Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Friend virus (FV) is a murine leukemia virus that infects progenitor red blood cells and causes an erythroleukemia in susceptible mouse strains, resulting in splenomegaly. Several genetic loci of the host have been identified that affect erythroleukemia development, differentiation status of target cells and virus replication. Since age may change expression of these loci, age may affect FV disease. To explore this possibility, FV expression in four genetically diverse strains of mice of different ages was examined. Extent of viral replication and of disease were evaluated by measuring spleen focus forming units (SFFU), spleen weight and reverse transcriptase (RT) activity in target organs. Young DBA/2 and (C57BL/6 x DBA/2)F1 mice exhibited a greater level of virus expression than their aged counterparts in all parameters investigated. Young CBA/Ca mice had slightly higher spleen weights and SFFU values than aged CBA/Ca mice, but a definitive age-related change was not observed in the RT activity of the target organs. C57BL/6 mice, which are genetically resistant to the development of FV-induced erythroleukemia, exhibited a limited degree of virus replication that was not effected by the age of the animal. Our results indicate that the age of the mouse, as well as the genetic background, can contribute to the level of susceptibility to FV.
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PMID:Differences between young and aged mice in susceptibility to Friend virus. 751 1

Previous studies in transgenic mice and cultured cells have indicated that the major enhancer function for erythroid cell expression of the globin genes is provided by the heterodimeric basic-leucine zipper transcription factor NF-E2. Globin gene expression within cultured mouse erythroleukemia cells is highly dependent on NF-E2. To examine the requirement for this factor in vivo, we used homologous recombination in embryonic stem cells to generate mice lacking the hematopoietic-specific subunit, p45 NF-E2. The most dramatic aspect of the homozygous mutant mice was an absence of circulating platelets, which led to the death of most animals due to hemorrhage. In contrast, the effect of loss of NF-E2 on the erythroid lineage was surprisingly mild. Although neonates exhibited severe anemia and dysmorphic red-cell changes, probably compounded by concomitant bleeding, surviving adults exhibited only mild changes consistent with a small decrease in the hemoglobin content per cell. p45 NF-E2-null mice responded to anemia with compensatory reticulocytosis and splenomegaly. Globin chain synthesis was balanced, and switching from fetal to adult globins progressed normally. Although these findings are consistent with the substitution of NF-E2 function in vivo by one or more compensating proteins, gel shift assays using nuclear extracts from p45 NF-E2-null mice failed to reveal novel complexes formed on an NF-E2 binding site. Thus, regulation of globin gene transcription through NF-E2 binding sites in vivo is more complex than has been previously appreciated.
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PMID:Erythropoiesis and globin gene expression in mice lacking the transcription factor NF-E2. 756 98

D-aspartic beta-hydroxamate (DAH), an aspartic acid analog, exerts antitumoral activity on murine leukemia L5178Y, both in vitro and in vivo. In this study, we show that DAH is also active in vivo against Friend virus (FV-P)-induced erythroleukemia, and we report the effects of DAH in vivo an in vitro on FV-P target cells, i.e. the mature erythroid colony-forming cells (CFU-E). DAH treatment (2 g/kg/day) given for 95 days as a single daily i.p. injection to DBA/2 mice either 3 or 12 days following inoculation with a high dose (10(3) plaque-forming units) of FV-P resulted in a marked increase in the mean survival time of treated animals (212 and 191%, respectively). Since FV-P elicits spleen enlargement and polycythemia, we examined the effects of DAH on spleen size, spleen-nucleated cell number, and hematocrit, in normal and FV-P infected mice, at different times in the course of continuous DAH treatments. DAH treatment initiated 3 days after viral infection inhibits the virus-induced splenomegaly, with at day 26 p.i. 1.15 x 10(8) and 12.6 x 10(8) nucleated cells per spleen observed in DAH-treated mice and untreated mice respectively, whereas only 1.03 x 10(8) nucleated cells were observed in uninfected mice. Furthermore, DAH prevents virus-induced polycythemia: on day 26, an hematocrit of 39% was measured in DAH-treated mice as compared to 60% in untreated mice. DAH treatment initiated 12 days after viral infection reduces splenomegaly, the number of nucleated spleen cells and the hematocrit of infected mice. DAH treatment initiated 3 days after viral infection prevents the tremendous increase of CFU-E in the spleen of infected mice: on day 11, the spleen of infected mice contained 4.6 x 10(6) CFU-E, while the spleen of treated mice only contained 26 x 10(3) CFU-E, and on day 26 the spleen CFU-E numbers were 45.4 x 10(6) and 1.5 x 10(6) in untreated and treated infected mice, respectively. In control uninfected mice, DAH treatment induced a transient decrease in spleen CFU-E followed by a rebound phenomenon. In vitro, preincubation with DAH inhibits colony formation by FV-P infected CFU-E, at doses starting at 3 mM, as compared to uninfected CFU-E. These data show that DAH inhibits the expression of the retroviral infection, and appears to preferentially inhibit the proliferation of infected target cells (CFU-E) in vivo.
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PMID:Antiproliferative effect of D-aspartic acid beta-hydroxamate (DAH) on Friend virus-infected erythropoietic progenitor cells. 793 66

A 19 years old male admitted to our hospital with fever, abdominal pain in May 1991. Physical examination revealed anemia, jaundice and marked splenomegaly. Severe pancytopenia with macrocytic hyperchronic anemia was noted along with elevated LDH and reduced serum folate. Blood smear showed nucleated RBCs, but only few microspherocytes. Bone marrow showed erythroid hyperplasia with remarkable megaloblastic changes. Megaloblasts were negative for PAS stain. Chromosome analysis revealed normal karyotype. Erythroleukemia was suspected initially, but his general condition as well as hematological data improved following 10 units of RBC transfusion. Following brief folic acid supplements, numerous microspherocytes became evident, typical osmotic fragility test revealed a pattern for hereditary spherocytosis. These observations led us to the diagnosis of hereditary spherocytosis complicated by megaloblastic anemia due to folate deficiency. As he developed folate deficiency again 10 months later, splenectomy were performed. The anemia improved after splenectomy.
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PMID:[Megaloblastic anemia due to folate deficiency associated with hereditary spherocytosis]. 802 87

D-aspartic acid beta-hydroxamate (DAH), an aspartic acid analogue, exerts anti-tumoral activity against murine leukemia L5178Y both in vitro and in vivo. We show here that DAH displays activity against Friend leukemia cells (FLC) in vitro: a concentration of 2 mM results in a total inhibition of cell growth. DAH is also active in vivo against Friend virus (FV-P)-induced erythroleukemia. Treatment with DAH, given for 95 days as a single daily i.p. injection to DBA/2 mice 3 days following FV-P inoculation, induced a marked increase of 212% in the mean survival time (MST) of treated animals. Since FV-P-induced erythroleukemia is characterized by the proliferation of mature erythroid precursors, we examined the effect of DAH treatment on erythroid colony-forming cells (CFU-E) and observed that the number of CFU-E per spleen was 30 times lower in DAH-treated mice than in the controls. To gain further insight into the early effects of DAH treatment on the early phase of Friend disease, we examined the effects of short DAH treatment on spleen size, hematocrit and viremia in FV-P-infected mice. DAH treatment initiated 3 days post infection (p.i.) inhibited splenomegaly, prevented virus-induced polycythemia, and reduced serum viremia. Late DAH treatment (18 days p.i.) induced regression of FVP-induced disease as evidenced by reduction of spleen weight.
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PMID:Therapeutic effects of D-aspartic acid beta-hydroxamate (DAH) on Friend erythroleukemia. 805 Aug 23

The proto-oncogene Fli-1 is a member of the ets family of transcription factor genes. Its high expression in the thymus and spleen and the presence of DNA binding sites for Fli-1 in a number of lymphoid cell-specific gene suggest that Fli-1 is involved in the regulation of lymphopoiesis. Activation of the Fli-1 gene by either chromosomal translocation or viral insertion leads to Ewing's sarcoma in humans and erythroleukemia in mice, respectively. Thus, Fli-1 is normally involved in pathways involved in the regulation of cell growth and differentiation. We have generated H-2Kk-Fli-1 transgenic mice that overexpress Fli-1 in various mouse tissues, with the highest levels of Fli-1 protein in the thymus and spleen. These Fli-1 transgenic mice developed a high incidence of a progressive immunological renal disease and ultimately died of renal failure caused by tubulointerstitial nephritis and immune-complex glomerulonephritis. The incidences of renal disease correlated with the levels of Fli-1 protein in lymphoid tissues of transgenic lines. The hypergammaglobulinemia, splenomegaly, B-cell hyperplasia, accumulation of abnormal CD3+ B220+ T lymphoid cells and CD5+ B220+ B cells in peripheral lymphoid tissues, and detection of various autoantibodies in the sera of diseased Fli-1 transgenic mice suggested the involvement of an immune dysfunction in the pathogenesis of the renal disease. In addition, splenic B cells from transgenic mice exhibited increased proliferation and prolonged survival in vitro in response to mitogens. Taken together, these data suggest that overexpression or ectopic expression of Fli-1 perturbs normal lymphoid cell function and programmed cell death. Thus, H-2Kk-Fli-1 transgenic mice may serve as a murine model for autoimmune disease in humans, such as systemic lupus erythematosus.
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PMID:An immunological renal disease in transgenic mice that overexpress Fli-1, a member of the ets family of transcription factor genes. 852 63

Rauscher murine leukemia virus induces an erythroleukemia in susceptible strains of mice that is associated with splenomegaly and viremia. This animal model has been used for evaluating the in vivo efficacy of potential anti-HIV agents. The in vivo antiviral activity of therapeutic agents has usually been determined by measuring a reduction in the spleen weights of compound-treated mice or by quantitating viremia with the UV-XC plaque assay. The UV-XC assay, however, is time-consuming and labor-intensive. Virions of Rauscher murine leukemia virus, like other retroviruses, contain the enzyme reverse transcriptase. Quantitating the level of this enzyme in infected mouse sera provides a more rapid measure of viremia in the animal. We have examined the effects of several reagents, including detergent, KCl, EGTA, dGMP, spermine, as well as protease and RNase inhibitors, on the reverse transcriptase assay. The optimized assay method was effective in evaluating the antiviral activity of AZT in the Rauscher murine leukemia virus in vivo model. The assay is also amenable to automation if large numbers of assays are required.
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PMID:Optimization of the reverse transcriptase assay for the detection of viral burden in mice infected with Rauscher murine leukemia virus. 891 Jun 49

Several immunological epitopes are known to be located within the Friend murine leukemia virus (F-MuLV) envelope protein, but their relative contributions to protection from Friend virus-induced disease are not known. To determine how expression of various immunological determinants affected protection, mice were immunized with recombinant vaccinia viruses expressing different portions of the F-MuLV envelope protein, and they were then challenged with a lethal dose of Friend virus complex. The disease parameters that were followed in the mice were early viremia, early splenomegaly, and late splenomegaly. Both the N-terminal and C-terminal portions of the F-MuLV gp70 were found to protect against late splenomegaly, the primary clinical sign associated with virus-induced erythroleukemia. However, neither region alone protected against early splenomegaly and early viremia, indicating poor immunological control over early virus replication and spread through the spleen and blood. In contrast, mice immunized with a vaccine expressing the entire F-MuLV envelope protein were protected against all three disease parameters. The results indicated that expression of multiple immunological determinants including both T-helper and B cell epitopes was necessary for full protection.
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PMID:Immunoprotective determinants in friend murine leukemia virus envelope protein. 970 56

The study of genetic resistance to retroviral diseases provides insights into the mechanisms by which organisms overcome potentially lethal infections. Fv-2 resistance to Friend virus-induced erythroleukemia acts through nonimmunological mechanisms to prevent early virus spread, but it does not completely block infection. The current experiments were done to determine whether Fv-2 alone could provide resistance or whether immunological mechanisms were also required to bring infection under control. Fv-2-resistant mice that were CD4(+) T-cell deficient were able to restrict early virus replication and spread as well as normal Fv-2-resistant mice, but they could not maintain control and developed severe Friend virus-induced splenomegaly and erythroleukemia by 6 to 8 weeks postinfection. Mice deficient in CD8(+) T cells and, to a lesser extent, B cells were also susceptible to late Friend virus-induced disease. Thus, Fv-2 resistance does not independently prevent FV-induced erythroleukemia but works in concert with the immune system by limiting early infection long enough to allow virus-specific immunity time to develop and facilitate recovery.
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PMID:Lymphocyte deficiencies increase susceptibility to friend virus-induced erythroleukemia in Fv-2 genetically resistant mice. 1040 Jul 41

The plant alkaloid camptothecin (CPT) has demonstrated the ability to inhibit replication of the equine anemia virus (E1AV) and the human immunodeficiency virus (HIV) in infected cells in culture. Further, CPT prevented the development of lymphoma and erythroleukemia in mice infected with the Moloney murine leukemia virus and the Friend erythroleukemia virus, respectively, as assessed by prevention or reduction of splenomegaly. These results were observed at concentrations that had no apparent toxic effects on the mice. It has been suggested that the antiretroviral activity of CPT is mediated by the host cell's enzyme topoisomerase I. Taken collectively, the findings indicate that CPT analogues may develop into potent drugs against various human and animal diseases caused by diverse retroviruses. Copyright 1996 S. Karger AG, Basel
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PMID:Camptothecin: A Promising Antiretroviral Drug. 1172 78


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