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Linda A. Robbie
University of Aberdeen
FibrinolysisPlasminogen activatorPlasminogen activator inhibitor-1FibrinMedicine
32Publications
14H-index
694Citations
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Publications 31
Newest
#1Linda A. RobbieH-Index: 14
#2Susan BerryH-Index: 2
Last. Bruce BennettH-Index: 8
view all 9 authors...
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#1Linda A. RobbieH-Index: 14
#2Bruce BennettH-Index: 26
Last. Nuala A. BoothH-Index: 35
view all 4 authors...
Source
#1Nicola J. MutchH-Index: 8
#2Elaine MoirH-Index: 4
Last. Nuala A. BoothH-Index: 35
view all 6 authors...
Human thrombi vary in their susceptibility to lysis and this is clinically important. Several potential contributory factors were examined in this study by using model thrombi, created under flow; these provide a robust, reproducible and easily-manipulated system. Here we identify the plasminogen activators (PA) active in model thrombi of known age and define the cellular and plasma contribution to activity in different areas. The cell-rich head of model thrombi had strong thrombin and PA activi...
6 CitationsSource
#1Elaine MoirH-Index: 4
#2Linda A. RobbieH-Index: 14
Last. Nuala A. BoothH-Index: 35
view all 4 authors...
Polymorphonuclear leucocytes (PMN) are important in the resolu-tion of human thrombi, with u-PA as a key player. We have shown that the u-PA activity of PMN depends on the presence of plasma; the study presented here provides an explanation for that requirement. Here we show that PMN degraded scu-PA and also tcu-PA, t-PA and plas-min, resulting in loss of fibrinolytic activity. Plasma protected against this degradation; 1 -antitrypsin was identified as a protective factor. Purified human neutrop...
25 CitationsSource
#1Nicola J. MutchH-Index: 8
#2Linda A. RobbieH-Index: 14
Last. Nuala A. BoothH-Index: 35
view all 3 authors...
This study assessed the abundance and activity of thrombin in human thrombi, removed at autopsy or during surgery. Arterial and venous thrombus sections showed thrombin activity by in situ zymography, based on conversion of fibrinogen to fibrin. Hirudin or antibodies to thrombin abolished the activity. Thrombin activity in extracts of 40 thrombi was quantified by cleavage of fibrinogen or small peptide substrates; the results correlated well (r = 0.87, p
49 CitationsSource
Abstract— Atherosclerosis is characterized by thickening of the vessel wall, smooth muscle cell proliferation, macrophage infiltration, and deposition of a fibrin network. Transglutaminases are a family of enzymes catalyzing the formation of stable covalent cross-links between proteins. Here, we show that tissue transglutaminase (tTG) synthesis by human umbilical vein endothelial cells is upregulated by thrombin, the serine protease that causes fibrin formation and many cellular inflammatory eff...
35 CitationsSource
#1Elaine Moir (Aberd.: University of Aberdeen)H-Index: 4
#2Nuala A. Booth (Aberd.: University of Aberdeen)H-Index: 35
Last. Linda A. Robbie (Aberd.: University of Aberdeen)H-Index: 14
view all 4 authors...
Many human thrombi lyse spontaneously without the administration of lytic drugs and cause no clinical symptoms. The mechanisms by which this occurs are incompletely understood. We found that model thrombi prepared from whole human blood in a Chandler loop also exhibited significant spontaneous lysis. Lysis was inhibited by chemical protease inhibitors, consistent with proteolysis resulting primarily from serine proteases, with a small contribution from matrix metalloproteinases. Whole blood was ...
43 CitationsSource
#1Linda A. Robbie (Aberd.: University of Aberdeen)H-Index: 14
#2Bruce Bennett (Aberd.: University of Aberdeen)H-Index: 26
Last. Nuala A. BoothH-Index: 35
view all 4 authors...
This study used two mutants of tissue-type plasminogen activator (t-PA) with resistance to inhibitors of fibrinolysis to define the contribution of plasminogen activator inhibitor (PAI)-1 and α2-antiplasmin (α2-AP) to the control of fibrin lysis. Wild-type t-PA was compared with KHRR296–299AAAA, which is resistant to PAI-1, and with A473S, which is resistant to α2-AP. We examined these forms of t-PA in model systems that are physiologically relevant. Neutralization of α2-AP was essential for lys...
9 CitationsSource
#1Linda A. Robbie (Aberd.: University of Aberdeen)H-Index: 14
#2Susan BerryH-Index: 2
Last. Bruce BennettH-Index: 8
view all 9 authors...
Purified preparations of circulating leukaemic blast cells from patients with acute myeloid (M1–7) or acute lymphoblastic leukaemia, and the myeloid or lymphoid cells from patients with chronic myeloid or lymphocytic forms of leukaemia, were incorporated into clots prepared from fibrinogen and plasminogen. Patterns of lysis were followed and measured by light transmission in a microtitre plate reader. Mature polymorphonuclear and mononuclear cell fractions from normal individuals were studied co...
7 CitationsSource
#1Linda A. Robbie (Aberd.: University of Aberdeen)H-Index: 14
#2S. DummerH-Index: 1
Last. Bruce BennettH-Index: 26
view all 5 authors...
Proteins influencing plasminogen activation to plasmin, namely plasminogen activators tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA) and their principal inhibitors, plasminogen activator inhibitor 1 (PAI-1) and PAI-2, were measured in the plasma, the polymorph and mononuclear cell fractions taken from patients with major sepsis who were entering a general intensive care unit. The purpose of this study was to elucidate the factors favouring the persistenc...
35 CitationsSource
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