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See detailLocal applications of GM-CSF induce the recruitment of immune cells in cervical low-grade squamous intraepithelial lesions.
Hubert, Pascale ULg; Doyen, Jean ULg; Capelle, Xavier ULg et al

in American Journal of Reproductive Immunology (2010), 64(2), 126-136

Abstract Problem Quantitative alterations of antigen-presenting cells (APC) in (pre)neoplastic lesions of the uterine cervix associated with human papillomavirus (HPV) infection suggest a diminished ... [more ▼]

Abstract Problem Quantitative alterations of antigen-presenting cells (APC) in (pre)neoplastic lesions of the uterine cervix associated with human papillomavirus (HPV) infection suggest a diminished capacity to capture viral antigens and to induce a protective immune response. Method of study To test if a cervical application of GM-CSF could restore an immune response against HPV in women with cervical low-grade squamous intraepithelial lesions (LSIL). We performed two clinical trials with11 healthy women and 15 patients with LSIL. Results GM-CSF applications were well tolerated in all enrolled women and no difference in toxicity between the treated and placebo groups was observed during the follow up (until 30 months). Interestingly, in the GM-CSF treated group, a significant increased APC and cytotoxic T lymphocyte infiltration was observed in the cervical biopsies with no change in regulatory T cell numbers. All the HPV16+ patients exhibited an immune response against HPV16 after GM-CSF applications, as shown by NK and/or T cells producing IFN-γ whereas no cellular immune response was observed before the treatment. Moreover, the anti-VLP antibody titers also increased after the treatment. Conclusion These encouraging results obtained from a limited number of subjects justify further study on the therapeutic effect of APC in cervical (pre)neoplastic lesions. [less ▲]

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See detailEffects of oral contraception with ethinylestradiol and drospirenone on oxidative stress in women 18-35 years old.
De Groote, D.; PERRIER d'HAUTERIVE, Sophie ULg; Pintiaux, Axelle ULg et al

in Contraception (2009), 80(2), 187-93

Background Oral contraceptives (OCs) with estrogens and progestins may affect oxidative stress (OS) status. Study design A group of 32 women using oral contraceptives (OCU) containing 0.03 mg ... [more ▼]

Background Oral contraceptives (OCs) with estrogens and progestins may affect oxidative stress (OS) status. Study design A group of 32 women using oral contraceptives (OCU) containing 0.03 mg ethinylestradiol and 3 mg drospirenone have been compared to a matched control group of 30 noncontraception users (NCU). Blood levels of antioxidants, trace elements and markers of lipid peroxidation were assessed by biochemical methods. A microarray analysis of whole blood mRNA levels of 200 genes involved in OS-dependant pathway was also performed. Results Levels of zinc, vitamin E and antibodies to oxidized low-density lipoproteins (LDLs) were not significantly different between the two groups. On the other hand, significant increases in the mean levels of lipid peroxides (+176%, p<.001), oxidized LDLs (+145%, p<.002), copper (+103%, p<.001), Cu/Zn ratio (+100%, p<.001) and a significant decrease in the mean level of β-carotene (−41%, p<.01) were observed in the OCU compared to NCU. There was a highly significant positive correlation between the lipid peroxide levels and the copper-to-zinc ratio. From the 200 genes tested by microarray, one coding for HSP70 was significantly up-regulated (log2 fold change=+ 0.45, p<.02) and one coding for inducible nitric oxide synthase significantly down-regulated (log2 fold change=−0.24, p<.05) in the OCU compared to the NCU. Conclusions The recently introduced combination of ethinylestradiol and drospirenone induced the heightening of lipid peroxidation correlated with high levels of copper, a situation that could be associated with increased cardiovascular risk. [less ▲]

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See detailPhase I/IIclinical trial of local GM-CSF application in patients with cervical HPV-associated low grade squamous intraepithelial lesions
Hubert, Pascale ULg; Doyen, Jean ULg; Chapelle, X. et al

Conference (2007)

Background: Quantitative and functional alterations of professional antigen-presenting cells (APC) in SIL suggest that these lesions may have a diminished capacity to capture viral antigens. Moreover, GM ... [more ▼]

Background: Quantitative and functional alterations of professional antigen-presenting cells (APC) in SIL suggest that these lesions may have a diminished capacity to capture viral antigens. Moreover, GM-CSF (whose production is decreased in HPV-transformed keratinocytes) is an essential factor for the migration of APC in cervical (pre)neoplastic lesions formed in vitro and transplanted in vivo on mouse. In this study we performed a phase I/II clinical trial in order to determine whether a local application of GM-CSF on cervical low-grade squamous intraepithelial lesions (LSIL) might increase the recruitment of APC into the epithelium and indirectly the viral antigen presentation to the immune system. Methods: Fifteen patients with LSIL (10 GM-CSF and 5 placebo) were enrolled in this study. Patients received 4 GM-CSF applications (or placebo gel) and were followed during 6-7 months. APC infiltration was quantified by immunostaining with anti-CD1a mAb. Cellular immune response was evaluated by using an IFN-gamma intracellular staining on PBMC stimulated in vitro with the E7 HPV16 protein and L1 HPV16 Virus-like particles (VLP). Hybrid capture was performed to semi-quantify the viral DNA in cervical brush specimens. Results: GM-CSF applications were well tolerated in all patients. No difference in the cytological/histological and viral parameters assessed at 2 and 6 months after the last application was observed between the GM-CSF and the placebo group. An increased number of CD1a+ APC was observed in 6/10 patients treated by GM-CSF compared to 1/5 patient in the placebo group. There was an increased immune response against HPV in the GM-CSF group showed by NK and T cells producing IFN-gamma. [less ▲]

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See detailLe streptocoque du groupe B en clinique antenatale et en salle de travail: un probleme d'attitude systematique
Lorquet, Sophie ULg; Melin, Pierrette ULg; Minon, Jean-Marc et al

in Journal de Gynécologie, Obstétrique et Biologie de la Reproduction (2005), 34(2), 115-27

OBJECTIVES: We wanted to evaluate the compliance to the local recommendations, similar to the CDC (Centers for Disease Control and prevention) recommendations launched in 1996, for the prevention of ... [more ▼]

OBJECTIVES: We wanted to evaluate the compliance to the local recommendations, similar to the CDC (Centers for Disease Control and prevention) recommendations launched in 1996, for the prevention of perinatal group B streptococcal (GBS) disease in the clinical practice of a academic maternity and to identify the causes of missed screening and antibiotic prophylaxis. MATERIALS AND METHODS: Retrospective study of 1249 consecutive pregnancies between 1st January and 31th August 2002. The screening methods for GBS colonisation were the culture of rectovaginal swabs collected between 35 and 37 weeks and/or a rapid antigenic screening performed on a vaginal swab collected at the patient's admission for labor. RESULTS: Rate of global screening was very high (97.8%): 28.8% of antenatal screening versus 90.3% during labor. An appropriate antibiotic prophylaxis was administered to only one-third of positive women when the screening was performed at admission to the labor room, whereas two-thirds of GBS-positive women screened between 35 and 37 weeks received their antibiotic prophylaxis. 2.4%o of the newborns were infected and 2.9% were colonized. Among the different risk factors, intrapartum fever was more often associated with maternal GBS colonisation. The observed sensitivity of the rapide antigenic test was 20.4%. CONCLUSION: Compliance to guidelines is sometimes difficult in the clinical practice of an academic maternity. In our hands the rapid test for GBS screening had low sensitivity. The analysis of these data led to introducing a computerized algorithm in our maternity to improve the prevention of perinatal group B streptococcal disease. [less ▲]

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See detailPhase I/II trial of immunogenicity of a human papillomavirus (HPV) type 16 E7 protein-based vaccine in women with oncogenic HPV-positive cervical intraepithelial neoplasia
Hallez, Sophie; Simon, Philippe; Maudoux, Frédéric et al

in Cancer Immunology, Immunotherapy (2004), 53(7), 642-650

Purpose: Infection with oncogenic human papillomavirus (HPV) and HPV-16 in particular is a leading cause of anogenital neoplasia. High-grade intraepithelial lesions require treatment because of their ... [more ▼]

Purpose: Infection with oncogenic human papillomavirus (HPV) and HPV-16 in particular is a leading cause of anogenital neoplasia. High-grade intraepithelial lesions require treatment because of their potential to progress to invasive cancer. Numerous preclinical studies have demonstrated the therapeutic potential of E7-directed vaccination strategies in mice tumour models. In the present study, we tested the immunogenicity of a fusion protein (PD-E7) comprising a mutated HPV-16 E7 linked to the first 108 amino acids of Haemophilus influenzae protein D, formulated in the GlaxoSmithKline Biologicals adjuvant AS02B, in patients bearing oncogenic HPV-positive cervical intraepithelial neoplasia (CIN). Methods: Seven patients, five with a CIN3 and two with a CIN1, received three intramuscular injections of adjuvanted PD-E7 at 2-week intervals. Three additional CIN1 patients received a placebo. CIN3 patients underwent conization 8 weeks postvaccination. Cytokine flow cytometry and ELISA were used to monitor antigen-specific cellular and antibody responses from blood taken before and after vaccine or placebo injection. Results: Some patients had preexisting systemic IFN-gamma CD4(+) (1/10) and CD8(+) (5/10) responses to PD-E7. Vaccination, not placebo injection, elicited systemic specific immune responses in the majority of the patients. Five vaccinated patients (71%) showed significantly increased IFN-gamma CD8(+) cell responses upon PD-E7 stimulation. Two responding patients generated long-term T-cell immunity toward the vaccine antigen and E7 as well as a weak H. influenzae protein D (PD)-directed CD4(+) response. All the vaccinated patients, but not the placebo, made significant E7- and PD-specific IgG. Conclusions: The encouraging results obtained from this study performed on a limited number of subjects justify further analysis of the efficacy of the PD-E7/AS02B vaccine in CIN patients. [less ▲]

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See detailCrystallization and preliminary X-ray analysis of a bacterial psychrophilic enzyme, phosphoglycerate kinase
Mandelman, D.; Bentahir, M.; Feller, Georges ULg et al

in Acta Crystallographica Section D-Biological Crystallography (2001), 57(Pt 11), 1666-8

The glycolytic enzyme phosphoglycerate kinase (PGK) from the Antarctic microorganism Pseudomonas sp. TACII18 is a cold-adapted enzyme that displays a high specific activity at low temperatures and ... [more ▼]

The glycolytic enzyme phosphoglycerate kinase (PGK) from the Antarctic microorganism Pseudomonas sp. TACII18 is a cold-adapted enzyme that displays a high specific activity at low temperatures and decreased thermostability relative to its mesophilic counterpart. Herein, the preliminary crystallization and structure solution of psychrophilic PGK in its native form and cocrystallized with 3-phosphoglyceric acid (3-PGA) and the ATP analogue adenylyl imidophosphate (AMP-PNP) is reported. The complexed form of PGK crystallized in 2-3 d at 290 K, whereas the native form of the enzyme required 8-12 months. Morphologically, both crystal forms are similar and X-ray diffraction experiments indicate that the crystals are isomorphous. The crystals diffracted to a resolution of 2.0 A and belong to the space group P3(2). with unit-cell parameters a = b = 58.5, c = 85.4 A. [less ▲]

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See detailSEARCH FOR PARVALBUMIN IN CARDIAC-MUSCLE OF NORMAL AND HEMOGLOBIN-MYOGLOBIN FREE ANTARCTIC FISH
Laforet, C.; Feller, Georges ULg; Gerday, Colette ULg

in Journal of Muscle Research and Cell Motility (1991), 12(1), 115-116

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