Alternative transcripts in the mouse neurofibromatosis type 2 (NF2) gene are conserved and code for schwannomins with distinct C-terminal domains

Mutations in the neurofibromatosis type 2 (NF2) gene predisposeindividuals to the development of nervous system tumors andocular abnormalities. The NF2 gene product, schwannomin, isa member of a superfamily of proteins thought to link cytoskeletalelements to cell membrane components. These proteins share significanthomologles in the N-terminal and     

Macromolecular therapeutic systems based on polyurethanes. Kinetic laws of the release of dioxidine

Pharmaceutical Chemistry Journal -     

Primitive stem cells derived from bone marrow express glial and neuronal markers and support revascularization in injured retina exposed to ischemic and mechanical damage

Ischemic or mechanical injury to the optic nerve is an irreversible cause of vision loss, associated with limited regeneration and poor response to neuroprotective agents. The aim of this study was to assess the capacity of adult bone marrow cells to participate in retinal regeneration following the induction of anterior ischemic optic neuropathy (AION) and optic nerve crush (ONC) in a rodent model. The small-sized subset of cells isolated by elutriation and lineage depletion (Fr25lin(-)) was found to be negative for the neuroglial markers nestin and glial fibrillary acidic protein (GFAP). Syngeneic donor cells, identified by genomic marker in sex-mismatched transplants and green fluorescent protein, incorporated into the injured retina (AION and ONC) at a frequency of 0.35%-0.45% after intravenous infusion and 1.8%-2% after intravitreous implantation. Perivascular cells with astrocytic morphology expressing GFAP and vimentin were of the predominant lineage that engrafted after AION injury; 10%-18% of the donor cells incorporated in the retinal ganglion cell layer and expressed NeuN, Thy-1, neurofilament, and beta-tubulin III. The Fr25lin(-) cells displayed an excellent capacity to migrate to sites of tissue disruption and developed coordinated site-specific morphological and phenotypic neural and glial markers. In addition to cellular reconstitution of the injured retinal layers, these cells contributed to endothelial revascularization and apparently supported remodeling by secretion of insulin-like growth factor-1. These results suggest that elutriated autologous adult bone marrow-derived stem cells may serve as an accessible source for cellular reconstitution of the retina following injury.     

VEGF Induces Neuroglial Differentiation in Bone Marrow-Derived Stem Cells and Promotes Microglia Conversion Following Mobilization with GM-CSF

Purpose

Evaluation of potential tropic effects of vascular endothelial growth factor (VEGF) on the incorporation and differentiation of bone-marrow-derived stem cells (BMSCs) in a murine model of anterior ischemic optic neuropathy (AION).

Methods

In the first approach, small-sized subset of BMCs were isolated from GFP donors mice by counterflow centrifugal elutriation and depleted of hematopoietic lineages (Fr25lin^-). These cells were injected into a peripheral vein (1?×?10⁶ in 0.2?ml) or inoculated intravitreally (2?×?10⁵) to syngeneic mice, with or without intravitreal injection of 5 ??g/2??L VEGF, simultaneously with AION induction. In a second approach, hematopoietic cells were substituted by myelablative transplant of syngeseic GFP + bone marrow cells. After 3?months, progenitors were mobilized with granulocyte-macrophage colony-stimulating factor (GM-CSF) followed by VEGF inoculation into the vitreous body and AION induction . Engraftment and phenotype were examined by immunohistochemistry and FISH at 4 and 24?weeks post-transplantation, and VEGF receptors were determined by real time PCR.

Results

VEGF had no quantitative effect on incorporation of elutriated cells in the injured retina, yet it induced early expression of neuroal markers in cells incorporated in the RGC layer and promoted durable gliosis, most prominent perivascular astrocytes. These effects were mediated by VEGF-R1/Flt-1, which is constitutively expresses in the elutriated fraction of stem cells. Mobilization with GM-CSF limited the differentiation of bone marrow progenitors to microglia, which was also fostered by VEGF.

Conclusions

VEGF signaling mediated by Flt-1 induces early neural and sustained astrocytic differentiation of stem cells elutriated from adult bone-marrow, with significant contribution to stabilization retinal architecture following ischemic injury.     

Immunohistochemistry for EGFR Mutation Detection in Non–Small-Cell Lung Cancer

Introduction

The sensitivity and specificity of immunohistochemistry (IHC) was compared with the standard polymerase chain reaction (PCR)-based method for detecting common activating epidermal growth factor receptor (EGFR) mutations in non–small-cell lung cancer (NSCLC). Additionally, we evaluated predictive value of IHC EGFR mutation–positive status for EGFR tyrosine kinase inhibitor (TKI) treatment outcome and estimated cost-effectiveness for the upfront IHC testing.