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 immunodeficiency virus (HIV) Rev protein is essential for viral structural protein expression (Gag, Pol, and Env) and, hence, for viral replication. In transient transfection assays, mutant forms of Rev have been identified that inhibit wild-type Rev activity and therefore suppress viral replication. To determine whether such transdominant Rev proteins could provide long-term protection against HIV infection without affecting T cell function, T leukemia cell lines were stably transduced with a retroviral vector encoding a transdominant mutant of the Rev protein, M10. While all the M10-expressing cell lines remained infectable by HIV-1, these same cells failed to support a productive replication cycle when infected with a cloned isolate of HIV-1. In addition, two out of three M10-expressing CEM clones were also resistant to highly productive infection by a heterogeneous HIV-1 pool. Expression of M10 did not affect induction of HIV transcription mediated by the kappa B regulatory element or Tat. Importantly, constitutive expression of Rev M10 did not alter the secretion of interleukin 2 in response to mitogen stimulation of EL-4 and Jurkat cells. The inhibition of HIV infection in cells stably expressing a transdominant Rev protein, in the absence of any deleterious effect on T cell function, suggests that such a strategy could provide a therapeutic effect in the T lymphocytes of acquired immunodeficiency syndrome patients.
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PMID:Stable expression of transdominant Rev protein in human T cells inhibits human immunodeficiency virus replication. 140 61

Oxygen radical scavengers, such as dithiocarbamates and cysteine derivatives, inhibit activation of the ubiquitous transcription factor nuclear factor kappa B (NF-kappa B) after treatment of cells with tumor necrosis factor, phorbol ester, and interleukin-1. An involvement of oxygen radicals was more directly evident from the induction of NF-kappa B by low concentrations of H2O2 and the demonstration that cells stimulated with various NF-kappa B inducers release H2O2 and superoxide. In this study, we used the antioxidant pyrrolidine dithiocarbamate (PDTC) to investigate whether the activation of NF-kappa B by the viral transactivator Tax from human T-cell leukemia virus type I also depends on the production of reactive oxygen intermediates. The Tax-induced activation of the DNA-binding activity of NF-kappa B in Jurkat T cells was potently suppressed by micromolar concentrations of PDTC. Within the same concentration range, PDTC and two other dithiocarbamates also strongly interfered with transactivation of the long terminal repeat (LTR) of human immunodeficiency virus type 1 by Tax but had no effect on transactivation of the same LTR by Tat. Transactivation of the human T-cell leukemia virus type I LTR by Tax was also barely influenced. Tax seems to activate NF-kappa B by a mechanism shared with all other inducers of NF-kappa B tested so far. It appears that one of the pleiotropic activities of Tax leads to an enhanced production of oxygen radicals that are required for activation of NF-kappa B.
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PMID:Antioxidants selectively suppress activation of NF-kappa B by human T-cell leukemia virus type I Tax protein. 140 92

Complex retroviruses are distinguished by their ability to control the expression of their gene products through the action of virally encoded regulatory proteins. These viral gene products modulate both the quantity and the quality of viral gene expression through regulation at both the transcriptional and posttranscriptional levels. The most intensely studied retroviral regulatory proteins, termed Tat and Rev, are encoded by the prototypic complex retrovirus human immunodeficiency virus type 1. However, considerable information also exists on regulatory proteins encoded by human T-cell leukemia virus type I, as well as several other human and animal complex retroviruses. In general, these data demonstrate that retrovirally encoded transcriptional trans-activators can exert a similar effect by several very different mechanisms. In contrast, posttranscriptional regulation of retroviral gene expression appears to occur via a single pathway that is probably dependent on the recruitment of a highly conserved cellular cofactor. These two shared regulatory pathways are proposed to be critical to the ability of complex retroviruses to establish chronic infections in the face of an ongoing host immune response.
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PMID:Mechanism of action of regulatory proteins encoded by complex retroviruses. 140 88

Two patients with haematologic malignancies developed Pneumocystis carinii pneumonia while under outpatient treatment, one on busulphan for chronic myelogen leukemia, and the other on prednisone plus chlorambucil for non-Hodgkin's lymphoma. The first patient was moderately ill and required hospitalization for 12 days while the second patient was critically ill and needed assisted ventilation for two weeks. Eventually they both recovered and returned to work. Tests for serum antibodies to the human immunodeficiency virus (HIV) were negative in both patients. We review the problem of P. carinii pneumonia in patients receiving immunosuppressive drugs.
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PMID:[Pneumocystis carinii pneumonia--not only in AIDS]. 141 21

During 1987-1988, a seroprevalence study of the human immunodeficiency virus (HIV-1) and the human T-cell lymphoma/leukemia virus (HTLV-I/II) was performed among Detroit intravenous drug users unaffiliated with substance abuse programs. Seroprevalence data along with patient demographic information were compared to a similar study performed in 1985-1986. In the earlier study, 12 (12.5%) of 96 individuals tested positive for HIV-1. Of the 74 available negative samples retested in 1987-1988 for retroviruses, 7 (9.5%) tested positive for HTLV-I/II. Thus, the overall retroviral (HIV-1, HTLV-I/II) seropositive rate for 1985-1986 was 22%. In 1987-1988, 11 (15.7%) of 70 individuals tested positive for HIV-1 and 7 (10%) tested positive for HTLV-I/II. Concomitant infection with both viruses was found in 2 (2.9%) of the 70 individuals. Thus, retrovirus seroprevalence in 1987-1988 was 22.9%. In 1987-1988, significant differences between the retroviral-positive group and the retroviral-negative group consisted of intravenous drug use greater than 16 years (P = 0.059) for an odds ratio of 3.80 (CI 1.12-12.89) and sex with female prostitutes (P = 0.029) for an odds ratio of 5.38 (CI 1.38-20.95).
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PMID:The emerging role of HTLV-I/II and HIV-1 among intravenous drug users in Detroit. 142 66

Serum and aqueous humor samples, collected from 14 clinically normal cats and 96 cats with clinical evidence of intraocular inflammation, were assayed with ELISA for Toxoplasma gondii-specific immunoglobulin M (IgM), T gondii-specific IgG, T gondii-specific antigens, total IgG, and total IgM. Additionally, serum was assayed with ELISA for feline leukemia virus p27 antigen and antibodies against the feline immunodeficiency virus as well as with an immunofluorescent antibody assay for antibodies against feline coronaviruses. Calculation of the Goldmann-Witmer coefficient (C-value) for the T gondii-specific antibodies detected in aqueous humor established the likelihood of local antibody production. Serologic evidence of present or prior infection by an infectious agent was found in 81.9% of the clinically affected cats from which serologic results were available (77/94 cats). Seropositive results for toxoplasmosis were found in 74.0% of the clinically affected cats. Anterior segment inflammation was found in 93.1% (81/87 cats from which information was available) of the clinically affected cats, most of which were older males. Toxoplasma gondii-specific antibodies were not detected in the aqueous humor of 6 seropositive, clinically normal cats. The C-values for aqueous T gondii antibodies were greater than 1 in 44.8% of the cats and greater than 8 in 24.0% of the cats. Response to treatment with clindamycin HCl was positive in 15/20 (75%) of the T gondii-seropositive, clinically affected cats treated with this drug. In 13/15 (86.7%) T gondii-seropositive, clinically affected cats having a C-value greater than 1, response to treatment with clindamycin HCl was positive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enzyme-linked immunosorbent assays for the detection of Toxoplasma gondii-specific antibodies and antigens in the aqueous humor of cats. 142 23

We have made 47 mutations that span the length of the human T-cell leukemia virus type I (HTLV-I) Tax open reading frame. Of the 47 mutations, 38 were substitutions of single amino acids, 5 were missense changes in two or more amino acids, and 4 were deletions. A subset of these mutations includes individual changes of all 26 naturally occurring serines to alanines. By assaying each mutant protein separately on the HTLV-I long terminal repeat (LTR) and the human immunodeficiency virus type 1 (HIV-1) LTR in parallel, we were able to identify regions of Tax selectively necessary for each promoter. A small region in the carboxyl terminus, amino acids 315 to 325, was found to be selectively important for activation of the HTLV-I LTR. Three changes at serine 113, serine 160, and serine 258 were found to specifically affect function on the HIV-1 LTR. Surprisingly, we found that the great preponderance of missense changes (32 of 42) in Tax did not affect function.
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PMID:Mutational analysis of human T-cell leukemia virus type I Tax: regions necessary for function determined with 47 mutant proteins. 143 11

The human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex proteins induce cytoplasmic expression of incompletely spliced viral mRNAs by binding to these mRNAs in the nucleus. Each protein binds a specific cis-acting element in its target RNAs. Both proteins also associated with nucleoli, but the significance of this association is uncertain because mutations that inactivate nucleolar localization signals in Rev or Rex also prevent RNA binding. Here we demonstrate that Rev and Rex can function when tethered to a heterologous RNA binding site by a bacteriophage protein. Under these conditions, cytoplasmic accumulation of unspliced RNA occurs without the viral response elements, mutations in the RNA binding domain of Rev do not inhibit function, and nucleolar localization can be shown to be unnecessary for the biological response.
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PMID:Posttranscriptional regulation by the human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex proteins through a heterologous RNA binding site. 143 16

Primate and non-primate species have been used to study the pathobiology of the simian immunodeficiency virus (SIV) and of the human immunodeficiency virus type 1 (HIV-1), respectively, and to develop new therapeutic regimes. Transgenic mice which express either the entire HIV-1 provirus or subgenomic fragments have been used to analyze viral gene products in vivo and may serve as models for the development of agents targeted to select viral functions. Chimeric mice which were created by transplanting human hematolymphoid cells into mice suffering from congenital severe combined immunodeficiency (scid/scid or so called SCID mice), can be infected with HIV-1 and allow one to study the entire HIV-1 replicative cycle. Type C murine leukemia virus models have been used to develop new prophylactic and therapeutic strategies but their use is restricted to the evaluation of select antiviral drug inhibition, targeted to retroviral genes common to both Lentivirinae and Oncovirinae. The role of various animal model systems in the development of anti-HIV-1 and anti-AIDS therapies is summarized.
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PMID:Animal models for anti-AIDS therapy. 144 26

This article reviews the virological and epidemiological data available on transmission of the human immunodeficiency virus type 1 (HIV-1) by breast milk. Colostrum and breast milk are considered major modes of transmission for many animal retroviruses as well as human T-cell leukemia virus, mainly as the consequence of ingestion of infected cells. Several cases that strongly suggest transmission of HIV-1 through breast-feeding have now been reported. In addition, recent evidence suggests that postpartum HIV-1 seroconversion of a mother may be associated with a high risk of postnatal transmission to offspring via breast milk. Preventive measures such as pasteurization of breast milk have not been fully examined. While the World Health Organization continues to promote breast-feeding in areas where no safe alternative exists, the Centers for Disease Control recommends that American women who are infected by HIV-1 not practice breast-feeding if a safe alternative is available. Large-scale, carefully controlled, prospective studies of the risk of HIV-1 infection associated with breast-feeding are of the utmost priority. Feasible and ethically acceptable feeding alternatives should be developed for countries where formula feeding has a strong negative effect on child morbidity and mortality.
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PMID:Mother-to-infant transmission of human immunodeficiency virus by breast milk: presumed innocent or presumed guilty? 144 96


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