Oncogenic properties of human viruses.
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Adenoviridae↗
Biomedical subjects
R Glaser
Publications and source records attributed to R Glaser.
Mechanisms of stress-induced modulation of viral pathogenesis and immunity.
A murine model of herpes simplex virus (HSV) infection was used to examine the roles of catecholamines and corticosterone in the restraint stress-induced suppression of viral immunity. Treatment of C57BL/6 mice with RU486, a glucocorticoid receptor antagonist, reversed the stress-induced diminution of cellularity in response to local HSV infection. Treatment of mice with both nadolol, a peripherally acting beta-adrenergic antagonist, and RU486 completely reversed the restraint stress-induced suppression of HSV-specific CTL activation. These findings demonstrate that both corticosterone and catecholamine-mediated mechanisms are operative in the stress-induced suppression of anti-viral cellular immunity.
Animals↗
A sensitive non-isotopic assay specific for HIV-1 associated reverse transcriptase.
A sensitive non-isotopic assay for specific detection of reverse transcriptase (RT) of the human immunodeficiency virus type 1 (HIV-1) is described using 5-bromo-2'-deoxyuridine triphosphate (BrdUTP) instead of tritiated thymidine triphosphate. After the RT reaction the template primer is degraded by alkaline hydrolysis. Single-stranded poly.(BrdU) is detected in an immunoenzymometric assay using monoclonal anti-BrdU antibodies. The specificity of the assay is demonstrated by the isolation of RT from virus lysate by an insolubilised monoclonal anti-HIV-1 RT antibody prior to the RT reaction. Immunological RT binding leads to a tenfold increase in analytical sensitivity since substances inhibiting the RT reaction can be removed. This non-isotopic assay is some 30 times more sensitive than the classical radioisotopic RT assay. In terms of RT determination, however, there is a good correlation between these tests (r = 0.96). Several filtrations are no longer necessary to remove non-incorporated nucleotides. The test can be adapted to microtitre plates and hence is easy to automate.
Antibodies, Monoclonal↗
Phorbol ester and Epstein-Barr virus dependent transformation of normal primary human skin epithelial cells.
Substantial evidence has implicated Epstein-Barr virus (EBV) in the aetiology of two human neoplasms, nasopharyngeal carcinoma (NPC) and Burkitt's lymphoma. This is supported by the presence of high antibody titres to EBV early antigen and virus capsid antigen, as well as antibody to two viral-associated enzymes, DNase and DNA polymerase. Patients with NPC, particularly the undifferentiated form, are commonly found to have EBV DNA in the tumour. Ito and others have presented strong epidemiological evidence that phorbol esters are related to the unusual geographic distribution of NPC in southeastern regions of China. There appears to be a close link between the widespread EBV infection of the Asian population and the distinct regional distribution in China of plants that produce diterpene ester. Naturally occurring phorbol esters are produced by plants of the Euphorbiaceae and Thymelaeaceae, which are used as traditional herbal medicines. Although it has been established that EBV can infect epithelial cells isolated from NPC as well as certain normal epithelial cells, there has been no in vitro evidence that EBV induces neoplastic transformation in normal human epithelial cells with or without exposure to phorbol esters. We report here evidence that transformation of normal human epithelial cells results from exposure to infectious EBV and that transformation is dependent on the presence of phorbol esters.
Carcinogens↗
Psychosocial modifiers of immunocompetence in medical students.
This study addressed the effects of a naturally occurring stressor on components of the immune response. Blood was drawn twice from 75 first-year medical students, with a baseline sample taken one month before their final examinations and a stress sample drawn on the first day of final examinations. Median splits on scores from the Holmes--Rahe Social Readjustment Rating Scale and the UCLA Loneliness Scale produced a 2 X 2 X 2 repeated measures ANOVA when combined with the trials variable. Natural killer (NK) cell activity declined significantly from the first to the second sample. High scorers on stressful life events and loneliness had significantly lower levels of NK activity. Total plasma IgA increased significantly from the first to second sample, while plasma IgG and IgM, C-reactive protein, and salivary IgA did not change significantly.
Adult↗
Urinary cortisol levels, cellular immunocompetency, and loneliness in psychiatric inpatients.
This study examined the associations among loneliness, stressful life events, urinary cortisol levels, and immunocompetency. Blood and urine were obtained from 33 psychiatric inpatients on the day after admission, at which time the patients completed the UCLA Loneliness Scale, the Psychiatric Epidemiology Research Interview Life Events Scale (PERI), and the MMPI. Patients who scored above the median on loneliness had significantly higher urinary cortisol levels. The high loneliness group also had significantly lower levels of natural killer cell activity, as well as a poorer T-lymphocyte response to phytohemagglutinin. The high loneliness subjects described themselves as more distressed than the low loneliness group on the MMPI. There were no consistent significant effects on either the immunologic measures or the MMPI associated with the PERI.
Adolescent↗
Marital quality, marital disruption, and immune function.
Marital disruption is associated with significant increases in a variety of psychologic and physical disorders. In order to examine psychologic and physiologic mediators, self-report data and blood samples were obtained from 38 married women and 38 separated/divorced women. Among married subjects, poorer marital quality was associated with greater depression and a poorer response on three qualitative measures of immune function. Women who had been separated 1 year or less had significantly poorer qualitative and quantitative immune function than their sociodemographically matched married counterparts. Among the separated/divorced cohort, shorter separation periods and greater attachment to the (ex)husband were associated with poorer immune function and greater depression. These data are consistent with epidemiologic evidence linking marital disruption with increased morbidity and mortality.
Adult↗
Chronic stress and immunity in family caregivers of Alzheimer's disease victims.
Although acute stress has been associated with transient immunosuppression, little is known about the immunologic consequences of chronic stress in humans. In order to investigate possible health-related consequences of a long-term stressor, we obtained blood samples for immunologic and nutritional analyses and psychologic data from 34 family caregivers of Alzheimer's disease (AD) victims and 34 sociodemographically matched comparison subjects. Family caregivers for AD victims were more distressed than comparison subjects without similar responsibilities. Greater impairment in the AD victim was associated with greater distress and loneliness in caregivers. Caregivers had significantly lower percentages of total T lymphocytes and helper T lymphocytes than did comparison subjects, as well as significantly lower helper-suppressor cell ratios; caregivers also had significantly higher antibody titers to Epstein-Barr virus than did comparison subjects, presumably reflecting poorer cellular immune system control of the latent virus in caregivers. The percentages of natural killer cells and suppressor T lymphocytes did not differ significantly. These data suggest that chronically stressed AD family caregivers do not show immunologic or psychologic adaptation to the level of their well-matched age peers.
Alzheimer Disease↗
Marital discord and immunity in males.
While limited data suggest significant gender differences in mental and physical health risks following marital disruption, men have not been studied as intensively as women. In this study, self-report data and blood samples were obtained from 32 separated or divorced men and 32 sociodemographically matched married men. Separated/divorced men were more distressed and lonelier, and reported significantly more recent illness than did married men; the former also had significantly poorer values on two functional indices of immunity (antibody titers to two herpesviruses), while not differing significantly on quantitative indices (percentages of helper and suppressor cells and their ratio). Among married men, poorer marital quality was associated with greater distress and a poorer response on one functional immunological measure, antibody to Epstein-Barr virus (EBV), as well as lower helper/suppressor ratios. Among separated/divorced subjects, those who had separated within the past year and who had initiated the separation were less distressed, reported better health, and had a better performance on one functional immunological assay (EBV antibody titers) than did noninitiators. These data are discussed in the context of research on longer-term adaptation to marital disruption.
Adult↗
Spousal caregivers of dementia victims: longitudinal changes in immunity and health.
Providing long-term care for a demented relative profoundly affects caregivers' lives. We assessed changes in depression, immune function, and health in 69 spousal caregivers who had already been caregiving for an average of five years and 69 sociodemographically matched control subjects. Between the initial sample ("intake") and the follow-up data collected an average of 13 months later, caregivers showed decrements relative to controls on three measures of cellular immunity. Caregivers also reported significantly more days of infectious illness, primarily upper respiratory tract infections. Caregivers had a much greater incidence of depressive disorders than controls, with 25% of caregivers meeting syndromal criteria at intake and 32% at follow-up, compared with no cases among controls at intake and 6% at follow-up. Caregivers who reported lower levels of social support at intake and who were most distressed by dementia-related behaviors showed the greatest and most uniformly negative changes in immune function at follow-up.
Adaptation, Psychological↗
Stress-induced modulation of the immune response to recombinant hepatitis B vaccine.
Each of a series of three hepatitis B (Hep B) inoculations was given to 48 second-year medical students on the 3rd day of a 3-day examination series to study the effect of academic stress on the ability to generate an immune response to a primary antigen. Those students who seroconverted after the first injection (25%) were significantly less stressed and anxious than those who did not seroconvert at that time. In addition, students who reported greater social support demonstrated a stronger immune response to the vaccine at the time of the third inoculation, as measured by antibody titers to Hep B surface antigen (HBsAg) and the blastogenic response to a HBsAg peptide (SAg).
Adult↗
Acute psychological stressors and short-term immune changes: what, why, for whom, and to what extent?
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Arousal↗
Negative behavior during marital conflict is associated with immunological down-regulation.
Although increased morbidity and mortality have been reliably associated with social isolation and less satisfying personal relationships, relatively little is known about the underlying biopsychosocial mechanisms. We assessed problem-solving behaviors and changes in immune function in 90 newlywed couples who were admitted to a hospital research unit for 24 hours. Subjects who exhibited more negative or hostile behaviors during a 30-minute discussion of marital problems showed greater decrements over 24 hours relative to low negative subjects on four functional immunological assays (natural killer cell lysis, blastogenic response to two mitogens, and the proliferative response to a monoclonal antibody to the T3 receptor), as well as larger increases in the numbers of total T lymphocytes and helper T lymphocytes. High negative subjects had higher antibody titers to latent Epstein-Barr virus than low negative subjects, consistent with down-regulated immune function. Women were more likely to show negative immunological changes than men. The discussion of marital problems also led to larger increases in blood pressure that remained elevated longer in high negative subjects than low negative subjects. Positive or supportive problem-solving behaviors were not related to either immunological or blood pressure changes. These physiological differences were particularly noteworthy because marital satisfaction was high in both groups, and couples had been selected on the basis of stringent mental and physical health criteria. These data provide additional support for the link between personal relationships and immune function.
Adult↗
Hostile behavior during marital conflict alters pituitary and adrenal hormones.
We evaluated hormonal changes and problem-solving behaviors in 90 newlywed couples who were admitted to a hospital research unit for 24 hours. The subjects were selected on the basis of stringent mental and physical health criteria, and admissions were scheduled during the follicular phase of the woman's menstrual cycle. For frequent, unobtrusive endocrine sampling during the interaction tasks, a long polyethylene tube was attached to a heparin well, allowing nurses to draw blood samples at set intervals, out of subjects' sight. Five blood samples were obtained before, during, and after a 30-minute structured problem-solving or conflict task. The conflict session was recorded on videotapes that were later scored for problem-solving behaviors using the Marital Interaction Coding System (MICS). Marital conflict and MICS-coded hostile or negative behavior during conflict was closely linked to changes in serum hormonal levels across five of the six hormones we studied, in spite of the high marital satisfaction of our newlywed couples and the healthy lifestyles demanded by our exclusion criteria. Hostile behavior was associated with decreased levels of prolactin (PRL) and increases in epinephrine (EPI), norepinephrine (NEPI), ACTH, and growth hormone (GH), but not cortisol. These data suggest that the endocrine system may be an important mediator between personal relationships and health.
Adrenocorticotropic Hormone↗
Heterogeneity in neuroendocrine and immune responses to brief psychological stressors as a function of autonomic cardiac activation.
Human responses to brief psychological stressors are characterized by changes and large individual differences in autonomic, neuroendocrine, and immune function. The authors examined the effects of brief psychological stressors on cardiovascular, neuroendocrine, and cellular immune response in 22 older women to investigate the common effects of stress across systems. They also used interindividual variation in heart rate reactivity, cardiac sympathetic reactivity (as indexed by preejection period reactivity in their reactivity paradigm), and cardiac vagal reactivity (as indexed by respiratory sinus arrhythmia reactivity) to explore the heterogeneity in human responses to brief psychological stressors. The results revealed that brief psychological stressors heightened cardiac activation, elevated plasma catecholamine concentrations, and affected the cellular immune response. It was also found that individuals characterized by high, relative to low, cardiac sympathetic reactivity showed higher stress-related changes in adrenocorticotropic hormone and cortisol plasma levels but comparable changes in epinephrine and norepinephrine concentrations. These data suggest that the effects of psychological stressors on cardiovascular and cellular immune response are governed by coordinated regulatory mechanism(s) and that going beyond the simple notion of heart rate reactivity to examine neural substrates may shed light on the interrelationships among and the regulatory mechanisms for the autonomic, endocrine, and immune responses to stressors.
Adaptation, Psychological↗
Psychoneuroimmunology and health consequences: data and shared mechanisms.
There is evidence linking psychosocially mediated immunological alterations with cancer, infectious illness, and HIV progression. The data reviewed suggest that immune modulation by psychosocial stressors and/or interventions may importantly influence health status. The research literature also suggests that the impact of chronic stressors and psychosocial factors on sympathetic nervous system and endocrine function influences the immune system, thereby providing shared mechanisms that may impact on disease susceptibility and progression across a broad spectrum of disorders. A better understanding of individual vulnerability, such as occurs with aging, may help to pinpoint those at greatest risk.
Adult↗
Psychosocial modulation of cytokine-induced natural killer cell activity in older adults.
The objective of this study was to address the cellular and psychological mechanisms underlying previously observed changes in natural killer (NK) cell cytotoxicity associated with chronic stress. We compared 28 current and former spousal caregivers of patients with Alzheimer's disease (AD) and 29 control subjects. NK cells were enriched (E-NK) using a 4-step procedure that resulted in a cell preparation consisting of 88.2% NK cells. These cells were then incubated with either recombinant interferon-gamma (rIFN-gamma) or recombinant interleukin-2 (rIL-2) for 65 hours. Although an average of over 3 years had elapsed since the death of the patient with AD for the former caregivers, current and former caregivers did not differ in the E-NK cell responses to rIFN-gamma and rIL-2. However, the E-NK cell response for the combined caregiver group was significantly suppressed compared with controls, which is consistent with a previous report from our laboratory. Higher E-NK cell responses to each cytokine were associated with heightened levels of positive emotional and tangible social support, independent of levels of depression. Preliminary data suggest that defects of NK cell function in response to rIFN-gamma and rIL-2 as a consequence of caregiver stress may be independent of non-NK cells. Finally, our data are consistent with other studies regarding the role of social support in immune modulation.
Aged↗
Marital conflict in older adults: endocrinological and immunological correlates.
OBJECTIVE: To assess endocrinological and immunological correlates of marital conflict and marital satisfaction, 31 older couples (mean age 67 years) who had been married an average of 42 years were studied. METHOD: Couples were admitted to the Clinical Research Center and a catheter was placed in each subject's arm. Blood was drawn on entry for immunological assays; for hormone analyses, five blood samples were drawn during a 30-minute conflict discussion and a 15-minute recovery session. The conflict session was recorded on videotapes that were later coded for problem-solving behaviors using the Marital Interaction Coding System (MICS). RESULTS: Among wives, escalation of negative behavior during conflict and marital satisfaction showed strong relationships to endocrine changes, accounting for 16% to 21% of the variance in the rates of change of cortisol, adrenocorticotropic hormone (ACTH), and norepinephrine (but not epinephrine). In contrast, husbands' endocrine data did not show significant relationships with negative behavior or marital quality. Both men and women who showed relatively poorer immunological responses across three functional assays (the blastogenic response to two T-cell mitogens and antibody titers to latent Epstein-Barr virus) displayed more negative behavior during conflict; they also characterized their usual marital disagreements as more negative than individuals who showed better immune responses across assays. CONCLUSION: Abrasive marital interactions may have physiological consequences even among older adults in long-term marriages.
Adrenocorticotropic Hormone↗