| pubmed-article:11146160 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11146160 | lifeskim:mentions | umls-concept:C0087111 | lld:lifeskim |
| pubmed-article:11146160 | lifeskim:mentions | umls-concept:C0079459 | lld:lifeskim |
| pubmed-article:11146160 | lifeskim:mentions | umls-concept:C0001617 | lld:lifeskim |
| pubmed-article:11146160 | lifeskim:mentions | umls-concept:C0034809 | lld:lifeskim |
| pubmed-article:11146160 | lifeskim:mentions | umls-concept:C0237284 | lld:lifeskim |
| pubmed-article:11146160 | lifeskim:mentions | umls-concept:C1853118 | lld:lifeskim |
| pubmed-article:11146160 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
| pubmed-article:11146160 | lifeskim:mentions | umls-concept:C0205195 | lld:lifeskim |
| pubmed-article:11146160 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:11146160 | pubmed:issue | 12 | lld:pubmed |
| pubmed-article:11146160 | pubmed:dateCreated | 2001-1-10 | lld:pubmed |
| pubmed-article:11146160 | pubmed:abstractText | More than 90% of patients with severe congenital neutropenia (SCN) respond to granulocyte colony-stimulating factor (G-CSF) therapy. The basis for the refractory state in the remaining patients is unknown. To address this issue, we studied a child with SCN who was totally unresponsive to G-CSF and had a novel point mutation in the extracellular domain of the G-CSF receptor (GCSF-R). Marrow stromal support of granulopoiesis was evaluated by plating CD34(+) cells on preformed stromal layers. Nonadherent cells were harvested and assayed in clonogenic assays for granulocytic colony production. The in vitro effect of G-CSF and corticosteroids on granulopoiesis was evaluated in clonogenic assays of marrow mononuclear cells, by proliferation studies of the murine myeloid cell line 32D expressing the patient's mutated G-CSFR, and by measuring STAT5 activation in nuclear extracts from stimulated cells.Patient's stroma supported granulopoiesis derived from control marrow CD34(+) cells in a normal manner. Normal stroma, however, failed to induce granulopoiesis from patient's CD34(+) cells. Clonogenic assays of the patient's marrow mononuclear cells incorporating either G-CSF or hydrocortisone produced little neutrophil growth. In contrast, inclusion of both G-CSF and hydrocortisone in the cytokine "cocktail" markedly increased the neutrophil numbers. Proliferation of 32D cells expressing the mutated receptor and STAT5 activation were improved by a combination of G-CSF and dexamethasone. When small daily doses of oral prednisone were then administered to the patient with conventional doses of subcutaneous G-CSF, the patient responded with increased neutrophil numbers and with a complete reversal of the infectious problems. These data provide insight into SCN unresponsive to standard G-CSF treatment and to the potential corrective action of combined treatment with G-CSF and corticosteroids through synergistic activation of STAT5. | lld:pubmed |
| pubmed-article:11146160 | pubmed:language | eng | lld:pubmed |
| pubmed-article:11146160 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11146160 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:11146160 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11146160 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11146160 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:11146160 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11146160 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11146160 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11146160 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11146160 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11146160 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11146160 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11146160 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11146160 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:11146160 | pubmed:issn | 0301-472X | lld:pubmed |
| pubmed-article:11146160 | pubmed:author | pubmed-author:FreedmanM HMH | lld:pubmed |
| pubmed-article:11146160 | pubmed:author | pubmed-author:WardA CAC | lld:pubmed |
| pubmed-article:11146160 | pubmed:author | pubmed-author:GaddK GKG | lld:pubmed |
| pubmed-article:11146160 | pubmed:author | pubmed-author:SERFBB | lld:pubmed |
| pubmed-article:11146160 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:11146160 | pubmed:volume | 28 | lld:pubmed |
| pubmed-article:11146160 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:11146160 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:11146160 | pubmed:pagination | 1381-9 | lld:pubmed |
| pubmed-article:11146160 | pubmed:dateRevised | 2009-11-3 | lld:pubmed |
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| pubmed-article:11146160 | pubmed:year | 2000 | lld:pubmed |
| pubmed-article:11146160 | pubmed:articleTitle | Combined corticosteroid/granulocyte colony-stimulating factor (G-CSF) therapy in the treatment of severe congenital neutropenia unresponsive to G-CSF: Activated glucocorticoid receptors synergize with G-CSF signals. | lld:pubmed |
| pubmed-article:11146160 | pubmed:affiliation | Department of Pediatrics, Division of Hematology and Oncology and Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. | lld:pubmed |
| pubmed-article:11146160 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:11146160 | pubmed:publicationType | Case Reports | lld:pubmed |
| pubmed-article:11146160 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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