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Biomedical subjects

Ronald Glaser

Publications and source records attributed to Ronald Glaser.

At least 19 recordsLinked to original sources
PubMed2006

Norepinephrine up-regulates the expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 in nasopharyngeal carcinoma tumor cells.

Recent studies using ovarian cancer cells have shown that the catecholamine hormones norepinephrine (norepi) and epinephrine (epi) may influence cancer progression by modulating the expression of matrix metalloproteinases (MMP) and vascular endothelial growth factor (VEGF). The purpose of this study is to determine if the stress hormone norepi can influence the expression of MMP-2, MMP-9, and VEGF in nasopharyngeal carcinoma (NPC) tumors by using three NPC tumor cell lines. The NPC cell lines HONE-1, HNE-1, and CNE-1 were treated with norepi. The effects of norepi on MMP-2, MMP-9, and VEGF synthesis were measured by ELISA; functional MMP activity was measured by the invasive potential of the cells using a membrane invasion culture system whereas functional activity of VEGF was analyzed using a human umbilical vein endothelial cell tube formation assay. Norepi treatment increased MMP-2, MMP-9, and VEGF levels in culture supernatants of HONE-1 cells, which could be inhibited by the beta-blocker propranolol. Norepi induced the invasiveness of all NPC cell lines in a dose-dependent manner, which was blocked by CMT-3, an MMP inhibitor, and propranolol. Norepi stimulated the release of functional angiogenic VEGF by HONE-1 cells as well. Finally, HONE-1 cells were shown to express beta-adrenergic receptors as did seven of seven NPC biopsies examined. The data suggest that catecholamine hormones produced by the sympathetic-adrenal medullary axis may affect NPC tumor progression, in part, through modulation of key angiogenic cytokines.

Biopsy↗
PubMed2006

Older spouses' cortisol responses to marital conflict: associations with demand/withdraw communication patterns.

We examined 31 older couples' wife demand/husband withdraw communication patterns and cortisol responses to marital conflict. Regression analyses indicated that wife demand/husband withdraw sequences during conflict related to cortisol responses only for wives. Based on a mixed model that accounted for the interdependence of spouses' perceptions of communication patterns and outcomes, older spouses who reported greater wife demand/husband withdraw patterns in their marriage had greater cortisol responses during a conflict discussion; actual demand-withdraw did not relate to cortisol responses in this model. Findings suggest that perceived communication patterns contribute to neuroendocrine responses to marital conflict, and implications for marriage and health research with older couples are discussed.

Aged↗
PubMed2006

EBV-encoded dUTPase induces immune dysregulation: Implications for the pathophysiology of EBV-associated disease.

Epstein-Barr virus (EBV) encodes for several enzymes that are involved in viral DNA replication. There is evidence that some viral proteins, by themselves, can induce immune dysregulation that may contribute to the pathophysiology of the virus infection. In this study, we focused on the EBV-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTPase) and present the first evidence that the dUTPase is able to induce immune dysregulation in vitro as demonstrated by the inhibition of the replication of stimulated peripheral blood mononuclear cells (PBMCs) and the upregulation of several proinflammatory cytokines including TNF-alpha, IL-1beta, IL-8, IL-6, and IL-10 produced by unstimulated PBMCs treated with purified EBV-encoded dUTPase. Depletion of CD14-positive cells (monocytes) eliminated the cytokine profile induced by EBV dUTPase treatment. The data support the hypothesis that at least one protein of the EBV early antigen complex can induce immune dysregulation and may be involved in the pathophysiology of EBV-associated disease.

Amino Acid Sequence↗
PubMed2006

Hostility and pain are related to inflammation in older adults.

Chronically elevated systemic inflammation has a dramatic impact on health for older individuals. As stress-related responses, both hostility and pain perception may contribute to inflammation which in turn may maintain negative emotion and pain over time. We used structural equation modeling to examine the degree to which trait hostility and pain were uniquely associated with C-reactive protein (CRP) and serum IL-6 levels over a 6-year span in a sample of older adults. The sample included 113 present or former caregivers of a spouse with dementia and 101 non-caregivers. After accounting for depression, health behaviours, and other risk factors, which were also assessed longitudinally, pain and, to a lesser extent, hostility were uniquely associated with plasma levels of CRP but not IL-6. When examined separately, the association between pain and CRP was significant only for caregivers, while the association between hostility and CRP was comparable for the two groups. These findings suggest that hostility may play a role in a cycle of inflammation among older adults, and that pain may be particularly problematic for those under chronic stress. Our results also shed light on inflammation as a mechanism underlying the effects of hostility on cardiovascular disease morbidity and mortality.

Age Factors↗
PubMed2006

Pain and wound healing in surgical patients.

BACKGROUND: Human and animal laboratory studies have shown that stress delays healing of standardized punch biopsy wounds. PURPOSE: This 5-week prospective study of 17 women who underwent elective gastric bypass surgery addressed the association between postsurgical pain intensity and subsequent healing of a standard 2.0-mm punch biopsy wound. METHODS: Participants were assessed 1 week before surgery, within 3 hr before surgery, 1 to 3 days postsurgery, and at weekly intervals for 4 weeks following surgery. RESULTS: Patient ratings of greater acute postsurgical pain, averaged over Days 1 and 2 postsurgery, and greater persistent postsurgical pain, averaged over 4 weekly postsurgery pain ratings, were significantly associated with subsequent delayed healing of the punch biopsy wound. Presence of depressive symptoms on the day of surgery, pre-existing persistent pain, and medical complications following initial discharge from the hospital were not related to wound healing. Depressive symptoms on the day of surgery and pre-existing persistent pain did predict persistent postsurgical pain intensity. CONCLUSIONS: These findings extend the previous laboratory models of wound healing to a surgical population, providing the first evidence that pain plays an important role in postsurgery wound healing, a key variable in postsurgical recovery.

Adult↗
PubMed2005

Hostile marital interactions, proinflammatory cytokine production, and wound healing.

CONTEXT: A growing epidemiological literature has suggested that marital discord is a risk factor for morbidity and mortality. In addition, depression and stress are associated with enhanced production of proinflammatory cytokines that influence a spectrum of conditions associated with aging. OBJECTIVE: To assess how hostile marital behaviors modulate wound healing, as well as local and systemic proinflammatory cytokine production. DESIGN AND SETTING: Couples were admitted twice to a hospital research unit for 24 hours in a crossover trial. Wound healing was assessed daily following research unit discharge. PARTICIPANTS: Volunteer sample of 42 healthy married couples, aged 22 to 77 years (mean [SD], 37.04 [13.05]), married a mean (SD) of 12.55 (11.01) years. INTERVENTIONS: During the first research unit admission, couples had a structured social support interaction, and during the second admission, they discussed a marital disagreement. MAIN OUTCOME MEASURES: Couples' interpersonal behavior, wound healing, and local and systemic changes in proinflammatory cytokine production were assessed during each research unit admission. RESULTS: Couples' blister wounds healed more slowly and local cytokine production (IL-6, tumor necrosis factor alpha, and IL-1beta) was lower at wound sites following marital conflicts than after social support interactions. Couples who demonstrated consistently higher levels of hostile behaviors across both their interactions healed at 60% of the rate of low-hostile couples. High-hostile couples also produced relatively larger increases in plasma IL-6 and tumor necrosis factor alpha values the morning after a conflict than after a social support interaction compared with low-hostile couples. CONCLUSIONS: These data provide further mechanistic evidence of the sensitivity of wound healing to everyday stressors. Moreover, more frequent and amplified increases in proinflammatory cytokine levels could accelerate a range of age-related diseases. Thus, these data also provide a window on the pathways through which hostile or abrasive relationships affect physiological functioning and health.

Adult↗
PubMed2005

Stress-associated immune dysregulation and its importance for human health: a personal history of psychoneuroimmunology.

Historically, clinicians have suspected that both major and minor stressful events can have health implications. Observations and case reports link severely stressful life events with a sudden onset or worsening of a variety of illnesses. The immune system was quickly implicated as a means to help explain how stressful life events could produce this relationship. The field of psychoneuroimmunology (PNI) is a field of research that deals with the complex interactions between the central nervous system, endocrine and immune systems, and how behavior/stress can modify these interactions. In this review, I have selected some of our papers that represent our efforts to study the effects of stress on the immune response and also include selected papers that describe how our PNI program at The Ohio State University Medical Center has evolved; virtually all of this research has been performed in collaboration with Janice Kiecolt-Glaser and others in our research group.

Adult↗
PubMed2005

Stress-associated changes in the steady-state expression of latent Epstein-Barr virus: implications for chronic fatigue syndrome and cancer.

Antibodies to several Epstein-Barr virus (EBV)-encoded enzymes are observed in patients with different EBV-associated diseases. The reason for these antibody patterns and the role these proteins might play in the pathophysiology of disease, separate from their role in virus replication, is unknown. In this series of studies, we found that purified EBV deoxyuridine triphosphate nucleotidohydrolase (dUTPase) can inhibit the replication of human peripheral blood mononuclear cells in vitro and upregulate the production of TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10. It also enhanced the ability of natural killer cells to lyse target cells. The EBV dUTPase also significantly inhibited the replication of mitogen-stimulated lymphocytes and the synthesis of IFN-gamma by cells isolated from lymph nodes and spleens obtained from mice inoculated with the protein. It also produced sickness behaviors known to be induced by some of the cytokines that were studied in the in vitro experiments. These symptoms include an increase in body temperature, a decrease in body mass and in physical activity. The data provide a new perspective on how an early nonstructural EBV-encoded protein can cause immune dysregulation and produce clinical symptoms observed in patients with chronic fatigue syndrome (CFS) separate from its role in virus replication and may serve as a new approach to help identify one of the etiological agents for CFS. The data also provide additional insight into the pathophysiology of EBV infection, inflammation, and cancer.

Animals↗
PubMed2005

Stress-induced immune dysfunction: implications for health.

Folk wisdom has long suggested that stressful events take a toll on health. The field of psychoneuroimmunology (PNI) is now providing key mechanistic evidence about the ways in which stressors--and the negative emotions that they generate--can be translated into physiological changes. PNI researchers have used animal and human models to learn how the immune system communicates bidirectionally with the central nervous and endocrine systems and how these interactions impact on health.

Aging↗
PubMed2005

Exercise accelerates wound healing among healthy older adults: a preliminary investigation.

BACKGROUND: Older adults are likely to experience delayed rates of wound healing, impaired neuroendocrine responsiveness, and increased daily stress. Exercise activity has been shown to have a positive effect on physiological functioning and psychological functioning among older adults. This study evaluated the effect of a 3-month exercise program on wound healing, neuroendocrine function, and perceived stress among healthy older adults. METHODS: Twenty-eight healthy older adults (mean age 61.0 +/- 5.5 years) were assigned randomly to an exercise activity group (n = 13) or to a nonexercise control group (n = 15). One month following baseline randomization, after exercise participants had acclimated to the exercise routine, all participants underwent an experimental wound procedure. Wounds were measured 3 times per week until healed to calculate rate of wound healing. All participants completed assessments of exercise endurance, salivary cortisol, and self-reported stress prior to randomization and at the conclusion of the intervention. RESULTS: Exercise participants achieved significant improvements in cardiorespiratory fitness, as reflected by increased oxygen consumption (VO(2)max) and exercise duration. Wound healing occurred at a significantly faster rate in the exercise group [mean = 29.2 (9.0) days] than in the nonexercise group [38.9 (7.4) days; p =.012]. Exercise participants also experienced increased cortisol secretion during stress testing following the intervention. Group differences in wound healing and neuroendocrine responsiveness were found despite low levels of self-reported stress. CONCLUSIONS: A relatively short-term exercise intervention is associated with enhanced rates of wound healing among healthy older adults. Thus, exercise activity may be an important component of health care to promote wound healing.

Aged↗
PubMed2005

Wound site neutrophil transcriptome in response to psychological stress in young men.

Communication between the central nervous and the immune system occurs through chemical messengers secreted by nerve cells, endocrine organs, or immune cells. Psychological stressors can disrupt these networks. We have previously observed that disruption of the neuroendocrine immune system adversely influences a broad range of physiological processes including wound healing. Migration of neutrophils to the wound site is an early event that induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing. In this study, we have sought to identify stress-sensitive transcripts in wound site neutrophils. A skin blister model was used to collect wound fluid and wound site neutrophils from four young men, experiencing or not examination stress. Self-reported stress was recorded using the Beck Depression Inventory. Stress decreased growth hormone levels at the wound site and was related to impaired wound healing in all subjects. High density microarray analyses were performed using RNA from wound site neutrophils. Results show that psychological stress had an overall suppressive effect on the neutrophil transcriptome. Of the 22,283 transcripts screened, 0.5% were downregulated whereas only under 0.3% were induced by stress in all four out of four subjects. Functionally, stress tilted the genomic balance towards genes encoding proteins responsible for cell cycle arrest, death, and inflammation. Further effort to gain a more comprehensive understanding of the functional significance of such behavior-genome interaction is warranted.

Adult↗
PubMed2004

Psychological, behavioral, and immune changes after a psychological intervention: a clinical trial.

PURPOSE: This randomized clinical trial tests the hypothesis that a psychological intervention can reduce emotional distress, improve health behaviors and dose-intensity, and enhance immune responses. PATIENTS AND METHODS: We studied 227 women who were surgically treated for regional breast cancer. Before adjuvant therapy, women completed interviews and questionnaires assessing emotional distress, social adjustment, and health behaviors. A 60-mL blood sample was drawn for immune assays. Patients were randomly assigned to either the intervention group or assessment only group. The intervention was conducted in small patient groups, with one session per week for 4 months. The sessions included strategies to reduce stress, improve mood, alter health behaviors, and maintain adherence to cancer treatment and care. Reassessment occurred after completion of the intervention. RESULTS: As predicted, patients receiving the intervention showed significant lowering of anxiety, improvements in perceived social support, improved dietary habits, and reduction in smoking (all P <.05). Analyses of adjuvant chemotherapy dose-intensity revealed significantly more variability (ie, more dispersion in the dose-intensity values) for the assessment arm (P <.05). Immune responses for the intervention patients paralleled their psychological and behavioral improvements. T-cell proliferation in response to phytohemagglutinin and concanavalin A remained stable or increased for the Intervention patients, whereas both responses declined for Assessment patients; this effect was replicated across three concentrations for each assay (all P <.01). CONCLUSION: These data show a convergence of significant psychological, health behavior, and biologic effects after a psychological intervention for cancer patients.

Adaptation, Psychological↗
PubMed2004

Epstein-Barr virus-encoded dUTPase modulates immune function and induces sickness behavior in mice.

Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis (IM). In addition, latent infections with EBV are associated with nasopharyngeal carcinoma (NPC) and Burkitt's Lymphoma (BL). Antibodies to several EBV-encoded early antigens (EA) are often observed in patients with NPC and BL, however, the role of EBV-encoded proteins in the etiology of these and other EBV-associated diseases is not completely understood. The EA complex encodes for at least six different viral enzymes including deoxyuridine triphosphate nucleotidohydrolase (dUTPase). dUTPase has recently been shown to modulate activation of human peripheral blood mononuclear cells in vitro (unpublished data). Therefore, these studies were designed to test whether dUTPase would modulate immune function in an in vivo model. Mice were injected with purified EBV dUTPase, and baseline immune function and sickness behaviors were measured. EBV dUTPase treatment inhibited replication of mitogen-stimulated lymphocytes obtained from treated mice. These lymphocytes were also less able to synthesize interferon-gamma after re-stimulation. In addition, treatment with dUTPase induced sickness behaviors. For example, as compared to control animals, dUTPase-treated animals lost body mass, had elevated body temperature, and displayed diminished locomotor activity. These data suggest that individual viral proteins may play a role in the pathophysiology of EBV associated disease.

Animals↗
PubMed2004

Spousal support satisfaction as a modifier of physiological responses to marital conflict in younger and older couples.

We investigated linkages between spousal support satisfaction and affective, cortisol, and blood pressure responses to conflict in two samples, 85 newlyweds and 31 older couples, married an average of 42 years. Couples were admitted to a hospital research unit and provided self-reports regarding the support received from their spouses. After a baseline period, couples engaged in a 30-min conflict discussion during which time blood was drawn for cortisol assessment. After the conflict, newlyweds' blood pressure was measured. Among newlywed wives, greater spousal support satisfaction was associated with smaller changes in negative affect and cortisol responses to conflict. Notably, newlywed wives and husbands demonstrated lower blood pressure after conflict when spousal support satisfaction was higher. In contrast, older husbands (but not wives) exhibited greater cortisol responses when spousal support satisfaction was lower. These relationships provide a window on mechanisms linking marriage and health for men and women across the life span.

Adult↗
PubMed2003

Chronic stress and age-related increases in the proinflammatory cytokine IL-6.

Overproduction of IL-6, a proinflammatory cytokine, is associated with a spectrum of age-related conditions including cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, certain cancers, periodontal disease, frailty, and functional decline. To describe the pattern of change in IL-6 over 6 years among older adults undergoing a chronic stressor, this longitudinal community study assessed the relationship between chronic stress and IL-6 production in 119 men and women who were caregiving for a spouse with dementia and 106 noncaregivers, with a mean age at study entry of 70.58 (SD = 8.03) for the full sample. On entry into this portion of the longitudinal study, 28 of the caregivers' spouses had already died, and an additional 50 of the 119 spouses died during the 6 years of this study. Levels of IL-6 and health behaviors associated with IL-6 were measured across 6 years. Caregivers' average rate of increase in IL-6 was about four times as large as that of noncaregivers. Moreover, the mean annual changes in IL-6 among former caregivers did not differ from that of current caregivers even several years after the death of the impaired spouse. There were no systematic group differences in chronic health problems, medications, or health-relevant behaviors that might have accounted for caregivers' steeper IL-6 slope. These data provide evidence of a key mechanism through which chronic stressors may accelerate risk of a host of age-related diseases by prematurely aging the immune response.

Aged↗
PubMed2003

Mild depressive symptoms are associated with amplified and prolonged inflammatory responses after influenza virus vaccination in older adults.

BACKGROUND: Depression is associated with enhanced production of proinflammatory cytokines that influence a spectrum of conditions associated with aging, including cardiovascular disease, osteoporosis, arthritis, type 2 diabetes mellitus, certain cancers, periodontal disease, frailty, and functional decline. In this prospective community study, we assessed the relationship between depressive symptoms and changes in inflammatory response after an influenza virus vaccination. METHODS: To study the dynamics of interleukin (IL) 6 levels in plasma in response to an immunological challenge, we obtained blood samples in 119 older adults (mean age, 71.21 +/- 8.68 years [SD]) immediately before an annual influenza vaccination and again 2 weeks later. The short form of the Beck Depression Inventory, completed at these same times, provided information on depressive symptoms. RESULTS: The number of depressive symptoms in this sample was low on average before vaccination (mean +/- SD number of symptoms, 3.07 +/- 3.09) and did not change significantly after vaccination. Participants with more depressive symptoms had higher levels of IL-6 before and after vaccination than did those who reported fewer symptoms; moreover, individuals reporting more depressive symptoms also showed an increase in plasma IL-6 levels 2 weeks later, while there was little change in IL-6 levels among those reporting few or no symptoms. CONCLUSIONS: Even a modest number of depressive symptoms may sensitize the inflammatory response system in older adults and produce amplified and prolonged inflammatory responses after infection and other immunological challenges. Sustained and/or amplified inflammatory responses could accelerate a range of age-related diseases.

Age Factors↗