INT239827

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Context Info
Confidence 0.33
First Reported 2008
Last Reported 2010
Negated 2
Speculated 0
Reported most in Body
Documents 13
Total Number 17
Disease Relevance 9.07
Pain Relevance 0.73

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

Anatomy Link Frequency
neuronal 1
immune system 1
HSR (Homo sapiens)
Pain Link Frequency Relevance Heat
Spinal cord 144 99.30 Very High Very High Very High
Multiple sclerosis 12 83.92 Quite High
ischemia 12 77.20 Quite High
Glutamate 24 66.72 Quite High
cINOD 12 65.48 Quite High
Bioavailability 22 63.92 Quite High
abdominal pain 5 34.88 Quite Low
methadone 25 5.00 Very Low Very Low Very Low
Immobilon 24 5.00 Very Low Very Low Very Low
alcohol 20 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Shock 804 100.00 Very High Very High Very High
Fever 20 99.52 Very High Very High Very High
Thrombosis 5 99.42 Very High Very High Very High
Stress 216 99.12 Very High Very High Very High
Hypersensitivity 80 98.88 Very High Very High Very High
Anaphylaxis 5 97.94 Very High Very High Very High
Disease 56 97.88 Very High Very High Very High
Injury 29 94.80 High High
Death 65 94.36 High High
Acquired Immune Deficiency Syndrome Or Hiv Infection 320 87.92 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Altered or unusual drug metabolism and a susceptible immune system are believed to be important cofactors for the development of drug-related hypersensitivity.24 HIV-infected persons are likely to be at special risk of developing hypersensitivity reactions because of the disease associated perturbations in the immune system.25 Two members of a family who were treated with ABC both developed the HSR suggesting a genetic component to ABC HSR.26 Multiple studies have shown an association of the ABC HSR with HLA-B*5701.27–29 The use of this screening test to identify high risk patients has been shown by Rauch et al to reduce the occurrence of the ABC HSR.30 In this cohort involving more than 260 patients, the authors observed that the use of HLA-B*5701 screening decreased ABC HSR from 7% to <1%.
Positive_regulation (decreased) of HSR in immune system associated with acquired immune deficiency syndrome or hiv infection, hypersensitivity and disease
1) Confidence 0.33 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2835563 Disease Relevance 0.79 Pain Relevance 0
In an analysis of 5,332 patients enrolled in ABC clinical trials, being ART-experienced at the start of ABC therapy and being of African descent were associated with a nearly 40% reduction in the risk of hypersensitivity.19 Patients of white race were found to be at significantly greater risk in another study of a population with a low percentage of ethnic minorities.14 Accumulated data suggest that factors that predict a lower likelihood to develop ABC HSR are: male sex, African racial origin, more advanced disease, and being an antiretroviral-experienced patient before initiation of ABC.12,14
Positive_regulation (develop) of HSR associated with hypersensitivity and disease
2) Confidence 0.33 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2835563 Disease Relevance 0.45 Pain Relevance 0
Among 112 patients with ABC HSR who were rechallenged, an anaphylactic or immediate type of hypersensitivity reaction occurred in 20%.15 Therefore, patients with clinically suspected ABC HSR should not be rechallenged.
Positive_regulation (suspected) of HSR associated with anaphylaxis and hypersensitivity
3) Confidence 0.33 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2835563 Disease Relevance 0.80 Pain Relevance 0
Disseminated intravascular coagulation has also been reported as a manifestation of ABC HSR.20
Positive_regulation (manifestation) of HSR associated with thrombosis
4) Confidence 0.29 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2835563 Disease Relevance 1.30 Pain Relevance 0
There have been case reports of patients who developed the ABC HSR after re-initiation of ABC after a hiatus in taking the medication, but this occurrence is believed to be rare.16 Interestingly, these patients had no symptoms of HSR during the first period of ABC administration.
Neg (no) Positive_regulation (symptoms) of HSR
5) Confidence 0.29 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2835563 Disease Relevance 0.76 Pain Relevance 0
Induction of the heat shock response (HSR) and increased expression of the heat shock proteins (HSPs) provide mechanisms to ensure proper protein folding, trafficking, and disposition.
Positive_regulation (Induction) of HSR associated with shock
6) Confidence 0.20 Published 2008 Journal PLoS ONE Section Abstract Doc Link PMC2481402 Disease Relevance 0.40 Pain Relevance 0
Their mechanisms of action likely involve the blockage of bulk protein degradation, leading to the buildup of abnormal, mis-folded proteins and consequently activation of the HSR.
Positive_regulation (activation) of HSR
7) Confidence 0.20 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2481402 Disease Relevance 0.06 Pain Relevance 0
In this context, our observation that riluzole increased HSF1 reserve to allow for a more robust mobilization of HSF1 and induction of the HSR would suggest that riluzole and conditioning heat shock could have synergistic effect in protecting cells against stress-induced injury and death.
Positive_regulation (induction) of HSR associated with stress, injury, shock and death
8) Confidence 0.14 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2481402 Disease Relevance 1.15 Pain Relevance 0
In Fig. 5B, we show that riluzole and conditioning heat shock increased cell survival under conditions of arsenite-induced oxidative stress, an effect that can be correlated with the enhanced HSR shown in Fig. 5A.
Positive_regulation (enhanced) of HSR associated with stress and shock
9) Confidence 0.14 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2481402 Disease Relevance 0.69 Pain Relevance 0.11
A major obstacle in harnessing such cytoprotective activity for therapeutic purposes is that agents/conditions that induce the HSR are proteotoxic, and the induction of HSPs under such conditions represents a compensatory mechanism to rectify the perturbation of protein homeostasis.
Positive_regulation (induce) of HSR
10) Confidence 0.13 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2481402 Disease Relevance 0.07 Pain Relevance 0
In particular, we are interested in candidates that are not proteotoxic and would not by themselves trigger the full HSR but nonetheless would enhance the effect of HSR elicitor.
Neg (not) Positive_regulation (trigger) of HSR
11) Confidence 0.13 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2481402 Disease Relevance 0.59 Pain Relevance 0.15
It is well known that the accumulation of abnormal proteins in cells, either due to genetic mutation or by the artificial introduction of denatured proteins, will trigger the HSR [45], [46].
Positive_regulation (trigger) of HSR
12) Confidence 0.13 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2481402 Disease Relevance 0.08 Pain Relevance 0
Induction of the HSR provides a ubiquitous and important cytoprotective mechanism.
Positive_regulation (Induction) of HSR
13) Confidence 0.13 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2481402 Disease Relevance 0.08 Pain Relevance 0
These considerations suggest that agents that upregulate the HSR and HSP chaperones may hold promise in therapeutics development for the prevention, management, and treatment of neurodegeneration [3], [4], [5], [6].
Positive_regulation (upregulate) of HSR
14) Confidence 0.13 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2481402 Disease Relevance 0.41 Pain Relevance 0.03
We believe that riluzole may be a prototype of drugs that can amplify the HSR for cytoprotection, and we will continue to use our cell-based reporter gene assay to screen for and identify such compounds.
Positive_regulation (amplify) of HSR
15) Confidence 0.13 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2481402 Disease Relevance 0.44 Pain Relevance 0.10
This observation is consistent with result of previous studies: spinal cord neurons have a high threshold for induction of the HSR both in terms of the severity of stress and the magnitude of induction [23], [24], [31], and induction of the HSR is inversely proportional to the “differentiation” state of neuronal cells [23], [24].
Positive_regulation (induction) of HSR in neuronal associated with stress and spinal cord
16) Confidence 0.13 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2481402 Disease Relevance 0.93 Pain Relevance 0.30
We show here that the FDA-approved ALS drug riluzole slows the turnover of HSF1 to effect a more robust HSR for cytoprotection.
Positive_regulation (effect) of HSR
17) Confidence 0.13 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2481402 Disease Relevance 0.05 Pain Relevance 0.04

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