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-cell leukemia virus type 1 (HTLV-1) immortalizes human CD4+ T lymphocytes in culture. Previous studies show that in the context of a herpesvirus saimiri vector, the sequence of the X region at the 3' end of the HTLV-1 genome is also capable of immortalizing CD4+ lymphocytes in the absence of HTLV-1 structural proteins. The X region of HTLV-1 encodes two trans-acting viral proteins, the 42-kDa Tax protein and the 27-kDa Rex protein. Infection of human cord blood cells with herpesvirus saimiri recombinants which contain HTLV-1 X region sequences defective for expression of tax, rex, or both tax and rex demonstrates that tax function is necessary and sufficient for immortalization of primary human CD4+ cord blood lymphocytes in culture in the context of the herpesvirus saimiri vector.
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PMID:Role of human T-cell leukemia virus type 1 X region proteins in immortalization of primary human lymphocytes in culture. 135 Nov 5

Sixty-four consecutive febrile episodes in 50 consecutive patients with malignancy and neutropenia were empirically treated with a combination of ceftazidime and amikacin. Of 52 analysable episodes, the response rate was 59.6% overall and 26.3% of episodes with microbiologically documented infections with septicaemia. Infection-related death occurred in 10 patients (19.2% of episodes). The response rates were similar in patients with acute leukaemia or other malignancies. Poor response is attributed to increased frequency of infections with Gram-positive and fungal organisms. A modified empiric regimen including cover for Gram-positive and fungal organisms is suggested in similar patient populations.
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PMID:Ceftazidime and amikacin as empiric treatment of febrile episodes in neutropenic patients in Saudi Arabia. 808 23

We have shown previously that infection of mononuclear cells derived from neonatal cord (CBMC) or adult peripheral (PBMC) blood with HTLV-1 can be controlled in vitro by treatment with interferon (IFN) alpha, beta or gamma. The activity of IFNs was mainly related to the induction of an active antiviral competence in host's immune effector cells. The antiviral activity of IFN-boosted CBMC could be ascribed both to a positive regulation of cell-mediated immunity and to inhibition of viral infection. Data described herein provide further information on the mechanisms of the antiviral activity of IFNs and compare the activity of each type of IFN with the association of alpha + beta, alpha + gamma and beta + gamma IFNs, at a concentration of 100 or 1000 IU/ml. When added at the onset of the co-culture of CBMC with lethally irradiated, virus-donor MT-2 cells, IFNs could protect host CBMC by inhibiting HTLV-1 infection in terms of reduced proviral integration and a lower percentage of virus-positive cells, until 4 weeks of culture. Infection of CBMC was inhibited at a comparable extent by either individual or combined IFN treatments. However, a clearcut inhibition of HTLV-I transcription was found only when alpha 100 + beta 1000 IU/ml and especially alpha 1000 + gamma 100 IU/ml combined treatments were tested. When the chronically infected, virus-producing MT-2 cells were treated with IFNs, a remarkable inhibition of HTLV-I transcription was found only after multiple treatments. However, MT-2 cells became resistant to the antiviral activity of IFN gamma, but not to that of IFN alpha or beta. These data provide further information on the control of HTLV-I replication mediated by IFNs at different steps of the viral life cycle, being therefore relevant to the clinical use of combined IFNs in the treatment of acute infection. Moreover, IFNs could be used to prevent the establishment of a persistent infection, which is a prerequisite for developing adult T-cell leukemia (ATL) and/or virus-associated myelopathy.
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PMID:Antiviral activity of individual versus combined treatments with interferon alpha, beta and gamma on early infection with HTLV-I in vitro. 142 62

The pathogenesis of progressive spastic paraparesis [HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)], a serious consequence of human T-cell leukemia virus type I (HTLV-I) infection, is unclear. T and B lymphocytes can be naturally infected by HTLV-I, but the susceptibility to HTLV-I infection of other cell types that could contribute to the pathogenesis of HAM/TSP has not been determined. We found that a human monocyte cell line (THP-1), primary human peripheral blood monocytes, and isolated microglial cells but not astrocytes or oligodendroglial cells derived from adult human brain were infected by HTLV-I in vitro. Infection with HTLV-I enhanced the secretion of interleukin 6 in human microglial cell-enriched cultures but did not stimulate the release of interleukin 1 from monocytes or microglial cells. Tumor necrosis factor alpha production was stimulated by HTLV-I infection of monocytes and microglial cells and could be enhanced by suboptimal amounts of lipopolysaccharide. Since both tumor necrosis factor alpha and interleukin 6 have been implicated in inflammatory demyelination and gliosis, our findings suggest that human microglial cells and monocytes infected with and activated by HTLV-I could play a role in the pathogenesis of HAM/TSP.
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PMID:Human T-cell leukemia virus type I infection of monocytes and microglial cells in primary human cultures. 146 99

Symptomatic patients with myelodysplastic syndromes (MDS) and 10-30% blasts in the bone marrow were treated with low-dose AraC (2 x 10 mg/m2 subcutaneously (sc) days 1-14) and GM-CSF (fully glycosylated, Sandoz/Schering-Plough, 2 x 150 micrograms protein/day sc) given either subsequently (days 15-21) or simultaneously (days 8-14 and one week rest). Evaluations were carried out after three courses (nine weeks); responding patients could be continued for two further cycles. Eighty-two patients with refractory anaemia and excess of blasts (RAEB), with (RAEBt) or without transformation, were evaluable: 45 RAEB and 37 RAEBt, mean age 64 years (range 17-80 years). A complete remission was achieved in 14 cases (17%), 11 had a good response (13%), and 12 a partial response (15%). Stable disease was found in 21 cases (26%). There were 12 cases of toxic death (15%), progression was noted in eight patients (10%), and death due to disease in three (4%). No difference existed between the two treatment arms with respect to response. Major adverse events during treatment were haemorrhage (25%), infections (23%), and fever with GM-CSF (21%). GM-CSF did not induce leukaemia nor contribute to haemorrhage induced by AraC, but gave rise to an overall response rate of 46% which is high and relatively durable as compared to other treatments in this disease.
Infection 1992
PMID:Treatment of myelodysplastic syndromes (MDS) and high leukaemic risk with low-dose cytosine arabinoside (LD-AraC) plus granulocyte-macrophage colony-stimulating factor (rh GM-CSF). The EORTC Leukaemia Group. 149 35

Retroviral interference is manifested in chronically infected cells as a decrease in susceptibility to superinfection by virions using the same cellular receptor. The pattern of interference reflects the cellular receptor specificity of the chronically infecting retrovirus and is mediated by the viral envelope glycoprotein, which is postulated to bind competitively all cellular receptors available for viral attachment. We established retroviral interference in mice by infecting them with Friend murine leukemia virus and them measured susceptibility to superinfection by challenging the mice with the erythroproliferative spleen focus-forming virus. Infection of approximately 10% of nucleated splenocytes rendered mice 1% as susceptible to superinfection as untreated controls. The magnitude of this effect was the same in mice incapable of producing neutralizing antibodies or genetically deficient for T cells. The results indicated that retroviral interference in vivo was established rapidly with infection of a fraction of the host cell population and that the decrease in susceptibility to superinfection occurred without a detectable contribution by immunologic factors.
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PMID:Interference established in mice by infection with Friend murine leukemia virus. 150 2

A statistical analysis of possible risk factors for relapse during maintenance therapy (MT) for acute lymphoblastic leukemia (ALL) has been performed. The patient material consists of 64 patients. Twenty-six patients were classified as standard risk (SR), 21 as intermediate risk (IR), and 17 as high-risk (HR) patients. Seventeen patients relapsed and 50 patients (78%) are alive at a median observation period of 86 months (range 39-146 months). Mean white blood cell count (mean WBC) based on weekly determinations, duration of treatment interruption, and the number of infectious episodes were calculated in each patient during the first 6 months of MT. In analyses starting at 6 months after the beginning of MT, these factors were related to relapse risk, time to relapse, and time to infection. Using the median WBC value (3.9 x 10(9)/L) of all patients during the first 6 months as a cutoff point, 14 patients with levels higher, and 3 patients with levels lower relapsed (p = .0004). Adjustment of mean WBC for leukemia risk groups had no influence on the analysis. Time to relapse was related to duration of interruption of MT (p less than .01). Time to relapse was not related to leukemia risk groups. Infection frequency was higher in HR patients compared to SR and IR risk patients (p = .04). As WBC level had a prognostic value and was previously shown to be related to 6-mercaptopurine (6-MP) peak plasma concentration, monitoring 6-MP plasma levels during MT could be helpful for optimizing treatment.
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PMID:Relapse factors during maintenance therapy of acute lymphoblastic leukemia in children. 155 73

Transgenic mice bearing a mutant, activated N-ras oncogene directed to express within hematopoietic cells by an immunoglobulin enhancer (E mu) sporadically develop T-cell lymphomas and non-lymphoid tumors that may be of macrophage origin. To identify genes that can collaborate with N-ras in hematopoietic neoplasia, Moloney murine leukemia virus was used as an insertional mutagen. Infection of newborn E mu-N-ras mice with the virus greatly accelerated tumorigenesis, and nearly all the tumors proved to be T-cell lymphomas. Their variable surface phenotype (CD4+CD8-, CD4+CD8+ and CD4-CD8-) suggested that cells at several stages of T-cell development were susceptible to tumorigenesis. Southern blot analysis revealed that 68% of the tumors bore a proviral insert 5' to the c-myc gene, while 13% had an insert within the 3' untranslated region of the N-myc gene. Insertion was associated with elevated expression of these genes. Hence, activation of a myc gene appears to be the dominant pathway to tumorigenesis by insertional mutagenesis in lymphoid cells expressing a mutant ras gene. However, since many of the tumors were not transplantable, even the partnership of myc and ras may not suffice for full lymphoid malignancy.
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PMID:Retroviral infection accelerates T lymphomagenesis in E mu-N-ras transgenic mice by activating c-myc or N-myc. 157 Jan 58

Natural transmission of bovine leukaemia virus (BLV) infection in south-eastern Queensland dairy herds was slow in 2 herds with a low to moderate (13 to 22%) prevalence of infection. Infection spread much more rapidly in a herd that had a higher prevalence (42%) when first tested. In a 13 month study of this herd, the cumulative incidence of infection was 24%. In one herd new infections were confined almost entirely to calves of uninfected dams. Following the end of feeding bulk milk to calves, a common practice in dairy herds, no more calves in this herd became infected. In laboratory experiments, neither prolonged housing of susceptible calves with infected cattle, consumption of drinking water contaminated with infected blood, nor inoculation of sheep with saliva from infected cattle resulted in transmission of BLV infection. Sheep were infected by subcutaneous inoculation of a suspension of purified lymphocytes from an infected heifer. The minimum infective dose was 10(3) lymphocytes, equivalent to the number of lymphocytes in approximately 0.1 microliter blood. Thus, procedures involving the transfer of a very small volume of blood from animal-to-animal have the potential to transmit infection.
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PMID:Factors affecting the natural transmission of bovine leukaemia virus infection in Queensland dairy herds. 165 25

Infection with human T-cell leukemia virus type-I (HTLV-1) is associated with a low incidence of morbidity in the form of adult T-cell leukemia as well as neurologic disease, including tropical spastic paraparesis/HTLV-I-associated myelopathy, suggesting that there are other important factors which determine outcome of infection. HTLV-I and the human herpesvirus, cytomegalovirus (HCMV), have both been shown to infect OKT4+ T lymphocytes in vitro as well as in vivo. We investigated the effects of expression of HCMV IE-2 protein(s) on the HTLV-I long terminal repeat (LTR) containing the promoter elements in T-cell lines and primary lymphocytes. A consistent repressive effect was observed on HTLV-I LTR-driven chloramphenicol acetyl transferase activity after cotransfection with the HCMV IE-2 gene region, both in HTLV-I-producing cell lines as well as in uninfected primary peripheral blood lymphocytes and cloned lymphocyte lines. This repressive effect on the HTLV-I LTR by the HCMV IE-2 gene product(s) represent a unique interaction between two viruses capable of infecting the same target cell in vivo. Such an interaction may have important implications for disease expression associated with HTLV-I infection.
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PMID:The promoter of human T-cell leukemia virus type-I is repressed by the immediate-early gene region of human cytomegalovirus in primary blood lymphocytes. 165 69


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