Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of a low-molecular-weight heparin, faxiparin (Nadroparin), on murine megakaryocytopoiesis in vitro and in vivo was studied in comparison with unfractionated heparin. The addition of fraxiparin at 1-20 IU/ml into plasma clot cultures but not serum-free agar culture significantly enhanced MK colony growth. Furthermore, fraxiparin was found to potentiate the stimulating activity of aplastic anaemia serum (AAS) but not stem cell factor (SCF), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo), on MK colony growth in vitro, and to neutralize the inhibitory effect of platelet factor 4 (PF4) in vitro and in vivo. Fraxiparin also acted synergistically with heparin cofactor II and antithrombin III to promote megakaryocyte colony formation. Intraperitoneal administration of fraxiparin twice daily for 4 d at 0.1-25 IU/injection increased in mice the level of blood platelet counts and the number of single MKs and CFU-MK in bone marrow. These data demonstrate that fraxiparin is able to positively regulate megakaryocytopoiesis.
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PMID:Fraxiparin, a low-molecular-weight heparin, stimulates megakaryocytopoiesis in vitro and in vivo in mice. 781 73

The effects of native thrombospondin (TSP), an 18 kd recombinant protein comprising residues 1-174 of TSP (TSP1-174) with heparin-binding domain and a fusion protein comprising residues 559-669 of TSP (TSP559-669) on murine hematopoiesis, were studied by using different in vitro culture systems. TSP by itself did not show an inhibitory effect on colony-forming unit-megakaryocyte (CFU-MK) growth in a serum-free agar system and on the growth of colony-forming unit-granulocyte and macrophage (CFU-GM) in a plasma clot system. It was, however, found that in the plasma clot culture system when using aplastic anemia serum as the source of thrombopoietin or C-Mpl ligand (TPO), TSP and TSP1-174, but not TSP559-669, were able to inhibit the growth of CFU-MK from unfractionated and lineage negative (Lin-) bone marrow cells in a dose-dependent manner. A statistically significant suppression was seen at 1 microg/ml of TSP and 5 microg/ml of TSP1-174. This inhibitory effect of TSP was further found in both the serum-free agar system and the plasma clot system without aplastic anemia serum, where megakaryocyte colony growth was stimulated by recombinant TPO, basic fibroblast growth factor (bFGF), or interleukin-3 (IL-3). In a methylcellulose system, where a combination of stem cell factor (SCF), IL-3, and granulocyte/macrophage colony-stimulating factor (GM-CSF) were used, TSP inhibited the growth of colony-forming unit-granulocyte-erythroblast, megakaryocyte, and macrophage (CFU-GEMM) but not CFU-GM and burst-forming unit-erythroblast (BFU-E). Interestingly, this inhibitory effect of TSP on megakaryocyte colony growth could be counteracted by Fraxiparin, a low-molecular-weight heparin. These results demonstrate that TSP is a negative modulator of megakaryocytopoiesis and suggest that its inhibitory effect is at least partially mediated by N-terminal heparin-binding domain.
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PMID:Thrombospondin, a negative modulator of megakaryocytopoiesis. 901 60