the last class of antiretroviral drugs appeared on the market. They raised an enormous enthusiasm, reinforced by recent studies results. These molecules prevent the formation of infectious viral particles, while inhibiting a viral enzyme that plays a key role in the cycle of replication of the HIV. Their efficiency, especially in association, is recognized for all stages of the infection and the intervening of a resistance often requires many mutations. However, the unexpected adverse events such as lipodystrophy and some interactions can limit their utilization in first intention. [less ▲]

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See detailIncreased Camp Levels and Protein Kinase (Pka) Type I Activation in Cd4+ T Cells and B Cells Contribute to Retrovirus-Induced Immunodeficiency of Mice (Maids): A Useful in Vivo Model for Drug Testing
Rahmouni, Souad ULg; Aandahl, Einar Martin; Trebak, Mohamed et al

in FASEB Journal (2001), 15(8), 1466-1468

Murine AIDS (MAIDS) is characterized by a lymphoproliferative disease and a profound anergy, which involves mostly CD4(+) T cells. To better define the mechanisms responsible for anergy, we measured cAMP ... [more ▼]

Murine AIDS (MAIDS) is characterized by a lymphoproliferative disease and a profound anergy, which involves mostly CD4(+) T cells. To better define the mechanisms responsible for anergy, we measured cAMP concentrations in the different lymphocyte subsets of the infected mice. CD4(+) T cells and B cells displayed a dramatic 10- to 30-fold increase of cAMP. cAMP was also significantly increased in CD8(+) T cells, although to a far lesser extent. The unusual CD4(+) CD90(-) T cells, typical of MAIDS, were characterized by a much higher cAMP level than their CD90(+) counterparts. T cells of the infected mice were much more sensitive to inhibition by the cAMP analogue 8-CPT-cAMP, which confirmed increased in vivo exposure to cAMP. In accordance with the increased cAMP levels, PKA type I was constitutively activated and its C subunit was translocated to the nucleus. Finally, the profound T-cell anergy associated with MAIDS could be reversed by treating T cells with a PKA type I-selective antagonist ex vivo. MAIDS could constitute a suitable model for the study of new pharmacological agents aimed at reversing the immunosuppressive effects of cAMP previously shown to be involved in several pathological states, including HIV infection and common variable immunodeficiency. [less ▲]

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See detailHydroxyuree et infection par le VIH
Nkoghe, D.; Kola, L.; Leonard, Philippe ULg et al

in Revue Médicale de Liège (2000), 55(7), 721-4

Hydroxyurea is an anticancerous product, used recently in the treatment of HIV-1 infection thanks to its inhibitory action in viral replication, potentialization of the nucleosides activity (particularly ... [more ▼]

Hydroxyurea is an anticancerous product, used recently in the treatment of HIV-1 infection thanks to its inhibitory action in viral replication, potentialization of the nucleosides activity (particularly ddI or didanosine) and its cytostatic properties on CD4 and CD8 lymphocytes. Many studies showed its efficiency, as further drug, in initial regimen of a tritherapy (containing ddI) and salvage therapy. The dosage of 500 mg bid seems tolerated well by adults, and 20 mg/kg by children. Long-term tolerance remains unknown. With ddI, it could be proposed in developing countries. [less ▲]

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See detailAntitumoral Vaccination with Granulocyte-Macrophage Colony-Stimulating Factor or Interleukin-12-Expressing Dhd/K12 Colon Adenocarcinoma Cells
Lechanteur, Chantal ULg; Moutschen, Michel ULg; Princen, Frederic et al

in Cancer Gene Therapy (2000), 7(5), 676-82

Immunomodulating gene therapy for the treatment of malignant diseases is under extensive investigation. In this study, we induced an antitumoral immune response with murine interleukin-12 (mIL-12) and ... [more ▼]

Immunomodulating gene therapy for the treatment of malignant diseases is under extensive investigation. In this study, we induced an antitumoral immune response with murine interleukin-12 (mIL-12) and murine granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor cells in a model of peritoneal carcinomatosis. Intraperitoneal injection of DHD/K12 tumoral cells engineered to produce IL-12 or GM-CSF did not generate any tumors, whereas untransduced DHD/K12 cells gave rise to peritoneal carcinomatosis. IL-12-expressing DHD/K12 cells also protected against tumors derived from coinjected parental cells. To test whether cytokine-producing cells could elicit a memory antitumoral immune response, animals received a challenge with parental DHD/K12 cells 35 days after the injection of proliferating or irradiated DHD/K12 engineered cells. Under our experimental conditions, irradiated tumor cells did not generate any antitumoral immunity. In contrast, tumor development was delayed and survival increased in the animals vaccinated with cytokine-secreting proliferating cells. A specific cytotoxic T-lymphocyte response against DHD/K12 parental cells was observed after vaccination with GM-CSF-expressing cells. Our results demonstrated that intraperitoneal vaccination with IL-12- or GM-CSF-expressing adenocarcinoma cells induced a systemic immune antitumoral response that may be useful as an adjuvant therapy after surgical resection of colorectal cancer. [less ▲]

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See detailLa commission d'hemovigilance du CHU.
Baudoux, Etienne ULg; Blaffart, Francine ULg; Bouffioux, Christian ULg et al

in Revue Médicale de Liège (2000), 55(9), 878-80

As suggested by the National Blood Council, a Hemovigilance Committee was set up in the University Hospital of Liege in 1995. A multidisciplinary discussion takes place on any action aiming at the ... [more ▼]

As suggested by the National Blood Council, a Hemovigilance Committee was set up in the University Hospital of Liege in 1995. A multidisciplinary discussion takes place on any action aiming at the improvement of transfusion safety, and the follow-up of its implementation. The first issue to be discussed was the set up of a detailed documentation of all blood transfusions. The data are now recorded on a single document allowing proper identification of people and products involved, and of the eventual incidents. This document has lead to a better transfusion safety and to an improved administrative management of blood transfusion. The Commission has been coordinating two multi-centric studies analyzing the consumption of fresh blood products and the incidence of transfusion reactions. Among blood-saving policies, autologous transfusion and volume reduction of samples drawn for laboratory purposes have been discussed. Other measures were taken to improve the labeling of samples for cross-mach and to actively follow-up transfusion reactions. By its actions and advises, the Commission aims to direct strategies towards a safe and rational use of blood products. [less ▲]

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See detailAnomalies fonctionnelles des lymphocytes T dans un modèle murin d'infection rétrovirale
Moutschen, Michel ULg

Thèse d’agrégation de l’enseignement supérieur (2000)

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See detailMice Transgenic for a Soluble Form of Murine Cytotoxic T Lymphocyte Antigen 4 Are Refractory to Murine Acquired Immune Deficiency Sydrome Development
de Leval, Laurence ULg; Debrus, S.; Lane, P. et al

in Immunology (1999), 98(4), 630-8

Interactions between B and CD4+ T cells are central to the pathogenesis of retrovirus-induced murine acquired immune deficiency virus (MAIDS). Prompted by previous work showing that treatment with ... [more ▼]

Interactions between B and CD4+ T cells are central to the pathogenesis of retrovirus-induced murine acquired immune deficiency virus (MAIDS). Prompted by previous work showing that treatment with cytotoxic T lymphocyte antigen 4 immunoglobulin (CTLA4Ig) partly inhibited the disease, we studied the course of infection in mice deficient for CD28-B7 interactions (mCTLA4-Hgamma1 transgenic mice). Despite a relative viral load identical to that of non-transgenic mice, the transgenic mice did not develop any of the major MAIDS symptoms (i.e. lymphoproliferation and immune anergy). The mCTLA4-Hgamma1 did not however, completely inhibit B-cell activation as indicated by a slight hypergammaglobulinaemia and microscopic blastic transformation. Absence of MAIDS in transgenic mice was associated with much lower levels of both interleukin-4 and interferon-gamma transcripts following viral infection. These results support the theory that the CD28/B7 costimulatory pathway is a critical determinant to MAIDS development. [less ▲]

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See detailPharma-clinics le médicament du mois. La nevirapine. Viramune
Nkoghe, D.; Leonard, Philippe ULg; Moutschen, Michel ULg et al

in Revue Médicale de Liège (1999), 54(12), 948-51

Nevirapine is the first non nucleoside reverse transcriptase inhibitor registered in Belgium and indicated in the treatment of HIV-1 infection. In association with 2 nucleoside analogues, its efficiency ... [more ▼]

Nevirapine is the first non nucleoside reverse transcriptase inhibitor registered in Belgium and indicated in the treatment of HIV-1 infection. In association with 2 nucleoside analogues, its efficiency is similar to a tritherapy with protease inhibitor, particularly in naive patients with low viral load. It has a good tolerance profile and is easy to take. Studies in progress should permit to widen its indications. [less ▲]

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See detailPharma-clinics comment je traite ... une infection par le VIH. III. Les inhibiteurs non nucléosidiques de la transcriptase inverse
Nkoghe, D.; Moutschen, Michel ULg; Leonard, Philippe ULg et al

in Revue Médicale de Liège (1999), 54(12), 909-11

Non nucleoside reverse transcriptase inhibitors (NNRTI) are a new arm in the treatment of the HIV infection. They inhibit the replication by direct non competitive binding to the enzyme, and do not ... [more ▼]

Non nucleoside reverse transcriptase inhibitors (NNRTI) are a new arm in the treatment of the HIV infection. They inhibit the replication by direct non competitive binding to the enzyme, and do not require phosphorylation. The fast emergence of resistance in monotherapy obliges to use them in a triple association. The 103 mutation confers a cross-resistance. The most common adverse event is rash. Association with nucleoside analogues is additive or even synergistic. They are metabolized by the cytochrome P450. Within a combined therapy, their efficiency is comparable to protease inhibitors, notably in patients with low viral load. [less ▲]

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See detailL'image du mois. Kyste hydatique hépatique
Radermecker, Régis ULg; Nkoghe, D.; Labasse, J. M. et al

in Revue Médicale de Liège (1999), 54(1), 4-5

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See detailDecreased Protein Levels of the C-Cbl Protooncogene in Murine Aids
Trebak, Mohamed; Lambert, Charles A; Rahmouni, Souad ULg et al

in Cellular Immunology (1998), 188(2), 151-7

Murine acquired immunodeficiency syndrome (MAIDS) can be viewed as a lymphoproliferative disease which involves B cells as well as T cells from spleen and lymph nodes while thymus and Peyer's patches do ... [more ▼]

Murine acquired immunodeficiency syndrome (MAIDS) can be viewed as a lymphoproliferative disease which involves B cells as well as T cells from spleen and lymph nodes while thymus and Peyer's patches do not participate in the process. The 120-kDa protooncogene product c-Cbl was initially cloned from the murine Cas NS-1 B cell lymphoma. It is a main target of immunoreceptor (TCR and BCR)-mediated protein tyrosine kinase activity. Moreover, recent data suggest that c-Cbl might play a crucial role in the regulation of cell proliferation through regulation of GTP-binding proteins. Therefore, the involvement of c-Cbl was evaluated in the lymphoproliferative disease induced by the MAIDS virus. The expression of the c-Cbl protein was dramatically reduced in the lymph node of infected mice while it remained normal in the thymus. In contrast, the expression of actin, TCR-zeta chain, ZAP-70, and p59(fyn) remained similar in controls and infected mice. Identical results were obtained with sorted B cells and T cells. Surprisingly, a B cell lymphoma line derived from late stage MAIDS mice displayed a normal level of c-Cbl. [less ▲]

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See detailCd28-B7 Costimulatory Blockade by Ctla4ig Delays the Development of Retrovirus-Induced Murine Aids
de Leval, Laurence ULg; Colombi, S.; Debrus, S. et al

in Journal of Virology (1998), 72(6), 5285-90

Mouse AIDS (MAIDS) induced in C57BL/6 mice by infection with a replication-defective retrovirus (Du5H) combines extensive lymphoproliferation and profound immunodeficiency. Although B cells are the main ... [more ▼]

Mouse AIDS (MAIDS) induced in C57BL/6 mice by infection with a replication-defective retrovirus (Du5H) combines extensive lymphoproliferation and profound immunodeficiency. Although B cells are the main target of viral infection, recent research has focused on CD4(+) T cells, the activation of which is a key event in MAIDS induction and progression. A preliminary observation of increased expression of B7 molecules on B cells in MAIDS prompted us to address the possible involvement of the CD28/B7 costimulatory pathway in MAIDS. Mice infected with the MAIDS-inducing viral preparation were treated with murine fusion protein CTLA4Ig (3 x 50 microg/week given intraperitoneally), a competitive inhibitor of physiological CD28-B7 interactions. In CTLA4Ig-treated animals, the onset of the disease was delayed, lymphoproliferation progressed at a much slower rate than in untreated mice, and the loss of in vitro responsiveness to mitogens was reduced. Relative expression of Du5H did not differ between treated and untreated animals. These results suggest that the CD28/B7 costimulatory pathway contributes to MAIDS development. [less ▲]

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See detailCorrelation of T-Helper Secretory Differentiation and Types of Antigen-Presenting Cells in Squamous Intraepithelial Lesions of the Uterine Cervix
al-Saleh, W.; Giannini, S. L.; Jacobs, Nathalie ULg et al

in Journal of Pathology (The) (1998), 184(3), 283-90

This study addressed the notion that the progression of cervical cancer is associated with a T-helper 2 (TH2) immunodeviation by analysing cytokine expression in 60 cervical biopsy specimens, spanning the ... [more ▼]

This study addressed the notion that the progression of cervical cancer is associated with a T-helper 2 (TH2) immunodeviation by analysing cytokine expression in 60 cervical biopsy specimens, spanning the spectrum from normal cervical tissue to high-grade squamous intraepithelial lesions (SILs). The biopsies were analysed by immunohistochemistry for the expression of TH1 [interleukin-2 (IL2), interferon gamma (IFN gamma)] and of TH2-type cytokines (IL4, IL6). Positive cells were usually observed in the subepithelial connective tissue, where most CD4+ cells were also detected. The density of IL2+ cells was significantly lower in high-grade SILs than in normal tissues taken either from the ectocervix or from the transformation zone. In contrast, significantly higher densities of IL4+ cells and, to a lesser degree, IL6+ cells were found in SIL biopsies compared with histologically normal tissues taken from the adjacent ectocervical region. A significantly higher IL4+/CD4+ cell ratio was also found in high-grade SILs (82 per cent) than in normal cervical biopsies taken from the transformation zone of healthy women showing squamous metaplasia (27 per cent). The elevated density of TH2+ cells in SIL biopsies was associated with both the expression of HLA-DR by keratinocytes and a diminished number of intraepithelial Langerhans' cells (CD1a+). In conclusion, the increased TH2+/CD4+ cell ratio in SIL biopsies suggest the presence, during cervical carcinogenesis, of a TH2 immunodeviation that could participate in the immunoescape of preneoplastic cervical keratinocytes. [less ▲]

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See detailInverse Modulation of Il-10 and Il-12 in the Blood of Women with Preneoplastic Lesions of the Uterine Cervix
Jacobs, Nathalie ULg; Giannini, Sandra L; Doyen, Jean ULg et al

in Clinical & Experimental Immunology (1998), 111(1), 219-24

It has been postulated that an impaired immune response may contribute to the progression of human papillomavirus (HPV)-associated preneoplastic lesions. Based on this hypothesis, we evaluated the ... [more ▼]

It has been postulated that an impaired immune response may contribute to the progression of human papillomavirus (HPV)-associated preneoplastic lesions. Based on this hypothesis, we evaluated the cytokine production in the blood of patients with squamous intraepithelial lesions (SIL) of the uterine cervix. The levels of type-1 (interferon-gamma (IFN-gamma) and IL-12) and type-2(IL-4 and IL-10) cytokines were measured in whole blood culture supernatants of patients with low- and high-grade SIL and control women. There was no difference in IL-4 and IFN-gamma levels between patients with SIL and the control group. In contrast, the ratio of IL-12/IL-10 levels was significantly lower in patients with SIL compared with the control group. A lower IL-12/IL-10 ratio in women with SIL was also observed when peripheral blood mononuclear cell (PBMC) culture supernatants and plasma samples were analysed. In patients, neither the lower expression of the CD3epsilon chain nor the higher frequency of HLA-DRB1*1501 expression could be correlated with abnormal cytokine production. These results suggest that a part of the cytokine network, namely IL-10 and IL-12, is perturbed in patients with SIL. A better knowledge of the role of these cytokines in regulating the growth of HPV-associated SIL might have practical implications for the development of vaccines or immunomodulatory strategies in the treatment of cervical cancers. [less ▲]

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See detailReciprocal regulation of protein tyrosine kinases p56lck and p59fyn, and altered tyrosine phosphorylation in murine AIDS.
Trebak, Mohamed; Lambert, Chantal ULg; Rahmouni, Souad ULg et al

in International Immunology (1998), 10(10), 1473-80

Murine AIDS (MAIDS), caused by a defective murine leukemia virus, is a severe lymphoproliferative disease associated with profound immunodeficiency and increased susceptibility to opportunistic infections ... [more ▼]

Murine AIDS (MAIDS), caused by a defective murine leukemia virus, is a severe lymphoproliferative disease associated with profound immunodeficiency and increased susceptibility to opportunistic infections. Most subsets of lymphocytes, including CD4+ and CD8+ T cells, are refractory to mitogen stimulation. As a first step to examine proximal signal transduction in the infected mice, Western and Northern blot analyses were performed, and showed that p56lck is dramatically decreased at the protein as well as the mRNA level in the lymph nodes (LN). In contrast, p59(fyn) and its mRNA were slightly increased in the LN of the same mice. Similar results were obtained with purified T cells. Interestingly, the thymus of the infected animals did not show any abnormality regarding p56(lck) or p59(fyn). Tyrosine phosphorylation was constitutively increased in the infected mice and was barely amplified by anti-CD3 mAb stimulation. A similar pattern was observed when tyrosine phosphorylation was selectively examined at the level of ZAP-70. Our results suggest that a reciprocal regulation of p56(lck) and p59(fyn) protein tyrosine kinases, previously described in various models of anergy, could also be involved in the pathogenesis of MAIDS. [less ▲]

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See detailPharma-clinics. Comment je traite ... Une infection par le VIH. II. Inhibiteurs nucléosidiques de la transcriptase reverse
Moutschen, Michel ULg; Nkoghe, D.; Leonard, Philippe ULg et al

in Revue Médicale de Liège (1997), 52(12), 750-2

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See detailComment je traite ... une infection par le VIH. I. Bases pathogéniques des choix thérapeutiques
Moutschen, Michel ULg; Nkoghe, D.; Leonard, Philippe ULg et al

in Revue Médicale de Liège (1997), 52(10), 622-4

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See detailPeyer's Patches in Murine Aids: Dissociation between Lymphoproliferation and Anergy
Colombi, S.; Moutschen, Michel ULg; de Leval, Laurence ULg et al

in Scandinavian Journal of Immunology (1997), 45(2), 175-81

RadLV-Rs infection induces a murine immunodeficiency syndrome associated with a dramatic enlargement of spleen and lymph nodes. Surprisingly, the lymphoproliferation excludes thymus and Peyer's patches ... [more ▼]

RadLV-Rs infection induces a murine immunodeficiency syndrome associated with a dramatic enlargement of spleen and lymph nodes. Surprisingly, the lymphoproliferation excludes thymus and Peyer's patches (PP). To understand the cellular interactions underlying lymphoproliferation further, the authors investigated the fate of PP in RadLV-Rs infected mice. The atrophy of PP was mostly due to the depletion of B cells, while the proportion of CD4+ and CD8+ T cells was increased. Nevertheless, B cell phenotype was modified with the emergence of lymphocytes with a low expression of B220 in infected PP. T cells characterized by a memory/activated phenotype in control PP did not undergo phenotypical changes after viral infection (i.e. regarding Thy-1 and CD44 expression). Despite the absence of lymphoproliferation, PP T and B cells displayed altered responses to mitogens in vitro. Finally, alterations of the expression of adhesion molecules and vascular addressins could not explain the atrophy of PP by a reduced homing to this lymphoid site. B cells and T cells from normal PP are clearly different from lymph nodes (LN) lymphocytes. The authors propose that the particular functional state which characterizes PP lymphocytes influences the B cell/T cell crosstalk necessary for RadLV-Rs-induced lymphoproliferation. [less ▲]

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