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)

The human T-lymphotropic virus type I (HTLV-I), the first human retrovirus to be characterized, is associated with adult T-cell leukaemia and a chronic progressive disease of the central nervous system termed tropical spastic paraparesis, or HTLV-I-associated myelopathy. Only 1% of individuals infected with HTLV-I develop clinical disease however. The various manifestations of an HTLV-I infection may be related to differences in the genetic backgrounds of individuals, infection with variant strains of HTLV-I, differences in viral tropism or host immune response to the virus. Whereas the humoral response to HTLV-I is well characterized, little is known about the human cellular immune response, such as the production of cytotoxic T lymphocytes. Here we report the presence of high levels of circulating HTLV-I-specific cytotoxic T lymphocytes in patients with HTLV-I associated neurological disease but not in HTLV-I seropositive individuals without neurological involvement. These cytotoxic T lymphocytes are CD8+, HLA class I- restricted and predominantly recognize the HTLV-I gene products encoded in the regulatory region pX. These findings suggest that HTLV-I-specific cytotoxic T lymphocytes may contribute to the pathogenesis of associated neurological disorders associated with HTLV-I.
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PMID:Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease. 214 11

Infection of certain strains of mice with the ecotropic Friend murine leukemia virus results in the generation of recombinant polytropic mink cell focus-inducing viruses and the development of erythroleukemia. We isolated a Friend mink cell focus-inducing virus (F-MCF-98D) from a Friend murine leukemia virus-infected BALB/c mouse which caused primarily a neurological disease as well as a low incidence of leukemia in susceptible IRW mice. Through genetic studies with the resistant C57BL/10 strain, we identified two genes which correlated with restricted viral replication and resistance to the development of disease caused by F-MCF-98D. One gene correlated with the expression of an endogenous gp70 linked to the Rmcf gene and might act by viral interference. The mechanism of action of the second gene was less clear, but it appeared to be associated with development of an antiviral antibody response.
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PMID:Host genes conferring resistance to a central nervous system disease induced by a polytropic recombinant Friend murine retrovirus. 215 19

The Cas-Br-E and ts-Mo BA-1 murine leukemia viruses (MuLV) induce a spongiform neurodegenerative disease with different clinical manifestations, namely, either hind limb paralysis (Cas-Br-E) or tremors, spasticity, and hind limb weakness (ts-Mo Ba-1). We constructed the chimeric NEBA-1 MuLV by replacing the long terminal repeat of Cas-Br-E MuLV with that of ts-Mo BA-1 MuLV. In SWR/J or CFW/D mice, NEBA-1 MuLV induced an ataxic neurological disease characterized by clinical signs different from those induced by both parents. Although NEBA-1 MuLV did not induce lesions in novel brain areas, the spongiform lesions were more severe in deep cerebellar nuclei and in the spinal cord than those found in paralyzed mice inoculated with Cas-Br-E MuLV. By in situ hybridization, we found that the distribution of the spongiform lesions closely correlated with the distribution of the infected central nervous system cells. In the spinal cord, a close correlation was found between the number of infected cells and the severity of the spongiform degeneration. Sequencing of the substituted ts-BA-1 MuLV fragment and comparison with homologous sequences of Cas-Br-E and Moloney MuLV showed differences mainly in the U3 tandem direct repeats. Our results show that a few modifications within the U3 long terminal repeat allow the virus to cause more severe lesions in some central nervous system regions and that the severity of the spongiform degeneration correlates with the level of viral replication.
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PMID:Substitution of the U3 long terminal repeat region of the neurotropic Cas-Br-E retrovirus affects its disease-inducing potential. 216 94

ts1, a spontaneous temperature-sensitive mutant of Moloney murine leukemia virus TB, causes hind-limb paralysis in mice. A Val-25----Ile substitution in gPr80env is responsible for temperature sensitivity, inefficient processing of gPr80env, and neurovirulence. In this study, the Ile-25 in gPr80env was replaced with Thr, Ala, Leu, Gly, and Glu by site-directed mutagenesis of the codon for Ile-25 to generate a new set of mutant viruses, i.e., ts1-T, -A, -L, -G, and -E, respectively. The phenotypic characteristics of these mutant viruses differed from those of ts1. For each mutant, the degree of temperature sensitivity was correlated with the degree of inefficient processing of gPr80env, and the following rank order was observed for both parameters: ts1-E greater than ts1-G greater than ts1-L greater than ts1-A greater than ts1 greater than ts1-T. In FVB/N mice, mutant viruses of low and intermediate temperature sensitivity and inefficiency in processing of gPr80env were neurovirulent and consistently caused mutant-specific disease profiles: ts1-T caused severe whole-body tremor, ts1-A generally caused hind-limb paralysis, and ts1-L generally caused a delayed-onset paraparesis. By 150 days postinfection, FVB/N mice that were infected with ts1-G and -E, mutants of high temperature sensitivity and inefficiency in processing of gPr80env, had lymphoid leukemia instead of a neurological disease. These results suggest that the dynamics of gPr80env processing are important in determining the neurovirulent phenotype in vivo.
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PMID:Site-directed mutagenesis of the codon for Ile-25 in gPr80env alters the neurovirulence of ts1, a mutant of Moloney murine leukemia virus TB. 221 16

A retrovirus was isolated from a T-cell line that was established from lymphocytes in the cerebrospinal fluid of a patient with human T-cell leukemia virus type I-associated myelopathy (HAM), and its genome was sequenced. The nucleotide sequence of the 3' half of the total genome was identical in 99.5% of the nucleotides to that of the prototype human T-cell leukemia virus type I that was derived from a patient with adult T-cell leukemia. These results indicate that the same retrovirus human T-cell leukemia virus type I is associated with both a neurological disease, HAM, and a lymphoproliferative disease, adult T-cell leukemia.
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PMID:Retrovirus from human T-cell leukemia virus type I-associated myelopathy is the same strain as a prototype human T-cell leukemia virus type I. 224 26

We have amplified and sequenced DNA in the envelope (env) and long terminal repeat (LTR) regions of human T-cell lymphotropic virus type I (HTLV-I) proviruses from the peripheral blood of 10 HTLV-I-seropositive patients with tropical spastic paraparesis (TSP) and two patients with adult T-cell leukemia. The aim was to examine variation in these regions and to test the hypothesis that the sequences of leukemogenic HTLV-I isolates differ from those causing the neurological disease TSP. In 5 of the 12 HTLV-I-seropositive patients, more than one HTLV-I sequence variant was identified in the same individual. No two individuals shared identical sequences in either env or LTR U3. Sequence variations were found at 73 positions in 1,416 bases amplified in env. Sequence variability was found throughout the LTR-U3 region, including the sequences of two transcriptional enhancers. Several nucleotide changes common to both Caribbean and Japanese HTLV-I isolates allowed us to identify a consensus sequence that differs from the HTLV-I prototype sequence (M. Seiki, S. Hattori, Y. Hirayama, and M. Yoshida, Proc. Natl. Acad. Sci. USA 80:3618-3622, 1983). No sequence in the env or LTR U3 region was found to be characteristic of isolates from TSP patients. Although each isolate was distinct at the nucleotide level, the predicted protein sequence of HTLV-I env is less variable than that of human immunodeficiency virus env, suggesting that these lymphotropic retroviruses use different strategies to evade host immune responses.
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PMID:Sequence variants of human T-cell lymphotropic virus type I from patients with tropical spastic paraparesis and adult T-cell leukemia do not distinguish neurological from leukemic isolates. 230 44

Neurological disorders, such as seizures, are not infrequently associated with anti-leukemic therapy. It has been hypothesized that a disrupted peptidergic transmission between neurons could be the cellular basis of the neurological dysfunction. Since endogenous opioids have been recently found to alter neuronal function and possess anticonvulsant properties, the cerebrospinal fluid (CSF) immunoreactive beta-endorphin levels in children with Acute Lymphoblastic Leukemia (ALL) during chemotherapy and cranial irradiation have been studied. Twenty-seven children, 2 at low, 20 at medium and 5 with high risk ALL, undergoing prophylactic treatment for meningeal leukemia, entered the study. Sequential lumbar punctures with introduction of MTX combined with oral prednisone therapy were performed; each lumbar puncture sample was collected and assayed for immunoreactive beta-endorphin. All the patients studied showed a biphasic profile of the peptide with the minimum levels reached during the induction (days 14-28) and the maximum levels detected at the end of the intensification chemotherapy (days 49-55). In the 3 groups the beta-endorphin decrease corresponded to the period of prednisone therapy; the increase was concomitant with the suspension of oral glucocorticoids. 3 patients showed tonic-clonic seizures which coincided with the lowest cerebrospinal fluid beta-endorphin levels and, in the follow-up, 13 out of 27 patients displayed EEG abnormalities. From these findings a relationship between cerebrospinal fluid beta-endorphin concentrations and neuronal excitability in patients with ALL can be suggested. It is also evidenced that oral glucocorticoid therapy has profound inhibitory effects on central beta-endorphin levels.
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PMID:Immunoreactive beta-endorphin levels in cerebrospinal fluid of children with acute lymphoblastic leukemia: relationship with glucocorticoid therapy and neurological complications. 253 Nov 80

Human immunodeficiency virus (HIV) is unique among retroviruses in its genetic complexity. Its genome encodes a number of positive, differential, and negative regulatory genes, whose interplay appears to be directed at maintaining a steady, low-level virus expression. Since clinical progression and CD4 cell depletion in HIV-infected individuals appear to correlate with increase in virus expression, and continuous recruitment of new infected cells, the role for cofactors which enhance HIV production becomes significant in the pathogenesis of AIDS. Many environmental and cellular factors have been found to activate HIV. In particular, some viral agents may interact with HIV in contributing to pathogenesis. The leukemia viruses, HTLV-1 and HTLV-2, and several herpesviruses have been shown to stimulate gene expression from the HIV LTR. In addition, HIV tat gene can also activate a DNA virus (JC virus) which is associated with a neurological disease. Finally, immunosuppression by HIV is likely to reactivate latent herpesvirus infections, thus initiating a vicious cycle for further CD4 cell depletion.
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PMID:HIV gene regulation and pathogenesis. 255 2

BALB/c mice infected with ts1, a mutant of Moloney murine leukemia virus-TB, develop generalized body wasting, profound neurologic disorders, severe thymic atrophy and lymphopenia due to destruction of T lymphocytes and drastic immunodeficiency. ts1 was found not only able to infect T lymphocytes but also to impair their function. In addition, ts1 also infects and induces syncyntia formation in macrophages. The genetic determinant(s) responsible for ts1's ability to induce immunodeficiency has been localized to the env gene.
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PMID:ts1, a mutant of Moloney murine leukemia virus-TB, causes both immunodeficiency and neurologic disorders in BALB/c mice. 272 46

Newborn homozygous BALB/c nude (nu/nu) mice, their heterozygous (+/nu) littermates, and normal BALB/c (+/+) mice were infected with ts1, a paralytogenic mutant of Moloney murine leukemia virus-TB (MoMuLV-TB). Our results indicate that while infection of +/nu and +/+ mice with ts1 results in severe pathological changes in the central nervous system (CNS) and paralysis, infection of nu/nu mice results in only mild to moderate pathology within the CNS and no paralysis. On the other hand, 50% of nude mice reconstituted with T cells when infected with ts1 developed paralysis and showed more pronounced degeneration of nervous tissue than nude mice infected with ts1 alone. These observations strongly suggest that the thymus, the functional T lymphocytes, or both play an important role in the ts1-induced neurologic disorders in infected mice.
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PMID:The role of the thymus in the pathogenesis of hind-limb paralysis induced by ts1, a mutant of Moloney murine leukemia virus-TB. 278 29


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