57 research outputs found

    CD105 (Endoglin) exerts prognostic effects via its role in the microvascular niche of paediatric high grade glioma

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    Paediatric high grade glioma (pHGG) (World Health Organisation astrocytoma grades III and IV) remains poor prognosis tumours, with a median survival of only 15 months following diagnosis. Current investigation of anti-angiogenic strategies has focused on adult glioblastoma multiforme (GBM) with phase III trials targeting vascular endothelial growth factor continuing. In this study we investigated whether the degree of vascularity correlated with prognosis in a large cohort of pHGG (n = 150) and whether different vessel markers carried different prognostic value. We found that CD105 (endoglin) had a strongly significant association with poor prognosis on multivariate analysis (p = <0.001). Supervised hierarchical clustering of genome wide gene expression data identified 13 genes associated with differential degrees of vascularity in the cohort. The novel angiogenesis-associated genes identified in this analysis (including MIPOL-1 and ENPP5) were validated by realtime polymerase chain reaction. We also demonstrate that CD105 positive blood vessels associate with CD133 positive tumour cells and that a proportion of CD105 positive vessel cells demonstrates co-positivity for CD133, suggesting that the recently described phenomenon of vasculogenic mimicry occurs in pHGG. Together, the data suggest that targeting angiogenesis, and in particular CD105, is a valid therapeutic strategy for pHGG

    Takotsubo Cardiomyopathy Precipitated by Tapering of Anxiolytic Medication: A Case Report

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    Takotsubo cardiomyopathy is a transient apical ballooning of the left ventricle typically with electrocardiographic changes and enzyme release without evidence of obstructive coronary artery disease. It typically occurs in postmenopausal women and may have a predilection for patients with anxiety disorders. The following is a case in which we believe takotsubo cardiomyopathy was induced by the tapering of antianxiety medications. We feel that health care professionals should be aware of this possibility in such a patient population especially when they have demonstrated cardiovascular symptomatology

    Characterization of Backbone Structures in Poly(vinylidene fluoride-<i>co</i>-hexafluoropropylene) Copolymers by Multidimensional <sup>19</sup>F NMR Spectroscopy

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    Advanced modern multidimensional solution NMR experiments have been used to deduce the sequence distribution in poly­(VDF-<i>co</i>-HFP) copolymers. Assignment of <sup>19</sup>F resonances from different monomer- and regio-sequences in poly­(VDF-<i>co</i>-HFP) copolymer were identified. In addition to corroborating some assignments reported in earlier literature, this work provides assignments of some new resonances from the spectra of poly­(VDF-<i>co</i>-HFP) copolymer, which resulted from better dispersion of the resonances. These assignments are used for the monomer sequence analyses of two polymers using first-order Markovian statistics, and the relative reactivities of the monomers during polymerization are discussed. The results from this study provide insight into the polymerization chemistry for this fluoropolymer

    Characterization of Backbone Structures in Poly(vinylidene fluoride-<i>co</i>-hexafluoropropylene) Copolymers by Multidimensional <sup>19</sup>F NMR Spectroscopy

    No full text
    Advanced modern multidimensional solution NMR experiments have been used to deduce the sequence distribution in poly­(VDF-<i>co</i>-HFP) copolymers. Assignment of <sup>19</sup>F resonances from different monomer- and regio-sequences in poly­(VDF-<i>co</i>-HFP) copolymer were identified. In addition to corroborating some assignments reported in earlier literature, this work provides assignments of some new resonances from the spectra of poly­(VDF-<i>co</i>-HFP) copolymer, which resulted from better dispersion of the resonances. These assignments are used for the monomer sequence analyses of two polymers using first-order Markovian statistics, and the relative reactivities of the monomers during polymerization are discussed. The results from this study provide insight into the polymerization chemistry for this fluoropolymer

    NMR Study of the Chain End and Branching Units in Poly(vinylidene fluoride-<i>co</i>-tetrafluoroethylene)

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    2D-NMR techniques were used to identify the detailed structures of chain end and branching units in poly­(vinylidene fluoride-<i>co</i>-tetrafluoroethylene), poly­(VDF-<i>co</i>-TFE). Atomic connectivity information was provided by selective <sup>19</sup>F–<sup>19</sup>F COSY (correlation spectroscopy), <sup>19</sup>F­{<sup>1</sup>H} gHETCOR (gradient heteronuclear correlated), and <sup>1</sup>H­{<sup>13</sup>C} HSQC (heteronuclear single quantum correlation) experiments. Diffusion ordered spectroscopy (DOSY) and spin–lattice relaxation (<i>T</i><sub>1</sub>) data permitted distinction of backbone, short chain branch, and chain end resonances from one another. Quantitative data on these structures are reported; quantitation also supported assignments through the consistent relative intensities of resonances from the same structures. Possible reactions during the polymerization which could lead to these structures are discussed

    2D-NMR Characterization of Sequence Distributions in the Backbone of Poly(vinylidene fluoride-<i>co</i>-tetrafluoroethylene)

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    NMR is a powerful tool to study the microstructures of poly­(vinylidene fluoride-<i>co</i>-tetrafluoroethylene), poly­(VDF-<i>co</i>-TFE). This study shows that the microstructures in this copolymer can be established completely on the basis of 2D-NMR, in which improved dispersion is achieved by the second dimension (<sup>19</sup>F or <sup>13</sup>C chemical shifts). 2D-NMR has been proven to be extremely effective for identifying the carbon sequence distributions in the polymer main chain. For lower level sequences (3- or 5-carbon sequences), resonance assignments on the basis of one- and two-bond <sup>19</sup>F­{<sup>13</sup>C} gradient heteronuclear single quantum coherence (gHSQC) experiments are in good agreement with assignments obtained by traditional methods. Higher level sequences (7- or 9-carbon sequences), which can not be assigned unambiguously by traditional methods, were determined by <sup>19</sup>F–<sup>19</sup>F gradient double quantum correlation spectroscopy (gdqCOSY), which provides <sup>19</sup>F–<sup>19</sup>F correlations over 3–5 bonds. A quantitative study was also conducted on the composition of this copolymer. Three different approaches were used to calculate the fraction of TFE and the inversion ratio of VDF units

    Characterization of the Chain-Ends and Branching Structures in Polyvinylidene Fluoride with Multidimensional NMR

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    Multidimensional solution NMR (<sup>19</sup>F, <sup>1</sup>H, and <sup>13</sup>C) has been used to determine chain-ends and backbone branching points and to obtain unambiguous <sup>19</sup>F and <sup>1</sup>H resonances assignments from these chain-ends and branching structures in poly­(vinylidene fluoride) (PVDF). The multidimensional NMR methods employed in this study not only enabled the resonance assignments of the last monomer of the chain but also provided assignments for the last three monomer units of chain-end structures. The chain-end signals from PVDF were determined using spin–lattice relaxation measurements and 2D diffusion ordered spectroscopy (DOSY) analysis. 2D-NMR analyses were also used to assign resonances of chain branching points along the backbone of the polymer
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