Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A fully automated instrument for multiple simultaneous peptide synthesis was constructed to provide large numbers of peptides for immunological research. The synthesis is performed in a flow-through mode with the conventional solid supports contained in 48 individual reaction columns. The instrument is based on a commercial autosampler equipped with a motor-driven syringe for accurate delivery of reagents and a robot arm carrying a dispenser needle. Dedicated software was developed to compile overlapping peptides from a given protein sequence and to control all functions of the robot. In situ activation by BOP was chosen as the optimized chemistry protocol. The peptides are cleaved from the resin in the reactors used for synthesis, thus minimizing handling. Performance of the instrument was demonstrated by synthesis of overlapping 14-mer peptides derived from the sequence of HIV reversed transcriptase. A second mode of operation allows the synthesis to be carried out on the surface of polyethylene pins. Peptides derived from the sequence of human TNF were synthesized using this method and used to characterize antibodies raised against the intact protein.
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PMID:Automated multiple peptide synthesis. 128 42

The recombinant plasmid pBHIV-1 carrying the long terminal repeat (LTR) of the human immunodeficiency virus 1 (HIV-1), linked to the reported chloramphenicol acetyl transferase (CAT) gene, was introduced into human and rat fibroblasts. Stable transfectants were obtained which were resistant to genetecin and expressed CAT-activity from the HIV-1 LTR. The response to TNF alpha was studied. It was found that, at the optimum concentration of 100 IU/ml in human and 1000 IU/ml in rat fibroblasts, the expression of CAT was stimulated by 2.1 and 2.5-fold respectively. Our findings suggest that TNF-alpha in physiological concentrations can transcriptionally activate the HIV-1 LTR sequences and this may play an important role in the pathogenesis of HIV infection.
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PMID:Transcriptional activation of the human immunodeficiency virus long terminal repeat sequences by tumor necrosis factor. 129 50

We report a new suppressor function of CD8+ CD57+ lymphocytes from HIV-seropositive patients recipients, on the cytolytic activity of allospecific CTL, NK and LAK cells. This inhibitory effect is mediated by a non-antigen specific soluble factor distinct from PGE2, TGF beta and TNF alpha and beta. Biochemical characterization indicates that the CD8+ CD57+ inhibitory activity: 1) is heat and trypsin resistant but remains sensitive to pronase E hydrolyse, 2) specifically bind to concanavalin A-sepharose column, 3) is mediated by a 20-30 kdaltons glycoprotein.
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PMID:[Cytotoxic response against human immunodeficiency virus (HIV): control with suppressor factor]. 130 Dec 26

The numerous biologic activities of TNF appear mediated by two types of specific cell surface receptors of 55 to 60 kDa (TR55) and 75 to 80 kDa (TR75) molecular mass, respectively. The role of TR55 in the activation of the nuclear transcription factor kappa B (NF-kappa B) was investigated using an antagonistic, mAb, H398, specific for the human TR55. The human leukemic T cell line, Jurkat, which expresses both types of receptors at comparable levels, was used to test for NF-kappa B activation by electrophoretic mobility shift assays using as a probe an oligonucleotide encompassing the two tandemly arranged kappa B sites of the HIV-1 LTR enhancer. mAb H398 is shown to efficiently block not only TNF- but also lymphotoxin-mediated activation of NF-kappa B. Furthermore mAb H398 also impeded TNF- or lymphotoxin-mediated activation of chloramphenicol acetyl transferase gene expression from the HIV-1-LTR as determined by transient transfection assays. These findings indicate that both, induction of NF-kappa B binding to DNA, and transcriptional activity can be efficiently inhibited by selective blockade of TR55. Finally it is shown, that human TR55 confers NF-kappa B inducibility when expressed in the mouse pre-B cell line 70Z/3, which does not respond to TNF in its parental state. Together, the results of this study indicate that TR55 is both necessary and sufficient for mediating TNF activation of NF-kappa B.
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PMID:Inhibition of tumor necrosis factor (TNF)-mediated NF-kappa B activation by selective blockade of the human 55-kDa TNF receptor. 131 30

Adherent cells from HIV-infected subjects as well as in vitro HIV-infected normal adherent cells produce spontaneously a 29-kD (p29) factor that inhibits mitogen-induced proliferation of normal T cells. p29 mediates a partial dose-dependent inhibition of total protein synthesis in both nonstimulated and PHA-activated cells that is associated with impaired PHA-induced expression of IL-2 receptor (IL-2R)alpha chain, HLA-class II molecules, and production of IL-2 by these cells; conversely, p29 does not modify the expression of IL-2R beta chain, 4F2, CD9, or transferrin receptor, or the production of IL-1 and TNF alpha by the cells. 1 h preincubation of the cells with p29 is sufficient to detect its biologic activity and added rIL-2 abrogates p29-induced inhibition of IL-2R alpha chain expression; however, p29 does not display any biologic effect on already expressed IL-2R alpha chains. The impaired expression of IL-2R alpha chain mediated by p29 is not due to a decreased accumulation of the corresponding mRNA transcripts, but is associated with a two-fold increase of intracellular cAMP. Binding experiments with 125I-rIL-2 reveals that p29 induces a 50% decrease in the number of both high and low affinity IL-2R per cell. p29 also inhibits alloantigen-induced proliferation of PBMC, whereas it does not modify IL-2-dependent proliferation of 48-h PHA-blasts that already express high affinity IL-2R. These findings indicate that p29 mediates its biologic activity during early stages of T cell activation affecting the expression of high affinity IL-2R and production of IL-2, through a nontranscriptional mechanism involving an increase of intracellular cAMP.
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PMID:Human immunodeficiency virus-infected adherent cell-derived inhibitory factor (p29) inhibits normal T cell proliferation through decreased expression of high affinity interleukin-2 receptors and production of interleukin-2. 132 45

Serum levels of the soluble form of tumour necrosis factor receptor type II (p75) (sTNF-R) were determined in HIV-infected individuals and risk groups and were then correlated with the course of infection and prognosis. sTNF-R levels were determined by an ELISA with MoAbs and polyclonal antibodies to urine-derived sTNF-R proteins. The mean +/- s.e. levels of sTNF-R in the sera of 49 HIV+ male homosexuals, 34 HIV- male homosexuals and 44 matched controls were 6.1 +/- 0.3 ng/ml, 4.4 +/- 0.3 ng/ml and 3.4 +/- 0.2 ng/ml, respectively. All these values were significantly different between each of the groups (P less than 0.001-0.05). Sequential studies of sTNF-R revealed higher levels following seroconversion in 5/8 individuals, remained persistently high during the asymptomatic phase of the infection and became even more elevated in some ARC and AIDS patients. At the same time TNF-alpha was undetectable in sera obtained from HIV+ male homosexuals and from healthy controls. This was independent of stage of HIV infection, serum sTNF-R level and type of ELISA kit used. These findings suggest that TNF-alpha/TNF-R system is turned on before and during HIV infection and raise the possibility that sTNF-R, the natural inhibitor of TNF, may be of importance in determining the course and probably prognosis of the disease.
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PMID:Elevated serum levels of soluble tumour necrosis factor receptors (sTNF-R) in patients with HIV infection. 132 3

Tumor necrosis factor-alpha (TNF-alpha) induces the expression of human immunodeficiency virus type-1 (HIV-1) in vitro in chronically infected cells of T and monocytic origin. The tat protein from the HIV-1 virus has been shown to be essential for HIV replication and in the immunosuppression associated with the virus infection. Previous studies in our laboratory have shown that HIV-1 tat gene induces TNF-beta (lymphotoxin) in human B-lymphoblastoid cells (Sastry et al., 1990, J. Biol. Chem. 265, 20091-20093). In an attempt to characterize further the relationship between the host and HIV-1, we investigated the effect of the functional HIV-1 tat gene on the expression of TNF receptors in a human B lymphoblastoid cell line (Raji). We report here that Raji cells transfected with HIV-1 tat gene express fewer cell surface TNF receptors than control cells. At least a 5-fold decrease in the receptor number without any significant change in receptor affinity was observed. The decrease in TNF receptors in tat-transfected Raji cells (Raji-tat cells) was found not to be due to receptor occupancy by the autocrine production of TNF-beta. The decrease in the cell surface expression of TNF receptors in Raji-tat cells was also found to be not due to a decrease in the gene expression of the receptor. The kinetics, amount of TNF binding and its internalization were temperature dependent, and it was different in Raji-tat cells than in the control cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Down-modulation of cell surface expression of p80 form of the tumor necrosis factor receptor by human immunodeficiency virus-1 tat gene. 133 62

Tumor necrosis factor alpha (TNF alpha) levels were determined by enzyme-linked immunosorbent assay (ELISA) and by cell culture bioassay in supernatants of lipopolysaccharide-stimulated feline monocyte cultures and in cat serum samples. There was a good correlation between the results obtained by the two methods. From the fact that TNF alpha was neutralized quantitatively by antibodies to human TNF alpha in feline monocyte supernatants and in feline sera, it was concluded that feline TNF alpha immunologically cross-reacts with human TNF alpha and that the human TNF alpha ELISA can be used to quantitate feline TNF alpha. During the first 6 months after experimental feline immunodeficiency virus (FIV) infection no differences in serum TNF alpha values were observed between infected and non-infected cats. TNF alpha levels increased significantly after primary vaccination with a feline leukemia virus (FeLV) vaccine in FIV infected cats over those in the non-infected controls. During secondary immune response TNF alpha levels rose transiently for a period of a few days in both the FIV positive and the FIV negative cats. After FeLV challenge, TNF alpha levels increased in all animals challenged with virulent FeLV for a period of 3 weeks. This period corresponded to the time necessary to develop persistent FeLV viremia in the control cats. It was concluded from these experiments that in the asymptomatic phase of FIV infection no increased levels of TNF alpha are present, similar to the situation in asymptomatic HIV infected humans. Activation of monocytes/macrophages in FIV infected cats by stimuli such as vaccination or FeLV challenge readily leads to increased levels of TNF alpha.
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PMID:Tumor necrosis factor alpha levels in cats experimentally infected with feline immunodeficiency virus: effects of immunization and feline leukemia virus infection. 133 3

Tumor necrosis factor is a cytokine that participates in the mediation of numerous diseases associated with inflammation, cachexia, shock, and tissue injury. Early studies of the biology of TNF delineated its hormonal actions as well as its systemic toxicity. More recent investigations have drawn attention to its paracrine actions that predominate when it is produced locally in the brain or vital organs. For instance, when compartmentalized production of TNF occurs in the central nervous system it directly mediates fever, anorexia, and altered whole-body metabolism. Since these changes are mediated within the neural network they occur independently of simultaneously sampled serum TNF levels. These paracrine actions of TNF have implications for diseases associated with production of TNF in tissues (e.g. HIV cerebritis, multiple sclerosis, cerebral malaria and cancer), because they may differ markedly from the hormone like-actions associated with systemic release. Since TNF may be beneficial in some diseases yet injurious in others, both the hormonal and paracrine actions must be precisely defined in order to formulate novel treatment strategies based on either enhancing its useful effects, or suppressing toxicity.
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PMID:Tumor necrosis factor in metabolism of disease: hormonal actions versus local tissue effects. 134 May 27

The mechanism for the gradual loss of CD4+ T lymphocytes and the development of the slowly progressive inflammatory/degenerative lesions that accompany human immunodeficiency virus infection are poorly understood. Using the Simian immunodeficiency virus (SIVmac) macaque model of AIDS, we found that persistently infected primary macrophages fuse with primary activated CD4+ lymphocytes and that this interaction results in production of tumour necrosis factor-alpha (TNF alpha) and interleukin 6 (IL-6). An earlier report had shown that SIV-infected macaque macrophages fuse with CEM174 cells (a human CD4+ cell line) and cause their lysis. In the present report, we have shown that TNF-alpha and IL-6 are also produced during the early stages of this interaction. Data from cocultivation of infected macrophages with several CD4+ T cell lines, including CEM174, suggested that the cytokines are produced by the T cells, and that cytokine production is restricted to those cells which not only express CD4, but are also capable of fusing with the infected macrophages. These data suggest that infected macrophages in vivo could fuse with and eliminate activated CD4+ lymphocytes and, during this interaction, release cytokines, which would contribute to the degenerative and inflammatory lesions characteristic of this disease.
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PMID:Tumour necrosis factor and interleukin 6 production during interaction between activated CD4+ lymphocytes and simian immunodeficiency virus-infected macrophages. 135 Mar 3


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