Lead differentially modifies cytokine production in vitro and in vivo

An imbalance between helper T cell type 1 (Th1) and helper T cell type 2 (Th2) activation can result in immunodysregulations leading to impaired cell-mediated immunity with an increased incidence of infectious disease or cancer and/or aberrant humoral immunity that may culminate with an autoimmune disease. Mercury, a heavy-metal toxicant, is known to induce renal autoimmunity characterized by a predominant Th2 response. Lead, another metal toxicant, causes enhanced B cell activities and impairs host resistance to several bacterial and viral infections. In addition, Pb was reported to enhance Th2 proliferation and inhibit Th1 proliferation. The differential effects of Pb on Th subset activation have been further investigated. In vitro IL-4 production by a Th2 clone was significantly increased by the addition of PbCl2, whereas IFN gamma production by a Th1 clone was decreased by the addition of PbCl2. When BALB/c mice were subcutaneously exposed to PbCl2, ex vivo Il-4 production by anti-CD3-stimulated splenic T cells was enhanced, but IFN gamma production was inhibited. Additionally, the plasma IL-4 and IgE levels of Pb-exposed mice were increased, and the plasma IFN gamma levels were significantly lowered in the absence of any additional exogenous antigen. In vitro, ex vivo, and in vivo treatment with HgCl2 produced similar findings. This study is the first report of the preferential activation of a Th2 response by Pb in vivo and suggests that PB, like Hg, may induce autoimmune responses by upsetting the balance between Th1- and Th2-like cells, which could enhance production of antibodies to self antigens.     

Physical and functional association of cortactin with Syk in human leukemic cell line K562

Human leukemic cell line K562 is induced to differentiate into the megakaryocytic lineage by stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA). We demonstrate here that TPA stimulation increases tyrosine phosphorylation of an 80-kDa protein at an early stage of megakaryocytic differentiation and that this 80-kDa protein is identical with cortactin. Since tyrosine kinase Syk was activated by TPA stimulation, we examined the possibility that cortactin is a potential substrate of Syk in K562 cells. TPA-induced tyrosine phosphorylation of cortactin was decreased profoundly by overexpression of dominant-negative Syk. Furthermore, cortactin was associated with Syk even before TPA stimulation. Since cortactin was previously referred as an 80/85-kilodalton pp60src substrate, we examined the association between Src and cortactin, whereas its association could not be detected. These data suggest that Syk phosphorylates cortactin in K562 cells upon TPA treatment.     

A 56 mm twin aperture model dipole magnet for the large hadroncollider

A 56 mm twin aperture model dipole magnet for the large hadron collider has been built at CERN. The magnet design incorporates stainless steel collars and a special yoke structure to minimize saturation-induced field errors. The magnet has proved to be the most successful model prototype constructed so far. In the tests the design field of 10.0 Tesla was achieved with a record-short training. In this paper, the quench performance and the electromagnetic behavior of the magnet are presented and discussed     

Heading towards an advanced signalling system for multimedia,multiparty services in broadband ISDN

Introduction of the broadband integrated services digital network (B-ISDN) will enable network users to make use of advanced multimedia, multiparty services. With this aim in view, RACE II project R2044, MAGIC, is investigating long-term signalling requirements, architecture and protocols for B-ISDN. New service concepts are being developed in MAGIC which will provide more flexibility when compared to narrowband ISDN (N-ISDN). The service requirements and other signalling requirements, such as the separation between call and associated connections at the network-node interface, are used to determine the distribution of functions over the network. The signalling protocols which are used to exchange the signalling information are subsequently developed. These signalling protocols are simulated to prove the performance and the feasibility of call handling concepts     

Patient's self-interpretation of tuberculin skin tests

BACKGROUND: In the outpatient use of tuberculin skin testing (purified protein derivative [PPD]), it is at times inconvenient to have a patient revisit for interpretation. Therefore, we assessed patients' ability to self-interpret these test results. METHODS: In keeping with prior custom, patients were seen by an experienced nurse, who performed skin testing with PPD intermediate strength as well as mumps and Candida anergy control tests in some cases, and explained the procedure. The patients were asked to return 48 to 72 h later, at which time one of the researchers recorded their test interpretations before they were again evaluated by the nurse. RESULTS: Sixty-eight patients were studied, of whom 59 returned at appropriate interval. Eighteen patients had a positive PPD test reaction of 10 to 20 mm induration, which only one patient correctly identified as a positive test result. However, positive anergy control tests were correctly interpreted in 10 of 27 cases. CONCLUSION: The small number of positive PPD test result recognition by these patients may be partially attributed to their lack of education, as well as foreign birth and denial of illness. PPD results should be checked by an experienced professional.     

Expression of V642 APP mutant causes cellular apoptosis as Alzheimer trait-linked phenotype

APP is a transmembrane precursor of beta-amyloid. In dominantly inherited familial Alzheimer's disease (FAD), point mutations V6421, V642F and V642G have been discovered in APP695. Here we show that expression of these mutants (FAD-APPs) causes a clone of COS cells to undergo apoptosis associated with DNA fragmentation. Apoptosis by the three FAD-APPs was the highest among all possible V642 mutants; normal APP695 had no effect on apoptosis, suggesting that apoptosis by APP mutants in this system is phenotypically linked to the FAD trait. FAD-APP-induced apoptosis was sensitive to bcl-2 and most probably mediated by heteromeric G proteins. This study presents a model system allowing analysis of the mechanism for FAD-APP-induced cytotoxicity.     

Direct finite element design optimisation of the cagelessreluctance synchronous machine

The finite element analysis method is used directly in optimisation algorithms to optimise in multidimensions the design of the cageless reluctance synchronous machine. Two optimisation methods are evaluated to minimise or maximise the function value. These are the direction set method of Powell and the quasi-Newton algorithm. Both methods proved to be successful, with some advantages and disadvantages. Using these methods at a power level below 10 kW, results are given of structures of the reluctance synchronous machine which have been optimised according to specific criteria. Calculated and measured results show that the maximum torque optimum designed reluctance synchronous machine has the advantages of high power density and high efficiency     

The application of transmission-line modelling to the simulation ofan induction motor drive

The simulation of a complete induction motor drive is presented. The entire network is modelled using the transmission-line modelling (TLM) technique. The network is split into three sections which are solved independently and are joined together by link transmission-line models. Advantages of this approach are the explicit nature of the algorithm which remains unaltered irrespective of the network topology, unconditional stability, and straightforward modelling of switching elements. Results are presented for a complete drive which illustrate the capabilities and flexibility of the simulation technique