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Patients with multiple sclerosis have significant atrophy of both white matter (WM) and gray matter (GM); secondary progressive patients have significantly more atrophy of both WM and GM than do relapsing-remitting patients and a significantly higher lesion load (abnormal WM fraction); lesion load is related to both WM and even more to GM atrophy; lesion load and WM and GM atrophy are significantly related to Expanded Disability Status Scale score and age at onset (suggesting that the younger the age at disease onset, the worse the lesion load and brain atrophy); and GM atrophy is the most significant MRI variable in determining the final disability.

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Melanoma is the most aggressive skin cancer; there is no cure in advanced stages. Identifying molecular participants in melanoma progression may provide useful diagnostic and therapeutic tools. FK506 binding protein 51 (FKBP51), an immunophilin with a relevant role in developmental stages, is highly expressed in melanoma and correlates with aggressiveness and therapy resistance. We hypothesized a role for FKBP51 in melanoma invasive behaviour. FKBP51 promoted activation of epithelial-to-mesenchymal transition (EMT) genes and improved melanoma cell migration and invasion. In addition, FKBP51 induced some melanoma stem cell (MCSC) genes. Purified MCSCs expressed high EMT genes levels, suggesting that genetic programs of EMT and MCSCs overlap. Immunohistochemistry of samples from patients showed intense FKBP51 nuclear signal and cytoplasmic positivity for the stem cell marker nestin in extravasating melanoma cells and metastatic brains. In addition, FKBP51 targeting by small interfering RNA (siRNA) prevented the massive metastatic substitution of liver and lung in a mouse model of experimental metastasis. The present study provides evidence that the genetic programs of cancer stemness and invasiveness overlap in melanoma, and that FKBP51 plays a pivotal role in sustaining such a program.

The purpose of this study was the development and testing of a method for unsupervised, automated brain segmentation. Two spin-echo sequences were used to obtain relaxation rates and proton-density maps from 1.5 T MR studies, with two axial data sets including the entire brain. Fifty normal subjects (age range, 16 to 76 years) were studied. A Three-dimensional (3D) spectrum of the tissue voxels was used for automatic segmentation of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) and for calculation of their volumes. Accuracy and reproducibility were tested with a three-compartment phantom simulating GM, WM, and CSF. In the normal subjects, a significant decrease of GM fractional volume and increased CSF volume with age were observed (P < 0.0001), with no significant changes in WM. This multispectral segmentation method permits reproducible, operator-independent volumetric measurements.

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