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Biomedical subjects

A G Dalgleish

Publications and source records attributed to A G Dalgleish.

At least 181 records · Page 10Linked to original sources
PubMed1987

Inhibition of HIV replication in vitro by fusidic acid.

A 58-year-old man with AIDS improved clinically after the introduction of fusidic acid, 500 mg three times a day orally, to his therapeutic regimen. Fusidic acid may have had a direct effect against HIV. Fusidic acid has anti-HIV activity in vitro at levels readily attainable in vivo. The drug does not appear to be a reverse transcriptase inhibitor and its mode of action against HIV is unknown. Fusidic acid can be given orally and has few side-effects. These results justify fuller evaluation of fusidic acid as therapy against AIDS and HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Human immunodeficiency virus infection of monocytic and T-lymphocytic cells: receptor modulation and differentiation induced by phorbol ester.

The monocytic leukemic cell line U937 can be infected with human immunodeficiency virus type 1 (HIV-1) to become permanently infected virus producers. Uninfected U937 cells express T4 (CD4) antigen and form syncytia when mixed with HIV-1 producing cells. Anti-T4 monoclonal antibodies block syncytium formation indicating that the HIV-1 receptors on U937 cells include T4 antigen. The promyelocytic leukemic cell line HL60, while expressing only low amounts of surface T4 and not forming syncytia on exposure to HIV-1, can be infected by HIV-1 at lower efficiency than U937 and T-cell lines. 12-O-Tetradecanoylphorbol-13-acetate (TPA) treatment induces the differentiation of U937 cells into macrophages. HIV-infected U937 cells retain the ability to differentiate, though less efficiently, as shown by the appearance of monocyte/macrophage surface markers. T4 antigen on both U937 and T-cell lines is down regulated by TPA treatment. Functional receptors for HIV-1, assayed by syncytium induction and pseudotype plating, are lost concomitantly with T4 antigen following TPA treatment of U937 cells and T cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Phosphonoformate (foscarnet): a pilot study in AIDS and AIDS related complex.

Phosphonoformate (PFA; a pyrophosphate analogue) is an effective inhibitor of the reverse transcriptase enzyme in many animal retroviruses. In vitro studies have shown that PFA is also an effective inhibitor of HIV (HTLV III/LAV) at doses readily attainable in vitro. A pilot study was therefore performed with a 3-week intravenous infusion of PFA in 11 patients with AIDS and AIDS-related complex (ARC). Viral isolations were performed before and at regular intervals up to 3 months post-infusion on treated patients, as well as on four untreated control patients. Virus isolation was negative after therapy in eight patients, six of whom were negative throughout the follow-up period. Virus was isolated on 70% of attempts from the four control subjects and on 20% of attempts from treated subjects. Three patients showed an improvement in delayed hypersensitivity responses. No obvious improvement was seen in patients' OKT4 positive lymphocyte counts. Treatment was not limited by side-effects with the exception of one patient who developed an axillary vein thrombosis within 4 days of treatment via a subclavian line. Treatment was therefore discontinued following administration of only one dose and the patient was excluded from further study. A further patient had reversible renal dysfunction. Other side-effects were minor, consisting of headache or thrombophlebitis at the site of infusion. These results suggest that a further trial with PFA administered over a longer period and with a longer follow-up period in AIDS and ARC patients may be warranted, particularly if an oral preparation becomes available.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex↗
PubMed1987

Lymphokine-activated killer cell activity in rheumatoid arthritis.

The lymphokine-activated killer (LAK) cell activity in the peripheral blood of 23 patients with rheumatoid arthritis has been studied. Two control groups comprised (a) nine patients with another chronic inflammatory disease (sarcoidosis) and (b) 19 normal healthy volunteers. The LAK activity induced by human recombinant IL-2 was very similar in controls and patients with rheumatoid arthritis but was significantly decreased in patients with sarcoidosis, although the frequency of LAK-cell precursors measured using a limiting dilution assay was comparable in all three groups. The DNA synthetic response of peripheral blood mononuclear (PBM) cells to IL-2 was slightly decreased in patients with both rheumatoid arthritis and sarcoidosis as compared to controls, but this decrease was not statistically significant. Spontaneous DNA synthesis in PBM cells cultured in the absence of IL-2 was essentially identical in all three groups. We conclude on the basis of these results that the higher risk of non-Hodgkin's lymphomas in patients with rheumatoid arthritis cannot be attributed to an impairment of LAK activity. Furthermore, the doses of gamma-irradiation, which abolished the 'background' cytotoxicity of PBM cells cultured without IL-2 and also blocked effectively both spontaneous and exogenous IL-2-dependent DNA synthesis, had little effect on the generation of LAK activity. These observations are discussed in regard to the role of non-specific cytotoxic cells and the therapeutic efficacy of antiproliferative drugs in rheumatoid arthritis.

Adult↗
PubMed1986

Epitopes of the CD4 antigen and HIV infection.

The CD4 (or T4) surface antigen of human T lymphocytes is an important part of the receptor for the human immunodeficiency virus (HIV). After binding to the receptor, the HIV may enter the T cell and induce the formation of syncytia. In an attempt to identify the receptor site more closely, monoclonal antibodies (Mab's) to CD4 were tested for their ability to block HIV infection in a syncytium formation assay, and the CD4 epitopes so identified were mapped by antibody cross-blocking. The antibodies that showed strong inhibition of HIV fell into two main families while a third group of Mab's blocked syncytia formation weakly or not at all. Several different isolates of HIV as well as the laboratory strain CBL1 grown in CEM cells were used to induce the syncytia. The data indicate that only some epitopes of CD4 are important for virus binding and imply that the virus-binding site for CD4 is conserved in different isolates of HIV with substantially divergent env gene sequences. Preliminary studies of patients suggest that polymorphism of these epitopes does not play a role in determining susceptibility to infection.

Acquired Immunodeficiency Syndrome↗
PubMed1986

The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain.

The isolation of clones encoding the human surface protein T4, and the expression of the T4 gene in new cellular environments, have enabled us to examine the role of this protein in the pathogenesis of AIDS. Our studies support a mechanism of AIDS virus infection that initially involves the specific interaction of the AIDS virus with T4 molecules on the cell surface. This association can be demonstrated on T4+ transformed T and B lymphocytes as well as epithelial cells. Furthermore, the presence of T4 on the surface of all human cells examined is sufficient to render these cells susceptible to AIDS virus infection. Our data suggest that the T4-AIDS virus complex is then internalized by receptor-mediated endocytosis. Finally, we find that the T4 gene is expressed in the brain as well as in lymphoid cells, providing an explanation for the dual neurotropic and lymphotropic character of the AIDS virus. In this manner, a T lymphocyte surface protein important in mediating effector cell-target cell interactions has been exploited by a human retrovirus to specifically target the AIDS virus to populations of T4+ cells.

Ammonium Chloride↗
PubMed1986

Studies in healthy human T-cell-leukemia lymphoma virus (HTLV-I) carriers from the Caribbean.

Six healthy relatives of 3 adult T-cell leukemia lymphoma (ATLL) patients and 6 members of a Caribbean family immigrant to the UK have been investigated for the presence of HTLV-I and expression of interleukin 2 (IL-2) receptors. Serum antibodies to HTLV-I were detected in all but 4 samples. Four to 10% of circulating cells from 3/4 seropositive donors studied displayed IL-2 receptors (anti-Tac+) and were shown to be convoluted lymphocytes by light microscopy morphology and immunoelectronmicroscopy. After 5 to 28 days in culture, cells from 4 seropositive donors reacted with monoclonal antibodies (MAbs) against the HTLV-I core proteins, p19 and p24, and released retrovirus particles. Similar experiments with blood from 3 seronegative donors from the same families and 4 normal controls proved negative. Our findings indicate that seropositive individuals harbour the virus in a population of T-lymphocytes which may then acquire receptors for IL-2. These individuals are at risk of developing ATLL.

Antibodies, Viral↗
PubMed1986

Isolation of retroviruses from two patients with "common variable" hypogammaglobulinaemia.

Retroviruses related to human T-lymphotropic virus III/lymphadenopathy-associated virus (HTLV-III/LAV) have been isolated from peripheral-blood mononuclear cells of two patients with "common variable" hypogammaglobulinaemia who were being treated with intravenous gammaglobulin. One has had three different opportunistic infections. In both patients hypogammaglobulinaemia developed within 6 years of a longlasting undiagnosed viral-like illness in adolescence, and it is suggested that the virus causing that illness also gave rise to the hypogammaglobulinaemia. However, iatrogenic infection from intravenous gammaglobulin cannot be ruled out.

Adolescent↗
PubMed1986

The T4 glycoprotein is a cell-surface receptor for the AIDS virus.

Taken together, our studies suggest a mechanism of AIDS virus infection that initially involves the specific association of the AIDS virus with T4 molecules on the cell surface. This association does not require additional T-cell-specific molecules and can be demonstrated on both B lymphocytes and epithelial cell lines. The T4-AIDS virus complex is likely to be internalized in endosomes via receptor-mediated endocytosis. The virus can then fuse with the vacuolar membrane, releasing the viral nucleocapsid into the cytoplasm to undergo uncoating. Viral replication does not appear to require the environment of a T lymphocyte because active infection is also observed in human T4+ B lymphocytes and epithelial cell lines. Moreover, the T4 gene is expressed in the brain as well as in lymphocytes, providing an explanation for the dual neurotropic and lymphotropic character of the virus. In this manner, a T-lymphocyte surface protein thought to be important in mediating effector cell-target cell interactions has been exploited by a human lymphotropic virus to target the AIDS virus specifically to populations of T4+ cells.

Acquired Immunodeficiency Syndrome↗
PubMed1986

A viral etiology for Hodgkin's disease?

There have been numerous suggestive but inconclusive reports of a possible infectious etiology for Hodgkin's disease. The discovery of the causative agent of the adult T cell leukemia-lymphoma syndrome suggests that a similar agent to the human T cell leukemia-lymphoma virus may have a causal role in Hodgkin's disease.

Adolescent↗
PubMed1985

Slim disease: a new disease in Uganda and its association with HTLV-III infection.

A new disease has recently been recognised in rural Uganda. Because the major symptoms are weight loss and diarrhoea, it is known locally as slim disease. It is strongly associated with HTLV-III infection (63 out of 71 patients) and affects females nearly as frequently as males. The clinical features are similar to those of enteropathic acquired immunodeficiency syndrome as seen in neighbouring Zaire. However, the syndrome is rarely associated with Kaposi's sarcoma (KS), although KS is endemic in this area of Uganda. Slim disease occurs predominantly in the heterosexually promiscuous population and there is no clear evidence to implicate other possible means of transmission, such as by insect vectors or re-used injection needles. The site and timing of the first reported cases suggest that the disease arose in Tanzania.

Acquired Immunodeficiency Syndrome↗