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)

An antisense phosphorothioate oligodeoxynucleotide 27-mer complementary to the rev gene mRNA of the human immunodeficiency virus (HIV-1) was administered to rats through intravenous injections and subcutaneous infusions in order to investigate the disposition of this compound. In addition, nonlethal toxic responses of the rat were evaluated. A biphasic plasma clearance with t1/2 alpha of 20-25 min and t1/2 beta of 27-41 hr was observed. Single doses ranging from 35 to 3257 micrograms were examined, and the plasma concentration and area under the plasma concentration-time curve (AUC) were found to be directly proportional to the dose. Continuous subcutaneous infusion of 50 mg over 28 days was also examined. The oligonucleotide is completely eliminated in the urine over 3 days. Electrophoretic analysis demonstrated that the excreted compound has the same mobility and UV-absorbance profile as the administered compound. Measurement of accumulation and distribution into tissues revealed unique tissue-specific rates and extent of oligonucleotide movement into and out of tissues. Results of the chronic infusion study suggest that uptake into tissue is not saturated, even after 28 days of infusion. Analysis of blood plasma from oligonucleotide-treated animals shows a possible transient elevation in levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), but not alkaline phosphatase (AP), gamma-glutamyltransferase (GT), and bilirubin. The data collectively support the potential utility of phosphorothioate oligonucleotides as therapeutic agents in vivo.
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PMID:Pharmacokinetics of an antisense phosphorothioate oligodeoxynucleotide against rev from human immunodeficiency virus type 1 in the adult male rat following single injections and continuous infusion. 806 15

We report the utility of a possible lymphocyte fraction of alkaline phosphatase (ALP band-10) activity in serum to predict human immunodeficiency virus type 1 (HIV-1) infection in children born to HIV-1-seropositive mothers. The presence of ALP band 10 in serum consistently correlated with HIV-1 infection status as judged by positive HIV-1 culture, two consecutive HIV-1 p24 antigen results greater than 30 pg/mL in serum, and the subsequent confirmation of seroconversion to HIV-1 antibody after clearance of maternal IgG anti-HIV-1 antibody ascertained between 15 to 24 months post partum. Infection with HIV-1 was correctly identified in 31 samples from 18 patients ranging in age between 0.1 to 10 years; the absence of similar infection was noted in 14 samples from nine patients who served as controls and whose serum samples did not exhibit ALP band-10 activity. This ability of serum ALP band-10 activity to predict HIV-1 infection status in children as young as 2 months may be useful as a surrogate marker for early identification of HIV-1 infection in infants born to HIV-1-seropositive women long before the clearance of maternal anti-HIV-1 antibodies can be ascertained.
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PMID:Alkaline phosphatase band-10 fraction as a possible surrogate marker for human immunodeficiency virus type 1 infection in children. 791 99

Infection due to the Mycobacterium avium complex (MAC) is the most common opportunistic disease of bacterial origin among patients with AIDS in the United States. The incidence of disseminated disease due to MAC (DMAC) has risen dramatically in recent years. The risk of developing DMAC increases as the CD4+ lymphocyte count declines to < 100/mm3. Preliminary analyses of several studies suggest that gender, racial or ethnic group, and individual risk factors for human immunodeficiency virus infection do not influence the incidence of DMAC but that prior Pneumocystis carinii pneumonia, the development of severe anemia, or the interruption of antiretroviral therapy may increase risk. Both the respiratory and the gastrointestinal tracts probably serve as portals of entry for MAC. Colonization may potentiate the risk of DMAC but does not always precede dissemination. Patients with AIDS and DMAC have a shorter duration of survival than do those with AIDS but without DMAC. While treatment for DMAC may extend survival, no well-controlled, prospective, randomized clinical trial has documented this point. Most patients with AIDS and DMAC have disseminated multiorgan disease; the most frequently described symptoms include fever, night sweats, weight loss or wasting, diarrhea, and abdominal pain. The most commonly identified laboratory abnormalities are anemia and elevated serum levels of alkaline phosphatase. Localized disease syndromes related to MAC infection occur less often.
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PMID:Disease due to the Mycobacterium avium complex in patients with AIDS: epidemiology and clinical syndrome. 820 73

An extremely sensitive and convenient microtiter plate solution hybridisation assay for the detection of HIV-1 PCR products was developed. The PCR product is labelled by direct incorporation of digoxigenin-dUTP and after denaturation is captured by a microtitre plate coated with a streptavidin-linked biotinylated probe. The PCR/probe hybrids are reacted with an alkaline phosphate conjugated anti-digoxigenin antibody and detected using an alkaline phosphatase enzyme amplification system. The use of uracil-N-glycosylase and dUTP instead of dTTP in the PCR is used to effectively control carry-over from previous PCR products. The assay can detect single HIV-1 DNA molecules in a background DNA of 0.75 microgram.
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PMID:Detection of HIV-1 by digoxigenin-labelled PCR and microtitre plate solution hybridisation assay and prevention of PCR carry-over by uracil-N-glycosylase. 822 79

To reduce the cost, time and waste in screening for HIV and HBV infections a combined assay for HIV-1 and -2 antibodies and HBsAg has been developed. Monoclonal anti-HBs antibodies were co-immobilized with synthetic peptides representing immunodominant regions of HIV-1 and -2. The presence of anti-HIV antibodies in the samples was detected with alkaline phosphatase-labelled anti-human IgG and of HBsAg with horseradish peroxidase-labelled monoclonal anti-HBs antibodies by a sequential substrate reaction. In this assay, HBsAg was detectable in a concentration range between 0.25 and 0.30 U/ml and the results were available within 3 h. The specificity, tested on 5000 serum samples from blood donors after confirmation, was 99.8% for HBsAg and 99.5% for anti-HIV antibody detection. All serum samples taken from 600 HIV-1- and 115 HIV-2-infected individuals were correctly classified as reactive. The two-colour HBsAg-anti-HIV-1/-2 combination ELISA meets all the requirements of single parameter assays with regard to precision, stability and robustness.
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PMID:Two-colour combination enzyme-linked immunosorbent assay for the simultaneous detection of HBV and HIV infection. 842 20

A rapid and nonradioactive detection method for polymerase chain reaction (PCR) amplified HIV-1 DNA was developed using a colorimetric detection system. Hybridization between biotin-labeled amplified targets and digoxigenin-capture probes occurs in solution followed by efficient and rapid capture onto streptavidin-magnetic beads. The presence of the digoxigenin-capture probe hybridized with biotin-labeled targets is then detected by antidigoxigenin-alkaline phosphatase conjugates using a colorimetric substrate. This approach is highly sensitive and can detect less than 10 HIV targets prior to PCR in approximately 50 min.
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PMID:Colorimetric detection for PCR amplified HIV-1 DNA using magnetic beads. 847 72

The effect of HIV infection on intestinal lamina propria macrophage subsets was investigated in 41 patients at various stages of HIV infection (asymptomatic HIV infection, n = 17; AIDS, n = 24). Duodenal biopsies taken from HIV patients at endoscopy were snap frozen and cryostat sections cut for immunohistochemical staining. MoAbs CD68 (EBM11, pan-macrophage marker), RFD1 (antigen-presenting cells) and RFD7 (mature phagocytic macrophages) were used to identify cell subsets using indirect immunoperoxidase or alkaline phosphatase. Double immunofluorescence using MoAbs to HIV proteins (p24, p17 and gp120) and RFD1 were used to identify HIV-infected antigen-presenting cells. Double immunofluorescence was also used to identify macrophages that expressed both RFD1 and RFD7 ('suppressor' macrophages). Intensity of HLA-DR expression in lamina propria cells was investigated using a MoAb to HLA-DR directly conjugated to glucose oxidase. The results show that there was no difference in overall density of macrophages, but there was a significant decrease in dendritic cells (RFD1+) in all clinical stages of HIV. There was no difference in the density of RFD7+ macrophages, nor was there a difference intensity of HLA-DR expression in lamina propria cells. Only four HIV-infected cells were positively identified in the 41 patients. This result suggests that the antigen-presenting arm of mucosal immune defences may be seriously compromised in HIV infection, and represents a further insult to mucosal immunity already impaired as a result of loss of CD4+ T lymphocytes. This may contribute to development of opportunist infection in the gut.
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PMID:Mucosal macrophage subsets of the gut in HIV: decrease in antigen-presenting cell phenotype. 851 76

A large filamentous phage library (1 x 10(9) clones) displaying random 30-amino-acid (aa) sequences on the N terminus of the pIII coat protein was constructed and characterized. Clones in the library were affinity selected for binding to monoclonal antibodies (mAb) against two viral antigens, the HIV gp120 protein and the HCV core protein. The obtained aa sequences precisely identified the epitopes recognized by the mAb. Binding of peptide-carrying phages to the Ab was demonstrated by ELISA, Western blot and the surface plasmon resonance (SPR) method. The mAb-specific peptides were transferred via genetic techniques onto the N terminus of Escherichia coli alkaline phosphatase (AP). When fused to the enzyme, the peptides maintained their ability to bind their respective mAb, indicating that the peptides contained the necessary contact residues for binding. The affinity of the peptides was estimated to be 100 nM by SPR. A comparison is presented of the relative affinities of phage-derived peptides to the native viral epitopes also displayed on the AP scaffold. The approach of transferring epitopes from phage to AP for further evaluation should be applicable to many other mAb or receptors.
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PMID:Epitope mapping of anti-HIV and anti-HCV monoclonal antibodies and characterization of epitope mimics using a filamentous phage peptide library. 854 61

Several lignans, mostly new, were isolated from Larrea tridentata by assay-guided counter-current chromatography (CCC). Using the secreted alkaline phosphatase bioassay of HIV Tat transactivation and the two-phase hexane-ethyl acetate-methanol-water solvent system, two major components (Gr and Lo) were identified as anti-HIV active principles. The chemical structures of the constituents of Gr (G1-G4) and Lo (L1-L4) were determined by GC-MS and NMR. After optimization of isolation conditions, a large-scale isolation with the chloroform-methanol-water system yielded five constituents (FB1-FB5). The most predominant anti-HIV compound FB2 (denoted Malachi 4:5-6 or mal.4), which occurs in 0.23% yield, was separated from its FB1 isomer (0.13% yield). Compound FB4 and two tricyclic lignans (FB3 and FB5) were also isolated in a substantial amount for further testing of their anti-HIV activities. These compounds may represent a new class of anti-HIV agents with important clinical relevance.
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PMID:Isolation of anti-HIV-1 lignans from Larrea tridentata by counter-current chromatography. 858 Nov 22

In a prospective study of HIV patients with suspected cytomegalovirus (CMV) disease (n = 144; 140 men, four women; aged 23-69 years, median 38 years; CD4 cells 0-400, median 20/microliters), 242 blood samples were examined for the presence of CMV-pp65 antigen in peripheral blood polymorphonuclear leucocytes by use of monoclonal antibodies and alkaline phosphatase-anti-alkaline phosphatase staining. All patients were thoroughly examined for existing CMV disease at first visit and during follow-up (at least 2 months or until death: 0-24 months, median 14 months). In 43/486 samples of patients with CMV disease, the antigen-test was positive and in 179/194 samples of patients without CMV disease the test was negative, resulting in a sensitivity of 90% and a specificity of 93% for the presence of CMV disease in HIV-infected patients.
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PMID:CMV-antigenemia in peripheral blood for the diagnosis of CMV disease in HIV-infected patients. 940 79


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