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)

A 21-year-old man was admitted to our hospital for acute hepatitis of unknown cause. His liver function improved with rest, but worsened 2 months later. He developed a high fever and pancytopenia. The serum level of cytokines including TNF-alpha, IFN-gamma, IL-6, and M-CSF was elevated, and hemophagocytes were seen in bone marrow. These findings suggested a hemophagocytic syndrome-like state. With prednisolone, gamma-globulin, and G-CSF, the high fever disappeared and the patient's liver function gradually recovered. However, the severe pancytopenia persisted. The bone marrow became acellular with a small number of hemophagocytes, and hepatitis-associated aplastic anemia was diagnosed. After immunosuppressive therapy with ATG, CyA and G-CSF was started, and the patient showed hematopoietic reconstitution. The bone marrow CD4+/CD8+ lymphocyte ratio recovered to within the normal range, and the serum cytokines including TNF-alpha and IFN-gamma decreased. The increase in serum cytokines, particularly TNF-alpha and INF-gamma, as well as the presence of activated T cells associated with the preceding hemophagocytic syndrome-like state may have predisposed this patient to aplastic anemia.
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PMID:[Hepatitis-associated aplastic anemia preceded by a hemophagocytic syndrome-like state]. 1463 47

The human granulocyte macrophage colony-stimulating factor (GM-CSF) is a glycoprotein with important clinical applications for the treatment of neutropenia and aplastic anemia and reducing infections associated with bone marrow transplants. We evaluated the potential for using a potato virus X (PVX) viral vector system for efficient expression of the biologically functional GM-CSF protein in Nicotiana benthamiana leaves. The GM-CSF gene was cloned into PVX viral expression vector, driven with the CaMV 35S promoter. Gene transfer was accomplished by inoculating N. benthamiana leaves with the plasmid DNA of PVX vector containing the GM-CSF gene. The expression level of the recombinant GM-CSF protein was determined with ELISA and its size was confirmed by Western blot analysis. The results showed that: (1) leaf age significantly affects GM-CSF protein concentration with younger leaves accumulating 19.8 mg g(-1) soluble protein which is 2.6 times the concentration in older leaves, (2) recombinant protein accumulation within a given leaf declined slightly over time but was not significantly different between 7 and 11 days post-inoculation (dpi), and (3) the two leaves immediately above the inoculated leaves play an important role for GM-CSF accumulation in the younger leaves. Protein extracts of infected N. benthamiana leaves contained recombinant human GM-CSF protein in concentrations of up to 2% of total soluble protein, but only when the pair of leaves immediately above the inoculated leaves remained intact. The recombinant protein actively stimulated the growth of human TF-1 cells suggesting that the recombinant human GM-CSF expressed via PVX viral vector was biologically active.
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PMID:Efficient transient expression of human GM-CSF protein in Nicotiana benthamiana using potato virus X vector. 1661 40

Immunosuppressive therapy is a treatment for aplastic anemia patients who are not candidates for hematopoietic stem cell transplantation. The aim of the study to evaluate the frequency and severity of immunosuppressive therapy-induced hepatotoxicity in patients with aplastic anemia. The records of 27 patients with aplastic anemia who had eceived immunosuppressive therapy were received and determined for evidence of hepatotoxicity. The patients were divided into three groups. Group 1 was treated with antithymocyte/antilymphocyte globulin and cyclosporin A, group 2 received onl yyclosporin-A and group 3 was treated with antithymocyte/antilymphocyte globulin + cyclosporin-A and granulocyte macrophage colony-stimulating factor. All patients in group 1 had an initial increase in AST and ALT levels after therapy, but these tests abnormalities returned to normal in each case (p> 0.05). There was no detectable change in AST and ALT levels in group 2 (p>0.05). In group 3, five patients had an increase in ALT and AST levels in the initial several days after therapy was started but he levels gradually returnedto normal by the second or third week of therapy.
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PMID:Immunosuppressive Therapy-Induced Hepatotoxicity in Patients with Aplastic Anemia. 2726

Interleukin-3 (IL-3) is a multipotent hematopoietic growth factor produced by activated T-cells, monocytes/macrophages and stroma cells. Human IL-3 gene is located on chromosome 5 near segment 5q31. The high affinity receptor for human IL-3 is composed of alpha and beta subunits. IL-3 shares common beta subunit with GM-CSF and IL-5 which has been mapped to chromosome 22q13.1. The biological effects of IL-3 have been studied in human and murine hematopoietic cell lines and normal human bone marrow cells. Addition of IL-3 to the culture medium induces proliferation, maturation and probably self renewal of pluripotent hematopoietic stem cells and cells of myeloid, erythroid and megakaryocytic lineages. Various clinical trials have assessed the in vivo potential of recombinant human interleukin 3 (rhIL-3). Initial results of phase I/II studies of IL-3 at a dose of 5-10 ug/kg subcutaneous (s/c) daily for 5-10 days in patients with relapsed lymphomas, small cell lung cancer, breast cancer and ovarian cancer have shown that post-chemotherapy application of IL-3 reduces chemotherapy delays and induces faster regeneration of granulocytes and platelets. However, these results were not confirmed in phase III studies. The role of IL-3 alone in the treatment of myelodysplastic syndromes (MDS), aplastic anemia (AA) and other bone marrow failure disorders have also been disappointing. However, preliminary studies of IL-3 in combination with chemotherapeutic agents and immunosuppression have demonstrated encouraging results in patients with MDS and aplastic anemia respectively. The therapeutic potential of IL-3 in peripheral blood stem cell harvesting and priming of stem cells before harvest is beginning to be identified. Initial results of IL-3 in combination with granulocyte macrophage colony stimulating factor (GM-CSF) or later acting growth factor like granulocyte colony stimulating factor (G-CSF) have yielded larger amounts of peripheral blood stem cells during PBSC harvesting. This approach and application of IL-3 with cocktail of other cytokines for ex-vivo expansion of stem cells, dendritic cell development and gene transfer requires further evaluation. The role of IL-3 in murine models of antiphospholipid syndrome (APLS) for prevention of recurrent abortion remains experimental and warrants careful assessment of adverse effects of IL-3 therapy on pregnant woman and fetus. The exact therapeutic role of IL-3 in oncology and nononcology patients is beginning to be identified. It appears that future application of IL-3 in combination with other cytokines is an attractive way forward in the prevention of treatment related mortality and morbidity in oncology patients. It also holds prospects for development of new therapeutic strategies for dose escalation and immune modulation for relapsed cancer patients.
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PMID:Interleukin-3: Promises and Perspectives. 2741 83


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