Preferential down-regulation of phospholipase C- β in Ewing's sarcoma cells transfected with antisense EWS-Fli-1

EWS-Fli-1, a fusion gene found in Ewing's sarcoma and primitive neuro-ectodermal tumour (PNET), encodes a transcriptional activator and promotes cellular transformation. We have made stable Ewing's sarcoma cells expressing antisense EWS-Fli-1 transcripts by transfecting the antisense EWS-Fli-1 expression plasmid. These cells showed partial loss of endogenous EWS-Fli-1 proteins and suppression of the cell growth. To elucidate the molecular mechanisms underlying the growth inhibition, we examined the changes of signal transducing proteins by immunoblot analysis in Ewing's sarcoma cells stably expressing antisense EWS-Fli-1 transcripts. Western blotting of the cell proteins revealed that expressions of phospholipase Cβ2 and β3 (PLCβ2, PLCβ3), and also protein kinase C α and β (PKCα, β) were significantly reduced by transfecting with antisense EWS-Fli-1. The inositol phosphates production by bradykinin (BK), but not platelet-derived growth factor (PDGF), was suppressed in these cells. These results suggest that the PLCβ2 and PLCβ3 may play a role in tumour proliferation in Ewing's sarcoma cells. © 2000 Cancer Research Campaig

Effects of phosphodiesterase inhibitors on secretions of human monokines

ABSTRACTThe purpose of this study was to evaluate the effect of newly developed selective phosphodiesterase (PDE) inhibitors, KF19514 (type l/IV) and cilostazol (type III), and theophylline on the secretions of tumor necrosis factor a (TNFα) and interleukin-1β (IL-1 β) from human peripheral monocytes stimulated by lipopolysaccha- ride (LPS). Human blood monocytes were incubated with LPS in the absence or presence of KF19514, cilostazol or theophylline. TNFα and IL-1in the cell- free supernatants were measured with enzyme-linked immunosorbent assay. KF19514 showed significant inhibition on the release of TNFα (% inhibition ± SEM was 82.8 ± 7.4% at 1 nmol/L) and IL-1 β (34.4 ± 7.5% at 10 (μmol/L). In addition, KF19514 inhibited the expression of TNFa mRNA. Cilostazol inhibited the release of TNFa significantly (60.2 ± 8.9% at 30 μmol/L) but not IL-1 β. Theophylline inhibited slightly but significantly the release of TNFa at a therapeutic concentration (1 7.4 ± 5.1% at 100 μmol/L). These results suggest that theophylline may not only have a bronchodilating action but also an anti-inflammatory property in the treatment of bronchial asthma, and that KF19514 may have an anti-inflammatory action on at least the transcriptional level

Pulmonary MR angiography and perfusion imaging—A review of methods and applications

The pulmonary vasculature and its role in perfusion and gas exchange is an important consideration in many conditions of the lung and heart. Currently the mainstay of imaging of the vasculature and perfusion of the lungs lies with CT and nuclear medicine perfusion scans, both of which require ionizing radiation exposure. Improvements in MRI techniques have increased the use of MRI in pulmonary vascular imaging. Here we review MRI methods for imaging the pulmonary vasculature and pulmonary perfusion, both using contrast enhanced and non-contrast enhanced methodology. In many centres pulmonary MR angiography and dynamic contrast enhanced perfusion MRI are now well established in the routine workflow of patients particularly with pulmonary hypertension and thromboembolic disease. However, these imaging modalities offer exciting new directions for future research and clinical use in other respiratory diseases where consideration of pulmonary perfusion and gas exchange can provide insight in to pathophysiology

MRI of the lung (3/3)-current applications and future perspectives

BACKGROUND: MRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women. METHODS: Provided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value. RESULTS: In interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a "buffet" of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice. CONCLUSION: New developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed. Main Messages • MRI evolves as a third lung imaging modality, combining morphological and functional information. • It may be considered first choice in cystic fibrosis and pulmonary embolism of young and pregnant patients. • In other cases (tumours, pneumonia in children), it is an alternative or adjunct to X-ray and CT. • In interstitial lung disease, it serves for research, but the clinical value remains to be proven. • New users are advised to make themselves familiar with the particular advantages and limitations

Quantum Transport in Nonuniform Magnetic Fields: Aharonov-Bohm Ring as a Spin Switch

We study the spin-dependent magneto conductance in mesoscopic rings subject to an inhomogeneous in-plane magnetic field. We show that the polarization direction of transmitted spin-polarized electrons can be controlled via an additional magnetic flux such that spin flips are induced at half a flux quantum. This quantum interference effect is independent of the strength of the nonuniform field applied. We give an analytical explanation for one-dimensional rings and numerical results for corresponding ballistic microstructures.Comment: 5 pages, 3 figures. To be published in Physical Review Letter

Assessing drug target suitability using TargetMine [version 1; peer review: 2 approved]

In selecting drug target candidates for pharmaceutical research, the linkage to disease and the tractability of the target are two important factors that can ultimately determine the drug efficacy. Several existing resources can provide gene-disease associations, but determining whether such a list of genes are attractive drug targets often requires further information gathering and analysis. In addition, few resources provide the information required to evaluate the tractability of a target. To address these issues, we have updated TargetMine, a data warehouse for assisting target prioritization, by integrating new data sources for gene-disease associations and enhancing functionalities for target assessment. As a data mining platform that integrates a variety of data sources, including protein structures and chemical compounds, TargetMine now offers a powerful and flexible interface for constructing queries to check genetic evidence, tractability and other relevant features for the candidate genes. We demonstrate these features by using several specific examples

Non-DMS related ferromagnetism in transition metal doped zinc oxide

We review pitfalls in recent efforts to make a conventional semiconductor, namely ZnO, ferromagnetic by means of doping with transition metal ions. Since the solubility of those elements is rather low, formation of secondary phases and the creation of defects upon low temperature processing can lead to unwanted magnetic effects. Among others, ion implantation is a method of doping, which is highly suited for the investigation of those effects. By focussing mainly on Fe, Co or Ni implanted ZnO single crystals we show that there are manifold sources for ferromagnetism in this material which can easily be confused with the formation of a ferromagnetic diluted magnetic semiconductor (DMS). We will focus on metallic as well as oxide precipitates and the difficulties of their identification.Comment: 24 pages, 22 figure

A Comprehensive Analysis of Fermi Gamma-Ray Burst Data. I. Spectral Components and Their Possible Physical Origins of LAT/GBM GRBs

We present a systematic analysis of the spectral and temporal properties of 17 GRBs co-detected by GBM and LAT on board the Fermi satellite by May 2010. We performed a time-resolved spectral analysis of all the bursts with the finest temporal resolution allowed by statistics, in order to avoid temporal smearing of different spectral components. We found that the time-resolved spectra of 14 out of 17 GRBs are best modeled with the Band function over the entire Fermi spectral range, which may suggest a common origin for emissions detected by LAT and GBM. GRB 090902B and GRB 090510 require the superposition between an MeV component and an extra power law component, with the former having a sharp cutoff above E_p. For GRB 090902B, this MeV component becomes progressively narrower as the time bin gets smaller, and can be fit with a Planck function as the time bin becomes small enough. In general, we speculate that phenomenologically there may be three elemental spectral components : (I) a Band-function component (e.g. in GRB 080916C) that extends in a wide energy range and does not narrow with reducing time bins, which may be of the non-thermal origin; (II) a quasi-thermal component (e.g. in GRB 090902B) with the spectra progressively narrowing with reducing time bins; and (III) another non-thermal power law component extending to high energies. The spectra of different bursts may be decomposed into one or more of these elemental components. We compare this sample with the BATSE sample and investigate some correlations among spectral parameters. We discuss the physical implications of the data analysis results for GRB prompt emission, including jet compositions (matter-dominated vs. Poynting-flux-dominated outflow), emission sites (internal shock, external shock or photosphere), as well as radiation mechanisms (synchrotron, synchrotron self-Compton, or thermal Compton upscattering).Comment: 61 pages, 25 figures, 3 tables. 2011 ApJ in pres

Extremely large d0 magnetism in krypton implanted polar ZnO films

Magnetization is produced in samples of ZnO by implanting krypton ions. Krypton is chemically inert hence the magnetization is the consequence of the radiation damage that occurred due to the implantation process. We have found magnetizations as large as 185 emu/cm3 at room temperature which corresponds to a moments of ~40 Bohr magnetons per implanted krypton ion. Results are compared for implantation into different ZnO samples, O and Zn polar thin films and thin ZnO crystal wafers. The structure of the films has been investigated using RHEED, AFM, XRD and EXAFS. The O-polar film grew in a layer-by-layer mode and after implantation, its lattice spacing increased and the grain size decreased which indicated that the Kr atoms had been incorporated into the lattice. In contrast the Zn-polar film grew in Stranski-Krastanov mode and its lattice spacing and grain size were almost unchanged by the implantation indicating that the Kr atoms were in the grain boundaries. Raman scattering is used to characterize the radiation damage and to identify scattering from amorphous regions in grain boundaries and the scattering from point defects. The largest magnetization is found in the O-polar ZnO films where there is a marked grain fragmentation, leading to an increase in the volume of the sample occupied by grain boundaries. The increase in the numbers of point defects, which were identified by Raman scattering for films of both polarity, was less effective at producing a magnetic signal than the grain boundaries