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)

Indirect immunofluorescence, competitive radioimmunoassay, HTLV I-enzyme linked immunosorbent assay and gelatin particle agglutination Serodia-ATLA were compared in terms of their ability to detect antibody to human T cell leukaemia virus I (HTLV I). The sensitivities were 96.9%, 92%, 97.0%, and 100%, respectively, and the specificities 99.3%, 98.9%, 98.6%, and 96.3%. Particle agglutination was very simple to perform and was the most sensitive, though the least specific test. Antibody titres were 10-100 times higher when measured by particle agglutination than by other tests, and antibody titers were considerably higher in patients with neurological disease related to HTLV I than in those with other conditions. Serodia-ATLA is the method of choice for preliminary screening of specimens for antibody to HTLV I, but positive results must be confirmed by another technique.
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PMID:Comparison of assays for antibody to HTLVI. 283 31

Human T-cell lymphotropic virus type 1 (HTLV-I), the etiologic agent of human T-cell leukemia, has recently been shown to be associated with neurologic disorders such as tropical spastic paraparesis, HTLV-associated myelopathy, and possibly with multiple sclerosis. In this communication, we have examined one specific case of neurologic disorder that can be classified as multiple sclerosis or tropical spastic paraparesis. The patient suffering from chronic neurologic disorder was found to contain antibodies to HTLV-I envelope and gag proteins in his serum and cerebrospinal fluid. Lymphocytes from peripheral blood and cerebrospinal fluid of the patient were shown to express viral RNA sequences by in situ hybridization. Southern blot analysis of the patient lymphocyte DNA revealed the presence of HTLV-I-related sequences. Blot-hybridization analysis of the RNA from fresh peripheral lymphocytes stimulated with interleukin 2 revealed the presence of abundant amounts of genomic viral RNA with little or no subgenomic RNA. We have cloned the proviral genome from the DNA of the peripheral lymphocytes and determined its restriction map. This analysis shows that this proviral genome is very similar if not identical to that of the prototype HTLV-I genome.
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PMID:Molecular cloning of human T-cell lymphotrophic virus type I-like proviral genome from the peripheral lymphocyte DNA of a patient with chronic neurologic disorders. 289 23

Human T-cell leukemia virus type 1 (HTLV-1) is known to be associated with adult T-cell leukemia (ATL). Recently, HTLV-1-associated myelopathy (HAM) was described as a neurological disease with which an etiological association of HTLV-1 is suspected. A provirus genome was cloned from a lymphoid cell line derived from the cerebrospinal fluid of a patient with HAM, in order to examine in detail the etiological virus associated with HAM. The nucleotide sequence of the long terminal repeat (LTR), protease, env and pX regions of the provirus shows over 97% homology with that of HTLV-1 derived from ATL. These results suggest that this provirus, derived from a patient with HAM, belongs to the same species as HTLV-1 derived from patients with ATL.
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PMID:Nucleotide sequence analysis of a provirus derived from HTLV-1-associated myelopathy (HAM). 289 12

Cas-Br-M is an ecotropic murine leukemia virus (MuLV) of wild-mouse origin that causes neurogenic hind-limb paralysis. By virtue of its N-tropism, the virus replicates well in tissues of mice bearing the n but not the b allele at the Fv-1 locus. To determine if different Fv-1n strains of mice were equally susceptible to virus-induced neurological disease, we inoculated NFS, C3H, DBA/2, CBA, AKR, C58, and NZB mice at birth with Cas-Br-M murine leukemia virus and observed them for the development of tremor and hind-limb paralysis. Three patterns of disease were observed: NFS and C3H mice developed disease within 3 months postinoculation; DBA/2 and CBA mice became affected between 8 and 15 months postinoculation; and no disease was observed in AKR, C58, or NZB mice up to 15 months after infection with Cas-Br-M murine leukemia virus. Studies of genetic crosses between intermediate-latency (DBA/2) or long-latency (AKR) strains with short-latency (NFS) strains showed that intermediate latency and long latency were semidominant traits determined by two or more interacting but independently assorting loci. These genes appear to determine the rate at which the virus replicates and at which viral gene products accumulate in the central nervous system.
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PMID:Host genetic determinants of neurological disease induced by Cas-Br-M murine leukemia virus. 298 60

The induction of poliomyelitis by lactate dehydrogenase-elevating virus (LDV) in C58 mice is dependent upon several host factors including old age, loss of immune competence and genetic predisposition. Two genetic components segregate with susceptibility to this neurological disease: the presence of multiple proviral copies of N-tropic endogenous murine leukemia viruses (MuLV) and homozygosity of the permissive allele for N-tropic viral replication (Fv-1n/n). We have quantified the levels of RNA for several endogenous retroviruses, using virus specific oligonucleotide probes, in various tissues of C58 mice in relation to age and immunosuppression. A tissue specific increase in expression of 3.0 kb AKR MuLV RNA in the spinal cords of mice occurred with increasing age of the mice and was enhanced several-fold by immunosuppression in old mice. Susceptibility to LDV-induced poliomyelitis occurs in the same age dependent manner as AKR MuLV expression and is also enhanced by immunosuppression. In contrast, the mink cell focus forming virus (MCF) RNA levels in the spinal cord remained constant despite apparent variations in MCF RNA expression in other tissues, and no xenotropic retrovirus RNA was detectable in spinal cords or brains of the C58 mice. The increased AKR MuLV RNA in the spinal cord was shown by in situ hybridization to be mainly located in the same motor neurons that become infected with LDV in these mice and are destroyed as paralysis develops. These results support a novel dual virus virus hypothesis for LDV-induced poliomyelitis in which increased endogenous retroviral expression in motor neurons renders these cells susceptible to cytocidal replication of LDV and hence to the development of LDV-induced poliomyelitis.
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PMID:Susceptibility of C58 mice to paralytic disease induced by lactate dehydrogenase-elevating virus correlates with increased expression of endogenous retrovirus in motor neurons. 323 56

Using chimeric murine leukemia viruses (MuLVs) constructed in vitro with parental viral genomes from the neurotropic Cas-BR-E MuLV and the nonneurotropic amphotropic 4070-A MuLV, we previously mapped the paralysis-inducing determinant of Cas-BR-E MuLV within a pol-env region. To assess the role of the long terminal repeats (LTRs) in influencing the neurological disease, we constructed another chimeric MuLV (pNEMO-1)m harboring the gag-pol-env from Cas-BR-E MuLV and the LTR region from the strongly T-cell tropic Moloney MuLV. Although the Cas-BR-E MuLV induced mainly nonthymic leukemia, pNEMO-1 MuLV induced a thymic form of leukemia, as the parental Moloney MuLV. The pNEMO-1 MuLV induced neurological diseases less frequently than Cas-BR-E MuLV when inoculated intraperitoneally into NIH/Swiss, SIM.S, and SWR/J mice. However, it induced neurological disorders more frequently and with a shorter latency than Cas-BR-E MuLV when inoculated intrathymically. Most mice with a neurological disorder induced with pNEMO-1 MuLV showed a new clinical syndrome not usually seen with the parental Cas-BR-E MuLV: They had no lower limb paralysis but were excessively tremulous, spastic, and immobile. The topographical distribution of the spongiform degeneration in the brain of mice with this new syndrome was different from that seen in mice with lower limb paralysis induced by Cas-BR-E MuLV. These results indicate that the 1.0-kilobase-pair Cla I-Pvu I LTR-containing fragment harbors sequences influencing the incidence and the clinical manifestation of the neurological disease and suggest a specificity of LTR sequences for a new tissue (brain).
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PMID:Retrovirus-induced spongiform encephalopathy: the 3'-end long terminal repeat-containing viral sequences influence the incidence of the disease and the specificity of the neurological syndrome. 386 55

NFS/N mice inoculated at birth with an ecotropic murine leukemia virus (Cas-Br-MuLV) obtained from wild mice developed hind limb paralysis beginning at 7 weeks of age and nonthymic lymphomas beginning at more than 20 weeks of age. Studies of 1- to 7-week-old Cas-Br-M MuLV-infected mice showed the following: (i) a marked increase in nonecotropic MuLV-related antigens on spleen cells but not thymocytes beginning at 2 weeks; (ii) the appearance of dual-tropic mink cell focus-forming (MCF) MuLV-related gp70 in spleen but not thymus or brain cells at 4 weeks; and (iii) the isolation of infectious MCF MuLV from spleen cells of 7-week-old mice. A role for MCF MuLV in Cas-Br-M MuLV-induced nonthymic lymphomas is indicated by these studies, and a role for recombinant MuLV in neurological disease is considered.
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PMID:Wild mouse ecotropic murine leukemia virus infection of inbred mice: dual-tropic virus expression precedes the onset of paralysis and lymphoma. 626 45

Among 12 recombinant inbred strains of mice derived from crossing two strains, C57BL/6J and C3H/HeJ, which have a low incidence of neoplastic disease, one strain (BXH-2) has been found to have a high incidence of lymphoma, of non-T-cell origin, at an early age. The BXH-2 strain carries the Fv-1b allele and spontaneously expresses a B-tropic murine leukemia virus beginning at as early as 10 days of gestation and continuing throughout their life. No significant differences in ecotropic virus titers were observed at any age tested (16 to 17 days of gestation through 7 months), whereas xenotropic virus was first detected in lymphoid tissues of 2-month-old mice and virus titers increased with age. Dual tropic virus(es), which induced cytopathic changes on mink lung cells, was isolated from BXH-2 lymphomatous tissues. Unlike AKR mink lung focus-forming virus (N-tropic recombinant), BXH-2 dual tropic virus is B tropic and induces cytopathic changes in mouse fibroblast cultures as well. The BXH-2 mouse provides a model system for studying the role of replication-competent viruses in spontaneously occurring leukemias of non-T-cell lineage and neurological disease.
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PMID:Expression of murine leukemia viruses in the highly lymphomatous BXH-2 recombinant inbred mouse strain. 626 48

We have used an experimental retrovirus infection to study the roles played by different antibodies in resistance to both infection and disease. A molecularly cloned chimeric murine leukemia virus was used to induce acute lethal neurological disease in neonatal mice. A panel of monoclonal antibodies directed against the Gag and Env proteins was tested for protective efficacy. In vitro neutralization assays demonstrated that anti-Env antibodies gave different degrees of neutralization, while no anti-Gag neutralized the virus. In vivo experimental endpoints were onset of clinical signs and premoribund condition. As expected, different anti-Env antibodies demonstrated different degrees of protection which correlated with their neutralizing abilities. Surprisingly, anti-Gag antibodies directed against both p15 (MA protein) and p30 (CA protein) were also protective, significantly delaying the onset of disease. No protection was seen with either of two control antibodies. The protection with anti-Gag was dose related and time dependent and was also produced with Fab fragments. Treatment with anti-Gag did not prevent viremia but resulted in a slight slowing in viremia kinetics and decreased levels of virus in the central nervous systems of mice protected from disease. These data indicate that nonneutralizing antiretroviral antibodies can influence the outcome of retroviral disease. The data also suggest a functional role for cell surface expression of Gag proteins on murine leukemia virus-infected cells.
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PMID:Protective efficacy of nonneutralizing monoclonal antibodies in acute infection with murine leukemia virus. 747 36

HTLV-I has a complex and finely regulated mechanism of replication, which can be used as a model to study both cellular and viral regulation pathways in T-cells. Understanding of the underlying mechanisms involved in the pleiotropic effects of HTLV-I in the host represents a real challenge. Immunological regulation likely plays a central role in HTLV-I induced neurological disease, uveitis, and perhaps arthritis, implicating the importance of host factors as well. Viral proteins, including tax and p12' might play a role in T-cell proliferation, but the event(s) that result in the late leukaemic phase are unknown. The lack of effective therapy against HTLV-I-induced leukaemia renders prevention of viral infection the best means to eliminate HTLV-I associated diseases. Elimination or reduction of breast feeding from seropositive mothers in Japan has already produced encouraging results. In developing countries, probably only a vaccine will prevent the spread of HTLV-I infection. The molecular epidemiology of HTLV and STLV will help understand not only the phylogeny of these viruses but also the migration of human populations in the past. Episodes of horizontal transmission in the past and probably the present, indicates that nonhuman primates are the natural reservoir of HTLVs. New related viruses will likely be discovered in monkeys (and humans) in the future.
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PMID:Human T-cell leukaemia virus. 766 44


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