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WFRF:(George Robert)
 

Sökning: WFRF:(George Robert) > (1995-1999) > Expression of hirud...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003761naa a2200409 4500
001oai:lup.lub.lu.se:a372514d-4cc9-4aac-a341-a37142b1596f
003SwePub
008190607s1998 | |||||||||||000 ||eng|
024a https://lup.lub.lu.se/record/a372514d-4cc9-4aac-a341-a37142b1596f2 URI
024a https://doi.org/10.1161/01.CIR.98.24.27442 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
100a Riesbeck, Kristianu Lund University,Lunds universitet,Klinisk mikrobiologi, Malmö,Forskargrupper vid Lunds universitet,Clinical Microbiology, Malmö,Lund University Research Groups,Skåne University Hospital,Hammersmith Hospital4 aut0 (Swepub:lu)mikr-kri
2451 0a Expression of hirudin fusion proteins in mammalian cells : A strategy for prevention of intravascular thrombosis
264 1c 1998
520 a Background - Intravascular thrombosis occurs in disorders of diverse pathogeneses, including allograft and xenograft rejection. In this in vitro study, we describe an approach for tethering the specific thrombin inhibitor hirudin to plasma membranes as part of a genetic strategy for regulating intravascular coagulation. Methods and Results - An HLA class I leader sequence was fused with hirudin linked to domains 3 and 4 of human CD4 and intracytoplasmic sequence from either CD4 or human P-selectin. The constructs were transfected into mouse fibroblasts, Chinese hamster ovary (CHO)-K1 cells, immortalized porcine endothelial cells (IPECs), and a pituitary secretory cell line (D16/16). Thrombin binding to the hirudin fusion proteins expressed on fibroblasts and CHO-K1 cells could be blocked by an anti- hirudin monoclonal antibody and by pretreatment of thrombin with either the synthetic tripeptide thrombin inhibitor PPACK or native hirudin. Hirudin expression significantly modified the procoagulant phenotype of IPECs in human plasma, leading to prolongation of clotting times. Hirudin-CD4-P- selectin fusion proteins accumulated in adrenocorticotropic hormone- containing granules in D16/16 cells, with no cell surface expression except on activation with phorbol ester, when hirudin relocated to the outer membrane. Conclusions - Hirudin fusion proteins were expressed on mammalian cells, where they reduced local thrombin levels and inhibited fibrin formation. Regulated expression was achieved on activated cells by use of the cytoplasmic sequence from P-selectin. In vivo, these fusion proteins may prove useful transgenic or gene therapy agents for preventing intravascular thrombosis.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cardiac and Cardiovascular Systems0 (SwePub)302062 hsv//eng
653 a Anticoagulants
653 a Coagulation
653 a Thrombosis
653 a Transplantation
700a Chen, Daxinu Hammersmith Hospital4 aut
700a Kemball-Cook, Geoffreyu Hammersmith Hospital4 aut
700a McVey, John H.u Hammersmith Hospital4 aut
700a George, Andrew J.T.u Hammersmith Hospital4 aut
700a Tuddenham, Edward G.D.u Hammersmith Hospital4 aut
700a Dorling, Anthonyu Hammersmith Hospital4 aut
700a Lechler, Robert I.u Hammersmith Hospital4 aut
710a Klinisk mikrobiologi, Malmöb Forskargrupper vid Lunds universitet4 org
773t Circulationg 98:24, s. 2744-2752q 98:24<2744-2752x 0009-7322
856u http://dx.doi.org/10.1161/01.CIR.98.24.2744y FULLTEXT
8564 8u https://lup.lub.lu.se/record/a372514d-4cc9-4aac-a341-a37142b1596f
8564 8u https://doi.org/10.1161/01.CIR.98.24.2744

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