INT12243

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Context Info
Confidence 0.70
First Reported 1981
Last Reported 2011
Negated 4
Speculated 0
Reported most in Body
Documents 91
Total Number 92
Disease Relevance 52.87
Pain Relevance 19.48

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 7
acinar cells 4
cleavage 3
plasma 2
stellate cells 2
PRSS1 (Homo sapiens)
Pain Link Frequency Relevance Heat
alcohol 137 99.92 Very High Very High Very High
antagonist 16 99.92 Very High Very High Very High
Chronic pancreatitis 2120 99.84 Very High Very High Very High
fibrosis 278 99.80 Very High Very High Very High
Cholecystokinin 40 99.62 Very High Very High Very High
agonist 70 98.92 Very High Very High Very High
cytokine 67 98.82 Very High Very High Very High
tolerance 19 97.60 Very High Very High Very High
Inflammation 293 97.16 Very High Very High Very High
Inflammatory response 28 94.24 High High
Disease Link Frequency Relevance Heat
Cystic Fibrosis 183 100.00 Very High Very High Very High
Exocrine Pancreatic Insufficiency 44 99.92 Very High Very High Very High
Death 28 99.92 Very High Very High Very High
Hypercalcemia 127 99.86 Very High Very High Very High
Pancreatitis 3596 99.84 Very High Very High Very High
Disease 496 99.82 Very High Very High Very High
Targeted Disruption 378 99.64 Very High Very High Very High
Viral Infection 2 99.64 Very High Very High Very High
Apoptosis 49 99.50 Very High Very High Very High
Autolysis 31 98.90 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Current opinion on the pathogenesis of hereditary pancreatitis suggests that the mutations lead to increased trypsin activity in the pancreatic tissue as a result of enhanced autoactivation of trypsinogen or decreased autocatalytic degradation (autolysis) of trypsin.
Positive_regulation (increased) of trypsin associated with autolysis and pancreatitis
1) Confidence 0.70 Published 2001 Journal Orv Hetil Section Abstract Doc Link 11324217 Disease Relevance 0.61 Pain Relevance 0.08
The N29T mutant, firstly described by Pfützer et al. in 2002, exhibited a phenotype similar to that of R122H, both increased trypsin stability and enhanced autoactivation were documented [11,64].
Positive_regulation (increased) of trypsin
2) Confidence 0.68 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 0.32 Pain Relevance 0
The Whitcomb model in its original form has remained very popular over the years, even though more detailed biochemical analysis indicated that the R122H mutation results not only in increased trypsin stability but also in increased zymogen stability and increased autoactivation [62,63].
Positive_regulation (increased) of trypsin
3) Confidence 0.68 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 0.28 Pain Relevance 0.05
In this study, the authors were not able to detect enhanced trypsin activity in the acinar cells of the SPINK -/- animals.
Positive_regulation (enhanced) of trypsin in acinar cells
4) Confidence 0.68 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 0.80 Pain Relevance 0.05
Destruction of this "failsafe mechanism" by the R122H mutation would increase intrapancreatic trypsin activity and disturb the protease-antiprotease equilibrium and eventually provoke pancreatitis [5].
Positive_regulation (increase) of trypsin associated with pancreatitis
5) Confidence 0.68 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 0.53 Pain Relevance 0.08
David Whitcomb proposed that the Arg122-Val123 autolytic peptide bond in trypsin plays an important role in the degradation of prematurely activated trypsin in the pancreas.
Positive_regulation (activated) of trypsin in pancreas
6) Confidence 0.68 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 0.58 Pain Relevance 0.14
Transgenic expression of SPINK1 did not hinder trypsinogen activation, but reduced trypsin activity after supramaximal stimulation with cerulein.
Neg (not) Positive_regulation (activation) of trypsinogen associated with targeted disruption
7) Confidence 0.68 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 0.76 Pain Relevance 0.03
Biochemical evidence supports the notion that Arg122 is important for autolysis of trypsin and mutations of this amino-acid result in increased trypsin stability [60-63].
Positive_regulation (increased) of trypsin associated with autolysis
8) Confidence 0.68 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 0.40 Pain Relevance 0.07
Interestingly, this hybrid gene had two independent gain-of-function effects: increased trypsinogen gene copy number and it contained the p.N29I pancreatitis-causing missense mutation.
Positive_regulation (increased) of trypsinogen gene associated with pancreatitis
9) Confidence 0.68 Published 2008 Journal Cytogenet. Genome Res. Section Abstract Doc Link 19287144 Disease Relevance 0.61 Pain Relevance 0.31
However, our investigations on the cleavability of the trypsinogen activation bond bond by active trypsin [3] and cathepsin B provide further evidence, that autoactivation rather than cathepsin B mediated trypsinogen activation is the key pathogenic event in the development of hereditary pancreatitis in D22G and K23R-carriers.
Positive_regulation (activation) of trypsinogen associated with pancreatitis
10) Confidence 0.68 Published 2002 Journal BMC Gastroenterol Section Body Doc Link PMC117221 Disease Relevance 0.59 Pain Relevance 0.06
This indicates a high control of cathepsin B action on trypsinogen activation by the amino acid structure of TAP and highlights the particular functional importance of the D22 residue within the tetraaspartic group D19-D20-D21-D22.
Positive_regulation (activation) of trypsinogen in D22
11) Confidence 0.68 Published 2002 Journal BMC Gastroenterol Section Body Doc Link PMC117221 Disease Relevance 0.18 Pain Relevance 0
Our data support the generally accepted hypothesis, that pancreatitis is caused by increased intrapancreatic trypsin activity.
Positive_regulation (increased) of trypsin associated with pancreatitis
12) Confidence 0.68 Published 2002 Journal BMC Gastroenterol Section Body Doc Link PMC117221 Disease Relevance 0.43 Pain Relevance 0.09
In contrast to the mutations N29I, N29T and R122H, which are located away from this cleavage site, trypsinogen mutations affecting the K23-I24 bond could potentially affect the cathepsin B action on trypsinogen activation.
Positive_regulation (activation) of trypsinogen in cleavage
13) Confidence 0.68 Published 2002 Journal BMC Gastroenterol Section Body Doc Link PMC117221 Disease Relevance 0.29 Pain Relevance 0.07
The resulting impaired cathepsin B mediated trypsinogen activation seems not be a pancreatitis promoting pathogenic step.


Positive_regulation (activation) of trypsinogen associated with pancreatitis
14) Confidence 0.68 Published 2002 Journal BMC Gastroenterol Section Body Doc Link PMC117221 Disease Relevance 0.46 Pain Relevance 0
Studies with cathepsin B deficient mice presented evidence, that the premature and intracellular activation of trypsinogen largely depends on the presence of cathepsin B [7].
Positive_regulation (activation) of trypsinogen
15) Confidence 0.68 Published 2002 Journal BMC Gastroenterol Section Body Doc Link PMC117221 Disease Relevance 0.57 Pain Relevance 0.13
The correlation was first observed in patients with hyperparathyroidism while trypsin activation, secretion stimulus and stabilization are suspected mechanisms [16].
Positive_regulation (activation) of trypsin associated with hypercalcemia
16) Confidence 0.67 Published 2003 Journal BMC Gastroenterol Section Body Doc Link PMC317302 Disease Relevance 1.30 Pain Relevance 0.66
Elevated serum calcium levels can lead to premature activation of trypsinogen inducing autodigestion of the pancreatic parenchyma [20].
Positive_regulation (activation) of trypsinogen in parenchyma
17) Confidence 0.67 Published 2003 Journal BMC Gastroenterol Section Body Doc Link PMC317302 Disease Relevance 0.97 Pain Relevance 0
Accumulation of active trypsin mutants are hypothesized to initiate a digestive enzyme activation cascade in the pancreatic acinar cells leading to autodigestion, an intense inflammatory response, and acute pancreatitis.
Positive_regulation (Accumulation) of trypsin in acinar cells associated with inflammatory response and pancreatitis
18) Confidence 0.66 Published 1999 Journal Baillieres Best Pract Res Clin Gastroenterol Section Abstract Doc Link 11030605 Disease Relevance 0.90 Pain Relevance 0.28
These may predispose to acute pancreatitis by eliminating one of the fail-safe mechanisms used by the pancreas to eliminate prematurely activated trypsin.
Positive_regulation (activated) of trypsin in pancreas associated with pancreatitis
19) Confidence 0.66 Published 1999 Journal Baillieres Best Pract Res Clin Gastroenterol Section Abstract Doc Link 11030605 Disease Relevance 0.88 Pain Relevance 0.27
The Whitcomb model in its original form has remained very popular over the years, even though more detailed biochemical analysis indicated that the R122H mutation results not only in increased trypsin stability but also in increased zymogen stability and increased autoactivation [62,63].
Positive_regulation (increased) of zymogen
20) Confidence 0.60 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC1774562 Disease Relevance 0.27 Pain Relevance 0.05

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