110 research outputs found
Characterization of proteins from human synovium and mononuclear leucocytes that induce resorption of cartilage proteoglycan in vitro
Pig catabolin is a form of interleukin 1. Cartilage and bone resorb, fibroblasts make prostaglandin and collagenase, and thymocyte proliferation is augmented in response to one protein
An Association of Multiple Well Differentiated Liposarcomas, Lipomatous Tissue and Hereditary Retinoblastoma
Well differentiated liposarcoma (atypical lipomatous tumour) is a low grade tumour, with no metastatic potential unless
dedifferentiation supervenes. When superficial, it recurs locally only occasionally after marginal excision. We present a
patient in whom bilateral childhood retinoblastoma was followed by later development of massive confluent areas of low
grade liposarcoma and lipomatous tissue affecting the upper extremities and trunk. We discuss the role of mutations in the
retinoblastoma gene (RB1) in linking these conditions and demonstrate the surgical management of an extremely unusual
and challenging case
What do we know of Roman wall painting technique? Potential confounding factors in ancient paint media analysis
Control of Oxo-Group Functionalization and Reduction of the Uranyl Ion
yesUranyl complexes of a large, compartmental
N8-macrocycle adopt a rigid, “Pacman” geometry that stabilizes
the UV oxidation state and promotes chemistry at a single
uranyl oxo-group. We present here new and straightforward
routes to singly reduced and oxo-silylated uranyl Pacman
complexes and propose mechanisms that account for the
product formation, and the byproduct distributions that are
formed using alternative reagents. Uranyl(VI) Pacman
complexes in which one oxo-group is functionalized by a
single metal cation are activated toward single-electron
reduction. As such, the addition of a second equivalent of a
Lewis acidic metal complex such as MgN″2 (N″ = N(SiMe3)2) forms a uranyl(V) complex in which both oxo-groups are Mg
functionalized as a result of Mg−N bond homolysis. In contrast, reactions with the less Lewis acidic complex [Zn(N″)Cl] favor
the formation of weaker U−O−Zn dative interactions, leading to reductive silylation of the uranyl oxo-group in preference to
metalation. Spectroscopic, crystallographic, and computational analysis of these reactions and of oxo-metalated products isolated
by other routes have allowed us to propose mechanisms that account for pathways to metalation or silylation of the exo-oxogroup
One-Step Preservation of Phosphoproteins and Tissue Morphology at Room Temperature for Diagnostic and Research Specimens
BACKGROUND: There is an urgent need to measure phosphorylated cell signaling proteins in cancer tissue for the individualization of molecular targeted kinase inhibitor therapy. However, phosphoproteins fluctuate rapidly following tissue procurement. Snap-freezing preserves phosphoproteins, but is unavailable in most clinics and compromises diagnostic morphology. Formalin fixation preserves tissue histomorphology, but penetrates tissue slowly, and is unsuitable for stabilizing phosphoproteins. We originated and evaluated a novel one-step biomarker and histology preservative (BHP) chemistry that stabilizes signaling protein phosphorylation and retains formalin-like tissue histomorphology with equivalent immunohistochemistry in a single paraffin block. RESULTS: Total protein yield extracted from BHP-fixed, routine paraffin-embedded mouse liver was 100% compared to snap-frozen tissue. The abundance of 14 phosphorylated proteins was found to be stable over extended fixation times in BHP fixed paraffin embedded human colon mucosa. Compared to matched snap-frozen tissue, 8 phosphoproteins were equally preserved in mouse liver, while AMPKβ1 Ser108 was slightly elevated after BHP fixation. More than 25 tissues from mouse, cat and human specimens were evaluated for preservation of histomorphology. Selected tissues were evaluated in a multi-site, independent pathology review. Tissue fixed with BHP showed equivalent preservation of cytoplasmic and membrane cytomorphology, with significantly better nuclear chromatin preservation by BHP compared to formalin. Immunohistochemical staining of 13 non-phosphorylated proteins, including estrogen receptor alpha, progesterone receptor, Ki-67 and Her2, was equal to or stronger in BHP compared to formalin. BHP demonstrated significantly improved immunohistochemical detection of phosphorylated proteins ERK Thr202/Tyr204, GSK3-α/β Ser21/Ser9, p38-MAPK Thr180/Tyr182, eIF4G Ser1108 and Acetyl-CoA Carboxylase Ser79. CONCLUSION: In a single paraffin block BHP preserved the phosphorylation state of several signaling proteins at a level comparable to snap-freezing, while maintaining the full diagnostic immunohistochemical and histomorphologic detail of formalin fixation. This new tissue fixative has the potential to greatly facilitate personalized medicine, biobanking, and phospho-proteomic research
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