INT8792

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Context Info
Confidence 0.78
First Reported 1992
Last Reported 2010
Negated 1
Speculated 1
Reported most in Body
Documents 20
Total Number 28
Disease Relevance 14.73
Pain Relevance 1.98

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

small molecule metabolic process (GBA) hydrolase activity, acting on glycosyl bonds (GBA) cell death (GBA)
carbohydrate metabolic process (GBA) lipid metabolic process (GBA)
Anatomy Link Frequency
ovary 3
macrophages 2
liver 1
skin 1
GBA (Homo sapiens)
Pain Link Frequency Relevance Heat
Buprenorphine 14 99.82 Very High Very High Very High
Opioid 1 96.72 Very High Very High Very High
Pain 51 94.00 High High
palliative 16 91.76 High High
Angina 4 89.04 High High
Central nervous system 13 79.56 Quite High
anesthesia 1 73.92 Quite High
nud 1 67.20 Quite High
Paracetamol 2 51.04 Quite High
imagery 26 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Disease 284 100.00 Very High Very High Very High
Diffuse Large B-cell Lymphoma 25 99.14 Very High Very High Very High
Targeted Disruption 10 97.16 Very High Very High Very High
Gauchers Disease 919 96.08 Very High Very High Very High
Parkinson's Disease 34 95.64 Very High Very High Very High
Leukemia 16 95.56 Very High Very High Very High
Exanthema 4 94.80 High High
Pain 38 94.00 High High
Rare Diseases 60 92.88 High High
Aseptic Necrosis Of Bone 40 92.72 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Imiglucerase, the recombinantly produced enzyme, is gradually replacing the human placental derived alglucerase in the treatment of gaucher patients.
Gene_expression (produced) of Imiglucerase
1) Confidence 0.78 Published 1999 Journal Blood Cells Mol. Dis. Section Abstract Doc Link 10389590 Disease Relevance 0.65 Pain Relevance 0
This sensitivity to imiglucerase but not to alglucerase, raises the question of future treatment for this patient, since the production of alglucerase may cease, once imiglucerase production will cover the need for replacement enzyme.
Gene_expression (production) of alglucerase
2) Confidence 0.78 Published 1999 Journal Blood Cells Mol. Dis. Section Abstract Doc Link 10389590 Disease Relevance 0.85 Pain Relevance 0.08
The engineered cells are cultured in a medium containing the powerful inhibitor kifunesine, which blocks the action of one of the processing glycosidases for glycoprotein biosynthesis, and as a result, a human glucocerebrosidase protein displaying terminal mannose sugars is produced.
Gene_expression (produced) of glucocerebrosidase protein
3) Confidence 0.78 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC3010821 Disease Relevance 0.16 Pain Relevance 0
Approximately 5 years after the licensing of alglucerase, the Genzyme Corporation launched Cerezyme, imiglucerase – a recombinant human glucocerebrosidase expressed in genetically engineered Chinese hamster ovary cells.
Gene_expression (expressed) of glucocerebrosidase in ovary
4) Confidence 0.78 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC3010821 Disease Relevance 0.53 Pain Relevance 0.09
Imiglucerase is expressed in Chinese hamster ovary cells, where as taliglucerase is produced in transgenic carrot cells.
Gene_expression (expressed) of Imiglucerase in ovary associated with targeted disruption
5) Confidence 0.78 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2909498 Disease Relevance 0.48 Pain Relevance 0
Alglucerase is a modified form of human placental glucocerebrosidase used as enzyme replacement therapy for patients with Gaucher's disease, in whom functional glucocerebrosidase is deficient.
Gene_expression (deficient) of Alglucerase associated with disease
6) Confidence 0.68 Published 1995 Journal Pharmacoeconomics Section Abstract Doc Link 10155294 Disease Relevance 0.43 Pain Relevance 0
Alglucerase is a modified form of human placental glucocerebrosidase used as enzyme replacement therapy for patients with Gaucher's disease, in whom functional glucocerebrosidase is deficient.
Gene_expression (deficient) of glucocerebrosidase associated with disease
7) Confidence 0.68 Published 1995 Journal Pharmacoeconomics Section Abstract Doc Link 10155294 Disease Relevance 0.43 Pain Relevance 0
Healthcare resources consumed by alglucerase therapy represent a large opportunity cost for other therapeutic areas.
Gene_expression (therapy) of alglucerase
8) Confidence 0.68 Published 1995 Journal Pharmacoeconomics Section Abstract Doc Link 10155294 Disease Relevance 0.24 Pain Relevance 0.09
-glucocerebrosidase may disable the protein sufficiently to disturb its enzymatic function in other cell lineages, including those of the nervous system and the skin, which may become diseased.3

Clinical manifestations

Gene_expression (disable) of glucocerebrosidase in skin
9) Confidence 0.67 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC3010821 Disease Relevance 0.37 Pain Relevance 0
Moreover, it is now known that mutations in the human GBA1 gene, present in the heterozygous state in individuals of numerous ethnic origins and not hitherto identified as suffering from Gaucher disease, are the most prevalent genetic determinants of Parkinson’s disease so far identified in many populations.10
Gene_expression (gene) of GBA1 associated with gauchers disease and disease
10) Confidence 0.67 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC3010821 Disease Relevance 1.35 Pain Relevance 0
-glucocerebrosidase deficiency in the kidney, brain, and other tissues, but not white cells or macrophages, in which it serves as a chaperone for delivery of nascent glucocerebrosidase polypeptide to the lysosomal compartment.4–6
Gene_expression (deficiency) of glucocerebrosidase in macrophages
11) Confidence 0.67 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC3010821 Disease Relevance 0.54 Pain Relevance 0
Functional glucocerebrosidase is deficient in Gaucher's disease, an autosomal recessive lipid storage disorder that affects people of all ethnic backgrounds, but has a higher incidence among East European Jews (Ashkenazim).
Gene_expression (deficient) of glucocerebrosidase associated with disease
12) Confidence 0.60 Published 1992 Journal Drugs Section Abstract Doc Link 1379912 Disease Relevance 0.64 Pain Relevance 0.07
Approximately 5 years after the licensing of alglucerase, the Genzyme Corporation launched Cerezyme, imiglucerase – a recombinant human glucocerebrosidase expressed in genetically engineered Chinese hamster ovary cells.
Gene_expression (expressed) of imiglucerase in ovary
13) Confidence 0.60 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC3010821 Disease Relevance 0.53 Pain Relevance 0.09
These results were particularly disappointing since a bicistronic retroviral vector expressing human glucocerebrosidase and a human small cell surface antigen (CD24) as a selectable marker, under the control of the Moloney murine leukemia viral promoter, were used to transform CD34+ hematopoietic progenitors.75 Latterly, there have been promising preclinical developments in the gene therapy of type I Gaucher disease from Stefan Karlsson and colleagues at the University of Lund, Sweden.
Gene_expression (expressing) of glucocerebrosidase associated with leukemia and gauchers disease
14) Confidence 0.60 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC3010821 Disease Relevance 0.52 Pain Relevance 0
From this case and a few others reported, it is clear that most, if not all, key aspects of the systemic disease are due to defective cells of mononuclear phagocytic lineage and thus may be corrected by supplying healthy exogenous hematopoietic stem cells or by transducing autologous stem cells with vectors for transferring the wild-type human glucocerebrosidase gene in order to restore the capacity of tissue macrophages to digest glycolipids normally.


Gene_expression (transferring) of glucocerebrosidase gene in macrophages associated with disease
15) Confidence 0.60 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC3010821 Disease Relevance 0.55 Pain Relevance 0
Alglucerase is a modified form of human placental glucocerebrosidase used as enzyme replacement therapy for patients with Gaucher's disease, in whom functional glucocerebrosidase is deficient.
Gene_expression (deficient) of glucocerebrosidase associated with disease
16) Confidence 0.59 Published 1995 Journal Pharmacoeconomics Section Abstract Doc Link 10155294 Disease Relevance 0.43 Pain Relevance 0
The majority of GBA mutations lead to the synthesis of GC with decreased catalytic function and/or stability.6 While it is assumed that disease severity depends on residual GC activity, this has been difficult to prove for most GBA mutations.7
Gene_expression (mutations) of GBA associated with disease
17) Confidence 0.59 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2909498 Disease Relevance 0.25 Pain Relevance 0
This sensitivity to imiglucerase but not to alglucerase, raises the question of future treatment for this patient, since the production of alglucerase may cease, once imiglucerase production will cover the need for replacement enzyme.
Gene_expression (production) of imiglucerase
18) Confidence 0.53 Published 1999 Journal Blood Cells Mol. Dis. Section Abstract Doc Link 10389590 Disease Relevance 0.84 Pain Relevance 0.07
IgG against alglucerase was undetectable.
Gene_expression (undetectable) of alglucerase
19) Confidence 0.53 Published 1999 Journal Blood Cells Mol. Dis. Section Abstract Doc Link 10389590 Disease Relevance 1.00 Pain Relevance 0.09
Using a nonlytic integrative plasmid expression system, we have successfully produced active human GBA in stable transformed Sf9 (Spodoptera frugiperda) cells.
Gene_expression (produced) of GBA
20) Confidence 0.53 Published 2006 Journal Biochem. Cell Biol. Section Abstract Doc Link 16609695 Disease Relevance 0.59 Pain Relevance 0.08

General Comments

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