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)

There is evidence to suggest that infectious feline leukemia viruses (FeLVs) may be altered biologically because of homologous recombination with non-infectious endogenous FeLV (enFeLV) sequences in the infected cells. To evaluate the role of such recombination events in FeLV pathogenesis, a molecular clone of subgroup C FeLV, Sarma strain (FSC), was tested for induction of aplastic anemia in the absence or presence of mixtures of recombinants between FSC and an enFeLV element. In the recombinants, FSC sequences in the viral surface glycoprotein (SU) protein were variably replaced by the corresponding sequences of the enFeLV. The results showed that the virus mixtures varied in their infectivity to neonatal specific pathogen-free cats. One group of mixtures, although exhibiting relatively reduced infectivity, represented the most acute disease-inducing agents. The presence of recombinants in this mixture significantly accelerated the development of erythrocyte aplasia compared to cats infected with FSC alone. In addition, infected cells appeared to be distributed differently in various hematopoietic organs with respect to infection with FSC versus viral mixture. Viral recombinants which were present in this inoculum mixture, however, could not be detected in the plasma or infected tissues of the cats at the end stage of the disease, although their presence in the plasma at the early stages could be detected. Clearly, parental FSC outgrew the recombinants in the infected animals, since its detection was prominent at all stages of the progression of the disease. Therefore, we hypothesize that recombinants initially present in the infected animals, while only poorly replicated compared to FSC in the host, might have had the opportunity to infect certain target cells (potentially erythroid progenitor cells) and then disappeared with the associated cytopathic effect.
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PMID:Pathogenicity of a subgroup C feline leukemia virus (FeLV) is augmented when administered in association with certain FeLV recombinants. 825 54

Brain tissues of domestic cats that died of aplastic anemia from infection with either parental feline leukemia virus (FeLV), subgroup C, or a mixture of FeLV-C and recombinants between FeLV-C and an endogenous FeLV provirus were examined by the immunoperoxidase staining technique using a monoclonal antibody (C11D8) directed against an epitope of the viral surface glycoprotein (SU). Positive staining of the central nervous system (CNS) capillary endothelial cells with no labeling on neuronal or glial cells was observed in cats that were inoculated with the virus mixture. This was in contrast to brain tissue of cats infected with FeLV-C alone, which showed no such staining. While non-CNS endothelial cells derived from human umbilical vein (HUVEC) could be readily infected in culture by FeLV-C, endothelial cells derived from human retina (REC) or brain (BEC) were resistant to infection by this parental virus. These latter cells in culture, however, could be infected by the viral mixture. The data suggested that at least one or more of the presumptive recombinant viruses could specifically infect CNS-derived endothelial cells. Using polymerase chain reaction and DNA sequencing strategies to amplify and analyze DNA fragments of the proviral SU region from cells infected with REC-selected viruses, we found the occurrence of a single recombinant in which two-thirds of the SU gene from the N-terminus of FeLV-C was replaced by the endogenous FeLV element. This recombinant virus, when molecularly cloned, should be useful in determining its potential in vivo neuropathogenicity.
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PMID:Recombination between feline exogenous and endogenous retroviral sequences generates tropism for cerebral endothelial cells. 831 Nov 18

Erythropoietin (EPO) is a prime stimulating factor for red cell production. EPO is a glycoprotein which has a molecular weight of 34,000, and is mainly produced by the kidney. EPO stimulates the differentiation and proliferation of erythroid progenitor cells in the bone marrow. The rate of production of EPO is regulated primarily by renal oxygen availability. Because anemia reduces renal oxygen availability, anemic stress accelerates EPO production in the kidney. Recently, EPO has mainly been determined by radioimmunoassay. Serum EPO titer is usually inversely correlated with hemoglobin concentration, as typically shown in iron deficiency anemia. Serum EPO titers in aplastic anemia are much higher than those in iron deficiency anemia relative to the hemoglobin concentration. Serum EPO titers in anemia caused by malignancies sometimes differ considerably among patients. Serum EPO in renal anemia usually show low titers irrespective of the degree of anemia. Serum EPO titers in untreated polycythemia vera are lower than those in treated polycythemia vera or secondary polycythemia. Determination of serum EPO is useful in differential diagnosis of polycythemia vera. Recombinant human EPO has been used to treat various anemias including renal anemia, refractory anemia, anemia in malignancies and secondary anemia. Determination of serum EPO titers is also valuable in many other situations of clinical medicine.
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PMID:[Erythropoietin determination in clinical medicine]. 835 Apr 98

Erythroid aplasia is induced in cats by feline leukemia virus (FeLV) of subgroup C but not by FeLV of subgroup A. In an investigation of the role of macrophages in FeLV-C-induced diseases, the concentrations of FeLV and tumor necrosis factor-alpha (TNF-alpha) were compared between feline peritoneal macrophages incubated with FeLV of subgroup A or C. FeLV of both subgroups infected macrophages, but expression of FeLV-C was 21-fold higher than FeLV-A in peritoneal macrophages (P = .004). The supernatants of FeLV-C-inoculated macrophage cultures contained significantly higher levels of TNF-alpha (70 +/- 14 U/mL) at 72 hours postincubation compared with FeLV-A-inoculated (38 +/- 8 U/mL) and uninoculated (31 +/- 8 U/mL) cultures. Moreover, a positive correlation was shown between cell-associated FeLV surface glycoprotein gp70 and TNF-alpha expression in FeLV-C-infected macrophages by immunofluorescence (r = .6; P = .001), measured with a computer-assisted, laser-based digital imaging system. The addition of TNF-alpha to a uniform population of FeLV-infected cells (feline embryonic fibroblasts) caused an enhancement of viral expression (P < .05). These results indicate that FeLV-C has tropism for macrophages, FeLV expression is positively correlated with TNF-alpha expression in macrophages, and TNF-alpha enhances FeLV replication in fibroblasts. We suggest that FeLV-C infection of macrophages and secretion of TNF-alpha may be important in hematopoietic suppression in FeLV-C-infected cats.
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PMID:Macrophage tropism of feline leukemia virus (FeLV) of subgroup-C and increased production of tumor necrosis factor-alpha by FeLV-infected macrophages. 838 34

This study was initiated to evaluate the in vivo infectivity and pathogenicity of a group of recombinant feline leukemia viruses (rFeLVs) previously generated by in vitro forced recombination between a FeLV subgroup A virus (FeLV-A) and an endogenous FeLV (enFeLV) envelope (env) element (Sheets et al., 1992, Virology 190, 849-855). To determine infectivity of rFeLVs, neonatal cats were inoculated with rFeLVs alone or in combination with FeLV-A. The recombinant viruses were able to replicate efficiently in vivo only when administered along with FeLV-A. Of six co-infected cats, three developed thymic lymphosarcomas, one severe aplastic anemia, and two cachexia and depression; all were viremic and seroconverted shortly after inoculation. While both virus types were detected in virtually all tissues examined from these tumor-bearing cats, there was a particularly noteworthy sequence reversion in the rFeLVs. It is known that exogenous FeLV isolates carry a conserved neutralizing MGPNL epitope in the middle of the surface glycoprotein domain of the env gene. In contrast, the parental recombinant viruses used to inoculate these cats harbored the enFeLV-derived MGPNP sequence at this position. However, all in vivo-propagated recombinants displayed the MGPNL sequence, while the env-encoded backbone flanking the MGPNL sequence was that of the parental recombinant virus. These results suggest that viruses with the MGPNL epitope have an in vivo proliferative advantage. The data also provide an explanation for the conservation of this epitope in exogenous FeLVs despite the existence of variant forms in enFeLV proviral elements with which they can recombine.
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PMID:Feline leukemia virus variants in experimentally induced thymic lymphosarcomas. 855 60

Erythropoietin (EPO) is the glycoprotein hormone that promotes differentiation of erythroid progenitor cells in bone marrow. The normal kidney produces EPO to maintain erythrocyte for oxygen supply. This hormone activity was found in the serum of anemic animals in the 1890s. Renal failure results in severe anemia because of reduced EPO production, therefore anemia patients expected EPO treatment for long time. However, this was difficult due to the limited amount of EPO. Many researchers have tried to isolate EPO since the 1950s. Finally Miyake and Goldwasser purified highly active EPO from the urine of aplastic anemia patients. Since then, the characteristics and structural information from the purified material accelerated the cloning of the EPO gene. Mammalian cells were essential to produce EPO, because EPO contains 40% carbohydrate that plays some important roles in its activity, stability and biosynthesis. In 1984, two groups succeeded in cloning the EPO gene and expressing this gene in mammalian cells. Recombinant human EPO is currently available for anemia treatment. In this paper, we review production in mammalian cells, molecular characterization, especially carbohydrate moieties, and clinical applications of recombinant EPO.
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PMID:The production of recombinant human erythropoietin. 970 92

To detect levels of platelet glycoprotein-specific autoantibody in idiopathic thrombocytopenic purpura (ITP), chronic aplastic anemia (CAA), hematologic malignancies and healthy volunteers, and evaluate the clinical significance of platelet glycoprotein-specific autoantibody level in diagnosis for ITP, anti-GPIb/IX, anti-GPIIb/IIIa, anti-GPIV and anti-GPV auto-antibodies were detected contemporaneously by a modified monoclonal antibody immobilization of platelet antigen assay (modified MAIPA). The results showed that the total positive rate of antibodies against platelet GPIb/IX, GPIIb/IIIa, GPIV, GPV were 69.99%, 10%, 20% and 0% in ITP, CAA, hematologic malignancy group and healthy volunteers respectively. There was significant difference between ITP and CAA (chi(2) = 20.71, P < 0.005), between ITP and hematologic malignancy group (chi(2) = 12.22, P < 0. 005). There was no positive finding in the healthy control. It is concluded that platelet glycoprotein-specific autoantibody has high value for the diagnosis of ITP,many kinds of antibodies detection at one time can enhance sensitivity, MAIPA is a specific assay for the diagnosis of idiopathic thrombocytopenic purpura.
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PMID:[The diagnostic value of platelet glycoprotein-specific autoantibody detection in idiopathic thrombocytopenic purpura]. 1515 34

Reticulated platelets (RP) and large platelets (LP) were measured by an automated hematology analyzer (modified R-2000) in 287 healthy volunteers and 131 patients with thrombocytopenia or thrombocytosis. RP was significantly higher in patients with idiopathic thrombocytopenic purpura (ITP), especially in active phase, while RP was markedly lower in patients with essential thrombocytosis (ET) or chronic myelocytic leukemia (CML). LP was significantly higher in patients with ITP, especially in active phase, while LP was markedly lower in patients with aplastic anemia (AA), ET, or CML. In ITP, RP and LP were significantly higher in patients positive for anti-glycoprotein (Gp) IIb/IIIa antibody. RP and LP were poorly correlated with platelet-associated IgG (PAIgG). RP and LP were poorly correlated with plasma thrombopoietin levels, and negatively correlated with platelet count. These results show that RP reflects the pathology of thrombocytopenic disorders, and that measurement of RP is useful for the differential diagnosis and analysis of platelet kinetics.
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PMID:Usefulness of measurement of reticulated platelets for diagnosis of idiopathic thrombocytopenic purpura. 1601 10

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

Paroxysmal nocturnal hemoglobinuria (PNH) is caused by the clonal expansion of hematopoietic stem cells with mutations of the phosphatidylinositol glycan-class A gene (PIGA). PNH clones then fail to generate glycosylphosphatidylinositol (GPI) or to express a series of GPI-linked membrane proteins including complement-regulatory proteins, resulting in complement-mediated intravascular hemolysis and thrombosis. Bone marrow failure is another characteristic feature of PNH. It is currently considered that immune-mediated injury of hematopoietic cells is implicated in PNH marrow failure as well as in aplastic anemia, a well-known PNH-related disorder. There is increasing evidence that the autoimmune attack allows PNH clones to selectively survive in the injured marrow, leading to clinical manifestations characteristic of PNH. As candidate molecules that trigger the immune attack on marrow cells, stress-inducible membrane proteins and Wilms' tumor protein WT1 have been proposed. Among the stress-inducible proteins, GPI-linked proteins, such as cytomegalovirus glycoprotein UL16-binding protein, are distinct candidates that not only induce immune attack, but also allow PNH clones to survive the attack. Here, we overview the current understanding of the molecular pathogenesis of bone marrow failure in PNH.
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PMID:New insights into molecular pathogenesis of bone marrow failure in paroxysmal nocturnal hemoglobinuria. 1767 63


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