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)

Temperature elevation constitutes a beneficial component of the host defence against viral pathogens. However, heat treatment may be detrimental to HTLV-I-infected cells by increasing virion and oncoprotein production. We investigated the effects of thermal elevation on the in vitro replication of HTLV-I (human T-cell leukaemia/lymphoma virus type I) in MT-2 cells, an HTLV-I-transformed lymphoid cell line. We found that HTLV-I replication in MT-2 cells was markedly increased as demonstrated by a nearly 2-fold increase in detection of viral p24 antigen and a 20-fold increase in reverse transcriptase activity during up to 5 h of heat treatment at 42 degrees C. The results suggest that physiologic thermal elevations may induce viral production in HTLV-I-infected individuals.
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PMID:In vitro thermal enhancement of human T-cell leukaemia/lymphoma virus type I (HTLV-I) in HTLV-I-transformed cells. 768 46

HAM (HTLV-I-associated myelopathy) rat disease, HAM/TSP (HTLV-I-associated myelopathy/tropical spastic paraparesis)-like myelopathy in rats, occurred in 8 of 8 HTLV-I (Human T cell leukemia virus type I) carrier rats of WKAH strain inoculated with MT-2 cells at either neonates or 4 to 6 months of age. We report here ultrastructural findings of the affected spinal cords and the peripheral nerves of perfusion-fixed HAM rats. They were infected at the age of 4 to 6 months old and showed gait disturbance and hind leg paraparesis 15 months after infection. Pathological alterations of HAM rat disease were mainly confined to marginal areas of white matter of the spinal cord. The affected lesion was rather symmetrical and distributed in the anterior and the lateral columns. A prominent ultrastructural change in the spinal cord was separation of myelin lamellae at the intraperiod line and vacuolation of myelin sheath. Many myelin-debris-filled macrophages and a marked astrogliosis were also observed. In the gliotic areas, lots of demyelinated and remyelinated axons were intermingled. Axons were relatively preserved, however, some of them had tubulo-reticular inclusions. Astrocytes appeared ultrastructurally normal. Lymphocytic infiltration was virtually absent. Ultrastructural alterations of the peripheral nerve were basically similar to those of the spinal cord. Separation of myelin lamellae, macrophages infiltration, demyelination, and remyelination were observed. Schwann cells had also alterations. We observed some apoptotic cell death of the oligodendrocytes and Schwann cells with condensed nucleus and phagocytosis of apoptotic bodies by macrophages. Collective evidence suggests that a series of demyelinating process described above may be caused by apoptosis. No virus particles were seen in the spinal cord and peripheral nerve. Although the precise mechanism of apoptosis is not known at present, possible pathogenetic pathway involving apoptosis in HAM rat disease may contribute greatly to a better understanding of mechanisms implicated in the pathogenesis of HAM/TSP in humans.
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PMID:[Rat model of HTLV-I infection--ultrastructural study of HAM rat disease]. 770 50

To analyze intrauterine transmission, MT-2 cells, a human T-cell line producing human T-cell leukemia virus type I (HTLV-I), were injected into eight pregnant F344 rats, and cesarean section was performed at day 23 of pregnancy. HTLV-I provirus was detected by PCR in the liver and spleen taken from one of the eight fetuses. Moreover, 71 offspring were delivered by cesarean section from the remaining seven dams and fostered by seven normal rats. HTLV-I provirus was detected in peripheral blood mononuclear cells in 2 of the 71 offspring 4 weeks after cesarean section. These results indicate for the first time the intrauterine transmission of HTLV-I. To confirm the postnatal transmission, MT-2 cells were injected into a dam within 24 h after delivery, and six offspring were fostered by this dam. HTLV-I provirus was detected in peripheral blood mononuclear cells of all six offspring. This animal model may be useful for analysis and prevention of mother-to-child transmission of HTLV-I.
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PMID:Intrauterine transmission of human T-cell leukemia virus type I in rats. 781 10

An infectious molecular clone of human T-cell leukemia virus type I (HTLV-I) was derived from an HTLV-I-transformed rabbit T-cell line, RH/K30, obtained by coculture of rabbit peripheral blood mononuclear cells (PBMC) with the human HTLV-I-transformed cell line MT-2. The RH/K30 cell line contained two integrated proviruses, an intact HTLV-I genome and an apparently defective provirus with an in-frame stop codon in the env gene. A genomic DNA fragment containing the intact HTLV-I provirus was cloned into bacteriophage lambda (K30 phi) and subcloned into a plasmid vector (K30p). HTLV-I p24gag protein was detected in culture supernatants of human and rabbit T-cell and fibroblast lines transfected with these clones, at levels comparable to those of the parental cell line RH/K30. Persistent expression of virus was observed in one of these lines, RL-5/K30p, for more than 24 months. Biologic characterization of this cell line revealed the presence of integrated HTLV-I provirus, spliced and unspliced mRNA transcripts, and typical extracellular type C retrovirus particles. As expected, these virus particles contained HTLV-I RNA and reverse transcriptase activity. The transfected cells also expressed surface major histocompatibility complex class II, whereas no expression of this molecule was detected in the parental RL-5 cell line. Virus was passaged by cocultivation of irradiated RL-5/K30p cells with either rabbit PBMC or human cord blood mononuclear cells, demonstrating in vitro infectivity. The virus produced in these cells was also infectious in vivo, since rabbits injected with RL-5/K30p cells became productively infected, as evidenced by seroconversion, amplification of HTLV-I-specific sequences by PCR from PBMC DNA, and virus isolation from PBMC. Availability of infectious molecular clones will facilitate functional studies of HTLV-I genes and gene products.
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PMID:Characterization of an infectious molecular clone of human T-cell leukemia virus type I. 788 47

We demonstrate a significantly high incidence of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM)-or tropical spastic paraparesis (TSP)-like symptoms in WKA rats after injection with HTLV-1-producing MT-2 cells, while no symptoms were observed in F344 rats injected with MT-2 cells or in control WKA rats. Five of the eight (63%) WKA rats injected with MT-2 cells showed HAM/TSP-like paraparesis at 105 weeks of age, but none of seven MT-2-injected F344 rats or eight control WKA rats showed symptoms. This high incidence of HAM/TSP-like symptoms in WKA rats was statistically significant (P < 0.05). Six of the eight (75%) WKA rats injected with MT-2 cells showed HAM/TSP-like paraparesis at 108 weeks of age. HAM/TSP-like symptoms were also observed in one of the two WKA rats injected with HTLV-1-producing Ra-1 cells at 128 weeks of age. HTLV-1 provirus was detected in peripheral blood mononuclear cells in both WKA and F344 rats. The provirus was detected in the spinal cords of the HAM/TSP-like WKA rats that had severe neuropathological changes. WKA and F344 rats showed no significant difference in antibody response against HTLV-1 Gag antigen. However, the antibody response against the C-terminal half of gp46 HTLV-1 envelope protein was lower in WKA rats than in F344 rats. Pathological analysis of the HAM/TSP-like rats showed degeneration of the white matter of the spinal cord and peripheral nerves. These findings suggest that both the genetic background of the host and HTLV-1 infection are important in neuropathogenesis of HAM/TSP-like paraparesis in rats.
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PMID:High incidence of HAM/TSP-like symptoms in WKA rats after administration of human T-cell leukemia virus type 1-producing cells. 793 4

Freshly isolated leukemic cells from patients with adult T-cell leukemia (ATL) and human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively produce high levels of interleukin-6 (IL-6) protein and mRNA. To clarify the mechanisms that lead to the activation of IL-6 gene in HTLV-I-infected cells, we first studied the regulatory regions in the IL-6 gene transcription by transfection of chloramphenicol acetyltransferase (CAT) reporter plasmids containing the IL-6 promoter. When transfected into HTLV-I-infected T-cell lines MT-2 and HUT-102, IL-6 promoter/CAT plasmids were strongly activated without any stimulation. By deletion analysis of 5' upstream region of IL-6 promoter, the DNA region between -73 and -59 bp from the transcription start site of IL-6 gene was important in the expression of IL-6/CAT activities in HTLV-I-infected cells. This region contains nuclear factor (NF)-kappa B binding site. The site-directed mutation of the kappa B motif in IL-6/CAT plasmid resulted in the complete abrogation of IL-6 promoter activity in these cells. Furthermore, when IL-6 promoter/CAT plasmid was introduced into an HTLV-I-uninfected T-cell line, Jurkat, IL-6 promoter activity was silent in the basal level, but strongly increased by the cotransfection with an HTLV-I tax expression plasmid. However, tax expression plasmid showed no transactivation activity, when kappa B site was mutated in IL-6 promoter/CAT plasmid. We found that the IL-6 kappa B site specifically formed a complex with NF-kappa B-containing nuclear extracts from MT-2 and HUT-102 cells. Finally, transfection of HTLV-I tax into Jurkat cells resulted in induction of specific binding of nuclear extracts to the NF-kappa B sequence. These results strongly suggest that HTLV-I tax gene may transactivate IL-6 gene through kappa B site in HTLV-I-positive T-cell lines and activation of NF-kappa B may be crucial in HTLV-I-induced IL-6 gene activation in ATL.
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PMID:Transcriptional regulation of the human interleukin-6 gene promoter in human T-cell leukemia virus type I-infected T-cell lines: evidence for the involvement of NF-kappa B. 794 64

We have previously reported an increase of human T-lymphotropic leukemia/lymphoma virus type I (HTLV-I) replication after heat treatment of MT-2 cells, an HTLV-I-transformed human lymphoid cell line. In this study, we investigated the effect of heat stress on the expression of Hsp27/28 in MT-2 cells. In contrast with previous studies of other cell types, a decrease of Hsp27/28 expression in MT-2 cells and an increase of Hsp70 family proteins in both MT-2 and uninfected lymphoid CEM cells were found following heat treatment at 42 degrees C. Furthermore, heat treatment resulted in an early rapid increase in the phosphorylated form of Hsp27/28 in both MT-2 and CEM cells. The results suggest that early post-translational phosphorylation of HSP27/28 could be a determinant of the ability of MT-2 cells to survive hyperthermia.
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PMID:Decrease of heat shock protein 27/28 with heat stress in HTLV-I-transformed cells. 795 75

Human T cell leukemia virus type I (HTLV-I) can be transmitted into several inbred strains of rats. Adult rats inoculated with HTLV-I immortalized human T cell line MT-2 at 8-37 weeks of age become seropositive HTLV-I carrier rats. Seropositive HTLV-I carrier rats of WKAH strain developed myelopathy similar to HAM/TSP (HTLV-I associated myelopathy/Tropical spastic paraparesis), designated as HAM rat disease. Neuropathological and immunohistochemical features of the affected spinal cord showed symmetrical white matter degeneration characterized by loss of myelin, vacuolar degeneration, infiltration with foamy macrophages and astrocytic gliosis. Lymphocytic infiltration was virtually absent throughout the disease process, and apoptotic cells were observed in the affected spinal cord. Clinical findings and pathological changes in seropositive HAM rats were, in general, milder than findings in seronegative HAM rats as previously described. Provirus genome in the affected spinal cord was evident in 1 of 2 seropositive HAM rats by polymerase chain reaction, but localization of HTLV-I antigen could not be detected by immunohistochemical staining. The collective evidence suggests that development of HAM rat disease is under strict genetic restriction of the host strain, and the primary cause is not mediated by immunological process with effector T cells as suggested in human HAM/TSP, and there seems to be a direct or indirect neurotoxicity for oligodendrocytes mediated by HTLV-I infection.
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PMID:[Analysis of HAM rat disease developed in HTLV-I carrier rat as an animal model of HAM/TSP in human]. 795 97

Human T-cell leukemia virus type I (HTLV-I) encodes a strong transcriptional activator, Tax, that stimulates transcription indirectly through the viral long terminal repeat and also activates a number of cellular genes via association with host transcription factors. The NF-kappa B/Rel pathway is a target for Tax trans-activation, and Tax has been correlated with increased NF-kappa B-binding activity and NF-kappa B-dependent gene expression in HTLV-I-infected cells. In this study we demonstrate that constitutive phosphorylation and increased turnover of the regulatory I kappa B alpha protein in HTLV-I-infected MT-2 and C8166 cells and Tax-expressing 19D cells contribute to constitutive NF-kappa B-binding activity, which consists primarily of c-Rel, p52(NFKB2), and p50(NFKB1). I kappa B alpha mRNA expression is also increased 7- to 20-fold in these cells, although the steady-state level of I kappa B alpha protein is reduced in HTLV-I-infected and Tax-expressing T cells. These results indicate that the viral Tax protein, by indirectly mediating phosphorylation of I kappa B, may target I kappa B alpha for rapid degradation, thus leading to constitutive NF-kappa B activity.
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PMID:Constitutive phosphorylation and turnover of I kappa B alpha in human T-cell leukemia virus type I-infected and Tax-expressing T cells. 798 56

Human Jurkat T cells containing a stably integrated human T cell leukaemia virus type 1 (HTLV-1) long terminal repeat (LTR) reporter gene construct were used to study the role of calcium-dependent cellular activation pathways in LTR trans-activation. Treatment of these cells with the calcium ionophore ionomycin resulted in a reduced basal response of the LTR and reduced responses to 12-O-tetradecanoylphorbol-13-acetate-and Tax-mediated trans-activation. This effect was also observed for virus production in the HTLV-1-producing T cell line MT-2. Experiments designed to determine the events underlying this inhibition, using inhibitors of calcium-related events, revealed that the ionomycin-induced repression of the LTR was alleviated in all cases by cyclosporin A. This compound was also effective in preventing the ionomycin-induced reduction in virus production in MT-2 cells. These results suggest a role for calcium-related events in the down-regulation of HTLV-1 expression.
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PMID:Calcium-mediated inhibition of phorbol ester and Tax trans-activation of the human T cell leukaemia virus type 1. 802 93


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