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

A summary of events at the Second International Conference for Non-Governmental Organizations working on AIDS, held in Paris November 1-4, 1990 is presented with comments on the effectiveness of arrangement, planning and sessions. The meeting was fraught with obstacles, the worst of which was a change of venue from San Francisco to Paris at the last minute, with serious consequences to speakers whose U.S. travel funds had to be found elsewhere. The goal of the conference was to facilitate international networking among AIDS Service, national and regional organizations. To this end 44 sessions were held informally. Plenary sessions were marked by moving presentations of such items as an international memorial quilt, and topics such as how children and women are affected by HIV, and how human rights abuses are often unseen. The need for solidarity among NGOs was stressed by Dr. J. Mann, who noted that NGOs perform up to half the health care in some countries. The major substance of the conference was 5 Seminar tracks of 5.5 hours duration on the topics of services and care, education and prevention, drugs and treatment, human rights, and organizational development. Human rights recognized internationally were described, but in some places lack of resources makes them a privilege. Illegal drug programs, decriminalization and research on cultural obstacles were within the broad range of issues addressed under services and care. While traditional symptomatic treatments and older drugs such as gentian violet as a treatment for candidiasis are being developed in African countries, serious social problems arise when people sell their possessions for a few doses of AZT or Kemron there. In the seminars on organizational development useful exchanges between major donors and project organizers explored professional methods of applying for grants, as well as accounting for funds spent later. ICASO the International Council of AIDS Service Organizations was ratified and a meeting in Florence in June 1991 was authorized, with reservations of those who felt that regional cooperation is needed even more. Problems and incidents marked other aspects of the meeting, from lack of translators, photocopiers, accommodations, refreshments, and late starting to an ill-timed demonstration during the last Plenary session address of Dr. Mann by ACT-UP France. Larger problems of balance of interests and priorities, and whether there are too many AIDS conferences must also be approached.
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PMID:Policies for solidarity. A personal view of the Second International Conference for non governmental organizations working on AIDS, Paris 1-4 November 1990. 167 73

Although changes in function of monocytes from AIDS patients have previously been reported, the functional deficits that could occur in monocytes from asymptomatic HIV-seropositive individuals has not been extensively investigated. The goal of this study was to evaluate the oxidative burst response and cell surface marker expression of monocytes from this group. Both the oxidative burst, as measured by 2',7'-dichlorofluorescin diacetate oxidation, and cell surface markers were evaluated on CD14+ (Leu-M3) monocytes by two-color flow cytometry. A significantly lower oxidative burst capacity was observed in asymptomatic, seropositives after phorbol myristate acetate and calcium ionophore stimulation when compared to seronegative controls. However, differences in oxidative burst between the two groups were not observed after stimulation with heat-aggregated IgG. The oxidative burst of monocytes from seropositive HIV antigen+ or antigen- subjects was not significantly different. The most significant difference in monocyte surface markers between seropositive and seronegative controls was a decrease in the proportion of complement receptor 3+ (CD11b+) cells while slightly decreased numbers of CD13+ and CD33+ monocytes were observed. The decreased expression of CD11b+ cells in seropositives was found entirely within the seropositive, HIV antigen+ group. Similarly, when monocytes from seropositive HIV antigen+ and antigen- were compared, significantly lower numbers of CD4+ and HLA-DR+ cells were noted. These results indicate that significant changes in monocyte function and surface markers occur early during the course of HIV infection and are associated with the expression of serum HIV antigen.
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PMID:Decreased oxidative burst activity of monocytes from asymptomatic HIV-infected individuals. 168 21

We and others have shown that several T cell responses induced by the mitogen phytohaemagglutinin (PHA), including T cell colony formation, IL-2 receptor (IL-2R) expression, and IL-2 production are impaired in patients with AIDS and lymphadenopathy syndrome (LAS). We investigated whether phorbol myristate acetate (PMA) could act in synergy with PHA (as it does in healthy subjects) to enhance in vitro T cell responses of patients at all stages of infection by HIV. In AIDS patients with opportunistic infections (AIDS/OI), PHA + IL-2 + PMA led to a total disappearance of T cell colonies in 10/11 patients, among whom six already displayed very low numbers of colonies induced by PHA + IL-2 (less than 50 colonies/5 x 10(4) cells). In contrast, T cell colony formation induced by PHA + IL-2 + PMA was maintained or increased, compared with that induced by PHA + IL-2, in five out of six AIDS patients with Kaposi's sarcoma (AIDS/KS), 10/14 LAS and six out of seven HIV-seropositive asymptomatic (HIV+/AS) homosexuals. In these three groups of patients, a low percentage of colony cells induced by PHA + IL-2 + PMA expressed CD3 and CD4 molecules, but 50-89% of cells were IL-2R (Tac) positive, as in healthy controls. Studies on T cell activation and IL-2 production were performed on a selected group of 12 HIV-infected patients for whom sufficient numbers of lymphocytes could be obtained. PMA induced CD4 down-modulation in controls and in HIV-infected patients. However, CD3 down-modulation and induction of the Tac chain of IL-2R by PMA were significantly impaired in patients, compared with controls, and these two parameters were correlated. Although PHA alone induced virtually normal levels of Tac antigen on patients' cells, Tac induction by PHA + PMA was significantly decreased in patients versus controls. Cells from five out of 10 patients tested failed to produce detectable amounts of IL-2 after PHA stimulation, whereas IL-2 production increased significantly in all patients tested (n = 9) after PHA + PMA, with a level of IL-2 activity significantly higher than in controls. No correlation was found in this group of patients between the effects of PMA + PHA on T cell colony formation, Tac expression, or IL-2 production, as compared with PHA alone. Taken together, our results indicate that in vitro T cell functional studies with PMA may be useful to evaluate better the defects of T cell activation in HIV-infected patients.
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PMID:Effect of phorbol myristate acetate on T cell colony formation, interleukin-2 (IL-2) receptor expression and IL-2 production by cells from patients at all stages of HIV infection. 169 61

The effect of HIV-1 infection on cytokine levels was studied in monocytic cells by using Northern blotting analysis. Monoblasts (THP-1, U937) did not express IL-1 beta RNA even if the cells were infected with HIV-1. After exposure to LPS (10 micrograms/ml) and 12-O-tetradecanoylphorbol-13-acetate (TPA, 100 nM) for 12 h, these HIV-1-infected monoblasts accumulated 8-15-fold greater levels of IL-1 beta RNA as compared with their HIV-1-uninfected counterparts that were similarly stimulated. In contrast, levels of RNAs coding for monocyte-colony-stimulating factor (M-CSF) and tumor necrosis factor-alpha (TNF alpha) were elevated less than twofold in the HIV-1-infected cells as compared with HIV-1-uninfected cells after their stimulation with LPS and TPA. Inhibition of new protein synthesis did not block the marked accumulation of IL-1 beta RNA produced by exposure to LPS and TPA in the HIV-1-infected cells. Time-course experiments showed that the maximal levels of IL-1 beta RNA occurred at 12 and 24 h after LPS and TPA stimulation of the HIV-1-infected and uninfected U937 cells, respectively. Studies of stability of RNA using actinomycin D showed that IL-1 beta RNA was equally stable in infected and uninfected U937 cells after their stimulation with TPA and LPS. Taken together, our data show that HIV-1 infection markedly augments IL-1 beta RNA accumulation in stimulated monocytic cells, probably through increasing rate of transcription of IL-1 beta.
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PMID:Modulation of interleukin-1 beta RNA in monocytic cells infected with human immunodeficiency virus-1. 169 20

The differentiation of U937 monoblastoid cells after human immunodeficiency virus type 1 (HIV-1) infection was studied using the following approaches: reverse transcriptase activity measurement, immunofluorescence labeling, and electron microscopy. For comparison, uninfected U937 cells were induced to differentiate from monocyte to macrophage by phorbol 12-myristate 13-acetate (PMA) or retinoic acid (RA) treatment. Both infected and drug-treated cells showed important and similar ultrastructural cell modifications, with a phenotype that decreased in monocyte specificity and increased in that of macrophages. When U937 cells were induced to differentiate upon HIV-1 infection, a very different pathway of viral production was observed. Production and accumulation of the virus in a vacuolar compartment of intracytoplasmic origin and escape to the antiviral lysosomal activity could explain virus persistence. This makes the cell system a good model with which to study the relationship between HIV-1 production and cell differentiation.
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PMID:Human immunodeficiency virus type 1 infection of U937 cells promotes cell differentiation and a new pathway of viral assembly. 170 May 41

The effects of glutathione (GSH), glutathione ester (GSE), and N-acetyl-L-cysteine (NAC) on the induction of human immunodeficiency virus (HIV) expression were investigated in the chronically infected monocytic U1 cell line, a previously described cellular model for HIV latency. U1 cells constitutively express low levels of virus, which can be increased by phorbol 12-myristate 13-acetate (PMA), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and other inducers. GSH, GSE, and NAC suppressed in a dose-dependent fashion the induction of HIV expression mediated by PMA, TNF-alpha, and IL-6, in the absence of cytotoxic or cytostatic effects. Reverse transcriptase activity, inducible by PMA, TNF-alpha, or IL-6, was decreased by 80-90% after pretreatment with GSH, GSE, or NAC. The induction of total HIV protein synthesis was also decreased appreciably after pretreatment with GSH, GSE, or NAC. The accumulation of HIV mRNA was substantially suppressed after pretreatment with NAC but to a lesser extent after pretreatment with GSH or GSE. Although PMA induces the expression of TNF-alpha in U1 cells, the suppressive effect of GSH, GSE, and NAC on PMA-induced HIV expression in U1 cells was not associated with the inhibition of TNF-alpha expression. The present findings, which elucidate relationships between cellular GSH and HIV expression, suggest that therapy with thiols may be of value in the treatment of HIV infection.
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PMID:Suppression of human immunodeficiency virus expression in chronically infected monocytic cells by glutathione, glutathione ester, and N-acetylcysteine. 170 37

We are implementing a series of complementary assays for initial follow-up confirmation and prioritization of new active anti-HIV compounds identified by the U.S. National Cancer Institute's large-scale in vitro primary anti-HIV screen. Two different kinds of cellular viability assays, in addition to specific assays for total cellular DNA content, supernatant reverse transcriptase activity, p24 core antigen production and the synthesis of infectious HIV virions are all performed from a single well of a 96-well microtiter plate containing human host cells infected with HIV. Antiviral activities of several known prototype HIV inhibitors including 3'-azido,3'-deoxythymidine, 2',3'-dideoxycytidine, dextran sulfate and phorbol myristate acetate were compared in these multiparameter assays as a means of validation. Procedures to automate the method optimally, as well as to maximize the safety of the technicians working with HIV and HIV-infected cells have been emphasized. The resulting semiautomated, highly reproducible battery of assays yields a maximum amount of antiviral and cytotoxicity information from a minimum amount of sample. This is especially crucial when analyzing new synthetic compounds and natural product extracts or fractions where the available amounts of sample may be very limited.
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PMID:A semiautomated multiparameter approach for anti-HIV drug screening. 171 15

The effects of human immunodeficiency virus 1 (HIV-1) infection on cellular differentiation and NF-kappa B DNA binding activity have been investigated in a new model of myeloid differentiation. PLB-985 cells represent a bipotential myelomonoblastic cell population capable of either granulocytic or monocytic differentiation after induction with appropriate inducers. By virtue of the presence of CD4 on the cell surface, PLB-985 cells were chronically infected with HIV-1 strain IIIB. PLB-IIIB cells clearly possessed a more monocytic phenotype than the parental myeloblasts, as determined by differential staining, increased expression of the myeloid-specific surface markers, and transcription of the c-fms proto-oncogene. NF-kappa B binding activity was inducible by tumor necrosis factor and phorbol myristate acetate in PLB-985. However, in PLB-IIIB cells, constitutive expression of a novel NF-kappa B complex was detected, composed of proteins ranging between 70 and 110 kD. These proteins interacted specifically with the symmetric NF-kappa B site from the interferon beta (IFN-beta) promoter. Mutations affecting the 5' guanine residues of the kappa B site were unable to compete for these NF-kappa B-related proteins. Inducibility of endogenous IFN-beta and IFN-alpha RNA was also increased in PLB-IIIB cells. These studies indicate that HIV-1 infection of myelomonoblastic cells may select for a more mature monocytic phenotype and that unique subunit associations of NF-kappa B DNA binding proteins may contribute to differential NF-kappa B-mediated gene expression.
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PMID:Induction of monocytic differentiation and NF-kappa B-like activities by human immunodeficiency virus 1 infection of myelomonoblastic cells. 174 Jun 63

Acemannan (ACE-M), a beta-(1,4)-linked acetylated mannan, was evaluated for in vitro activity against human immunodeficiency virus type 1 (HIV-1). Castanospermine (CAS), deoxymannojirimycin (DMN), swainsonine (SWS), azidothymidine (AZT), and dideoxythymidine (DDC) were tested in parallel as control compounds. In vitro antiviral efficacy of ACE-M was evaluated in a variety of cell lines including human peripheral mononuclear, CEM-SS1 and MT-2(2) cells. The virus strain, number of infectious units per cell, and target cell line were important factors in determining the degree of inhibition of viral cytopathic effect in the presence of ACE-M and other control compounds tested. Maximum inhibitory effect was observed in CEM-SS cells infected with the RFII strain of HIV-1. This inhibitory effect was determined to be concentration-dependent. Assay design included primary screening to measure cell viabilities of infected target cells in the presence and absence of test compounds. When tested on HIV-1/RFII-infected CEM-SS cells, the 50% inhibitory effect of CAS (IC50 = 28), an inhibitor of alpha-glucosidase I, was determined to be similar to that observed for ACE-M (IC50 = 45). However, DMN and SWS, inhibitors of mannosidase I and II, tested in parallel to CAS and ACE-M, exhibited no IC50 values. Antiviral potential of ACE-M as an inhibitor of syncytia formation was also explored using CEM-SS cells. Suppression of syncytia formation was observed at an ACE-M concentration of 31.25 micrograms/ml, and complete inhibition was observed at 62.5 micrograms/ml. In addition, HIV-1 RNA levels were studied to establish the antiviral potential of ACE-M in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of AIDS virus replication by acemannan in vitro. 176 65

High levels of the soluble form of the CD8 molecule (sCD8) are detectable in the serum of HIV-1-infected patients. To investigate the mechanisms accountable for the release of this molecule we evaluated the presence of sCD8 in the supernatants obtained from in vitro cultures of highly purified CD8 cells isolated from 20 HIV-1-infected patients. At resting conditions cultured CD8 cells from HIV-1-infected patients released low amounts of sCD8; no statistically significant differences were observed between unstimulated cultures from HIV-1-seropositive patients and from HIV-1-seronegative subjects at risk for HIV-1 infection or normal healthy controls. Following in vitro activation of highly purified CD8 cells with a series of stimulatory agents, including phorbol myristate acetate, phytohemagglutinin (PHA) and recombinant interleukin-2, CD8 cells of HIV-1-infected patients significantly increased the shedding of sCD8. By expressing the results of activation-related release index (ARRI = sCD8 levels detected in the cultures with stimulatory agent/sCD8 levels detected in the unstimulated cultures), significantly higher values were observed upon PHA stimulation in HIV-1-infected patients than in control subjects. In order to identify the cell subset responsible for the enhanced release of sCD8 by PHA-stimulated cultures, we correlated the amounts of sCD8 detected in the supernatants with the phenotypic profile of CD8+ cells recovered from the cultures. A significant relationship was demonstrated between the percentage of CD8+/HLA-DR+ lymphocytes and sCD8 levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Shedding of the soluble form of the CD8 complex by CD8+/HLA-DR+ cells in HIV-1-infected patients. 183 45


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