Activated Protein C−Protein C Inhibitor Complex Formation:  Characterization of a Neoepitope Provides Evidence for Extensive Insertion of the Reactive Center Loop

Biochemistry ◽  
2000 ◽  
Vol 39 (51) ◽  
pp. 15713-15720 ◽  
Author(s):  
Karin Strandberg ◽  
Margareta Kjellberg ◽  
Eva-Maria Erb ◽  
Ulla Persson ◽  
Deane F. Mosher ◽  
...  
1995 ◽  
Vol 74 (04) ◽  
pp. 1079-1087 ◽  
Author(s):  
Klaus-P Radtke ◽  
José A Fernández ◽  
Bruno O Villoutreix ◽  
Judith S Greengard ◽  
John H Griffin

SummarycDNAs for protein C inhibitor (PCI) were cloned from human and rhesus monkey 1 liver RNAs by reverse transcription and polymerase chain reaction (PCR) amplification. Sequencing showed that rhesus monkey and human PCI cDNAs were 93% identical. Predicted amino acid sequences differed at 26 of 387 residues. Pour of these differences (T352M, N359S, R362K, L3631) were in the reactive center loop that is important for inhibitory specificity, and two were in the N-terminal helix (M8T, E13K) that is implicated in glycosaminoglycan binding. PCI in human or rhesus monkey plasma showed comparable inhibitory activity towards human activated protein C in the presence of 10 U/ml heparin. However, maximal acceleration of the inhibition of activated protein C required 5-fold lower heparin concentration for rhesus monkey than for human plasma, consistent with the interpretation that the additional positive charge (E13K) in a putative-heparin binding region increased the affinity for heparin.


2000 ◽  
Vol 65 (1) ◽  
pp. 35-40 ◽  
Author(s):  
Rika Watanabe ◽  
Hideo Wada ◽  
Miho Sakakura ◽  
Yoshitaka Mori ◽  
Takahiro Nakasaki ◽  
...  

Critical Care ◽  
2008 ◽  
Vol 12 (Suppl 5) ◽  
pp. P21
Author(s):  
Lars Heslet ◽  
Rikke Hald ◽  
Camilla Recke ◽  
Kristian Bangert ◽  
Lars Uttenthal

2010 ◽  
Vol 24 (5) ◽  
pp. 588-595 ◽  
Author(s):  
David Blomstrand ◽  
Tilo Kölbel ◽  
Bengt Lindblad ◽  
Anders Gottsäter

2009 ◽  
Vol 19 (2) ◽  
pp. 152-158 ◽  
Author(s):  
Olof Rask ◽  
Katarina Hanséus ◽  
Rolf Ljung ◽  
Karin Strandberg ◽  
Erik Berntorp

AbstractObjectiveChildren who undergo surgery for complex congenital cardiac disease are reported to be at increased thrombotic risk. Our aim was to evaluate long-term changes in the haemostatic system after surgery, to compare markers of activated coagulation in children having surgery with those in a healthy control population, and to relate them to adverse clinical outcome.Patients and methodsWe studied, prior to surgery, the coagulation profiles of a cohort of 28 children admitted for a modified Fontan operation, studying them again after a period of mean follow-up of 9.6 years. Median age at the time of final surgery was 18.5 months, with a range from 12 to 76 months. We compared generation of thrombin, and levels of the activated protein C-protein C inhibitor complex to controls at follow-up. Thrombophilia and clinical outcome were evaluated.ResultsAt long-term follow-up, a lower incidence of procoagulant abnormalities was observed compared to that before surgery. Of 27 patients, 3 (11%), but none of 45 controls, had levels of activated protein C-protein C inhibitor complex above the reference range. There were no significant differences in generation of thrombin between patients and controls. No thrombotic events were recorded, and the patients were generally in good clinical condition.ConclusionsOverall, haemostasis appeared to be in balance, and less prothrombotic, after surgery. A subset of the cohort did show indications of activated coagulation. The current therapeutic approach seems to be sufficient to protect the majority of patient. New tests of global coagulation, nonetheless, may be helpful in improving identification of individuals at increased thrombotic risk.


1994 ◽  
Vol 5 (2) ◽  
pp. 173-178 ◽  
Author(s):  
T. Nakase ◽  
H. Wada ◽  
K. Minamikawa ◽  
Y. Wakita ◽  
M. Shimura ◽  
...  

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