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Biomedical subjects

R Glaser

Publications and source records attributed to R Glaser.

At least 55 records · Page 3Linked to original sources
PubMed1998

Stress-induced neuroendocrine modulation of viral pathogenesis and immunity.

Physical restraint (RST) was used to examine the interactions among the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system, and the immune response to infection. In these studies, mice were infected with either herpes simplex virus (HSV) or influenza A/PR8 virus so that the impact of neuroendocrine activation could be assessed on disease pathophysiology and anti-viral immunity. RST suppressed lymphadenopathy in draining lymph nodes, reduced mononuclear cellular infiltration in the lungs, and suppressed virus-specific cytokine and cytolytic T-cell responses. Blockade of type II glucocorticoid receptors (by RU486) restored cellularity and cytokine responses to both organs in restraint-stressed, infected mice. Thus, the HPA axis modulated cell trafficking and T-cell cytokine responses. However, RU486 treatment failed to restore cytolytic T-cell responses. Blockade of beta-adrenergic receptors (by nadolol), in combination with RU486 treatment, fully restored cytolytic T-cell responses, suggesting that catecholamines were involved in suppressing the virus-specific CD8+ cytolytic T-cell response. RST also modulated the local development or expression of antibody-secreting cells (ASC) in the lungs draining lymph nodes, and spleen following infection of restrained mice. RST significantly suppressed the number of virus-specific ASC (IgM, IgG and subclasses IgG1 and IgG2a) in the lungs, mediastinal (MLN) lymph nodes and spleen, while it enhanced the responses in the superficial cervical (SCV) lymph nodes. This observation of differential modulation of ASC responses in the MLN and SCV lymph nodes supports the concept of tissue-specific immunoregulation in response to stress.

Animals↗
PubMed1998

Epstein-Barr virus growth-transformed cells are converted to malignancy following transfection of a 1.3-kb CATR1 antisense construct independent of a change in the level of c-myc expression followed by a 8;14 chromosomal translocation.

The AGLCL Epstein-Barr virus (EBV) growth-transformed cell line is incapable of inducing tumors in nude mice. When the cells were transfected with a 1.3-kb CATR1 antisense cDNA construct, progressively growing lymphomas could be induced in nude mice. Chromosome analysis of the parental, transfected, and tumor cells revealed that a chromosomal translocation t(8;14)(q24.1;q32) had occurred in the transfected cells and was retained in cells derived from tumors. Moreover, enhanced c-myc expression, usually associated with this translocation, was either unchanged or under-expressed. These data suggest that the malignant transformation of the EBV growth-transformed cells was independent of c-myc expression and suggest that the CATR1 gene may act synergistically with the chromosomal translocation facilitating the conversion of AGLCL cells from a growth-transformed state to a malignant phenotype.

Animals↗
PubMed1998

Stress and immune responses after surgical treatment for regional breast cancer.

BACKGROUND: Adults who undergo chronic stress, such as the diagnosis and surgical treatment of breast cancer, often experience adjustment difficulties and important biologic effects. This stress can affect the immune system, possibly reducing the ability of individuals with cancer to resist disease progression and metastatic spread. We examined whether stress influences cellular immune responses in patients following breast cancer diagnosis and surgery. METHODS: We studied 116 patients recently treated surgically for invasive breast cancer. Before beginning their adjuvant therapy, all subjects completed a validated questionnaire assessing the stress of being cancer patients. A 60-mL blood sample taken from each patient was subjected to a panel of natural killer (NK) cell and T-lymphocyte assays. We then developed multiple regression models to test the contribution of psychologic stress in predicting immune function. All regression equations controlled for variables that might exert short- or long-term effects on these responses, and we also ruled out other potentially confounding variables. RESULTS: We found, reproducibly between and within assays, the following: 1) Stress level significantly predicted lower NK cell lysis, 2) stress level significantly predicted diminished response of NK cells to recombinant interferon gamma, and 3) stress level significantly predicted decreased proliferative response of peripheral blood lymphocytes to plant lectins and to a monoclonal antibody directed against the T-cell receptor. CONCLUSIONS: The data show that the physiologic effects of stress inhibit cellular immune responses that are relevant to cancer prognosis, including NK cell toxicity and T-cell responses. Additional, longitudinal studies are needed to determine the duration of these effects, their health consequences, and their biologic and/or behavioral mechanisms.

Adult↗
PubMed1998

Human osteoblast-like cells respond not only to the extracellular calcium concentration but also to its changing rate.

The effect of extracellular calcium on human osteoblast-like cells (HOS) has been demonstrated. An experimental setup was used for applying defined rates of change in the extracellular calcium concentration. The intracellular calcium concentration was monitored using the fluorescence dye fura-2. HOS cells showed qualitatively different responses of the intracellular calcium concentration to changes of the extracellular calcium concentration depending on its changing rate. A small rate caused only a small and slow increase of the intracellular calcium concentration, whereas faster changes are able to cause a rapid transient increase followed by a sustained elevation of the internal calcium level. Surprisingly, both an increasing as well as a decreasing external calcium concentration is able to cause cellular responses. These signals could be reduced by the IP3-inhibitor neomycin. We propose that the G-protein dependent signalling pathway of HOS cells can not only sense the extracellular calcium concentration but also its time derivative.

Biophysical Phenomena↗
PubMed1998

Psychological influences on surgical recovery. Perspectives from psychoneuroimmunology.

Greater fear or distress prior to surgery is associated with a slower and more complicated postoperative recovery. Although anxiety presumably interferes with recuperation through both behavioral and physiological mechanisms, the pathways have been unclear. Recent work in psychoneuroimmunology (PNI) has demonstrated that stress delays wound healing. In addition, a second line of research has illustrated the adverse effects of pain on endocrine and immune function. A biobehavioral model is described that is based on these and other data; it suggests a number of routes through which psychological and behavioral responses can influence surgery and post-surgical outcomes. Clinical and research implications are highlighted.

General Surgery↗
PubMed1998

Cellular immune responses to acute stress in female caregivers of dementia patients and matched controls.

This study investigated whether the stress of caregiving alters cellular immune responses to acute psychological stressors. Twenty-seven women caring for a spouse with a progressive dementia (high chronic stress) and 37 controls matched for age and family income performed a 12-min laboratory stressor. Cellular immune function was assessed by both functional and quantitative measures taken before (low acute stress), immediately after (high acute stress), and 30 min after (recovery from stress) exposure to the laboratory stressors. The laboratory challenges were associated with diminished proliferative responses but elevated natural killer (NK) cell cytotoxicity; however, subsequent analyses suggested that this elevated cytotoxicity was largely attributable to an increase in the number of NK cells in peripheral blood. The results suggest that although the stress of caregiving diminishes cellular immune function, caregiving appears to have little effect on cellular immune responses to or recovery from brief psychological challenges.

Aged↗
PubMed1997

Differential effects of estrogen and medroxyprogesterone on basal and stress-induced growth hormone release, IGF-1 levels, and cellular immunity in postmenopausal women.

We evaluated the influence of continual estrogen replacement therapy (ERT) as presently practiced by postmenopausal women with conjugated estrogens and medroxyprogesterone acetate (MPA) on the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and cellular immunity. Thirty-nine postmenopausal women were evaluated (12 on no replacement, 14 on estrogen only, and 13 on estrogen and MPA). In the women receiving only conjugated estrogens, increased GH levels and decreased IGF-1 levels were found, which replicated previous research and probably reflected estrogen inhibition of hepatic IGF-1 production with a secondary increase in GH release because of reduced feedback inhibition. In women taking both MPA and estrogen, GH was increased and the previously observed estrogen induced decrease in IGF-1 levels was inhibited. In order to determine the influence of ERT on psycho-social stress-induced GH release, math (mental stress) and speech (social stress) challenges were utilized, and they produced significant increases in heart rate in all three groups. The heart rate following stress was significantly enhanced by estrogen replacement. These stressors also led to increased GH secretion in the women taking estrogen and MPA, but not in the other two groups. Gonadal steroids and GH can influence cellular immunity. We observed that ERT in both groups was associated with significantly enhanced lymphocyte responsiveness to the T-cell mitogens phytohemaglutinin (PHA) and Conconavalin A (Con A), and basal GH levels were correlated with the PHA response in the estrogen only group. ERT did not influence natural killer (NK) cell activity. We also found significant differences in the steady-state expression of latent Epstein-Barr virus (EBV) with increased antibody titers in the women in the estrogen only group and lower antibody titers in the MPA plus estrogen group. GH levels were correlated with EBV antibody titers in the estrogen plus MPA group. This study supports the hypothesis that GH and immune modulation can be influenced by ERT in postmenopausal woman. Given the extant literature on the immune-enhancing effects of GH, these data suggest that ERT may slow the decline of GH secretion with aging, an event that has been implicated in immunosenescence.

Aged↗
PubMed1997

Chronic stress modulates the virus-specific immune response to latent herpes simplex virus type 1.

We compared 71 family caregivers of dementia sufferers and 58 control subjects on three different immune measures relevant to latent herpes simplex virus Type 1 (HSV-1) infection: neutralizing antibody titers, antibody titers to a total viral antigen, and a proliferative memory T-cell response. Caregivers had significantly higher antibody titers to the total viral antigen and a poorer HSV-1 specific T-cell response than controls, but no significant difference in neutralizing antibody titers between groups was observed. These data provide additional evidence that psychological stress can modulate a virus-specific immune response associated with caregiving.

Adult↗
PubMed1997

Predictors of risk for different stages of adolescent smoking in a biracial sample.

This investigation was designed to identify the risk factors associated with different stages of cigarette use in a large biracial adolescent sample. A questionnaire assessing smoking habits and variables thought to be related to smoking was administered to 6,967 7th graders. Analysis revealed that the best predictor of experimentation with cigarettes was the perception that they were easily available. Regular smoking appeared to be heavily influenced by cost. Social influences contributed to both experimental and regular smoking, but the impact of social models varied with ethnicity and gender. Analysis further revealed that weight-related variables were closely tied to regular smoking. Implications of the findings for smoking prevention programs are discussed.

Adolescent↗
PubMed1997

Alterations of intracellular calcium concentration in mice neuroblastoma cells by electrical field and UVA.

By using a FURA2 ratio imaging method, the intracellular free calcium concentration was investigated in cultured mice neuroblastoma cells under the influence of an amplitude-modulated (AM) field (5 kHz sine wave AM 16 Hz sinusoidal 800 V/m and 80 V/m), as well as of electric field pulses (300-ms unipolar pulses of 1000 V/m and 800 V/m, 5 pulses during 10 s and 50 pulses during 100 s). An increase in free intracellular calcium was found in about 50% of cells after field application, whereas in control experiments only about 20% of the cells showed similar increases. However, this effect depended on the amount of UV irradiation used for excitation of FURA2 fluorescence. Experiments with 1/30 to former total illumination no longer demonstrated an increase in control cells or in cells treated with AM fields. The number of cells showing calcium increase after the application of pulsed fields was reduced significantly. Therefore, the UV light itself, applied as double flashes for the fluorescence measurement, activates the cellular calcium regulation. These findings offer a possible explanation for the low reproducibility of field effects found in different laboratories, in which investigations were performed with different equipment using different intensities of UV excitation.

Animals↗
PubMed1997

I-symmetry, the highest chiral point group, and the icosahedral structure of virus particles.

Small molecules exhibiting I-symmetry, the member of highest order amongst the five chiral point groups, have yet to be made. However, many virus particles such as the human adenovirus exhibit icosahedral symmetry. The handedness of the subunits being exchanged or permutated by symmetry operations in these supramolecular structures remain invariant since their protein constituents contain L-amino acids. This is only consistent with the existence of symmetry operations of the first kind, and thus these chiral icosahedral ensembles provide suitable examples of I-symmetry.

Adenoviridae↗
PubMed1996

Chronic stress alters the immune response to influenza virus vaccine in older adults.

To determine whether a chronic stressor (caregiving for a spouse with a progressive dementia) is associated with an impaired immune response to influenza virus vaccination, we compared 32 caregivers' vaccine responses with those of 32 sex-, age-, and socioeconomically matched control subjects. Caregivers showed a poorer antibody response following vaccination relative to control subjects as assessed by two independent methods, ELISA and hemagglutination inhibition. Caregivers also had lower levels of in vitro virus-specific-induced interleukin 2 levels and interleukin 1beta; interleukin 6 did not differ between groups. These data demonstrate that down-regulation of the immune response to influenza virus vaccination is associated with a chronic stressor in the elderly. These results could have implications for vulnerability to infection among older adults.

Aged↗
PubMed1996

Diffusion layer caused by local ionic transmembrane fluxes.

Ionic concentrations in the close proximity of a carrier may be different from those in the bulk solution. An immediate layer in the solution in which this situation occurs is known as a diffusion layer. Such diffusion layers were calculated using general diffusion equations and postulating a membrane to be homogeneous in the plane with respect to its permeability. In contrast, the present mathematical model considers single-carrier mediated transport of ions across the membrane and their diffusion away from the carrier site into the electrolyte solution. In particular, the transport of Ca2+ ions is considered. The diffusion of electrolyte ions (Na+ and Cl-) and of Ca2+ ions is described by the Nernst-Planck electrodiffusion equation. The relation between the local electric potential and the ion concentrations is taken into account by the Poisson equation. The equations are solved numerically for radial symmetry by the relaxation method. The model predicts concentration and potential profiles in dependence of the flux rate of Ca2+ ions. It is shown that for fluxes mediated by a single carrier, a diffusion layer becomes significant if the flux is larger than 10(5) Ca2+ ions per second.

Calcium↗
PubMed1996

Marital conflict and endocrine function: are men really more physiologically affected than women?

This study assessed marital conflict behavior and endocrine function in 90 newlywed couples. Blood samples acquired hourly from 8:00 a.m. through 10:00 p.m. were combined to provide composite daytime values for 3 stress hormones -- epinephrine (EPI), norepinephrine (NEPI), and cortisol -- and 3 related hormones (ACTH, growth hormone, and prolactin). These pooled data provided a window on endocrine function in couples for whom the day included a conflict. For wives, higher probabilities of husband's withdrawal in response to wife's negative behavior were associated with higher NEPI and cortisol levels. In addition, higher frequencies of positive behaviors were associated with lower EPI and higher prolactin levels among wives. Husbands' endocrine data were not associated with behavioral data. These findings are discussed in the context of gender models of marital conflict.

Adrenocorticotropic Hormone↗
PubMed1995

Slowing of wound healing by psychological stress.

There is evidence that psychological stress adversely affects the immune system. We have investigated the effects of such stress, caused by caring for a relative with Alzheimer's disease, on wound healing. We studied 13 women caring for demented relatives (mean age 62.3 [SE 2.3] years) and 13 controls matched for age (60.4 [2.8] years) and family income. All subjects underwent a 3.5 mm punch biopsy wound. Healing was assessed by photography of the wound and the response to hydrogen peroxide (healing was defined as no foaming). Wound healing took significantly longer in caregivers than in controls (48.7 [2.9] vs 39.3 [3.0] days, p < 0.05). Peripheral-blood leucocytes from caregivers produced significantly less interleukin-1 beta mRNA in response to lipopolysaccharide stimulation than did controls' cells. Stress-related defects in wound repair could have important clinical implications, for instance for recovery from surgery.

Aged↗
PubMed1995

The reliability and validity of a structured interview for the assessment of infectious illness symptoms.

Respiratory infections are the leading cause of morbidity in community populations. We developed a structured interview based on the Health Review (Rose et al., Psychosom. Med. 40: 142-165, 1978) to provide a simple method for periodic assessment of infectious illness, particularly upper respiratory infections. Congruence between interview data and physician diagnoses demonstrated excellent agreement regarding the presence or absence of an infection. Subjects who showed a clinically significant increase in antibody titers to an influenza virus vaccine reported fewer than half as many respiratory infections in the subsequent year as subjects who did not show a significant response. Interrater and test-retest reliabilities were satisfactory. These data support the reliability and validity of this method of assessing infectious illnesses.

Aged↗