Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low oxygen tension is a feature of many physiologic and pathologic conditions, including wound healing, fibrosis, and neoplasia. Increasing evidence suggests that low oxygen tension induces the transcription of a number of genes, and that this process depends on the cellular context. The proteins synthesized from these genes enable cells to adapt to the hypoxic environment and/or to fulfill their functional roles. The regulatory regions responsible for the induction of erythropoietin gene transcription and synthesis in response to hypoxia/anemia appear to be cis-acting deoxyribonucleic acid sequences located within the 5' and 3' flanking regions of the erythropoietin gene. Other proteins induced by hypoxia include cytokines (platelet-derived growth factor-beta chain, endothelin-1, transforming growth factor-beta), enzymes (tyrosine hydroxylase, glycolytic enzymes), and stress proteins. The molecular mechanisms of the hypoxia-induced expression of these genes are poorly understood. A heme protein may act as the oxygen tension sensor, or the redox state of certain nuclear transcription factors may function as second messengers.
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PMID:Gene expression in low oxygen tension. 832 8

Local or systemic injection of peptidoglycan-polysaccharide polymers, which are the primary structural components of cell walls of nearly all bacteria, leads to acute inflammation, which can develop into chronic, spontaneously relapsing, granulomatous inflammation in a number of organs. Evolution into chronic granulomatous inflammation is dependent upon persistence of poorly biodegradable cell wall polymers within tissues, genetically determined host susceptibility, and generation of a T-lymphocyte-mediated immune response. Intraperitoneal injection of peptidoglycan-polysaccharide fragments from group A streptococci or selected intestinal bacteria into susceptible Lewis rats leads to chronic, spontaneously reactivating erosive arthritis and hepatic granulomas. Subserosal (intramural) injection of poorly biodegradable cell wall fragments into the distal intestine of Lewis rats induces chronic, spontaneously relapsing granulomatous enterocolitis with associated arthritis, hepatic granulomas, anemia, and leukocytosis. Chronic inflammation does not occur in T-lymphocyte-deficient rats and is prevented by cyclosporin-A therapy and degradation of peptidoglycan by the muralytic enzyme, mutanolysin. Moreover, resistant Buffalo and Fischer F344 rats, the latter sharing identical MHC antigens with Lewis rats, develop only acute inflammation with no chronic granulomatous response. Peptidoglycan-polysaccharide polymers activate almost every limb of the inflammatory response. Blockade of specific pathways suggests that interleukin-1, transforming growth factor-beta, plasma kallikrein, and T lymphocytes are dominant mediators of peptidoglycan-polysaccharide-induced arthritis, hepatic granulomas, and enterocolitis. Because of the similarity of immune mechanisms of these rat models to human disease, bacterial cell wall-induced inflammation provides unique opportunities to study pathogenic mechanisms of granuloma formation in response to ubiquitous microbial agents and to test novel therapeutic agents.
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PMID:Bacterial Cell Wall Polymer-Induced Granulomatous Inflammation 881 75

The unstimulated and induced production of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), IL-3, IL-6, stem cell factor (SCF), IL-1beta, tumour necrosis factor-alpha (TNF-alpha), TNF-beta, interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) was determined after culture of blood mononuclear cells from 22 patients with severe beta-thalassaemia in a regular transfusion programme, five non-regularly transfused patients with beta-thalassaemia intermedia and nine normal persons. A distinct pattern of cytokine production in thalassaemic patients was detected, namely a low unstimulated production of all cytokines and a significant increase in the stimulated production of IFN-gamma, TNF-alpha and IL- 1beta; these abnormalities were more pronounced in the more heavily transfused older patients. The increased production of the above cytokines, which usually characterize the acute response to infectious agents and have a negative effect on erythropoiesis, may explain the deterioration of anaemia found in thalassaemic patients during acute infections.
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PMID:A distinct pattern of cytokine production from blood mononuclear cells in multitransfused patients with beta-thalassaemia. 906 38

Foals infected with equine infectious anemia virus become thrombocytopenic 7 to 20 days after virus inoculation, and within a few days following the onset of detectable viremia. The thrombocytopenia is associated with suppression of platelet production. Possible mediators of suppression of thrombopoiesis include tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), cytokines that are released during inflammation. To assess effects of plasma or serum from infected foals on megakaryocyte (MK) growth and maturation in vitro, equine low-density bone marrow cells were cultured for clonogenic and ploidy assays. Neutralizing antibodies to TNF-alpha and TGF-beta were added to cultures to determine the contribution of these cytokines to suppression of thrombopoiesis. Plasma from the immediately pre-thrombocytopenia (Pre-Tp) period significantly reduced MK colony numbers. This suppression was partially reversed upon antibody neutralization of plasma TNF-alpha, TGF-beta, or both. There were no differences in ploidy distribution of MK grown in the presence of preinfection serum compared with those grown in the presence of Pre-Tp serum. These results indicate that TNF-alpha and TGF-beta may contribute to suppression of MK proliferation and represent likely factors in the pathogenesis of thrombocytopenia.
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PMID:Suppression of megakaryocyte colony growth by plasma from foals infected with equine infectious anemia virus. 931 Apr 86

Thrombocytopenia is a common finding in infection with equine infectious anaemia virus (EIAV), a lentivirus with some homology to human immunodeficiency virus (HIV). The thrombocytopenia of EIA, like that in some HIV patients, appears to have a multifactorial pathogenesis. To investigate the decreased platelet production seen in experimental EIA, the levels of three potential negative regulators of platelet production--tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and interferon-alpha (IFN-alpha)--were measured in serum and bone marrow of six severe combined immunodeficient (SCID) foals and ten immunocompetent EIAV-infected foals. Levels of cytokines in pre-infection foal sera and bone marrow were compared with levels observed during clinical EIA. Mean serum levels of TNF-alpha and IFN-alpha were significantly higher (P < 0.05) on days -4 to 0 of thrombocytopenia than before infection. Serum TGF-beta was significantly elevated on all days except day -1 of thrombocytopenia. Bone marrow TNF-alpha levels were significantly increased in infected foals just before clinical thrombocytopenia. TGF-beta activity was not different in pre-infection and pre-thrombocytopenia bone marrows, but levels of TGF-beta protein as determined by immunohistochemical staining were significantly higher in pre-thrombocytopenia bone marrow. IFN-alpha activity in bone marrow increased just before thrombocytopenia, but the difference was not significant at P < 0.05. Serum TNF-alpha levels were 2-2.5 times higher in SCID foals on three of the days prior to thrombocytopenia than in immunocompetent foals. No significant differences were found between the levels in SCID and immunocompetent foals of serum and bone marrow TGF-beta or IFN-alpha at any of the times examined.
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PMID:Elevation of cytokines associated with the thrombocytopenia of equine infectious anaemia. 934 75

The Fanconi anemia group C gene (FAC) encodes a 63-kDa protein that plays a role in the growth and differentiation of hematopoietic progenitor cells and in cellular resistance to bifunctional cross-linking agents. The function of the gene product is unknown, as are the factors that govern expression of the gene itself. Seeking to associate a function of this protein with a general metabolic pathway, we attempted to identify factors that induce or repress expression of the gene encoding it. Using two plasmids from which mutant FAC mRNA molecules were transcribed in vitro to serve as competitor mRNAs in quantitative-competitive reverse transcriptase-polymerase chain reaction analysis and novel rabbit antisera raised to recombinant FAC proteins, we quantified gene expression in human hematopoietic cells. We determined that FAC is expressed constitutively in unstimulated normal peripheral blood mononuclear leukocytes, in Epstein-Barr virus (EBV)-transformed B lymphocytes, and in the factor-dependent human myeloid leukemic cell line MO7e at levels of approximately 2000, 200, and 200 FAC mRNA molecules/cell, respectively, and in CD34+ cells from normal human bone marrow at approximately 2000 FAC mRNA molecules/cell. Neither mRNA nor protein increased in any of the cells studied after exposure to mitomycin C, diepoxybutane, hydrogen peroxide, gamma radiation, heat, transforming growth factor-beta, or interferon-gamma. Using these sensitive methods, we confirmed that the FAC gene is constitutively expressed, even in the face of extracellular factors for which the gene product is a known effector of resistance. We conclude that the protective functions of the FAC gene product do not depend upon stressor-induced FAC gene expression.
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PMID:Expression of the Fanconi anemia group C gene in hematopoietic cells is not influenced by oxidative stress, cross-linking agents, radiation, heat, or mitotic inhibitory factors. 943 May 10

A hemoglobin F (HbF) level between eight and nine percent divides sickle cell anemia (SS) patients into two populations, according to the kinetics of circulating burst forming units-erythroid (BFU-E), long term culture-initialing cells (LTC-IC), and cytokine plasma concentrations. The SS patients with HbF levels lower than 8-9% are more anemic (LFSS patients) than those with HbF levels higher than 8-9% who have less severe anemia (HFSS patients). We report here that the level of erythropoiesis [evaluated by the levels of soluble transferin receptors (sTfR)] is not identical in these two patient populations, supporting the idea that a different set of regulatory mechanisms might be required to maintain the two levels of increased hematopoiesis. The plasma sTfR concentration was increased in all SS samples compared with controls (P < 0.002) and sTfR levels were negatively correlated with peripheral HbF%. (r = -0.574, P < 0.002). Furthermore, sTfR levels were higher in LFSS than in HFSS patients. Erythropoietin (Epo) levels were increased in the plasma of LFSS individuals (range = 34-215 ml U/ml), while the values in HFSS patients were in the normal range (3-20 ml U/ml). Furthermore, we identify here stem cell factor (SCF) and transforming growth factor-beta (TGF-beta) as regulatory factors specifically affected by the presence of SS genotype and its level of severity. The plasma concentrations of SCF and TGF-beta were increased compared with normal controls and high levels of SCF (up to 7,000 pg/ml) were detected in LFSS patients. The latter also showed increased proportion of SCF+ CD34 enriched circulating cells (49%). Low SCF in HFSS patients is associated with elevated TGF-beta, suggesting a regulatory role of the latter on either SCF release or c-kit expression in progenitor cells. Occasional elevation of granulocyte macrophage-colony stimulating factor (G-CSF), interleukin (IL)-7, and macrophage inflammatory protein (MIP)-1alpha in plasma of SS patients is not specific because no relation to HbF could be demonstrated. All plasma tested for leukemia inhibitory factor (LIF) were negative. Data presented here, complementing previously published information, supports a model in which HFSS patients achieve a balance between inhibitory (TGF-beta) and stimulatory (SCF, IL-3) factors, resulting in moderate erythropoietic response. In contrast, in LFSS patients, low levels of TGF-beta and the increased release of GM-CSF and SCF maintain the intense erythropoiesis in response to higher erythropoietic stress, in these more severe patients.
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PMID:Circulating cytokines response and the level of erythropoiesis in sickle cell anemia. 992 1

Idiopathic myelofibrosis (IMF) is a chronic myeloproliferative disorder characterized by fibrosis of the bone marrow, varying degrees of extramedullary hematopoiesis, splenomegaly, anemia, and a leukoerythroblastic peripheral blood smear. Bone marrow fibrosis develops as a secondary phenomenon and is caused by increased intramedullary activity of mitogens such as platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and calmodulin. Because of the variable clinical course of IMF, attempts have been made to define prognostic parameters that can be helpful in detecting patients with a shortened life expectancy. The most important adverse prognostic parameters that have been reported are hemoglobin concentration, age, leukocyte count, number of thrombocytes, and cytogenetic abnormalities. However, no standardized prognostic score for IMF has yet been established. Therapeutic strategies in IMF remain predominantly supportive. The most common are blood transfusions, androgens, and cytoreductive agents such as hydroxyurea. Bone marrow transplantation is increasingly being taken into consideration, but it still has to be regarded as an experimental approach. Interferon-alpha (IFN-alpha) has shown promising results in early hyperproliferative stages of IMF but has no or only very little effect in more advanced stages of the disease. Whether IFN-alpha is able to postpone marrow fibrosis if administered in early disease stages remains to be determined in future clinical trials.
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PMID:The role of interferon-alpha in the treatment of idiopathic myelofibrosis. 1113 27

The relationship between malaria-related outcomes and cytokine production in whole blood cultures associated with cellular immune responses and immunity to Plasmodium falciparum malaria was examined in a study in southern Ghana. Production of malaria-specific interferon (IFN)-gamma was associated with reduced risk of fever and clinical malaria. Protective IFN-gamma responses were induced by live schizonts but not by dead parasites. Production of malaria-specific tumor necrosis factor (TNF)-alpha was associated with reduced risk of fever during follow-up. Baseline levels of TNF-alpha and phytohemagglutinin (PHA)-induced interleukin (IL)-10 were positively associated with hemoglobin concentration. IL-12 production was associated with reduced risk of parasitemia. PHA-induced transforming growth factor-beta production was associated with reduced risk of fever during follow-up. High ratios of proinflammatory to anti-inflammatory cytokines were associated with increased risk of fever and higher hemoglobin concentrations. Thus, absolute levels and ratios of proinflammatory and anti-inflammatory cytokines influence susceptibility to infection, clinical disease, and anemia. These data contradict data from cross-sectional clinical studies and indicate a need for detailed analysis of the relationship between cellular immunity to malaria and resistance to disease.
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PMID:Absolute levels and ratios of proinflammatory and anti-inflammatory cytokine production in vitro predict clinical immunity to Plasmodium falciparum malaria. 1255 63

We describe the characterization of a spontaneously transformed chicken monocytic cell line that developed as a single colony of cells in a heterophil culture that was inadvertently left in the incubator over a period of 25 days. These cells, hitherto named HTC, grow efficiently at both 37 or 41 degrees C in culture medium containing either 5% FBS or 2% chicken serum. The HTC cells are acid phosphatase positive, show expressions of both class I and class II major histocompatibility complex (MHC), CD44, K1, and K55 cell surface antigens, and engulf latex beads, produce nitrite and interleukin-6 on stimulation with bacterial lipopolysaccharide (LPS). Treatment with phorbol myristate acetate (PMA) induces respiratory burst in HTC cells and the secretion of matrix metalloproteinase (MMP) into culture medium. Using gene-specific primers and reverse transcriptase-polymerase chain reaction (RT-PCR), the presence of mRNA trancripts for interferon-gamma (IFN-gamma), interleukin-1 (IL-1), interleukin-6 (IL-6), nitric oxide synthase (NOS), matrix metalloproteinase-2 (MMP-2), and transforming growth factor-beta (TGF-beta) were detected. Lipopolysaccharide (LPS) treatment of HTC cells modulated IL-1, IL-6, IFN-gamma, NOS mRNA levels as detected by RT-PCR analyses. Using different avian tumor virus gene-specific primers and PCR, the HTC cells were positive for the presence of avian leukosis virus (ALV) and Marek's disease virus (MDV) but negative for reticuloendothelial virus (REV), chicken infectious anemia virus (CIAV), and herpes virus of turkeys (HVT). The production of ALV antigens by HTC cells was further confirmed using p27 gag protein ELISA. Collectively, these results show that the HTC cells belong to myeloid/macrophage lineage and were likely transformed by ALV and MDV but retain many interesting and useful biological activities.
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PMID:Characterization of a spontaneously transformed chicken mononuclear cell line. 1452 38


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