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Biomedical subjects

R Redfield

Publications and source records attributed to R Redfield.

At least 19 recordsLinked to original sources
PubMed1995

Increased anticardiolipin antibodies associated with the development of anetoderma in HIV-1 disease. Military Medical Consortium for the Advancement of Retroviral research (MMCARR).

BACKGROUND AND OBJECTIVE: Anetoderma has been reported in patients with HIV-1 disease. In patients with autoimmune disease, anetoderma has been associated with increased levels of antiphospholipid antibodies (APL) that include anticardiolipin antibodies (ACA) and lupus anticoagulant (LA). This has led to speculation that the autoimmune phenomena seen in HIV-1 disease and the immune dysregulation induced by HIV-1 disease may play a role in the development of these lesions. We have seen both primary and secondary lesions of anetoderma in patients followed for HIV-1 disease. In this study, we wanted to determine whether there was an association in the development of anetoderma and elevated anticardiolipin antibodies (ACA) in HIV-1 patients. METHODS: Quantitative ACA levels were measured in eight HIV-1-infected patients with anetoderma and four HIV-1-infected patients without anetoderma. RESULTS: Anticardiolipin antibodies were moderately elevated in seven of eight patients with lesions and were borderline in the four HIV-1-positive patients without lesions of anetoderma. CONCLUSIONS: There appears to be a correlation between increased ACA and the development of cutaneous lesions of anetoderma in HIV-1 disease. Patterns of immune dysregulation, including APL, may predispose to the development of lesions of anetoderma in HIV-1-positive patients. Although some of the lesions appear to represent primary anetoderma, the majority of our patients develop lesions in areas secondary to well characterized eruptions.

Adult↗
PubMed1993

Ethical dilemmas in continuing a zidovudine trial after early termination of similar trials.

Ethical dilemmas caused by external events and an interim subset analysis raised concerns about continuing a long-term VA clinical trial comparing early with later zidovudine therapy for symptomatic human immunodeficiency virus (HIV) infection. The first external event was the early termination of other, apparently similar, trials conducted by the AIDS Clinical Trials Group (ACTG) and the announced clear benefits for the zidovudine-treated patients. Interim analysis of the VA trial at this time did not show similar benefits. Subset analyses were performed to explore factors that might explain the different results. These suggested a difference in response to zidovudine in white and minority groups. The Data Monitoring Board and a special advisory panel reviewed these data and concluded that, since the VA results were neutral overall and the subset analyses based on small numbers, the trial should continue. By conference call, the study cochairmen and biostatistician discussed this decision with study personnel without revealing interim results, and study personnel passed the information on to patients at the participating centers. The second event was in March 1990, when the Food and Drug Administration (FDA) approved earlier use of zidovudine, which applied to patients still in the VA trial. Patients were asked to reaffirm their participation by signing a new informed consent that explained the findings reported by the ACTG, the FDA-approved revised recommendations, and the rationale for continuation of the VA trial. The consent form emphasized that continued masked therapy was optional and that unmasked treatment and follow-up would be provided to patients requesting it. Seventy-four percent of the participants chose to continue masked therapy. We conclude that when new external data are announced, informed participation in a long-term clinical trial may require a revised consent form and that it is ethical and practical to present this without disclosure of interim study results.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Association of interleukin-6 in the pathogenesis of acutely fatal SIVsmm/PBj-14 in pigtailed macaques.

Infection with a variant of simian immunodeficiency virus (SIVsmm/PBj-14) causes death in juvenile pigtailed macaques within 8 days of infection. The primary pathology is localized to the lymphoid tissues of the gut and spleen. Although the virus is present, the lesions are most consistent with acute reactive inflammation. We studied the serum and tissues for evidence of acute cytokine production often associated with acute inflammation. One factor, IL-6, was found to be significantly increased (> 1000-fold) over all other measured cytokines in all the pigtailed macaques who died acutely. Increased levels of IL-6 were found both in the serum and in the inflamed tissues. mRNA for IL-6 was found in the tissues with the highest protein levels of IL-6. The marked increase in IL-6 and IL-6 mRNA correlated with the virus levels in the tissues and serum as determined by viral isolation, immunohistochemistry, and Northern blot analysis. These findings suggest that the underlying pathogenesis of primary tissue damage, necrosis, and death by PBj-14 is the induction of cytokine production. Although the presence of the virus may be critical for the initiation of these events, the intense inflammatory reaction is associated with the cause of death.

Animals↗
PubMed1993

Effects of adjuvants and multiple antigen peptides on humoral and cellular immune responses to gp160 of HIV-1.

The capacity of five different adjuvants, AlPO4, a muramyldipeptide formulation (MDP.TSL), Freund's adjuvant, immunostimulating complex and its matrix components to elicit humoral and cellular responses in rabbits immunized with the human immunodeficiency virus type 1 (HIV-1) envelope protein rgp160IIIB was compared. The highest antibody titers against gp160 and gp41/gp120 epitopes were seen with rgp160 in MDP.TSL or Freund's adjuvant, whereas the broadest responses were seen in rabbits immunized with rgp160 in matrix or MDP.TSL. The broadest spectrum of high-avidity antibodies was also induced by rgp160 in MDP.TSL. Neutralizing titers against HIV-1IIIB, low titers to HIV-1MN, and the most efficient inhibition of viral cell-to-cell spread was seen with rgp160 in MDP.TSL. The strongest and most persisting cellular responses were induced by rgp160 in AlPO4 or MDP.TSL. Using MDP.TSL as the adjuvant, we also improved the immune response against gp120 epitopes by boosting rgp160-primed rabbits with rgp160, multiple antigenic peptides (MAPs), or unconjugated peptides. The MAPs induced high neutralizing titers and were superior to rgp160 alone in inducing both humoral and cellular reactivity. MAPs are therefore strong candidates for inclusion into future HIV-1 vaccines.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Human immunodeficiency virus type 1 has an additional coding sequence in the central region of the genome.

Eight coding regions designated gag, pol, env, sor, R, tat, art/trs, and 3' orf have been identified in the genome of the human immunodeficiency virus type 1 (HIV-1). Several other open reading frames have the potential to encode additional viral proteins. In this study, we show that HIV-1 has another coding sequence whose product is expressed during natural infection. Unlike antibody to other HIV-1 proteins, the prevalence of antibody to the product encoded by this region is elevated in patients with acquired immune deficiency syndrome (AIDS). Because no analogous coding region has been identified in HIV-2, the antibody to the product of this coding region may serve as a marker to distinguish infection with HIV-1 from infection with HIV-2.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Absence of antibodies to HIV-2/HTLV-4 in six central African nations.

We studied 1508 individuals from Zaire, Burundi, Tanzania, Zambia, Kenya, and Cameroon for antibodies to HIV-2/HTLV-4. AIDS, ARC, other disease or tumor patients and healthy people were sampled from 1984-1986. By radioimmunoprecipitation and SDS/PAGE analysis and/or Western blot we failed to find any samples with specific antibodies to HIV-2/HTLV-4 indicative of infection. In contrast, 363 of these 1508 individuals demonstrated antibodies to HIV-1/HTLV-3B by the same serologic assays. HIV-2/HTLV-4 infection appears to be quite rare in Central Africa. AIDS and related syndromes in this study were exclusively correlated with HIV-1 infection. Studies in West Africa have shown high rates of infection with HIV-2/HTLV-4 where cases of AIDS are still relatively uncommon. These results indicate that HIV-2/HTLV-4 has a distinct geographic distribution from that of HIV-1 in Africa. Further studies are necessary to better define the pathogenicity and natural history of this distinct new virus, HIV-2/HTLV-4.

Antibodies, Viral↗
PubMed1986

Flow-cytometric detection of circulating immune complexes.

In an effort to develop an assay which would rapidly detect and analyze circulating immune complexes, we have adapted the Raji cell radioimmunoassay (RIA) to a flow cytometric (FCM) analysis. The advantages of immune complex analysis by FCM are many. Foremost is the effectiveness and efficiency of the FCM method relative to the radioimmunoassay (RIA) method. The data demonstrated that FCM detection is three times more sensitive than RIA detection. Only populations of viable Raji cells bearing immune complexes are analyzed because parameters of the FCM analysis permitted the elimination (gating out) of dead cells. The determinations are rapid and the data are immediately available for several additional analyses. Because of the availability of many fluorescent monoclonal antibodies to complement components, viral antigens, light chains and immunoglobulin isotypes, it is possible to detect many components that might be present in the Raji cell bound complexes. Finally, the Raji cells can be characterized in different stages of their cell cycle to generate information about the state of the cells and the density of the receptors involved in binding the complexes.

Antigen-Antibody Complex↗
PubMed1986

A model for the selective loss of major histocompatibility complex self-restricted T cell immune responses during the development of acquired immune deficiency syndrome (AIDS).

Functional analyses of peripheral blood leukocytes (PBL) from high risk HTLV-III antibody-negative and antibody-positive donors, as well as from patients with acquired immune deficiency syndrome (AIDS), lymphadenopathy syndrome (LAS), and AIDS-related complex (ARC) were performed by the in vitro generation of cytotoxic T lymphocyte (CTL) and proliferative responses to the HLA self-restricted antigens of influenza virus (S + X) and to nonself restricted HLA alloantigens (ALLO). All 40 antibody-negative donors tested responded to both S + X and ALLO in the CTL response, whereas six of 14 antibody-positive, two of three LAS, four of five ARC, and seven of 17 AIDS patients exhibited a selective absence of CTL to S + X, but generated normal or elevated CTL responses to ALLO. Of the remaining 10 AIDS patients, nine did not respond to either S + X or ALLO, and one responded to both S + X and ALLO. A similar selective loss of the proliferative response to S + X was found. We also observed antibody-positive donors who initially generated CTL responses to S + X and ALLO, but lost the S + X response as a function of time. We were able to restore the selective loss of S + X CTL activity in vitro by the addition of IL 2 and, to some extent, by co-stimulation with S + X plus ALLO. Depletion of CD4+ T helper cells and removal of autologous antigen-presenting cells from the PBL of healthy antibody-negative donors indicated that distinct T helper cell subsets exist in human PBL, and that S + X responses must use a CD4+ T helper population, whereas ALLO responses can utilize an alternate CD4- T helper pathway. A model is presented indicating the selective depletion of CD4+ T helper function in the developmental stages of AIDS. The functional test for T helper activity to self restricted antigens may be the earliest indicator of immune functional loss in the development of AIDS, and may precede a reduction in the absolute number of CD4+ cells.

AIDS-Related Complex↗
PubMed1986

Susceptibility of normal human lymphocytes to infection with HTLV-III/LAV.

Normal human peripheral blood lymphocytes were tested for their susceptibility to infection with retroviruses isolated from patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Of 10 normal individuals tested, lymphocytes from all subjects became infected and produced virus as detected by assay for Mg+2-dependent reverse transcriptase. Lymphocytes from different individuals were demonstrated to be either high or low producers of reverse transcriptase after infection. The kinetics of virus production were similar in cells from both high- and low-producing individuals. A significant correlation was observed between high and low viral-producing lymphocytes and expression of the Leu-3/T4 (CD4) surface molecule. Mitogen-stimulated peripheral blood lymphocytes exposed to HTLV-III/LAV manifested productive viral infection, as reflected by the appearance of early syncytia, followed by reverse transcriptase. Unstimulated peripheral blood lymphocyte cultures displayed late syncytia but no detectable reverse transcriptase upon exposure to virus. The addition of anti-human interferon-alpha did not appear to have an appreciable effect on viral production in normal peripheral blood lymphocytes exposed to the virus.

Acquired Immunodeficiency Syndrome↗
PubMed1986

On the relation between joint moments and pedalling rates at constant power in bicycling.

Joint moments are of interest because they bear some relation to muscular effort and hence rider performance. The general objective of this study is to explore the relation between joint moments and pedalling rate (i.e. cadence). Joint moments are computed by modelling the leg-bicycle system as a five-bar linkage constrained to plane motion. Using dynamometer pedal force data and potentiometer crank and pedal position data, system equations are solved on a computer to produce moments at the ankle, knee and hip joints. Cadence and pedal forces are varied inversely to maintain constant power. Results indicate that average joint moments vary considerably with changes in cadence. Both hip and knee joints show an average moment which is minimum near 105 rotations min-1 for cruising cycling. It appears that an optimum rotations min-1 can be determined from a mechanical approach for any given power level and bicycle-rider geometry.

Bicycling↗
PubMed1986

Prediction of pedal forces in bicycling using optimization methods.

The bicycle-rider system is modeled as a planar five-bar linkage with pedal forces and pedal dynamics as input. The pedal force profile input is varied, maintaining constant average bicycle power, in order to obtain the optimal pedal force profile that minimizes two cost functions. One cost function is based on joint moments and the other is based on muscle stresses. Predicted (optimal) pedal profiles as well as joint moment time histories are compared to representative real data to examine cost function appropriateness. Both cost functions offer reasonable predictions of pedal forces. The muscle stress cost function, however, better predicts joint moments. Predicted muscle activity also correlates well with myoelectric data. The factors that lead to effective (i.e. low cost) pedalling are examined. Pedalling effectiveness is found to be a complex function of pedal force vector orientation and muscle mechanics.

Bicycling↗
PubMed1986

Impaired antibody-dependent cell-mediated cytotoxic activity in patients with the acquired immunodeficiency syndrome.

Since the acquired immunodeficiency syndrome (AIDS) is characterized by opportunistic infections and malignancies indicative of a profound suppression in cell-mediated immunity, we investigated the antibody-dependent cell-mediated cytotoxicity (ADCC) of peripheral blood mononuclear cells of patients with AIDS against chicken red blood cells (CRBC). A marked decrease in ADCC-CRBC activity was observed from patients with AIDS as compared to healthy controls. Furthermore, suppression in ADCC activity was seen when mononuclear cells from healthy subjects were assayed using media containing 25% or 40% sera from AIDS patients. Two of two patients with AIDS and impaired ADCC-CRBC activity were also found to have in vivo impaired reticuloendothelial system Fc-specific clearance of 51Cr-labelled, anti-Rho (D) IgG-sensitized autologous erythrocytes. These data provide further evidence of monocyte-macrophage dysfunction in AIDS and help explain the widespread occurrence of opportunistic pathogens in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Genomic diversity of human T-lymphotropic virus type III (HTLV-III).

The DNA genomes of human T-lymphotropic virus type III (HTLV-III) isolated from 18 individuals with AIDS or who were at risk for AIDS were evaluated for evidence of variation. Although all of the 18 viral DNA's hybridized throughout their entire genomes to a full-length cloned probe of the original HTLV-III isolate, each of the 18 isolates showed a different restriction enzyme pattern. The number of restriction site differences between isolates ranged from only 1 site in 23 to at least 16 sites in 31. No particular viral genotype was associated with a particular disease state and 2 of the 18 patients had evidence of concurrent infection by more than one viral genotype. Propagation of three different viral isolates in vitro for up to 9 months did not lead to detectable changes in their restriction patterns. These findings indicate that different isolates of HTLV-III comprise a spectrum of highly related but distinguishable viruses and have important implications regarding the pathogenicity of HTLV-III and attempts to develop effective diagnostic, therapeutic, and preventive measures for this virus.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Circulating IgA immune complexes in AIDS.

Circulating immune complexes were isolated from the serum of patients with AIDS, as well as patients with other acute and chronic viral diseases. Analysis of these immune complexes by methods of flow cytometry and by radioimmune (Raji cell) assay revealed a prevalence of IgA complexes in the serum of AIDS patients and a prevalence of IgG complexes in the serum of patients with other viral diseases. Raji cells bind immune complexes via Fc and complement (C3) receptors and may detect IgA immune complexes more efficiently than a C1q assay since IgA has no affinity for C1q.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS.

Peripheral blood lymphocytes from patients with the acquired immunodeficiency syndrome (AIDS) or with signs or symptoms that frequently precede AIDS (pre-AIDS) were grown in vitro with added T-cell growth factor and assayed for the expression and release of human T-lymphotropic retroviruses (HTLV). Retroviruses belonging to the HTLV family and collectively designated HTLV-III were isolated from a total of 48 subjects including 18 of 21 patients wih pre-AIDS, three of four clinically normal mothers of juveniles with AIDS, 26 of 72 adult and juvenile patients with AIDS, and from one of 22 normal male homosexual subjects. No HTLV-III was detected in or isolated from 115 normal heterosexual subjects. The number of HTLV-III isolates reported here underestimates the true prevalence of the virus since many specimens were received in unsatisfactory condition. Other data show that serum samples from a high proportion of AIDS patients contain antibodies to HTLV-III. That these new isolates are members of the HTLV family but differ from the previous isolates known as HTLV-I and HTLV-II is indicated by their morphological, biological, and immunological characteristics. These results and those reported elsewhere in this issue suggest that HTLV-III may be the primary cause of AIDS.

Acquired Immunodeficiency Syndrome↗