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)

Results reported herein describe the expansion of erythroid stem cells (CFU-e and BFU-e) from marrow and spleen cells from mice infected with Rauscher leukemia virus (RLV). Maximum colony numbers were seen by 5 weeks after viral inoculation. The increase in splenic CFU-e and BFU-e was related to development of splenomegaly, the latter being a characteristic feature of murine oncornavirus infection. Both splenic and marrow RLV-derived CFU-e were erythropoietin (Ep) dependent. However, splenic and marrow RLV-derived BFU-e proliferation occurred at Ep levels considered suboptimal for normal colony formation. This increased erythroid stem cell proliferation may be due in part to the increased demand on erythropoiesis as a result of the profound fatal anemia which occurs in RLV-induced erythroleukemia. These studies suggest that factors operating at the level of BFU-e may enhance erythropoiesis, and hence may be a direct result of murine oncornavirus infection.
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PMID:Erythroid stem cells in Rauscher viral erythroleukemia. 657 88

Two distinct clones of Friend spleen focus-forming virus (SFFV), differing in their erythroleukemic potential, are described. These isolates have been cloned free of their associated helper viruses and shown to be replication-defective. Both SFFV isolates have been rescued from rat fibroblast nonproducer cell clones with cloned replication-competent viruses, F-MuLVA and F-MuLVP, obtained from the anemia- or polycythemia-inducing isolates of Friend virus complex, respectively. These rescued viruses induce a rapid proliferative disease associated with the appearance of macroscopic spleen foci and splenomegaly. In addition, each is subject to regulation by the W, Steel (Sl), and Fv-2 host gene loci. These two isolates of SFFV can, however, be distinguished by both biological and molecular criteria. Friend SFFVP induces a rapid polycythemia associated with the appearance of large numbers of erythropoietin (EPO)-independent erythroid colony-forming cells in the marrow and spleen. In contrast, SFFVA induces a rapid anemia associated with a progressive decrease in the number of EPO-dependent erythroid colony-forming cells in marrow, and a rapid increase in the number of EPO-dependent erythroid colony-forming cells in spleen. Furthermore, the nature of the disease induced by the two isolates of SFFV is independent of the Friend helper virus: SFFVP, rescued from a nonproducer cell clone with either F-MuLVA or F0MuLVP, induced a polycythemic transformation, whereas SFFVA, rescued with either F-MuLVA or F-MuLVP, induced an anemic transformation. The two Friend SFFV isolates can also be discriminated on the basis of translational products encoded by their gag and env genes: SFFVP encodes the amino-terminal gag-gene protein p15, whereas SFFVA encodes the gag-gene proteins p15, p12, and p30. In addition, the SFFV isolates encode nonidentical 55,000-mol wt env gene-related proteins that can be distinguished by analysis of their methionine-containing tryptic peptides.
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PMID:Anemia- and polycythemia-inducing isolates of Friend spleen focus-forming virus. Biological and molecular evidence for two distinct viral genomes. 692 80

The prognostic value of different clinical and laboratory findings at diagnosis of chronic myeloid leukemia (CML) was analyzed in a series of 121 cytogenetically studied patients. From the univariate and multivariate analysis of the whole series it was apparent that the minority of Ph1-negative patients (11.5%) could be considered as a poor prognosis group. The analysis was then restricted to the Ph1-positive patients. From a multivariate survival analysis (Cox's regression model) of the latter group the following poor prognosis factors emerged: splenomegaly, hepatomegaly, presence of erythroid precursors in peripheral blood, and bone marrow myeloblasts over 5%. From the contribution of each one of these factors to the regression model, a clinical staging of Ph1-positive CML was derived: stage I (low risk, 32% of patients), including patients with one or no factors; stage II (intermediate risk, 38%), including cases with two factors; and stage III (high risk, 30%), including patients with three or four factors. The difference in survival of the patients at different stages was highly significant (p less than 0.001).
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PMID:A multivariate analysis of prognostic factors in chronic myeloid leukemia. 695 36

Myelomonocytic myeloproliferative disease in a horse was diagnosed on the basis of hematologic, enzymatic, and histopathologic findings. It was characterized clinically by depression, weight loss splenomegaly, lymphadenopathy, coagulopathy, and bacteremia. Hematologic findings included severe refractory anemia, thrombocytopenia, monocytosis, and pleomorphic leukocytes, with a left shift of the myeloid series. The serum lysozyme concentration was 14.5 microgram/ml (normal, less than 5 microgram/ml). The bone marrow contained many immature cells of the myeloid series and had a myeloid-to-erythroid ratio of 30.5 to 1. The horse died after brief hospitalization. Necropsy revealed generalized lymphadenopathy and hemorrhages throughout the body. Histopathologically, primitive cells were seen in several tissues. Cells that proliferated in the bone marrow were primarily myeloblastic, with some additional erythropoietic cells. Myeloblastic cells with evidence of normal erythropoiesis were seen in numerous lymph nodes and in the spleen, whereas primarily normal erythropoietic cells proliferated in the adrenal glands. Myeloid blast-type cells predominated in the lungs, myocardium, liver, and kidneys.
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PMID:Myelomonocytic myeloproliferative diseases in a horse. 705 85

Infection of mice with Friend erythroleukemia virus initially causes massive proliferation of erythroid precursors accompanied by splenomegaly and reticulocytosis. Strains of mice differ among themselves in susceptibility to Friend virus and one of the major genes affecting the early response to viral infection is Fv-2. Allophenic mice compounded from a resistant strain C57BL/6 (Fv-2rr) and a susceptible one DBA/2 (Fv-2ss) were infected with the polycythemic strain of Friend virus to determine whether susceptibility/resistance was limited to cells of the respective genotypes or if there was an influence across the genotypic barriers. The manifestations of viral pathogenesis monitored were splenomegaly, reticulocytosis and leukocytosis. In addition, the proportion of red cells of the two genotypes in each animal was monitored before and after viral infection by analyses for strain specific electrophoretic variants of hemoglobin and glucose phosphate isomerase. The group of allophenic mice with 25% or more susceptible-strain red blood cells all developed symptoms of virus-induced disease and also revealed dramatic increases in the number of red cells of the susceptible-strain genotype. Thus, no evidence for protection of susceptible-strain cells by ones of the resistant strain could be observed and the disease developed primarily in susceptible strain cells. On the other hand infected animals with 15% or less DBA/2 red cells were severely retarded in the development of Friend disease. Under these circumstances susceptible strain target cells might fail to undergo viral induced replication as a result of direct protection by resistant strain cells. Alternatively, other more complex mechanisms might be involved such as protective anti-viral immune reactions.
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PMID:Friend viral pathogenesis in C57BL/6 reversible DBA/2 allophenic mice. 717 42

The effects of low-dose gamma radiation to haemopoietic progenitor cell compartments of the marrow and spleen of virgin female mice and pregnant mice were studied. Microplasma clot cultures were used to asses burst-forming unit-erythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) activity, and double-layer agar cultures were established to evaluate granulocyte-macrophage colony-forming cell (GM-CFC) and macrophage colony-forming cell (M-CFC). The apparent shift in maternal erythropoiesis from the bone marrow to the enlarged spleen was reflected by an increase in the numbers of CFU-E and BFU-E per spleen and a concomitant decrease in CFU-E and BFU-E per femur. Whereas maternal GM-CFC values per femur increased 36%, maternal GM-CFC per spleen increased by 172% compared to virgin values. There was a greater decrease in M-CFC per spleen than per femur in the pregnant animal when values were compared to the virgin animal. Total-body irradiation to the day-10.5 pregnant mouse caused a further suppression of day-14.5 medullary erythropoiesis (i.e. decreased CFU-E values) compared to the response of the virgin female mouse. An ability of the maternal spleen to support further compensatory erythropoiesis following increasing doses of radiation was demonstrated. 4 d after 1.0 Gy exposure, maternal values for GM-CFC per femur or spleen decreased to nonirradiated virgin mice values. M-CFC per maternal femur decreased following 1.5 Gy, but M-CFC per spleen appeared to be unaffected with doses from 0.5 to 2.0 Gy.
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PMID:Effect of low-dose irradiation on pregnant mouse haemopoiesis. 724 84

Hematological effects of tilorone, an interferon inducer, on the hematopoietic cell system of normal CBA/Ca mice and on the development of Friend virus (FV-P)-induced polycythemia in DBA/2 mice were studied. In normal mice 80 mg/kg IP had a marked depressive effect on pluripotent (CFU-s), granuloid committed (CFU-C), and erythroid committed (CFU-E) stem cells with regeneration between days 5 and 12. In bone marrow smears only lymphopenia was detected. Treatment of mice before FV-P infection caused a slight retardation in the development of the splenomegaly and the transformation of bone marrow cells to Ep independence. Repeated treatment after FV-P infection also reduced the increase in spleen weight and the development of reticulocytosis, but the Ep independence of bone marrow and spleen cells was not influenced. In vitro exposure of normal cells and cells from FV-P-infected animals to the drug showed the same sensitivity of colony growth in normal as well as in Ep-independent CFU-E. The action of the drug on Friend leukemia is at least in part considered a toxic effect on the hematopoietic stem cell system.
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PMID:Effects of tilorone on hemopoietic stem cells and on the development of Friend leukemia. 746 Jan 94

Synthetic peptide vaccines containing a single Th cell epitope identified in the gp70 envelope glycoprotein of Friend murine leukemia helper virus induced potent protective immunity against Friend virus infection. H-2a/b mice immunized by a single s.c. injection of the CFA emulsion containing a peptide that represented the N-terminal gp70 epitope recovered slowly from initial development of splenomegaly, and most did not develop late leukemia, whereas most of the control mice given an injection of CFA alone showed sustained leukemic splenomegaly after the challenge with Friend virus. The mice of the same genetic background immunized with the C-terminal Th cell epitope by a single injection of a separate synthetic peptide eliminated virus-producing cells from the spleen within 12 days after inoculation of Friend virus complex, and did not develop early splenomegaly or polycythemia. H-2a/a mice were not protected by immunization with either one of the two synthetic peptides. Earlier production and more rapid class switching of virus-neutralizing Abs were observed in H-2a/b mice immunized with the peptide vaccines after the challenge with Friend virus, compared with the responses of the control mice. Detailed kinetic and immunohistopathologic analyses suggested that Th cells might be directly involved in the growth inhibition and elimination of virus-infected erythroid precursor cells.
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PMID:Immunization with a single T helper cell epitope abrogates Friend virus-induced early erythroid proliferation and prevents late leukemia development. 754 23

It has been suggested that acquired abnormalities of the red cell membrane due to various injuries [azidothymidine (AZT) therapy, immunoglobulin coating of red cells, differentiation abnormalities of erythroid precursors] contribute to the onset of anaemia in HIV-infected patients. In vitro proteolysis of erythrocyte membrane proteins is regarded as a molecular marker of membrane damage induced in vivo by different agents. We therefore investigated in vitro proteolysis of ghosts derived from red blood cells of 30 HIV-infected patients. Considered collectively, there was no significant increase in in vitro proteolysis in ghosts from anaemic HIV patients. However, a significantly higher degree of in vitro self-digestion of RBC membrane proteins was evident in HIV-infected patients with spleen enlargement, but not in splenomegalic patients suffering from liver cirrhosis. Neither AZT therapy nor the presence of a positive direct antiglobulin test seemed to be directly associated with increased in vitro protein breakdown. The results seem to suggest damage of the red cell membrane in HIV infection, induced by injuries on red cells during their prolonged retention inside an enlarged spleen, while it seems unlikely that AZT therapy or immunoglobulin coating of red cells play major roles in red cell damage.
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PMID:In vitro proteolysis of the red cell membrane in patients with HIV infection. 754 74

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


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