Optic glioma tumors were generated in Nf1+/- mice lacking Nf1 expression in GFAP+ cells (astrocytes). Standard immunohistochemistry methods were employed to identify astrocytes (GFAP, S100 beta), proliferating progenitor cells (sox2, nestin), microglia (Iba1), endothelial cells (CD31) and retinal ganglion cell (RGC) see more axons (Neurofilament 68k) in Nf1+/-, Nf1(GFAP)CKO (wild-type mice with Nf1 loss in glial cells), and Nf1+/-(GFAP)CKO (Nf1+/-

mice with Nf1 loss in glial cells) mice. Ultrastructural changes in the optic chiasm and nerve were assessed by electron microscopy (EM). RGC were counted in whole retina preparations using high-resolution, mosaic confocal microscopy following their delineation by retrograde FluoroGold labeling. We found that only Nf1+/-(GFAP)CKO mice exhibited gross pre-chiasmatic click here optic nerve and chiasm enlargements containing aggregated GFAP+/nestin+ and S100 beta+/sox2+ cells (neoplastic glia) as well as increased numbers of blood vessels and microglia. Optic gliomas in Nf1+/-(GFAP)CKO mice contained axon fiber irregularities and multilamellar

bodies of degenerated myelin. EM and EM tomographic analyses showed increased glial disorganization, disoriented axonal projections, profiles of degenerating myelin and structural alterations at nodes of Ranvier. Lastly, we found reduced RGC numbers in Nf1+/-(GFAP)CKO mice, supporting a model in which the combination of optic nerve Nf1 heterozygosity and glial cell Nf1 loss results in disrupted BMS-754807 axonal-glial relationships, subsequently culminating in the degeneration of optic nerve axons and loss of their parent RGC neurons. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Skeletal-related events (SREs) are common in patients with osteolytic lesions from multiple myeloma (MM), and result in substantial morbidity. We report herein a comprehensive, retrospective, multivariate analysis of prognostic factors for survival and first on-study SRE in MM patients using data from the phase III, randomized study comparing zoledronic acid with pamidronate in

MM or breast cancer. Cox regression analyses were used to assess 22 variables for prognostic significance (defined as associations with P<0.05) in patients with bone metabolism marker assessments and complete baseline variable data. Of 510 evaluable MM patients, 282 had complete covariate information and were included in models. Reduced Cox multivariate models identified five significant prognostic factors for first SRE (weight, race, high N-terminal cross-linked telopeptide of type I collagen (NTX), high pain score, and need for narcotic analgesics) and seven for survival (age, SRE history, myeloma subtype, anemia, high lactate dehydrogenase, high NTX, and low albumin levels). High NTX was the only variable associated with elevated risks of both first SRE and death (P <= 0.02 for each). These analyses identified prognostic factors for SREs and survival in patients with MM.