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Coello A.F.,Hospital Universitario Of Bellvitge | Duvaux S.,Montpellier University | De Benedictis A.,Bambino Gesu Children Hospital | De Benedictis A.,University of Insubria | And 3 more authors.
Journal of Neurosurgery | Year: 2013

Neural foundations underlying visual agnosia are poorly understood. The authors present the case of a patient who underwent awake surgery for a right basal temporooccipital low-grade glioma in which direct electrostimulation was used both at the cortical and subcortical level. Brain mapping over the inferior longitudinal fascicle generated contralateral visual hemiagnosia. These original findings are in agreement with recent tractography data that have confirmed the existence of an occipitotemporal pathway connecting occipital visual input to higher-level processing in temporal lobe structures. This is the first report of a true transient visual hemiagnosia elicited through electrostimulation, supporting the crucial role of inferior longitudinal fascicle in visual recognition. ©AANS, 2013.

Rucci N.,University of LAquila | Capulli M.,University of LAquila | Piperni S.G.,University of LAquila | Cappariello A.,Bambino Gesu Children Hospital | And 4 more authors.
Journal of Bone and Mineral Research | Year: 2015

Mechanical loading represents a crucial factor in the regulation of skeletal homeostasis. Its reduction causes loss of bone mass, eventually leading to osteoporosis. In a previous global transcriptome analysis performed in mouse calvarial osteoblasts subjected to simulated microgravity, the most upregulated gene compared to unit gravity condition was Lcn2, encoding the adipokine Lipocalin 2 (LCN2), whose function in bone metabolism is poorly known. To investigate the mechanoresponding properties of LCN2, we evaluated LCN2 levels in sera of healthy volunteers subjected to bed rest, and found a significant time-dependent increase of this adipokine compared to time 0. We then evaluated the in vivo LCN2 regulation in mice subjected to experimentally-induced mechanical unloading by (1) tail suspension, (2) muscle paralysis by botulin toxin A (Botox), or (3) genetically-induced muscular dystrophy (MDX mice), and observed that Lcn2 expression was upregulated in the long bones of all of them, whereas physical exercise counteracted this increase. Mechanistically, in primary osteoblasts transfected with LCN2-expression-vector (OBs-Lcn2) we observed that Runx2 and its downstream genes, Osterix and Alp, were transcriptionally downregulated, and alkaline phosphatase (ALP) activity was less prominent versus empty-vector transduced osteoblasts (OBs-empty). OBs-Lcn2 also exhibited an increase of the Rankl/Opg ratio and IL-6 mRNA, suggesting that LCN2 could link poor differentiation of osteoblasts to enhanced osteoclast stimulation. In fact, incubation of purified mouse bone marrow mononuclear cells with conditioned media from OBs-Lcn2 cultures, or their coculture with OBs-Lcn2, improved osteoclastogenesis compared to OBs-empty, whereas treatment with recombinant LCN2 had no effect. In conclusion, our data indicate that LCN2 is a novel osteoblast mechanoresponding gene and that its regulation could be central to the pathological response of the bone tissue to low mechanical forces. © 2014 American Society for Bone and Mineral Research.

Although high-dose chemotherapy (HDC) represents the standard of treatment for high-risk neuroblastoma (NBL), the most effective conditioning regimen still remains to be identified. Forty-one high-risk NBL entered into local protocol based on induction chemotherapy, surgery and HDC with either etoposide/thiotepa/cyclophophamide (ETC) or i.v. busulfan and L-PAM (Bu/L-PAM). Thirty-seven patients underwent HDC; 29 with ETC and 8 with Bu/L-PAM. No toxic deaths were recorded. The 5-year progression-free survival (PFS) of patients given ETC was 21% (95% confidence interval CI (9-36%), while PFS for patients given Bu/L-PAM was 88% (95% CI=39-98%) (p<0.05). In multivariate analysis, treatment with the ETC regimen predicted progression/recurrence with a hazard ratio (HR) of 16.8 (p<0.05), as well as MYCN amplification which had an HR of 4.4 (p<0.05). Although the number of studied cases is limited, our data suggest that in high-risk NBL the combination of Bu/L-PAM is superior to the ETC regimen.

Li Pira G.,Bambino Gesu Children Hospital | Ivaldi F.,G Gaslini Institute | Manca F.,G Gaslini Institute
Journal of Immunological Methods | Year: 2012

Adherent antigen presenting cells (APC) pulsed with protein or peptide antigens were used to capture specific CD4 or CD8 T-cells derived from established T-cell lines or from PBMC of immune subjects based on physiological interaction between TCR and MHC-peptide complex. This method could be applied independently of epitope specificity, HLA restriction alleles, activation markers and secreted cytokines, parameters required by other methods for selection of specific T cells. Non specific T-cells were removed by applying a 1. g force that did not affect binding of specific T-lymphocytes. Lymphocyte selection was specific and the average recovery was 36% for CD4 T-cells. CD8 T-cells proved trickier to purify, since solid phase APC were recognized as targets for cytotoxicity. Specificity was comparable to CD4 cells, but the average recovery for CD8 cells was 26%. No residual alloreactivity was detected in expanded T-cells. Frequency and recovery of specific T-cells were comparable to other current technologies, such as generation of T-cell lines and cytokine capture method. Since antigen and IL2 are the only reagents added to the cultures, this physiological procedure can be proposed for selection and expansion of pathogen specific T-cells not only for research purposes, but also for adoptive reconstitution of immunocompromised subjects if performed under GMP conditions. © 2012 Elsevier B.V..

Rooryck C.,University College London | Diaz-Font A.,University College London | Osborn D.P.S.,University College London | Chabchoub E.,University Hospitals of Leuven | And 19 more authors.
Nature Genetics | Year: 2011

3MC syndrome has been proposed as a unifying term encompassing the overlapping Carnevale, Mingarelli, Malpuech and Michels syndromes. These rare autosomal recessive disorders exhibit a spectrum of developmental features, including characteristic facial dysmorphism, cleft lip and/or palate, craniosynostosis, learning disability and genital, limb and vesicorenal anomalies. Here we studied 11 families with 3MC syndrome and identified two mutated genes, COLEC11 and MASP1, both of which encode proteins in the lectin complement pathway (collectin kidney 1 (CL-K1) and MASP-1 and MASP-3, respectively). CL-K1 is highly expressed in embryonic murine craniofacial cartilage, heart, bronchi, kidney and vertebral bodies. Zebrafish morphants for either gene develop pigmentary defects and severe craniofacial abnormalities. Finally, we show that CL-K1 serves as a guidance cue for neural crest cell migration. Together, these findings demonstrate a role for complement pathway factors in fundamental developmental processes and in the etiology of 3MC syndrome. © 2011 Nature America, Inc. All rights reserved.

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