Browsing by Subject "Disease progression"

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    Disrupted network topology in patients with stable and progressive mild cognitive impairment and alzheimer's disease
    (Oxford University Press, 2016) Pereira, J. B.; Mijalkov, M.; Kakaei, E.; Mecocci, P.; Vellas, B.; Tsolaki, M.; Kłoszewska, I.; Soininen, H.; Spenger, C.; Lovestone, S.; Simmons, A.; Wahlund, L.-O.; Volpe, G.; Westman, E.
    Recent findings suggest that Alzheimer's disease (AD) is a disconnection syndrome characterized by abnormalities in large-scale networks. However, the alterations that occur in network topology during the prodromal stages of AD, particularly in patients with stable mild cognitive impairment (MCI) and those that show a slow or faster progression to dementia, are still poorly understood. In this study, we used graph theory to assess the organization of structural MRI networks in stable MCI (sMCI) subjects, late MCI converters (lMCIc), early MCI converters (eMCIc), and AD patients from 2 large multicenter cohorts: ADNI and AddNeuroMed. Our findings showed an abnormal global network organization in all patient groups, as reflected by an increased path length, reduced transitivity, and increased modularity compared with controls. In addition, lMCIc, eMCIc, and AD patients showed a decreased path length and mean clustering compared with the sMCI group. At the local level, there were nodal clustering decreases mostly in AD patients, while the nodal closeness centrality detected abnormalities across all patient groups, showing overlapping changes in the hippocampi and amygdala and nonoverlapping changes in parietal, entorhinal, and orbitofrontal regions. These findings suggest that the prodromal and clinical stages of AD are associated with an abnormal network topology.
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    Frequent and specific immunity to the embryonal stem cell-associated antigen SOX2 in patients with monoclonal gammopathy
    (Rockefeller University Press, 2007) Spisek, R.; Kukreja, A.; Chen, L. -C.; Matthews, P.; Mazumder, A.; Vesole, D.; Jagannath, S.; Zebroski, H. A.; Simpson, A. J. G.; Ritter, G.; Durie, B.; Crowley, J.; Shaughnessy, Jr. J.D.; Scanlan, M. J.; Gure, A. O.; Barlogie, B.; Dhodapkar, M. V.
    Specific targets of cellular immunity in human premalignancy are largely unknown. Monoclonal gammopathy of undetermined significance (MGUS) represents a precursor lesion to myeloma (MM). We show that antigenic targets of spontaneous immunity in MGUS differ from MM. MGUS patients frequently mount a humoral and cellular immune response against SOX2, a gene critical for self-renewal in embryonal stem cells. Intranuclear expression of SOX2 marks the clonogenic CD138? compartment in MGUS. SOX2 expression is also detected in a proportion of CD138+ cells in MM patients. However, these patients lack anti-SOX2 immunity. Cellular immunity to SOX2 inhibits the clonogenic growth of MGUS cells in vitro. Detection of anti-SOX2 T cells predicts favorable clinical outcome in patients with asymptomatic plasmaproliferative disorders. Harnessing immunity to antigens expressed by tumor progenitor cells may be critical for prevention and therapy of human cancer.