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)

The aim of this work was to increase sensitivity in the detection of antigens from HIV-infected patients, through a process of immune complex dissociation without loss of antigenicity. 500 microliters of sera were mixed with 100 microliters of PEG 12%, stored one night in refrigerator, and centrifuged at 2000 g during 20 minutes. 200 microliters of buffer AcH/Ac- (pH 3.5) were added to the sediment, and incubated at 37 degrees C during one hour with periodic shaking. This was neutralized with 100 microliters of buffer TRIS/CIH (pH 8.6). The antigen was investigated in the original sample, supernatant and sediment. Samples of 105 patients with positive serology, confirmed by Western Blot following CDC criteria, were processed. The antigen was detected in 62 (59%) samples precipitated with PEG, but only 35 (33%) when conventional methods were used. Applying statistics X2: 13.97, P < 0.001, a highly significant association can be observed between PEG dissociation treatment and antigen detection. 27 negative sera by the standard method became positive in the whole sediment, and only 8 in the supernatant. In addition, 40 negative sera were processed, which had not become positive for the antigen by PEG treatment.
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PMID:[Detection of human immunodeficiency virus antigen both free and in immune complexes]. 858 50

Human serum albumin (HSA) derivatized with cis-aconitic anhydride (Aco-HSA) that was earlier shown to inhibit replication of human immunodeficiency virus type 1 (HIV-1), was covalently coupled to conventional liposomes, consisting of phosphatidylcholine, cholesterol and maleimido-4-(p-phenylbutyryl)phosphatidylethanolamine, using the heterobifunctional reagent N-succinimidyl-S-acetylthioacetate (SATA). The amount of HSA that could be coupled to the liposomes depended on derivatization of the HSA and ranged from 64.2 +/- microgram HSA/micromol total lipid for native HSA to 29.5 +/- 2.7 microgram HSA/micromol total lipid for HSA in which 53 of the epsilon amino groups of lysine were derivatized with cis-aconitic anhydride (Aco53-HSA). Incorporation of 3.8 mol% of total lipid of a poly(ethylene glycol) derivative of phosphatidylethanolamine (PEG-PE) in the liposomes resulted in a lower coupling efficiency of Aco-HSA. The elimination and distribution of the liposomal conjugates in rats in vivo was largely dependent on the modification of the HSA coupled to the liposomes. With native HSA-liposomes, more than 70% of the conjugate was still found in the blood plasma 30 min after i.v. injection in rats, while at this time Aco-HSA-liposomes were completely cleared from the circulation. The rapid clearance of conventional Aco-HSA-liposomes was due to a rapid uptake into the liver and could be considerably decreased by incorporating PEG-PE in the liposomal bilayer. After 3 h 60% of Aco-HSA-PEG-liposome conjugates were found in the blood. In an in vitro anti-HIV-1 assay, the 50% inhibitory concentrations (IC50) for Aco39-HSA-liposomes and Aco53-HSA-liposomes expressed as protein weight, were 2.87 microgram/ml and 0.154 microgram/ml, respectively. When PEG-PE was incorporated, the Aco53-HSA-liposomes retained anti HIV-1 activity (IC50:3.13 microgram/ml). The possibility to modulate the residence time in the bloodstream of Aco-HSA-liposomes and the potent anti-HIV-1 activity of these conjugates, may allow the development of an intrinsically active drug carrier system. By incorporating anti HIV-1 drugs such as AZT into such liposomes a drug delivery system can be designed that might act simultaneously on the virus/cell binding by virtue of the coupled Aco-HSA and on the RNA/DNA transcription of the HIV-1 replication cycle through the nucleoside analogue.
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PMID:Preparation and characterization of conjugates of (modified) human serum albumin and liposomes: drug carriers with an intrinsic anti-HIV activity. 859 75

Human immunodeficiency virus type 1 integrase (HIV-1 IN) catalyzes both 3'-donor processing and strand transfer reactions. Previous studies have determined that the N-terminal region, a putative zinc finger, is capable of binding Zn2+. The function of zinc coordination to this domain, however, is still unknown. In this report, we present evidence that Mg2+-dependent 3'-donor processing by HIV-1 IN is enhanced by the addition of Zn2+ in vitro. This activity is inhibited in the presence of the chelator 1,10-phenanthroline (OP). In addition, the Mg2+-dependent 3'-donor processing activity is more sensitive to the concentration of IN than is the Mn2+-dependent activity. A combination of dimethyl sulfoxide (DMSO) and poly(ethylene glycol) (PEG) was found to further activate the Mg2+-dependent 3'-donor processing activity while diminishing the Mn2+-dependent activity. These results suggest factors such as substrate-length, concentration of IN, Zn2+ coordination, and protein-protein interactions are important for efficient and specific donor processing activity with Mg2+ in vitro.
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PMID:Zinc stimulates Mg2+-dependent 3'-processing activity of human immunodeficiency virus type 1 integrase in vitro. 862 7

Interference of binding of Tat protein to TAR RNA in HIV-1-infected cells may be a useful therapeutic strategy for AIDS. An electrophoretic assay to screen potential low-molecular-weight (< 2 kDa) Tat antagonists has been established. A radiolabeled TAR RNA fragment (delta TAR) is retarded in mobility when bound by a Tat peptide-polyethylene glycol conjugate (Tat-PEG), which is used in place of the Tat protein. The assay determines the ability of a potential antagonist to compete with Tat-PEG for binding to delta TAR, as measured by interference with the gel shift of delta TAR. To discriminate between specific and nonspecific interactions, the assay is done in the absence or the presence of a 250-fold molar excess of tRNA.
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PMID:Use of a polyethylene glycol-peptide conjugate in a competition gel shift assay for screening potential antagonists of HIV-1 Tat protein binding to TAR RNA. 874 81

The Mpl ligands are a family of closely related hematopoietic growth factors that bind to the thrombopoietin receptor, c-Mpl. In addition to the endogenous Mpl ligand, thrombopoietin, two recombinant Mpl ligands, recombinant thrombopoietin and pegylated megakaryocyte growth and development factor (PEG-MGDF) are under investigation. Endogenous thrombopoietin regulates most of the normal production of platelets but also is essential for the normal development of other lineages. When recombinant thrombopoietin or PEG-MGDF is administered to normal animals or humans, there is a dose-dependent increase in the platelet count but no effect on leukocytes or erythrocytes. When administered following chemotherapy in animal models or humans, Mpl ligands reduce the duration and sometimes the degree of thrombocytopenia. The Mpl ligands also may be effective in reducing the thrombocytopenia of patients with HIV infection, liver disease, myelodysplasia, or after plateletpheresis.
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PMID:In vivo effects of Mpl ligand administration and emerging clinical applications for the Mpl ligands. 920 31

Electrospray ionization mass spectrometry (ESI-MS) has been used to study the noncovalent complexes formed from the interaction between HIV-1 Tat peptide and Tat protein with TAR RNA. Both positive ion and negative ion ESI mass spectra showed a maximum stoichiometry of 3:1 between Tat peptide and TAR RNA. However, the higher order complexes only occurred at high relative concentrations of Tat peptide. The 1:1 Tat peptide-TAR RNA complex is believed to involve only specific interactions, whereas the higher order complexes involve nonspecific interactions. Relative binding affinities between Tat peptide and TAR RNA and its various mutants (TAR missing the three-nucleotide bulge, TAR with a poly(ethylene glycol) linker in the bulge region, and TAR with a poly(ethylene glycol) linker in the loop region) can be differentiated by competitive binding experiments and ESI-MS measurements. The gas phase mass spectrometry experiments are consistent with solution phase studies, as they show that mutations in the bulge region reduce TAR RNA affinity to Tat peptide.
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PMID:HIV-1 Tat peptide binding to TAR RNA by electrospray ionization mass spectrometry. 941 17

The life-cycle of human immunodeficiency virus type 1 (HIV-1) has been studied using several techniques including immunoelectron microscopy and cryomicroscopy. The HIV-1 particle consists of an envelope, a core and the region between the core and the envelope (matrix). Virus particles in the extracellular space are observed as having various profiles: a central or an eccentric round electron-dense core, a bar-shaped electron-dense core, and immature doughnut-shaped particle. HIV-1 particles in the hydrated state were observed by high-resolution electron cryomicroscopy to be spherical and the lipid membrane was clearly resolved as a bilayer. Projections around the circumference were seen to be knob-like. The shapes and sizes of the projections, especially the head parts, were found to vary with each projection. HIV-1 cores were isolated with a mixture of Nonidet P40 and glutaraldehyde, and were confirmed to consist of HIV-1 Gag p24 protein by immunogold labelling. On infection, the HIV-1 virus was found to enter the cell in two ways: membrane fusion and endocytosis. After viral entry, no structures resembling virus particles could be seen in the cytoplasm. In the infected cells, positive reactions by immunolabelling suggest that HIV-1 Gag is produced in membrane-bound structures and transported to the cell surface by the cytoskeletons. A crescent electron-dense layer is then formed underneath the cell membrane. Finally, the virus particle is released from the cell surface and found extracellularly to be a complete virus particle with an electron-dense core. However, several cell clones producing defective mature, doughnut-shaped (immature) or teardrop-shaped particles were found to be produced in the extracellular space. In the doughnut-shaped particles, Gag p17 and p24 proteins exist facing each other against an inner electron-dense ring, suggesting that the inner ring consists of a precursor Gag protein showing a defect at the viral proteinase.
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PMID:The life-cycle of human immunodeficiency virus type 1. 968 49

The rapid/high and slow/low phenotypic variants of primary HIV-1 isolates can be distinguished by their differential co-receptor utilization and their ability to productively infect established cell lines. To reveal possible differences in Tat-mediated transactivation, the potential for primary isolate Tat proteins to transactivate the LTR from the laboratory strain HIVLAV/Lai-1 was examined. Using either cell-mediated or PEG-induced fusion of cells infected with primary HIV-1 isolates and HeLaT4LTRbeta-gal cells, it was clear that the Tat protein encoded by all patient isolates efficiently activated transcription from the HIVLAV/Lai-1 LTR. However, infection of HeLaT4LTRbeta-gal cells by primary HIV-1 isolates was transient, suggesting the development of a postpenetration host control of HIV-1 replication at the level of tat activation, a feature not observed for the laboratory-adapted strain HIVIIIB. Although plasmid vectors based on the HIVLAV/Lai-1 LTR remain useful for the development of susceptible established cell lines for titrating primary HIV-1 isolates, the efficacy of such a system would depend upon the stability/duration of Tat activation.
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PMID:Transient Tat activation of the HIVLAV/Lai-1 LTR by primary HIV-1 phenotypic variants in HeLaT4LTRbeta-gal cells. 1033 53

A method and approach are described to differentiate classic autoimmune thrombocytopenia (ATP) from immune complex-associated thrombocytopenia in systemic lupus (SLE), hepatitis/chronic liver disease (LIV-ITP) and HIV-1 related thrombocytopenia (HIV-1-ITP). The platelet immunologic profile of IgG, C3C4 and IgM was measured with a solid-phase ELISA, employing 125I-staphylococcal protein A to detect indicator antibody binding. Polyethylene glycol was employed to precipitate immune complexes (PEG-IC). Platelet-associated IgG (PAIgG) was 2.8-, 5.6- and 5.8-fold higher in SLE, LIV-ITP and HIV-1-ITP patients respectively compared to ATP patients: platelet C3C4 was 3.2-, 4.8- and 4.5-fold higher respectively; platelet IgM was 2.2-, 3.7- and 3.8-fold higher respectively; serum PEG-IC levels were 4.2-, 4.8- and 2.1-fold higher respectively. With all parameters measured, there was no overlap between the 75th percentile for ATP patients and the 25th percentile for all three cohorts. The likelihood of having a platelet C3C4 level higher than the highest ATP level was 69% for SLE, 90% for LIV-ITP and 94% for HIV-1-ITP respectively; with PEG-IC measurements the likelihood was 83%, 100% and 100% respectively. Serum IgG, C3, C4, IgM and PEG-IC were examined for a possible relationship with platelet measurements. Except for a positive correlation between serum and platelet IgM in ATP, r = 0.5, P < 0.04, there was no positive correlation with any of the parameters measured. An inverse correlation was noted between PEG-IC level and platelet C3C4 in SLE, r = 0.7, P < 0.04. Thus platelet immunologic profile and serum PEG-IC level measurements differentiated classic ATP from immune complex-associated thrombocytopenias (SLE, LIV-ITP, HIV-1-ITP). Except for IgM measurements in ATP, platelet measurements could not be attributed to their respective serum concentration.
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PMID:Differentiation of autoimmune thrombocytopenia from thrombocytopenia associated with immune complex disease: systemic lupus erythematosus, hepatitis-cirrhosis, and HIV-1 infection by platelet and serum immunological measurements. 1055 25

The ability of liposomes bearing anti-HLA-DR Fab' fragments at the end termini of polyethyleneglycol chains (sterically stabilized immunoliposomes) to target HLA-DR expressing cells and increase the accumulation of liposomes into lymphoid organs has been evaluated and compared to that of conventional liposomes, sterically stabilized liposomes and conventional immunoliposomes after a single subcutaneous injection to mice. The accumulation of sterically stabilized liposomes in lymph nodes was higher than that of conventional liposomes. Sterically stabilized immunoliposomes accumulated much better than conventional immunoliposomes in all tissues indicating that the presence of PEG has an important effect on the uptake of immunoliposomes by the lymphatic system. Fluorescence microscopy studies showed that sterically stabilized liposomes are mainly localized in macrophage-rich areas such as the subcapsular region of lymph nodes and in the red pulp and marginal zone of the spleen. In contrast, sterically stabilized immunoliposomes mostly accumulated in the cortex in which follicles are located and in the white pulp of the spleen. As the human HLA-DR determinant of the major histocompatibility complex class II is expressed on activated CD4+ T lymphocytes and antigen presenting cells such as monocyte/macrophages and dendritic cells, known as the cellular reservoirs of HIV-1, liposomes bearing anti-HLA-DR antibodies constitute an attractive approach to concentrate drugs in HIV-1 reservoirs and improve their therapeutic effect.
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PMID:Sterically stabilized liposomes bearing anti-HLA-DR antibodies for targeting the primary cellular reservoirs of HIV-1. 1101 61


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