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  • 1
    Publication Date: 2018-10-23
    Description: Genome-wide association studies have recently illuminated that WDFY4 is genetically associated with systemic lupus erythematosus (SLE) susceptibility in various ethnic groups. Despite strong genetic evidence suggesting a role of WDFY4 in SLE pathogenesis, its functional relevance is largely unknown. In this study, we generated Wdfy4 B lymphocyte conditional knockout ( Wdfy4 -CKO) mice and found that loss of Wdfy4 led to a decrease in number of total B cells and several subpopulations of B cells in the periphery and a defect in the transition from the pro– to pre–B cell stage in bone marrow. Also, Wdfy4 -CKO mice showed impaired Ab responses as compared with controls when challenged with Ag. SLE phenotypes were effectively alleviated in Wdfy4 -CKO mice, with significantly diminished pristane-elicited production of autoantibodies and glomerulonephritis. Genetic silencing of WDFY4 in B cells increased lipidation of LC3 independent of p62 and Beclin1, which are essential proteins of canonical autophagy. Our in vivo and in vitro data suggest that WDFY4 facilitates noncanonical autophagic activity. Our findings provide a novel functional link underlying the mechanism of SLE in which WDFY4 influences B cell fate via noncanonical autophagy.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 51 (1996), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Twenty-five patients undergoing elective cataract day surgery were studied after receiving a dual-injection peribulbar block with a mixture consisting of equal volumes of 2% lignocaine and 0.75% bupivacaine with hyaluronidase. A maximum of 10ml of solution was used for the initial block; supplementary injections of up to 10 ml were given to five patients. Venous blood was taken prior to the block and then 1, 10, 20, 30, 60 and 90 min after the block. The peak mean concentrations of lignocaine (0.722 μg. ml−1) and bupivacaine (0.353 μg. ml−1)were found at 10–20 min after injection when no top-up was given and at 10 min after the top-up injection when required. All measured serum concentrations of lignocaine and bupivacaine were below the accepted toxic levels of the two drugs. However, the highest individual toxicity score after a top-up was 0.915 which was very close to the toxicity threshold (= 1) when a scoring system was used to assess the combined levels.
    Type of Medium: Electronic Resource
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