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See detailImpaired LTP induction in dentate gyrus of calretinin-deficient mice
Schurmans, Stéphane ULg; Schiffmann, S. N.; Gurden, H. et al

in Proceedings of the National Academy of Sciences of the United States of America (1997), 94

Calretinin (Cr) is a Ca21 binding protein present in various populations of neurons distributed in the central and peripheral nervous systems. We have generated Cr-deficient (Cr2/2) mice by gene targeting ... [more ▼]

Calretinin (Cr) is a Ca21 binding protein present in various populations of neurons distributed in the central and peripheral nervous systems. We have generated Cr-deficient (Cr2/2) mice by gene targeting and have investigated the associated phenotype. Cr2/2 mice were viable, and a large number of morphological, biochemical, and behavioral parameters were found unaffected. In the normal mouse hippocampus, Cr is expressed in a widely distributed subset of GABAergic interneurons and in hilar mossy cells of the dentate gyrus. Because both types of cells are part of local pathways innervating dentate granule cells andyor pyramidal neurons, we have explored in Cr2/2 mice the synaptic transmission between the perforant pathway and granule cells and at the Schaffer commissural input to CA1 pyramidal neurons. Cr2/2 mice showed no alteration in basal synaptic transmission, but long-term potentiation (LTP) was impaired in the dentate gyrus. Normal LTP could be restored in the presence of the GABAA receptor antagonist bicuculline, suggesting that in Cr2/2 dentate gyrus an excess of g-minobutyric acid (GABA) release interferes with LTP induction. Synaptic transmission and LTP were normal in CA1 area, which contains only few Cr-positive GABAergic interneurons. Cr2/2 mice performed normally in spatial memory task. These results suggest that expression of Cr contributes to the control of synaptic plasticity in mouse dentate gyrus by indirectly regulating the activity of GABAergic interneurons, and that Cr2/2 mice represent a useful tool to understand the role of dentate LTP in learning and memory [less ▲]

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See detailImpaired Accumulation of Granulocytes in the Lung During Ozone Adaptation
Fievez, Laurence ULg; Kirschvink, N.; Dogne, S. et al

in Free Radical Biology & Medicine (2001), 31(5), 633-641

Respiratory alterations induced by an acute exposure to ozone (O(3)) paradoxically resolve during multiday exposure. This adaptation is characteristically accompanied by a gradual attenuation of lung ... [more ▼]

Respiratory alterations induced by an acute exposure to ozone (O(3)) paradoxically resolve during multiday exposure. This adaptation is characteristically accompanied by a gradual attenuation of lung neutrophilia. As maintenance of neutrophilia at the site of inflammation is due to cytokine-mediated delayed neutrophil apoptosis, which is associated with reduced levels of Bax, a proapoptotic protein, we sought to determine whether defects in these mechanisms could account for O(3) adaptation. Lung granulocytes obtained at different time points from calves exposed to 0.75 ppm O(3) for 12 h/d for 7 consecutive days neither showed enhancement of survival nor Bax deficiency, when compared to blood granulocytes. To further investigate the effects of an exogenous oxidative stress on neutrophil survival, human granulocytes were treated with hydrogen peroxide alone, or in combination with granulocyte/macrophage colony-stimulating factor, an antiapoptotic cytokine. Both treatments led to rapid apoptosis associated with downregulation of Bcl-x(L) and Bcl-2, two antiapoptotic proteins. This study shows that O(3) adaptation is associated with a failure in the mechanisms leading to accumulation of neutrophils at the site of inflammation, and suggests that this defect is due to direct proapoptotic effects of exogenous oxidative stress on granulocytes [less ▲]

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See detailImpaired Acquisition Of A Mirror-Reading Skill In Alzheimer’s Disease
Merbah, Sarah ULg; Salmon, Eric ULg; Meulemans, Thierry ULg

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2011), 47

Several studies using the mirror-reading paradigm have shown that procedural learning and repetition priming may be preserved in the early stages of Alzheimer's disease (AD) (e.g., Deweer et al., 1994 ... [more ▼]

Several studies using the mirror-reading paradigm have shown that procedural learning and repetition priming may be preserved in the early stages of Alzheimer's disease (AD) (e.g., Deweer et al., 1994). According to the classical interpretation, improved reading time for repeated words is sustained by a repetition priming effect, while procedural learning is demonstrated when this improvement is also observed for new words. Following Masson (1986), the hypothesis tested in the present study was that improved reading of new words could also be due to a repetition priming effect rather than to the acquisition of a mirror-reading skill. Indeed, because the same letters are presented throughout the task, a repetition priming effect for the letters could suffice to explain the improvement in performance. To test this hypothesis, we administered to 30 healthy young and elderly subjects and to 30 AD patients a new mirror-reading task in two phases: an acquisition phase comprising pseudo-words constructed with one part of the alphabet, and a test phase in which both pseudo-words constructed with the same part of the alphabet and pseudo-words constructed with another part of the alphabet were presented. If the new pseudo-words composed with repeated letters were read faster, it would reflect a repetition priming effect; if pseudo-words composed of ‘new’ letters were read faster, it would reflect a procedural learning effect. The results show comparable repetition priming effects in AD patients and in healthy elderly subjects, whereas only healthy subjects showed a procedural learning effect. These results suggest, contrary to previous studies, that the learning of a new perceptual skill may not always be preserved in AD. [less ▲]

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See detailImpaired angiogenesis and tumor development by inhibition of the mitotic kinesin Eg5.
Exertier, Prisca; Javerzat, Sophie; Wang, Baigang et al

in Oncotarget (2013), 4(12), 2302-16

Kinesin motor proteins exert essential cellular functions in all eukaryotes. They control mitosis, migration and intracellular transport through interaction with microtubules. Small molecule inhibitors of ... [more ▼]

Kinesin motor proteins exert essential cellular functions in all eukaryotes. They control mitosis, migration and intracellular transport through interaction with microtubules. Small molecule inhibitors of the mitotic kinesin KiF11/Eg5 are a promising new class of anti-neoplastic agents currently evaluated in clinical cancer trials for solid tumors and hematological malignancies. Here we report induction of Eg5 and four other mitotic kinesins including KIF20A/Mklp2 upon stimulation of in vivo angiogenesis with vascular endothelial growth factor-A (VEGF-A). Expression analyses indicate up-regulation of several kinesin-encoding genes predominantly in lymphoblasts and endothelial cells. Chemical blockade of Eg5 inhibits endothelial cell proliferation and migration in vitro. Mitosis-independent vascular outgrowth in aortic ring cultures is strongly impaired after Eg5 or Mklp2 protein inhibition. In vivo, interfering with KIF11/Eg5 function causes developmental and vascular defects in zebrafish and chick embryos and potent inhibition of tumor angiogenesis in experimental tumor models. Besides blocking tumor cell proliferation, impairing endothelial function is a novel mechanism of action of kinesin inhibitors. [less ▲]

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See detailImpaired automatic and unconscious motor processes in Parkinson's disease
D'Ostilio, Kevin ULg; CREMERS, Julien ULg; DELVAUX, Valérie ULg et al

in Scientific Reports (2013)

While it is increasingly recognized that voluntary movements are produced by an interaction between conscious and unconscious processes, the role of the latter in Parkinson’s disease has received little ... [more ▼]

While it is increasingly recognized that voluntary movements are produced by an interaction between conscious and unconscious processes, the role of the latter in Parkinson’s disease has received little attention to date. Here, we administered a subliminal masked prime task to 15 Parkinson’s disease patients and 15 age-matched healthy elderly subjects. Compatibility effects were examined by manipulating the direction of the arrows and the interstimuli interval. Analysis of the positive compatibility effect revealed performance differences between the most and the least affected hand in Parkinson’s disease patients. Additionally, patients did not show the same tendency toward a negative compatibility effect as compared to elderly controls. These novel findings provide evidence supporting the role of basal ganglia circuits in controlling the balance between automatic motor response facilitation and inhibition. [less ▲]

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See detailImpaired bone formation in ovariectomized mice reduces implant integration as indicated by longitudinal in vivo micro-computed tomography
Li, Zihui; Kuhn, Gisela; Schirmer, Michael et al

in PLoS ONE (2017), 12(9), 1-22

Although osteoporotic bone, with low bone mass and deteriorated bone architecture, provides a less favorable mechanical environment than healthy bone for implant fixation, there is no general agreement on ... [more ▼]

Although osteoporotic bone, with low bone mass and deteriorated bone architecture, provides a less favorable mechanical environment than healthy bone for implant fixation, there is no general agreement on the impact of osteoporosis on peri-implant bone (re)modeling, which is ultimately responsible for the long term stability of the bone-implant system. Here, we inserted an implant in a mouse model mimicking estrogen deficiency-induced bone loss and we monitored with longitudinal in vivo micro-computed tomography the spatio-temporal changes in bone (re)modeling and architecture, considering the separate contributions of trabecular, endocortical and periosteal surfaces. Specifically, 12 week-old C57BL/6J mice underwent OVX/SHM surgery; 9 weeks after we inserted special metal-ceramics implants into the 6th caudal vertebra and we measured bone response with in vivo micro-CT weekly for the following 6 weeks. Our results indicated that ovariectomized mice showed a reduced ability to increase the thickness of the cortical shell close to the implant because of impaired peri-implant bone formation, especially at the periosteal surface. Moreover, we observed that healthy mice had a significantly higher loss of trabecular bone far from the implant than estrogen depleted animals. Such behavior suggests that, in healthy mice, the substantial increase in peri-implant bone formation which rapidly thickened the cortex to secure the implant may raise bone resorption elsewhere and, specifically, in the trabecular network of the same bone but far from the implant. Considering the already deteriorated bone structure of estrogen depleted mice, further bone loss seemed to be hindered. The obtained knowledge on the dynamic response of diseased bone following implant insertion should provide useful guidelines to develop advanced treatments for osteoporotic fracture fixation based on local and selective manipulation of bone turnover in the peri-implant region. [less ▲]

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See detailImpaired cerebral connectivity in vegetative state
Laureys, Steven ULg; Faymonville, Marie ULg; Goldman, S. et al

in Physiological imaging of the brain with PET (2000)

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See detailImpaired controlled recollection processes in depression and subjective memory complaints
Jermann, Françoise; Adam, Stéphane ULg; Ceschi, Grazia et al

Poster (2001, July 18)

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See detailImpaired diaphragmatic function in the pneumonic calf
Desmecht, Daniel ULg; Linden, Annick ULg; Amory, Hélène ULg et al

in Proceedings of the 10th Comparative Respiratory Society Meeting (1991)

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See detailImpaired effective cortical connectivity in vegetative state : Preliminary investigation using PET
Laureys, Steven ULg; Goldman, Serge; Phillips, Christophe ULg et al

in Neuroimage (1999), 9(4), 377-382

Vegetative state (VS) is a condition of abolished awareness with persistence of arousal. Awareness is part of consciousness, which itself is thought to represent an emergent property of cerebral neural ... [more ▼]

Vegetative state (VS) is a condition of abolished awareness with persistence of arousal. Awareness is part of consciousness, which itself is thought to represent an emergent property of cerebral neural networks. Our hypothesis was that part of the neural correlate underlying VS is an altered connectivity, especially between the associative cortices. We assessed regional cerebral glucose metabolism (rCMRGlu) and effective cortical connectivity in four patients in VS by means of statistical parametric mapping and [F-18]fluorodeoxyglucose-positron emission tomography. Our data showed a common pattern of impaired rCMRGlu in the prefrontal, premotor, and parietotemporal association areas and posterior cingulate cortex/precuneus in VS. In a next step, we demonstrated that in VS patients various prefrontal and premotor areas have in common that they are less tightly connected with the posterior cingulate cortex than in normal controls. These results provide a strong argument for an alteration of cortical connectivity in VS patients. (C) 1999 Academic Press. [less ▲]

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See detailImpaired emotional facial expression in alcoholism compared with obsessive compulsive disorder and normal controls
Kornreich, C; Blairy, Sylvie ULg; Philippot, P et al

in Psychiatry Research (2001), 102

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See detailImpaired emotional facial expression recognition is associated with interpersonal problems in alcoholism
Kornreich, C; Philippot, P; Foisy, ML et al

in Alcohol & Alcoholism (2002), 37(4), 394-400

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See detailImpaired familiarity in individuals at risk for Alzheimer's disease: Commentary on Schoemaker et al. (2016)
Bastin, Christine ULg; Besson, Gabriel ULg

in Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring (2017), 6

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See detailImpaired immune responses in diabetes mellitus: analysis of the factors and mechanisms involved. Relevance to the increased susceptibility of diabetic patients to specific infections.
Moutschen, Michel ULg; Scheen, André ULg; Lefebvre, Pierre ULg

in Diabète & Métabolisme (1992), 18(3), 187-201

The reasons why diabetic patients present with an increased susceptibility to frequent and protracted infections remain unclear. The virtual absence of epidemiological studies of the independent risk ... [more ▼]

The reasons why diabetic patients present with an increased susceptibility to frequent and protracted infections remain unclear. The virtual absence of epidemiological studies of the independent risk factors involved contrasts with the multitude of in vitro models focused on the metabolism and function of immune cells from diabetic patients. This review analyzes some of these models and their clinical relevance. The different levels of diabetes pathogenesis: genetic (Type 1), autoimmune (Type 1) and metabolic (Type 1 and Type 2) are responsible for immune abnormalities demonstrated in in vitro models. The participation of genetic and autoimmune factors has been mainly characterized on T lymphocyte function. The B8 DR3 haplotype is associated with several minor immunologic abnormalities in vitro. However, the high frequency of this haplotype in healthy individuals argues against its involvement in significant defects of antimicrobial immunity. Genetic deficiency of C4, present in 25% of Type 1 diabetic patients could, on the other hand, be responsible for opsonization defects against encapsulated pathogens. Several immunological abnormalities related to the autoimmune process preceding the onset of Type 1 diabetes mellitus, such as the depletion of memory CD4+ cells and the defective natural killer activity could transiently impair host defences against viral diseases. Several in vitro functional defects of the immune system have been correlated with the metabolic control of diabetic patients. This suggests the involvement of insulinopenia in some of the abnormalities observed. Insulinopenia-induced enzymatic defects have often been proposed to inhibit energy-requiring functions of phagocytes and lymphocytes. However, the relevance of this mechanism could be confined to patients with extremely severe metabolic abnormalities. The importance of systemic consequences of insulinopenia such as hyperglycaemia and ketosis has also been addressed. Usually, the defects induced in vitro by these factors are slight and require supraphysiologic concentrations of glucose or ketone bodies. Recent studies have shown abnormalities of signal transduction mechanisms in which insulinopenia itself and other factors such as circulating immune complexes could be involved. Despite numerous controversies, many in vitro studies of the immune cells of diabetic patients have demonstrated significant defects which bear quantitative similarities with abnormalities described in other immunodeficiency syndromes. Furthermore, several mechanisms have been proposed to link the different defects observed with the specific infections encountered in diabetic patients. [less ▲]

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See detailImpaired insulin-induced erythrocyte magnesium accumulation is correlated to impaired insulin-mediated glucose disposal in type 2 (non-insulin-dependent) diabetic patients.
Paolisso, G.; Sgambato, S.; Giugliano, D. et al

in Diabetologia (1988), 31(12), 910-5

Plasma and erythrocyte magnesium levels were measured by atomic absorption spectrometry in 12 healthy subjects and 12 moderately obese patients with Type 2 (non-insulin-dependent) diabetes mellitus. Basal ... [more ▼]

Plasma and erythrocyte magnesium levels were measured by atomic absorption spectrometry in 12 healthy subjects and 12 moderately obese patients with Type 2 (non-insulin-dependent) diabetes mellitus. Basal plasma and erythrocyte magnesium levels were significantly lower in diabetic patients than in control subjects. In vitro incubation in the presence of 100 mU/l insulin significantly increased magnesium erythrocyte levels in both control subjects (p less than 0.001) and patients with diabetes (p less than 0.001). However, even in the presence of 100 mU/l insulin, the erythrocyte magnesium content of patients with Type 2 diabetes was lower than that of control subjects. The in vitro dose-response curve of the effect of insulin on magnesium erythrocyte accumulation was shifted to the right when red cells of diabetic patients were used, with a highly significant reduction of the maximal effect. Such reduction of the maximal effect of insulin suggests that the impairment of insulin-induced erythrocyte magnesium accumulation observed in Type 2 diabetic patients results essentially from a post-receptor defect.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]

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See detailImpaired iodide organification in autonomous thyroid nodules
Moreno-Reyes, Rodrigo; Tang, Bich-Ngoc-Thanh; Seret, Alain ULg et al

in Journal of Clinical Endocrinology and Metabolism (2007), 92(12), 4719-4724

Context: The clinical evolution of autonomous thyroid nodules (ATN) is unpredictable, and thyrotoxicosis is observed at variable nodule size. In vitro data suggest that hydrogen peroxide production is ... [more ▼]

Context: The clinical evolution of autonomous thyroid nodules (ATN) is unpredictable, and thyrotoxicosis is observed at variable nodule size. In vitro data suggest that hydrogen peroxide production is decreased in ATN, indicating intranodular iodide organification impairment. Objective: We aimed to determine iodide organification efficiency in ATN and its relationship with thyroid status in patients. Design: Forty-six patients with a single ATN on the I-123 thyroid scan were included in the study. Biological evaluation and iodine perchlorate (I-ClO4) discharge test were carried out in all subjects. Setting: The study took place at an academic hospital. Results: Among the 46 patients, 28 patients (61%) had a positive I-ClO4 discharge test with a mean +/- SD value of discharge of 42 +/- 13%, and 18 (39%) had a negative discharge test with mean +/- SD of 5 +/- 9%. In the group of patients with a negative discharge test but not in the group with a positive test, serum-free T-3 and free T-4 concentrations were significantly correlated with the I-123 uptake. The severity of hyperthyroidism was not different between both groups. Conclusions: Intranodular iodide organification was impaired in most patients with ATN. Whether differences in organification capability could predict the risk for evolution to overt hyperthyroidism in patients with ATN remains to be established. [less ▲]

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See detailImpaired LTP in the dentate gyrus of calretinin deficient mice
Schiffman, S. N.; Schurmans, Stéphane ULg; Gurden, H. et al

in Cell Biology International (1998), 22(5), 386-387

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See detailImpaired mental simulation of specific past and future personal events in non-depressed multiple sclerosis patients
Ernst, Alexandra ULg; Blanc, Frédéric; Sellal, François et al

in Journal of the Neurological Sciences (2014), 345

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See detailImpaired motor coordination and Purkinje cell excitability in mice lacking calretinin
Schiffmann, Serge N.; Cheron, Guy; Lohoff, Ann et al

in Proceedings of the National Academy of Sciences of the United States of America (1999), 96

n the cerebellum, the parallel fiber-Purkinje cell synapse can undergo long-term synaptic plasticity suggested to underlie motor learning and resulting from variations in intracellular calcium ... [more ▼]

n the cerebellum, the parallel fiber-Purkinje cell synapse can undergo long-term synaptic plasticity suggested to underlie motor learning and resulting from variations in intracellular calcium concentration ([Ca2+]i). Ca2+ binding proteins are enriched in the cerebellum, but their role in information processing is not clear. Here, we show that mice deficient in calretinin (Cr-/-) are impaired in tests of motor coordination. An impairment in Ca2+ homeostasis in Cr-/- Purkinje cells was supported by the high Ca2+-saturation of calbindin-D28k in these cells. The firing behavior of Purkinje cells is severely affected in Cr-/- alert mice, with alterations of simple spike firing rate, complex spike duration, and simple spike pause. In contrast, in slices, transmission at parallel fiber- or climbing fiber-Purkinje cell synapses is unaltered, indicating that marked modifications of the firing behavior in vivo can be undetectable in slice. Thus, these results show that calretinin plays a major role at the network level in cerebellar physiology [less ▲]

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