David A. Lane
University of Cambridge
Binding siteInternal medicineEndocrinologyMolecular biologyChemistryImmunologyThrombinHeparinAnticoagulantCoagulationAntithrombinFibrinogenThrombosisADAMTS13ChromatographyFibrinGeneticsBiochemistryMedicineBiology
Publications 409
#1David A. Lane (University of Cambridge)H-Index: 73
AbstractHistorical materialism envisages law-like tendencies (‘scientific’ Marxism) promoting the development of productive forces and, concurrently, a political praxis (‘active’ Marxism) requiring...
1 CitationsSource
#1David Lane (University of Cambridge)H-Index: 17
The lifting of the iron curtain separating the Soviet bloc from the rest of the world led to high expectations from the established powers in the West and the reformers in the East. On both sides o...
1 CitationsSource
#1Josefin Ahnström (Imperial College London)H-Index: 16
#2Magdalena Gierula (Imperial College London)H-Index: 8
Last. David A. Lane (Imperial College London)H-Index: 73
view all 5 authors...
BACKGROUND: Activated coagulation factor X (FXa) is the serine protease component of prothrombinase, the physiological activator of prothrombin. Factor X Nottingham (A404T) and Taunton (R405G) are two naturally occurring mutations, identified in families with a bleeding phenotype. OBJECTIVE: To characterize these FX variants functionally. METHODS: The activity and inhibition of recombinant FX variants were quantified in plasma-based and pure component assays. RESULTS: The prothrombin times in FX...
1 CitationsSource
#1Magdalena Gierula (Imperial College London)H-Index: 8
#2Isabelle I. Salles-Crawley (Imperial College London)H-Index: 6
Last. Josefin Ahnström (Imperial College London)H-Index: 16
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BACKGROUND: Activated protein C (APC)-mediated inactivation of factor (F)Va is greatly enhanced by protein S. For inactivation to occur, a trimolecular complex among FVa, APC, and protein S must form on the phospholipid membrane. However, direct demonstration of complex formation has proven elusive. OBJECTIVES: To elucidate the nature of the phospholipid-dependent interactions among APC, protein S, and FVa. METHODS: We evaluated binding of active site blocked APC to phospholipid-coated magnetic ...
5 CitationsSource
#1Salvatore Santamaria (Imperial College London)H-Index: 14
#2Kazuhiro Yamamoto (University of Liverpool)H-Index: 17
Last. Josefin Ahnström (Imperial College London)H-Index: 16
view all 8 authors...
ADAMTS (A Disintegrin-like and Metalloproteinase domain with Thrombospondin type 1 Motif)-1, -4 and -5 share the abilities to cleave large aggregating proteoglycans including versican and aggrecan. These activities are highly relevant to cardiovascular disease and osteoarthritis and during development. Here, using purified recombinant ADAMTS-1, -4 and -5, we quantify, compare, and define the molecular basis of their versicanase activity. A novel sandwich-ELISA detecting the major versican cleava...
13 CitationsSource
#1James T. B. Crawley (Hammersmith Hospital)H-Index: 30
#2Argita Zalli (Hammersmith Hospital)H-Index: 1
Last. Isabelle I. Salles-Crawley (Hammersmith Hospital)H-Index: 6
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BACKGROUND: Bone morphogenetic and activin membrane-bound inhibitor (BAMBI) is a transmembrane protein related to the type I transforming growth factor- β (TGF-β) receptor family that is present on both platelets and endothelial cells (ECs). Bambi-deficient mice exhibit reduced hemostatic function and thrombus stability characterized by an increased embolization. OBJECTIVE: We aimed to delineate how BAMBI influences endothelial function and thrombus stability. METHODS: Bambi-deficient mice were ...
2 CitationsSource
#1Michael Newnham (University of Cambridge)H-Index: 8
#2Kieron South (Imperial College London)H-Index: 10
Last. Mark Toshner (University of Cambridge)H-Index: 30
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Chronic thromboembolic pulmonary hypertension (CTEPH) is an important consequence of pulmonary embolism that is associated with abnormalities in haemostasis. We investigated the ADAMTS13–von Willebrand factor (VWF) axis in CTEPH, including its relationship with disease severity, inflammation, ABO groups and ADAMTS13 genetic variants. ADAMTS13 and VWF plasma antigen levels were measured in patients with CTEPH (n=208), chronic thromboembolic disease without pulmonary hypertension (CTED) (n=35), re...
14 CitationsSource
#1Kieron South (Imperial College London)H-Index: 10
#2Frederik Denorme (Katholieke Universiteit Leuven)H-Index: 14
Last. David A. Lane (Imperial College London)H-Index: 73
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: Essentials ADAMTS13 requires a substrate-induced conformational change to attain full activity in vitro. The efficacy of wild type ADAMTS13 in models of thrombosis/stroke may be enhanced by pre-activation. A pre-activated ADAMTS13 variant exhibits enhanced proteolysis of platelet agglutinates. This ADAMTS13 variant is protective in a murine model of stroke at a lower dose than WT ADAMTS13. SUMMARY: Background ADAMTS-13 circulates in a closed conformation, only achieving full proteolytic activi...
8 CitationsSource
#1Ryan S Thwaites (NIH: National Institutes of Health)H-Index: 12
#2Natasha C. Gunawardana (NIH: National Institutes of Health)H-Index: 3
Last. Trevor T. Hansel (Imperial College London)H-Index: 30
view all 13 authors...
Abstract Complement, coagulation and fibrinolysis contribute to the pathology of many respiratory diseases. Here we detail the biphasic activation of these pathways following nasal allergen challenge. Understanding these mechanisms may lead to therapeutic insight in common respiratory diseases.
2 CitationsSource
#1Kieron South (Imperial College London)H-Index: 10
#2David A. Lane (Imperial College London)H-Index: 73
VWF is a key player in haemostasis, acting as a carrier for FVIII and capturing platelets at sites of vascular damage. To capture platelets, it must undergo conformational changes, both within its A1 domain and at the macromolecular level through A2 domain unfolding. Its size and this function are regulated by the metalloproteinase, ADAMTS13. Recently, it has been shown that ADAMTS13 undergoes a conformational change upon interaction with VWF and that this enhances its activity towards its subst...
32 CitationsSource