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See detailUse of histone deacetylase 8 (HDAC8), a new marker of smooth muscle differentiation, in the classification of mesenchymal tumors of the uterus
de Leval, Laurence ULg; Waltregny, David ULg; Boniver, Jacques ULg et al

in American Journal of Surgical Pathology (2006), 30(3), 319-327

Uterine smooth muscle tumors (SMTs) are usually recognized on the basis of their routine morphologic features; however, their distinction from endometrial stromal tumors (ESTs), the second most common ... [more ▼]

Uterine smooth muscle tumors (SMTs) are usually recognized on the basis of their routine morphologic features; however, their distinction from endometrial stromal tumors (ESTs), the second most common mesenchymal tumor of the uterus, is sometimes problematic. Histone deacetylases (HDACs) were originally identified as nuclear enzymes regulating histone acetylation. We have recently shown that in normal human tissues, HDAC8 is exclusively expressed in the cytoplasm of cells showing smooth muscle differentiation. In this study, we examined HDAC8 expression in SMTs and ESTs of the uterus to determine whether HDAC8 may be a useful diagnostic tool in the classification of problematic uterine mesenchymal tumors. HDAC8 immunohistochemical staining was performed in 15 leiomyomas (LMs), 9 highly cellular leiomyomas (HCLs), 8 epithelioid SMTs, 13 leiomyosarcomas (LMSs), and 17 ESTs, including 3 with sex-cord differentiation and 5 with smooth muscle differentiation. All tumors were also stained for other smooth muscle markers (desmin, h-caldesmon, smooth muscle actin [SMA], smooth muscle myosin heavy chain) and for CD 10. All LMs had moderate to strong expression of all smooth muscle markers. HDAC8 was detected in 8 of 9 HCLs and in all epithelioid SMTs (8 of 8); however, it was weak in 4 epithelioid SMTs. In contrast, desmin, h-caldesmon and smooth muscle myosin were positive in only 2 of 8, 1 of 8 and 4 of 8 epithelioid SMTs, respectively. All smooth muscle markers had similar frequency of staining in LMSs; however, HDAC8 showed overall moderate intensity compared with other smooth muscle markers, which showed stronger staining. HDAC8, h-caldesmon, and smooth muscle myosin did not stain conventional areas of ESTs or ESTs with sex-cord differentiation, whereas SMA and desmin were positive in those areas in 4 of 12 and 3 of 12 ESTs, respectively. Areas of smooth muscle differentiation in ESTs were positive for HDAC8 in all cases, but they were less constantly positive for the other smooth muscle markers. CD10 was expressed in most ESTs (14 of 17), but it was also positive in 15 of 45 SMTs. In conclusion: 1) HDAC8 seems to be a specific marker of SM differentiation because conventional ESTs and ESTs with sex-cord differentiation are negative for HDAC8, whereas areas of smooth muscle differentiation in these tumors are consistently positive; 2) HDAC8 gives similar results to those obtained with desmin, h-caldesmon, and smooth muscle myosin in both LMs and LMSs, although the staining for HDAC8 in LMSs tends to be less intense; 3) HDAC8 may be a more sensitive marker than desmin and h-caldesmon in epithelioid SMTs. Thus, HDAC8 detection may be useful in helping the differential diagnosis of uterine mesenchymal tumors. [less ▲]

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See detailDoes psychological characteristic influence physicians' communication styles? Impact of physicians' locus of control on interviews with a cancer patient and a relative
Libert, Yves; Merckaert, Isabelle; Reynaert, Christine et al

in Supportive Care in Cancer (2006), 14(3), 230-242

Context: Physicians' psychological characteristics may influence their communication styles and may thus interfere with patient-centred communication. Objective: Our aim was to test the hypothesis that ... [more ▼]

Context: Physicians' psychological characteristics may influence their communication styles and may thus interfere with patient-centred communication. Objective: Our aim was to test the hypothesis that, in interviews with a cancer patient and a relative, physicians with an "external" locus of control (LOC; who believe that life outcomes are controlled by external forces such as luck, fate or others) have a communication style different from that of physicians with an "internal" LOC (who believe that life outcomes are controlled by their own characteristics or actions). Design, setting, participants and intervention: Eighty-one voluntary physicians practising in the field of oncology were recorded while performing an actual and a simulated interview with a cancer patient and a relative. Main outcome measures: Physicians' communication skills were assessed using the Cancer Research Campaign Workshop Evaluation Manual. Physicians' LOC was assessed using the Rotter I-E scale. The communication skills of the upper and lower quartiles of physicians in respect of their scores on this scale were compared using Student's t test. Results: In actual interviews, physicians with an "external" LOC talked more to the relative (P=0.017) and used more utterances with an assessment function (P=0.010) than physicians with an "internal" LOC. In simulated interviews, physicians with an "external" LOC used less utterances that give premature information (P=0.031) and used more utterances with a supportive function, such as empathy and reassurance (P=0.029), than physicians with an "internal" LOC. Conclusion: These results provide evidence that physicians' LOC can influence their communication styles. Physicians' awareness of this influence constitutes a step towards a tailoring of their communication skills to every patient's and relative's concerns and needs and thus towards a patient-centred communication. [less ▲]

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See detailUterine tumors resembling ovarian sex-cord tumors: A study of 14 cases showing a diverse phenotypic profile
de Leval, Laurence ULg; Waltregny, David ULg; Dupuis, Léon-Marie et al

in Laboratory Investigation : Journal of Technical Methods & Pathology (2006, January), 86(Suppl. 1), 176

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See detailUterine tumors resembling ovarian sex-cord tumors: A study of 14 cases showing a diverse phenotypic profile
de Leval, Laurence ULg; Waltregny, David ULg; Dupuis, Léon-Marie et al

in Modern Pathology (2006, January), 19(Suppl. 1), 176

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See detailTeaching communication and stress management skills to junior physicians dealing with cancer patients: a Belgian Interuniversity Curriculum
Bragard, Isabelle ULg; Razavi, Darius; Marchal, Serge et al

in Supportive Care in Cancer (2006), 14(5), 454-461

Background: Ineffective physicians' communication skills have detrimental consequences for patients and their relatives, such as insufficient detection of psychological disturbances, dissatisfaction with ... [more ▼]

Background: Ineffective physicians' communication skills have detrimental consequences for patients and their relatives, such as insufficient detection of psychological disturbances, dissatisfaction with care, poor compliance, and increased risks of litigation for malpractice. These ineffective communication skills also contribute to everyday stress, lack of job satisfaction, and burnout among physicians. Literature shows that communication skills training programs may significantly improve physicians' key communication skills, contributing to improvements in patients' satisfaction with care and physicians' professional satisfaction. This paper describes a Belgian Interuniversity Curriculum (BIC) theoretical roots, principles, and techniques developed for junior physicians specializing in various disciplines dealing with cancer patients. Curriculum description: The 40-h training focuses on two domains: stress management skills and communication skills with cancer patients and their relatives. The teaching method is learner-centered and includes a cognitive, behavioral, and affective approach. The cognitive approach aims to improve physicians' knowledge and skills on the two domains cited. The behavioral approach offers learners the opportunity to practice these appropriate skills through practical exercises and role plays. The affective approach allows participants to express attitudes and feelings that communicating about difficult issues evoke. Such an intensive course seems to be necessary to facilitate the transfer of learned skills in clinical practice. Conclusions: The BIC is the first attempt to bring together a stress management training course and a communication training course that could lead not only to communication skills improvements but also to burnout prevention. [less ▲]

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See detailChromosomal patterns of gene expression from microarray data: methodology, validation and clinical relevance in gliomas.
Turkheimer, Federico E; Roncaroli, Federico; Hennuy, Benoît ULg et al

in BMC Bioinformatics (2006), 7

BACKGROUND: Expression microarrays represent a powerful technique for the simultaneous investigation of thousands of genes. The evidence that genes are not randomly distributed in the genome and that ... [more ▼]

BACKGROUND: Expression microarrays represent a powerful technique for the simultaneous investigation of thousands of genes. The evidence that genes are not randomly distributed in the genome and that their coordinated expression depends on their position on chromosomes has highlighted the need for mathematical approaches to exploit this dependency for the analysis of expression data-sets. RESULTS: We have devised a novel mathematical technique (CHROMOWAVE) based on the Haar wavelet transform and applied it to a dataset obtained with the Affymetrix HG-U133_Plus_2 array in 27 gliomas. CHROMOWAVE generated multi-chromosomal pattern featuring low expression in chromosomes 1p, 4, 9q, 13, 18, and 19q. This pattern was not only statistically robust but also clinically relevant as it was predictive of favourable outcome. This finding was replicated on a data-set independently acquired by another laboratory. FISH analysis indicated that monosomy 1p and 19q was a frequent feature of tumours displaying the CHROMOWAVE pattern but that allelic loss on chromosomes 4, 9q, 13 and 18 was much less common. CONCLUSION: The ability to detect expression changes of spatially related genes and to map their position on chromosomes makes CHROMOWAVE a valuable screening method for the identification and display of regional gene expression changes of clinical relevance. In this study, FISH data showed that monosomy was frequently associated with diffuse low gene expression on chromosome 1p and 19q but not on chromosomes 4, 9q, 13 and 18. Comparative genomic hybridisation, allelic polymorphism analysis and methylation studies are in progress in order to identify the various mechanisms involved in this multi-chromosomal expression pattern. [less ▲]

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See detailL'echinococcose alveolaire: une zoonose d'apparition recente en Wallonie
Wauters, Odile ULg; Honore, Charles ULg; Detry, Olivier ULg et al

in Revue Médicale de Liège (2005), 60(11), 867-74

Alveolar echinococcosis is a serious parasitic disease, leading to large hepatic lesions. It must be distinguished from cystic echinococcosis, or hydatic cyst, caused by Echinococcus granulosus. Early ... [more ▼]

Alveolar echinococcosis is a serious parasitic disease, leading to large hepatic lesions. It must be distinguished from cystic echinococcosis, or hydatic cyst, caused by Echinococcus granulosus. Early diagnosis may allow surgical removal of the lesions by segmental hepatectomy, the only curative treatment. Parasitostatic medical treatment with albendazole may promote stabilization of the disease. Until recently, Belgium was considered a country at very low risk for alveolar echinococcosis, as no human case was reported, despite up to 51% of fox infection in southern Belgium autopsy series. Recently four patients presented with alveolar echinococcosis at the University Hospital Center of Liege, leading to the fear of a possible alveolar echinococcosis endemy in southern Belgium. Two of these patients underwent curative hepatectomy, but the other two had already pulmonary metastases at diagnosis and received palliative albendazole therapy. This article presents these cases, and reviews the clinical features of this parasitic disease. [less ▲]

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See detailFactors that influence physicians' detection of distress in patients with cancer - Can a communication skills training program improve physicians' detection?
Merckaert, Isabelle; Libert, Yves; Delvaux, Nicole et al

in Cancer (2005), 104(2), 411-421

BACKGROUND. No study to date has assessed the impact of skills acquisition after a communication skills training program on physicians' ability to detect distress in patients with cancer. METHODS. First ... [more ▼]

BACKGROUND. No study to date has assessed the impact of skills acquisition after a communication skills training program on physicians' ability to detect distress in patients with cancer. METHODS. First, the authors used a randomized design to assess the impact, on physicians' ability to detect patients' distress, of a 1-hour theoretical information course followed by 2 communication skills training programs: a 2.5-day basic training program and the same training program consolidated by 6 3-hour consolidation workshops. Then, the investigate contextual, patient, and communication variables or factors associated with physicians' detection of patients' distress were investigated. After they attended the basic communication skills training program, physicians were assigned randomly to consolidation workshops or to a waiting list. Interviews with a cancer patient were recorded before training, after consolidation workshops for the group that attended consolidation workshops, and approximate to 5 months after basic training for the group that attended basic training without the consolidation workshops. Patient distress was recorded with the Hospital Anxiety and Depression Scale before the interviews. Physicians rated their patients' distress on a visual analog scale after the interviews. Physicians' ability to detect patients' distress was measured through computing differences between physicians' ratings of patients' distress and patients' self-reported distress. Communication skills were analyzed according to the Cancer Research Campaign Workshop Evaluation Manual. RESULTS. Fifty-eight physicians were evaluable. Repeated -measures analysis of variance showed no statistically significant changes over time and between groups in physicians' ability to assess patient distress. Mixed-effects modeling showed that physicians' detection of patients' distress was associated negatively with patients' educational level (P = 0.042) and with patients' self-reported distress (P < 0.000). Mixed-effects modeling also showed that physicians' detection of patient distress was associated positively with physicians breaking bad news (P = 0.022) and using assessment skills (P = 0.015) and supportive skills (P = 0.045). CONCLUSIONS. Contrary to what was expected, no change was observed in physicians' ability to detect distress in patients with cancer after a communication skills training programs, regardless of whether physicians attended the basic training program or the basic training program followed by the consolidation workshops. The results indicated a need for further improvements in physicians' detection skills through specific training modules, including theoretical information about factors that interfere with physicians' detection and through role-playing exercises that focus on assessment and supportive skills that facilitate detection. (c) 2005 American Cancer Society. [less ▲]

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See detailPhysicians' communication with a cancer patient and a relative - A randomized study assessing the efficacy of consolidation workshops
Delvaux, N.; Merckaert, I.; Marchal, S. et al

in Cancer (2005), 103(11), 2397-2411

BACKGROUND. Although patients with cancer are often accompanied by a relative during medical interviews, to the authors' knowledge little is known regarding the efficacy of communication skills training ... [more ▼]

BACKGROUND. Although patients with cancer are often accompanied by a relative during medical interviews, to the authors' knowledge little is known regarding the efficacy of communication skills training programs on physicians' communication skills in this context. The objective of the current study was to assess the efficacy of 6 consolidation workshops, 3 hours in length, that were conducted after a 2.5-day basic training program. METHODS. After attending the basic training program, physicians were assigned randomly to consolidation workshops or to a waiting list. Training efficacy was assessed through simulated and actual interviews that were recorded on an audio tape at baseline, after consolidation workshops for the consolidation-workshops group, and 5 months after the end of basic training for the waiting-list group. Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual. Patients' and relatives' perceptions of and satisfaction with physicians' communication performance were assessed using a 15-item questionnaire. RESULTS. Sixty-two physicians completed the training program. Compared with physicians who participated to the basic training program, when addressing the patient, physicians who were randomized to the consolidation workshops used more open, open directive, and screening questions (P = 0.011 in simulated patient interviews and P = 0.005 in actual patient interviews) and elicited and clarified psychologic concerns more often (P = 0.006 in simulated patient interviews and P < 0.001 in actual patient interviews). When they addressed the relative, physicians who were randomized to the consolidation workshops gave less premature information (P = 0.032 in simulated patient interviews and P < 0.001 in actual patient interviews). When they addressed the patient and the relative simultaneously, physicians who were randomized to the consolidation workshops used more empathy, educated guesses, alerting to reality, confronting, negotiating, and summarizing (P = 0.003 in simulated patient interviews and P = 0.024 in actual patient interviews). Patients, but not relatives, who interacted with physicians in the consolidation-workshops group were more satisfied globally with the interviews (P = 0.022). CONCLUSIONS. Six 3-hour consolidation workshops resulted in improved communication skills addressed to patients and to relatives. The current results showed that the transfer of skills addressing relatives' concerns remained limited and that consolidation workshops should focus even more systematically on the practice of three-person interviews. (c) 2005 American Cancer Society. [less ▲]

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See detailProduction of large numbers of Langerhans' cells with intraepithelial migration ability in vitro
Hubert, Pascale ULg; Bousarghin, Latifa; Greimers, Roland ULg et al

in Experimental Dermatology (2005), 14(6), 469-477

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See detailSentinel lymph node mapping in colon cancer: a feasability study
Laurent, S.; Detroz, Bernard ULg; Detry, Olivier ULg et al

in Acta Gastro-Enterologica Belgica (2005, January), 68(1), 15

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See detailMurine bone marrow stromal cells sustain in vivo the survival of hematopoietic stem cells and the granulopoietic differentiation of more mature progenitors.
Hubin, Frederique; Humblet, Chantal ULg; Belaid, Zakia ULg et al

in Stem Cells (2005), 23(10), 1626-33

The study of the human hematopoietic system would be facilitated by availability of a relevant animal model. Because the medullar microenvironment is made of different types of cells, interactions between ... [more ▼]

The study of the human hematopoietic system would be facilitated by availability of a relevant animal model. Because the medullar microenvironment is made of different types of cells, interactions between hematopoietic cells and stromal cells are difficult to analyze in detail. As an approach for establishing an in vivo model to dissect these interactions, we grafted murine bone marrow fibroblastic cells (MS-5 cell line) with hematopoietic cells into the kidney capsule of syngenic mice. To identify the origin of cells present in the graft, we used green fluorescent protein-stable transfected MS-5 cells for the transplantation. To analyze the evolution of stromal cells and identify hematopoietic cells able to develop in these conditions, we performed morphology, histochemistry, and immunohistology on tissue sections at different times after transplantation. When injected alone, MS-5 cells differentiate into adipocytes. When injected with a bone marrow suspension or with isolated CD45+ cells (leukocytes), the stromal cells keep their fibroblastic morphology and their alkaline phosphatase expression and sustain granulopoiesis. When injected with hematopoietic stem cells called c-kit+ Sca-1+ Lin- suspension, clusters of hematopoietic cells are also observed: They do not present any granulopoietic activity and do not belong to B or T population nor to erythroid lineage. They are quiescent, induce bone marrow recovery and survival of lethally irradiated recipients, are able to form macroscopic colonies in the spleen, and are able to form very few colonies in vitro, suggesting that they are hematopoietic stem cells. In conclusion, our results show that reticular fibroblastic stromal cells MS-5 sustain the survival of stem cells and are not able to induce their differentiation. However, they can control differentiation, proliferation, and/or survival of hematopoietic cells engaged in myeloid lineage. [less ▲]

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See detailDifferential expression of vascular endothelial growth factor and its receptors in hematopoietic and fatty bone marrow: evidence that neuropilin-1 is produced by fat cells.
Belaid, Zakia ULg; Hubint, Frederique; Humblet, Chantal ULg et al

in Haematologica (2005), 90(3), 400-1

Vascular endothelial growth factor (VEGF), its receptors (VEGFR-1, VEGFR-2) and neuropillin-1 (NRP-1) are expressed at variable levels in bone marrow. NRP-1expression is higher in fatty bone marrow than ... [more ▼]

Vascular endothelial growth factor (VEGF), its receptors (VEGFR-1, VEGFR-2) and neuropillin-1 (NRP-1) are expressed at variable levels in bone marrow. NRP-1expression is higher in fatty bone marrow than in hematopoietic marrow. Adipocytes are responsible for NRP-1 expression suggesting that they may play a role in hematopoiesis by producing NRP-1 or that NRP-1 may regulate adipocyte activity. [less ▲]

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See detailApproche de la complexité contextuelle et de la pluridisciplinarité de l'action médicale : mise en place de séances d'Apprentissage à la résolution de Problèmes complexes (ARPc) en fin de 2ème cycle d'études médicales
Giet, Didier ULg; Massart, Valérie ULg; Stir, Arielle et al

in Pédagogie Médicale (2005), (6), 88-97

Contexte: La formation des futurs médecins doit prendre en compte la portée éthique, socio-environnementale, économique, juridique et psychologique de l’action médicale ainsi que ses aspects ... [more ▼]

Contexte: La formation des futurs médecins doit prendre en compte la portée éthique, socio-environnementale, économique, juridique et psychologique de l’action médicale ainsi que ses aspects pluridisciplinaires. Dans le cadre d’un renouveau pédagogique décidé en Faculté de Médecine de l’Université de Liège, une modalité particulière de l’apprentissage par problèmes, les séances d’Apprentissage à la Résolution de Problèmes complexes (ARPc), a été instaurée. Buts : Les auteurs rapportent la méthodologie spécifique, étayée par des exemples concrets, développée lors de l’instauration des séances d’ARPc ainsi que les premières analyses d’une procédure d’évaluation qualitative. Sujet : Le dispositif s’adresse aux étudiants des deux dernières années du 2e cycle de formation médicale. Les objectifs pédagogiques spécifiques des ARPc sont l’approche de la complexité contextuelle de toute pratique médicale et l’initiation au travail pluridisciplinaire. Résultats : Les premières procédures d’évaluation qualitatives ciblant étudiants et enseignants donnent des résultats assez favorables. Conclusion : L’expérience est poursuivie moyennant quelques aménagements organisationnels mineurs. Elle s’ouvre à d’autres disciplines médicales et fait l’objet d’une évaluation quantitative à publier ultérieurement. [less ▲]

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See detailHuman papillomavirus 16 virus-like particles use heparan sulfates to bind dendritic cells and colocalize with langerin in Langerhans cells.
Bousarghin, Latifa; Hubert, Pascale ULg; Franzen, Elisabeth et al

in Journal of General Virology (The) (2005), 86(Pt 5), 1297-305

Langerhans cells (LC), the immature dendritic cells (DC) that reside in epithelial tissues are among the first immune cells to encounter human papillomavirus (HPV) and are not activated by HPV virus-like ... [more ▼]

Langerhans cells (LC), the immature dendritic cells (DC) that reside in epithelial tissues are among the first immune cells to encounter human papillomavirus (HPV) and are not activated by HPV virus-like particles (VLPs) in contrast to DC. The notion that the differences in response to HPV VLPs between LC and DC are associated with different types of cell binding and intracellular trafficking has been addressed. Inhibition experiments with heparin and sodium chlorate showed that heparan sulfates are necessary for HPV 16 VLPs to bind to DC but not to LC. Electron microscopy analysis demonstrated a colocalization of HPV 16 VLPs and langerin, which is expressed only by LC. This colocalization was observed on the cell surface but also in cytoplasmic vesicles. As anti-langerin antibodies, HPV 16 VLPs were associated with a faster entry kinetics in LC, as reflected by the fact that VLPs were observed near the nuclear membrane of LC within 10 min whereas more than 60 min were needed in DC. However, no difference between LC and DC was observed for the endocytosis pathway. HPV 16 VLPs entered in both DC and LC by a clathrin-dependent-pathway and were then localized in large cytoplasmic vesicles resembling endosomes. [less ▲]

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See detailProstaglandin E2 induces the expression of functional inhibitory CD94/NKG2A receptors in human CD8+ T lymphocytes by a cAMP-dependent protein kinase A type I pathway.
Zeddou, Mustapha ULg; Greimers, Roland ULg; de Valensart, Nicolas et al

in Biochemical Pharmacology (2005), 70(5), 714-24

The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small ... [more ▼]

The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small fraction of activated T cells, predominantly of CD8+ phenotype. Abnormal upregulation of the CD94/NKG2A inhibitory NKR on cytotoxic T cells (CTLs) could be responsible for a failure of immunosurveillance in cancer or HIV infection. In an attempt to identify the mechanisms leading to inhibitory NKR upregulation on T cells, we analyzed the expression of the CD94/NKG2A heterodimer on human CTLs activated with anti-CD3 mAb in the presence of PGE2 or with 8-CPT-cAMP, an analogue of cyclic AMP. As previously described, anti-CD3 mAb-mediated activation induced the expression of CD94/NKG2A on a small fraction of CD8+ T cells. Interestingly, when low concentrations of PGE2 or 8-CPT-cAMP were present during the culture, the proportion of CD8+ T cells expressing CD94/NKG2A was two- to five-fold higher. This upregulation was partially prevented by PKA inhibitors, such as KT5720 and Rp-8-Br-cAMP (type I selective). We also report that cAMP induces upregulation of NKG2A at the mRNA level. We further demonstrated that cross-linking of CD94 on CD8+ T cells expressing the CD94/NKG2A heterodimer inhibits their cytotoxic activity in a bispecific antibody redirected lysis assay. Our findings clearly demonstrate that the PGE2/cAMP/PKA type I axis is involved in the expression of CD94/NKG2A receptor on human CD8+ T lymphocytes. [less ▲]

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See detailHigh levels of p105 (NFKB1) and p100 (NFKB2) proteins in HPV16-transformed keratinocytes: role of E6 and E7 oncoproteins.
Havard, Laurence; Rahmouni, Souad ULg; Boniver, Jacques ULg et al

in Virology (2005), 331(2), 357-66

We have previously shown that functional components of the NF-kappaB signaling pathway are up-regulated and sequestered in the cytoplasm of human papillomavirus 16 (HPV16)-transformed cell lines leading ... [more ▼]

We have previously shown that functional components of the NF-kappaB signaling pathway are up-regulated and sequestered in the cytoplasm of human papillomavirus 16 (HPV16)-transformed cell lines leading to a reduced activity of NF-kappaB. In this study, we examined the expression of the NF-kappaB precursors p100 and p105 in keratinocytes transformed or not by HPV16. Western immunoblotting experiments demonstrated high levels of p100 and p105 proteins not only in HPV16+ cervical carcinoma-derived keratinocytes but also in keratinocytes stably transfected by HPV16 E6 or E7 oncogenes. Moreover, p100 and p105 proteins were predominantly cytoplasmic and nuclear in keratinocytes expressing E7 and E6, respectively. A predominantly cytoplasmic localization of E7 protein was also detected in all keratinocytes expressing E7. Our results suggest that HPV16 E6 and E7 proteins modulate the expression and the subcellular localization of p100 and p105 NF-kappaB precursors. [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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