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Biomedical subjects

M A Fletcher

Publications and source records attributed to M A Fletcher.

160 records · Page 9Linked to original sources

The relationship of the influenza virus inhibitory activity of glycoproteins to their molecular size and sialic acid content.

Twenty-four different glycoproteins were investigated for their ability to inhibit hemagglutination by the A/PRS and the B/Md influenza virus strains. A relationship between activity, the molecular size, and sialic acid content was found. This relationship was readily shown for the A/PR8 virus if the properties of the glycoproteins were compared with one another on a per cent basis. A proportion of approximately 1:1:1 for activity (weight basis) to moles sialic acid content to molecular weight existed for each inhibitory glycoprotein with more than 3 per cent sialic acid, on comparison with any other active glycoprotein.A 1:3 correspondence between viral subunit and sialic acid residues of the inhibitor ovine submaxillary mucin was found experimentally and confirmed by calculation on a molecular model. The most potent inhibitors, were the antigens of the human blood-group MN system and the Tamm-Horsfall urinary glycoprotein.

Glycoproteins↗

Changes in immune and psychological measures as a function of anticipation and reaction to news of HIV-1 antibody status.

We assessed changes in psychological and immunological functioning during 5-week periods preceding and following notification of serostatus among gay males taking the HIV-1 antibody test. Forty-six asymptomatic homosexual men between the ages of 18 and 40 yrs were recruited from a gay men's organization and through advertisements in a local newspaper. Measures of cell-mediated immunity (lymphocyte phenotypic markers, mitogen responsivity, and natural killer cell cytotoxicity) and psychological functioning (state anxiety, intrusive thoughts, and avoidant behaviors) were obtained at baseline, five weeks later and 72 hr before serostatus notification, and 1 week, 3 weeks and 5 weeks postnotification. Results suggested a dissociation between psychological and immunological phenomena among seropositives wherein lymphocyte proliferative responses to the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM) remained unchanged in the face of significant increases in state anxiety and intrusive thoughts following serostatus notification. These findings suggested that asymptomatic HIV-1 infected individuals, even at the earliest stages of infection, may be unable to mount an immune response to potent psychosocial stressors (i.e., serostatus notification), due perhaps, to the fact that the viral contribution to immune functioning overrides any influence of environmental stimuli. Among the seronegative subjects studied, blastogenic responses to PHA and PWM were depressed at baseline (relative to a group of age and gender-matched controls who were not undergoing HIV-1 antibody testing) but PHA values returned to normal values 5 weeks later. Natural killer (NK) cell cytotoxicity and CD4+CD45R+ inducer cell counts appeared to parallel these changes in seronegatives. Seropositives did display fluctuations in NK cell cytotoxicity that were similar to those noted for seronegatives. Correlational analyses suggested that individual differences in anxiety responses at the time of notification of seropositivity predicted subsequent (1-week lag) declines in NK cell cytotoxicity but not other functional markers. Although most seropositives displayed clinical levels of anxiety, intrusive thoughts and avoidant responses during the week of serostatus notification, these measures returned to their initial nonclinical baseline levels within 5 weeks after notification in both the seropositive and seronegative groups.

AIDS Serodiagnosis↗

Psychological and neuroendocrine measures related to functional immune changes in anticipation of HIV-1 serostatus notification.

Our previous work indicated that gay males ultimately found to be seronegative showed impaired lymphocyte proliferative responses to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) upon entering a study in which they would be notified of their human immunodeficiency virus-Type 1 (HIV-1) antibody status. To examine the degree to which alterations in various neuroendocrine and psychological markers might be related to this phenomenon we measured plasma cortisol, beta-endorphin, denial coping strategies, intrusive thoughts related to AIDS risk, and several affective distress markers in 46 HIV-1 seronegative subjects at each of the timepoints previously studied. Results indicated that cortisol levels were elevated at study entry and decreased across the subsequent five-week period--mirroring the changes in mitogen responsivity across these timepoints. Analyses of individual differences showed that higher baseline cortisol and lower denial coping scores predicted lower PHA values at baseline. Persisting intrusive thoughts about risk of HIV-1 infectivity (after seronegativity notification) were consistently associated with higher plasma cortisol levels. Finally, beta-endorphin levels did not change significantly across the 10-week observation period, were not associated with psychological variables, and were inconsistently associated with immune functioning.

AIDS Serodiagnosis↗

Psychosocial modulation of antibody to Epstein-Barr viral capsid antigen and human herpesvirus type-6 in HIV-1-infected and at-risk gay men.

We investigated the effects of two behavioral interventions--aerobic exercise and cognitive behavioral stress management (CBSM)--on Epstein-Barr virus viral capsid antigen (EBV-VCA) and human herpesvirus type-6 (HHV-6) antibody modulation in 65 asymptomatic gay men measured at several time points in the 5 weeks preceding and following notification of their human immunodeficiency virus-type 1 (HIV-1) serostatus. After accounting for potential immunomodulatory confounds, we found that HIV-1 seropositive men had higher EBV-VCA antibody titers than those diagnosed as seronegative at every time point during the study; however, no significant differences were found with respect to HHV-6. Among HIV-1 seropositive and seronegative subjects, respectively, those randomized to either behavioral intervention had significant decreases in both EBV-VCA and HHV-6 antibody titers over the course of the intervention as compared with assessment-only controls (of HIV-1 seropositive and seronegative status) whose antibody titers did not significantly change and which remained consistently higher than either serostatus-matched intervention group over subsequent time points, independent of total immunoglobulin G levels and degree of polyclonal B cell activation. In attempting to explain serostatus differences in EBV and HHV-6 values, it was found that HIV-1 seropositive men had significantly lower CD4 cells, CD4:CD8 ratio, and blastogenic response to phytohemagglutinin (PHA), as well as significantly higher CD8 cells at baseline. No significant differences were found between the HIV-1 seropositive and seronegative men with respect to anxiety and depression at baseline. Since the greatest changes in EBV and HHV-6 occurred between baseline and week 10, we correlated changes in immune (CD4, CD8, CD4:CD8 ratio, PHA stimulation) and distress-related markers (state depression and anxiety) with EBV and HHV-6 change scores over this time period. No significant correlations were found between any of these immune- or distress-related variable and the antibody change scores suggesting that the mechanisms by which EBV and HHV-6 antibodies are being modulated by these interventions possibly involve other, yet to be determined, immune, neuroendocrine, and/or psychologic variables.

Acquired Immunodeficiency Syndrome↗

Physical symptoms of chronic fatigue syndrome are exacerbated by the stress of Hurricane Andrew.

This study examined the effects of Hurricane Andrew on physical symptoms and functional impairments in a sample of chronic fatigue syndrome (CFS) patients residing in South Florida. In the months after Hurricane Andrew (September 15-December 31, 1992), 49 CFS patients were assessed for psychosocial and physical functioning with questionnaires, interviews, and physical examinations. This sample was made up of 25 CFS patients living in Dade county, a high impact area, and 24 patients in Broward and Palm Beach counties, areas less affected by the hurricane. Based on our model for stress-related effects on CFS, we tested the hypothesis that the patients who had the greatest exposure to this natural disaster would show the greatest exacerbation in CFS symptoms and related impairments in activities of daily living (illness burden). In support of this hypothesis, we found that the Dade county patients showed significant increases in physician-rated clinical relapses and exacerbations in frequency of several categories of self-reported CFS physical symptoms as compared to the Broward/Palm Beach county patients. Illness burden, as measured on the Sickness Impact Profile, also showed a significant increase in the Dade county patients. Although extent of disruption due to the storm was a significant factor in predicting relapse, the patient's posthurricane distress response was the single strongest predictor of the likelihood and severity of relapse and functional impairment. Additionally, optimism and social support were significantly associated with lower illness burden after the hurricane, above and beyond storm-related disruption and distress responses. These findings provide information on the impact of environmental stressors and psychosocial factors in the exacerbation of CFS symptoms.

Activities of Daily Living↗

Posttraumatic stress symptoms, intrusive thoughts, loss, and immune function after Hurricane Andrew.

OBJECTIVE: To examine the impact of and relationship between exposure to Hurricane Andrew, a severe stressor, posttraumatic stress symptoms and immune measures. METHODS: Blood draws and questionnaires were taken from community volunteer subjects living in the damaged neighborhoods between 1 and 4 months after the Hurricane. RESULTS: The sample exhibited high levels of posttraumatic stress symptoms by questionnaire (33% overall; 76% with at least one symptom cluster), and 44% scored in the high impact range on the Impact of Events (IES) scale. A substantial proportion of variance in posttraumatic stress symptoms could be accounted for by four hurricane experience variables (damage, loss, life threat, and injury), with perceived loss being the highest correlate. Of the five immune measures studied Natural Killer Cell Cytotoxicity (NKCC) was the only measure that was meaningfully related (negatively) to both damage and psychological variables (loss, intrusive thoughts, and posttraumatic stress disorder (PTSD). White blood cell counts (WBCs) were significantly positively related with the degree of loss and PTSD experienced. Both NKCC (lower) and WBC were significantly related to retrospective self-reported increase of somatic symptoms after the hurricane. Overall, the community sample was significantly lower in NKCC, CD4 and CD8 number, and higher in NK cell number compared to laboratory controls. Finally, evidence was found for new onset of sleep problems as a mediator of the posttraumatic symptom-NKCC relationship. CONCLUSIONS: Several immune measures differed from controls after Hurricane Andrew. Negative (intrusive) thoughts and PTSD were related to lower NKCC. Loss was a key correlate of both posttraumatic symptoms and immune (NKCC, WBC) measures.

Adolescent↗

Changes in cognitive coping skills and social support during cognitive behavioral stress management intervention and distress outcomes in symptomatic human immunodeficiency virus (HIV)-seropositive gay men.

OBJECTIVE: We have previously reported decreases in dysphoria, anxiety, and total mood disturbance in symptomatic HIV seropositive gay men after a 10-week cognitive behavioral stress management (CBSM) group intervention. This structured intervention was designed a) to increase cognitive and behavioral coping skills related to managing the distress of symptomatic HIV, and b) to increase social support among group members. Here we examine the relative contribution of changes in coping skills and social support during the intervention period to reductions in dysphoria, anxiety, and distress-related symptoms in this sample. METHODS: Participants were randomized to a 10-week CBSM group intervention or to a wait-list control condition. Coping, social supports, and mood were measured before and after the intervention period. RESULTS: Members of the CBSM group (N = 22) showed significant improvement in cognitive coping strategies involving positive reframing and acceptance, and in social supports involving attachment, alliances, and guidance at the end of the 10-week CBSM program compared with controls (N = 18) who showed decrements in these coping abilities and no changes in social support. Improved cognitive coping, specifically acceptance of the HIV infection, was strongly related to lower dysphoria, anxiety, and total mood disturbance in both conditions. Changes in social support and in cognitive coping skills seem to mediate the effects of the experimental condition on the changes in distress noted during the intervention. CONCLUSIONS: These results suggest that cognitive coping and social support factors can be modified by psychosocial interventions and may be important determinants of the changes in psychological well-being and quality of life during symptomatic HIV infection that can be achieved through this form of intervention.

Adaptation, Psychological↗

Stressful events, pessimism, natural killer cell cytotoxicity, and cytotoxic/suppressor T cells in HIV+ black women at risk for cervical cancer.

OBJECTIVE: This study examines whether stressful negative life events and pessimism were associated with lower natural killer cell cytotoxicity (NKCC) and T cytotoxic/suppressor cell (CD8+CD3+) percentage in black women co-infected with human immunodeficiency virus Type 1 (HIV-1) and human papillomavirus (HPV), a viral initiator of cervical cancer. METHOD: Psychosocial interviews, immunological evaluations, and cervical swabs for HPV detection and subtyping were conducted on 36 HIV+ African-American, Haitian, and Caribbean women. RESULTS: Greater pessimism was related to lower NKCC and cytotoxic/suppressor cells after controlling for presence/absence of HPV Types 16 or 18, behavioral/lifestyle factors, and subjective impact of negative life events. CONCLUSIONS: A pessimistic attitude may be associated with immune decrements, and possibly poorer control over HPV infection and increased risk for future promotion of cervical dysplasia to invasive cervical cancer in HIV+ minority women co-infected with HPV.

AIDS-Related Opportunistic Infections↗

Reductions in herpes simplex virus type 2 antibody titers after cognitive behavioral stress management and relationships with neuroendocrine function, relaxation skills, and social support in HIV-positive men.

OBJECTIVE: Coinfection with herpes simplex virus type 2 (HSV-2) is common in individuals infected with human immunodeficiency virus (HIV) and may have health implications. This study examined the effect of a 10-week cognitive behavioral stress management (CBSM) intervention on immunoglobulin G (IgG) antibody titers to HSV-2 in a group of mildly symptomatic HIV-infected gay men and the degree to which these effects were mediated by psychosocial and endocrine changes during the 10-week period. METHODS: Sixty-two HIV+ gay men were randomly assigned to either a 10-week CBSM intervention (N = 41) or a wait-list control condition (N = 21). Anxious mood, social support, cortisol/dehydroepiandrosterone sulfate (DHEA-S) ratio levels, and HSV-2 IgG antibody titers were assessed at baseline and after the 10-week period. CBSM participants also recorded their stress levels before and after at-home relaxation practice. RESULTS: HSV-2 IgG titers were significantly reduced in the CBSM participants but remained unchanged in the control group after the 10-week intervention period. Increases in one type of social support, perceived receipt of guidance, during the 10 weeks was associated with and partially mediated the effect of the intervention on HSV-2 IgG. Similarly, decreases in cortisol/DHEA-S ratio levels were associated with decreases in HSV-2 IgG, and lower mean stress levels achieved after home relaxation practice were associated with greater decreases in HSV-2 IgG among CBSM participants. CONCLUSIONS: These findings suggest that behavioral and psychosocial changes occurring during CBSM interventions, including relaxation, enhanced social support, and adrenal hormone reductions, may help to explain the effects of this form of stress management on immune indices such as HSV-2 antibody titers.

Adaptation, Psychological↗