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Biomedical subjects

D R Lucey

Publications and source records attributed to D R Lucey.

At least 55 records · Page 3Linked to original sources
PubMed1991

Comparison of spinal fluid beta 2-microglobulin levels with CD4+ T cell count, in vitro T helper cell function, and spinal fluid IgG parameters in 163 neurologically normal adults infected with the human immunodeficiency virus type 1.

Beta 2-microglobulin levels were measured in the cerebrospinal fluid (CSF) and serum of 163 human immunodeficiency virus-positive (HIV+) persons with normal neurologic physical examinations. None were on antiretroviral therapy. Only 3% had a positive CSF HIV p24 antigen test. The CSF beta 2-microglobulin levels increased as the CD4+ T cell count decreased. Intrathecal production of beta 2-microglobulin was suggested by finding CSF concentrations greater than serum concentrations in 15% of patients. The CSF beta 2-microglobulin levels rose as in vitro T helper cell function deteriorated, independent of CD4+ T cell count. CSF beta 2-microglobulin levels paralleled CSF IgG, IgG index, and IgG synthesis. Higher CSF beta 2-microglobulin levels were found in persons with positive CSF oligoclonal bands. CSF beta 2-microglobulin concentration may serve as a marker for subclinical neurologic damage due to HIV. If this is established, defining the effect of anti-HIV interventions on CSF beta 2-microglobulin would be warranted.

Albumins↗
PubMed1991

Human immunodeficiency virus infection in the US Air Force: seroconversions, clinical staging, and assessment of a T helper cell functional assay to predict change in CD4+ T cell counts.

As of January 1990, 933 persons with human immunodeficiency virus type 1 (HIV-1) infection were clinically evaluated at Wilford Hall US Air Force (USAF) Medical Center. The Walter Reed HIV staging system was used in these evaluations to describe disease status and progression. Most persons were diagnosed through mandatory HIV testing in the USAF and were asymptomatic at the time of diagnosis. As of May 1990, 161 HIV-positive seroconverters (estimated overall seroconversion rate of 0.156/1000 person-years between 30 June 1988 and 1 July 1990) had been identified among active-duty USAF personnel, as they had previously tested negative for antibody to HIV. Men constitute 95% of the USAF HIV-positive population. An in vitro T helper cell functional assay was assessed to predict rate of CD4+ T cell decline over the subsequent year (mean, 15 months) in patients with greater than 200 CD4+ T cells/mm3. This assay may prove useful for prognostication and comparisons of patients in clinical trials of anti-HIV interventions.

Adult↗
PubMed1991

Negative correlation between blood cell counts and serum neopterin concentration in patients with HIV-1 infection.

Hematopoietic disturbances are common in patients with HIV-1 infection. Recent studies on immune activation markers such as neopterin demonstrate that HIV-1 infection is associated with chronic immune activation. We investigated a possible association between serum neopterin concentrations and blood cell counts (CD4+ T cells, white blood cells, platelets, red blood cells) and hemoglobin and hematocrit in 94 HIV-1-seropositive individuals [52 Walter Reed (WR) stage 1, 31 WR2, one WR5, and 10 WR6]. There were significant negative correlations between neopterin concentrations and CD4+ T cells, hemoglobin, hematocrit and platelets. These correlations were also significant if either only WR1 and WR2 patients or the entire set of data were considered for calculations. Thus, hematological abnormalities are associated with chronic immune activation in patients with HIV-1 infection. Large amounts of neopterin are released by human macrophages on stimulation with interferon-gamma (IFN gamma), and tumor necrosis factor alpha (TNF alpha) further enhances the effect of IFN gamma. Therefore, our data suggest that activated immune cells and specific cytokines such as IFN gamma and TNF alpha are involved inhibiting hematopoiesis.

Biopterins↗
PubMed1991

Construction of peptides encompassing multideterminant clusters of human immunodeficiency virus envelope to induce in vitro T cell responses in mice and humans of multiple MHC types.

To make synthetic peptide vaccines effective in a broad population of outbred humans, one would have to incorporate enough antigenic determinants to elicit recognition by T cells of most HLA types. We have previously defined multideterminant regions of the human immunodeficiency virus (HIV) envelope that include overlapping determinants seen by proliferating T cells of three or four haplotypes of mice. We have now tested the hypothesis that synthetic peptides encompassing such multideterminant regions will be recognized by T cells of multiple murine MHC types as well as by human T cells representing multiple HLA types. Six such peptides of 20-33 residues in length were prepared, and tested for their ability to stimulate T cells from mice of four distinct MHC types immunized with recombinant envelope protein rgp 160, as well as from 42 HIV-infected humans of different HLA types. Results identify several such peptides that are broadly recognized by mice of four H-2 types and by 52-73% of infected humans who still retain IL-2 productive responses to control recall antigens such as influenza A virus or tetanus toxoid. 86% of such infected donors tested against at least three peptides respond to at least one of the six peptides, and 77% of an additional group of seropositives respond to a mixture of the peptides. Moreover, the peptides can be used to immunize mice to elicit T cells reactive with the intact HIV envelope protein. These peptides therefore may be useful for both vaccine development in the broad human population, and diagnostic or prognostic use.

Animals↗
PubMed1991

The first decade of human retroviruses: a nomenclature for the clinician.

The decade of the 1980s has provided at least 10 terms for human retroviruses, of which five are currently recognized as defining distinct human infectious disease agents. Of these five, three are human T-cell lymphotropic viruses (HTLV-I, HTLV-II, HTLV-V) and two are human immunodeficiency viruses (HIV-1, HIV-2). HIV-1 and HIV-2 can cause the acquired immunodeficiency syndrome (AIDS), whereas HTLV-I, HTLV-II, and HTLV-V do not. HTLV-I can cause a T-cell leukemia/lymphoma as well as a progressive myelopathy. Disease(s) caused by HTLV-II and HTLV-V have yet to be conclusively established. Screening of the blood supply in the United States is currently designed to detect two of these retroviruses (HIV-1, HTLV-I). This review seeks to clarify the nomenclature of human retroviruses as we begin the second decade of their recognition.

Deltaretrovirus↗
PubMed1991

CD4+ monocyte counts in persons with HIV-1 infection: an early increase is followed by a progressive decline.

In this study, we asked whether there is a difference in the number of CD4+ and CD4- peripheral blood monocytes as CD4+ T cells decrease during HIV-mediated immunodeficiency. Monocytes and T cells from 90 HIV-positive and 43 HIV-negative persons were analyzed by flow cytometry. The 90 HIV-positive patients represented the entire spectrum of CD4+ T-cell counts. We report that as CD4+ T cells decrease, the number of CD4+ monocytes decrease in parallel. Moreover, significantly higher CD4+ monocyte counts were observed in persons with early stage HIV disease, i.e., greater than 800 CD4+ T cells/mm3, than in HIV-negative persons with greater than 800 CD4+ T cells/mm3. Potential implications of these findings are discussed.

Analysis of Variance↗
PubMed1991

CSF changes in a longitudinal study of 124 neurologically normal HIV-1-infected U.S. Air Force personnel.

Over a 2 year period, 124 neurologically normal HIV-1-infected patients had three successive cerebrospinal fluid (CSF) examinations approximately 1 year apart. Immunological status as measured by absolute CD4 counts in the blood identified two groups of patients over time: (a) a group with progressive CD4 decline (66 patients), and (b) a group with stable CD4 counts (58 patients). These two study groups provided us the opportunity to compare CSF changes (cells, protein, albumin index, IgG, IgG index, and IgG synthesis rate) in neurologically normal individuals with respect to immunological status over time. We found significantly increased intrathecal cellular response and IgG production over time independent of CD4 group. We conclude that any clinical study comparing CSF findings in neurologically symptomatic HIV-infected individuals must recognize and control for these CSF changes in neurologically asymptomatic patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

An epitope in human immunodeficiency virus 1 reverse transcriptase recognized by both mouse and human cytotoxic T lymphocytes.

T-cell-mediated cytotoxicity may play an important role in control of infection by the human immunodeficiency virus (HIV). In this study, we have identified and characterized a relatively conserved epitope in the HIV-1 reverse transcriptase recognized by murine and human cytotoxic T cells. This epitope was identified using a murine antigen-specific CD8+ class I major histocompatibility complex-restricted cytotoxic T-cell (CTL) line, a transfected fibroblast cell line expressing the HIV-1 pol gene, recombinant vaccinia viruses containing different truncated versions of the pol gene, and overlapping synthetic peptides. The optimal antigenic site was identified as residues 203-219 by synthesizing extended or truncated peptide analogs of the antigenic fragment. The optimal peptide was then tested for sensitization of autologous Epstein-Barr virus-transformed B-cell targets for killing by fresh human peripheral blood mononuclear cells. It was recognized by CTLs from several HIV-seropositive patients but not from any seronegative donor. Therefore, this peptide is a good candidate for inclusion in an AIDS vaccine. This study demonstrates that the same CTL epitope can be seen by murine and human CD8+ CTLs, as previously demonstrated for epitopes recognized by CD4+ helper T cells, and suggests the utility of screening for immunodominant CTL epitopes in mice prior to carrying out studies in humans.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Hepatitis C antibody in a non-hemophiliac cohort infected with the human immunodeficiency virus.

Development of a serologic test which detects antibody to hepatitis C virus (anti-HCV) allowed us to compare the seroprevalence of hepatitis C and hepatitis B in 493 persons infected with the human immunodeficiency virus (HIV). These persons, none of whom are hemophiliacs, are part of the US Air Force HIV Natural History Study. We found that Hepatitis B core antibody (anti-HBc) was far more prevalent (59%) than anti-HCV (8%). Anti-HBc prevalence was not different between those with and those without anti-HCV, being present in the majority of persons in both groups. In addition, we compared anti-HCV+ and anti-HCV negative persons in terms of syphilis serologies (Reactive Plasma Reagent [RPR] and Fluorescent Treponemal Antibody Absorption [FTA-ABS]), hepatic transaminase levels, and racial composition. In this cohort, we found that anti-HCV+ persons are significantly more likely to have a positive RPR but not FTA-ABS, increased hepatic transaminase levels, and to be Black rather than Caucasian.

Adult↗
PubMed1989

Human eosinophils express CD4 protein and bind human immunodeficiency virus 1 gp120.

The CD4 glycoprotein, expressed on leukocytes belonging to subsets of T lymphocytes and to cells of monocyte/macrophage lineage, participates in the functioning of T cells and serves as a receptor for HIV-1 and HIV-2. Human eosinophils, a class of granulocytic leukocytes, have been found to express CD4. With anti-CD4 mAbs CD4 was demonstrable on eosinophils from both normal and eosinophilic donors. Eosinophils synthesized a 55-kD CD4 polypeptide immunoprecipitable with two anti-CD4 mAbs. Eosinophil CD4 bound HIV-1 gp120 as assessed by competition for anti-OKT4A, but not anti-OKT4, mAb binding. Eosinophils, normally rich in gastrointestinal and genitourinary tract tissues, increase in numbers in patients with metazoan parasitic infections. In these sites and diseases, CD4 expression by eosinophils may be pertinent to their immunologic functions and could make these cells susceptible to HIV infection.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Mature human eosinophils have the capacity to express HLA-DR.

Human eosinophils are known to lose Ia antigen expression as they mature, and, accordingly, eosinophils obtained from the blood of five eosinophilic donors and three of four normal donors failed to display the major histocompatibility complex class II antigen HLA-DR, as determined by flow cytometry. However, when eosinophils from these nine donors were maintained in culture with recombinant human granulocyte-macrophage colony-stimulating factor and murine 3T3 fibroblasts, HLA-DR consistently developed on the eosinophils. By days 4-6 of culture, 24-97% of eosinophils were HLA-DR+, and the eosinophils remained morphologically mature. In contrast, another class II antigen, HLA-DQ, was not detectable by flow cytometry on eosinophils from eight of nine donors. Cultured eosinophils were able to synthesize HLA-DR, as documented by the incorporation of [35S]methionine into immunoprecipitable HLA-DR heavy and light chains. These findings show that mature eosinophils can synthesize and express HLA-DR and provide a means whereby eosinophils may interact with CD4+ lymphocytes.

Cells, Cultured↗
PubMed1989

Detection of three distinct patterns of T helper cell dysfunction in asymptomatic, human immunodeficiency virus-seropositive patients. Independence of CD4+ cell numbers and clinical staging.

We have tested the T helper cell (TH) potential of asymptomatic, HIV seropositive (HIV+) patients, using an in vitro assay for IL-2 production. Peripheral blood leukocytes (PBL) from 74 HIV+ patients and 70 HIV- control donors were tested for TH function when stimulated with influenza A virus (FLU), tetanus toxoid (TET), HLA alloantigens (ALLO), or PHA. Of the HIV+ patients, four different response patterns were observed: (a) patients who responded to all four stimuli (16%); (b) patients who were selectively unresponsive to FLU and TET, but responded to ALLO and PHA (54%); (c) patients who were unresponsive to FLU, TET, or ALLO, but responsive to PHA (16%); and (d) patients who failed to respond to any of these stimuli (14%). Our results indicate a time-dependent progression from a stage responsive to all four stimuli to a stage unresponsive to any of the stimuli tested, progressing in the order outlined above. The earliest TH defect is the loss of responses to FLU and TET, indicating a selective defect in CD4+ MHC self-restricted TH function. The later loss of ALLO and PHA IL-2 responses suggests more severe TH dysfunction involving both CD4+ and CD8+ T cells. None of these patterns of TH unresponsiveness in asymptomatic HIV+ individuals were correlated with CD4+ cell numbers nor with Walter Reed staging criteria. This study indicates that the in vitro TH assay used can detect multiple stages of immune dysregulation early in the course of HIV infection and raises the possibility that staging of HIV+ patients should include in vitro TH functional analyses of the type described here.

Acquired Immunodeficiency Syndrome↗