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Biomedical subjects

M A Fletcher

Publications and source records attributed to M A Fletcher.

At least 55 records · Page 3Linked to original sources
PubMed1996

Bereavement is associated with time-dependent decrements in cellular immune function in asymptomatic human immunodeficiency virus type 1-seropositive homosexual men.

Seventy-nine human immunodeficiency virus type 1 (HIV-1)-seropositive homosexual men participating in a longitudinal study of HIV-1 infection were assessed twice, 6 months apart, to investigate associations between bereavement and cellular immune function. Subjects were assessed by using a theory-driven model comprising life stressors, social support and coping style, and control variables. Natural killer cell cytotoxicity was decreased among the bereaved at both times. Lymphocyte proliferative response to phytohemagglutinin was decreased among the bereaved at the second time point but not at the first. These functional immune decrements are associated with increased neuroendocrine responses of the sympathetic adrenomeduallary system as well as the limbic-hypothalamic-pituitary-adrenal axis. Implications for differential neuroendocrine responses over time are discussed. Active coping style was independently and positively related to both immune measures. The results imply that a bereavement support group intervention merits investigation for an effect on immunological measures and clinical progression of HIV-1 infection as well as grief resolution.

Adaptation, Psychological↗
PubMed1996

Predictors of survival in human immunodeficiency virus type 1-seropositive intravenous drug users.

In an ongoing prospective study of street-recruited intravenous drug users (IDUs) in Miami, Fla., 116 human immunodeficiency virus type 1 (HIV-1)-infected IDUs were monitored for up to 7 years. This provided an opportunity to evaluate baseline immunological parameters as potential predictors of survival among HIV-1-infected IDUs. As expected, HIV-1-infected IDUs who had an advanced stage of the disease (Centers for Disease Control and Prevention classification III or IV); p24 antigenemia; human T-cell leukemia virus type 1/2 seropositivity; low CD4 counts (< or = 200); low hemoglobin (< or = 14), high serum immunoglobulin A (IgA) (> 500 mg/dl), or high serum IgG (> or = 3,500 mg/dl) levels; or low proliferative responses to pokeweed mitogen (< or = 1,500 cpm) and to phytohemagglutinin (< or = 80,000 cpm) at baseline had worse survival rates. Results from multivariate Cox's models of survival showed that the baseline serum IgG level, serum IgA level, and CD4 count independently predict survival in HIV-1-infected IDUs. Cross-validation procedures verified the above-mentioned findings. These findings support the routine consideration of serum immunoglobulin levels in addition to CD4 count, especially in early evaluation of disease stage, as these evaluations may modify application of prophylaxis and treatment for HIV-1-infected IDUs. We recommend consideration of use of serum IgG and IgA as immunological markers for long-range prediction of survival in HIV-1-infected IDUs. These determinations are less onerous and more appropriate for use in field studies and financially less favored settings.

Adult↗
PubMed1996

Massage therapy is associated with enhancement of the immune system's cytotoxic capacity.

Twenty-nine gay men (20 HIV+, 9 HIV-) received daily massages for one month. A subset of 11 of the HIV+ subjects served as a within subject control group (one month with and without massages). Major immune findings for the effects of the month of massage included a significant increase in Natural Killer Cell number, Natural Killer Cell Cytotoxicity, soluble CD8, and the cytotoxic subset of CD8 cells. There were no changes in HIV disease progression markers (CD4, CD4/CD8 ratio, Beta-2 microglobulin, neopterin). Major neuroendocrine findings, measured via 24 hour urines included a significant decrease in cortisol, and nonsignificant trends toward decrease of catecholamines. There were also significant decreases in anxiety and increases in relaxation which were significantly correlated with increases in NK cell number. Thus, there appears to be an increase in cytotoxic capacity associated with massage. Implications for HIV+ men as those with other illnesses, particularly cancer, are discussed.

Adult↗
PubMed1995

Micronutrients and HIV-1 disease progression.

OBJECTIVE: To determine whether nutritional status affects immunological markers of HIV-1 disease progression. DESIGN: A longitudinal study, to evaluate the relationship between plasma levels of nutrients and CD4 cell counts, along and in combination with beta 2-microglobulin (beta 2M; AIDS index) over an 18-month follow-up. METHODS: Biochemical measurements of nutritional status including plasma proteins, zinc, iron and vitamins B1, B2, B6, B12 (cobalamin), A, E, C and folate and immunological markers [lymphocyte subpopulations (CD4) and beta 2M] were obtained in 108 HIV-1-seropositive homosexual men at baseline and over three 6-month time periods. Changes in nutrient status (e.g., normal to deficient, deficient to normal), were compared with immunological parameters in the same time periods using an autoregressive model. RESULTS: Development of deficiency of vitamin A or vitamin B12 was associated with a decline in CD4 cell count (P = 0.0255 and 0.0377, respectively), while normalization of vitamin A, vitamin B12 and zinc was associated with higher CD4 cell counts (P = 0.0492, 0.0061 and 0.0112, respectively). These findings were largely unaffected by zidovudine use. For vitamin B12, low baseline status significantly predicted accelerated HIV-1 disease progression determined by CD4 cell count (P = 0.041) and the AIDS index (P = 0.005). CONCLUSIONS: These data suggest that micronutrient deficiencies are associated with HIV-1 disease progression and raise the possibility that normalization might increase symptom-free survival.

Adult↗
PubMed1995

Immunoglobulin E levels in relationship to HIV-1 disease, route of infection, and vitamin E status.

Our recent studies have demonstrated that in early HIV-1 infection, elevation of plasma immunoglobulin E (IgE) levels precedes the decline of CD4 cell count and is influenced by vitamin E status. In order to further investigate the role of IgE elevation in HIV-1 infection, we determined IgE levels in HIV-1-seropositive and -seronegative intravenous drug users (IDUs) (n = 38), in relationship to cellular and humoral immune function, liver enzymes, and vitamin E status. To examine the possible impact of the route of HIV-1 infection on IgE levels, comparisons between the cohorts of the HIV-1-seropositive and -seronegative IDUs and homosexual men (n = 45) were also conducted. All HIV-1-seropositive participants had significantly higher (P = 0.003) IgE levels than the HIV-1-seronegative subjects. The HIV-1-seropositive IDUs, moreover, demonstrated significantly higher (P = 0.01) IgE levels than HIV-1-seropositive homosexual men, despite similar CD4 cell counts. Stepwise regression analysis was used to evaluate the possible variables contributing to the IgE variation. HIV-1 status (P = 0.0009), intravenous drug use (P = 0.014), CD8 cell counts (P = 0.0001), plasma level of vitamin E (P = 0.006), and alcohol intake (P = 0.047) were significant, accounting for 71% of the IgE elevation. These findings suggest that IgE may serve as a sensitive marker to reflect the evolution of HIV-1 disease in individuals from different risk groups.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Adoptive CD8+ T-cell immunotherapy of AIDS patients with Kaposi's sarcoma.

This article reviews published and original findings from two clinical trials of adoptive CD8+ T-cell immunotherapy of patients with acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma (KS). In the first trial, AIDS patients with either KS or oral hairy leukoplakia (OHL) received five rounds of reinfusions of 10(8)-10(10) ex vivo expanded and activated autologous CD8+ T cells. Recombinant interleukin-2 (rIL-2) was coadministered only with the fifth and final infusion. Improvement, and in some cases, resolution of OHL, KS, and candidiasis was observed with no side effects. The observation that clinical improvement of KS was more pronounced when reinfusion of CD8+ T cells was followed by rIL-2 infusion led to a second clinical trial designed to examine the effect of repeated infusions of autologous CD8+ T cells with concomitant rIL-2 administration in the treatment of AIDS-related KS. Improvement of KS status was observed in four out of the eight patients studied (three partial and one complete response). The CD8+ T-cell immunotherapy protocol also provided the opportunity to comparatively study CD8+ T-cell-associated genetic programs. Baseline expression patterns of soluble and surface immune markers by CD8+ T cells from AIDS patients and uninfected controls were predominantly of the type 1 type and differed mainly at a quantitative or kinetic level. Deficiencies in immune mediator expression by CD8+ T cells from AIDS patients tended to dissipate with progression through the protocol. Findings are discussed in the context of current knowledge and therapeutic implications of CD8+ T-cell function in AIDS and neoplasia.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Structure and pathophysiology of the erythrocyte membrane-associated Paul-Bunnell heterophile antibody determinant in Epstein-Barr virus-associated disease.

Epstein-Barr virus (EBV), which was first isolated by Epstein, Barr, and Achong (1964) from a cultured Burkitt's lymphoma lymphoblast cell line, is the etiological agent for infections mononucleosis (IM), polyclonal oligoclonal lymphomas associated with primary and acquired immunodeficiencies, and the complications of X-linked lymphoproliferative syndrome (XLP) (Cantani and Mastrantoni, 1989; Englund, 1988; Ernberg et al., 1990; Jones and Straus, 1987; Okano et al., 1988; Purtilo et al., 1981; Shearer et al., 1985; Wilmes and Wolf, 1989). EBV also contributes to the pathogenesis of Burkitt's lymphoma (Frizzera, 1987; Harrington et al., 1988; Henle et al., 1968; Purtilo et al., 1981; Rowe et al., 1986; Saemundsen et al., 1981) and nasopharyngeal cancer (Pearson et al., 1984). Furthermore, people who have had IM have higher rates of subsequent development of malignant lymphoproliferative disorders (Abo et at., 1982; Snydman et al., 1982) and Hodgkin's disease (Green et al., 1979; Mueller, 1987; Poppema et al., 1985; Weiss et al., 1989), while patents with XLP have a higher incidence of non-Hodgkin's malignant lymphoma (Harrington et at., 1987). The precise role of EBV in these diseases is not well understood. Nonetheless, it is known that EBV infection triggers the formation of heterophile antibodies that, for many decades, have formed the basis for serologic diagnosis of IM. In this review, we discuss the discovery, species variation, and structure of the erythrocyte membrane-associated Paul-Bunnell (PB) heterophile antibody determinant, its implications to IM diagnosis, and its potential contribution to defective immune surveillance and associated uncontrolled proliferation of EBV-infected cells.

Animals↗
PubMed1995

Effects of benzalkonium salts on eukaryotic and microbial G-protein-mediated processes and surface membranes.

Benzalkonium salts comprise a group of positively charged surface-active alkylamine biocides with the general formula alkyldimethylbenzylammonium chloride or bromide. They interact with guanine nucleotide triphosphate-binding proteins (G proteins), thereby affecting signal transduction in a variety of cell types and processes. The present report reviews the known and potential basic science research and clinical applications and manifestations of benzalkonium salts. Benzalkonium salts have antiproliferative effects on a variety of cells through G-protein-dependent pathways, affect cytokine gene expression, and are also effective bactericidal, fungicidal, and virucidal agents with multisite (direct and immunologically-mediated) inhibitory activity against many pathogens, including the human immunodeficiency virus (HIV), papillomavirus, and herpesviruses. Therefore, benzalkonium salts not only appear to be effective as disinfectants and spermicides but may also prove useful in the prevention and treatment of neoplasias and other disease, particularly those linked to viruses and originating at the skin or mucosal surface.

Anti-HIV Agents↗
PubMed1995

Assessment of immune mediator expression levels in biological fluids and cells: a critical appraisal.

The realization that dysregulation of the soluble immune mediator network can contribute to the progression of a wide variety of clinical disorders, including neoplasias, has opened up the possibility of designing new forms of therapy and has established the need for accurate methods of detection of immune mediator expression levels in biological fluids and cells. The purpose of this review is to provide a summary of current knowledge and experience in the area of immune mediator expression level assessment from the clinical, basic science, epidemiological, technical, and therapeutic perspectives.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Effect of low- and intermediate-purity clotting factor therapy on progression of human immunodeficiency virus infection in congenital clotting disorders. Transfusion Safety Study Group.

Low- and intermediate-purity clotting-factor therapies are believed to accelerate human immunodeficiency virus (HIV) progression in hemophiliacs through adverse immune effects of the other plasma proteins in the preparations. To investigate this postulate, we evaluated data from six clinical centers that observed persons with congenital factor deficiencies at 6-month intervals. The present analysis is based on HIV-infected subjects who received intermediate purity factor VIII or factor IX concentrates, or cryoprecipitate. For long-term outcome, we classified 374 subjects by the type and amount of treatment during our first year of observation, and determined the subsequent rate of progression to a CD4 count less than 200 cells/microL. A second analysis of this group used a repeated-measures, random-effect model that allowed for individual differences in CD4 decline. Finally, we compared short-term rates of change in CD4 count in each treatment interval of 525 subjects with the type and amount of factor therapy received in the same interval. There was no overall or dose-related deleterious effect of any form of treatment on CD4 trend. The CD4 decrease was less when cryoprecipitate was administered alone or combined with concentrate, but not significantly so. Our results counter the assertion that low- and intermediate-purity products accelerate the rate of CD4 decrease in HIV-1-infected hemophiliacs.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Psychosocial counseling to improve quality of life in HIV infection.

Psychosocial interventions such as cognitive behavioral stress management (CBSM), may enhance coping and social support which contribute to an improvement of quality of life factors such as emotional functioning, social functioning, and sense of well-being, for HIV-infected men during several phases of HIV spectrum disease. These phases include the acutely stressful period immediately following notification of HIV+ status, the adjustment period following this news, and the process of dealing with chronic symptomatic HIV infection. Normalization of some aspects of immunological status were found to accompany some of these psychosocial changes in the short-run. Longer-term follow-up indicated relationships between psychosocial factors and improved immunological status and physical functioning up to 2 years later. Factors such as an increased use of active coping strategies, including relaxation exercises, use of more functional appraisals and elicitation of social support, and decreased use of denial/avoidance coping strategies, may be key predictors of longer-term emotional well-being, social functioning, and physical functioning in HIV-infected populations. Special issues need to be addressed in emerging models of quality of life assessment in HIV populations. For example, the way resurgence of stigmatization and self-doubt affects sense of identity and well-being need to be addressed in quality of life research as well as in psychosocial interventions. Loss of employment and its financial and existential consequences are also factors which impact sense of self and well-being, and need to be addressed both in research as well as in interventions. The effect of repeated HIV-related bereavements upon an individual's social network and the emotional, social, and physical sequelae of bereavement have implications for HIV quality of life research as well. Quality of survival time has become a paramount issue in the context of HIV spectrum disease. Examining the relationships among coping strategies, social support, emotional well-being, realistic appraisals of one's functioning in comparison to their aspirations, and the influence of psychosocial functioning on disease course are central missions of our research program.

Adult↗
PubMed1994

Emotional disclosure through writing or speaking modulates latent Epstein-Barr virus antibody titers.

Healthy Epstein-Barr virus (EBV) seropositive undergraduates (N = 57) completed a personality inventory, provided blood samples, and were randomly assigned to write or talk about stressful events, or to write about trivial events, during three weekly 20-min sessions, after which they provided a final blood sample. Individuals assigned to the verbal/stressful condition had significantly lower EBV antibody titers (suggesting better cellular immune control over the latent virus) after the intervention than those in the written/stressful group, who had significantly lower values than those in the written/trivial control group. Subjects assigned to the written/stressful condition expressed more negative emotional words than the verbal/stressful and control groups and more positive emotional words than the verbal/stressful group at each time point. The verbal/stressful group expressed more negative emotional words compared with the control group at baseline. Content analysis indicated that the verbal/stressful group achieved the greatest improvements in cognitive change, self-esteem, and adaptive coping strategies.

Adaptation, Psychological↗
PubMed1994

Effects of aerobic exercise training on lymphocyte subpopulations.

This study was conducted to determine the effects of an aerobic exercise training program on subpopulations of lymphocyte phenotypes. Fourteen healthy but sedentary males, 18-40 years of age, were randomly assigned to either an aerobic exercise training or control condition. Aerobic exercise training consisted of three 45-minute sessions of cycle ergometry exercise per week at 70-80% of age-predicted maximum heart rate for ten weeks. The aerobic exercise training resulted in a significant decrease in submaximal heart rate from 176 to 150 beats per minute to a fixed work rate of 150 watts (p < .01). This training effect was accompanied by increases in the resting level of the following lymphocyte subpopulations: CD2 (1717 vs 2183 mm3; p < .01), CD4 (942 vs 1280 mm3; p < .01), CD45RA+CD4+ (312 vs 595 mm3; p < .01), CD8 (655 vs 816 mm3; p < .05), and CD20 (162 vs 244 mm3; p < .01) cell counts. These findings indicate that several lymphocyte subpopulations are increased following a 10-week program of aerobic exercise training.

Adolescent↗