INT254400

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Context Info
Confidence 0.57
First Reported 2008
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 22
Total Number 23
Disease Relevance 18.15
Pain Relevance 5.89

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

cytosol (GSN) extracellular space (GSN) vesicle-mediated transport (GSN)
aging (GSN) extracellular region (GSN) protein complex (GSN)
Anatomy Link Frequency
plasma 4
blood 4
joints 2
respiratory 2
liver 1
GSN (Homo sapiens)
Pain Link Frequency Relevance Heat
rheumatoid arthritis 484 99.84 Very High Very High Very High
Inflammation 382 99.54 Very High Very High Very High
Multiple sclerosis 554 98.72 Very High Very High Very High
intrathecal 8 95.32 Very High Very High Very High
Inflammatory mediators 38 90.60 High High
cytokine 17 85.92 High High
ischemia 1 83.84 Quite High
Arthritis 12 58.32 Quite High
Abeta 8 50.64 Quite High
cINOD 14 50.40 Quite High
Disease Link Frequency Relevance Heat
Rheumatoid Arthritis 486 99.84 Very High Very High Very High
INFLAMMATION 408 99.54 Very High Very High Very High
Injury 164 99.44 Very High Very High Very High
Arthritis 36 99.36 Very High Very High Very High
Disease 204 99.16 Very High Very High Very High
Demyelinating Disease 484 98.72 Very High Very High Very High
Familial Dysautonomia 242 97.36 Very High Very High Very High
Adult Respiratory Distress Syndrome 40 96.12 Very High Very High Very High
Sepsis 54 95.48 Very High Very High Very High
Burns 24 94.48 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Such mobilization would account for the decrease of gelsolin in blood, assuming that normal blood levels cannot be maintained by increasing production, which in the case of gelsolin occurs in muscle and neurons, but not liver.
Negative_regulation (decrease) of gelsolin in muscle
1) Confidence 0.57 Published 2010 Journal BMC Neurol Section Body Doc Link PMC2989318 Disease Relevance 0.67 Pain Relevance 0.38
Similar to what was previously reported, our study revealed the downregulation of gelsolin (GSN), a protein involved in cell motility, that causes defects in cytoskeleton reorganization and cell migration in FD [10], [11], [22], [34].
Negative_regulation (downregulation) of gelsolin associated with familial dysautonomia
2) Confidence 0.49 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.39 Pain Relevance 0
Similar to what was previously reported, our study revealed the downregulation of gelsolin (GSN), a protein involved in cell motility, that causes defects in cytoskeleton reorganization and cell migration in FD [10], [11], [22], [34].
Negative_regulation (downregulation) of GSN associated with familial dysautonomia
3) Confidence 0.49 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.39 Pain Relevance 0
On the other hand, we observed a decrease of GSN in blood and CSF, which agrees with a study showing that a decrease of blood gelsolin level is inversely related to the intensity of systemic inflammation in patients with rheumatoid arthritis (RA) [7].
Negative_regulation (decrease) of GSN in blood associated with inflammation and rheumatoid arthritis
4) Confidence 0.42 Published 2010 Journal BMC Neurol Section Body Doc Link PMC2989318 Disease Relevance 1.01 Pain Relevance 0.43
The QAlb values indicate lack of CSF-barrier dysfunction in MS subjects included in our study, and it is very likely that the depletion of GSN and DBP from CSF that occurs as these proteins bind actin cannot be compensated for by an increased production or transport of gelsolin.
Negative_regulation (depletion) of GSN associated with multiple sclerosis
5) Confidence 0.42 Published 2010 Journal BMC Neurol Section Body Doc Link PMC2989318 Disease Relevance 0.49 Pain Relevance 0.24
Similar to gelsolin depletion, low DBP levels (both the total level and the actin-free level, which is an index of residual actin-scavenging capacity), was proposed to serve as a prognostic marker in situations of organ damage such as acute liver failure, and multiple trauma [18].
Negative_regulation (depletion) of gelsolin in liver associated with acute liver failure and multiple trauma
6) Confidence 0.42 Published 2010 Journal BMC Neurol Section Body Doc Link PMC2989318 Disease Relevance 1.05 Pain Relevance 0.06
The direction of gelsolin and DBP concentration changes in CSF (average values calculated based on 40 MS patients included in each group) suggests the possibility that depletion of CSF gelsolin levels might be compensated for by an increase in DBP concentration (Figure 2), but this statement is not supported by r (r = 0.4242) and p (p < 0.005) values calculated using Pearson's correlation test (it included 24 subjects in which GSN and DBP was analyzed in the same samples) indicating occurrence of positive correlation between those values in the same patients, potentially meaning that in subjects with higher CSF gelsolin concentration, higher DBP concentration is more likely to be observed (Figure 3).


Negative_regulation (depletion) of gelsolin associated with multiple sclerosis
7) Confidence 0.42 Published 2010 Journal BMC Neurol Section Body Doc Link PMC2989318 Disease Relevance 0.44 Pain Relevance 0.22
On the other hand, we observed a decrease of GSN in blood and CSF, which agrees with a study showing that a decrease of blood gelsolin level is inversely related to the intensity of systemic inflammation in patients with rheumatoid arthritis (RA) [7].
Negative_regulation (decrease) of gelsolin in blood associated with inflammation and rheumatoid arthritis
8) Confidence 0.42 Published 2010 Journal BMC Neurol Section Body Doc Link PMC2989318 Disease Relevance 1.10 Pain Relevance 0.47
As plasma gelsolin has the ability to bind actin, blood gelsolin depletion was observed in diverse states of inflammation associated with tissue injury and actin release: adult respiratory distress syndrome, sepsis, myocardial infarction, hepatitis, myonecrosis and rheumatoid arthritis [4-7].
Negative_regulation (depletion) of gelsolin in respiratory associated with rheumatoid arthritis, adult respiratory distress syndrome, sepsis, inflammation, injury, anaerobic bacterial infections, myocardial infarction and hepatitis
9) Confidence 0.42 Published 2010 Journal BMC Neurol Section Body Doc Link PMC2989318 Disease Relevance 0.99 Pain Relevance 0.14
Catastrophic or prolonged pGSN depletion, however, hypothetically accommodates dysfunctional and destructive actions of the mediators, leading to secondary organ damage and even death.
Negative_regulation (depletion) of pGSN associated with death
10) Confidence 0.36 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2592804 Disease Relevance 1.08 Pain Relevance 0.30
We have documented a decrease in levels of circulating pGSN in RA, the first example of such depletion during chronic inflammation. pGSN levels are even lower intra-articularly in affected joints.
Negative_regulation (decrease) of pGSN in joints associated with inflammation and rheumatoid arthritis
11) Confidence 0.36 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2592804 Disease Relevance 0.40 Pain Relevance 0.20
The finding that circulating pGSN levels decrease during chronic joint inflammation is consistent with observations of acute inflammatory disease states, such as sepsis and acute respiratory distress syndrome, in which a drop in pGSN concentration precedes more severe injuries [5-14] and the beneficial action of pGSN during re-administration in traumatized animals suggests that it has a protective role in inflammation [12,14,20].
Negative_regulation (decrease) of pGSN in respiratory associated with inflammation, injury, adult respiratory distress syndrome, disease, sepsis and arthritis
12) Confidence 0.36 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2592804 Disease Relevance 1.32 Pain Relevance 0.47
Our findings suggest that the reason for the decreased pGSN levels is local exposure of actin to the extracellular environment in these joints.


Negative_regulation (decreased) of pGSN in joints
13) Confidence 0.36 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2592804 Disease Relevance 1.03 Pain Relevance 0.43
Levels of plasma gelsolin decrease during acute injury and inflammation, and administration of recombinant plasma gelsolin to animals improves outcomes following sepsis or burn injuries.
Negative_regulation (decrease) of plasma gelsolin in plasma associated with inflammation, burns, injury and sepsis
14) Confidence 0.36 Published 2008 Journal Arthritis Res Ther Section Abstract Doc Link PMC2592804 Disease Relevance 0.87 Pain Relevance 0.20
MMP-induced pGSN cleavage would most likely be interpreted as a decrease in pGSN concentration in our functional assay since the nucleating activity of pGSN cut in half is weaker than for the full-length protein [47-49].
Negative_regulation (decrease) of pGSN in cleavage
15) Confidence 0.36 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2592804 Disease Relevance 0.43 Pain Relevance 0.22
We report here that pGSN levels are diminished in the blood of RA patients and that analysis of synovial fluids (SFs) suggests that pGSN is consumed in the inflamed joint.
Negative_regulation (diminished) of pGSN in blood associated with rheumatoid arthritis
16) Confidence 0.36 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2592804 Disease Relevance 1.13 Pain Relevance 0.39
Circulating pGSN levels were significantly diminished in patients with RA compared with those of matched healthy controls (141 ± 32 versus 196 ± 40 mg/L, P = 0.0002) (Figure 1a).
Negative_regulation (diminished) of pGSN associated with rheumatoid arthritis
17) Confidence 0.36 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2592804 Disease Relevance 0.55 Pain Relevance 0.24
Decreased levels of the gelsolin plasma isoform in patients with rheumatoid arthritis

Introduction

Negative_regulation (Decreased) of gelsolin in plasma associated with rheumatoid arthritis
18) Confidence 0.36 Published 2008 Journal Arthritis Res Ther Section Title Doc Link PMC2592804 Disease Relevance 0.78 Pain Relevance 0.19
These findings suggest that pGSN is a broad-spectrum anti-inflammatory buffer and that local pGSN depletion by a shift of binding toward actin during actin exposure following injury allows mediators to promote appropriate defense and repair functions.
Negative_regulation (depletion) of pGSN associated with inflammation and injury
19) Confidence 0.36 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2592804 Disease Relevance 0.99 Pain Relevance 0.26
This is the first study to show that pGSN levels are reduced in plasma of patients with RA.
Negative_regulation (reduced) of pGSN in plasma associated with rheumatoid arthritis
20) Confidence 0.36 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2592804 Disease Relevance 0.96 Pain Relevance 0.36

General Comments

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