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61.
Francesca Rossi Antonio Giorgio Marco Battaglini Maria Laura Stromillo Emilio Portaccio Benedetta Goretti Antonio Federico Bahia Hakiki Maria Pia Amato Nicola De Stefano 《PloS one》2012,7(11)
Objective
To assess the relationship between cognition and brain white matter (WM) lesion distribution and frequency in patients with relapsing-remitting multiple sclerosis (RR MS).Methods
MRI-based T2 lesion probability map (LPM) was used to assess the relevance of brain lesion location for cognitive impairment in a group of 142 consecutive patients with RRMS. Significance of voxelwise analyses was p<0.05, cluster-corrected for multiple comparisons. The Rao Brief Repeatable Battery was administered at the time of brain MRI to categorize the MS population into cognitively preserved (CP) and cognitively impaired (CI).Results
Out of 142 RRMS, 106 were classified as CP and 36 as CI. Although the CI group had greater WM lesion volume than the CP group (p = 0.001), T2 lesions tended to be less widespread across the WM. The peak of lesion frequency was almost twice higher in CI (61% in the forceps major) than in CP patients (37% in the posterior corona radiata). The voxelwise analysis confirmed that lesion frequency was higher in CI than in CP patients with significant bilateral clusters in the forceps major and in the splenium of the corpus callosum (p<0.05, corrected). Low scores of the Symbol Digit Modalities Test correlated with higher lesion frequency in these WM regions.Conclusions
Overall these results suggest that in MS patients, areas relevant for cognition lie mostly in the commissural fiber tracts. This supports the notion of a functional (multiple) disconnection between grey matter structures, secondary to damage located in specific WM areas, as one of the most important mechanisms leading to cognitive impairment in MS. 相似文献62.
Fagoonee S Caorsi C Giovarelli M Stoltenberg M Silengo L Altruda F Camussi G Tolosano E Bussolati B 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(3):1937-1947
Several factors affect the autoimmune response, including iron-dependent modulation of T cells. Hemopexin is the plasma protein with the highest binding affinity to heme. It mediates heme-iron recovery in the liver, thus controlling heme-iron availability in peripheral cells. The aim of the present study was to investigate the role of hemopexin in the progress of an autoimmune response. To this end, we chose a mouse model of mercury-induced autoimmunity and evaluated the susceptibility of hemopexin-null mice to mercury treatment compared with wild-type controls. In this study we show that lack of hemopexin dampens mercury-induced autoimmune responses in mice. Hemopexin-null mice produced fewer antinuclear autoantibodies and had reduced deposits of immune complexes in the kidney after mercuric chloride treatment compared with wild-type mice. These features were associated with a reduction in activated T cells and lower absolute B cell number in spleen and impaired IgG1 and IgG2a production. In contrast, in hemopexin-null mice the response to OVA/CFA immunization was maintained. In addition, hemopexin-null mice had reduced transferrin receptor 1 expression in T cells, possibly due to the increase in heme-derived iron. Interestingly, CD4(+)T cells isolated from mercury-treated hemopexin-null mice show reduced IFN-gamma-dependent STAT1 phosphorylation compared with that of wild-type mice. Our data suggest that hemopexin, by controlling heme-iron availability in lymphocytes, modulates responsiveness to IFN-gamma and, hence, autoimmune responses. 相似文献
63.
65.
Simone Bettini Valeria Franceschini Laura Astolfi Edi Simoni Benedetta Mazzanti Alessandro Martini Roberto P. Revoltella 《Cytotherapy》2018,20(2):189-203
Background
Kanamycin, mainly used in the treatment of drug-resistant-tuberculosis, is known to cause irreversible hearing loss. Using the xeno-transplant model, we compared both in vitro and in vivo characteristics of human mesenchymal stromal cells (MSCs) derived from adult tissues, bone marrow (BM-MSCs) and adipose tissue (ADSCs). These tissues were selected for their availability, in vitro multipotency and regenerative potential in vivo in kanamycin-deafened nod-scid mice.Methods
MSCs were isolated from informed donors and expanded ex vivo. We evaluated their proliferation capacity in vitro using the hexosaminidase assay, the phenotypic profile using flow-cytometry of a panel of surface antigens, the osteogenic potential using alkaline phosphatase activity and the adipogenic potential using oil-red-O staining. MSCs were intravenously injected in deafened mice and cochleae, liver, spleen and kidney were sampled 7 and 30 days after transplantation. The dissected organs were analyzed using lectin histochemistry, immunohistochemistry, polymerase chain reaction (PCR) and dual color fluorescence in situ hybridization (DC-FISH).Results
MSCs showed similar in vitro characteristics, but ADSCs appeared to be more efficient after prolonged expansion. Both cell types engrafted in the cochlea of damaged mice, inducing regeneration of the damaged sensory structures. Several hybrid cells were detected in engrafted tissues.Discussion
BM-MSCs and ADSCs showed in vitro characteristics suitable for tissue regeneration and fused with resident cells in engrafted tissues. The data suggest that paracrine effect is the prevalent mechanism inducing tissue recovery. Overall, BM-MSCs and ADSCs appear to be valuable tools in regenerative medicine for hearing loss recovery. 相似文献66.
Benedetta Boari Raffaella Salmi Massimo Gallerani Anna Maria Malagoni Fabio Manfredini Roberto Manfredini 《Biological Rhythm Research》2007,38(3):155-167
Convincing evidence has demonstrated that cardiovascular diseases do not occur randomly throughout the day, the week, or the year but show a well defined temporal organization. This article will review circadian, weekly, and seasonal patterns of occurrence of acute myocardial infarction, along with their underlying pathophysiological triggering factors. 相似文献
67.
Nicole J. Lake Bryn D. Webb David A. Stroud Tara R. Richman Benedetta Ruzzenente Alison G. Compton Hayley S. Mountford Juliette Pulman Coralie Zangarelli Marlene Rio Nathalie Boddaert Zahra Assouline Mingma D. Sherpa Eric E. Schadt Sander M. Houten James Byrnes Elizabeth M. McCormick Zarazuela Zolkipli-Cunningham David R. Thorburn 《American journal of human genetics》2018,102(4):713
68.
Thatjana Gardeitchik Miski Mohamed Benedetta Ruzzenente Daniela Karall Sergio Guerrero-Castillo Daisy Dalloyaux Mariël van den Brand Sanne van Kraaij Ellyze van Asbeck Zahra Assouline Marlene Rio Pascale de Lonlay Sabine Scholl-Buergi David F.G.J. Wolthuis Alexander Hoischen Richard J. Rodenburg Wolfgang Sperl Zsolt Urban Eva Morava 《American journal of human genetics》2018,102(4):685-695
69.
Reinier Oropesa-Nuñez Sandeep Keshavan Silvia Dante Alberto Diaspro Benedetta Mannini Claudia Capitini Cristina Cecchi Massimo Stefani Fabrizio Chiti Claudio Canale 《Biophysical journal》2018,114(6):1357-1367
The deposition of fibrillar protein aggregates in human organs is the hallmark of several pathological states, including highly debilitating neurodegenerative disorders and systemic amyloidoses. It is widely accepted that small oligomers arising as intermediates in the aggregation process, released by fibrils, or growing in secondary nucleation steps are the cytotoxic entities in protein-misfolding diseases, notably neurodegenerative conditions. Increasing evidence indicates that cytotoxicity is triggered by the interaction between nanosized protein aggregates and cell membranes, even though little information on the molecular details of such interaction is presently available. In this work, we propose what is, to our knowledge, a new approach, based on the use of single-cell force spectroscopy applied to multifunctional substrates, to study the interaction between protein oligomers, cell membranes, and/or the extracellular matrix. We compared the interaction of single Chinese hamster ovary cells with two types of oligomers (toxic and nontoxic) grown from the N-terminal domain of the Escherichia coli protein HypF. We were able to quantify the affinity between both oligomer type and the cell membrane by measuring the mechanical work needed to detach the cells from the aggregates, and we could discriminate the contributions of the membrane lipid and protein fractions to such affinity. The fundamental role of the ganglioside GM1 in the membrane-oligomers interaction was also highlighted. Finally, we observed that the binding of toxic oligomers to the cell membrane significantly affects the functionality of adhesion molecules such as Arg-Gly-Asp binding integrins, and that this effect requires the presence of the negatively charged sialic acid moiety of GM1. 相似文献