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Context Info
Confidence 0.35
First Reported 2003
Last Reported 2008
Negated 0
Speculated 2
Reported most in Body
Documents 2
Total Number 22
Disease Relevance 10.49
Pain Relevance 0.81

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

cytosol (ABR) plasma membrane (ABR)
Anatomy Link Frequency
hepatocytes 3
liver 2
ABR (Homo sapiens)
Pain Link Frequency Relevance Heat
alcohol 63 97.72 Very High Very High Very High
fibrosis 168 97.28 Very High Very High Very High
Inflammation 64 94.32 High High
headache 1 79.60 Quite High
Bile 63 72.96 Quite High
Paracetamol 84 5.00 Very Low Very Low Very Low
Potency 21 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Inflammatory Bowel Disease 27 99.76 Very High Very High Very High
End Stage Liver Disease 21 99.66 Very High Very High Very High
Targeted Disruption 294 99.32 Very High Very High Very High
Stress 378 99.00 Very High Very High Very High
Disease Progression 42 98.72 Very High Very High Very High
Disease 357 98.60 Very High Very High Very High
Alcohol Addiction 21 97.72 Very High Very High Very High
Fibrosis 63 97.28 Very High Very High Very High
Aging 42 96.96 Very High Very High Very High
Cirrhosis 168 96.72 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Similarly, proteasomes seem to interact with MDBs and inhibition of proteasomal degradation leads to formation of MDB-like structures both in vitro and in DDC-primed mice (Harada et al. 2003; Bardag-Gorce et al. 2002; Riley et al. 2002; French et al. 2001).
MDB Binding (interact) of
1) Confidence 0.35 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.09 Pain Relevance 0
To our knowledge, it is the first report of MDB associated with UC.
MDB Binding (associated) of associated with inflammatory bowel disease
2) Confidence 0.31 Published 2003 Journal Neurologia Section Abstract Doc Link 12721869 Disease Relevance 1.08 Pain Relevance 0.12
Among posttranslational modifications, MDB formation is associated with K8 hyperphosphorylation and transamidation (Zatloukal et al. 1992; Stumptner et al. 2000).
MDB Binding (formation) of
3) Confidence 0.06 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.35 Pain Relevance 0
MDB formation in mice is reversible, since MDBs disappear after recovery on standard diet for 1 month.
MDB Binding (formation) of
4) Confidence 0.06 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.57 Pain Relevance 0.14
Furthermore, p62 inhibition attenuated, whereas p62 overexpression enhanced MDB formation in DDC-primed hepatocytes (Nan et al. 2006).
MDB Binding (formation) of in hepatocytes
5) Confidence 0.06 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.08 Pain Relevance 0
The elevated K8/K18 ratio is crucial for MDB formation as shown in K18-knockout and K8 overexpressing animals, who are predisposed to MDB formation already upon short exposure to DDC and even form MDBs spontaneously during aging (Magin et al. 1998; Nakamichi et al. 2005).
MDB Binding (formation) of associated with targeted disruption and aging
6) Confidence 0.06 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.70 Pain Relevance 0
An exception is idiopathic copper toxicosis of children in which end stage liver disease associated with MDB formation occurs at very early age (Müller et al. 2004; Zatloukal et al. 2007).
MDB Binding (formation) of in liver associated with end stage liver disease
7) Confidence 0.06 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.72 Pain Relevance 0.09
However, ballooning (with concomitant cytoskeletal alterations) and MDB formation are not entirely interchangeable since not all ballooned hepatocytes contain MDBs.
MDB Binding (formation) of in hepatocytes
8) Confidence 0.05 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.57 Pain Relevance 0.06
Major factors that determine MDB formation in vivo are the type of stress (with oxidative stress as a major player), the extent of stress-induced protein misfolding and resulting chaperone, proteasome and autophagy overload, keratin 8 excess, transglutaminase activation with transamidation of keratin 8 and p62 upregulation.



MDB Binding (formation) of associated with stress
9) Confidence 0.05 Published 2008 Journal Histochem Cell Biol Section Abstract Doc Link PMC2386529 Disease Relevance 0.95 Pain Relevance 0.04
Keratins are major constituents of MDBs and both altered K8/K18 expression and keratin modification seems to affect MDB formation (Zatloukal et al. 2007; Ku et al. 2007).
MDB Binding (formation) of
10) Confidence 0.05 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.72 Pain Relevance 0
Alternatively, K8 hyperphosphorylation may induce MDB formation through inhibition of K8 degradation, which results in increased K8/K18 ratio (Ku and Omary 2000).
MDB Binding (formation) of
11) Confidence 0.05 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.13 Pain Relevance 0
The MDB-inducing conditions both in humans and mice cause elevated levels of oxidative stress (Tephly et al. 1981; Mehta et al. 2002; Dey and Cederbaum 2006; Farrell and Larter 2006) and MDBs themselves were shown to contain misfolded keratins with increased ?
MDB Binding (conditions) of associated with stress
12) Confidence 0.05 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.24 Pain Relevance 0.07
P38 kinase-induced keratin network reorganization might be a necessary prerequisite for MDB formation, since p38 kinase inhibition prevented MDB formation in vitro (Nan et al. 2006).
MDB Spec (might) Binding (formation) of
13) Confidence 0.05 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.13 Pain Relevance 0
The elevated K8/K18 ratio is crucial for MDB formation as shown in K18-knockout and K8 overexpressing animals, who are predisposed to MDB formation already upon short exposure to DDC and even form MDBs spontaneously during aging (Magin et al. 1998; Nakamichi et al. 2005).
MDB Binding (formation) of associated with targeted disruption and aging
14) Confidence 0.05 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.68 Pain Relevance 0
P38 kinase-induced keratin network reorganization might be a necessary prerequisite for MDB formation, since p38 kinase inhibition prevented MDB formation in vitro (Nan et al. 2006).
MDB Spec (might) Binding (formation) of
15) Confidence 0.05 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.14 Pain Relevance 0
Of note, supplementation of S-adenosylmethionine or mitochondrially targeted antioxidants effectively diminishes MDB formation, thereby pointing to a central role of oxidative stress in MDB generation
MDB Binding (formation) of associated with stress
16) Confidence 0.05 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.35 Pain Relevance 0
In patients, MDB formation is usually a chronic process requiring several years of alcohol intoxication or metabolic imbalance, that is, in association with the metabolic syndrome, Wilson disease, other metabolic disorders, and chronic cholestasis.
MDB Binding (formation) of associated with metabolic disorder, hepatolenticular degeneration, metabolic syndrome, gallstones and alcohol
17) Confidence 0.05 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.68 Pain Relevance 0.08
Further studies are needed to definitely characterize the molecular consequences of MDB formation.



MDB Binding (formation) of
18) Confidence 0.05 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0 Pain Relevance 0
Also in other studies, hepatocellular ballooning and MDB formation was positively correlated with disease progression, development of fibrosis, and cirrhosis and liver-related mortality (Orrego et al. 1987; Matteoni et al. 1999; Gramlich et al. 2004; Mendler et al. 2005).


MDB Binding (formation) of in liver associated with fibrosis, cirrhosis and disease progression
19) Confidence 0.05 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.88 Pain Relevance 0.14
Accordingly, K8-null or K18 overexpressing mice are resistant to MDB formation and the protective function of K18 is not affected by its phosphorylation status or mutation (Zatloukal et al. 2000; Harada et al. 2007).
MDB Binding (formation) of
20) Confidence 0.05 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2386529 Disease Relevance 0.67 Pain Relevance 0

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