INT227519

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Context Info
Confidence 0.55
First Reported 2008
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 22
Total Number 22
Disease Relevance 16.38
Pain Relevance 3.83

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

unfolded protein binding (Hspa9) protein folding (Hspa9) mitochondrion (Hspa9)
enzyme binding (Hspa9) response to stress (Hspa9) cytoplasm (Hspa9)
Anatomy Link Frequency
muscle 3
muscle fibers 1
limb 1
Hspa9 (Mus musculus)
Pain Link Frequency Relevance Heat
Inflammatory stimuli 51 99.90 Very High Very High Very High
headache 1 99.56 Very High Very High Very High
cytokine 51 99.16 Very High Very High Very High
Inflammation 619 99.12 Very High Very High Very High
Opioid 1 97.56 Very High Very High Very High
antinociception 2 96.52 Very High Very High Very High
Pain 43 87.76 High High
Fibrositis 1 86.20 High High
Arthritis 10 83.36 Quite High
Osteoarthritis 60 80.64 Quite High
Disease Link Frequency Relevance Heat
Disease 123 99.88 Very High Very High Very High
Myositis 714 99.84 Very High Very High Very High
Organ Transplantation 1 99.80 Very High Very High Very High
INFLAMMATION 516 99.74 Very High Very High Very High
Headache 1 99.56 Very High Very High Very High
Stress 479 99.16 Very High Very High Very High
Muscle Disease 17 98.88 Very High Very High Very High
Disorder Of Lipid Metabolism 1 97.88 Very High Very High Very High
Recurrence 6 97.84 Very High Very High Very High
Muscular Atrophy 12 97.56 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Indeed, experimental animal investigations indicated that mechanisms other than MHC-I overexpression are responsible for the upregulation of Grp75, such as a systemic cytokine release.
Positive_regulation (upregulation) of Grp75 associated with cytokine
1) Confidence 0.55 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2888201 Disease Relevance 0.89 Pain Relevance 0.12
Conversely, Grp75 levels increased in nonregenerating, adult, myofibers of myositis patients who were positive for sarcolemmal MHC-I immunoreactivity (Groups I and II), but also involving MHC-I-negative myofibers.
Positive_regulation (increased) of Grp75 associated with myositis
2) Confidence 0.55 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2888201 Disease Relevance 0.93 Pain Relevance 0.11
Grp75 is, at the same time, upregulated by and protective against oxidative stress [9,18].
Positive_regulation (upregulated) of Grp75 associated with stress
3) Confidence 0.55 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2888201 Disease Relevance 0.88 Pain Relevance 0.16
Inflammatory stimuli and Grp75 upregulation in myositis patients
Positive_regulation (upregulation) of Grp75 associated with myositis and inflammatory stimuli
4) Confidence 0.55 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2888201 Disease Relevance 0.81 Pain Relevance 0.05
It would therefore appear that preoperative increases in QFM CSA due to both exercise and NMES prehabilitation may attenuate muscle atrophy following TKA.
Positive_regulation (increases) of CSA in muscle associated with muscular atrophy
5) Confidence 0.44 Published 2010 Journal BMC Musculoskelet Disord Section Body Doc Link PMC2896350 Disease Relevance 0.84 Pain Relevance 0.39
Preoperatively, there was a trend towards an increase in QFM CSA of the involved limb in the NMES group (7.4%, p = 0.036; alpha level = 0.017) (Figure 2).
Positive_regulation (increase) of CSA in limb
6) Confidence 0.44 Published 2010 Journal BMC Musculoskelet Disord Section Body Doc Link PMC2896350 Disease Relevance 0 Pain Relevance 0
Interestingly, a single LPS injection increased significantly Grp75 protein levels in skeletal muscle fibers, in the absence of both Grp94 [24] and MHC-I upregulation (present manuscript), proving that systemic inflammatory stimuli do raise the expression of this antioxidant stress-protein in muscle fibers.
Positive_regulation (increased) of Grp75 protein in muscle fibers associated with stress and inflammatory stimuli
7) Confidence 0.40 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2888201 Disease Relevance 0.92 Pain Relevance 0.25
Although the contribution of autoantibodies in myositis remains obscure [44-46], seven out of 10 patients of the MHC-I grade + subgroup, who showed strongly increased immunoreactivity for Grp75, were positive for myositis-specific or associated autoantibodies.
Positive_regulation (increased) of Grp75 associated with myositis
8) Confidence 0.40 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2888201 Disease Relevance 1.00 Pain Relevance 0.18
In addition to being upregulated by oxidative stress and involved in the antioxidant defense, increased Grp75 levels might participate in and enhance myofiber protection against complement-mediated lysis [10,43].
Positive_regulation (increased) of Grp75 associated with stress
9) Confidence 0.40 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2888201 Disease Relevance 1.15 Pain Relevance 0.25
The relative amount of Grp75 significantly increased twofold in Group I patients, compared with Group 0 and Group III levels (Figure 3b; P = 0.01, ANOVA).
Positive_regulation (increased) of Grp75
10) Confidence 0.37 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2888201 Disease Relevance 0.08 Pain Relevance 0
A significant increase of Grp75 and calreticulin protein levels (P = 0.007 and P = 0.004, respectively) was observed in murine tibialis anterior muscles excised 48 hours after LPS administration, compared with muscles of untreated animals (Figure 5a, b).
Positive_regulation (increase) of Grp75 in muscles
11) Confidence 0.37 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2888201 Disease Relevance 0.31 Pain Relevance 0.11
Figure 3c shows that biopsies from patients with a sarcolemmal MHC-I expression detectable only in a proportion of myofibers (grade +; n = 10) displayed significantly increased Grp75 levels compared with values detected in Group 0 and Group III subjects (P = 0.002, ANOVA), similarly to those detected in biopsies with ubiquitous distribution of sarcolemmal MHC-I immunoreactivity (grade ++).


Positive_regulation (increased) of Grp75
12) Confidence 0.37 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2888201 Disease Relevance 0 Pain Relevance 0
The present study was undertaken to characterize in more detail the ER stress-response occurring in myofibers of patients with inflammatory myopathies, focusing on the expression and distribution of Grp94, calreticulin and Grp75, three ER chaperones involved in immunomodulation.


Positive_regulation (distribution) of Grp75 associated with stress and inflammation
13) Confidence 0.37 Published 2010 Journal Arthritis Res Ther Section Abstract Doc Link PMC2888201 Disease Relevance 0.83 Pain Relevance 0.16
Grp75 is an Hsp70 analog, mostly localized within ER and mitochondria [9]; in the present study, however, the increase in Grp75 immunoreactivity involved glycolytic fibers too, and its expression could therefore not be simply related to fiber mitochondrial content.
Positive_regulation (increase) of Grp75
14) Confidence 0.37 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2888201 Disease Relevance 0.91 Pain Relevance 0.14
Whereas one pattern of ER stress-response occurs independently from the pathogenesis of the disease, the increase in Grp75 levels might represent a myositis-specific feature - especially for those patients classified following Bohan and Peter's criteria and showing occasional immunoreactivity for sarcolemmal MHC-I.


Positive_regulation (increase) of Grp75 associated with stress, disease and myositis
15) Confidence 0.37 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2888201 Disease Relevance 0.82 Pain Relevance 0.08
Conversely, levels of calreticulin and Grp75 increased about fourfold and twofold, respectively, in patient biopsies positive for sarcolemmal MHC-I immunoreactivity, compared with healthy subjects and patients negative for both inflammation and MHC-I labeling (P < 0.005).
Positive_regulation (increased) of Grp75 associated with inflammation
16) Confidence 0.37 Published 2010 Journal Arthritis Res Ther Section Abstract Doc Link PMC2888201 Disease Relevance 0.81 Pain Relevance 0.19
Differently from calreticulin, the Grp75 level increased significantly also in patient biopsies that displayed occasional sarcolemmal MHC-I immunoreactivity (P = 0.002), suggesting the interference of other mechanisms.
Positive_regulation (increased) of Grp75
17) Confidence 0.37 Published 2010 Journal Arthritis Res Ther Section Abstract Doc Link PMC2888201 Disease Relevance 0.86 Pain Relevance 0.22
At variance with Grp94, Grp75 protein levels increased significantly in myositis biopsies with negligible levels of regeneration, and especially in those displaying a restricted sarcolemmal MHC-I immunoreactivity to a few clusters of myofibers [40].
Positive_regulation (increased) of Grp75 protein associated with myositis
18) Confidence 0.37 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2888201 Disease Relevance 0.79 Pain Relevance 0.05
The increase in the muscle Grp75 level in patients showing occasional immunoreactivity for sarcolemmal MHC-I might be considered further as a broader indicator of idiopathic inflammatory myopathy.



Positive_regulation (increase) of Grp75 in muscle associated with inflammation and myositis
19) Confidence 0.32 Published 2010 Journal Arthritis Res Ther Section Abstract Doc Link PMC2888201 Disease Relevance 0.79 Pain Relevance 0.20
The beneficial training effect of NMES is further supported by the observed trend towards an increase in preoperative QFM CSA (7.4%).
Positive_regulation (increase) of CSA
20) Confidence 0.29 Published 2010 Journal BMC Musculoskelet Disord Section Body Doc Link PMC2896350 Disease Relevance 0.13 Pain Relevance 0.06

General Comments

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