Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An 8-year-old boy had been suffering from chronic autoimmune neutropenia for more than 5 years. The neutropenia proved to be resistant to high-dose steroids and intravenous (either low-or high-dose) immunoglobulin (Ig) therapy. The chronic autoimmune thrombocytopenia and recurrent phases of autoimmune haemolytic anaemia did, however, respond to high-dose prednisone. Other signs of immune dysregulation in this patient consisted of insulin-dependent diabetes mellitus type I (IDDM) and an acquired hypogammaglobulinaemia, most compatible with common variable immunodeficiency (CVI). Prior to rhG-CSF therapy the child had suffered for more than 2 years from recurrent life-threatening bacterial infections. Anti-neutrophil autoantibodies had pan-Fc gamma RIII (CD116, NA1/NA2) specificity. The neutropenia as well as the antineutrophil autoantibodies disappeared when subcutaneous rhG-CSF therapy was started. Upon tapering rhG-CSF, anti-Fc gamma RIII antibodies reappeared together with an absolute neutropenia. Renewed administration resulted again in the normalization of symptoms. Soluble Fc gamma RIII (sFc gamma RIII) antigen levels in plasma increased dramatically during rhG-CSF treatment. These high levels of sFc gamma RIII together with increased numbers as well as decreased apoptotic reactions of neutrophils apparently result in adsorption of the autoantibodies in vivo, contributing to the normalization of autoimmune-mediated neutropenia upon rhG-CSF treatment. Long-term administration of rhG-CSF represents as alternative in the treatment of autoimmune neutropenia.
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PMID:The use of rhG-CSF in chronic autoimmune neutropenia: reversal of autoimmune phenomena, a case history. 907 39

The use of myeloid growth factors has markedly reduced the complications of chemotherapy-induced neutropenia, however, abrogation of severe thrombocytopenia remains a major clinical problem. Platelet transfusions remain the standard method of preventing or treating thrombocytopenia but are associated with a variety of complications and are a limited resource. A number of cytokines have been clinically investigated for their thrombopoietic activity, the most promising of which is the recently cloned ligand to the hematopoietic growth factor receptor, c-Mpl. The c-Mpl ligand, also referred to as thrombopoietin, megakaryocyte growth and development factor (MGDF) and megapoietin, is a potent lineage-specific agent that promotes growth and maturation of megakaryocytes and their progenitors. It holds promise for clinical use in the treatment of iatrogenic or disease-associated bone marrow failure states and possibly in syndromes of excessive platelet consumption. Early clinical trials assessing the safety and activity of recombinant human MGDF are now underway.
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PMID:The role of platelet growth factors in cancer therapy. 1101 31

In vitro exposure of murine bone marrow cells to increasing concentrations of zidovudine (AZT, 0.1-50 microM) had a concentration dependent suppressive effect on the growth of granulocyte-monocyte colony forming unit (CFU-GM) derived colonies. In our previous published study, the mechanism of AZT-induced suppression of erythroid colony forming unit (CFU-E) derived colonies was linked to a decrease in erythropoitin receptor (Epo-R) gene expression. In this study, we have observed that AZT exposure also induced a concentration dependent suppressive effect (35-90%) on GM-CSF receptor type alpha (GM-CSFR alpha) gene expression. The suppression of GM-CSFR alpha mRNA expression was specific, since AZT caused a much lower decrease (15-22%) on the IL-3 receptor type alpha (IL-3R alpha) message level, and had an insignificant effect on glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and c-myc message levels. Erythropoietin (Epo) therapy has been used for reversal of AZT induced erythroid toxicity. Exposure to increasing concentrations (10-500 U/ml) of GM-CSF was unable to override the suppressive effect of AZT on CFU-GM derived colonies, however, treatment in combination with IL-3 (10-250 U/ml) ameliorated the suppressive effects of AZT on CFU-GM and on GM-CSFR alpha and IL-3R alpha gene expression. These findings suggest a mechanism via which AZT may suppress granulocyte-monocyte specific differentiation in murine bone marrow cells. These data also suggest that a combination of GM-CSF and IL-3 may be a superior therapeutic intervention for AZT-induced neutropenia.
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PMID:Zidovudine (AZT) treatment suppresses granulocyte-monocyte colony stimulating factor receptor type alpha (GM-CSFR alpha) gene expression in murine bone marrow cells. 1208 93

A girl with congenital dysgranulopoietic neutropenia (CDN) and her non-neutropenic mother with aphthae (A) were investigated. Apoptosis in lymphocytes and granulocytes of both patients (mother A+) were documented by high annexin and electron microscopic morphology. CD11b/CD18 of the daughter's granulocytes ranged between low to normal while that of the mother changed between very low to high levels through A(-) to A(+) periods. In both patients, CD11b/CD18 on lymphocytes were high; GM-CSF receptor was negative; CD4-/CD8- lymphocytes were high and the leukocytes which showed abnormal cell cycle were stained by senescence associated beta-galactosidase. We think that increased apoptosis and rapid cell senescence of leukocytes underlies the pathophysiology of CDN.
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PMID:Rapid cell senescence and apoptosis in lymphocytes and granulocytes and absence of GM-CSF receptor in congenital dysgranulopoietic neutropenia. 1768 17