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S R Lewin

Publications and source records attributed to S R Lewin.

7 recordsLinked to original sources
PubMed1998

HIV-1 DNA and mRNA concentrations are similar in peripheral blood monocytes and alveolar macrophages in HIV-1-infected individuals.

OBJECTIVE: To determine the relative contribution of alveolar macrophages, peripheral blood monocytes (PBM) and peripheral blood lymphocytes (PBL) from HIV-infected individuals to HIV-1 viral load. METHODS: Alveolar macrophages were obtained by flexible bronchoscopy, and PBM and PBL by venipuncture from HIV-1-infected individuals. Alveolar macrophages and PBM were purified using immunomagnetic bead selection to deplete CD3+ and CD19+ cells from bronchoalveolar lavage and peripheral blood mononuclear cells, respectively. DNA and mRNA were extracted and gag copy number quantified using polymerase chain reaction (PCR) and reverse transcriptase PCR. The titres of infectious cell-associated HIV-1 in cells were determined by the endpoint dilution coculture technique for alveolar macrophages and PBM. RESULTS: Alveolar macrophages and PBM from HIV-1-infected subjects (n=11) contained equivalent concentrations of HIV-1 DNA and HIV-1 mRNA as determined by PCR and reverse transcriptase PCR, respectively. Antiretroviral therapy was associated with reduced viral DNA concentrations in alveolar macrophages but not in PBM. PBL had a significantly higher level of proviral DNA and mRNA than alveolar macrophages or PBM. CONCLUSIONS: Although alveolar macrophages infected in vitro are more permissive for HIV-1 replication than PBM, this difference could not be demonstrated in vivo.

Cells, Cultured↗
PubMed1997

Constitutive expression of p50 homodimer in freshly isolated human monocytes decreases with in vitro and in vivo differentiation: a possible mechanism influencing human immunodeficiency virus replication in monocytes and mature macrophages.

Human immunodeficiency virus type 1 (HIV-1) replicates more efficiently in vitro in differentiated macrophages than in freshly isolated monocytes. We investigated whether this may be partly explained by changes in expression of NF-kappaB with monocyte differentiation. We demonstrated that constitutive expression of NF-kappaB in primary human monocytes changed significantly with differentiation in vitro to monocyte-derived macrophages (MDMs) and differentiation in vivo to alveolar macrophages (AMs). Freshly isolated monocytes constitutively expressed high levels of transcriptionally inactive p50 homodimer which decreased with time in culture in favor of the transcriptionally active p50/p65 and p50/RelB heterodimers. As in MDMs, AMs constitutively expressed p50/p65 and p50/RelB although at lower levels. HIV infection of fresh monocytes failed to induce p50/p65 as seen in MDMs. The replacement of p50 homodimers with transcriptionally active heterodimers following time in culture may partially explain the progressive increase in susceptibility of monocytes to HIV infection during in vitro culture. The change in NF-kappaB components with monocyte differentiation in vivo may also explain the different transcriptional activities of these cell populations in HIV-infected individuals.

Cell Differentiation↗
PubMed1996

Surface CD4 is critical to in vitro HIV infection of human alveolar macrophages.

The CD4 glycoprotein is the major cellular receptor for HIV. CD4 surface expression of monocytes decreases with time in culture while their susceptibility to HIV-1 increases. Our aim was to investigate whether this phenomenon occurs in macrophages that have differentiated in vivo by investigating CD4 expression and HIV-1 infection of human alveolar macrophages (AMs). Using flow cytometry to detect CD4 expression by Leu-3a labeled indirectly with fluorescein isothiocyanate or allophycocyanin, we found that CD4 was expressed at low but detectable levels, despite the high background autofluorescence well described in AMs. This finding was supported by the detection of CD4 mRNA in AMs using RT-PCR. T cell contamination of mRNA extracts of AMs was excluded by amplifying in parallel with primers to the constant region of the T cell receptor. Despite this low level of surface CD4, recombinant soluble CD4 and anti-CD4 antibody completely inhibited HIV-1 infection of AMs. We conclude that CD4, although expressed at low levels on the surface of AMs, appears to be critical to HIV-1 infection of these cells.

Acquired Immunodeficiency Syndrome↗
PubMed1995

The role of bronchoscopy in the diagnosis and treatment of pulmonary disease in HIV-infected patients.

BACKGROUND: Pulmonary disease is the most common reason for presentation and the major cause of death in HIV-infected patients. There has been an evolution in the optimal approach to the investigation of a pulmonary infiltrate in HIV-infected patients since the introduction of induced sputum for the diagnosis of Pneumocystis carinii pneumonia (PCP). AIMS: To evaluate the usefulness of flexible fibreoptic bronchoscopy (FFB), bronchoalveolar lavage (BAL), transbronchial biopsy (TBB) and bronchial brushings (BB) in the diagnosis of pulmonary disease in HIV-infected patients and to examine the effect of FFB on changes in therapy and survival. METHODS: The histories of all HIV-infected patients referred to Fairfield Hospital for FFB between January 1990 and June 1993 were examined retrospectively. RESULTS: Forty-two FFB were performed on 41 patients (40 male and one female). Definitive diagnoses made at FFB included Kaposi's sarcoma (KS) (n = 9), invasive aspergillosis (n = 5), PCP (n = 4), Mycobacterium avium complex (MAC) pneumonia (n = 2), cytomegalovirus (CMV) pneumonia (n = 1), Cryptococcus neoformans pneumonia (n = 1), microsporidium (n = 1) and Pseudomonas aeruginosa pneumonia (n = 1). TBB and BB did not provide a diagnosis for diseases not seen macroscopically at FFB or diagnosed by BAL. FFB findings altered diagnosis in 21/42 (50%) presentations and changed therapy in 26/42 (62%) cases. CONCLUSIONS: FFB together with BAL altered the working diagnosis and changed therapy in a significant number of patients. TBB and BB should not be routinely performed in all patients as these procedures are of limited value in this setting.

AIDS-Related Opportunistic Infections↗
PubMed1994

AIDS pathogenesis.

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Acquired Immunodeficiency Syndrome↗