Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Human T lymphotropic virus type I (HTLV-I) is a human retrovirus etiologically linked to Adult T cell leukemia (ATL) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although most HAM/TSP patients have high anti-HTLV-I antibody titers in their sera, HTLV-I infected but seronegative patients with neurological diseases have been reported. To clarify whether seronegative, HTLV-I related neurological disease may exist, we have developed a method that measures the production of interleukin-2 (IL-2) from HTLV-I synthetic peptide-stimulated peripheral blood lymphocytes (PBL) of HTLV-I infected persons. This method is sensitive enough to detect exposure to HTLV-I before seroconversion or even before detection by PCR. We examined 12 patients with chronic progressive myelopathy and eight patients with multiple sclerosis (MS) in central Japan, where the prevalence rate of HTLV-I is between one and four percent among asymptomatic blood donors, using the IL-2 production assay. None of them were positive by the assay, suggesting seronegative HTLV-I myelopathy is very rare among patients with chronic progressive myelopathy and MS in Japan.
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PMID:Human T lymphotropic virus type I (HTLV-I)-specific T helper cell responses from HTLV-I seronegative patients with chronic myelopathy and MS in Japan. 934 34

Human T-cell lymphotrophic virus type 2 (HTLV-2), a common infection of intravenous drug users and subpopulations of Native Americans, is uncommon in the general population. In contrast with the closely related HTLV-1, which is associated with both leukemia and neurologic disorders, HTLV-2 lacks a strong etiologic association with disease. HTLV-2 does shares many properties with HTLV-1, including in vitro lymphocyte transformation capability. To better assess the ability of HTLV-2 to transform lymphocytes, a limiting dilution assay was used to generate clonal, transformed lymphocyte lines. As with HTLV-1, the transformation efficiency of HTLV-2 producer cells was proportionately related to the number of lethally irradiated input cells and was comparable to HTLV-1-mediated transformation efficiency. HTLV-2-infected cells were reproducibly isolated and had markedly increased growth potential compared to uninfected cells; HTLV-2 transformants required the continued presence of exogenous interleukin 2 for growth for several months and were maintained for over 2 years in culture. All HTLV-2-transformed populations were CD2 and/or CD3 positive and B1 negative and were either CD4+ or CD8+ populations or a mixture of CD4+ and CD8+ lymphocytes. Clonality of the HTLV-2 transformants was confirmed by Southern blot analysis of T-cell receptor beta chain rearrangement. Southern blot analysis revealed a range of integrated full-length genomes from one to multiple. In situ hybridization analysis of HTLV-2 integration revealed no obvious chromosomal integration pattern.
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PMID:Human T-lymphocyte transformation with human T-cell lymphotropic virus type 2. 942 Feb 97

Investigators have hypothesized that occupations involving electric and magnetic field exposure are associated with a variety of health problems, including neurological disease. The authors conducted a case-control study, and they used U.S. death certificates with occupational coding to compare male cases of Alzheimer's disease (n = 256), Parkinson's disease (n = 168), and amyotrophic lateral sclerosis (n = 114) with controls matched for age and calendar time. The authors selected controls in a 3:1 ratio to cases from persons who died of causes other than leukemia, brain cancer, and breast cancer. Overall associations with electrical occupations were modest (i.e., adjusted odds ratios of 1.2, 1.1, and 1.3 for Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, respectively). Individual electrical occupations were associated more strongly with disease than overall electrical occupations, particularly amyotrophic lateral sclerosis, for which relative risks ranged from 2 to 5 across several job categories. The largest associations with all three diseases occurred for power plant operators.
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PMID:Electrical occupations and neurodegenerative disease: analysis of U.S. mortality data. 957 Mar 11

Murine leukemia virus (MuLV) clone Fr98 is a recombinant polytropic virus that causes neurological disease characterized by ataxia in susceptible mouse strains. The envelope gene of Fr98 has been previously shown to encode at least two separate neurovirulence determinants. In the present study, the determinant encoded within the EcoRI/AvrII fragment of the envelope gene was further defined. In these experiments, neurovirulence was associated with a change from a serine to an arginine at position 195 and a glycine to an alanine at position 198 within the envelope protein. Neurovirulent and nonvirulent virus clones, which differed only at these two amino acid residues, showed no difference in the type or location of cells infected. Furthermore, equivalent levels of viral p30 capsid protein were detected in the brains of mice infected with either the neurovirulent or nonvirulent virus clones. These results were consistent with the interpretation that the envelope protein of the neurovirulent virus differed from that of the nonvirulent virus by having a greater toxic effect on central nervous system function.
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PMID:Mapping of a neurovirulence determinant within the envelope protein of a polytropic murine retrovirus: induction of central nervous system disease by low levels of virus. 972 Dec 29

Following intraperitoneal (IP) inoculation of neonatal mice, the polytropic recombinant murine leukemia virus (MuLV), Fr98, induces a severe brain disease characterized by ataxia, seizures and death. In contrast, no apparent clinical neurological disease is seen after IP infection with Fr54, a polytropic MuLV differing from Fr98 in its envelope gene sequences. In the brain both Fr98 and Fr54 infect primarily capillary endothelial cells and microglia. However, the level of microglial infection by Fr98 is twofold higher than by Fr54, which might account for the difference in neurovirulence. In the present study, in order to test directly whether an increase in the number of microglia infected by Fr54 would be sufficient to induce clinical disease, we attempted to increase the level of Fr54 in the brain by changing the route of infection. After intraventricular inoculation with Fr54-infected neural stem cells (clone C17.2), a well-established vehicle for delivery of viruses and genes to the brain, mice became ataxic and died 4 weeks postinfection. In these mice induction of brain disease was correlated with a higher level of viral antigen in the cerebrum and an increase in the number of infected microglial cells in all brain regions examined compared with mice inoculated IP. In contrast, mice inoculated with neural stem cells infected with an ecotropic nonneurovirulent murine leukemia virus, FB29, developed no clinical disease in spite of evidence for widespread infection of microglia in brain. Since the main differences between Fr54 and FB29 are in the SU (gp70) region of the envelope gene, this region is most likely to account for the differences in induction of CNS disease seen in the current experiments.
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PMID:Increased neurovirulence of polytropic mouse retroviruses delivered by inoculation of brain with infected neural stem cells. 1054 79

Upon inoculation into neonatal rats, murine leukemia virus (MuLV) NT40 causes a non-inflammatory degeneration of the central nervous system. While microglia cells appear to be the major target cells within the brain parenchyma for neurovirulent MuLV, degenerating neurons do not express retroviral gene products. In order to protect rats from neuronal damage we treated retrovirally infected rats once with monoamine oxidase (MAO) B inhibitor Selegiline which--under different conditions--exerts neuroprotective effects. Unexpectedly, when administered at 17 days post-infection (d.p.i.) a single intraperitoneal dose of Selegilin (1 mg/kg bodyweight) significantly shortened the incubation period for neurological disease. In contrast, Selegiline given in a lower dosage (0.05 mg/kg bodyweight) and/or at a different time point (13 d.p.i.) at the low (0.05 mg/kg bodyweight) and the high dose (1.0 mg/kg bodyweight) had no effect on the outcome of neurological disease. Animals treated with Selegiline (1.0 mg/kg bodyweight at 17 d.p.i.) contained higher amounts of viral loads in the CNS, higher numbers of brain cells expressing major histocompatibility complex class II molecules, and exhibited inhibition of MAO-B in comparison to untreated yet infected (control) animals. Supposedly, Selegiline activated the major target cell population of the CNS for MuLV-NT40, microglia, with the consequence of enhanced susceptibility for retroviral infection and triggered endogenous mechanism(s) involved in the pathogenesis of retroviral neurodegeneration.
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PMID:Effects of Selegiline in a retroviral rat model for neurodegenerative disease. 1056 82

Human T cell leukemia virus type 1 (HTLV-1) and 2 (HTLV-2) are distinct oncogenic retroviruses that infect several cell types, but display their biologic/pathogenic activity only in T lymphocytes. HTLV-1 is associated with adult T cell leukemia, a malignancy of mature CD4(+) T cells, and a chronic neurological disorder termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-2 is less pathogenic and has been associated with a few cases of a variant of hairy cell leukemia and neurological disease. Previous studies have indicated that in vivo HTLV-1 has a preferential tropism for CD4(+) T cells, whereas HTLV-2 in vivo tropism is less clear, but appears to favor CD8(+) T cells. The molecular mechanism that determines the cellular tropism of HTLV-1 and HTLV-2 has not been precisely determined. However, one study by our group has provided evidence that HTLV-1-enhanced viral transcription in CD4(+) T cells may be responsible for its tropism. In an effort to understand HTLV-2 tropism we tested the ability of HTLV-2 to infect, replicate in, and transform purified CD4(+) or CD8(+) T cells in cell culture. After cocultures of purified primary human CD4(+) and CD8(+) T cells with an HTLV-2-producer cell line we measured viral transcription by reverse transcription PCR analysis, virus production by p19(gag) ELISA, proviral integration by DNA slot-blot analysis, surface phenotype by FACS analysis, and cellular transformation. We also measured HTLV-2 long terminal repeat-directed transcription in the presence and absence of Tax in purified CD4(+) and CD8(+) T cells, using transient transfection assays. Our data indicate that CD4(+) and CD8(+) T cells are equally susceptible to HTLV-2 infection. We observed no significant difference in viral transcription based on mRNA and virus production in CD4(+) and CD8(+) T cell cocultures. Although LTR transcription was enhanced 12- to 16-fold in the presence of Tax, there was no significant difference in CD4(+) or CD8(+) T cells. Interestingly, we show that HTLV-2 preferentially transforms CD8(+) T cells in culture. Together, our data indicate that, unlike HTLV-1, HTLV-2 cell tropism is not due to inhibition of viral infection and inefficient gene expression in CD4(+) versus CD8(+) T cells, and likely involves unique interactions with viral and CD8(+) T cell-specific proteins.
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PMID:In vitro cellular tropism of human T cell leukemia virus type 2. 1108 Aug 7

Human T cell leukemia virus type I (HTLV-I) is etiologically associated with adult T cell leukemia (ATL) and chronic neurological disease, tropical spastic paraparesis (TSP). In our study, a unique IL-2 dependent human T cell line, designated TY8-3, was established from a thymoma obtained from a myasthenia gravis patient. The cells were heterogeneous and mainly consisted of those with CD4 , CD8 as well as activation markers and adhesion molecules including IL-2Ralpha,beta,gamma, CD45RO, Tf-R, HLA-DR, LFA-1alpha,beta, LFA-3, ICAM-1 and OX40 but without CD3 surface markers. Furthermore, these cells underwent an efficient and reproducible IL-2 independent transformation upon cocultivation with HTLV-I/II producing cell lines. Interestingly, although the infected cells became IL-2 independent, the growth rate of infected cells was significantly lower than those of parental TY8-3 cells. Clonal HTLV-I proviral DNA and viral particles were detected in the cells. Down-regulation of the lck and fyn genes and activation of the lyn gene was demonstrated in the IL-2 independent HTLV-positive TY8-3 cells. Subclones of TY8-3 cells were again able to be efficiently transformed and became IL-2 independent several months after coculture. Our results thus exhibit that TY8-3 cells and its subclones provide us with a very unique model whereby IL-2 independent transformation events of human T cells by HTLV-I/II in vitro can be studied at a clonal level.
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PMID:IL-2 independent transformation of a unique human T cell line, TY8-3, and its subclones by HTLV-I and -II. 1114 27

Cantab is developing its DISC technology as a potential gene therapy product for cancer (DISC-Onc) and neurological and blood disorders (DISC-GT). Clinical trials are expected to commence in early 1999 [296831]. The DISC technology utilizes a herpes virus that has had a gene removed to prevent it from replicating [250526]. Phase I trials in leukemia were scheduled to commence in 1998 [250526], however, it was decided that although DISC-Onc is capable of carrying genes into leukemic cells, the levels of immunomodulator genes did not meet the target initially set for the commencement of trials. Hence, Cantab turned its attention to other cancers, and hoped to identify an alternative target for phase I trials in the first half of 1998 [279798]. Additional preclinical work using a murine version of the lead construct produced a significant therapeutic effect in animal tumor models [289716]. DISC-Onc is envisaged to deliver immunogenic genes such as cytokine or stimulatory protein genes [275129]. Cantab, in collaboration with Nottingham Trent University and Birmingham University, has shown that the DISC-Onc has delivered genes effectively to human colorectal, gastric and ovarian cancer tumors. Transfection rates have been shown to be favorable and have been proven to be at least as good as, if not better than, other vectors [279798]. Also, DISC-Onc carrying a functional GM-CSF, has antitumor activity in mouse models of renal cancer and leukemia [250526], [261768]. The DISC Neurology technology (DISC-GT), for gene therapy of neurological disease, is being developed in collaboration with Cambridge University, and enables HSV-driven long-term gene expression in nerve cells [279798].
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PMID:Technology evaluation: DISC. 1124 75

Recombinant p40 produced by baculovirus was used in an ELISA to screen samples of serum taken from 80 cats in Istanbul. The sera were also analysed for feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV). Antibodies to Borna disease virus- (BDV) p40 were detected in 34 (42-5 per cent) of the 80 cats. Seventy-three per cent of the sera which were positive for FIV and 26 per cent of the sera which were negative for FIV had antibodies to BDV. There was no difference in the percentage of sera which were positive for BDV between the cats that were positive or negative for FeLV. Three of the cats had neurological disease and two of these had antibodies to BDV. Six sera with low, medium or high optical densities (ODS) by ELISA were analysed by Western blotting. Only the sera with medium and high ODS reacted specifically with p40 at a dilution of 1 in 1,000.
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PMID:Detection of antibodies to Borna disease virus in Turkish cats by using recombinant p40. 1176 26


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