Supernatants of HIV-infected immune cells affect the barrier function of human HT-29/B6 intestinal epithelial cells.

Objectives: Characterization of the diarrhoea-inducing effect of altered cytokine production in HIV infection.

Methods: Monocyte-derived macrophages (MDM) were infected with macrophagetropic (SF162) and lymphocytotropic (IIIB) HIV-1 strains and cocultured with autologous peripheral blood mononuclear cells (PBMC). After 24 h the supernatants were collected and tested for their immunoreactive levels of cytokines by enzyme-linked immunosorbent assay.

Inactivation of viruses by beta-propiolactone in human cryo poor plasma and IgG concentrates.

Virus inactivation by cold treatment with beta-propiolactone (BPL) was investigated in human cryo poor plasma and purified IgG concentrates spiked with relevant human viruses or appropriate animal model viruses. The samples were treated with 0.1 or 0.

Epithelial uptake and transport of cell-free human immunodeficiency virus type 1 and gp120-coated microparticles.

Cell-free human immunodeficiency virus type 1 (HIV-1) can be taken up and released by a monolayer of primary human gingival cells and remain infectious for CD4+ cells. Virus-sized latex particles covalently coated with purified native HIV-1 envelope glycoprotein gp120 are also transported through the primary epithelial cells. This process is significantly stimulated by increasing the intracellular cyclic AMP (cAMP) concentration.

Transport of viruses through fetal membranes: an in vitro model of perinatal transmission.

A model system for perinatal transmission of viral infections was developed and transport of infectious virus particles through fetal membranes was investigated. Viruses of different families known to cause serious intrauterine infections were selected, including relevant and model viruses: the DNA-viruses HSV-1 and -2 as well as the animal herpes viruses BHV-1 and SHV-1, the RNA-virus BVDV as a model for hepatitis C virus, HIV-1 and -2, and PPV as a model for parvovirus B19. Migration of infectious virus from the maternal to the fetal side of the membrane could be detected as early as 20 min after the start of incubation.

Selective endocytosis of fluorothymidine and azidothymidine coupled to LDL into HIV infected mononuclear cells.

Drug targeting via lipoproteins may be of benefit for use of cytotoxic drugs like fluorothymidine (FLT) or azidothymidine (AZT). Both drugs are potent inhibitors of the human immunodeficiency virus (HIV) reverse transcriptase and are used in the therapy of HIV infection. With regard to this project, the selective endocytosis in HIV infected human macrophages was studied after covalent coupling of AZT and LDL to low density lipoproteins (LDL).

Replication pattern of human immunodeficiency virus type 1 in mature Langerhans cells.

Langerhans cells (LC), the dendritic antigen presenting cells of the skin, mature into potent immunostimulatory cells during migration to regional lymph nodes, where they are identified as interdigitating cells (IDC). Since mature Langerhans cells (mLC) resemble IDC in phenotype and immunostimulatory capacity, we examined whether these cells were susceptible to infection with macrophagetropic and lymphotropic strains of human immunodeficiency virus type 1 (HIV-1). Highly purified cell preparations of mLC migrating from human epidermis expressed high amounts of major histocompatibility complex (MHC) class I and II antigens and of the accessory molecules CD40, CD80 and CD86, indicative of the phenotype of potent immunostimulatory cells.

Cell specific uptake of antiretroviral drugs: AZT coupled to LDL inhibits HIV replication in human macrophages.

Macrophages, besides helper T-lymphocytes, are target cells for the human immunodeficiency virus (HIV). We report on a mechanism to deliver selectively antiretroviral drugs to cells of the monocyte/macrophage lineage. These cells and cells of the endothelium express scavenger receptors which mediate the transport of modified low density lipoprotein (LDL).

Expression of nef, vpu, CA and CD4 during the infection of lymphoid and monocytic cell lines with HIV-1.

The expression of the capsid antigen (CA) and the two regulatory proteins nef and vpu as well as the CD4 cell surface receptor was followed in HIV-infected lymphoid and promonocytic cells. In the lytic phase of infection all three viral proteins were expressed; production of these proteins coincided with the increase of CA antigen and infectious virus in culture supernatants and with prominent cytopathic effects. After selection of persistently infected cells, the number of lymphoid cells expressing detectable levels of nef decreased to zero; the number of cells positive for CA ranged between 40 to 70%.

Interferon induction by cell-cell interaction of HIV-infected monocytes/macrophages with lymphocytes.

An in vitro model of interferon (IFN) induction in HIV infection was established. IFN are induced by a cooperative mechanism, involving monocytes/macrophages (M/M) as well as lymphocytes. M/M non-lytically infected with HTLV-IIIB did not produce IFN, but were able to induce high titres of IFN activity when cocultured with peripheral blood lymphocytes, cell-cell contact being required.

Altered urinary excretion of pteridines in neoplastic disease. Determination of biopterin, neopterin, xanthopterin, and pterin.

Urinary pteridine concentrations in healthy control subjects and patients with cancer and non-malignant diseases were determined by HPLC and TLC after partial purification by ion exchange and Sephadex chromatography. Elevated concentrations of neopterin were found in 70% of the 50 cancer patients investigated. In patients with non-Hodgkin's lymphoma (seven cases) or with liver metastases (12 cases) neopterin concentrations were significantly higher than in control subjects (p < 0.