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See detailEvidence That Breast Cancer Associated Microcalcifications Are Mineralized Malignant Cells
Castronovo, Vincenzo ULg; Bellahcene, Akeila ULg

in International Journal of Oncology (1998), 12(2), 305-8

Microcalcifications are often associated with both benign and malignant human breast lesions. Around 40% of mammary carcinoma present such ectopic mineralization and frequently, they are the only ... [more ▼]

Microcalcifications are often associated with both benign and malignant human breast lesions. Around 40% of mammary carcinoma present such ectopic mineralization and frequently, they are the only mammographic feature that indicate the presence of a tumoral lesion. Microcalcifications associated with breast cancer are usually composed of hydroxyapatite, the bone specific mineral. The mechanisms responsible for the formation of such crystals within breast malignant tissue have not been elucidated. A possible clue could be provided by the recent demonstration that breast cancer cells express several bone matrix proteins including osteonectin, osteopontin and bone sialoprotein (BSP). This latter phospho-protein is involved in the initiation of hydroxyapatite crystallisation and its expression in breast cancer has been associated to the presence of hydroxyapatite microcalcifications. We examined 10 human breast cancer lesions which were characterized by the presence of microcalcifications and high expression of BSP. Histological examination of the lesions suggested, in most of the cases, that the microcalcifications were breast cancer cells which became mineralized. Hydroxyapatite stained in blue by hematoxylin appears concentrated around single of associated cancer cells. Staining of these tissue sections with 4',6 diamidino-2-phenylindole which specifically labels DNA led us to demonstrate that the mineralizated structures contain cells. These data are the first direct demonstration that breast microcalcifications are fossils of cancer cells. The mechanisms for such a phenomenon remain to be demonstrated. We speculate that the high expression of BSP could create an appropriate microenvironment for the crystallisation of calcium and phosphate into hydroxyapatite. [less ▲]

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See detailEvidence that insulin-like growth factor 2 (IGF2) is the dominant thymic peptide of the insulin superfamily
Geenen, Vincent ULg; Achour, Imane; Martens, Henri ULg et al

in The Endocrine Society (Ed.) Proceedings of the 75th Annual Meeting of the Endocrine Society (1993)

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See detailEvidence that insulin-like growth factor 2 (IGF2) is the dominant thymic peptide of the insulin superfamily
Geenen, Vincent ULg; Achour, Imane; Robert, Françoise et al

in Thymus (1993), 21(2), 115-127

Central T-cell tolerance of neurondocrine functions has been proposed to be primarily induced by the thymic repertoire of neuroendocrine self antigens. The present study aimed at characterizing the human ... [more ▼]

Central T-cell tolerance of neurondocrine functions has been proposed to be primarily induced by the thymic repertoire of neuroendocrine self antigens. The present study aimed at characterizing the human thymic insulin-related self antigen able to represent the pancreatic islet ß cell function in face of the developing T cells. Immunofluorescence studies were performed on human and rat thymic sections, as wess as on the rat IT-45R1 thymic epithelial cell line using several antibodies to epitopes of the insulin peptide family. These studies identify beyond any doubt that IGF2 is the dominant thymic peptide of the insulin family. The sequence of an insulin-derived autoantigen is proposed. This autoantigen is a nonamer and has a hydrophobic residue leucine at position 9. In human species, this autoantigen would primarily be tolerogenic for the pancreatic ß-cell endocrine function during fetal development. [less ▲]

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See detailEvidence that oral tiludronate is a first line prevention of post-menopausal osteoporosis
Reginster, Jean-Yves ULg; Ethgen, D; DEROISY, Rita ULg et al

in Calcified Tissue International (1991), 48

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See detailEvidence that oral tiludronate is a first line prevention of postmenopausal osteoporosis
Reginster, Jean-Yves ULg; Ethgen, D; DEROISY, Rita ULg et al

in Revue du Rhumatisme et des Maladies Osteo-Articulaires (1992), 59

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See detailEvidence that oral tiludronate is a highly effective therapy of Paget's disease of bone
Reginster, Jean-Yves ULg; Roux, C; Picot, C et al

in Journal of Bone and Mineral Research (1994), 25

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See detailEvidence that the interaction between circulating IgA and fibronectin is a normal process enhanced in primary IgA nephropathy.
Davin, J. C.; Li Vecchi, M.; Nagy, J. et al

in Journal of Clinical Immunology (1991), 11(2), 78-94

A solid-phase ELISA was set up to measure the direct binding capacity (BC) of different, commercially available, purified human IgA preparations to plates coated with human fibronectin (FN). It was found ... [more ▼]

A solid-phase ELISA was set up to measure the direct binding capacity (BC) of different, commercially available, purified human IgA preparations to plates coated with human fibronectin (FN). It was found that secretory, polymeric, and, to a much lesser extent, monomeric IgA exhibited elevated FN-BC as compared to their BC to plates coated with bovine serum albumin. This binding was specific since not observed with human IgG or IgM antibodies. In addition, we noted that this interaction was dose dependent, Ca2+ dependent, saturable, and not covalent, was inhibited by soluble FN, but not by a prior incubation of FN-coated plates with anti-human fibronectin antibodies, and appeared to involve on the dimeric FN other structures than its heparin-binding, collagen-binding, or C1q-binding domains. Similar experiments conducted with normal plasma indicated that plasma IgA, but not plasma IgG or IgM, was also capable of significant binding to FN-coated plates. In contrast, serum IgA did not significantly bind to those plates under otherwise identical experimental conditions. Thus, the coagulation process induces a strong decrease in the FN-BC of circulating IgA, which implies the necessity of using plasma rather than serum to study such interactions. The apparent molecular weight of plasma IgA interacting with FN-coated plates ranged between 450 and 900 kd, and its major binding characteristics were quite similar to those observed with purified polymeric IgA. The FN-BC of plasma IgA was then measured by the same ELISA in 30 patients with primary IgA nephropathy (IgAN) and in 23 healthy controls. The mean FN-BC of plasma IgA was significantly higher in patients than in normal controls. This enhancement was due mainly to the augmentation in the concentration of circulating "macromolecular" IgA and was significantly correlated with the plasma levels of IgA-FN complexes. However, the pathogenetic role of these findings was probably not determinant since similar observations were made in alcoholic liver cirrhosis without urinary abnormalities and since the FN-BC of plasma IgA or the plasma levels of IgA-FN complexes were not correlated with the various biological parameters of evolutivity of primary IgAN. In conclusion, these studies suggest that the ability of polymeric IgA to directly bind to FN is involved in the formation of circulating IgA-FN complexes and that this normal binding process, although enhanced in IgAN, is probably not responsible for kidney injury, at least in the patients studied. [less ▲]

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See detailEvidence that the phagocytosis mediated by the peanut agglutinin-like activity of IgG(Fc) receptors of human monocytes is selectively modulated by estradiol and natural estrogens
Malaise, Michel ULg; Franchimont, P.; Mahieu, P. R.

in Journal of Clinical Immunology (1988), 8(6), 495-502

The percentage of human monocytes (MCs) that are able to form rosettes with, and to phagocytose, IgG-coated sheep red blood cells (IgG-SRBCs) has been first determined in vitro by a classical rosette ... [more ▼]

The percentage of human monocytes (MCs) that are able to form rosettes with, and to phagocytose, IgG-coated sheep red blood cells (IgG-SRBCs) has been first determined in vitro by a classical rosette assay in 12 postmenopausal (PM) women. Half of them never received any suppletive estrogen (E) therapy at the time of testing, whereas the other six were chronically treated with E. Three different preparations of the same anti-SRBC IgG antibody batch were coated to SRBCs: the first one was the starting antibody preparation [IgG(total] and the other two were purified by affinity chromatography either on Sepharose-concanavalin A (Con A) or on agarose-peanut agglutinin (PNA) columns specifically recognizing terminal, and/or accessible, alpha-mannosyl [IgG(Con A)] or beta-galactosyl [IgG(PNA)] residues of the Fc domain, respectively. The three IgG preparations exhibited similar hemagglutinating antibody titers (1/100). All experiments were conducted using a coating range of 5000 to 6000 IgG antibody molecules per SRBC. In PM women with E, the rosetting capacity of autologous MCs (percentage of MCs rosetting at least three IgG-SRBCs), their phagocytosing capacity (percentage of MCs ingesting at least three IgG-SRBCs), and the phagocytosis index (number of SRBCs ingested/100 MCs) were similar for each IgG-SRBC preparation considered. In contrast, in PM women without E, the capacity of MCs to phagocytose IgG(PNA)-SRBCs, as well as the phagocytosis index measured with those SRBCs, was strongly reduced (P less than 0.01 at least), when compared to the same parameters determined using IgG(total)-SRBCs and IgG(Con A)-SRBCs. [less ▲]

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See detailEvidence that the relations between novelty-induced activity, locomotor stimulation and place preference induced by cocaine qualitatively depend upon the dose: A multiple regression analysis in inbred C57BL/6J mice
Brabant, Christian ULg; Quertemont, Etienne ULg; Tirelli, Ezio ULg

in Behavioural Brain Research (2005), 158(2), 201-210

It has been speculated that an individual's response to novelty is a reliable predictor of its vulnerability to develop addiction. However, the relationships between response to novelty and the ... [more ▼]

It has been speculated that an individual's response to novelty is a reliable predictor of its vulnerability to develop addiction. However, the relationships between response to novelty and the development of drug-induced conditioned place preference are still unclear. The present study investigates the relationships between locomotor responses to novelty, cocaine-induced locomotor stimulation and conditioned place preference in C57BL/6J mice with multiple regression analyses. Four groups of mice receiving saline, 4, 8 or 12 mg/kg cocaine (i.p.) were submitted to an 8-day unbiased counterbalanced place conditioning protocol. Levels of locomotion on the pre-conditioning session were used as a score of locomotor response to a novel environment. The locomotor activity on the first cocaine-pairing session of the conditioning procedure served as a measure of the locomotion-activating response to a single injection of cocaine. Cocaine-induced dose-dependent locomotor stimulant effects and a significant place preference at all tested doses. A positive correlation was found between the locomotor responses to novelty and the locomotor stimulant effects of cocaine, but was significant only for the highest dose of cocaine (12 mg/kg). In contrast, there was a negative correlation between the locomotor response to novelty and the conditioned place preference induced by 4 mg/kg cocaine. Finally, the locomotor stimulant effects of cocaine do not correlate with cocaine-induced conditioned place preference at any tested dose of cocaine. The relationships between locomotor response to novelty and both cocaine-induced stimulant and rewarding effects can be differentially affected by the dose in inbred C57BL/6J mice. (C) 2004 Elsevier B.V. All rights reserved. [less ▲]

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See detailEvidence that the Two-Way Communication Checklist identifies patient-doctor needs discordance resulting in better 6-month outcome.
van Os, J.; Triffaux, Jean-Marc ULg

in Acta Psychiatrica Scandinavica (2008), 118(4), 322-6

OBJECTIVE: To assess an intervention aimed at reducing patient-professional carer needs discordance. METHOD: In a group of 460 patients with schizophrenia, the Two-Way Communication Checklist (2-COM), an ... [more ▼]

OBJECTIVE: To assess an intervention aimed at reducing patient-professional carer needs discordance. METHOD: In a group of 460 patients with schizophrenia, the Two-Way Communication Checklist (2-COM), an instrument to rate needs, was completed at baseline, 2 months and 6 months by both the patient and the professional carer, allowing for the quantification of patient-carer needs discordance. RESULTS: Reduction in patient-reported 2-COM needs in the group with low baseline needs discordance was much greater at 2 and 6 months (2 months: beta = -0.65, P < 0.001; 6 months: beta = -1.00, P < 0.001) than in the group with high baseline discordance (2 months: beta = -0.35, P < 0.001; 6 months: beta = -0.49, P < 0.001). Reduction in needs discordance between baseline and 2 months (beta = -0.07, P = 0.004) as well between 2 and 6 months (beta = -0.05, P = 0.020) was associated with greater levels of CGI clinical improvement. CONCLUSION: The fact that patient-carer needs discordance impacts negatively, and its reduction positively, on 6-month outcome suggests that systematic inventory of patient-carer views on needs is necessary. [less ▲]

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See detailEvidence that tiludronate is an interesting perspective for prevention and treatment of postmenopausal osteoporosis
Reginster, Jean-Yves ULg; Ethgen, D; Barbier, A et al

in Journal of Bone and Mineral Research (1993), 8(S1), 326

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See detailEvidence that two tilapia (Oreochromis niloticus) prolactins have different osmoregulatory functions during adaptation to a hyperosmotic environment
Auperin, B.; Rentier-Delrue, Françoise ULg; Martial, Joseph ULg et al

in Journal of Molecular Endocrinology (1994), 12(1), 13-24

Two forms of prolactin (tiPRLI and tiPRLII), with only 69% sequence identity, have been previously described in the cichlid fish tilapia (Oreochromis species). In the present study we have attempted to ... [more ▼]

Two forms of prolactin (tiPRLI and tiPRLII), with only 69% sequence identity, have been previously described in the cichlid fish tilapia (Oreochromis species). In the present study we have attempted to investigate the biological activity of these two prolactin forms during adaptation to a hyperosmotic environment. For this purpose, we have developed two highly sensitive (sensitivity: 0.05 ng/ml) and specific (cross-reactivity < 0.04%) radioimmunoassays for tiPRLI and tiPRLII, using recombinant hormones. When fish were directly transferred from fresh to brackish water, the measured levels of plasma tiPRLI and tiPRLII dropped abruptly until 12 h after transfer. Thereafter, plasma tiPRLII remained stable (around 0.5 ng/ml) until the end of the experiment, whereas plasma tiPRLI continued to decrease to undetectable levels. These different patterns of change are reflected in the calculated ratio of plasma tiPRLII to tiPRLI, which increased from 2-3 in fresh water-adapted fish to over 10 in fish which had spent 3 days or more in brackish water. The pituitary contents of tiPRLI and tiPRLII varied in a qualitatively similar fashion after transfer to brackish water. The tiPRLI content dropped continuously after 12 h, reaching one-twelfth of its initial level after 2 weeks. The pituitary tiPRLII content, on the other hand, did not decrease significantly until day 7, and after a 2-week exposure to brackish water it had only decreased by 50%. When injected into tilapia adapted to brackish water, both ovine prolactin and recombinant tiPRLI induced a clear dose-dependent ion-retaining effect. In contrast, the effect induced by tiPRLII treatment was markedly smaller and not dose-dependent. Northern blot analysis of tiPRL mRNAs using either a tiPRLI or a tiPRLII cDNA probe indicated the presence of two mRNAs differing in size: a 1.7 kb mRNA coding for tiPRLI and a 1.3 kb mRNA coding for tiPRLII. After transfer to brackish water, levels of the two mRNAs decreased similarly. The present study indicates that, in O. niloticus, the two forms of prolactin have different osmoregulatory roles during adaptation to brackish water. Accordingly, their synthesis are differentially regulated after transfer to a hyperosmotic environment, presumably at a post-transcriptional level. [less ▲]

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See detailEvidence-based early clinical detection of emerging diseases in food animals and zoonoses: two cases.
Saegerman, Claude ULg; Humblet, Marie-France ULg; Porter, Sarah ULg et al

in Veterinary Clinics of North America. Food Animal Practice (2012), 28(1), 121-131

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See detailEvidence-based guidelines for the pharmacological treatment of postmenopausal osteoporosis: a consensus document by the Belgian Bone Club.
Body, J. J.; Bergmann, P.; Boonen, S. et al

in Osteoporosis International (2010), 21(10), 1657-80

Several drugs are available for the management of postmenopausal osteoporosis. This may, in daily practice, confuse the clinician. This manuscript offers an evidence-based update of previous treatment ... [more ▼]

Several drugs are available for the management of postmenopausal osteoporosis. This may, in daily practice, confuse the clinician. This manuscript offers an evidence-based update of previous treatment guidelines, with a critical assessment of the currently available efficacy data on all new chemical entities which were granted a marketing authorization. Osteoporosis is widely recognized as a major public health concern. The availability of new therapeutic agents makes clinical decision-making in osteoporosis more complex. Nation-specific guidelines are needed to take into consideration the specificities of each and every health care environment. The present manuscript is the result of a National Consensus, based on a systematic review and a critical appraisal of the currently available literature. It offers an evidence-based update of previous treatment guidelines, with the aim of providing clinicians with an unbiased assessment of osteoporosis treatment effect. [less ▲]

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See detailEvidence-based guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis: a consensus document of the Belgian Bone Club
Devogelaer, J. P.; Goemaere, S.; Boonen, S. et al

in Osteoporosis International (2006), 17(1), 8-19

Glucocorticoids (GCs) are frequently prescribed for various inflammatory and/or life-threatening conditions concerning many systems in the body. However, they can provoke many aftereffects, of which ... [more ▼]

Glucocorticoids (GCs) are frequently prescribed for various inflammatory and/or life-threatening conditions concerning many systems in the body. However, they can provoke many aftereffects, of which osteoporosis (OP) is one of the most crippling complications, with its host of fractures. The dramatic increase in bone fragility is mainly attributable to the GC-induced rapid bone loss in all skeletal compartments. We have reviewed the meta-analyses and randomized controlled studies reporting medical therapeutic interventions currently registered in Belgium for the management of GC-OP comparatively with a placebo. Based on this research, an expert meeting developed a consensus on the prevention and therapy of GC-OP. The pathophysiology of GC-OP is complex. Several factors, acting separately or synergistically, have been described. Their great number could help to understand the rapidity of bone loss and of bone fragility occurrence, indicating that a rapid therapeutic intervention should be implemented to avoid complications. All patients on GCs are threatened with OP, so the prevention and/or therapy of GC-OP should be considered not only for postmenopausal females, but also for osteopenic premenopausal females and for males put on a daily dose of at least 7.5 mg equivalent prednisolone that is expected to last at least 3 months. Non-pharmacological interventions, such as exercise and avoidance of tobacco and alcohol, should be recommended, even if their role is not definitely settled in GC-OP prevention. Supplemental calcium and vitamin D should be considered as the first-line therapy because of the decrease in intestinal calcium absorption provoked by GCs. They also could be considered either as isolated therapy in patients taking less than 7.5 mg prednisolone daily and/or for a predicted period shorter than 3 months or as adjuvant therapy to other more potent drugs. Hormone replacement therapy could be considered in young postmenopausal females on GC, such as in postmenopausal OP, or in men with low androgen levels. Calcitonin appears to have a protective effect on trabecular bone in GC-OP, just as in postmenopausal OP. There is an increasing body of evidence supporting the antifracture efficacy of bisphosphonates, notably alendronate and risedronate. Preventative and curative therapy of GC-OP should be maintained as long as the patient is on GC treatment and could be stopped after weaning from GC, because there is more than circumstantial evidence of some recovery of BMD when GCs are stopped. There is no indication in GC-OP for any combination of two antiresorptive agents (except for calcium and vitamin D) or for an antiresorptive and an anabolic agent. There is indeed no proof that the increased costs of combined treatments will translate into increased therapeutic efficacy. [less ▲]

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See detailEvidence-based guidelines for the treatment of postmenopausal osteoporosis: a consensus document of the Belgian Bone Club
Boonen, S.; Body, Jean-Jacques; Boutsen, Y. et al

in Osteoporosis International (2005), 16(3), 239-254

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See detailEvidence-based guidelines for the use of biochemical markers of bone turnover in the selection and monitoring of bisphosphonate treatment in osteoporosis: a consensus document of the Belgian Bone Club.
Bergmann, Pierre; Body, Jean-Jacques; Boonen, Steven et al

in International Journal of Clinical Practice (2009), 63(1), 19-26

OBJECTIVES: To review the clinical value of bone turnover markers (BTM), to initiate and/or monitor anti-resorptive treatment for osteoporosis compared with bone mineral density (BMD) and to evaluate ... [more ▼]

OBJECTIVES: To review the clinical value of bone turnover markers (BTM), to initiate and/or monitor anti-resorptive treatment for osteoporosis compared with bone mineral density (BMD) and to evaluate suitable BTM and changes in BTM levels for significance of treatment efficiency. METHODOLOGY: Consensus meeting generating guidelines for clinical practice after review and discussion of the randomised controlled trials or meta-analyses on the management of osteoporosis in postmenopausal women. RESULTS: Although the correlation between BMD and BTM is statistically significant, BTM cannot be used as predictive markers of BMD in an individual patient. Both are independent predictors of fracture risk, but BTM can only be used as an additional risk factor in the decision to treat. Current data do not support the use of BTM to select the optimal treatment. However, they can be used to monitor treatment efficiency before BMD changes can be evaluated. Early changes in BTM can be used to measure the clinical efficacy of an anti-resorptive treatment and to reinforce patient compliance. DISCUSSION: Determining a threshold of BTM reflecting an optimal long-term effect is not obvious. The objective should be the return to the premenopausal range and/or a decrease at least equal to the least significant change (30%). Preanalytical and analytical variability of BTM is an important limitation to their use. Serum C-terminal cross-linked telopeptide of type I collagen (CTX), procollagen 1 N terminal extension peptide and bone specific alkaline phosphatase (BSALP) appear to be the most suitable. Conclusion: Consensus regarding the use of BTM resulted in guidelines for clinical practice. BMD determines the indication to treat osteoporosis. BTM reflect treatment efficiency and can be used to motivate patients to persist with their medication. [less ▲]

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See detailEvidence-Based Medicine
Krzesinski, Jean-Marie ULg

Learning material (2001)

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See detailEvidence-based medicine. Apport des essais cliniques controles.
Scheen, André ULg

in Revue Médicale de Liège (2000), 55(4), 216-9

Controlled clinical trials are the support of Evidence-Based Medicine. In most instances, only them can indeed provide the demonstration of both the efficacy and safety of a pharmacological treatment ... [more ▼]

Controlled clinical trials are the support of Evidence-Based Medicine. In most instances, only them can indeed provide the demonstration of both the efficacy and safety of a pharmacological treatment, based upon rigorous scientific experimental observations avoiding potential bias due to subjective interpretation. In order to be able to extrapolate conclusions of drug trials to clinical practice and to positively influence physician's attitudes, "explanatory" trials, which aim at proving the intrinsic activity of the molecule, should be completed by "pragmatic" trials, which aim at demonstrating the clinical utility of the drug. [less ▲]

Detailed reference viewed: 21 (3 ULg)