A Granulin-Like Growth Factor Secreted by the Carcinogenic Liver Fluke, Opisthorchis viverrini, Promotes Proliferation of Host Cells

The human liver fluke, Opisthorchis viverrini, infects millions of people throughout south-east Asia and is a major cause of cholangiocarcinoma, or cancer of the bile ducts. The mechanisms by which chronic infection with O. viverrini results in cholangiocarcinogenesis are multi-factorial, but one such mechanism is the secretion of parasite proteins with mitogenic properties into the bile ducts, driving cell proliferation and creating a tumorigenic environment. Using a proteomic approach, we identified a homologue of human granulin, a potent growth factor involved in cell proliferation and wound healing, in the excretory/secretory (ES) products of the parasite. O. viverrini granulin, termed Ov-GRN-1, was expressed in most parasite tissues, particularly the gut and tegument. Furthermore, Ov-GRN-1 was detected in situ on the surface of biliary epithelial cells of hamsters experimentally infected with O. viverrini. Recombinant Ov-GRN-1 was expressed in E. coli and refolded from inclusion bodies. Refolded protein stimulated proliferation of murine fibroblasts at nanomolar concentrations, and proliferation was inhibited by the MAPK kinase inhibitor, U0126. Antibodies raised to recombinant Ov-GRN-1 inhibited the ability of O. viverrini ES products to induce proliferation of murine fibroblasts and a human cholangiocarcinoma cell line in vitro, indicating that Ov-GRN-1 is the major growth factor present in O. viverrini ES products. This is the first report of a secreted growth factor from a parasitic worm that induces proliferation of host cells, and supports a role for this fluke protein in establishment of a tumorigenic environment that may ultimately manifest as cholangiocarcinoma

Gradient-enhanced TOCSY experiments with improved sensitivity and solvent suppression

NRC publication: Ye

Factory and site tests on the 25 MW GTO power amplifier for the control of the JET plasma vertical position

SIGLEAvailable from British Library Document Supply Centre- DSC:4672.262(JET-P--93/31) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

AC/DC converters for the ITER poloidal field circuit

AC/DC converters will provide the power necessary to generate the Poloidal Field (PF) scenario and to control the plasma shape and position. Moreover, in order to provide additional voltage during the plasma initiation phase, Booster Converter and Switching Networks are used. About 2.6 GVA is the total installed power presently foreseen for the main AC/DC converters. Capability to supply 650 MW, 500 MV Ar are the site assumptions. Starting from the reference scenario, the requirements and the design criteria for the present AC/DC converter system are presented. Then, studies to optimize the design are discussed. Finally the ratings and the main characteristics of the present basic units are describe

Design, construction and operation of the 66 kA life test facility for the ITER magnet protection vacuum circuit breaker

The characteristics of the 66 kA test facility built up at the Consorzio RFX are presented and discussed together with the results of interruption and life tests performed on a new vacuum circuit breaker intended to fulfil possible ITER requirements for the Fast Discharge Unit

Status of ITER coil power supply design

This paper focuses on the recent modifications of the Coil Power Supply and Distribution System (CPSDS) to adapt it to the revised magnet configuration and plasma scenarios. Updated performance of the main components (AC/DC converters, switching networks and discharge circuits) are presented. The layout of the equipment is described with emphasis on the revision made to meet the new seismic requirements and to reduce the cost of busbars