Upregulation of vascular endothelial growth factor receptor-3 in the spinal cord of Lewis rats with experimental autoimmune encephalomyelitis.

We investigated the spatiotemporal expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in the spinal cord of Lewis rats with experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. VEGFR-3 mRNA and protein were constitutively expressed in gray matter neurons and in a few white matter astrocytes. Induction of VEGFR-3 occurred predominantly in perivascular infiltrated macrophages in the spinal cord white matter during the inductive phase of EAE. VEGFR-3 expression was also induced in activated microglial cells in the gray and white matter, mainly in the peak phase. In addition, reactive astrocytes in the white matter, but not in the gray matter, expressed VEGFR-3 as disease severity increased. These data suggest that VEGFR-3 is involved in the recruitment of monocytic macrophages and in glial reactions during EAE.

Induction of vascular endothelial growth factor receptor-3 expression in perivascular cells of the ischemic core following focal cerebral ischemia in rats.

Vascular endothelial growth factor receptor (VEGFR)-3, a receptor for VEGF-C and VEGF-D, has recently been reported to be induced within vessel-like structures in the ischemic brain. The purpose of the present study was to characterize and define further the cellular phenotypes of vascular-associated cells that manifest induced VEGFR-3 expression in a rat model of ischemic stroke. Vessel-associated cells expressing VEGFR-3 were found to be perivascular astrocytes in the peri-infarct region, whereas in the ischemic core, where astrocytes had virtually disappeared, induction of VEGFR-3 mRNA and protein was still prominent in vascular structures 3-7 days after reperfusion. VEGFR-3 and nestin expression were colocated in almost all cells associated with the vasculature in the ischemic core, and most (~82%) of the VEGFR-3/nestin double-labeled cells were proliferative. A subpopulation of these VEGFR-3-expressing cells appeared to be included in two immunophenotypically distinct perivascular cells: NG2-positive pericytes and ED2- or OX6-perivascular macrophages. However, most of these cells did not show markers for vasculature-associated cell types such as endothelial cells, microglia/macrophages, and smooth muscle cells. Thus, our data indicated that vasculature-associated VEGFR-3-expressing cells in the ischemic core may represent a heterogeneous population of cells with functional diversity, rather than a uniform cell type.

Partially cystic thyroid nodules: ultrasound findings of malignancy.

OBJECTIVE: To seek for the ultrasound (US) findings of partially cystic thyroid nodules that are associated with malignancy. MATERIALS AND METHODS: We reviewed the US characteristics of 22 surgically confirmed partially cystic papillary carcinomas, and compared them with those of 80 benign partially cystic nodules. The review cases were selected in a random order from a total of 1029 partially cystic nodules that were diagnosed with an US-guided fine needle aspiration biopsy over a period of 8 years (June 2003 to October 2010) at our institution. RESULTS: In partially cystic thyroid nodules, a taller-than-wide shape (100%, p < 0.001) and spiculated or microlobulated margin (58.3%, p = 0.003) were significantly associated with malignancy. In terms of internal solid portion of the nodule, eccentric configuration (68.0%, p < 0.001), non-smooth margin (81.3%, p < 0.001), hypoechogenecity (30.0%, p < 0.042), and microcalcification (89.5%, p < 0.001) were more frequently demonstrated in malignant nodules than benign ones. CONCLUSION: In partially cystic thyroid nodules, understanding the characteristics of US findings is important to make a precise diagnosis of malignant nodules.

Overlapping distribution of osteopontin and calcium in the ischemic core of rat brain after transient focal ischemia.

Osteopontin (OPN), an adhesive glycoprotein, has recently been proposed to act as an opsonin that facilitates phagocytosis of neuronal debris by macrophages in the ischemic brain. The present study was designed to elucidate the process whereby OPN binds to neuronal cell debris in a rat model of ischemic stroke. Significant co-localization of the OPN protein and calcium deposits in the ischemic core were observed by combining alizarin red staining and OPN immunohistochemistry. In addition, electron microscopy (EM) using the osmium/potassium dichromate method revealed that electron-dense precipitates, typical of calcium deposits, were localized mainly along the periphery of putative degenerating neurites. This topical pattern of calcium precipitates resembled the distribution of OPN as detected by immunogold-silver EM. Combining immunogold-silver EM and electron probe microanalysis further demonstrated that the OPN protein was localized at the periphery of cell debris or degenerating neurites, corresponding with locally higher concentrations of calcium and phosphorus, and that the relative magnitude of OPN accumulation was comparable to that of calcium and phosphorus. These data suggest that calcium precipitation provides a matrix for the binding of the OPN protein within the debris or degenerating neurites induced by ischemic injury. Therefore, OPN binding to calcium deposits may be involved in phagocytosis of such debris, and may participate in the regulation of ectopic calcification in the ischemic brain.