INT1767

Context Info Confidence 0.67 First Reported 1979 Last Reported 2010 Negated 5 Speculated 7 Reported most in Abstract Documents 83 Total Number 90 Disease Relevance 54.14 Pain Relevance 17.00

peptidase activity (PROC) extracellular space (PROC) extracellular region (PROC) plasma membrane (PROC)

Anatomy Link Frequency platelet 4 plasma 2 PC-3 2 monocyte 2 immune cells 2 PROC (Homo sapiens)

Pain Link Frequency Relevance Heat palliative 208 100.00 Chronic pancreatitis 12 100.00 Nerve growth factor 10 100.00 Inflammation 533 99.98 Opioid 33 99.98 Bile 20 99.98 opioid receptor 3 99.98 c fibre 1 99.88 Kinase C 81 99.84 bradykinin 1 99.80

Disease Link Frequency Relevance Heat Pancreatitis 189 100.00 Prostate Cancer 168 100.00 Pancreatic Cancer 134 100.00 Reprotox - General 1 76 100.00 Parathyroid Cancer 54 100.00 Aneurism 31 100.00 INFLAMMATION 605 99.98 Infection 87 99.98 Thrombosis 182 99.92 Neurodegenerative Disease 57 99.90

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

In sepsis, both the coagulation and the fibrinolytic system may be affected, as indicated by decreased activation of thrombomodulin and protein C as well as reduction of anti-fibrinolysis and enhancement of plasminogen activator inhibitor (PAI)-1 expression [2].

Positive_regulation (activation) of protein C as associated with sepsis

1) Confidence 0.67 Published 2006 Journal Crit Care Section Body Doc Link PMC1751084 Disease Relevance 1.03 Pain Relevance 0.08

The maximum enhancement of Pc is attained at a conditioning pressure of 80 ATA.

Positive_regulation (enhancement) of Pc

2) Confidence 0.67 Published 1986 Journal J. Appl. Physiol. Section Abstract Doc Link 3804908 Disease Relevance 0.27 Pain Relevance 0.28

In humans, the functional role in vivo was tested in venous thrombosis, where elevated levels of PCI constituted a mild risk factor for thrombosis (Meijers et al. 2002) indicating that of the possible actions of PCI: anticoagulant by inhibition of coagulation enzymes, anti-antifibrinolytic by inhibition of the thrombin activatable fibrinolysis inhibitor (TAFI) activation by thrombin-thrombomodulin, anti-anticoagulant by inhibition of activated protein C and protein C activation by thrombomodulin, and antifibrinolytic by the inhibition of urokinase, the last two options predominate in vivo.

Positive_regulation (activation) of protein C and protein C associated with thrombosis related under development and thrombosis

3) Confidence 0.49 Published 2010 Journal J Mol Histol Section Body Doc Link PMC2852590 Disease Relevance 0.40 Pain Relevance 0

Activation of platelets and blood coagulation factors may play a major role in triggering the syndrome.

Positive_regulation (Activation) of factors in platelets associated with syndrome

4) Confidence 0.41 Published 1987 Journal Circulation Section Abstract Doc Link 2882869 Disease Relevance 1.18 Pain Relevance 0.43

Australian researchers were perceived to have a competitive advantage in database development and developing research networks that could advance PC research (see Table 1).

Positive_regulation (advance) of PC associated with pancreatic cancer

5) Confidence 0.40 Published 2010 Journal Cancer Causes Control Section Body Doc Link PMC2855814 Disease Relevance 0.64 Pain Relevance 0.12

Human factors were also claimed as contributing factors.

Positive_regulation (contributing) of factors

6) Confidence 0.39 Published 2008 Journal J Med Assoc Thai Section Body Doc Link 19127793 Disease Relevance 0 Pain Relevance 0

Furthermore, reserpine blocks the increase in Pc during prolonged pressure exposure.

Positive_regulation (increase) of Pc

7) Confidence 0.39 Published 1986 Journal J. Appl. Physiol. Section Abstract Doc Link 3804908 Disease Relevance 0.25 Pain Relevance 0.33

Different pathophysiologic mechanisms have been proposed: changes in epithelial permeability, pelvic floor dysfunction, mastocytosis, activation of c-fibers, and increase of nerve growth factors and bradykinin.

Positive_regulation (increase) of factors in nerve associated with c fibre, stress incontinence, nerve growth factor, mastocytosis and bradykinin

8) Confidence 0.38 Published 2000 Journal Curr Rev Pain Section Abstract Doc Link 10998726 Disease Relevance 0.76 Pain Relevance 0.78

Although earlier studies have demonstrated postprandial activation of coagulation factors VII and XII, platelets and monocytes, conclusive evidence for intravascular fibrin formation after a fat-rich meal has not been reported yet.

Positive_regulation (activation) of factors VII in monocytes

9) Confidence 0.38 Published 2007 Journal Int. J. Cardiol. Section Abstract Doc Link 16730815 Disease Relevance 0.34 Pain Relevance 0.13

Specific research recommendations included the following: researching better modalities to deliver chemotherapy, reducing the deleterious effects of pancreatectomy on nutrition, finding simpler and faster screening tests, developing targeted screening for people at increased risk of PC, and exploring the role of genetic testing in disease prevention.

Positive_regulation (increased) of PC associated with pancreatic cancer and disease

10) Confidence 0.37 Published 2010 Journal Cancer Causes Control Section Body Doc Link PMC2855814 Disease Relevance 0.72 Pain Relevance 0

Therefore, in good accordance with the study by Liaw and colleagues in adult septic patients [28], we assume that the lack of elevated free APC levels in the presence of activated coagulation in patients with AP in most cases reflected dysfunctional PC activation on the endothelium, or possibly enhanced inhibition of APC by plasma protease inhibitors.

Spec (possibly) Positive_regulation (activation) of PC in plasma associated with pancreatitis

11) Confidence 0.34 Published 2006 Journal Crit Care Section Body Doc Link PMC1550818 Disease Relevance 0.67 Pain Relevance 0

Due to their location internal iliac artery (IIA) aneurysms are not directly accessible for stent-graft placement.

Neg (not) Positive_regulation (accessible) of IIA in internal iliac artery associated with aneurism

12) Confidence 0.32 Published 2007 Journal Cardiovasc Intervent Radiol Section Body Doc Link PMC1964782 Disease Relevance 0.73 Pain Relevance 0.06

The intrapatient variation in PC levels from day to day was large.

Positive_regulation (variation) of PC

13) Confidence 0.25 Published 2006 Journal Crit Care Section Body Doc Link PMC1550818 Disease Relevance 0.10 Pain Relevance 0

The total PC was measured by activating the bound PC in the wells by Protac (American Diagnostica, Greenwich, CT, USA) and then measuring the amidolytic activity with the chromogenic substrate S-2366 (Chromogenix AB).

Positive_regulation (activating) of PC

14) Confidence 0.25 Published 2006 Journal Crit Care Section Body Doc Link PMC1550818 Disease Relevance 0 Pain Relevance 0

It thus seems that, in patients developing MOF, the PC activation system reached its limits prior to the diagnosis of MOF, resulting in secondary deficiency of PC concomitantly with a failure to maintain steady APC levels similar to those observed in AP patients without MOF.

Positive_regulation (activation) of PC associated with multiple organ failure and pancreatitis

15) Confidence 0.25 Published 2006 Journal Crit Care Section Body Doc Link PMC1550818 Disease Relevance 1.57 Pain Relevance 0.06

In rabbits, both the stimulation of alpha1-adrenoceptors and ischemic preconditioning (PC) reduce infarct size.

Positive_regulation (stimulation) of PC

16) Confidence 0.24 Published 1997 Journal Heart Vessels Section Abstract Doc Link 9860197 Disease Relevance 0.07 Pain Relevance 0.37

The consequence is an increased flow velocity and therefore increased shear stress in the collateral arteries, which leads to a marked activation of the endothelium with the subsequent morphological changes, vascular remodeling and activation of growth factors involved in angiogenesis and arteriogenesis.

Positive_regulation (activation) of factors in endothelium associated with stress

17) Confidence 0.20 Published 2004 Journal Arch Cardiol Mex Section Abstract Doc Link 15216748 Disease Relevance 0.63 Pain Relevance 0.14

Since LDL has a high affinity for heparin and heparin for growth factors, LDL accumulation may be a mechanism for the concentration of such materials in the intima.

Positive_regulation (accumulation) of factors

18) Confidence 0.17 Published 1987 Journal Ann. N. Y. Acad. Sci. Section Abstract Doc Link 3439738 Disease Relevance 0.41 Pain Relevance 0.06

These results seem to exclude the possibility of enhanced PC breakdown and further suggest that the main inhibitory effect is on the CDP-choline pathway for PC biosynthesis.

Spec (possibility) Positive_regulation (enhanced) of PC

19) Confidence 0.16 Published 1994 Journal Cell Biochem. Funct. Section Abstract Doc Link 8044894 Disease Relevance 0 Pain Relevance 0.45

Activation of platelets and blood coagulation factors may play a major role in triggering the syndrome.

Positive_regulation (Activation) of factors in blood associated with syndrome

20) Confidence 0.14 Published 1987 Journal Circulation Section Abstract Doc Link 2882869 Disease Relevance 1.18 Pain Relevance 0.43

General Comments

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