Spindle cell sarcoma of sphenoid bone

Primary bone tumors involving skull are extremely rare and they constitute 0.8% of all bone tumors. The common tumors that are seen in skull base include fibrous dysplasia, giant cell tumor, chordoma, ossifying fibroma, angiosarcoma. We report a rare case of spindle cell sarcoma arising from right sphenoid bone in a 70-year-old male which presented as unilateral defective vision with mild proptosis

Adult hematopoietic progenitors are pluripotent in chimeric mice

18 pages, 7 figures.Embryonic stem cells (ESCs) and adult somatic cells, induced to pluripotency (iPSCs) by genetic manipulation, display high self-­‐renewal potential and the capacity to differentiate into multiple cell lineages. We asked whether there are in adult mammals natural stem cells that are pluripotent. We previously reported that normal adult mammalian bone marrow contains a sub-­‐population of CD34+ cells, that naturally expresses genes characteristic of ESCs and those required to generate iPSCs, but have a limited lifespan and do not form teratomas. In addition, these CD34+ cells spontaneously express, without genetic manipulation, genes characteristic of the three embryonic germ layers: i.e., ectodermal neural, mesodermal cardiac muscle, and endodermal pancreatic and intestinal lineage genes (Pessac, B, et al. 2011. Hematopoietic progenitors express embryonic stem cell and germ layer genes. Comptes Rendus Biologies 334: 300-­‐306). This suggested that these cells may be pluripotent. Here we have transplanted these CD34+ bone marrow stem cells from adult male C56Bl/6J ROSA mice, that carry two markers: the ß-­‐galactosidase gene and the male Y chromosome, into blastocysts of wildtype C57Bl/6J mice. These blastocysts develop normally and give rise to healthy adult chimeric mice. Each female ROSA chimeric mouse had a distinct pattern of male organs expressing ß-­‐galactosidase derived from each of the three embryonic germ layers: ectodermal brain, dorsal root ganglia and skin; mesodermal heart, bone and bone marrow; and endodermal pancreas, intestine, and liver. Thus, adult mammals still carry cells that appear to exhibit a developmental potential comparable to ESCs and iPSCs suggesting that CD34+ cells from adult bone marrow could be used for cell therapy

Deciphering the relative roles of matrix metalloproteinase‐ and plasmin‐mediated matrix degradation during capillary morphogenesis using engineered hydrogels

Extracellular matrix (ECM) remodeling is essential for the process of capillary morphogenesis. Here we employed synthetic poly(ethylene glycol) (PEG) hydrogels engineered with proteolytic specificity to either matrix metalloproteinases (MMPs), plasmin, or both to investigate the relative contributions of MMP‐ and plasmin‐mediated ECM remodeling to vessel formation in a 3D‐model of capillary self‐assembly analogous to vasculogenesis. We first demonstrated a role for both MMP‐ and plasmin‐mediated mechanisms of ECM remodeling in an endothelial‐fibroblast co‐culture model of vasculogenesis in fibrin hydrogels using inhibitors of MMPs and plasmin. When this co‐culture model was employed in engineered PEG hydrogels with selective protease sensitivity, we observed robust capillary morphogenesis only in MMP‐sensitive matrices. Fibroblast spreading in plasmin‐selective hydrogels confirmed this difference was due to protease preference by endothelial cells, not due to limitations of the matrix itself. In hydrogels engineered with crosslinks that were dually susceptible to MMPs and plasmin, capillary morphogenesis was unchanged. These findings highlight the critical importance of MMP‐mediated degradation during vasculogenesis and provide strong evidence to justify the preferential selection of MMP‐degradable peptide crosslinkers in synthetic hydrogels used to study vascular morphogenesis and promote vascularization. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2507–2516, 2019.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151850/1/jbmb34341_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151850/2/jbmb34341.pd

Derivation of guidelines for uranium residual radioactive material in soil at the New Brunswick Site, Middlesex County, New Jersey

Residual radioactive material guidelines for uranium in soil were derived for the New Brunswick Site, located in Middlesex County, New Jersey. This site has been designated for remedial action under the Formerly Utilized Sites Remedial Action Program of the US Department of Energy (DOE). Residual radioactive material guidelines for individual radionuclides of concern and total uranium were derived on the basis of the requirement that the 50-year committed effective dose equivalent to a hypothetical individual who lives or works in the immediate vicinity of the New Brunswick Site should not exceed a dose of 30 mrem/yr following remedial action for the current-use and likely future-use scenarios or a dose of 100 mrem/yr for less likely future-use scenarios. The DOE residual radioactive material guideline computer code, RESRAD, was used in this evaluation; RESRAD implements the methodology described in the DOE manual for establishing residual radioactive material guidelines. The guidelines derived in this report are intended to apply to the remediation of these remaining residual radioactive materials at the site. The primary radionuclides of concern in these remaining materials are expected to be radium-226 and, to a lesser extent, natural uranium and thorium. The DOE has established generic cleanup guidelines for radium and thorium in soil; however, cleanup guidelines for other radionuclides must be derived on a site-specific basis

Vasohibin inhibits angiogenic sprouting in vitro and supports vascular maturation processes in vivo

<p>Abstract</p> <p>Background</p> <p>The murine homologue of human vasohibin (mVASH1), a putative antiangiogenic protein, was investigated for its effects on <it>in vitro </it>and <it>in vivo </it>angiogenesis.</p> <p>Methods</p> <p>Cell growth and migration were analyzed in murine fibroblasts, smooth muscle cells and endothelial cells. Angiogenic sprouting was studied in human umbilical vein endothelial cells (HUVECs) in the spheroid sprouting assay. <it>In vivo </it>effects on blood vessel formation were investigated in the chorioallantoic membrane (CAM) assay and in the C57BL/6 melanoma xenograft model.</p> <p>Results</p> <p>Purified murine and human VASH1 protein induced apoptosis of murine fibroblasts <it>in vitro</it>, but not of vascular aortic smooth muscle cells (AoSMC) or endothelial cells. Adenoviral overexpression of murine and human VASH1 inhibited capillary sprouting of HUVECs in the spheroid assay. Administration of recombinant murine and human VASH1 inhibited growth of large vessels in the CAM assay and promoted the formation of a dense, fine vascular network. Murine VASH1-overexpressing B16F10 melanomas displayed a reduction in large vessels and vascular area. Moreover, tumors showed more microvessels that stained positive for the mural cell markers α-smooth muscle cell actin (ASMA) and proteoglycan (NG2).</p> <p>Conclusion</p> <p>Our data imply that murine VASH1 causes angiogenic remodelling by inhibiting angiogenic sprouting and large vessel growth, thereby supporting the formation of a vascular bed consisting predominantly of mature microvessels.</p

Near-infrared molecular imaging of tumors via chemokine receptors CXCR4 and CXCR7

The chemokine CXCL12/SDF-1 and its receptors CXCR4 and CXCR7 play a major role in tumor invasion, proliferation and metastasis. Since both receptors are overexpressed on distinct tumor cells and on the tumor vasculature, we evaluated their potential as targets for detection of cancers by molecular imaging. We synthesized conjugates of CXCL12 and the near-infrared (NIR) fluorescent dye IRDye®800CW, tested their selectivity, sensitivity and biological activity in vitro and their feasibility to visualize tumors in vivo. Purified CXCL12-conjugates detected in vitro as low as 500 A764 human glioma cells or MCF-7 breast cancer cells that express CXCR7 alone or together with CXCR4. Binding was time- and concentration-dependent, and the label could be competitively displaced by the native peptide. Control conjugates with bovine serum albumin or lactalbumin failed to label the cells. In mice, the conjugate distributed rapidly. After 1–92 h, subcutaneous tumors of human MCF-7 and A764 cells in immunodeficient mice were detected with high sensitivity. Background was observed in particular in liver within the first 24 h, but also skull and hind limbs yielded some background. Overall, fluorescent CXCL12-conjugates are sensitive and selective probes to detect solid and metastatic tumors by targeting tumor cells and tumor vasculature

Sympathetic Effects of Internal Carotid Nerve Manipulation on Choroidal Vascularity and Related Measures

Purpose: To investigate specific effects of denervation and stimulation of the internal carotid nerve (ICN) on the choroid and retina. Methods: Female Sprague Dawley rats underwent unilateral ICN transection (n = 20) or acute ICN electrical stimulation (n = 7). Rats in the denervation group were euthanized 6 weeks after nerve transection, and eyes were analyzed for changes in choroidal vascularity (via histomorphometry) or angiogenic growth factors and inflammatory markers (via ELISA). Rats in the stimulation group received acute ICN electrical stimulation with a bipolar cuff electrode over a range of stimulus amplitudes, frequencies, and pulse widths. Choroidal blood flow and pupil diameter were monitored before, during, and after stimulation. Results: Six weeks after unilateral ICN transection, sympathectomized choroids exhibited increased vascularity, defined as the percentage of choroidal surface area occupied by blood vessel lumina. Vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) protein levels in denervated choroids were 61% and 124% higher than in contralateral choroids, respectively. TNF-α levels in denervated retinas increased by 3.3-fold relative to levels in contralateral retinas. In animals undergoing acute ICN electrical stimulation, mydriasis and reduced choroidal blood flow were observed in the ipsilateral eye. The magnitude of the reduction in blood flow correlated positively with stimulus frequency. Conclusions: Modulation of ICN activity reveals a potential role of the ocular sympathetic system in regulating endpoints related to neovascular diseases of the eye

Detection of paralytic shellfish toxins in mussels and oysters using the qualitative neogen lateral-flow immunoassay: an interlaboratory study

Paralytic shellfish toxins (PSTs) in bivalve molluscs represent a public health risk and are controlled via compliance with a regulatory limit of 0.8 mg saxitoxin (STX)center dot 2HCl equivalents per kilogram of shellfish meat (eq/kg). Shellfish industries would benefit from the use of rapid immunological screening tests for PSTs to be used for regulation, but to date none have been fully validated. An interlaboratory study involving 16 laboratories was performed to determine the suitability of the Neogen test to detect PSTs in mussels and oysters. Participants performed the standard protocol recommended by the manufacturer and a modified protocol with a conversion step to improve detection of gonyautoxin 1&4. The statistical analysis showed that the protocols had good homogeneity across all laboratories, with satisfactory repeatability, laboratory, and reproducibility variation near the regulatory level. The mean probability of detection (POD) at 0.8 mg STX center dot 2HCl eq/kg using the standard protocol in mussels and oysters was 0.966 and 0.997, respectively, and 0.968 and 0.966 using the modified protocol. The estimated LOD in mussels was 0.316 mg STX center dot 2HCl eq/kg with the standard and 0.682 mg STX center dot 2HCl eq/kg with the modified protocol, and 0.710 and 0.734 mg STX center dot 2HCl eq/kg for oysters, respectively. The Neogen test may be acceptable for regulatory purposes for oysters in accordance with European Commission directives in which the standard protocol provides, at the regulatory level, a probability of a negative response of 0.033 on 95% of occasions. Its use for mussels is less consistent at the regulatory level due to the wide prediction interval around the POD