INT234954

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Context Info
Confidence 0.42
First Reported 2008
Last Reported 2009
Negated 0
Speculated 0
Reported most in Body
Documents 22
Total Number 22
Disease Relevance 19.50
Pain Relevance 0.62

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

cytosol (DSG1) plasma membrane (DSG1)
Anatomy Link Frequency
epidermis 4
keratinocyte 3
B cells 1
cleavage 1
DSG1 (Homo sapiens)
Pain Link Frequency Relevance Heat
Chronic pancreatitis 60 97.76 Very High Very High Very High
Kinase C 221 72.88 Quite High
metalloproteinase 102 5.00 Very Low Very Low Very Low
agonist 85 5.00 Very Low Very Low Very Low
corticosteroid 38 5.00 Very Low Very Low Very Low
addiction 34 5.00 Very Low Very Low Very Low
Inflammatory mediators 17 5.00 Very Low Very Low Very Low
antagonist 17 5.00 Very Low Very Low Very Low
Pain 17 5.00 Very Low Very Low Very Low
imagery 17 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Adhesions 915 100.00 Very High Very High Very High
Bullous Skin Disease 5170 99.82 Very High Very High Very High
Pancreatic Cancer 152 99.48 Very High Very High Very High
Adenocarcinoma 56 99.40 Very High Very High Very High
Alopecia 34 98.72 Very High Very High Very High
Pemphigoid 61 98.60 Very High Very High Very High
Acantholysis 1105 98.44 Very High Very High Very High
Disease 333 97.84 Very High Very High Very High
Pancreatitis 68 97.76 Very High Very High Very High
Heart Defects 68 95.92 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The pancreatic cancer samples, however, showed an almost complete loss of cells displaying intense (3+) Dsg1 staining and a marked decrease in cells with 2+ intensity with a concomitant increase in cells with weak (1+) or absent (0+) Dsg1 staining.
Negative_regulation (decrease) of Dsg1 associated with pancreatic cancer
1) Confidence 0.42 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2628383 Disease Relevance 0.77 Pain Relevance 0.23
In this report we have shown that the levels of cell-surface resident Dsg1 and Dsg2 are reduced in pancreatic adenocarcinomas compared with normal and chronic pancreatitis tissues.
Negative_regulation (reduced) of Dsg1 associated with adenocarcinoma and chronic pancreatitis
2) Confidence 0.42 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2628383 Disease Relevance 0.51 Pain Relevance 0.10
The levels of immunoreactive Dsg1 and Dsg2 were reduced in pancreatic adenocarcinomas compared with both normal pancreatic and chronic pancreatitis tissues.
Negative_regulation (reduced) of Dsg1 associated with adenocarcinoma and chronic pancreatitis
3) Confidence 0.42 Published 2008 Journal BMC Cancer Section Abstract Doc Link PMC2628383 Disease Relevance 0.67 Pain Relevance 0.10
A reduction in the amount of the cell adhesion components Dsg1 and Dsg2 in pancreatic tumors suggests that loss of these desmosomal proteins may play a role in pancreatic cancer invasion.
Negative_regulation (reduction) of Dsg1 associated with pancreatic cancer and adhesions
4) Confidence 0.42 Published 2008 Journal BMC Cancer Section Abstract Doc Link PMC2628383 Disease Relevance 0.79 Pain Relevance 0.09
Some evidence exists that depletion of Dsg 1 may also occur in pemphigus.
Negative_regulation (depletion) of Dsg associated with bullous skin disease
5) Confidence 0.29 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.64 Pain Relevance 0
Similarly, depletion of Dsg 3 has been convincingly shown in PV whereas depletion of Dsg 1 in both PV and PF is less clear (Yamamoto et al. 2007a).
Negative_regulation (depletion) of Dsg associated with bullous skin disease
6) Confidence 0.29 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 2.26 Pain Relevance 0.11
Recently, it has been shown that PV- and PF-IgG-induced epidermal splitting, keratinocyte dissociation, as well as loss of Dsg 1 and Dsg 3 binding in vitro were accompanied by p38MAPK-dependent inactivation of Rho A and that specific activation of Rho A by the bacterial toxin cytotoxic necrotizing factor y (CNFy) abolished these effects (Spindler et al. 2007; Waschke et al. 2006).
Negative_regulation (loss) of Dsg in keratinocyte associated with bullous skin disease
7) Confidence 0.29 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.75 Pain Relevance 0
According to this concept, in the deep epidermis which contains both Dsg 1 and Dsg 3, Dsg 3 compensates for the functional loss of Dsg 1 induced by Dsg 1-specific autoantibodies, resulting in more superficial blistering in PF (Fig. 9).
Negative_regulation (loss) of Dsg in epidermis associated with bullous skin disease
8) Confidence 0.29 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.75 Pain Relevance 0
On the other hand, mutations in Dsg 1 and plakophilin 1, which are primarily expressed in the epidermis, cause skin defects whereas loss of Dsg 4 in hair follicles results in hair loss.
Negative_regulation (loss) of Dsg in skin associated with alopecia
9) Confidence 0.29 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 1.14 Pain Relevance 0
Similar in keratinocyte cultures, depletion of Dsg 1-specific antibodies from PF-IgG by preincubation with recombinant Dsg 1 but not after preincubation with VE-cadherin completely abolished keratinocyte dissociation (Waschke et al. 2005).
Negative_regulation (depletion) of Dsg in keratinocyte associated with bullous skin disease
10) Confidence 0.21 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.62 Pain Relevance 0
The discrepancy between these conflicting findings may be explained in part by the notion that the desmoglein compensation hypothesis is based on the following two assumptions: (1) the expression pattern of Dsg 3 and Dsg 1 do not substantially overlap in epidermal and mucosal layers where the cleavage plane in PV and PF is located. (2) Dsg 1- and Dsg 3-specific autoantibodies only lead to inactivation of either Dsg 1 or Dsg 3, respectively.
Negative_regulation (inactivation) of Dsg in cleavage associated with bullous skin disease
11) Confidence 0.21 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.73 Pain Relevance 0
With respect to the second assumption the desmoglein compensation is based on, i.e. selective inactivation of Dsg 1 but not of Dsg 3 by Dsg 1-specific antibodies, it was shown recently that both PF-IgG (only containing Dsg 1-specific antibodies) and PV-IgG from patients with only Dsg 3-specific antibodies were equally effective to reduce binding of Dsg 1- and Dsg 3-coated beads to the surface of cultured keratinocytes (Heupel et al. 2007; Spindler et al. 2007).
Negative_regulation (inactivation) of Dsg in keratinocytes associated with bullous skin disease
12) Confidence 0.21 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.59 Pain Relevance 0
Taken together, it is unclear at present to which extent Dsg depletion from desmosomes causes antibody-mediated acantholysis.
Negative_regulation (depletion) of Dsg associated with acantholysis
13) Confidence 0.21 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.88 Pain Relevance 0
In PV, epidermal involvement would occur only when autoantibodies against both Dsg 1 and Dsg 3 are present because Dsg 1 is found in all epidermal layers and could compensate for loss of Dsg 3 binding when antibodies to Dsg 3 are solely presentFig. 10Immunostaining of Dsg 1 and Dsg 3 in PV lesional epidermis.
Negative_regulation (10Immunostaining) of Dsg in epidermis associated with bullous skin disease
14) Confidence 0.21 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 1.00 Pain Relevance 0
According to this model, blistering in PF affects the superficial epidermis because Dsg 3 is present in the deep epidermis to compensate for the autoantibody-induced loss of Dsg 1 binding.
Negative_regulation (loss) of Dsg in epidermis associated with bullous skin disease
15) Confidence 0.21 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 1.11 Pain Relevance 0
After 24 h, Dsg 3 but not Dsg 2, plakoglobin or desmoplakin was also depleted from the cytoskeletal fractions leading to reduced total cellular Dsg 3 levels (Calkins et al. 2006; Yamamoto et al. 2007a).
Negative_regulation (depleted) of Dsg
16) Confidence 0.21 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.25 Pain Relevance 0
Because of the latter, the desmoglein compensation hypothesis has been used to promote the idea that autoantibodies reduce Dsg binding by direct inhibition rather than by unspecific proteolysis (Mahoney et al. 1999).
Negative_regulation (reduce) of Dsg
17) Confidence 0.21 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.65 Pain Relevance 0
However, because PF-IgG were shown to induce cellular signalling events but not to directly reduce Dsg 1 binding, it seems that direct inhibition of Dsg transinteraction is not essential to alter Dsg-mediated signalling (Heupel et al. 2007; Waschke et al. 2005).
Negative_regulation (reduce) of Dsg associated with bullous skin disease
18) Confidence 0.21 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 1.11 Pain Relevance 0
At present, compelling evidence indicates that acantholysis in PV and in PF is initiated by cellular signalling pathways rather than by direct inhibition of Dsg binding (Fig. 11).
Negative_regulation (inhibition) of Dsg associated with acantholysis and bullous skin disease
19) Confidence 0.21 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 1.42 Pain Relevance 0
It is possible that antibody-mediated direct inhibition of Dsg binding may contribute to trigger cellular signalling events (Muller et al. 2008a; Sharma et al. 2007; Tsunoda et al. 2003).
Negative_regulation (inhibition) of Dsg
20) Confidence 0.21 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 1.20 Pain Relevance 0

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