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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A colinear molecular clone of the Lilly-Steeves polycythemia strain of Friend spleen focus-forming virus (SFFV) was modified by inserting a 215-base-pair tag of simian virus 40 DNA into its nonfunctional pol gene region. The DNA was then transfected into psi-2 packaging cells, and helper-free tagged SFFV was recovered in the culture medium. Injection of this helper-free virus into NIH/Swiss mice caused transient mild splenomegaly and formation of spleen foci at 9 to 10 days. Although the vast majority of infected erythroblast clones then differentiated and died out, rare cell clones that were present in only 20 to 30% of the mice grew extensively by 26 to 33 days to form transplantable leukemias. The clonality of these leukemias was established by Southern blot analysis of their DNAs by using several restriction endonucleases and the simian virus 40 tag as a hybridization probe. All transplantable leukemias lacked helper virus contamination and contained a single tagged SFFV provirus that expressed the mitogenic env gene product gp55. The SFFV proviruses in these leukemias also appeared to be integrated into a few tightly clustered sites in the cellular genome. Although the tagged SFFV caused polycythemia during the polyclonal early stage of erythroblastosis, growth of the helper-free clonal erythroleukemias caused severe anemia. These results suggest that a single SFFV can cause mitosis of erythroblasts, and that cell immortalization also occurs when the provirus integrates into a critical site in the host genome. We propose that mice with clonal-stage leukemia become anemic because the immortalizing proviral integrations interfere with the cellular commitment to differentiate.
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PMID:A tagged helper-free Friend virus causes clonal erythroblast immortality by specific proviral integration in the cellular genome. 284 27

Purified recombinant human heavy-chain (acidic) ferritin (rHF) was assessed in vivo in mice for effects on the proliferation (percentage of cells in S-phase) and absolute numbers of granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells in the femur and spleen and on the nucleated cells in the marrow, spleen, and blood. rHF significantly decreased cycling rates and absolute numbers of marrow and splenic hematopoietic progenitors and marrow and blood nucleated cellularity. These effects were apparent in BDF1, C3H/Hej and DBA/2 mice and were dose dependent, time related, and reversible. Suppressive effects were noted within three hours for progenitor cell cycling, within 24 hours for progenitor cell numbers, and within 48 hours for circulating neutrophils. Additionally, hematopoietic progenitor cells in DBA/2 mice infected with the polycythemia-inducing strain of the Friend virus complex (FVC-P) were insensitive to the in vivo administration of rHF. These studies demonstrate activity of rHF in vivo on myelopoiesis of normal but not FVC-P-infected mice. Since rHF suppresses hematopoietic progenitor cell proliferation from normal donors in vitro and from normal mice in vitro and in vivo but does not suppress progenitor cells from patients with leukemia in vitro or from mice with FVC-P-infection in vitro or in vivo, rHF may be useful as a candidate adjunct molecule for the protection of normal hematopoietic progenitor cells during chemotherapy.
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PMID:Suppressive effects in vivo of purified recombinant human H-subunit (acidic) ferritin on murine myelopoiesis. 291 Mar 70

To define the action of the retroviral src gene on hematopoietic stem cells, C57BL/6 x DBA/2 (B6D2F1) mouse long-term marrow cultures were infected at initiation with Moloney murine leukemia virus (MuLV) pseudotypes of src-recombinant retroviruses with the src gene inserted in the env region of an amphotropic MuLV (src-Ampho), or in the gag region of Moloney MuLV (src-Mo). Other cultures were infected with Friend spleen focus-forming virus polycythemia-inducing strain (SFFVp), Moloney MuLV, or amphotropic MuLV, or were uninfected controls. Harvested nonadherent cells were tested weekly for multilineage, granulocyte-erythroid-megakaryocyte macrophage (CFU-GEMM) colony formation in vitro in recombinant murine IL-3 and erythropoietin, and individual colonies were removed, split 1:2, with half of each replated for in vitro self-renewal and the other half examined morphologically for number of hematopoietic cellular lineages, or tested for release of MuLV and src virus. Cultures infected with src-Ampho, src-Mo, or SFFVp demonstrated a significant increase in cumulative nonadherent cell and CFU-GEMM production. There was prolonged self-renewal over seven serial transfers of individual CFU-GEMM from src virus-infected cultures over seven serial transfers, and five of 61 individual colonies from the second or third generations contained detectable v-src gene sequences, but none released detectable src virus. Self-renewal of CFU-GEMM was similar to that with permanent IL-3-dependent cell line B6SUtA. In contrast, MuLV-infected or control uninfected cultures produced fewer cells, and self-renewal of CFU-GEMM did not exceed three generations. IL-3-dependent clonal hematopoietic progenitor cell lines, derived from each culture group, formed no detectable tumors in vivo; however, each released the original helper and/or transforming virus. Adherent cell lines, derived from src-Ampho-infected cultures released src virus and formed fibro-sarcomas in vivo. The data support the conclusion that src-recombinant virus expression in long-term marrow cultures increases the self-renewal capacity of multilineage hematopoietic stem cells.
Leukemia 1989 Mar
PMID:Retroviral src gene expression in continuous marrow culture increases the self-renewal capacity of multilineage hematopoietic stem cells. 291 58

Effects of Friend leukemia virus (FLV) inoculation in F1 specific pathogen free (SPF) mice were examined. Resistance to FLV was dominantly inherited both in F1 hybrid mice (BDF1) (FLV-resistant & FLV-sensitive with polycythemia) and F1 hybrid mice (B6C3F1) (FLV-resistant & FLV-sensitive with anemia). But the population dynamics of the nucleated cell components of F1 mice after FLV inoculation differed from those of FLV-resistant inbred mice. A small number of mature erythroblasts appeared in the peripheral blood of BDF1 mice. In B6C3F1 mice, erythroblastosis with splenomegaly and polycythemia occurred. However, all of these findings in BDF1 and B6C3F1 mice regressed spontaneously. In F1 mice, FLV induced an intermediate reactive pattern of the two patterns that had been induced in the parental strains. The results indicate that FLV may induce leukemia with various degrees of differentiation, according to the genetic difference of the host.
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PMID:Effects of Friend leukemia virus (FLV) inoculation in F1 mice and differentiation of FLV-induced leukemia. 298 Jan 28

The polycythemia-inducing strain of Friend virus (FV-P) causes a multistage erythroleukemia in susceptible mice. FV-P is a complex of two viruses, a replication-competent virus [Friend murine leukemia virus (F-MuLV)] and a replication-defective spleen focus-forming virus (SFFVp). We have addressed directly the role of SFFVp in the induction of the early stages of Friend disease by constructing stocks of SFFVp free of detectable F-MuLV, using a recently described retroviral helper-cell line. These preparations are capable of inducing erythroid bursts (vBFU-E) whose inducibility, kinetics, and responsiveness to erythropoietin suggest that they are very similar, if not identical, to the vBFU-E induced by FV-P. Single injections of helper-free SFFVp had no apparent effects in vivo, although the addition of exogenous helper virus to the inoculum resulted in the induction of classic Friend disease. Increasing the effective titer by giving mice five daily virus injections resulted in the induction of splenomegaly and a large increase in the number of erythroid colony-forming units that were independent of erythropoietin. When the injections were discontinued, the spleens regressed and all the mice survived. When the injections were continued, all the mice died within 25 days of the first injection. These results demonstrate that SFFVp alone can alter the growth characteristics of erythroid progenitors and is directly responsible for the induction of vBFU-E in vitro and the erythroid hyperplasia in vivo. They also demonstrate that the initial polyclonal stage of Friend disease is reversible and can be reproduced by using preparations of SFFVp free of detectable F-MuLV.
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PMID:Induction of the early stages of Friend erythroleukemia with helper-free Friend spleen focus-forming virus. 299 92

A novel murine retrovirus complex was derived from the in vivo passage of a molecularly cloned Friend ecotropic helper virus. The virus isolate, myeloproliferative leukemia virus (MPLV), causes an acute (2-3 weeks) and generalized myeloproliferative disorder in adult mice. All strains of mice examined, including the C57BL/6J strain, developed the acute syndrome. This syndrome is characterized by a rapid hepatosplenomegaly, no thymus or lymph node involvement, granulocytosis, thrombocytosis, and erythroblastosis leading to polycythemia. The most prominent feature at the terminal phase of the disease is a granulocytic hyperplasia. The MPLV isolate replicates in vitro on NIH 3T3 fibroblasts but does not induce foci of transformed cells. Thus, MPLV exhibits unique biological properties that distinguish it either from the Friend virus complexes or from acutely transforming sarcomatogenic murine retrovirus which also induced a rapid splenomegaly.
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PMID:MPLV: a retrovirus complex inducing an acute myeloproliferative leukemic disorder in adult mice. 300 28

The erythroleukemia induced by the Friend spleen focus-forming virus (SFFV) in mice exemplifies a multistep oncogenic process. Its sequential steps include a rapid polyclonal hyperplastic stage and a more slowly developing malignant stage characterized by autonomous erythroid cells. We report here that the helper virus normally present in mice infected by SFFV is not required for development of the second stage of transformation. In this study, mice were infected with a polycythemia-inducing variant of SFFV which was prepared as a helper-free stock (L. Wolff and S. Ruscetti, 1985, Science 228, 1549). Highly malignant cells could be detected in helper-free SFFV-infected mice by their transplantability into the omentum of sublethally irradiated mice, and erythroleukemia cell lines, typical of previously isolated Friend murine erythroleukemia cell lines, could be established from diseased spleens. Like their helper virus-containing counterparts, the lines established with helper-free SFFV are inducible for hemoglobin synthesis with a variety of chemicals, but not erythropoietin, and express p53, a marker of malignant transformation. Although the cells expressed SFFV encoded proteins, none expressed gene products of replication competent murine leukemia viruses.
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PMID:Induction of the autonomous stage of transformation in erythroid cells infected with SFFV: helper virus is not required. 301 73

Purified iron-saturated human lactoferrin (LF) was assessed in vivo for effects on the survival rates of C57BL X DBA/2 f1 (hereafter called BD2F1) (Fv-2sr) mice and titers of spleen focus-forming viruses (SFFV) in BD2F1 and DBA/2 (Fv-2ss) mice inoculated with the polycythemia-inducing strain of the Friend virus complex (FVC-P). LF prolonged the survival rates and decreased the titers of SFFV in mice given FVC-P. Titers of SFFV, assayed 14 days after administration of FVC-P, were measured by the spleen focus-forming unit assay in secondary mouse recipients. Decreases in titers of SFFV were apparent when LF was given in vivo as a single bolus dose of 200 micrograms within 2 h of the Friend virus complex (FVC), or as a total dosage of 200 micrograms given on days 1, 2, 4, 7, 9, and 11 after FVC-P, and to a lesser degree when LF was given as a total dosage of 200 micrograms on days 3, 4, 7, 9, and 11 after FVC-P. No decreases in titers of SFFV were detected when LF was given up to 3 days before or more than 3 days after FVC-P. LF did not appear to be directly inactivating the viruses as it did not inactivate the SFFV or the Friend murine leukemia helper virus in vitro. The results suggest that the protective effect of LF in vivo is probably due to an action on cells responding to the FVC or to an action on cells which influence the cells responding to the FVC or which influence the virus. It has been shown elsewhere that LF decreases the percentage of marrow and spleen hematopoietic progenitor cells that are in DNA synthesis in vivo and this may be the means by which the protective effect of LF is mediated in mice given the FVC.
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PMID:Protective influence of lactoferrin on mice infected with the polycythemia-inducing strain of Friend virus complex. 303 9

A multitude of general disorders of the vascular system may also affect the blood circulation of the cochlea and cause symptoms such as fluctuating or permanent hearing loss. Such is the case for arteriosclerosis combined with hypertension or hypotension, collagenosis, and diabetes. Blood disorders, like leukemia, sickle cell anemia, and polycythemia, and infectious diseases involving the blood vessels, such as lues, may also present their primary symptoms in the ear. The otorhinolaryngologist must be able to establish the correct diagnosis and refer patients requiring more general treatment to other specialists. The use of specific vasoactive treatment should be continued to those patients with symptoms of acute or fluctuating hearing loss, vertigo, or tinnitus who exhibit no other signs. Modern techniques for cochlear blood flow measurements have verified that several of the treatment protocols in use, which have a sound theoretical background, do indeed increase cochlear blood flow.
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PMID:Clinical treatment of vascular inner ear diseases. 306 94

Mice infected with the polycythemia-inducing strain of Friend virus complex (FVC-P) develop a fatal erythroid disease similar in some respects to leukemia. Six- to eight-week-old DBA/2 female mice were injected i.v. with 0.5 ml of a virus suspension containing approximately 5 X 10(4) plaque-forming units and 5 X 10(3) spleen focus-forming units. Four treatment regimens were begun 3 days postinjection: (a) no treatment; (b) whole-body hyperthermia (WBH) alone; (c) cyclophosphamide (CY) alone; (d) WBH combined with CY. WBH treatment utilized a microwave generator operating at 2450 MHz. The i.p. temperature of the mice receiving WBH was maintained at 39.5-40 degrees C for 30 min. The CY was given i.p. at a dosage of 20 mg/kg of body weight. The various treatments, CY, WBH, CY + WBH were given once a week for 2 weeks. Natural killer cell activity was examined in all four groups of mice and was found to be significantly higher in the animals treated with WBH or CY. Our results show that WBH, either alone or in combination with CY, can prolong the lifespan of mice infected with lethal dosages of the FVC-P, possibly via a mechanism involving natural killer cells.
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PMID:Effect of whole-body hyperthermia and cyclophosphamide on natural killer cell activity in murine erythroleukemia. 316 52


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