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Biomedical subjects

C Leen

Publications and source records attributed to C Leen.

16 recordsLinked to original sources
PubMed2004

Management of hepatitis B in patients coinfected with the human immunodeficiency virus.

The human immunodeficiency virus (HIV) and the hepatitis B virus share common routes of transmission, and hence, coinfection with these two viruses is common. Chronic hepatitis B does not influence the progression of HIV disease or the response to highly active antiretroviral therapy. It is clear, however, that HIV infection does impact the course of hepatitis B, as higher rates of chronic carriage, lower seroconversion rates, and accelerated progression towards cirrhosis have been observed. Vaccination against hepatitis B is less effective in HIV-infected individuals. Coinfected subjects have a poor response to interferon therapy. Lamivudine is more effective in coinfected subjects but must not be used as monotherapy because of the risk of resistance developing. Combination therapy with lamivudine and tenofovir has shown promise and is currently being investigated in clinical trials, while new drugs and other combinations are in development.

Antiviral Agents↗
PubMed2003

Phenotypic analysis of peripheral blood gammadelta T lymphocytes and their targeting by human immunodeficiency virus type 1 in vivo.

There is increasing evidence that a wider range of lymphoid cell types other than CD4(+) T helper lymphocytes are infected with HIV-1 in vivo, including CD8 lymphocytes, natural killer cells, and reticulodendritic cells. Each potentially contributes to the reservoir of infected cells that resist antiviral treatment and to the impairment of immune responses in AIDS. By quantitative PCR for HIV proviral sequences we have now obtained evidence for substantial infection of gammadelta lymphocytes, contributing 3-45% of the proviral load in peripheral blood. A large proportion of gammadelta lymphocytes constitutively expressed the chemokine receptors CCR5 and CXCR4, with evidence for marked up-regulation of CD8 in samples from HIV-infected individuals, corresponding to an activated phenotype. That gammadelta lymphocytes might be susceptible to HIV infection was investigated using in vitro infectivity assays of recombinant HIV-expressing green fluorescent protein, followed by flow cytometry. gammadelta, CD4, and CD8 lymphocytes were each productively infected, with gammadelta lymphocytes showing the greatest susceptibility. For each cell type, blocking assays with an anti-CD4 monoclonal antibody indicated that entry was CD4-dependent.

Adult↗
PubMed2001

Activated peripheral CD8 lymphocytes express CD4 in vivo and are targets for infection by human immunodeficiency virus type 1.

There is increasing evidence that CD8 lymphocytes may represent targets for infection by human immunodeficiency virus type 1 (HIV-1) in vivo whose destruction may contribute to the loss of immune function underlying AIDS. HIV-1 may infect thymic precursor cells destined to become CD4 and CD8 lymphocytes and contribute to the numerical decline in both subsets on disease progression. There is also evidence for the induction of CD4 expression and susceptibility to infection by HIV-1 of CD8 lymphocytes activated in vitro. To investigate the relationship between CD8 activation and infection by HIV-1 in vivo, activated subsets of CD8 lymphocytes in peripheral blood mononuclear cells (PBMCs) of HIV-seropositive individuals were investigated for CD4 expression and HIV infection. Activated CD8 lymphocytes were identified by expression of CD69, CD71, and the human leukocyte antigen (HLA) class II, the beta-chain of CD8, and the RO isoform of CD45. CD4(+) and CD4(-) CD8 lymphocytes, CD4 lymphocytes, other T cells, and non-T cells were purified using paramagnetic beads, and proviral sequences were quantified by PCR using primers from the long terminal repeat region. Frequencies of activated CD8 lymphocytes were higher in HIV-infected study subjects than in seronegative controls, and they frequently coexpressed CD4 (mean frequencies on CD69(+), CD71(+), and HLA class II(+) cells of 23, 37, and 8%, respectively, compared with 1 to 2% for nonactivated CD8 lymphocytes). The level of CD4 expression of the double-positive population approached that of mature CD4 lymphocytes. That CD4 expression renders CD8 cell susceptible to infection was indicated by their high frequency of infection in vivo; infected CD4(+) CD8 lymphocytes accounted for between 3 and 72% of the total proviral load in PBMCs from five of the eight study subjects investigated, despite these cells representing a small component of the PBMC population (<3%). Combined, these findings provide evidence that antigenic stimulation of CD8 lymphocytes in vivo induces CD4 expression that renders them susceptible to HIV infection and destruction. The specific targeting of responding CD8 lymphocytes may provide a functional explanation for the previously observed impairment of cytotoxic T-lymphocyte (CTL) function disproportionate to their numerical decline in AIDS and for the deletion of specific clones of CTLs responding to HIV antigens.

Adult↗
PubMed2001

Infection of the CD45RA+ (naive) subset of peripheral CD8+ lymphocytes by human immunodeficiency virus type 1 in vivo.

To investigate the mechanism and functional significance of infection of CD8+ lymphocytes by human immunodeficiency virus type 1 (HIV-1) in vivo, we determined frequencies of infection, proviral conformation, and genetic relationships between HIV-1 variants infecting naive (CD45RA+) and memory (CD45RO+) peripheral blood CD4+ and CD8+ lymphocytes. Infection of CD3+ CD8+ CD45RA+ cells was detected in 9 of 16 study subjects at frequencies ranging from 30 to 1,400 proviral copies/10(6) cells, more frequently than CD3+ CD8+ lymphocytes expressing the RO isoform of CD45 (n = 2, 70 and 260 copies /10(6) cells). In agreement with previous studies, there was no evidence for a similar preferential infection of CD4+ naive lymphocytes. Proviral sequences in both CD4+ and CD8+ lymphocyte subsets were complete, as assessed by quantitation using primers from the long terminal repeat region spanning the tRNA primer binding site. In six of the seven study subjects investigated, variants infecting CD8+ lymphocytes were partially or completely genetically distinct in the V3 region from those recovered from CD4+ lymphocytes and showed a greater degree of compartmentalization than observed between naive and memory subsets of CD4+ lymphocytes. In two study subjects, arginine substitutions at position 306, associated with use of the chemokine coreceptor CXCR4, were preferentially found in CD4 lymphocytes. These population differences may have originated through different times of infection rather than necessarily indicating a difference in their biological properties. The preferential distribution of HIV-1 in naive CD8+ lymphocytes indeed suggests that infection occurred early in T-lymphocyte ontogeny, such as during maturation in the thymus. Destruction of cells destined to become CD8+ lymphocytes may be a major factor in the decline in CD8+ lymphocyte frequencies and function on disease progression and may contribute directly to the observed immunodeficiency in AIDS.

Amino Acid Sequence↗
PubMed1998

Intravitreal sustained-release ganciclovir implantation to control cytomegalovirus retinitis in AIDS.

A novel form of therapy, the intravitreal ganciclovir implant (Vitrasert), was used to treat cytomegalovirus (CMV) retinitis in AIDS, when it was not possible to continue systemic therapy or disease progression was evident despite conventional intravenous treatment. A review of the ophthalmic and general health data, operative records and fundus photographs of 9 individuals who had Vitrasert implantation surgery in Edinburgh. Two patients received bilateral replacement implant procedures. Visual acuity, concomitant anti-CMV therapy, complications of implantation and control of retinitis were documented until final follow-up. Control of CMV retinitis was achieved in all individuals at one month postoperatively and remained controlled for a mean period of 5.8 months. Postoperative complications were mild and transient in all but 2 eyes of 2 patients who developed non-progressive macula oedema. Blinding complications as a result of surgery were not encountered and retinal detachment was not observed in this series. Vitrasert implantation is an acceptable and well tolerated treatment for CMV retinitis when systemic therapy fails to control disease progression.

AIDS-Related Opportunistic Infections↗
PubMed1997

Features and outcome of Pneumocystis carinii pneumonia according to risk category for HIV infection.

A retrospective study of Pneumocystis carinii pneumonia (PCP) was undertaken to examine differences between the presentation and outcome of PCP in AIDS patients from different risk categories for HIV infection. There were 176 PCP episodes recorded in 126 patients from the following risk categories: 69 intravenous drug misusers (IDMs), 36 homosexually infected men and 21 heterosexually infected patients. Most clinical features did not differ significantly between the 3 groups but hypercapnia was almost exclusively seen in IDMs and, if recorded, was associated with a poorer survival. Pneumothorax was more likely to complicate PCP in IDMs and, although present in all groups, concomitant bacterial respiratory infections were more common in IDMs. Recovery from PCP and the incidence of adverse events during treatment did not differ according to risk category. Subsequent survival time was shorter amongst IDMs, but the uptake of antiretrovirals in this group was significantly lower. We conclude that there are few differences in the presentation of PCP between IDMs and other risk categories for HIV infection and that these do not influence the outcomes of illness. The lower post-PCP survival in IDMs can be accounted for by a reduced uptake of antiretroviral drugs by this group.

AIDS-Related Opportunistic Infections↗
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Humans↗