Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perinatal infection of susceptible mice with the neurotropic retrovirus CasBrE leads to a noninflammatory spongiform degeneration of the central nervous system with a long incubation period of up to 1 year. Virus replication in infected animals can be suppressed by administration of antiviral antibodies, cytotoxic T cells, or by AZT treatment, which results in partial to complete protection from neurological disease. A highly neuropathogenic chimeric retrovirus, FrCasE, which contains the envelope gene of CasBrE, induces rapid neurodegeneration within only 16 days. Here we report that this fatal disease could be prevented if a nonneuropathogenic Friend murine leukemia virus was administered to mice prior to their infection with FrCasE. This double inoculation led to a substantial reduction of the replication level of FrCasE in spleen and CNS. Only live but not heat-inactivated nonneuropathogenic virus was able to protect from FrCasE-induced neurological disease. The extent of protection was influenced by the viral envelope gene and the kinetics of replication of the nonneuropathogenic virus. These observations in addition to the rapidity of the effect make it likely that competition for replication sites through the mechanism of viral interference is responsible for the protection. Resistance was demonstrable in vivo even when the "protecting" and "challenge" virus belonged to different in vitro interference groups. However, the protection was considerably weaker than that seen between viruses belonging to the same interference group.
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PMID:Prevention of retrovirus-induced neurological disease by infection with a nonneuropathogenic retrovirus. 783 92

AZT (7.5 or 15 mg/kg/dose) and the neuropeptide methionine enkephalin (Met-ENK, 1 or 3 mg/kg/dose) were used in a combined protocol for therapy of established murine retroviral infection. In both models used, Friend virus leukemia (FV) and BM5 complex (lymphadenopathy and immune deficiency), the drug combination was able to reduce mortality and splenomegaly. While increasing mean survival time of those animals that did not survive infection by FV, when compared to infected control mice or mice treated with AZT alone, Met-ENK used alone at 1 and 3 mg/kg/mouse had no effect in reducing morbidity or mortality due to either virus. This suggested that Met-ENK had no direct antiviral effect at the concentrations used. In fact, mice treated with either single drug therapy or the combination still yielded virus in their spleen, even when splenomegaly was absent. The data suggest that Met-ENK, which has been reported to be immunostimulatory, acts in combination to improve the efficacy of AZT in reducing progression of disease in murine retrovirus models for human AIDS.
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PMID:Methionine enkephalin combined with AZT therapy reduce murine retrovirus-induced disease. 786 96

Combinations of ddC with either the ribonucleotide reductase inhibitor hydroxyurea (HU) or with the natural nucleoside thymidine have been investigated on the cycle of a defective (psi neo) Moloney Leukemia Virus (MoMLV) using 3T3 fibroblasts as host cells. In this experimental model, ddC displayed very poor antiviral action which was obvious given an IC50 value close to 100 microM, i.e. an efficiency about thirty thousand fold lower than that of AZT. Both HU and thymidine alone resulted in significant inhibition of MoMLV replication with IC50 values of 40 microM and 100 microM respectively. The combination of ddC with 50 microM HU lowered the IC50 of ddC by a factor of 10. A similar but more pronounced effect was obtained by combining ddC and 100 microM thymidine, which decreases the IC50 value of ddC by a factor of 50. Combining 40 microM ddC and 100 microM thymidine resulted in the quite complete inhibition of viral replication. These results show that in cell types with strongly restricted ddC action, combination treatment with compounds known to ultimately decrease dCTP biosynthesis leads to the restoration of efficient antiviral activity.
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PMID:Potentiation of 2',3'-dideoxycytidine (ddC) by hydroxyurea and thymidine on the Moloney murine leukemia virus (MoMLV) early replicative steps. 799 21

The viremia of a mouse carrying a murine retrovirus, the Friend virus, was taken as a model for screening drugs which could be active on the human HIV retrovirus. Ellipticine and two of its analogues injected ip at appropriate doses drastically reduced the viremia of the Friend virus-injected mice, as measured by transfer of their serum on day 8 of the treatment to secondary recipients and numeration, in the spleens of the latter, of the foci the remaining virus had induced. Since phase I and II trials have already been published (for leukemia treatment), the efficacy of those drugs on HIV-1 positive AZT-resistant patients can be tested directly.
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PMID:The in vivo effect of ellipticine analogues on the blood concentration of Friend virus: a murine model for studying anti-HIV drugs. 806 Dec 46

Zidovudine (3'-azido-2',3'-dideoxythymidine) resistant isolates of human immunodeficiency virus type I (HIV-1) were previously demonstrated in zidovudine-treated AIDS patients. The genetic linkage of multiple mutations characteristic of zidovudine-resistance as well as dideoxyinosine-resistance were demonstrated by examining clones of viral reverse transcriptase after polymerase chain reaction (PCR) amplification of plasma culture DNA. The zidovudine-resistance mutations persisted in seven timepoints from four patients for 5 to 22 months despite cessation of zidovudine therapy (and while patients underwent ddI therapy). One patient's plasma virus isolate at 14 months possessed a genotype doubly resistant to ZDV and ddI. Virus recovered from four timepoints showed Intermediate to high levels of zidovudine-resistance. As these genotypes were mainly derived from plasma culture, the zidovudine resistant virus appears to persist and replicate well in vivo after cessation of zidovudine therapy.
Leukemia 1994 Apr
PMID:Long-term persistence of AZT-resistance mutations in the plasma HIV-1 of patients removed from AZT therapy. 815 87

Breast cancer chemotherapy and HIV-1 viral infection (AIDS) can result in respective transient or irreversible losses of up to 40-50% of circulating lymphocytes. The relationship of lymphopenia on tumor immunosurveillance and the control of opportunistic infections has yet to be established. The objective of this study was to characterize the changes in natural killer (NK) and lymphokine activated killer (LAK) cell function associated with cytotoxic drug therapy, breast cancer and HIV-1 infection. NK and LAK activities were measured at multiple effector to target ratios. Exponential regression analysis of target cell lysis determined the maximal % target kill and the lytic potential of effector cells. Flow cytometric analysis of lymphocyte subsets in seropositive populations was performed to determine the % of NK(CD56+) cells. Taken together, our findings indicate that cytotoxic NK pool sizes increased in breast cancer patients, diminish consequent to chemotherapy. The functional capacity of individual NK and LAK cells remains intact. In contrast, the diminution of NK and LAK functional responses in HIV-1 seropositive individuals is associated with reductions in cytotoxic NK and LAK pool sizes, as well as marked reductions in cytolytic function of individual cells. Zidovudine (AZT) treatment did not affect LAK activity in HIV+ subgroups. Our findings indicate that NK and activated LAK functions are affected both by chemotherapy and disease etiology.
Leukemia 1994 Apr
PMID:Different effects of breast cancer, HIV-1 infection and chemotherapy on inducible natural immunity. 815 88

We studied the impact of zidovudine (AZT) in Cas-Br-M murine leukemia virus-infected NFS-N mice after administration by once-daily bolus or continuous infusion. While higher peak concentrations of AZT were achieved by once-daily dosing, continuous AZT infusion at 25 micrograms/h maintained levels > 1 microM in plasma and > 0.2 microM in the brain. Continuous infusion provided significantly better viral inhibition, even though total doses were only one-third that of the once-daily therapy group.
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PMID:Impact of dosing schedule upon suppression of a retrovirus in a murine model of AIDS encephalopathy. 820 66

We demonstrated earlier that post-exposure prophylaxis with 3'-azido-3'-deoxythymidine (AZT, zidovudine) or with AZT + interferon-alpha (IFN-alpha) prevented viremia and disease in BALB/c mice inoculated with Rauscher murine leukemia virus (RLV). After the 20-day treatment course, most animals were resistant to rechallenge with live virus. Adoptive transfer of T cells from such resistant but not from normal mice into naive recipients provided full protection against virus challenge. From these experiments, we concluded that post-exposure chemoprophylaxis restricted virus replication and allowed the animals to form protective, long-lasting cellular immune responses. Here, the role for cellular immunity during antiviral chemoprophylaxis was tested by comparing treatment success in normal BALB/c mice and in their nude, athymic counterparts. Both were inoculated with equal doses of RLV (10(4) plaque-forming units, pfu). Single-agent AZT or combination therapy with AZT + IFN-alpha, started before or after RLV inoculation, prevented viremia in all normal but not in most nude mice. A significant number of nude mice were completely protected by chemoprevention only when given a 10 times lower virus dose. When normal mice were injected with a 10 times higher virus dose (10(5) pfu), complete protection by chemoprevention was lost. These results demonstrate that the success of chemoprevention depends critically on the virus inoculum. The differential success of chemoprevention in normal and T-cell-deficient mice implies that effective cellular immunity plays an important role in protecting virus-exposed animals against viremia and disease.
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PMID:Chemoprevention of retroviral infection: success is determined by virus inoculum strength and cellular immunity. 828 40

Lactate dehydrogenase-elevating virus (LDV) replicates in mouse macrophages in vivo and in vitro. It has been shown that LDV infects and replicates in motorneurons of the spinal cord of old, immunosuppressed C58 mice, which results in an acute poliomyelitis. In spite of extensive study, cells or cell lines other than macrophages which could support LDV infection and replication in vitro have not yet been detected. We have shown that LDV can replicate in mouse or rat cell lines which were previously infected with ecotropic murine leukaemia virus (MuLV). It was examined in this study whether other types of MuLV (dualtropic, amphotropic and xenotropic viruses) can also render the mouse cells or cells of other species susceptible to LDV infection as well as the ecotropic viruses. LDV infection and replication were seen in mouse cells infected with ecotropic, dual-tropic and amphotropic viruses. These were also seen in mink, rabbit and human cell lines infected with dual-, ampho- and xenotropic viruses. These results suggested that virtually all four classes of MuLV have the ability to elicit, in mouse cells or cells from heterologous species, permissiveness to LDV infection. The percent of LDV-infected cells increased up to approximately 80% in concentrated neurovirulent LDV-C-infected ecotropic MuLV-infected-mouse cells. The susceptibility of the cells gradually declined when they were maintained for more than one month. The LDV antigen-positive cells appeared as early as 6-8 h p.i., when a large amount of LDV and MuLV were added simultaneously. The replication of LDV was inhibited in MuLV-infected cells which had been treated previously with actinomycin D and cycloheximide, but not with zidovudine (AZT). A small percent of mouse cells became susceptible to LDV, when the cells were treated with iododeoxyuridine. This suggested that the induction of endogenous MuLV or part(s) of its genome from mouse chromosomes resulted in cells that were permissive to LDV.
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PMID:Replication of lactate dehydrogenase-elevating virus in various species cell lines infected with dual-, ampho- and xenotropic murine leukaemia viruses in vitro. 838 19

Previous experimental studies utilizing human recombinant interferon-alpha-2b (IFN alpha-2b) alone or with zidovudine (AZT) to treat established feline leukemia virus (FeLV) infection resulted in a significant reduction in circulating virus throughout a 49-day treatment period. However, the anti-FeLV effect of IFN alpha was limited by the production of IFN alpha-neutralizing antibodies detected 7 weeks after the start of treatment. AZT without IFN alpha had no effect on circulating virus load. To examine the hypothesis that combination chemoimmunotherapy might induce the clearance of FeLV infection, persistently infected cats were infused with activated lymphocytes, IFN alpha, and AZT 12 weeks after infection with FeLV. Recipient cats received weekly infusions of 1.46 x 10(8) lymphocytes activated in vitro with lectin/IL-2 comprised of 98% T cells and an even distribution of CD4+ and CD8+ lymphocytes. FeLV infection was cleared in 4 of 9 cats receiving combined therapy after four adoptive cell transfers. These cats remained negative for circulating virus during a 63-day treatment period (17 adoptive cell transfers) despite the production of anti-IFN alpha-neutralizing antibodies. Sequential development of virus-neutralizing and virus envelope antibody titers were detected in those cats which cleared retroviremia, an antiviral response that was absent in untreated control animals or nonresponders. Three of four responder cats remained negative for FeLV 95 days after treatment was discontinued. Treatment of cats with lymphocytes without chemotherapy failed to influence the course of FeLV infection. These results suggest that combined treatment using IFN alpha and adoptive lymphocyte transfer served to reconstitute antiviral humoral immunity, counteract immunosuppression, and induce the reversal of retroviremia.
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PMID:Reversal of feline leukemia virus infection by adoptive transfer of lectin/interleukin-2-activated lymphocytes, interferon-alpha, and zidovudine. 839 67


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