INT74443

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Context Info
Confidence 0.53
First Reported 1998
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 11
Total Number 11
Disease Relevance 12.52
Pain Relevance 1.21

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

endosome (PML) nucleoplasm (PML) endoplasmic reticulum (PML)
intracellular (PML) protein complex assembly (PML) DNA binding (PML)
Anatomy Link Frequency
leukocytes 1
nucleus 1
band 1
central nervous system 1
PML (Homo sapiens)
Pain Link Frequency Relevance Heat
Multiple sclerosis 247 97.20 Very High Very High Very High
antagonist 14 96.42 Very High Very High Very High
headache 17 93.44 High High
Central nervous system 33 91.48 High High
Inflammation 39 90.76 High High
imagery 112 82.80 Quite High
drug abuse 1 78.16 Quite High
rheumatoid arthritis 11 77.60 Quite High
cytokine 5 59.84 Quite High
Infliximab 4 45.44 Quite Low
Disease Link Frequency Relevance Heat
Progressive Multifocal Leukoencephalopathy 171 100.00 Very High Very High Very High
Leukemia 21 100.00 Very High Very High Very High
Systemic Lupus Erythematosus 24 99.68 Very High Very High Very High
Infection 45 99.66 Very High Very High Very High
Acquired Immune Deficiency Syndrome Or Hiv Infection 29 97.64 Very High Very High Very High
Disease 133 97.44 Very High Very High Very High
Demyelinating Disease 280 97.20 Very High Very High Very High
Adhesions 28 97.08 Very High Very High Very High
Toxicity 5 96.88 Very High Very High Very High
Epilepsy 66 95.36 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
One must also note that reconstitution of the immune system is considered the only truly effective treatment for PML, which in HIV-infected individuals consists of administering highly active antiretroviral therapy.8 In cases involving natalizumab induced PML, this may require allowing significant time for the biological effects of the drug to wear off, which has been shown to be approximately 3 months.16 In the previously discussed case, the patient did experience a central nervous system inflammatory reaction 3 months after his last dose of natalizumab, which represents a reconstitution of the immune system and offers another reason for his overall improvement.
Positive_regulation (induced) of PML in central nervous system associated with progressive multifocal leukoencephalopathy, inflammation, acquired immune deficiency syndrome or hiv infection and central nervous system
1) Confidence 0.53 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2724189 Disease Relevance 0.91 Pain Relevance 0.13
As previously mentioned, reconstitution of the immune system appears to be the most promising approach to treating PML.8 Plasma exchange or immunoadsorption may offer some benefit for accelerating the clearance of natalizumab and thus restoring the function of leukocytes, which may prove vital for improving survival in natalizumab-induced PML cases.
Positive_regulation (induced) of PML in leukocytes associated with progressive multifocal leukoencephalopathy
2) Confidence 0.53 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2724189 Disease Relevance 0.90 Pain Relevance 0.17
Several patients in CR became polymerase chain reaction (PCR) negative for promyelocytic leukemia/retinoic acid receptor-alpha (PML/RARalpha) after liposomal ATRA alone.
Positive_regulation (negative) of PML associated with leukemia
3) Confidence 0.49 Published 2001 Journal Blood Section Abstract Doc Link 11133744 Disease Relevance 1.15 Pain Relevance 0.09
In vitro, 5-HT2a receptor antagonists inhibited JC virus infection.25 Mirtazapine is a 5-HT2a receptor antagonist that has been used to treat HIV-infected patients with PML.26 Data supporting the use of these agents are limited, but these therapies may be considered for treating natalizumab-induced PML.


Positive_regulation (induced) of PML associated with progressive multifocal leukoencephalopathy, antagonist, acquired immune deficiency syndrome or hiv infection and infection
4) Confidence 0.38 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2724189 Disease Relevance 1.44 Pain Relevance 0.12
Further research is imperative to establish a mechanism for natalizumab in causing PML and more importantly, to establish risk factors for identifying those at higher risk.
Positive_regulation (causing) of PML associated with progressive multifocal leukoencephalopathy
5) Confidence 0.35 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2724189 Disease Relevance 1.05 Pain Relevance 0.19
In some cases, exposure to topoisomerase II poisons has been associated with the formation of specific types of leukemia that involve the MLL (mixed lineage leukemia) gene at chromosome band 11q23 or the chromosome 15;17 translocation that joins the PML (promyelocytic leukemia) and RARA (retinoic acid receptor ?)
Positive_regulation (joins) of PML in band associated with leukemia
6) Confidence 0.33 Published 2009 Journal Nucleic Acids Research Section Body Doc Link PMC2647315 Disease Relevance 0.46 Pain Relevance 0
There was a 12-fold increase in the frequency of PML between 1981-1984 and 1991-1994.
Positive_regulation (increase) of PML associated with progressive multifocal leukoencephalopathy
7) Confidence 0.31 Published 1998 Journal J. Neurovirol. Section Abstract Doc Link 9531012 Disease Relevance 1.77 Pain Relevance 0.10
During infections with HHV-1, new PML-NBs are generated at the sites where infecting viral genomes enter the nucleus [82].
Positive_regulation (generated) of PML in nucleus associated with infection
8) Confidence 0.14 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2936540 Disease Relevance 0.40 Pain Relevance 0
As no interactions with AED drugs were described for natalizumab and recent clinical data show that safety may be increased for PML associated with natalizumab therapy [35], our results suggest that anti-adhesion therapies such as natalizumab may complement traditional therapies, and might be useful in treating refractory epilepsy and epilepsy following MS or inflammatory inciting events such as trauma, stroke and infections.
Positive_regulation (increased) of PML associated with progressive multifocal leukoencephalopathy, stroke, infection, epilepsy, multiple sclerosis, inflammation, injury and adhesions
9) Confidence 0.09 Published 2010 Journal BMC Neurol Section Body Doc Link PMC2954970 Disease Relevance 2.01 Pain Relevance 0.28
Subsequent to these reports of PML, an extensive safety evaluation revealed no additional cases of PML among 3116 patients who received natalizumab in clinical studies.
Neg (no) Positive_regulation (cases) of PML associated with progressive multifocal leukoencephalopathy
10) Confidence 0.05 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721353 Disease Relevance 0.79 Pain Relevance 0.04
It is unclear whether these cases were related to rituximab treatment, since only two cases have been reported and PML has also been reported in >20 SLE patients not treated with rituximab.


Positive_regulation (reported) of PML associated with progressive multifocal leukoencephalopathy and systemic lupus erythematosus
11) Confidence 0.05 Published 2007 Journal Rheumatol Int Section Body Doc Link PMC2134974 Disease Relevance 1.63 Pain Relevance 0.07

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