Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stem cell inhibitor (SCI) has been shown to inhibit the proliferation of primitive progenitors. The inhibitor, a product of bone marrow macrophages, activated lymphocytes, and monocytes, is identical to macrophage inflammatory protein (MIP-1 alpha). We report homologous (SCI/hMIP-1 alpha) sequences in freshly isolated lymphocytes, monocytes, and granulocytes and have found that SCI mRNA can be induced in monocytes by lipopolysaccharide (LPS) and interleukins 1, 2, and 6. In contrast, interferon gamma (IFN-gamma) decreases the expression of SCI/hMIP-1 alpha. Although only a low level expression of SCI/hMIP-1 alpha mRNA can be detected in normal human bone marrow nucleated cells (NCBM), very significant increases in the levels of SCI/hMIP-1 alpha RNA transcripts are observed in NCBM from patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). These data suggest that the expression of SCI/hMIP-1 alpha in bone marrow may reflect dysregulated cytokine production and activation of the immune system that may possibly contribute to disease progression.
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PMID:Expression of stem cell inhibitor (SCI) gene in patients with bone marrow failure. 146 44

TNF-alpha is a pleitropic cytokine that expresses both pro- and anti-inflammatory activity and transgenic mice expressing human tumor necrosis factor-alpha (TNF-alpha) exhibit a progressive polyarthritis that models rheumatoid arthritis (RA). One of the common comorbidities of RA is anemia of chronic disease (ACD). The purpose of these experiments was to study the changes in the bone marrow and peripheral blood that accompany polyarthritis in TNF-alpha transgenic mice in an effort to better understand the pathogenesis of myelodysplasia and ACD. Polychromatic cytometry, hematology and serum cytokine analysis were used to study the pathogenesis of ACD in human TNF-alpha transgenic mice. Our hematological evaluation revealed a mild, compensated, microcytic hypochromic anemia, and monocytosis. In the bone marrow, we observed alterations in cell kinetics, decreased relative expression of transferrin receptor and increased apoptosis and cell death in several late precursor cell populations. Although significant levels of human TNF-alpha were found in the serum, neither change in serum murine erythropoietin nor any significant difference observed in serum levels of murine IL-beta, IL-5, IL-6, IL-10, IL-12(p70), IL-17, TNF-alpha, IFNgamma, GM-CSF, MIP-1alphaJE, MCP-5 was observed. Tg197 mice develop a compensated, microcytic, hypochromic anemia, and a functional iron deficiency by 9 weeks of age. Changes in peripheral blood are reflected in alterations in cell kinetics, transferrin receptor expression and markedly increased apoptosis and cell death in the bone marrow indicating that TNF-alpha may contribute to myelodysplasia in ACD. Moreover, since human TNF-alpha can interact only with murine TNFR1, our data suggest that TNFR1 may play an important role in the development of ACD.
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PMID:Myelodysplasia and anemia of chronic disease in human tumor necrosis factor-alpha transgenic mice. 1820 95