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)

Chloramphenicol is an antibiotic that consistently suppresses the bone marrow and induces sideroblastic anemia. It is also a rare cause of aplastic anemia. These toxicities are thought to be related to mitochondrial dysfunction, since chloramphenicol inhibits mitochondrial protein synthesis. We hypothesized that chloramphenicol-induced mitochondrial impairment alters the synthesis of ferritin and the transferrin receptor. After treating K562 erythroleukemia cells with a therapeutic dose of chloramphenicol (10 microg/ml) for 4 days, there was a marked decrease in cell surface transferrin receptor expression and de novo ferritin synthesis associated with significant decreases in cytochrome c oxidase activity, ATP levels, respiratory activity, and cell growth. Decreases in the transferrin receptor and ferritin were associated with reduced and unchanged message levels, respectively. The mechanism by which mitochondrial dysfunction alters these important proteins in iron homeostasis is not clear. A global decrease in synthetic processes seems unlikely, since the expression of the cellular adhesion proteins VLA4 and CD58 was not significantly decreased by chloramphenicol, nor were the message levels of beta-actin or ferritin. The alterations were not accompanied by changes in binding of the iron response protein (IRP) to the iron-responsive element (IRE), although cytosolic aconitase activity was reduced by 27% in chloramphenicol-treated cells. A disturbance in iron homeostasis due to alterations in the transferrin receptor and ferritin may explain the hypochromic-microcytic anemia and the accumulation of nonferritin iron in the mitochondria in some individuals after chloramphenicol therapy. Also, these studies provide evidence of a link between mitochondrial impairment and iron metabolism in K562 cells.
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PMID:Chloramphenicol-induced mitochondrial dysfunction is associated with decreased transferrin receptor expression and ferritin synthesis in K562 cells and is unrelated to IRE-IRP interactions. 1043 Jan 73

Mice with immune-induced aplastic anemia (AA) were given 5 mg ligustrazine intraperitoneally twice a day. On the 14th day, the expression of CD49d, CD49c, cyclinD2 in bone marrow mononuclear cells (MNC) was examined by flow cytometry, and VCAM-1 on stromal cells was immunohistochemically measured by Strept Avidin-Biotin Complex (SABC). The expression of CD49d, CD49c, VCAM-1 and cyclinD2 in ligustrazine-treated group was significantly higher than that in AA group (P < 0.01), but the ratio of G0 + G1 phase cells was significantly lower than that in AA group (P < 0.01). The results showed that ligustrazine could improve the expression of adherent molecule and cyclin D2 in the bone marrow of mice with immune-induced aplastic anemia, thereby promoting the growth of hematopoietic cells.
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PMID:Expression of adherent molecule and cyclin by ligustrazine in bone marrow of mice with immune-induced aplastic anemia. 1284 Aug 71

Appropriate adhesion between bone marrow stem cells and the marrow microenvironment is necessary for hematopoiesis, since signals that promote maturation or apoptosis are transmitted from stromal cells to stem cells. In aplastic anemia (AA), interferon-gamma produced by stromal cells has more influence on the pathogenesis of marrow failure than interferon-gamma produced by lymphocytes. We evaluated the expression of cell adhesion molecules, such as very late antigen-4 (CD49d), and -5 (CD49e) or c-kit receptor (CD117), by CD34-positive bone marrow cells in patients with AA who achieved hematological complete remission after immunosuppressive therapy. Before treatment, CD34-positive cells showed markedly higher expression of CD49d and CD49e than cells from healthy controls, indicating the strong adhesion of stem cells to the bone marrow stroma. Expression of CD49d and CD49e was significantly decreased, reaching normal levels, after hematological recovery. These findings suggest that changes in adhesion molecule expression by stem cells are important in the pathology of AA.
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PMID:Adhesion molecule expression by bone marrow CD34-positive cells in aplastic anemia before and after immunosuppressive therapy. 1464 Nov 44

To explore the cell adhesion molecules (CAMs) CD11a and CD49d in patients with chronic aplastic anemia (CAA) and its clinical implications, the expression of CD11a and CD49d in mononuclear cell (MNC) of bone marrow (BM) and peripheral blood (PB) were measured using APAAP techniques in 20 patients with CAA before and after SSL/C therapy. The results showed that the expression of CD11a and CD49d in MNC of BM and CD11a in MNC of PB increased significantly (P < 0.05) after SSL/C therapy, and there was no significant change of CD49d in MNC of PB in both groups. In conclusion, the decrease of CAMs of CD11a and CD49d participated in the pathogenesis of CAA. The expression of CAMs increases with effective treatment, so the restoration or improvement of altered CAMs of CAA might be beneficial to the proliferation and differentiation of hematopoietic stem cell, and improvement of hematopoiesis in CAA.
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PMID:[Change of expression of cell adhesion molecules CD11a and CD49d in patients with chronic aplastic anemia before and after therapy]. 1470 55

Hematopoietic stem cell transplantation (HSCT) has become the standard of care for the treatment of many hematologic malignancies, chemotherapy sensitive relapsed acute leukemias or lymphomas, multiple myeloma; and for some non-malignant diseases such as aplastic anemia and immunodeficient states. The hematopoietic stem cell (HSC) resides in the bone marrow (BM). A number of chemokines and cytokines have been shown in vivo and in clinical trials to enhance trafficking of HSC into the peripheral blood. This process, termed stem cell mobilization, results in the collection of HSC via apheresis for both autologous and allogeneic transplantation. Enhanced understanding of HSC biology, processes involved in HSC microenvironmental interactions and the critical ligands, receptors and cellular proteases involved in HSC homing and mobilization, with an emphasis on G-CSF induced HSC mobilization, form the basis of this review. We will describe the key features and dynamic processes involved in HSC mobilization and focus on the key ligand-receptor pairs including CXCR4/SDF1, VLA4/VCAM1, CD62L/PSGL, CD44/HA, and Kit/KL. In addition we will describe food and drug administration (FDA) approved and agents currently in clinical development for enhancing HSC mobilization and transplantation outcomes.
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PMID:Cytokines and hematopoietic stem cell mobilization. 1688 4