Type 1 cytokine production and low prevalence of viral isolation correlate with long-term nonprogression in HIV infection.

Cytokine production, prevalence of viral isolation, and surface marker expression of peripheral blood mononuclear cells (PBMCs) were analyzed in HIV+ individuals with different patterns of disease progression to establish correlations between these parameters. Thus, mitogen-stimulated in vitro production of interferon gamma (IFN-gamma) and interleukin 2 (IL-2) (type 1 cytokines), and of IL-4 and IL-10 (type 2 cytokines) as well as prevalence of viral isolation were evaluated in 26 HIV+ long-term nonprogressors (LTNPs), in 28 HIV+ patients with progressive HIV infection (PI), and in 24 HIV-seronegative controls (HCs). Surface expression of activation and nonactivation markers was also analyzed in a group of these donors.

Amelioration of experimental systemic lupus erythematosus (SLE) by retrovirus infection.

Experimental SLE can be induced in susceptible 129/J mice by immunization with a human anti-DNA antibody bearing a common idiotype designated 16/6 Id. Immunized mice develop autoantibodies, leukopenia, proteinuria, and immune complex deposits in renal glomeruli. Case reports have described clinical improvement in SLE in individuals becoming infected with HIV-1.

Molecular analysis of decreased interleukin-12 production in persons infected with human immunodeficiency virus.

Human immunodeficiency virus (HIV) disease is associated with loss of type 1 responses, including interleukin (IL)-12 production. The dramatic drop in p70 production seen at early stages of disease was found not to be associated with a similarly decreased p40 mRNA expression. p35 mRNA expression was more extensively reduced than p40 mRNA expression at these early stages.

Lamivudine in children with human immunodeficiency virus infection: a phase I/II study. The National Cancer Institute Pediatric Branch-Human Immunodeficiency Virus Working Group.

The safety, tolerability, pharmacokinetic profile, and preliminary activity of lamivudine (2'-deoxy-3'-thiacytidine), a novel cytidine nucleoside analogue with antiretroviral activity, in human immunodeficiency virus (HIV)-infected children beyond the neonatal period were studied. Ninety children received dosages of 1-20 mg/kg/day. Pharmacokinetic evaluation demonstrated serum and cerebrospinal fluid concentrations that increased proportionally to dose.

Correlates of protection in HIV infection and the progression of HIV infection to AIDS.

Exposure to human immunodeficency virus (HIV) can result in HIV infection which is defined by seroconversion and the detection of HIV-specific antibodies. Nevertheless, in every cohort at risk for HIV infection, individuals are present in whom seroconversion is not observed despite multiple documented exposures to HIV. Recent studies have shown that HIV-specific T-lymphocytes are present in the peripheral blood of these HIV-exposed seronegative individuals, suggesting that cell-mediated immunity (CMI) could have a protective role in the prevention of HIV infection.

Isolation and characterization of a calmodulin-encoding cDNA from the pathogenic fungus Histoplasma capsulatum.

We describe in this paper the isolation and complete sequence of a calmodulin (CaM) encoding cDNA from the dimorphic pathogenic fungus Histoplasma capsulatum (GenBank accession U12505). The deduced amino acid sequence was identical to the CaM of Aspergillus nidulans and had only one amino acid difference from the CaM of Neurospora crassa. Saccharomyces cerevisiae CaM, however, has only about 60% amino acid identity compared with H.

Antigen-stimulated apoptotic T-cell death in HIV infection is selective for CD4+ T cells, modulated by cytokines and effected by lymphotoxin.

Objective: To characterize the mechanism of in vitro antigen-induced apoptotic T-cell death in the peripheral blood mononuclear cells (PBMC) of HIV-1-infected individuals.

Design And Methods: PBMC from HIV-1 infected and uninfected individuals were unstimulated or stimulated with HIV-1 envelope synthetic peptides (Env) or influenza A virus to determine the extent of antigen-stimulated apoptotic T-cell death, whether this death was limited to the CD4+ subset, and the effects of cytokines on T-cell death. Death was assessed by apoptotic nuclear morphology after 7 days of culture by fluorescence microscopy using a DNA-specific dye.

Potential clinical applications of interleukin-12.

Interleukin-12 is a central modulatory cytokine with potent effects on the development and differentiation of the cellular immune response. Because of its biologic activities, interleukin-12 could either mediate or contribute to the control of a large range of critical world-wide pathologic conditions, including infectious diseases and cancer. Its potential efficacy has been demonstrated in several animal models of intracellular pathogens and tumors, as well as in vitro in some human pathologies.

In vitro restoration of T cell immune function in human immunodeficiency virus-positive persons: effects of interleukin (IL)-12 and anti-IL-10.

Cells from human immunodeficiency virus (HIV)-positive patients were evaluated for their in vitro responsiveness to recall antigen, alloantigen, and phytohemagglutinin (PHA) following the in vitro addition of interleukin (IL)-12 or anti-IL-10. Three-color flow cytometric analysis of CD4 and CD8 subsets was done to determine whether specific in vivo alterations in cell surface markers are associated with in vitro function changes. The results demonstrated a hierarchical response pattern to recall antigens versus alloantigen versus PHA, and these in vitro responses were associated with the number and activation status of CD4 cells.

On-line metal chelate affinity chromatography clean-up for the high-performance liquid chromatographic determination of tetracycline antibiotics in animal tissues.

An on-line high-performance liquid chromatographic (HPLC) method for the determination of tetracycline, oxytetracycline, chlortetracycline and demeclocycline using metal chelate affinity chromatography-reversed-phase HPLC has been developed. The drugs were extracted with succinate buffer and the extract diluted with EDTA-pentanesulphonate buffer. Diluted extract was then absorbed onto a C8 or XAD-2 solid-phase extraction (SPE) cartridge and eluted with methanol.

The effect of cooking on veterinary drug residues in food: 4. Oxytetracycline.

The heat stability of oxytetracycline (OTC) in water and vegetable oil was investigated. Results showed that the drug was unstable in water at 100 degrees C with a half-life of about 2 min, but more stable in oil at 180 degrees C where the half-life was about 8 min. The effect of a range of cooking processes including microwaving, boiling, roasting, grilling, braising and frying on OTC residues in incurred animal tissues was investigated.

Modulation of T cell responses to recall antigens presented by Langerhans cells in HIV-discordant identical twins by anti-interleukin (IL)-10 antibodies and IL-12.

Decreased antigen (Ag)-specific T cell (TC) proliferation and IL-2 production are detected in all stages of HIV disease. To determine whether dendritic cell dysfunction and/or abnormal cytokine production contribute to HIV-induced immune dysregulation, we studies TC responses to recall Ags (influenza virus and tetanus toxoid) presented by Langerhans cells (LC) in six pairs of HIV-discordant identical twins, and the modulation of these responses by anti-IL-10 (alphaIL-10) mAbs and IL-12. LC from HIV+ twins induced IL-2 comparable to normal LC in cultures containing TC from uninfected twins.

Human immunodeficiency virus type 1 (HIV-1)-seronegative injection drug users at risk for HIV exposure have antibodies to HLA class I antigens and T cells specific for HIV envelope.

The question of whether persistently seronegative persons at high risk for human immunodeficiency virus type 1 (HIV-1) infection exhibit HIV-1-specific T cell responses and antibodies to HIV-1 envelope epitopes shared with selected HLAs was assessed. These antibodies are not detectable by conventional serologic methods. Envelope-specific helper T (Env-Th) cell responses and antibodies specific for the HIV/HLA epitopes were studied in 21 HIV-1-negative injection drug users (IDUs).

Effect of metacycloprodigiosin, an inhibitor of killer T cells on murine skin and heart transplants.

Metacycloprodigiosin is an antibiotic that has been shown to suppress T-cell proliferation induced by concanavalin A in vitro. We examined the effect of metacycloprodigiosin on murine allogenic skin and heart transplantation models, and compared graft rejection with donor-specific cytotoxic T-cells and antibody activity. The antibiotic slightly prolonged the survival of C57Bl/6 heart and skin grafts in BALB/c mice, although the effect was less that that of cyclosporin A.

Isolation, DNA sequence analysis, and mutagenesis of a proline dehydrogenase gene (putA) from Bradyrhizobium japonicum.

We report here the cloning and sequencing of the gene for proline dehydrogenase (putA) of Bradyrhizobium japonicum. An open reading frame coding for 1,016 amino acids was identified. The B.

The effect of cooking on veterinary drug residues in food: 3. Sulphamethazine (sulphadimidine).

The heat stability of sulphamethazine was investigated. The drug was shown to be stable in boiling water at 100 degrees C. In cooking oil at 260 degrees C, losses were observed, indicating a half-life of about 5 min.

T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years.

In 1990, a clinical trial was started using retroviral-mediated transfer of the adenosine deaminase (ADA) gene into the T cells of two children with severe combined immunodeficiency (ADA- SCID). The number of blood T cells normalized as did many cellular and humoral immune responses. Gene treatment ended after 2 years, but integrated vector and ADA gene expression in T cells persisted.

Cloning and analysis of cDNA encoding an elongation factor 1 alpha from the dimorphic fungus Histoplasma capsulatum.

The cDNA encoding translation elongation factor 1 alpha (EF-1 alpha) was isolated from the dimorphic fungus, Histoplasma capsulatum (Hc), an important pathogen of man. A cDNA library was probed with the tef1 gene from the fungus Mucor racemosus. Ten independent clones were isolated, all with similar restriction patterns.