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Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress, and immune parameters in breast and prostate cancer outpatients.

OBJECTIVES: This study investigated the relationships between a mindfulness-based stress reduction meditation program for early stage breast and prostate cancer patients and quality of life, mood states, stress symptoms, lymphocyte counts, and cytokine production. METHODS: Forty-nine patients with breast cancer and 10 with prostate cancer participated in an 8-week MBSR program that incorporated relaxation, meditation, gentle yoga, and daily home practice. Demographic and health behavior variables, quality of life (EORTC QLQ C-30), mood (POMS), stress (SOSI), and counts of NK, NKT, B, T total, T helper, and T cytotoxic cells, as well as NK and T cell production of TNF, IFN-gamma, IL-4, and IL-10 were assessed pre- and postintervention. RESULTS: Fifty-nine and 42 patients were assessed pre- and postintervention, respectively. Significant improvements were seen in overall quality of life, symptoms of stress, and sleep quality. Although there were no significant changes in the overall number of lymphocytes or cell subsets, T cell production of IL-4 increased and IFN-gamma decreased, whereas NK cell production of IL-10 decreased. These results are consistent with a shift in immune profile from one associated with depressive symptoms to a more normal profile. CONCLUSIONS: MBSR participation was associated with enhanced quality of life and decreased stress symptoms in breast and prostate cancer patients. This study is also the first to show changes in cancer-related cytokine production associated with program participation.

Adenocarcinoma↗

Sex as a response to oxidative stress: stress genes co-opted for sex.

Despite a great deal of interest, the evolutionary origins and roles of sex remain unclear. Recently, we showed that in the multicellular green alga, Volvox carteri, sex is a response to increased levels of reactive oxygen species (ROS), which could be indicative of the ancestral role of sex as an adaptive response to stress-induced ROS. To provide additional support for the suggestion that sex evolved as a response to oxidative stress, this study addresses the hypothesis that genes involved in sexual induction are evolutionarily related to genes associated with various stress responses. In particular, this study investigates the evolutionary history of genes specific to the sexual induction process in V. carteri--including those encoding the sexual inducer (SI) and several SI-induced extracellular matrix (ECM) proteins. Surprisingly, (i) a highly diversified multigene family with similarity to the V. carteri SI and SI-induced pherophorin family is present in its unicellular relative, Chlamydomonas reinhardtii (which lacks both a SI and an ECM) and (ii) at least half of the 12 identified gene members are induced (as inferred from reported expressed sequence tags) under various stress conditions. These findings suggest an evolutionary connection between sex and stress at the gene level, via duplication and/or co-option.

Algal Proteins↗

The biological limitations of transcriptomics in elucidating stress and stress responses.

Global analysis of mRNA abundance via genomic arrays (i.e. transcriptomics or transcriptional profiling) is one approach to finding the genes that matter to organisms undergoing environmental stress. In evolutionary analyses of stress, mRNA abundance is often invoked as a proxy for the protein activity that may underlie variation in fitness. To provoke discussion of the utility and sensible application of this valuable approach, this manuscript examines the adequacy of mRNA abundance as a proxy for protein activity, fitness and stress. Published work to date suggests that mRNA abundance typically provides little information on protein activity and fitness and cannot substitute for detailed functional and ecological analyses of candidate genes. While the transcriptional profile can be an exquisitely sensitive indicator of stress, simpler indicators will often suffice. In view of this outcome, transcriptomics should undergo careful cost-benefit analysis before investigators deploy it in studies of stress responses and their evolution.

Adaptation, Biological↗

Reduction of heart lesions after experimental restraint stress: a study in stress-susceptible pigs.

Pigs, crossbreeds of Swedish Landrace and Yorkshire, about 6 months old and susceptible to develop malignant hyperthermia when exposed to halothane, were subjected to a 12-min experimental stress provoked by the myorelaxant succinylcholine. The experimental pigs were pre-treated before the stress: five were given propranolol for one week, six were given alpha-tocopherol (vitamin E) combined with selenium for 11 days, and five pigs were pre-treated with zinc (ZnSO4) for 1 month. A total of 12 untreated, stress-susceptible pigs served as controls. The blood levels of noradrenaline and adrenaline recorded during the stress were significantly reduced in the groups pre-treated with propranolol or alpha-tocopherol combined with selenium. The results show significant reduction of myocardial necrosis by beta-adrenoceptor-blocking agents and free-radical scavengers during stress-induced increased sympathetic activity.

Animals↗

Vulnerability to stress: self-criticism and stress-induced changes in biochemistry.

It has been hypothesized that individuals who are high on the attribute of self-criticism are particularly vulnerable to failure stress. To test this hypothesis, we examined the relationship between self-criticism and changes in plasma homovanillic acid (HVA; the metabolite of dopamine) and emotion during exposure to an induced-failure task. Participants consisted of 21 women. Plasma HVA and emotion were assessed at three time points: baseline (T1), during stress exposure (T2), and 40 minutes after cessation of the stressor (T3). We found that self-criticism was significantly and positively related to changes in plasma HVA during stress exposure. In addition, the personality attribute was significantly and positively related to subjective ratings of stress and changes in scores on the Confusion-Bewilderment scale of the Profile of Mood States during the task. To our knowledge, this is the first study to report that self-criticism is related to stress-induced changes in biochemistry.

Adult↗

Moderate level alcohol during pregnancy, prenatal stress, or both and limbic-hypothalamic-pituitary-adrenocortical axis response to stress in rhesus monkeys.

This study examined the relationship between moderate-level prenatal alcohol exposure, prenatal stress, and postnatal response to a challenging event in 6-month-old rhesus monkeys. Forty-one rhesus monkey (Macaca mulatta) infants were exposed prenatally to moderate level alcohol, maternal stress, or both. Offspring plasma cortisol and adrenocorticotrophic hormone (ACTH) were determined from blood samples before maternal separation and after separation. Behavioral observations were made repeatedly across separation. Moderate-level prenatal alcohol exposure was associated with significantly higher plasma ACTH response to maternal separation. Offspring exposed to prenatal alcohol, prenatal stress, and prenatal alcohol and stress showed reduced behavioral adaptation to stress compared with controls. Baseline, 2-hr, and 26-hr plasma ACTH levels were intercorrelated and predicted behavior during separation.

Adaptation, Psychological↗

Plasma catecholamine levels in SART-stressed rats and effects of drugs on stress-induced alteration in plasma and brain catecholamine levels.

1. Plasma catecholamine (CA) levels were examined in rats exposed to SART (specific alternation of rhythm in temperature) stress, a repeated cold stress. Effects of neurotropin, a sedative analgesic, and alprazolam, an anxiolytic, on the changes in plasma and brain CA levels were then studied. 2. SART stress induced remarkable increases in plasma levels of noradrenaline (NA) and dopamine (DA). The plasma adrenaline (Adr) level also increased significantly, but the extent was smaller than that of NA or DA. 3. Repeated treatments with neurotropin reduced the stress-induced increases in plasma and brain NA and DA levels significantly and dose-dependently. 4. Repeated treatments with alprazolam markedly reduced all increases in plasma and brain CA levels. 5. The above findings suggest that SART-stressed animals are in an increasing state of sympathetic neuronal activity and in a slightly increasing state of adrenal function. Neurotropin is also suggested to have modulating effects on autonomic imbalance in both catecholaminergic and cholinergic nerves.

Alprazolam↗

Socioeconomic status and chronic stress. Does stress account for SES effects on health?

Socioeconomic status (SES) is an important predictor of a range of health and illness outcomes. Research seeking to identify the extent to which this often-reported effect is due to protective benefits of higher SES or to toxic elements of lower social status has not yielded consistent or conclusive findings. A relatively novel hypothesis is that these effects are due to chronic stress that is associated with SES; lower SES is reliably associated with a number of important social and environmental conditions that contribute to chronic stress burden, including crowding, crime, noise pollution, discrimination, and other hazards or stressors. In other words, chronic stress may capture much of the variance in health and social outcomes associated with harmful aspects of lower social status. Low SES is generally associated with distress, prevalence of mental health problems, and with health-impairing behaviors that are also related to stress. Research targeting this hypothesis is needed to determine the extent to which stress is a pathway linking SES and health.

Chronic Disease↗

Stress-modulated growth, residual stress, and vascular heterogeneity.

A simple phenomenological model is used to study interrelations between material properties, growth-induced residual stresses, and opening angles in arteries. The artery is assumed to be a thick-walled tube composed of an orthotropic pseudoelastic material. In addition, the normal mature vessel is assumed to have uniform circumferential wall stress, which is achieved here via a mechanical growth law. Residual stresses are computed for three configurations: the unloaded intact artery, the artery after a single transmural cut, and the inner and outer rings of the artery created by combined radial and circumferential cuts. The results show that the magnitudes of the opening angles depend strongly on the heterogeneity of the material properties of the vessel wall and that multiple radial and circumferential cuts may be needed to relieve all residual stress. In addition, comparing computed opening angles with published experimental data for the bovine carotid artery suggests that the material properties change continuously across the vessel wall and that stress, not strain, correlates well with growth in arteries.

Animals↗

Polysome-bound endonuclease PMR1 is targeted to stress granules via stress-specific binding to TIA-1.

The generalized process of mRNA decay involves deadenylation followed by release from translating polysomes, decapping, and exonuclease decay of the mRNA body. In contrast the mRNA endonuclease PMR1 forms a selective complex with its translating substrate mRNA, where it initiates decay by cleaving within the mRNA body. In stressed cells the phosphorylation of the alpha subunit of eukaryotic initiation factor 2 causes translating mRNAs to accumulate with stalled 48S subunits in large subcellular structures termed stress granules (SGs), wherein mRNAs undergo sorting for reinitiation, storage, or decay. Given the unique relationship between translation and PMR1-mediated mRNA decay, we examined the impact of stress-induced dissociation of polysomes on this process. Arsenite stress disrupts the polysome binding of PMR1 and its substrate mRNA but has no impact on the critical tyrosine phosphorylation of PMR1, its association with substrate mRNA, or its association with the functional approximately 680-kDa mRNP complex in which it normally resides on polysomes. We show that arsenite stress drives PMR1 into an RNase-resistant complex with TIA-1, and we identify a distinct domain in the N terminus of PMR1 that facilitates its interaction with TIA-1. Finally, we show that arsenite promotes the delayed association of PMR1 with SGs under conditions which cause tristetraprolin and butyrate response factor 1, proteins that facilitate exonucleolytic mRNA, to exit SGs.

Animals↗

hnRNP A1 relocalization to the stress granules reflects a role in the stress response.

hnRNP A1 is a nucleocytoplasmic shuttling protein that is involved in many aspects of mRNA metabolism. We have previously shown that activation of the p38 stress-signaling pathway in mammalian cells results in both hyperphosphorylation and cytoplasmic accumulation of hnRNP A1, affecting alternative splicing regulation in vivo. Here we show that the stress-induced cytoplasmic accumulation of hnRNP A1 occurs in discrete phase-dense particles, the cytoplasmic stress granules (SGs). Interestingly, mRNA-binding activity is required for both phosphorylation of hnRNP A1 and localization to SGs. We also show that these effects are mediated by the Mnk1/2 protein kinases that act downstream of p38. Finally, depletion of hnRNP A1 affects the recovery of cells from stress, suggesting a physiologically significant role for hnRNP A1 in the stress response. Our data are consistent with a model whereby hnRNP A1 recruitment to SGs involves Mnk1/2-dependent phosphorylation of mRNA-bound hnRNP A1.

Animals↗

Luman/CREB3 induces transcription of the endoplasmic reticulum (ER) stress response protein Herp through an ER stress response element.

Luman/CREB3 (also called LZIP) is an endoplasmic reticulum (ER) membrane-bound transcription factor which is believed to undergo regulated intramembrane proteolysis in response to cellular cues. We previously found that Luman activates transcription from the unfolded protein response element. Here we report the identification of Herp, a gene involved in ER stress-associated protein degradation (ERAD), as a direct target of Luman. We found that Luman was transcriptionally induced and proteolytically activated by the ER stress inducer thaspsigargin. Overexpression of Luman activated transcription of cellular Herp via ER stress response element II (ERSE-II; ATTGG-N-CCACG) in the promoter region. Mutagenesis studies and chromatin immunoprecipitation assays showed that Luman physically associates with the Herp promoter, specifically the second half-site (CCACG) of ERSE-II. Luman was also necessary for the full activation of Herp during the ER stress response, since Luman small interfering RNA knockdown or functional repression by a dominant negative mutant attenuated Herp gene expression. Like Herp, overexpression of Luman protected cells against ER stress-induced apoptosis. With Luman structurally similar to ATF6 but resembling XBP1 in DNA-binding specificities, we propose that Luman is a novel factor that plays a role in ERAD and a converging point for various signaling pathways channeling through the ER.

Animals↗

Chronic stress affects immunologic but not cardiovascular responsiveness to acute psychological stress in humans.

This study deals with the effect of chronic stress on physiological responsiveness to an acute psychological stressor in male high school teachers. Chronic stress was operationalized as the self-reported number of everyday problems. Twenty-seven subjects reporting extremely low or high numbers of everyday problems were exposed to an acute psychological stressor, and changes in immunologic, endocrine, and cardiovascular parameters were monitored. The stressor included a learning process followed by a teaching session in which a confederate to the researchers was involved. Twenty subjects served as controls. The stressor had no effect on the endocrine variables measured but induced increases in heart rate and blood pressure, which were similar in both chronic stress groups. Analysis of subsets of blood lymphocytes revealed differences in natural killer (NK) and T cell responses in the low and the high stress groups. It is concluded that 1) immunologic responsiveness to an acute psychological stressor is related to problems experienced in daily life, and that 2) chronic stress differentially modifies the sensitivity of biological systems to mild acute stressors.

Acute Disease↗

Sensitization of the colonic response to novel stress after previous stressful experience.

Stressful life events may be important causative or precipitating factors for functional gastrointestinal disorders such as the irritable bowel syndrome in humans. In the rat, a single session of foot shocks is known to sensitize the behavioral and hormonal responses to subsequent stress, but intestinal responses have not been investigated. Rats were fitted with bipolar electrodes on proximal colon and exposed to a single session of foot shocks (10 x 6 s in 15 min; preshocked) or no shocks (control). Weight gain after foot shocks was identical to that in controls. Two weeks after foot shocks, basal colonic spike burst frequency did not differ from controls or from that recorded before shock treatment. Unlike controls, however, preshocked rats showed a significant increase in colonic spike burst frequency to a novel stressful challenge in the home cage, an electrified prod. Because the behavioral responses to this challenge did not differ, colonic hyperresponsiveness in preshocked rats may represent a form of stress-induced autonomic sensitization. The model should be a useful tool to study mechanisms and pharmacotherapeutic approaches of the gastrointestinal consequences of traumatic stress.

Animals↗

The 'Trier Social Stress Test'--a tool for investigating psychobiological stress responses in a laboratory setting.

This paper describes a protocol for induction of moderate psychological stress in a laboratory setting and evaluates its effects on physiological responses. The 'Trier Social Stress Test' (TSST) mainly consists of an anticipation period (10 min) and a test period (10 min) in which the subjects have to deliver a free speech and perform mental arithmetic in front of an audience. In six independent studies this protocol has been found to induce considerable changes in the concentration of ACTH, cortisol (serum and saliva), GH, prolactin as well as significant increases in heart rate. As for salivary cortisol levels, the TSST reliably led to 2- to 4-fold elevations above baseline with similar peak cortisol concentrations. Studies are summarized in which TSST-induced cortisol increases elucidated some of the multiple variables contributing to the interindividual variation in adrenocortical stress responses. The results suggest that gender, genetics and nicotine consumption can influence the individual's stress responsiveness to psychological stress while personality traits showed no correlation with cortisol responses to TSST stimulation. From these data we conclude that the TSST can serve as a tool for psychobiological research.

Adrenal Cortex Hormones↗

Chronic caregiving stress alters peripheral blood immune parameters: the role of age and severity of stress.

BACKGROUND: To examine the impact of chronic psychological stress on the immune system, a series of cellular and humoral immunological parameters was compared in 18 female caregivers of handicapped people and 18 age- and sexmatched controls. METHODS: The immunological parameters included assessment of T cell number (T cells, T helper, and T suppressor/cytotoxic) and function (delayed-type cutaneous hypersensitivity), antibody titers for latent herpesviruses (cytomegalovirus and herpes simplex virus 1 and 2), and markers of inflammation (complement C3 and C4 factors and c-reactive protein). Serum immunoglobulins (IgG, IgM, IgA, IgE) and titers for the nonlatent virus roseola were used to control for nonspecific elevations in serum proteins. Results were associated with the age of the investigated subjects, the severity of stress (family burden) and the degree of disability of the handicapped people. RESULTS: Caregivers had a significantly lower percentage of T cells, a significantly higher percentage of T suppressor/cytotoxic cells and a significantly lower T helper:suppressor ratio. Subjects were also analyzed after division into two groups according to the median age (45 years). Compared to their matched controls, older caregivers (mean age = 50.3) also had lower numbers of T cells and T helper cells and higher antibody titers for cytomegalovirus. In addition, in the caregiver population severity of stress was significantly positively correlated with T suppressor/cytotoxic cells and negatively correlated with T helper:suppressor ratio. No other differneces in the immune parameters were found between caregivers and controls. CONCLUSIONS: The results indicate that psychological stress differentially affects various aspects of the immune system and confirm the relevant role of age and severity of stress in modulating these influences.

Adult↗

Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction.

BACKGROUND: To test the hypothesis that the heat shock response is associated with myocardial salvage, the heat stress protein (HSP) content of cardiac tissue was increased by either ischemic or thermal stress. METHODS AND RESULTS: Rabbits were divided into four groups. Ischemic pretreatment (n = 15) comprised four 5-minute episodes of coronary ligation separated by 10 minutes of reperfusion. The corresponding control group (n = 21) underwent surgical preparation without coronary ligation. Thermal pretreatment (n = 16) involved whole-body temperature elevation to 42 degrees C for 15 minutes; corresponding controls (n = 15) were treated with anesthetic alone. Twenty-four hours later, hearts were removed for HSP estimation or infarct size assessment after a 30-minute coronary ligation. Myocardial HSP72 content assessed by Western blotting was elevated by both ischemic and thermal pretreatments (2.5 +/- 0.2 units, n = 4, and 2.8 +/- 0.3 units, n = 4, mean +/- SEM; P = NS, respectively) compared with the corresponding control groups (1.0 +/- 0.3, n = 4, P < or = .01 and 0.3 +/- 0.1, n = 4, P < or = .01, respectively). HSP60 was preferentially elevated by ischemic pretreatment. After a 30-minute coronary occlusion and 120 minutes of reperfusion, ischemic and thermal pretreatments limited infarct size as a percentage of the volume at risk by 28.8 +/- 5.2% vs 52.0 +/- 5.2%, P < or = .01 and 32.8 +/- 3.8% vs 56.9 +/- 6.5%, P < or = .01, respectively. CONCLUSIONS: Myocardial stress protein induced by either sublethal thermal or ischemic injury is associated with myocardial salvage. Our findings suggest that stress protein elevation, rather than the nonspecific effects of thermal or ischemic stress, may be responsible for the myocardial protection seen in this model. Our observations may have important implications regarding myocardial adaptation to brief periods of ischemia.

Animals↗

Stress radiography and stress examination of the talocrural and subtalar joint on helical computed tomography.

The main objective of this study was to compare subtalar inversion stress views using the Brodén view with inversion stress views on helical computed tomography (CT). One of the drawbacks of routine radiography is the imaging of three-dimensional structures in a two-dimensional plane. We investigated whether the use of helical CT would lead to a more objective and clearer measurable method to determine the amount of tilt in the subtalar joint. A group of 15 patients with unilateral chronic instability complaints and clinically suspected subtalar instability was examined. The contralateral asymptomatic foot was used as control. A variable amount of subtalar tilt (range, 4 degrees to 18 degrees) was demonstrated in all cases on stress radiographs, without finding significant difference between the symptomatic and asymptomatic feet. However, contrary to the findings at the talocrural level, subtalar tilt was found in none of the patients using helical CT. Thus, we now doubt that the tilt seen during stress examination using the Brodén view is the true amount of tilt. It may be that the lateral opening, seen on these radiographs, largely results from imaging two planes that have made a translatory and rotary movement relative to each other in an oblique direction. It is concluded that the Brodén stress examination might not be useful for screening patients with subtalar instability. Associated anomalies not visible on the radiographs were detected by helical CT. In four cases, narrowing of the articular cartilage and irregular and hypertrophic bone formation at the middle facet joint of the subtalar joints were found. It is likely that these changes cause disturbance of function of this joint and it is suggested that the subjective complaint of instability with "giving way" is not only caused by hypermobility, but can be caused by other disturbance of normal motion.

Adolescent↗