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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a community study in Guinea-Bissau, West Africa, 47 HIV-2-seropositive cases and 87 matched controls were evaluated immunologically using immuno-alkaline phosphatase linked to avidin-biotin complex for the assessment of CD4 and CD8 status. HIV-2-seropositive individuals had significantly lower total numbers of CD4 cells and CD4/CD8 ratios, 38% having a total number of CD4 cells less than or equal to 0.5 x 10(9)/l and 36% having a CD4/CD8 ratio less than or equal to 0.8. Total numbers of CD4 cells less than or equal to 0.5 x 10(9)/l or CD4/CD8 ratio less than or equal to 0.8 were found in 53% of the HIV-2 seropositives compared with 11% among controls [odds ratio (OR) = 7.3; 95% confidence interval (CI): 3.1-17.1]. Lymphadenopathy was significantly more frequent among HIV-2 seropositives than among controls (OR = 3.4; 95% Cl: 1.5-7.6). HIV-2 seropositives with lymphadenopathy had significantly fewer lymphocytes (P = 0.008) and lower total CD4 (P = 0.029) and total CD8 number (P = 0.011) than HIV-2 seropositives without lymphadenopathy. This study indicates that HIV-2 has a significant immunosuppressive effect.
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PMID:Immunodeficiency in HIV-2 infection: a community study from Guinea-Bissau. 198 11

Patients with the acquired immune deficiency syndrome (AIDS) frequently develop hepatic dysfunction. Although hepatic injury may indirectly result from malnutrition, hypotension, administered medications, sepsis, or other conditions, the hepatic injury is frequently due to opportunistic hepatic infection, directly related to AIDS. Infection with Mycobacterium avium intracellulare typically occurs in patients with advanced immunocompromise and with systemic symptoms due to widely disseminated infection. In contrast, hepatic tuberculosis often occurs with less advanced immunocompromise. Cytomegaloviral infection may produce a hepatitis. Cytomegaloviral and cryptosporidial infections have been implicated as causes of acalculous cholecystitis and of a secondary sclerosing cholangitis. About 10-20% of patients with AIDS have chronic hepatitis B infection. These patients tend to develop minimal hepatic inflammation and necrosis. The clinical findings in patients with hepatic cryptococcal infection are usually due to concomitant extrahepatic infection. Hepatic histoplasmosis usually develops as part of a widely disseminated infection with systemic symptoms. Hepatic involvement by Kaposi's sarcoma is rarely documented ante mortem because an unguided liver biopsy is an insensitive diagnostic procedure. Patients with non-Hodgkin's lymphoma of the liver typically have lymphadenopathy, hepatomegaly, and systemic symptoms. As a pragmatic approach, patients with liver dysfunction and HIV-related disease should have a sonographic or computerized tomographic examination of the liver. Patients with dilated bile ducts should undergo endoscopic retrograde cholangiopancreatography because opportunistic infection may produce biliary obstruction. Patients with a focal hepatic lesion should be considered for a guided liver biopsy. Patients with a significantly elevated serum alkaline phosphatase level should be considered for a percutaneous liver biopsy. When performed for these indications, liver biopsy will demonstrate a significant disease involving the liver in about 50% of patients with AIDS and in about 25% of patients who are HIV seropositive but who are not known to have AIDS. The clinical impact of a diagnostic biopsy is blunted by a lack of efficacious therapy for many opportunistic infections.
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PMID:Hepatobiliary manifestations of the acquired immune deficiency syndrome. 198 33

An enzyme-linked immunosorbent assay (ELISA) that can measure picogram quantities of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 120 (gp120) in cell culture medium or body fluids has been developed. Recombinant, soluble CD4 immobilized in microtiter trays was used to capture gp120, which was then detected with polyclonal sheep antibody to gp120 followed by biotinylated rabbit anti-sheep immunoglobulin G and an avidin-alkaline phosphatase indicator system. With a reference recombinant gp120, the assay showed a linear relationship between optical density and concentrations ranging from 60 to 6,000 pg/100-microliters well; precision of the assay varied with the concentrations and ranged from +/- 40% with amounts smaller than 200 pg to +/- 10% with amounts larger than 200 pg. In a group of coded samples containing 60 pg (approximately 10(7) molecules) of reference gp120, the assay correctly identified the samples as containing gp120 99% of the time, with no false-positive results recorded for blank samples. Recombinant gp120 prepared in another cell culture system demonstrated a binding coefficient 13-fold lower than that of reference gp120. Mixing standard amounts of reference gp120 with increasing concentrations of human sera reduced assay sensitivity, although the linear relationship between gp120 concentration and optical density remained. With this assay we were able to detect gp120 in HIV-1 suspensions prepared from cultured lymphoblastoid cells and in the sera of HIV-1-infected patients. This ELISA for gp120 should be useful for studying the biological role of gp120 in HIV infection.
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PMID:Enzyme-linked immunoassay for human immunodeficiency virus type 1 envelope glycoprotein 120. 199 48

A 22 year old man developed sclerosing cholangitis within two months of documented HIV-1 seroconversion. Sclerosing cholangitis should be included in the differential diagnosis of causes of abdominal pain and raised alkaline phosphatase enzyme levels in HIV-1 antibody positive patients without established CDC stage IV disease.
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PMID:Sclerosing cholangitis rapidly following anti-HIV-1 seroconversion. 207 Nov 28

The aim of this study was to detect HIV-1 proviral DNA in lysates of peripheral blood mononuclear cells (PBMCs) by the polymerase chain reaction (PCR) and hybridization with a nonradioactive probe. PBMCs were lysed in 1% Triton X-100. PCR was then carried out using primers complementary to a conserved region of the HIV-1 pol gene. Bracket and nested amplification protocols were used. Products were identified by dot-blot hybridization or agarose gel electrophoresis and Southern hybridization, using an alkaline phosphatase-linked oligonucleotide probe specific for amplified sequences. Colorimetric and chemiluminescent substrates were used. HIV-1 DNA was detected in PBMCs of 57/59 HIV-1-seropositive individuals, 8 of which were positive only following the use of nested primers. Of 12 seropositive samples that were negative by other HIV-1 diagnostic tests (PBMC coculture and serum p24 antigen detection), 11 were positive by PCR. PCR using PBMC lysates is a very sensitive method of detecting HIV-1 proviral sequences. The use of nested primers appears to increase the sensitivity of the procedure.
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PMID:Detection of HIV-1 DNA in crude cell lysates of peripheral blood mononuclear cells by the polymerase chain reaction and nonradioactive oligonucleotide probes. 212 Apr 19

3'-Azido-2',3'-dideoxyuridine (AzdU, CS-87) is a potent inhibitor of human immunodeficiency virus replication in human peripheral blood mononuclear cells (PBMC) with limited toxicity for human bone marrow cells (BMC). In the present study, metabolism of AzdU was investigated in human PBMC and BMC after exposure of cells to 2 or 10 microM [3H]AzdU. 3'-Azido-2',3'-dideoxyuridine-5'-monophosphate (AzdU-MP) was the predominant metabolite, representing approximately 55 to 65% of intracellular radioactivity in both PBMC and BMC at all times. The AzdU-5'-diphosphate and -5'-triphosphate intracellular levels were 10- to 100-fold lower than the AzdU-MP levels and, of note, AzdU-5'-triphosphate was not detected in human BMC. Using anion exchange chromatography, a new peak of radioactivity, distinct from any known anabolites, was detected. This chromatographic peak was found to be resistant to alkaline phosphatase but was hydrolyzed by 5'-phosphodiesterase, yielding AzdU-MP. Incubation of [3H]AzdU and D-[1-14C]glucose in PBMC and BMC produced a double-labeled peak with the same retention time as the anabolite, suggesting formation of a hexose derivative of AzdU. A novel high performance liquid chromatography method was developed that allowed for the separation of nucleosides, nucleotides, and carbohydrate derivatives thereof. Using this highly specific method, the putative AzdU-hexose actually was separated into two chromatographic peaks. These novel metabolites were identified as 3'-azido-2',3'-dideoxyuridine-5'-O-diphosphoglucose and 3'-azido-2',3'-dideoxyuridine-5'-O-diphospho-N-acetylglucosamine. Following 48 hr of incubation with [3H] AzdU, as much as 20 and 30% of these AzdU metabolites accumulated in PBMC and BMC, respectively. When AzdU was removed from the cell cultures, intracellular AzdU diphosphohexose concentrations decayed in a monophasic manner, with an elimination half-life of 14.3 hr. By 48 hr, levels of 0.3 pmol/10(6) cells were still detected, reflecting a gradual anabolism of these metabolites. Elimination of AzdU-MP and AzdU-5'-diphosphate was characterized by a two-phase process, with a short initial half-life of 0.83 and 0.24 hr and a long terminal half-life of 14.10 and 8.24 hr, respectively. Similar diphosphohexoses of deoxyuridine (dUrd) were also detected in human PBMC and BMC after exposure to [3H]dUrd, suggesting that dUrd derivatives are metabolized in a similar manner. In summary, the discovery of novel metabolic pathways for dUrd analogs demonstrates that AzdU has unique metabolic features that may contribute to the low toxicity of this anti-HIV agent in human BMC and also affect its mechanism of action.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cellular metabolism of 3'-azido-2',3'-dideoxyuridine with formation of 5'-O-diphosphohexose derivatives by previously unrecognized metabolic pathways for 2'-deoxyuridine analogs. 225 Jun 66

A method has been developed to measure the concentration of total phosphorylated zidovudine (ZDV) inside peripheral blood leucocytes (PBLs) using a modified commercial radioimmunoassay (RIA) specific for ZDV. ZDV 5'-monophosphate was readily synthesized and used as a procedural control for RIA modification. PBLs were isolated from healthy volunteers and incubated with ZDV for 24 h to allow metabolic phosphorylation. Viable cells were counted, washed, and extracted overnight with 60% methanol. After evaporation, the extract was reconstituted in Tris buffer, pH 9.5. Because of minimal RIA antibody cross reactivity with phosphorylated ZDV, samples were split into two fractions, one of which was treated with alkaline phosphatase (AP) to liberate phosphate groups. Each fraction was then assayed for ZDV. Concentrations of phosphorylated ZDV were determined by subtracting the concentration of the non-AP-treated fraction from that of the treated fraction. Recovery of phosphorylated ZDV from cell extracts was approximately 90%, and reproducibility was acceptable (coefficients of variation less than 15% for concentrations greater than or equal to 0.25 ng/ml). Intracellular concentrations (0.1-1.4 pmoles/10(6) cells) followed a nonlinear dose-response relationship over the range 0-50 microM extracellular ZDV, with concentration-dependent saturation. These results demonstrate the feasibility of determining concentrations of phosphorylated ZDV in HIV-infected patients, a potentially key step in establishing a therapeutic range and optimal dosing regimen for these patients.
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PMID:In vitro measurement of phosphorylated zidovudine in peripheral blood leucocytes. 229 12

Monoclonal antibodies (MAbs) were raised against gag proteins of human immunodeficiency virus type 1 (HIV-1), strain HTLV-IIIB. One of 29 antibodies was specific for p17 of HIV-1. Twenty of 28 MAbs reactive with the major core protein p24 of HIV-1 showed cross-reactivity with HIV-2, and five of these also detected the corresponding antigens of simian immunodeficiency virus (SIVmac). The MAbs were reactive in several tests, i.e. ELISA, immunostaining of Western blots, immunofluorescence, alkaline phosphatase-anti-alkaline phosphatase immunocytochemistry and immunoelectron microscopy. The submembrane protein p17 was clearly localized within the virion.
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PMID:Monoclonal antibodies directed against human immunodeficiency virus (HIV) gag proteins with specificity for conserved epitopes in HIV-1, HIV-2 and simian immunodeficiency virus. 245 67

We have developed an enzyme-linked immunosorbent assay (ELISA) specific for antibodies to the envelope glycoproteins gp120 and gp160 of HIV-1. An antibody to a conserved epitope on gp120 is adsorbed to a solid phase and used to capture gp120 and/or gp160 from solution. This may be purified recombinant protein or in simple, non-denaturing detergent extracts of different strains of HIV-1. Human serum antibodies bound to the captured antigen are subsequently detected with an anti-human antibody conjugated to alkaline phosphatase, and the AMPAK ELISA amplification system (Novo BioLabs, Cambridge, UK). With this procedure, antibodies can be detected that recognize gp120 from a wide range of divergent HIV-1 strains. The ELISA is sufficiently sensitive to detect env antibodies in sera from HIV-positive individuals at dilutions of 1:300,000. No repeatable false-positives were detected in a screen of 250 normal serum samples. Env antibodies were detected in all 37 strongly HIV-positive sera tested, and in four sera that were borderline or weakly positive in commercial ELISA. However, 55 sera positive in commercial ELISA but unconfirmable by Western blot ('ambiguously' positive) did not contain detectable env antibodies.
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PMID:An enzyme-linked immunosorbent assay for antibodies to the envelope glycoproteins of divergent strains of HIV-1. 254 Jul 72

The disorder, benign transient hyperphosphatasia, has been defined previously as a condition occurring in a normal child with spontaneous, transient elevation of alkaline phosphatase. We report three cases of hyperphosphatasia in patients with congenital HIV infection and underlying liver disease which appear to satisfy the criteria for benign transient hyperphosphatasia despite the presence of chronic disease. These three children, when compared with three normal children with transient hyperphosphatasia exhibited similar patterns of change in serum alkaline phosphatase. Extreme elevation of serum alkaline phosphatase in HIV infected patients does not of itself suggest alterations in clinical status nor indicate the need for extensive evaluation.
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PMID:Benign transient hyperphosphatasia and HIV infection. 278 57


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