Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human T-cell lymphotropic virus type I (HTLV-I), the cause of adult T-cell leukemia, is also associated with the neurological disease, TSP/HAM (tropical spastic paraparesis/HTLV-I associated myelopathy). The HTLV-I genome encodes a protein, Tax, that trans activates viral and cellular gene transcription. To understand the mechanisms for the production of cytokines by HTLV-I in nervous tissue, we examined their expression in glial cells which carried the Tax-expressing vector. We demonstrated that Tax expression enhanced the production by glial cells of interleukin (IL)-1, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor (TGF) beta. We suggest that the excessive production of cytokines in nervous tissue may play a role in pathogenesis of TSP/HAM. Glial cells that carry the tax gene may provide a model useful for in vitro study of the mechanism of production of cytokines in the nervous system.
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PMID:Induction of cytokines in glial cells by trans activator of human T-cell lymphotropic virus type I. 142 68

The development of human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is closely associated with the activation of T cells which are HTLV-1 specific but may cross-react with neural antigens (Ags). Immature dendritic cells (DCs), differentiated from normal donor monocytes by using recombinant granulocyte-macrophage colony-stimulating factor and recombinant interleukin-4, were pulsed with HTLV-1 in vitro. The pulsed DCs contained HTLV-1 proviral DNA and expressed HTLV-1 Gag Ag on their surface 6 days after infection. The DCs matured by lipopolysaccharides stimulated autologous CD4(+) T cells and CD8(+) T cells in a viral dose-dependent manner. However, the proliferation level of CD4(+) T cells was five- to sixfold higher than that of CD8(+) T cells. In contrast to virus-infected DCs, DCs pulsed with heat-inactivated virions activated only CD4(+) T cells. To clarify the role of DCs in HAM/TSP development, monocytes from patients were cultured for 4 days in the presence of the cytokines. The expression of CD86 Ag on DCs was higher and that of CD1a Ag was more down-regulated than in DCs generated from normal monocytes. DCs from two of five patients expressed HTLV-1 Gag Ag. Furthermore, both CD4(+) and CD8(+) T cells from the patients were greatly stimulated by contact with autologous DCs pulsed with inactivated viral Ag as well as HTLV-1-infected DCs. These results suggest that DCs are susceptible to HTLV-1 infection and that their cognate interaction with T cells may contribute to the development of HAM/TSP.
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PMID:The role of human T-lymphotropic virus type 1 (HTLV-1)-infected dendritic cells in the development of HTLV-1-associated myelopathy/tropical spastic paraparesis. 1023 16

MLL gene rearrangement is common in both adult and childhood acute myeloid leukaemia (AML), and its role in oncogenesis has been investigated. While over 50 translocated-partner genes have been identified so far, few studies have detailed the molecular mechanism of partial tandem duplication (PTD) of the MLL gene. The prognostic impact and contribution to leukaemogenesis of MLL-PTD, especially in childhood cases, remain unknown. We have established a novel cell line containing MLL-PTD derived from an 11-year-old patient with AML and designated as KOPM-88. KOPM-88 cells exhibited certain characteristics associated with the myeloid lineage including abundant primary granules in the cytoplasm and the expression of myeloperoxidase. The cell growth of KOPM-88 was cytokine independent but was accelerated by granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. MLL-PTD of exon 2 to exon 6 and exon 2 to exon 8 was revealed using Southern blotting, fluorescence in situ hybridisation, and reverse transcription polymerase chain reaction/DNA sequencing. Furthermore, non-obese diabetic/severe combined immunodeficient mice inoculated with KOPM-88 cells exhibited leukaemic infiltrations in the bone marrow and hemiparalysis because of compression myelopathy. This is the first report of an in vivo animal model exhibiting the systemic involvement of childhood AML containing MLL-PTD. KOPM-88 cells and our murine model may be useful for investigating the pathogenesis of childhood AML associated with MLL gene rearrangement.
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PMID:Establishment of a novel childhood acute myeloid leukaemia cell line, KOPM-88, containing partial tandem duplication of the MLL gene and an in vivo model for childhood acute myeloid leukaemia using NOD/SCID mice. 1740 61