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Biomedical subjects

A G Dalgleish

Publications and source records attributed to A G Dalgleish.

At least 163 records · Page 9Linked to original sources
PubMed1989

Thrombophlebitis migrans following co-trimoxazole therapy.

We report an unusual and severe vasculitic disorder following co-trimoxazole, given orally for a urinary tract infection. The vasculitis was manifest solely as thrombophlebitis migrans and involving only veins without evidence of polyarteritis nodosa, or underlying malignancy.

Anti-Infective Agents, Urinary↗
PubMed1989

The relevance of HIV env/CD4 interactions to the pathogenesis of acquired immune deficiency syndrome.

The survey of the characteristics of HIV infection implicates the binding of HIV env to the CD4 receptor as the principal cause of the resulting immunodeficiency. There is evidence that such binding selectively impairs self-recognition. The resulting immunodeficiency syndrome has the characteristics of graft vs. host disease, consistent with chronic allogeneic and semiallogeneic GVHD in mouse-models. since these syndromes are believed to result from triggering the established immunoregulatory mechanisms necessary to maintain self-tolerance, vaccination to prevent AIDS should aim to correct the inability of the HIV host mount an immune response against CD4 binding epitopes on HIV gp120, preferably without exposing the vaccine to intact envelope glycoprotein. Since the AIDS syndrome is probably a defect in net-work immunoregulation, the most appropriate target for therapy and for vaccination is the idiotype of anti-CD4 antibodies that block CD4/env interaction.

Acquired Immunodeficiency Syndrome↗
PubMed1988

HIV infection does not require endocytosis of its receptor, CD4.

The T cell surface molecule CD4 interacts with class II MHC molecules on the surface of target cells as well as with the envelope glycoprotein of human immunodeficiency virus (HIV). Internalization of CD4 molecules is observed after exposure of CD4+ T cells to either phorbol esters or appropriate antigen-bearing target cells. To determine whether HIV entry proceeds via receptor-mediated endocytosis or direct viral fusion with the cell membrane, we have constructed two mutants in the cytoplasmic domain of the CD4 protein that severely impair the ability of CD4 molecules to undergo endocytosis. Quantitative infectivity studies reveal that HeLa cell lines expressing wild-type or mutant CD4 molecules are equally susceptible to HIV infection. In addition, HIV binding does not lead to CD4 endocytosis. These studies indicate that although the CD4 molecule can be internalized, HIV entry proceeds via direct fusion of the viral envelope with the cell membrane.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Surgical gloves as a mechanical barrier against human immunodeficiency viruses.

A wide variety of surgical gloves are presently available. Seven different types of gloves were investigated for the ability to prevent transmission of the human immunodeficiency virus (HIV), the causative agent of AIDS. Six types of gloves withstood severe compression tests and also exhibited direct antiviral properties. No penetration of HIV through the intact glove was detected.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Infection of B lymphocytes by the human immunodeficiency virus and their susceptibility to cytotoxic cells.

The T4 molecule (CD4) is an important component of the human immunodeficiency virus (HIV) receptor. As yet, no other component has been demonstrated. We report here that two cell lines, a B lymphoblastoid cell line (Gupta) and a glial cell line (HEB) derived from human embryonal brain tissue, are productively infectable with two distinct isolates of HIV as judged by electron microscopy and immunological and virological studies. These two cell lines do not display detectable surface CD4 glycoprotein. However, using S1 nuclease analysis, we have found that both cell lines do express low levels of CD4 mRNA. Neither of them produced syncytia formation upon HIV infection, a recognized feature of HIV-infected cells strongly expressing the CD4 glycoprotein. It is conceivable that the CD4 mRNA is translated, resulting in meager surface expression of CD4 molecules undetectable by conventional techniques. Therefore, infection with HIV may be one of the most sensitive methods of demonstrating low levels of CD4 expression by human cells. Furthermore, HIV-infected Gupta cells have here been shown to be more susceptible to the lytic activity of natural killer (NK) cells than their uninfected counterparts. These phenomena may be important for pathogenesis of HIV-associated disorders.

Antibodies, Monoclonal↗
PubMed1988

Neutralization of diverse HIV-1 strains by monoclonal antibodies raised against a gp41 synthetic peptide.

Three IgM monoclonal antibodies raised against synthetic peptide analogs of a hydrophilic region of the gp41 transmembrane env protein of HIV-1 neutralize different HIV-1 isolates but not HIV-2 isolates, as determined by HIV titration and by syncytial inhibition assays. VSV (HIV-1) pseudotypes, however, were not neutralized, indicating that gp41 was not accessible to these antibodies on the pseudotype particles. The antibodies affect early steps in adsorption and penetration of HIV-1.

Antibodies, Monoclonal↗
PubMed1988

Anti-idiotypic antibodies as immunogens: idiotype-based vaccines.

Numerous studies have documented that antibodies may regulate the immune system and form the basis of vaccines, namely anti-idiotype vaccines. Antibodies carry individual idiotype antigenic determinants against which antibodies can be formed. When the anti-idiotype recognizes the same site that recognizes the primary antigen, a mirror image or combining site antibody may be generated. Other anti-idiotypes which recognize non-combining antigenic determinants have also been used. The evidence is reviewed for the existence of a broad range of anti-idiotypes and details are given of how an anti-idiotype vaccine based on the hepatitis B surface antigen has protected against virus challenge in the most relevant animal model system, namely the chimpanzee. Furthermore, the definition of the CD4 molecule as the conserved binding site for all known human and similar immunodeficiency viruses, (in marked contradiction to their varied neutralizing properties) has led to the raising of anti-idiotypes in mice based on the CD4 receptor which have the capacity to neutralize a broad range of isolates.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Human retroviruses.

After many unsuccessful years of searching, the first pathogenic human retrovirus, the human T-cell leukaemia lymphoma virus (HTLV-I), was reported as recently as 1980 and since that time has been causally linked to the adult T-cell leukaemia lymphoma syndrome. A second HTLV (HTLV-II) isolated shortly afterwards is less clearly linked to some leukaemic and chronic lymphoid malignancies. The second major family of human retroviruses are the human immunodeficiency viruses (HIV) the first group of isolates (HIV-I) of which cause the acquired deficiency syndrome (AIDS). A second group of these viruses (HIV-II), have recently been identified in West Africa. They appear to be less clearly associated with disease and more similar in molecular structure to the Simian immunodeficiency viruses. AIDS has now become a major global pandemic, and vaccine and therapeutic strategies are urgently being investigated in an effort to control the disease. Unfortunately, current results are not very encouraging. In the meantime, preventative and educational measures are of utmost priority in order to prevent further spread. It is not unlikely that new human retroviruses will be discovered over the next few years.

Deltaretrovirus Infections↗
PubMed1988

A search for retrovirus infection in systemic lupus erythematosus and rheumatoid arthritis.

Evidence for retroviral infection in general and human immunodeficiency virus (HIV) infection in particular was sought in freshly isolated peripheral blood T cells, B cells, and monocyte-macrophages from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and also in T cell and B cell lines established from the same source. Similar cells isolated from rheumatoid synovial membrane were also examined. The strategy used for the detection of virus was cocultivation with susceptible cell lines looking for syncytia formation, reverse transcriptase production, and nucleic acid hybridisation with HIV cDNA probes. No evidence for infection was obtained.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Human immunodeficiency viruses: neutralization and receptors.

The envelope glycoproteins of HIV, gp120 and gp41, contain epitopes recognized by neutralizing antibodies. Studies of human sera from infected individuals indicate that group-specific neutralization antigens common to most isolates of HIV-1 exist, and that some HIV-2 antisera cross-neutralize HIV-1. Neutralization epitopes for HIV-1 have been identified and mapped, including a group-specific antigen on gp41, and a type-specific antigen on gp120. Neutralization "escape" mutants have been selected in vitro with a neutralizing mab to the type-specific antigenic loop. The CD4 antigen binds HIV-1 gp120 with high affinity and acts as the receptor on human and simian T-lymphocytes and monocytes for all strains of HIV-1, HIV-2, and SIV tested. Following binding to the CD4 receptor, HIV becomes internalized by a pH-independent process. The principle binding domain for gp120 is located in the N-terminal V domain of CD4. Anti-idiotypic sera to CD4 mabs recognizing the same site weakly neutralize HIVs of many strains, and soluble, recombinant forms of CD4 strongly neutralize HIV. Neither anti-CD4 mabs nor sCD4 inhibit the low level of plating of HIV observed on tumour cells in culture of glial (brain) and muscle origin, indicating that CD4 is not essential for infection of these cell types.

Animals↗
PubMed1988

Antibody-dependent cell-mediated cytotoxicity: comparison between HTLV-I and HIV-1 assays.

This study confirms the presence of detectable antibody-dependent cell-mediated cytotoxicity (ADCC) towards both HTLV-I- and HIV-1-infected cell lines, mediated by normal donor peripheral blood mononuclear cells and either by antibody from adult T-cell lymphoma and tropical spastic paraparesis patients (HTLV-I) or by antibody from sera of patients with persistent generalized lymphadenopathy, AIDS-related complex, AIDS and asymptomatic patients seropositive for HIV-1 infection. A comparison of ADCC towards these two retroviruses, under carefully controlled laboratory conditions, indicates major differences between the capacity of HTLV-I-seropositive sera and HIV-1-seropositive sera to mediate ADCC. In all cases, HIV sera showed low-titre ADCC, in contrast to the high titre (greater than 1:800,000) ADCC mediated by HTLV-I-positive sera. Both sets of sera showed the prozone phenomenon, and heat inactivation may abolish ADCC towards HIV-1-infected cells. Quantitation of surface antigen expression on HTLV-I- and HIV-1-infected cell lines indicated the presence of easily detectable amounts of virus-specific antigen. We conclude that, in contrast to some previous reports, ADCC mediated by HIV-1-specific immunoglobulin G (IgG) antibody is rather weak and of low titre when compared with HTLV-I ADCC. This is true for all cell lines and HIV-1 virus isolate combinations tested.

Antibodies, Monoclonal↗
PubMed1987

Neutralisation of HIV isolates by anti-idiotypic antibodies which mimic the T4 (CD4) epitope: a potential AIDS vaccine.

Polyclonal anti-idiotypic antibodies were raised in mice against anti-Leu3a, a mouse monoclonal anti-human T4 (CD4) antibody that blocks the in-vitro binding of human immunodeficiency virus (HIV) to the CD4 molecule. The anti-idiotypes recognized anti-Leu3a but not OKT4, an anti-human T4 antibody that does not inhibit HIV binding to CD4. The anti-idiotypes specifically reacted with the HIV envelope glycoprotein in solid-phase immunoassays. More importantly, the anti-idiotypes neutralised three distinct isolates of HIV-1 and one isolate of HIV-2 in a syncytial inhibition assay. These results have implications for a potential AIDS vaccine of anti-CD4 preparations to induce an anti-idiotypic response with the capacity to bind HIV at its receptor site.

Acquired Immunodeficiency Syndrome↗