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See detailCyclin dependent kinase inhibitor (CDKN1B) gene variants in AIP mutation-negative familial isolated pituitary adenomas (FIPA) kindreds
Tichomirowa, M.; Lee, M.; Barlier, A. et al

in Endocrine-Related Cancer (2012), 19

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See detailCyclin dependent kinase inhibitor 1B (CDKN1B) gene mutations in FIPA
Tichomirowa, M. A.; Pellegata, N. S.; Barlier, A. et al

in European Neuroendocrine Association - Liège, 22-25 septembre 2010 (2010, September)

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See detailCyclin-dependent kinase-2 controls oligodendrocyte progenitor cell cycle progression and is downregulated in adult oligodendrocyte progenitors.
Belachew, Shibeshih ULg; Aguirre, Adan A.; Wang, Hang et al

in Journal of Neuroscience (2002), 22(19), 8553-62

Proliferation of oligodendrocyte progenitor (OP) cells is a crucial process controlling myelination in the CNS. Previous studies demonstrated a correlation between OP proliferation rate and cyclin E ... [more ▼]

Proliferation of oligodendrocyte progenitor (OP) cells is a crucial process controlling myelination in the CNS. Previous studies demonstrated a correlation between OP proliferation rate and cyclin E/cyclin-dependent kinase-2 (cdk2) activity. To establish a causal link between cyclin E/cdk2 activity and OP proliferation, we selectively modulated cdk2 activity in vitro by transfection of cultured OP cells. Dominant-negative (Dn)-cdk2 overexpression inhibited mitogen-induced OP cell proliferation, whereas wild-type (wt)-cdk2 prevented cell cycle arrest caused by anti-mitotic signals. Dn-cdk2- or wt-cdk2-mediated regulation of G(1)/S transition, per se, did not influence initiation of OP differentiation. To study the function of cyclin E/cdk2 in OP cells during development in vivo, we analyzed cdk2 and cyclin E expression in cells acutely isolated from transgenic mice expressing the green fluorescent protein (GFP) under the control of the 2'-3'-cyclic nucleotide 3'-phosphodiesterase gene promoter. Both cyclin E/cdk2 protein levels and activity were decreased in GFP(+) oligodendrocyte lineage cells between postnatal days 4 and 30. Immunostaining of NG2(+)/GFP(+) OP cells in brain tissue sections showed a 90% decrease in overall cell proliferation and cdk2 expression between perinatal and adult cells. However, cdk2 expression within the proliferating (i.e., expressing the proliferating cell nuclear antigen) OP cell population was maintained throughout development. Our data indicate that: (1) cyclin E/cdk2 activity plays a pivotal function in OP cell cycle decisions occurring at G(1)/S checkpoint; (2) initiation of OP differentiation is independent of cyclinE/cdk2 checkpoint, and (3) intrinsic differences in cyclin E/cdk2 expression and activity may underlie the slowly proliferative state that characterizes so-called "quiescent" adult OP cells in vivo. [less ▲]

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See detailCyclinD1-negative mantle cell lymphoma with cryptic t(12;14)(p13;q32) and cyclin D2 overexpression
Herens, Christian ULg; Lambert, Frédéric ULg; Quintanilla-Martinez, L. et al

in Blood (2008), 111(3), 1745-1746

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See detailCycling or not cycling: cell cycle regulatory molecules and adult neurogenesis.
Beukelaers, Pierre ULg; Vandenbosch, Renaud ULg; Caron, Nicolas ULg et al

in Cellular and Molecular Life Sciences : CMLS (2012), 69(9), 1493-1503

The adult brain most probably reaches its highest degree of plasticity with the lifelong generation and integration of new neurons in the hippocampus and olfactory system. Neural precursor cells (NPCs ... [more ▼]

The adult brain most probably reaches its highest degree of plasticity with the lifelong generation and integration of new neurons in the hippocampus and olfactory system. Neural precursor cells (NPCs) residing both in the subgranular zone of the dentate gyrus and in the subventricular zone of the lateral ventricles continuously generate neurons that populate the dentate gyrus and the olfactory bulb, respectively. The regulation of NPC proliferation in the adult brain has been widely investigated in the past few years. Yet, the intrinsic cell cycle machinery underlying NPC proliferation remains largely unexplored. In this review, we discuss the cell cycle components that are involved in the regulation of NPC proliferation in both neurogenic areas of the adult brain. [less ▲]

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See detailCyclo-oxygenase type 2-dependent prostaglandin E-2 secretion is involved in retrovirus-induced T-cell dysfunction in mice
Rahmouni, Souad ULg; Aandahl, Einar Martin; Nayjib, Btissam ULg et al

in Biochemical Journal (2004), 384(Pt 3), 469-476

MAIDS (murine AIDS) is caused by infection with the murine leukaemia retrovirus RadLV-Rs and is characterized by a severe immunodeficiency and T-cell anergy combined with a lymphoproliferative disease ... [more ▼]

MAIDS (murine AIDS) is caused by infection with the murine leukaemia retrovirus RadLV-Rs and is characterized by a severe immunodeficiency and T-cell anergy combined with a lymphoproliferative disease affecting both B- and T-cells. Hyperactivation of the cAMP-protein kinase A pathway is involved in the T-cell dysfunction of MAIDS and HIV by inhibiting T-cell activation through the T-cell receptor. In the present study, we show that MAIDS involves a strong and selective up-regulation of cyclo-oxygenase type 2 in the CD11b+ subpopulation of T- and B-cells of the lymph nodes, leading to increased levels of PGE2 (prostaglandin E2). PGE2 activates the cAMP pathway through G-protein-coupled receptors. Treatment with cyclo-oxygenase type 2 inhibitors reduces the level of PGE2 and thereby reverses the T-cell anergy, restores the T-cell immune function and ameliorates the lymphoproliferative disease. [less ▲]

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See detailCYCLODEXTRIN INCLUSIONS COMPLEXES OF PYRIMIDINE-2,4,6-TRIONES
Evrard, Brigitte ULg; Bartsch, Pierre ULg; Endele, Richard et al

Patent (2007)

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See detailCyclodextrin-mediated drug release from liposomes dispersed within a bioadhesive gel
Piel, Géraldine ULg; Boulmedarat, Laila; Bochot, Amelie et al

in Pharmaceutical Research (2005), 22(6), 962-971

Purpose. The aim of the present study was to design a new mucosal drug delivery system composed of liposomes dispersed within a bioadhesive hydrogel containing methyl-beta-cyclodextrin (Me beta CD) for ... [more ▼]

Purpose. The aim of the present study was to design a new mucosal drug delivery system composed of liposomes dispersed within a bioadhesive hydrogel containing methyl-beta-cyclodextrin (Me beta CD) for controlled drug release. Methods. A hydrophilic model molecule, inulin, was encapsulated within positively charged and PEGylated liposomes and its release was measured in the presence of Me beta CD after vesicle dispersion within the bioadhesive Carbopol(R) 974P gel. Freeze-fracture electron microscopy (FFEM) was used to follow liposome morphological changes when dispersed within the hydrogel. Liposome- Me beta CD interactions were investigated by turbidity monitoring during continuous addition of Me beta CD to liposomes and by FFEM. Results. Inulin diffusion within the gel was influenced by Carbopol(R) 974P concentration since no gel erosion occurred. When dispersed within the gel, positively charged liposomes displayed a higher stability than PEG-ylated vesicles. In the presence of Me beta CD, higher amounts of free inulin were released from liposomes, especially in Carbopol(R)-free system. Me beta CD appeared to diffuse towards lipid vesicles and permeabilized their bilayer allowing inulin leakage. Indeed, freeze-fracture experiments and liposome turbidity monitoring have shown that Me beta CD behaved as a detergent behavior, resulting in lipid vesicle solubilization. Conclusion. Me beta CD is able to mediate, within a bioadhesive hydrogel, the release of a liposome-encapsulated molecule allowing further application of this delivery system for mucosal administration. [less ▲]

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See detailCyclodextrins as a potential carrier in drug nebulization
Evrard, Brigitte ULg; Bertholet, P.; Guéders, Maud ULg et al

in Journal of Controlled Release (2004), 96(3), 403-410

The inhalation route is widely studied for many drug applications focusing on either local or systemic distributions. One matter of concern is the solubilization of hydrophobic drugs. We have studied the ... [more ▼]

The inhalation route is widely studied for many drug applications focusing on either local or systemic distributions. One matter of concern is the solubilization of hydrophobic drugs. We have studied the feasibility of using different cyclodextrins (CDs) to elaborate pharmaceutical formulations for the inhalation route and tested the short-term toxicity of such formulations administered by inhalation to C57BL/6 mice. We have shown that HP-beta-CD, gamma-CD, as well as RAMEB aqueous solutions can undergo aerosolization and that the resulting droplet-size ranges are compatible with pulmonary deposition. In vivo, we have demonstrated that short-term exposure to inhaled HP-beta-CD, gamma-CD and RAMEB solutions are non-toxic after assessing bronchoalveolar lavage (BAL), lung and kidney histology, bronchial responsiveness to methacholine and blood urea. The only change noted is a slight increase in lymphocyte count in the BAL after HP-beta-CD and gamma-CD inhalation. We conclude that CDs are useful in significantly enhancing the solubility of apolar drugs with a view to inhalation therapy although an increase in lymphocyte counts in the BAL after CDs inhalations needs further investigations. (C) 2004 Elsevier B.V. All rights reserved. [less ▲]

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See detailCyclodextrins as a potential carrier in drug nebulization.
Evrard, Brigitte ULg; Bertholet, P.; Guéders, Maud ULg et al

in Journal of Controlled Release (2004), 96(3), 403-10

The inhalation route is widely studied for many drug applications focusing on either local or systemic distributions. One matter of concern is the solubilization of hydrophobic drugs. We have studied the ... [more ▼]

The inhalation route is widely studied for many drug applications focusing on either local or systemic distributions. One matter of concern is the solubilization of hydrophobic drugs. We have studied the feasibility of using different cyclodextrins (CDs) to elaborate pharmaceutical formulations for the inhalation route and tested the short-term toxicity of such formulations administered by inhalation to C57BL/6 mice. We have shown that HP-beta-CD, gamma-CD, as well as RAMEB aqueous solutions can undergo aerosolization and that the resulting droplet-size ranges are compatible with pulmonary deposition. In vivo, we have demonstrated that short-term exposure to inhaled HP-beta-CD, gamma-CD and RAMEB solutions are non-toxic after assessing bronchoalveolar lavage (BAL), lung and kidney histology, bronchial responsiveness to methacholine and blood urea. The only change noted is a slight increase in lymphocyte count in the BAL after HP-beta-CD and gamma-CD inhalation. We conclude that CDs are useful in significantly enhancing the solubility of apolar drugs with a view to inhalation therapy although an increase in lymphocyte counts in the BAL after CDs inhalations needs further investigations. [less ▲]

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See detailCyclodextrins as topical permeation enhancers : in vitro and in vivo testing
Henry de Hassonville, S.; Christiaens, B.; Piel, Géraldine ULg et al

Poster (2003)

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See detailCyclodimerization by ring-closing metathesis: synthesis, computational and biological evaluation of novel bis-azetidinyl-macrocycles
Sliwa, Aline; Dive, Georges ULg; Habib Jiwan, Jean-Louis et al

in Tetrahedron (2010), 66

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See detailCyclopentenone prostaglandins at low concetrations exert pro-inflammatory effects through oxidative stress-induced ERK1/2 activation
Bureau, Fabrice ULg; Desmet, Christophe ULg; Mélotte, C. et al

in Proceedings: Spring Meeting of the Belgian Society of Physiology and Pharmacology (2002)

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See detailCyclosporin A, rapamycin and FK506 decrease prolactin release from rat pituitary cells in primary culture
Wera, S.; Zheng, L.; Hooghe-Peters, E. L. et al

in Endocrine Research (1995), 21(3), 623-33

It is at present well established that prolactin exerts a non-specific immunoactivating function. In this work we tested whether the immunosuppressant drugs cyclosporin A, FK506 and rapamycin influence ... [more ▼]

It is at present well established that prolactin exerts a non-specific immunoactivating function. In this work we tested whether the immunosuppressant drugs cyclosporin A, FK506 and rapamycin influence prolactin release from rat pituitary cells in primary culture. The tested drugs had no effect on the prolactin release measured during a 2h incubation period, indicating that they do not influence the secretion of prolactin from intracellular stores into the culture medium. During longer incubation times (48h), however, prolactin release was diminished to 56% +/- 18 (10 microM cyclosporin A), 64% +/- 14 (1 microM rapamycin) or 64% +/- 7 (1 microM FK506), suggesting an effect on prolactin production. At these drug concentrations no toxic effects were observed. The data indicate that inhibition of pituitary prolactin synthesis might contribute to the immunosuppressant action of cyclosporin A, rapamycin and FK506. [less ▲]

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See detailCyclosporin C Is the Main Antifungal Compound Produced by Acremonium Luzulae
Moussaif, M.; Jacques, P.; Schaarwachter, P. et al

in Applied and Environmental Microbiology (1997), 63(5), 1739-43

A strain of Acremonium luzulae (Fuckel) W. Gams was selected in screening new microorganisms for biological control of fruit postharvest diseases, especially gray and blue mold diseases on apples and ... [more ▼]

A strain of Acremonium luzulae (Fuckel) W. Gams was selected in screening new microorganisms for biological control of fruit postharvest diseases, especially gray and blue mold diseases on apples and strawberries. This strain manifests a very strong activity against a large number of phytopathogenic fungi. In this work, the product responsible for this antifungal activity was isolated from modified Sabouraud dextrose broth cultures of A. luzulae. It was purified to homogeneity by reverse-phase column chromatography. On the basis of UV, infrared, and 1H and 13C nuclear magnetic resonance spectra, mass spectral analysis, and the amino acid composition of the acid hydrolysates, the antibiotic was determined to be cyclosporin C. Cyclosporin C showed a broad-spectrum activity against filamentous phytopathogenic fungi but no activity against bacteria or yeasts. Its antifungal activity is only fungistatic. In contrast to Tolypocladium inflatum, another cyclosporin-producing strain, A. luzulae, did not produce additional cyclosporins. This was confirmed by in vivo-directed biosynthesis. [less ▲]

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See detailCyclosporin-A differentially affects apoptosis during in vivo rat thymocyte maturation
Damoiseaux, JGMC; Defresne, Marie-Paule ULg; Reutelingsperger, C. P. M. et al

in Scandinavian Journal of Immunology (2002), 56(4), 353-360

Maturation arrest and interference with selection are two well-documented effects of cyclosporin-A (CsA) on the thymus. We recently hypothesized that these effects are related and owing to the reduced T ... [more ▼]

Maturation arrest and interference with selection are two well-documented effects of cyclosporin-A (CsA) on the thymus. We recently hypothesized that these effects are related and owing to the reduced T-cell receptor (TCR)-CD3 complex-mediated signal transduction in thymocytes upon CsA treatment. In this hypothesis, the maturation arrest is the result of the additional depletion of thymocytes that normally survive by positive selection, whereas the impaired self-tolerance induction is caused by an increased survival of thymocytes that normally undergo negative selection. In this view, it is anticipated that CsA differentially affects thymocyte apoptosis during in vivo thymocyte maturation. Indeed, we report in this study a strong increase in apoptotic cells in the thymic cortex on in situ analysis. Simultaneously, the number of apoptotic cells had decreased at the cortico-medullary zone which is held to be the site for negative selection. Rapamycin (Rapa) also interferes with thymocyted maturation by inhibiting cytokine-driven proliferation. Hence, Rapa preferentially affects the early maturational stages of thymoctye development and is considered not to alter thymocyte selection and subsequent apoptotic events. Indeed, the number of apoptotic events appears not to be altered. However, possibly owing to the decrease in cortical macrophages, the apoptotic cells revealed an atypical enumeration around blood vessels. Taken together, our results favour the hypothesis that the dominant effect of CsA on the thymus is the reduction of the TCR-CD3 complex-mediated signal transduction in thymocytes upon interaction with stromal cells. Furthermore, the preferential localization of apoptotic cells next to blood vessels upon Rapa administration may indicate that endothelial cells are a back-up system for the removal of apoptotic cells. [less ▲]

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See detailCyclosporine a Inhibits Partially Spermine-Induced Differentiation but Not Cell Loss of Suckling Rat Small Intestine
Peulen, Olivier ULg; Dandrifosse, Guy ULg

in Digestive Diseases & Sciences (2000), 45(4), 750-4

The polyamines are of great importance in several biological processes, such as cell proliferation, and differentiation. The ingestion of spermine by suckling rats induces the precocious maturation of ... [more ▼]

The polyamines are of great importance in several biological processes, such as cell proliferation, and differentiation. The ingestion of spermine by suckling rats induces the precocious maturation of their small intestine. This phenomenon is preceded by a cell elimination at the villus tip. We hypothesize that these two phenomena could be mediated by the immune system and thus inhibited by an immunosuppressive agent such as cyclosporine A. Cyclosporine A inhibits, at least partially, the spermine-induced increase of the maltase- and sucrase-specific activities in the small intestine but failed to inhibit lactase-specific activity decrease and cell loss. Spermine does not act by the same mechanism in differentiation and in cell loss. Moreover, spermine acts in a different way on lactase-specific activity compared to maltase- or sucrase-specific activity. We hypothesize that spermine acts on differentiation by a T-cell/IL-2-dependent mechanism. [less ▲]

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See detailCyclosporine, a P-glycoprotein modulator, increases [18F]MPPF uptake in rat brain and peripheral tissues: microPET and ex vivo studies.
Lacan, Goran; Plenevaux, Alain ULg; Rubins, Daniel J. et al

in European Journal of Nuclear Medicine and Molecular Imaging (2008), 35(12), 2256-66

PURPOSE: Pretreatment with cyclosporine, a P-glycoprotein (P-gp) modulator increases brain uptake of 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethylpiperaz ine ([(18)F]MPPF) for ... [more ▼]

PURPOSE: Pretreatment with cyclosporine, a P-glycoprotein (P-gp) modulator increases brain uptake of 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethylpiperaz ine ([(18)F]MPPF) for binding to hydroxytryptamine(1A) (5-HT(1A)) receptors. Those increases were quantified in rat brain with in vivo microPET and ex vivo tissue studies. MATERIALS AND METHODS: Each Sprague-Dawley rat (n = 4) received a baseline [(18)F]MPPF microPET scan followed by second scan 2-3 weeks later that included cyclosporine pretreatment (50 mg/kg, i.p.). Maximum a posteriori reconstructed images and volumetric ROIs were used to generate dynamic radioactivity concentration measurements for hippocampus, striatum, and cerebellum, with simplified reference tissue method (SRTM) analysis. Western blots were used to semiquantify P-gp regional distribution in brain. RESULTS: MicroPET studies showed that hippocampus uptake of [(18)F]MPPF was increased after cyclosporine; ex vivo studies showed similar increases in hippocampus and frontal cortex at 30 min, and for heart and kidney at 2.5 and 5 min, without concomitant increases in [(18)F]MPPF plasma concentration. P-gp content in cerebellum was twofold higher than in hippocampus or frontal cortex. CONCLUSIONS: These studies confirm and extend prior ex vivo results (J. Passchier, et al., Eur J Pharmacol, 2000) that showed [(18)F]MPPF as a substrate for P-gp. Our microPET results showed that P-gp modulation of [(18)F]MPPF binding to 5-HT(1A) receptors can be imaged in rat hippocampus. The heterogeneous brain distribution of P-gp appeared to invalidate the use of cerebellum as a nonspecific reference region for SRTM modeling. Regional quantitation of P-gp may be necessary for accurate PET assessment of 5-HT(1A) receptor density when based on tracer uptake sensitive to P-gp modulation. [less ▲]

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See detailCyclostratigraphic implications of Devonian-climate astronomical forcing.
De Vleeschouwer, David; Da Silva, Anne-Christine ULg; Boulvain, Frédéric ULg et al

in Geological Society of America Abstracts with Programs (2010), 42(5), 540

Detailed reference viewed: 10 (1 ULg)