RESUMEN
Purpose: We investigated potentially promising imaging findings and their combinations in the evaluation of cognitive decline. Materials and Methods: This retrospective study included 138 patients with subjective cognitive impairments, who underwent brain MRI. We classified the same group of patients into Alzheimer's disease (AD) and non-AD groups, based on the neuropsychiatric evaluation. We analyzed imaging findings, including white matter hyperintensity (WMH) and cerebral microbleeds (CMBs), using the Kruskal-Wallis test for group comparison, and receiver operating characteristic (ROC) curve analysis for assessing the diagnostic performance of imaging findings. Results: CMBs in the lobar or deep locations demonstrated higher prevalence in the patients with AD compared to those in the non-AD group. The presence of lobar CMBs combined with periventricular WMH (area under the ROC curve [AUC] = 0.702 [95% confidence interval: 0.599-0.806], p < 0.001) showed the highest performance in differentiation of AD from non-AD group. Conclusion: Combinations of imaging findings can serve as useful additive diagnostic tools in the assessment of cognitive decline.
RESUMEN
CD200 is a glycoprotein that is expressed on the surfaces of neurons and other cells. It interacts with its receptor, CD200R, which is expressed on cells of the myeloid lineage, including microglia. The interaction of CD200 with its receptor plays a significant role in maintaining microglia in a quiescent state; thus, a decrease in CD200 expression in the brain is associated with evidence of microglial activation. However, their roles in pathological progression remain unclear. We examined the expression of CD200 in kainic acid (KA)-induced neurodegeneration of the mouse hippocampus. Our quantitative analysis revealed that CD200 was constitutively expressed in the normal brain and transiently upregulated by KA treatment. At the cellular level, CD200 was expressed in neurons in control, and was upregulated primarily in the microglia of KA-treated mouse hippocampi. We examined the contribution of CD200 to both the classical and alternative activation of microglia in vitro using an adult microglia culture, which was exposed to interleukin-4 (IL-4) with and without lipopolysaccharide (LPS). CD200 expression was increased after exposure to IL-4, but not to LPS. These in vivo experiments demonstrated that CD200 was transiently expressed in microglia in a process mediated by the inflammatory response. Based on CD200R expression in microglia, it suggests that microglia is maintained in an activated state with autocrine signaling by interactions between microglial CD200 and its CD200R. Moreover, we suggest that CD200 may be expressed in the alternative activation of microglia and play a beneficial role in neuroinflammation.
Asunto(s)
Antígenos CD/metabolismo , Encefalitis/inducido químicamente , Encefalitis/metabolismo , Hipocampo/metabolismo , Hipocampo/patología , Microglía/metabolismo , Animales , Modelos Animales de Enfermedad , Agonistas de Aminoácidos Excitadores/toxicidad , Interleucina-4/farmacología , Ácido Kaínico/toxicidad , Lipopolisacáridos/farmacología , Masculino , Ratones , Ratones Endogámicos , Microglía/citología , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/metabolismo , Cultivo Primario de Células , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The genetic control of prostate cancer development is poorly understood. Large numbers of gene-expression datasets on different aspects of prostate tumorigenesis are available. We used these data to identify and prioritize candidate genes associated with the development of prostate cancer and bone metastases. Our working hypothesis was that combining meta-analyses on different but overlapping steps of prostate tumorigenesis will improve identification of genes associated with prostate cancer development. METHODS: A Z score-based meta-analysis of gene-expression data was used to identify candidate genes associated with prostate cancer development. To put together different datasets, we conducted a meta-analysis on 3 levels that follow the natural history of prostate cancer development. For experimental verification of candidates, we used in silico validation as well as in-house gene-expression data. RESULTS: Genes with experimental evidence of an association with prostate cancer development were overrepresented among our top candidates. The meta-analysis also identified a considerable number of novel candidate genes with no published evidence of a role in prostate cancer development. Functional annotation identified cytoskeleton, cell adhesion, extracellular matrix, and cell motility as the top functions associated with prostate cancer development. We identified 10 genes--CDC2, CCNA2, IGF1, EGR1, SRF, CTGF, CCL2, CAV1, SMAD4, and AURKA--that form hubs of the interaction network and therefore are likely to be primary drivers of prostate cancer development. CONCLUSIONS: By using this large 3-level meta-analysis of the gene-expression data to identify candidate genes associated with prostate cancer development, we have generated a list of candidate genes that may be a useful resource for researchers studying the molecular mechanisms underlying prostate cancer development.