Sökning: WFRF:(George Robert) > (1995-1999) > Expression of hirud...
Fältnamn | Indikatorer | Metadata |
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000 | 03761naa a2200409 4500 | |
001 | oai:lup.lub.lu.se:a372514d-4cc9-4aac-a341-a37142b1596f | |
003 | SwePub | |
008 | 190607s1998 | |||||||||||000 ||eng| | |
024 | 7 | a https://lup.lub.lu.se/record/a372514d-4cc9-4aac-a341-a37142b1596f2 URI |
024 | 7 | a https://doi.org/10.1161/01.CIR.98.24.27442 DOI |
040 | a (SwePub)lu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a art2 swepub-publicationtype |
072 | 7 | a ref2 swepub-contenttype |
100 | 1 | a 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 |
245 | 1 0 | a Expression of hirudin fusion proteins in mammalian cells : A strategy for prevention of intravascular thrombosis |
264 | 1 | c 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 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe |
650 | 7 | a 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 | |
700 | 1 | a Chen, Daxinu Hammersmith Hospital4 aut |
700 | 1 | a Kemball-Cook, Geoffreyu Hammersmith Hospital4 aut |
700 | 1 | a McVey, John H.u Hammersmith Hospital4 aut |
700 | 1 | a George, Andrew J.T.u Hammersmith Hospital4 aut |
700 | 1 | a Tuddenham, Edward G.D.u Hammersmith Hospital4 aut |
700 | 1 | a Dorling, Anthonyu Hammersmith Hospital4 aut |
700 | 1 | a Lechler, Robert I.u Hammersmith Hospital4 aut |
710 | 2 | a Klinisk mikrobiologi, Malmöb Forskargrupper vid Lunds universitet4 org |
773 | 0 | t Circulationg 98:24, s. 2744-2752q 98:24<2744-2752x 0009-7322 |
856 | 4 | u http://dx.doi.org/10.1161/01.CIR.98.24.2744y FULLTEXT |
856 | 4 8 | u https://lup.lub.lu.se/record/a372514d-4cc9-4aac-a341-a37142b1596f |
856 | 4 8 | u https://doi.org/10.1161/01.CIR.98.24.2744 |
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