INT122896

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Context Info
Confidence 0.57
First Reported 2004
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 23
Total Number 28
Disease Relevance 9.27
Pain Relevance 6.88

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

pigmentation (TH) cytosol (TH) mitochondrion (TH)
small molecule metabolic process (TH) nucleus (TH) cellular nitrogen compound metabolic process (TH)
Anatomy Link Frequency
striatum 5
muscle 2
brain 1
mere 1
neurites 1
TH (Homo sapiens)
Pain Link Frequency Relevance Heat
Dopamine 396 100.00 Very High Very High Very High
midbrain 153 100.00 Very High Very High Very High
Neurotransmitter 32 100.00 Very High Very High Very High
Serotonin 9 100.00 Very High Very High Very High
Substantia nigra 609 99.90 Very High Very High Very High
Locus ceruleus 1044 99.64 Very High Very High Very High
Catecholamine 1 99.22 Very High Very High Very High
substance P 40 97.32 Very High Very High Very High
excitatory amino acid 3 94.84 High High
Central nervous system 12 90.84 High High
Disease Link Frequency Relevance Heat
Restless Legs Syndrome 336 99.84 Very High Very High Very High
Sleep Disorders 133 99.78 Very High Very High Very High
Rheumatoid Arthritis 25 99.00 Very High Very High Very High
Stress 23 98.74 Very High Very High Very High
Enteropathy 4 98.52 Very High Very High Very High
Diabetes Mellitus 180 98.12 Very High Very High Very High
Aging 36 98.12 Very High Very High Very High
Gastric Motility Disorder 108 98.06 Very High Very High Very High
Toxicity 106 98.00 Very High Very High Very High
Syndrome 28 97.84 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Striatal tyrosine hydroxylase (TH) levels are decreased while the number of DA neurones in substantia nigra (SN) appears normal.
Negative_regulation (decreased) of TH in substantia nigra associated with dopamine and substantia nigra
1) Confidence 0.57 Published 2004 Journal Exp. Neurol. Section Abstract Doc Link 15530890 Disease Relevance 0.36 Pain Relevance 0.51
If this is true, then gastroparesis symptoms themselves may be due to changes that either occur earlier (such as perhaps the slight loss of TH immunoreactive fibers in the circular muscle layer) or are too subtle to be detected by the techniques we have used (e.g. abnormalities in subcellular signaling pathways in the absence of morphological changes, as has been described in gastric muscle from diabetic animals [38].
Negative_regulation (loss) of TH in muscle associated with diabetes mellitus, congenital anomalies and gastric motility disorder
2) Confidence 0.41 Published 2008 Journal BMC Gastroenterol Section Body Doc Link PMC2442096 Disease Relevance 0.48 Pain Relevance 0
There was a slight decrease in the number of TH positive fibers in the muscle layers in this patient; however, TH immunoreactivity around ganglia was normal, suggesting an intact extrinsic innervation to the intrinsic nervous system (Figure 1).


Negative_regulation (decrease) of TH in nervous system
3) Confidence 0.30 Published 2008 Journal BMC Gastroenterol Section Body Doc Link PMC2442096 Disease Relevance 0.29 Pain Relevance 0.24
The only finding of note in the tissue from this patient was a slight decrease in TH immunoreactivity in the circular muscle layer but not in the myenteric plexus.
Negative_regulation (decrease) of TH in muscle
4) Confidence 0.30 Published 2008 Journal BMC Gastroenterol Section Body Doc Link PMC2442096 Disease Relevance 0.90 Pain Relevance 0
While TH is inhibited by dopamine, self-limiting dopamine production, AADC has no such innate control mechanism (Carlsson et al 2007).
Negative_regulation (inhibited) of TH associated with dopamine
5) Confidence 0.28 Published 2008 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2626922 Disease Relevance 0.05 Pain Relevance 0.43
The neural progenitors acquired a spinal positional identity because the RA treatment completely suppressed or significantly downregulated the rostral markers RX, BF1, GBX2 as well as midbrain dopaminergic markers PTX3, PAX2, NURR1, LMX1B, and TH (Figures 4E and 4F).
Negative_regulation (downregulated) of TH in spinal associated with rheumatoid arthritis and midbrain
6) Confidence 0.28 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2346555 Disease Relevance 0.35 Pain Relevance 0.12
To determine whether the TH-immunoreactive cell loss in the SN of the current study was indicative of a down-regulation of TH or frank neuronal cell loss, stereological assessment of NeuN-positive cells was performed [22,36,37].
Negative_regulation (loss) of TH in neuronal associated with substantia nigra
7) Confidence 0.23 Published 2010 Journal Mol Neurodegener Section Body Doc Link PMC2984491 Disease Relevance 0.19 Pain Relevance 0.23
There was a reduced number of nigral TH-immunoreactive neurons, as well as reduction in total neuronal (NeuN) number, and, within the striatum, a loss of TH-immunoreactive fibre density and the presence of ?
Negative_regulation (loss) of TH-immunoreactive in striatum
8) Confidence 0.23 Published 2010 Journal Mol Neurodegener Section Body Doc Link PMC2984491 Disease Relevance 0.16 Pain Relevance 0.11
-syn induced damage in the nigra, being significantly less, and being limited to the SN (no loss in striatal TH-immunoreactive or signs of dystrophic neurites).
Neg (no) Negative_regulation (loss) of TH-immunoreactive in neurites associated with substantia nigra
9) Confidence 0.20 Published 2010 Journal Mol Neurodegener Section Body Doc Link PMC2984491 Disease Relevance 0.34 Pain Relevance 0.16
Similar morphology was observed in these same animals using TH-immunoreactive, although, given the significant decrease in TH optical density in this region (Figure 5), less fibres were strongly labelled (data not shown).
Negative_regulation (decrease) of TH
10) Confidence 0.20 Published 2010 Journal Mol Neurodegener Section Body Doc Link PMC2984491 Disease Relevance 0.07 Pain Relevance 0.04
-syn and, to a lesser extent, AAV1/2-GFP resulted in significant reductions in TH-immunoreactive neurons compared to AAV1/2-EV injected rats.
Negative_regulation (reductions) of TH-immunoreactive in neurons
11) Confidence 0.20 Published 2010 Journal Mol Neurodegener Section Body Doc Link PMC2984491 Disease Relevance 0.27 Pain Relevance 0.19
Furthermore, this reduction in TH fibre density was present through 6 weeks with a concomitant reduction in striatal DAT demonstrating a persistence of effect.
Negative_regulation (reduction) of TH
12) Confidence 0.20 Published 2010 Journal Mol Neurodegener Section Body Doc Link PMC2984491 Disease Relevance 0.17 Pain Relevance 0.10
The latter is also associated with loss of nNOS and TH expression but by contrast, presents with increased expression of SP [26], suggesting regional variations in the effects of diabetes on the enteric nervous system.
Negative_regulation (loss) of TH in enteric nervous system associated with diabetes mellitus and substance p
13) Confidence 0.15 Published 2008 Journal BMC Gastroenterol Section Body Doc Link PMC2442096 Disease Relevance 0.70 Pain Relevance 0.11
The Drosophila ortholog to H13N06.5 is Catsup (Catecholamines up, Q9V3A4), which encodes a negative regulator of tyrosine hydroxylase (TH) activity [34].
Negative_regulation (regulator) of TH associated with catecholamine
14) Confidence 0.12 Published 2004 Journal BMC Genomics Section Body Doc Link PMC533873 Disease Relevance 0.20 Pain Relevance 0.16
Indeed, qualitatively, extensive loss of both TH+ and NeuN+ cells was observed in these regions when compared to saline controls (Figure 5C, D).
Negative_regulation (loss) of TH
15) Confidence 0.12 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2824797 Disease Relevance 0.26 Pain Relevance 0.21
Consistent with loss of nigral TH/NeuN+ cell bodies, densitometry analysis revealed a 69.6 ± 2.5% reduction of TH+ fibre density in the ipsilateral striatum, relative to the non-injected contralateral striatum of lactacystin-lesioned animals (61.29 ± 1.99 vs. 18.61 ± 1.54; p < 0.001; Figure 5E, F) confirming significant loss of DA axon terminals.
Negative_regulation (loss) of TH in striatum
16) Confidence 0.12 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2824797 Disease Relevance 0.23 Pain Relevance 0.13
Unbiased stereology cell counts revealed that intranigral injection of lactacystin resulted in an 81.4 ± 1.1% reduction of TH-positive (+) cells in the ipsilateral substantia nigra pars compacta (SNc) compared to the intact contralateral hemisphere (10,030 ± 214 vs. 1861 ± 219; p < 0.001; Figure 5A).
Negative_regulation (reduction) of TH in substantia nigra pars compacta associated with substantia nigra
17) Confidence 0.10 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2824797 Disease Relevance 0.07 Pain Relevance 0.31
Consistent with loss of nigral TH/NeuN+ cell bodies, densitometry analysis revealed a 69.6 ± 2.5% reduction of TH+ fibre density in the ipsilateral striatum, relative to the non-injected contralateral striatum of lactacystin-lesioned animals (61.29 ± 1.99 vs. 18.61 ± 1.54; p < 0.001; Figure 5E, F) confirming significant loss of DA axon terminals.
Negative_regulation (reduction) of TH in striatum
18) Confidence 0.10 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2824797 Disease Relevance 0.22 Pain Relevance 0.12
Although TH+ fibre density was dramatically reduced in the ipsilateral striatum of lactacystin-lesioned animals, qualitatively, no gross loss of either NeuN+ or DARPP-32+ cells was apparent.
Negative_regulation (reduced) of TH in striatum
19) Confidence 0.10 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2824797 Disease Relevance 0.06 Pain Relevance 0.35
Importantly, in the current study, volume decreases were significantly correlated with the number of surviving TH+ and NeuN+ cell numbers in the ipsilateral SN, but also the density of TH+ fibres in the ipsilateral striatum.
Negative_regulation (surviving) of TH in striatum associated with substantia nigra
20) Confidence 0.10 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2824797 Disease Relevance 0.32 Pain Relevance 0.30

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