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)

It has been shown that the autosomal recessive mutation, gray tremor (gt) was associated in the homozygous state (gt/gt) with a rapidly fatal spongiform encephalopathy. Heterozygotes (+/gt) developed mild asymptomatic spongiform brain lesions as did recipient inbred mice inoculated with gt/gt brain homogenates, some of whom also showed behavioral abnormalities [Sidman, R. L., Kinney, H. C. & Sweet, H. O. (1985) Proc. Natl. Acad. Sci. USA 82, 253-257]. In these studies, inbred NFS/N mice inoculated intracerebrally at birth or as adults with gt/gt or first passage gt brain homogenates developed a progressive disease characterized by tremor, ataxia, and spasticity. The symptoms were milder and more slowly progressive than in the gt/gt homozygote, in the paralytic syndrome that followed neonatal inoculation of NFS/N mice with a wild murine leukemia virus (Cas-Br-M MuLV), or in the rapidly progressive ataxia and terminal bradykinesia that followed scrapie inoculation of NFS/N mice. The noninflammatory spongiform encephalopathy in affected NFS/N mice resembled that observed in gt/gt homozygotes, +/gt heterozygotes, and asymptomatic recipient inbred mice inoculated with gt/gt brain homogenates. Neither infectious MuLV nor MuLV proteins were detected in gt/gt brain homogenates or in affected recipient mouse brains. Scrapie-associated fibrils, readily identifiable in subcellular fractions of brains from scrapie-inoculated NFS/N mice, were not detected in similar brain fractions from NFS/N mice inoculated with gt brain homogenates. These results confirm and extend the suggestion that gt spongiform encephalopathy has both heritable and transmissible properties. Moreover, the transmissible agent of gt disease differs from both Cas-Br-M MuLV and scrapie in its disease-inducing properties in NFS/N mice. The capacity of NFS/N mice to express transmitted gt encephalopathy as clinical disease, to rapidly express Cas-Br-M MuLV spongiform encephalomyelopathy, and to develop mouse-adapted scrapie after a very short incubation time suggest a distinct sensitivity of NFS/N mice to transmissible spongiform encephalopathy.
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PMID:Transmission in NFS/N mice of the heritable spongiform encephalopathy associated with the gray tremor mutation. 347 86

A progressive neurodegenerative disease occurred following infection of mice with a temperature-sensitive (ts) isolate of Moloney (Mo) murine leukemia virus (MuLV), ts Mo BA-1 MuLV. This NB-tropic ecotropic MuLV, which was ts for a late function, induced a syndrome of tremor, weakness of the hind limbs, and spasticity following infection of several strains of laboratory neonatal mice, including NFS, C3H/He, CBA, SJL, and BALB/c. The latent period of 8 to 16 weeks was considerably longer than that observed for the acute paralytic diseases observed following neonatal infection with other ts Mo-MuLV, rat-passaged Friend MuLV, and some wild mouse ecotropic MuLVs. Spongiform pathology without inflammation and degeneration of neurons devoid of budding virions occurred in the cerebellar grey matter, brain stem, and upper spinal cord; but lower spinal cord anterior horn cells were less obviously affected than in other MuLV-associated neuroparalytic syndromes. ts Mo BA-1 MuLV differed from other ts Mo-MuLV mutants that are capable of inducing a neuroparalytic syndrome in that while infected nervous system tissue contained high levels of MuLV p30 and gp70, no evidence of precursor accumulation or abnormal processing of MuLV p30 or gp70 could be demonstrated. The localization of virus within the nervous system suggests that direct neuronal infection may not be the etiologic mechanism in this MuLV-induced neurodegenerative disease.
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PMID:Characterization of a progressive neurodegenerative disease induced by a temperature-sensitive Moloney murine leukemia virus infection. 373 86

Friend-MCF virus induces erythroid leukemia when injected into newborn NFS mice whereas Moloney virus induces T-cell lymphoma. To identify the portion of Friend-MCF virus responsible for erythroid leukemia induction four in vitro recombinant viruses were constructed in which env regions or U3 regions of LTR were reciprocally exchanged between Friend-MCF and Moloney viruses. A FrMCF-Mol (LTR) virus whose genome was derived primarily from Friend-MCF virus together with 621 nucleotides of Moloney virus at its 3' end including the U3 region of LTR was a thymic lymphoma-inducing virus. A Mol-FrMCF (LTR) virus with the genome derived primarily from Moloney virus but 596 nucleotides of Friend-MCF virus information at the same region as FrMCF-Mol (LTR) was an erythroid leukemia-inducing virus. A Mol-FrMCF (env) virus whose genome was derived primarily from Moloney virus but which had 2.3 kbp of Friend MCF at the 3' end of the pol gene including most of the env gene with all of gp70 and the N terminal of p15E was a lymphoid leukemia-inducing mink cell focus-inducing virus. FrMCF-Mol (env) virus whose genome was derived primarily from Friend-MCF virus but had 2.7 kbp of Moloney virus at the same region as Mol-FrMCF (env) virus was an erythroid leukemia-inducing ecotropic virus. The Mol-FrMCF (LTR) and Mol-FrMCF (env) viruses induced mixed leukemia of erythroid and lymphoid cells in some mice.
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PMID:Long terminal repeat of Friend-MCF virus contains the sequence responsible for erythroid leukemia. 385 71

NFS/N mice inoculated with Moloney murine leukemia virus (M-MuLV) developed T-cell lymphoma after a 10-week latent period. Expression of lymphoid differentiation antigens, appearance of M-MuLV-encoded cell surface antigens, and rates of cellular proliferation were measured in splenic and bone marrow subpopulations during this latent period. At 2 weeks of age, Thy-1-and surface immunoglobulin-negative null cells of spleen and bone marrow expressed M-MuLV antigens whereas T- and B-lymphocytes did not. During the 3d and 4th weeks, the number of splenic null cells increased to six times the number found in uninfected controls. These null cells included the precursors of lymphocytes and hematopoietic cells. For the remainder of the latent period, the percentage of null cells undergoing proliferation was three times greater in the infected mice, while the total number of null cells remained constant. This proliferation was not accompanied by terminal differentiation or emigration of mature cell types from the spleen. Proliferation was substantially delayed in CBA mice, which are resistant to lymphoma induction.
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PMID:Proliferation of infected lymphoid precursors before Moloney murine leukemia virus-induced T-cell lymphoma. 387 91

We used AKR/J mice to produce monoclonal antibodies specific for a neurotropic ecotropic (WM-E) virus initially isolated from wild mice. The rationale for this approach involved the observation that these mice were immunologically hyporesponsive to endogenous ecotropic virus (Akv) but fully responsive to type-specific determinants of WM-E. Hybridoma cell lines derived from mice immunized with both denatured and viable virus produced antibodies with specificity for three viral membrane-associated polypeptides, gp70, p15(E), and p15gag. Epitopes specific for WM-E virus were detected in each of these polypeptides. Cross-reactivity with Friend ecotropic virus (Friend murine leukemia virus) was observed with some gp70- and p15gag-specific antibodies, but no reactivity with endogenous Akv ecotropic virus was seen. The majority of these antibodies did not react with either xenotropic or mink cell focus-forming viruses. Two WM-E-specific anti-gp70 antibodies reacting with different determinants had virus-neutralizing activity in the absence of complement, suggesting that the respective epitopes may participate in receptor binding or virus penetration events. We used these monoclonal antibodies in initial studies to examine the replication of WM-E virus in neonatally inoculated AKR/J mice which are fully resistant to the paralytic disease induced by this virus. Since these mice express high levels of endogenous ecotropic virus, standard assays for ecotropic virus cannot be used to study this question. We present evidence that the resistance to disease does not involve a resistance to virus replication, since these mice expressed levels of viremia and virus replication in spleen and lumbar spinal cord comparable to susceptible NFS/N mice at a time when the latter began to manifest clinical signs of lower-motor-neuron pathology.
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PMID:Monoclonal antibodies specific for wild mouse neurotropic retrovirus: detection of comparable levels of virus replication in mouse strains susceptible and resistant to paralytic disease. 387 18

NFS/N mice congenic for ecotropic murine leukemia virus (MuLV) induction loci from AKR and C58 mice ("NFS V-congenics") were evaluated for the development of spontaneous neoplasms in comparison to such development in virus-negative NFS/N mice. Congenic mice developed thymic lymphomas, whereas NFS/N did not. However, the frequency of thymic lymphomas was reduced, and the latent period for their development was prolonged in NFS V-congenics as compared to that in AKR/N or C58/Lw mice. In addition, the frequencies of nonthymic lymphomas and myelogenous leukemias were increased more than threefold in the congenics over NFS/N. The increased frequencies of hematopoietic neoplasms in congenic animals were related to early expression of high systemic levels of ecotropic MuLV.
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PMID:Spontaneous tumors of NFS mice congenic for ecotropic murine leukemia virus induction loci. 608 9

Nondefective Friend helper murine leukemia virus (Fr-MuLV) induces primarily erythroleukemias in NFS mice, whereas Moloney murine leukemia virus (Mo-MuLV) induces T cell lymphomas. Using molecular clones of these two viruses, we constructed a recombinant in which a 0.62-kilobase fragment encompassing the U3 region at the 3' end of the Fr-MuLV genome replaced the corresponding region of Mo-MuLV. The recombinant virus obtained by transfection of this clone, whose genome is derived primarily from Mo-MuLV, induces almost exclusively erythroleukemias in NFS mice. This and the previous result of Chatis et al. (Proc. Natl. Acad. Sci. U.S.A. 80:4408-4411), showing that the reciprocal recombinant whose genome is primarily derived from Fr-MuLV induces almost exclusively lymphomas, argue that a strong determinant of the distinct disease specificities of Fr-MuLV and Mo-MuLV lies in this 3' end 0.62-kilobase fragment which contains the putative virus enhancers. To more precisely define this determinant, we have begun to construct recombinants in which smaller 3' end fragments of the Fr-MuLV and Mo-MuLV genomes are exchanged. Analysis of the first such recombinant showed that Fr-MuLV can be converted to a lymphoma-inducing virus in NFS mice by substitution of a 0.38-kilobase fragment encompassing the virus enhancers in U3 with the corresponding region of the Mo-MuLV genome.
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PMID:A 3' end fragment encompassing the transcriptional enhancers of nondefective Friend virus confers erythroleukemogenicity on Moloney leukemia virus. 609 Jul 1

Resistance to the paralytic effects of a wild mouse (Cas-Br-M) murine leukemia virus infection develops with age and is complete by 10 days of age in susceptible NFS mice. The possibility that cell-mediated immunity plays a significant role in this resistance was suggested by the observation that treatment of 10-day-old mice with antithymocyte serum rendered them susceptible to paralysis. By comparison, mice rendered incapable of generating a humoral immune response by treatment from birth to 1 month of age with anti-immunoglobulin M serum did not develop paralysis after challenge with virus at day 10. Transfer of unseparated and T-cell-enriched populations of Cas-Br-M murine leukemia virus-immune spleen cells protected neonatally infected NFS recipients from paralysis; transfer of Cas-Br-M murine leukemia virus-immune populations enriched for B cells delayed the onset but did not ultimately protect neonatally infected NFS mice from paralysis. Transfer of naive adult spleen cells had no protective effect in neonatally infected NFS mice. High-level virus replication occurred in the spleens and brains of all mice that developed paralysis regardless of treatment; low-level virus replication in spleen and barely detectable replication in brain occurred in mice that remained clinically normal. These studies suggest that the age-acquired resistance to the paralytic effect of Cas-Br-M murine leukemia virus infection is immunologically mediated and that T cells may play a major role.
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PMID:Role of immunity in age-related resistance to paralysis after murine leukemia virus infection. 609 5

A new strain of Friend recombinant mink cell focus-inducing retrovirus, FMCF -1-E, was found to induce leukemias in NFS and IRW mice. Although the isolate was obtained from a stock of FMCF -1 ( Troxler et al., J. Exp. Med. 148:639-653, 1978), FMCF -1-E was distinguishable from FMCF -1 by oligonucleotide fingerprinting and antigenic analysis, using monoclonal antibodies. These analyses suggested that FMCF -1-E is a distinct FMCF isolate rather than a simple variant of FMCF -1. After neonatal inoculation, the latency for leukemia induction was 3 to 8 months. A similar long latency was also seen when Friend murine leukemia virus 57 was inoculated into adult (6-week-old) IRW mice. However, sequential inoculation of FMCF -1-E at birth followed by Friend murine leukemia 57 at 6 weeks of age led to a shortened latency period (2.5 to 4 months). Only neonatal inoculation of Friend murine leukemia virus 57 was able to induce a more rapid appearance of leukemia. The leukemia cell type in the majority of cases, regardless of virus inoculation protocol, was erythroid, but occasional myeloid, lymphoid, and mixed leukemias were also observed. In contrast to NFS and IRW mice, BALB/c mice were resistant to leukemia induction by FMCF -1-E and also showed some transient resistance to leukemia induction by Friend murine leukemia virus 57.
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PMID:Leukemia induction by a new strain of Friend mink cell focus-inducing virus: synergistic effect of Friend ecotropic murine leukemia virus. 620 86

A specific probe for detecting ecotropic murine leukemia virus sequences was constructed by cloning a 500-base-pair DNA segment, corresponding to a portion of the env region of the AKR ecotropic virus, in a pBR322/Escherichia coli K-12 host/vector system. This probe was used to screen the cellular DNAs of six inbred strains of mice for the presence of ecotropic retroviral DNA sequences by the Southern blot hybridization procedure. Three copies of ecotropic viral DNA were detected in AKR/N (a high-ecotropic virus strain) and two were found in BALB/c (a low-ecotropic virus strain) DNAs. As expected, no sequences reactive with this probe were found in NFS mouse DNA (a virus-negative strain). However, cellular DNA sequences that reacted strongly with the ecotropic-specific DNA probe were detected in certain NZB, C57L, and 129 mice (all virus-negative strains). In contrast to the reactive sequences in AKR and BALB/c, the reactions were chiefly associated with EcoRI segments that were subgenomic in size.
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PMID:Identification of ecotropic proviral sequences in inbred mouse strains with a cloned subgenomic DNA fragment. 625 65


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