INT12240

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Context Info
Confidence 0.57
First Reported 1982
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 46
Total Number 46
Disease Relevance 29.50
Pain Relevance 10.77

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

peptidase activity (PRSS1) extracellular space (PRSS1) extracellular region (PRSS1)
Anatomy Link Frequency
pancreas 2
plasma 1
tube 1
stellate cell 1
cleavage 1
PRSS1 (Homo sapiens)
Pain Link Frequency Relevance Heat
Cholecystokinin 22 100.00 Very High Very High Very High
fibrosis 146 99.80 Very High Very High Very High
Chronic pancreatitis 1004 99.28 Very High Very High Very High
Inflammation 248 98.64 Very High Very High Very High
tetrodotoxin 4 96.00 Very High Very High Very High
cytokine 115 94.76 High High
metalloproteinase 1 94.20 High High
bradykinin 17 86.80 High High
Inflammatory response 20 85.92 High High
anesthesia 58 80.36 Quite High
Disease Link Frequency Relevance Heat
Targeted Disruption 248 100.00 Very High Very High Very High
Cystic Fibrosis 125 100.00 Very High Very High Very High
Urinary Tract Infection 52 100.00 Very High Very High Very High
Multiple Organ Failure 3 99.40 Very High Very High Very High
Pancreatitis 1496 99.28 Very High Very High Very High
Acid Reflux 18 99.02 Very High Very High Very High
Disease 272 98.64 Very High Very High Very High
INFLAMMATION 246 98.64 Very High Very High Very High
Primary Sclerosing Cholangitis 5 98.62 Very High Very High Very High
Disseminated Intravascular Coagulation 9 98.24 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
In contrast to this attractive hypothesis of gain-of-function trypsins in hereditary pancreatitis, recent in vitro studies have challenged these assumptions and suggested that a loss of trypsin function could impair the inactivation of other (more pancreatotoxic?)
Negative_regulation (loss) of trypsin associated with pancreatitis
1) Confidence 0.57 Published 2002 Journal BMC Gastroenterol Section Body Doc Link PMC117221 Disease Relevance 0.48 Pain Relevance 0.08
The mild phenotype in these animals is probably caused by a low expression level of R122H mutated trypsinogen.
Negative_regulation (level) of trypsinogen
2) Confidence 0.50 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 0.99 Pain Relevance 0.17
However, the absence of trypsinogen in the stones from two of the 13 patients also suggests that trypsinogen is not the sole protein initiating precipitate formation.
Negative_regulation (absence) of trypsinogen
3) Confidence 0.43 Published 1994 Journal Dig. Dis. Sci. Section Abstract Doc Link 8200269 Disease Relevance 0.34 Pain Relevance 0.06
SPINK1 is a potent protease inhibitor thought to be a specific inactivation factor of intrapancreatic trypsin activity.
Negative_regulation (inactivation) of trypsin
4) Confidence 0.42 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 1.23 Pain Relevance 0.66
These in vivo results underline the hypothesis that enhanced inhibitory capacity of trypsin protects against pancreatitis.
Negative_regulation (capacity) of trypsin associated with pancreatitis
5) Confidence 0.42 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 0.78 Pain Relevance 0.03
The analysis of the recombinantly expressed G191R variant revealed a complete loss of trypsin activity due to the introduction of a novel tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis.
Negative_regulation (loss) of trypsin in cleavage
6) Confidence 0.42 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 1.06 Pain Relevance 0.70
These new insights suggest, that structural alterations, which impair the function of trypsin, could eliminate a protective mechanism rather than triggering an aggressive mechanism in initiating pancreatitis.
Negative_regulation (impair) of trypsin associated with pancreatitis
7) Confidence 0.42 Published 2002 Journal BMC Gastroenterol Section Body Doc Link PMC117221 Disease Relevance 0.49 Pain Relevance 0.07
Thus, this animal model, which gives a significant expression level of R122H mutated trypsinogen, seems to recapitulate the human disease.
Negative_regulation (level) of trypsinogen associated with disease
8) Confidence 0.42 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 1.11 Pain Relevance 0.19
Transgenic expression of SPINK1 did not hinder trypsinogen activation, but reduced trypsin activity after supramaximal stimulation with cerulein.
Neg (not) Negative_regulation (reduced) of trypsin associated with targeted disruption
9) Confidence 0.42 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 0.76 Pain Relevance 0.03
However, we hypothesize that in the case of the SPINK1 N34S high-risk haplotype, the variation in reported effect sizes may be a result of differences in the proportion of subjects with pathogenic pathways linking environmental stressors to pancreatic stellate cell (PSC) activation through recurrent trypsinogen activation and inadequate trypsin inhibition by SPINK1.
Negative_regulation (inhibition) of trypsin in stellate cell associated with primary sclerosing cholangitis
10) Confidence 0.42 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2289874 Disease Relevance 0.74 Pain Relevance 0.18
These may predispose to acute pancreatitis by eliminating one of the fail-safe mechanisms used by the pancreas to eliminate prematurely activated trypsin.
Negative_regulation (eliminate) of trypsin in pancreas associated with pancreatitis
11) Confidence 0.41 Published 1999 Journal Baillieres Best Pract Res Clin Gastroenterol Section Abstract Doc Link 11030605 Disease Relevance 0.88 Pain Relevance 0.27
In vitro analysis of recombinant wild-type and mutant enzymes revealed that catalytic activity of E79K trypsin was normal, and its inhibition by pancreatic secretory trypsin inhibitor was unaffected.
Negative_regulation (inhibitor) of trypsin
12) Confidence 0.37 Published 2004 Journal Hum. Mutat. Section Abstract Doc Link 14695529 Disease Relevance 0.69 Pain Relevance 0.07
Results from a mouse with targeted disruption of the pancreatic secretory trypsin inhibitor are puzzling [69].
Negative_regulation (disruption) of trypsin associated with targeted disruption
13) Confidence 0.37 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 0.78 Pain Relevance 0.04
Results from a mouse with targeted disruption of the pancreatic secretory trypsin inhibitor are puzzling [69].
Negative_regulation (inhibitor) of trypsin associated with targeted disruption
14) Confidence 0.37 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 0.77 Pain Relevance 0.04
Lastly, we identified two loss-of-function copy number mutations (deletions) in the SPINK1 gene, which encodes pancreatic secretory trypsin inhibitor (PSTI).
Negative_regulation (inhibitor) of trypsin
15) Confidence 0.37 Published 2008 Journal Cytogenet. Genome Res. Section Abstract Doc Link 19287144 Disease Relevance 0.61 Pain Relevance 0.31
In an actual study of 2466 patients with chronic pancreatitis (including 1857 with hereditary or idiopathic pancreatitis) and 6459 controls by Witt et al., the G191R variant of the anionic trypsinogen was over represented in controls (32 vs. 220, odds ratio 0.37; P = 1.1 × 10-8).
Negative_regulation (represented) of trypsinogen associated with pancreatitis and chronic pancreatitis
16) Confidence 0.37 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 0.98 Pain Relevance 0.66
"Loss of function" mutations in the cationic trypsinogen gene (PRSS1) may act as a protective factor against pancreatitis.
Negative_regulation (Loss) of PRSS1 associated with pancreatitis
17) Confidence 0.30 Published 2003 Journal Mol. Genet. Metab. Section Title Doc Link 12765848 Disease Relevance 0.62 Pain Relevance 0.43
These findings in genetically determined forms of chronic pancreatitis indicate that an imbalance between trypsin activity and trypsin inhibition in favour of enhanced proteolytic activity is the central pathogenetic factor in pancreatitis.
Negative_regulation (inhibition) of trypsin associated with pancreatitis and chronic pancreatitis
18) Confidence 0.20 Published 2006 Journal BMC Gastroenterol Section Body Doc Link PMC1637108 Disease Relevance 1.20 Pain Relevance 0.38
Effects of trypsin were largely reduced by low Cl(-), by basolateral bumetanide, and in the presence of barium or clotrimazole, but not by tetrodotoxin.
Negative_regulation (reduced) of trypsin associated with tetrodotoxin
19) Confidence 0.19 Published 2002 Journal Am. J. Physiol. Gastrointest. Liver Physiol. Section Abstract Doc Link 11804840 Disease Relevance 0.37 Pain Relevance 0.28
BACKGROUND: Mutations of the pancreatic serine protease inhibitor, Kazal type 1 (SPINK1), the cationic trypsinogen (PRSS1) and the cystic fibrosis transmembrane conductance regulator (CFTR) were reported to be genetic risk factors of chronic pancreatitis (CP).
Negative_regulation (inhibitor) of PRSS1 associated with fibrosis, cystic fibrosis and chronic pancreatitis
20) Confidence 0.17 Published 2002 Journal Scand. J. Gastroenterol. Section Abstract Doc Link 11916201 Disease Relevance 0.27 Pain Relevance 0.30

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