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Not only osmotic stress but also repeated restraint stress causes structural plasticity in the supraoptic nucleus of the rat hypothalamus.

Magnocellular neuroendocrine cells (MNCs) in the supraoptic nucleus (SON) of the hypothalamus have been known to undergo dramatic structural changes during chronic stimulation such as osmotic stress. In the present study, we examined whether this anatomical neural plasticity is associated with an another stress, such as restraint. Rats were chronically stimulated by either dehydration with 2% saline drinking instead of water or daily restraint with leg immobilization. The structural reorganizations of MNCs in the SON were analyzed morphometrically with use of light and electron microscopy. The results were compared to control animals that had free access to water and food. In restraint rats, the soma size of both oxytocin (OXT) and arginine vasopressin (AVP) neurons was enlarged, and the percent of soma-somatic/dendritic membrane contact (juxtaposition) was elevated significantly. The number of total synapses per 100 microns soma membrane was not changed, although soma profiles were enlarged. However, the number of multiple synapses (which contacted with more than one postsynaptic element) per 100 microns soma membrane was significantly increased. Similar structural changes were observed in dehydrated animals, and the degree of morphological changes was stronger than the restraint one. These findings indicate that NMCs undergo structural plasticity during not only osmotic stress but also restraint stress.

Animals↗

DNA damage and stress protein synthesis induced by oxidative stress proceed independently in the human premonocytic line U937.

Heat shock proteins (HSPs) function as stress-inducible molecular chaperones and exert protective effects against cellular injury. The induction of the HSPs is considered to be mediated by the presence of abnormal proteins within the cell and/or by classical second messengers. Several lines of evidence have however suggested a relationship between DNA damage, HSP induction and thermotolerance. We investigated whether DNA alterations could represent a common signal for the induction of stress protein synthesis during heat shock or exposure to reactive oxygen species in the human premonocytic line U937. We measured, in parallel, DNA damage (both strand breaks and fragmentation) and HSP synthesis (by biometabolic labeling and Western blotting) after exposure to heat shock, hydrogen peroxide, bleomycin, cadmium or erythrophagocytosis. Heat shock induced DNA alterations along with HSP synthesis. In contrast, exposure to hydrogen peroxide or bleomycin induced DNA damage, but no HSP synthesis, suggesting that oxidation-induced DNA damage and HSP synthesis proceed independently in U937 cells. Erythrophagocytosis and cadmium induced the classical HSPs but no detectable DNA damage. Since these latter stresses also induced the oxidation-specific stress protein heme oxygenase, we suggest a protective role for heme oxygenase against oxidative DNA damage.

Bleomycin↗

Myocardial blood volume and perfusion reserve responses to combined dipyridamole and exercise stress: a quantitative approach to contrast stress echocardiography.

BACKGROUND: Qualitative interpretation of myocardial contrast echocardiography (MCE) improves the accuracy of wall-motion analysis for assessment of coronary artery disease (CAD). We examined the feasibility and accuracy of quantitative MCE for diagnosis of CAD. METHODS: Dipyridamole/exercise stress MCE (destruction-replenishment protocol with real-time imaging) was performed in 90 patients undergoing quantitative coronary angiography, 48 of whom had significant (> 50%) stenoses. MCE was repeated with exercise alone in 18 patients. Myocardial blood flow (A*beta) was obtained from blood volume (A) and time to refill (beta). RESULTS: Quantification of flow reserve was feasible in 88%. The mean A*beta reserve in the anterior wall was significantly impaired for patients with left anterior descending coronary artery disease (n = 28) compared with those with no disease (1.6 +/- 1.2 vs 4.0 +/- 2.5, P < or = .001). This reflected impaired beta reserve, with no difference in the A reserve. Applying a receiver operating characteristic curve derived cutoff of 2.0 for A*beta reserve, quantitative MCE was 76% sensitive and 71% specific for the diagnosis of significant left anterior descending coronary artery stenosis. Posterior circulation results were similar, with 78% sensitivity and 59% specificity for detection of posterior CAD. Overall, quantitative MCE was similarly sensitive to qualitative approach for diagnosis of CAD (88% vs 93%), but with lower specificity (52% vs 65%, P = .07). In 18 patients restudied with pure exercise stress, the mean myocardial blood flow reserve was less than after combined stress (2.1 +/- 1.6 vs 3.7 +/- 1.9, P = .01). CONCLUSION: Quantitative MCE is feasible for the diagnosis of CAD with dipyridamole/exercise stress. Dipyridamole prolongs postexercise hyperemia, augmenting the degree of hyperemia at the time of imaging.

Blood Volume Determination↗

Assessment of coronary artery disease in women by dobutamine stress echocardiography: comparison with stress thallium-201 single-photon emission computed tomography and exercise electrocardiography.

BACKGROUND: Dobutamine stress echocardiography (DSE) is sensitive and specific in detecting myocardial ischemia of male patients. However, there have been few reports about the use of DSE for the detection of coronary artery disease (CAD) in women. METHODS: DSE was evaluated in 51 consecutive women who underwent concomitant quantitative coronary angiography. Forty-four of the 51 patients received stress thallium-201 single-photon emission computed tomography (SPECT), and 30 of the 51 patients had interpretable results (exercise level > or = 85% of age-predicted maximal heart rate) of treadmill exercise. Twenty-nine patients had angiographically documented CAD defined as > or = 50% diameter stenosis. RESULTS: The overall sensitivity of DSE and stress 201Tl SPECT in detecting CAD was 93% and 79% (p = nonsignificant), and the specificity was 82% and 75% (p = nonsignificant), respectively. A combination of both tests increased the sensitivity (96%) at the expense of some decrease in specificity (60%). The agreement of DSE and 201Tl SPECT was 68% (30 of 44; kappa statistic = 0.35; p < 0.0001). The overall sensitivity, specificity, and accuracy in detecting CAD by treadmill exercise test and DSE were 71% vs 93% (p = nonsignificant), 44% vs 82% (p = 0.036), and 57% vs 88% (p = 0.003). In patients with abnormal results of treadmill exercise testing, the false-positive rate in detecting CAD was 2 (18%) of 11 in patients with abnormal results of DSE and 7 (88%) of 8 in those with normal results of DSE (p = 0.005). In patients with normal results of treadmill exercise testing, the false-negative rate in detecting CAD was 4 (100%) of 4 in patients with abnormal results of DSE and 0 (0%) of 7 in those with normal results of DSE (p = 0.003). CONCLUSION: The diagnostic accuracy of DSE was similar to that of stress 201Tl SPECT in women. DSE was able to stratify female patients with either abnormal or normal results of treadmill exercise testing and to avoid unnecessary cardiac catheterization.

Cardiotonic Agents↗

Pacing stress echocardiography: an alternative to pharmacologic stress testing.

OBJECTIVES: We sought to evaluate the diagnostic accuracy and feasibility of bedside pacing stress echocardiography (PASE) as a potential substitute for pharmacologic stress echocardiography in patients admitted to the hospital with new-onset chest pain or worsening angina pectoris. BACKGROUND: Accurate and rapid noninvasive identification and evaluation of the extent of coronary artery disease (CAD) is essential for optimal management of these patients. METHODS: Bedside transthoracic stress echocardiography was performed in 54 consecutive patients admitted to a community hospital with new-onset chest pain, after acute myocardial infarction had been excluded. We used 10F transesophageal pacing catheters and a rapid and modified pacing protocol. The PASE results were validated in all patients by coronary angiography performed within 24 h of the test. Significant CAD was defined as > or =75% stenosis in at least one major epicardial coronary artery. RESULTS: The sensitivity of PASE for identifying patients with significant CAD was 95%, specificity was 87% and accuracy was 92%. The extent of significant CAD (single- or multivessel disease) was highly concordant with coronary angiography (kappa = 0.73, p<0.001). Pacing stress echocardiography was well tolerated, and only 4% of the patients had minor adverse events. The mean rate-pressure product at peak pacing was 22,313+/-5,357 beats/min per mm Hg, and heart rate >85% of the age-predicted target was achieved in 94% of patients. The average duration of the bedside PASE test, including image interpretation, was 38+/-6 min. CONCLUSIONS: Bedside PASE is rapid, tolerable and accurate for identification of significant CAD in patients admitted to the hospital with new-onset chest pain or worsening angina pectoris.

Aged↗

Cross-stress tolerance and expression of stress-related proteins in osmotically desiccated entomopathogenic Steinernema feltiae IS-6.

Infective juveniles (IJs) of the entomopathogenic nematode (EPN) Steinernema feltiae IS-6 can survive exposure to 24% glycerol solution by entering an osmotically desiccated state. Exposure of osmotically desiccated nematodes to extreme temperature assays (40 degrees C for 10 h and -20 degrees C for 360 h) resulted in gradual reduction in survival, whereas non-desiccated IJs died within a short exposure to the assay conditions. Through SDS-PAGE, a stress-related protein UNC-87 was found in osmotically desiccated IJs exposed to 40 degrees C for 3, 6, and 8 h, whose survival rates were 98.9+/-1.43, 78.5+/-5.87 and 20.9+/-4.93%, respectively. The protein was not found in IJs following exposure of osmotically desiccated individuals to 40 degrees C for 10 h, in which none of the IJs survived. After exposure to -20 degrees C for 360 h, the survival of osmotically desiccated EPNs with a weak band of UNC-87 was 13.0+/-3.32%. To identify other responsive proteins that are required for osmotic stress, we used 2-dimensional electrophoresis to analyse the proteins in osmotically desiccated EPNs. The results revealed that 10 novel protein spots and 10 up-regulated protein spots in osmotically desiccated IJs were detected by digital image analysis. Mass spectrometry analysis of 7 significant spots indicated that osmotic stress in desiccated IJs was associated with the induction of actin, Proteasome regulatory particle (ATPase-like), GroEL chaperonin, GroES co-chaperonin and transposase family member. It seems to show actin, UNC-87 and Proteasome regulatory particle may play distinct roles in specific aspects of organization of macromolecular structures under desiccation stress. GroEL and GroES are members of the Hsp60 family of chaperons.

Amino Acid Sequence↗

Up-regulation of PTEN (phosphatase and tensin homolog deleted on chromosome ten) mediates p38 MAPK stress signal-induced inhibition of insulin signaling. A cross-talk between stress signaling and insulin signaling in resistin-treated human endothelial cells.

The key feature of metabolic syndrome, a cluster of metabolic and cardiovascular disorders, is systemic insulin resistance, which is associated with dysregulated endothelial nitric-oxide synthase (eNOS). Stress signaling induced by inflammation can inhibit insulin signaling. However, molecular mechanisms for the cross-talk between stress signaling and insulin resistance are only partially understood. Resistin, an adipokine/cytokine, is involved in inflammatory processes that could lead to insulin resistance status and vascular diseases. In the current study, we observed that resistin inhibited insulin signaling and eNOS activation in endothelial cells. Up-regulation of PTEN (phosphatase and tensin homolog deleted on chromosome ten) expression by resistin may mediate the inhibitory effects. Activated stress signaling p38 MAPK, but not JNK, is involved in PTEN up-regulation. We further found that p38 target transcriptional factor activating transcription factor-2 (ATF-2) bound to ATF sites in the PTEN promoter. The phosphorylation/activation of ATF-2 and its binding to PTEN promoter were increased by resistin treatment. In summary, up-regulation of PTEN is involved in the inhibitory effects of resistin on insulin signaling and eNOS activation in endothelial cells. Resistin induces PTEN expression by activating stress signaling p38 pathway, which may activate target transcription factor ATF-2, which in turn induces PTEN expression. Our findings suggest that resistin-mediated inhibition of insulin signaling and eNOS activation may contribute to cardiovascular diseases.

Activating Transcription Factor 2↗

Stress protein CSP 310 causes oxidation and phosphorylation uncoupling during low-temperature stress only in cereal but not in dycotyledon mitochondria.

It was found that an addition of antiserum obtained against stress protein 310 kD increased coupling of oxidation and phosphorylation in mitochondria isolated from cold-stress winter rye shoots and had no influence on dycotiledon mitochondria (pumpkins and sunflower). The data obtained showed a difference between molecular weights of dycotyledon polypeptides with immunochemical affinity to CSP 310 and CSP 310 subunits. It was shown that low-temperaturestress caused a transition to a low-energy state ("cold uncoupling") of free from endogenous free fatty acid cereal mitochondria. At the same time, this "cold uncoupling" in mitochondria of dycotyledon species investigated was not detected. We suppose that a special mechanism of low-temperature stress reaction in mitochondria dealing with uncoupling activity of stress protein CSP 310 exists in cereals.

Blotting, Western↗

Mutualism based on stress: selective synthesis and phosphorylation of a stress protein by an intracellular symbiont.

The effects of a temperature shift-up and various metabolic inhibitors on the protein synthesis of an endosymbiont isolated from the pea aphid were studied. The syntheses of at least three major polypeptides were stimulated transiently immediately after a temperature shift-up, and treatment with ethanol and heavy metals (Cd2+ and As2+). One of these proteins, the 63 kDa heat-shock protein (63-kDa HSP), was immunoprecipitated with antiserum raised against symbionin, which is selectively synthesized by the endosymbiont harbored by the aphid bacteriocytes. The 63 kDa heat-shock protein has a molecular mass of 800 kDa and is more acidic than symbionin. It was also shown that symbionin is subject to phosphorylation in vivo and in vitro after a temperature shift-up. It was thought likely that forms of environmental stress such as heat shock and metabolic inhibitors stimulate the synthesis of a phosphorylated form of symbionin. It was also suggested that the in vitro phosphorylation of symbionin is due to its own catalytic activity. Since symbionin is a homolog of the Escherichia coli groEL protein, a stress protein, it is likely that the endosymbiont suffers stress when harbored by the bacteriocytes and responds in a similar manner to environmental stress when outside these cells.

Animals↗

The effects of mindfulness-based stress reduction on nurse stress and burnout: a quantitative and qualitative study.

Mindfulness-based Stress Reduction, a stress-reduction program, has increasing empirical support as a patient-care intervention. Its emphasis on self-care, compassion, and healing makes it relevant as an intervention for helping nurses manage stress and reduce burnout. This article describes the implementation of Mindfulness-based Stress Reduction in a hospital system as a way to lower burnout and improve well-being among nurses, using both quantitative and qualitative data.

Adult↗

Stress, sources of stress and ways of coping among psychiatric nursing students.

This study measured levels of distress, sources of stress and ways of coping of a convenience sample of psychiatric nursing students (n = 35). Instruments used were the 30-item General Health Questionnaire, the Jones and Johnson (1997) Student Nurse Stress Index, Parkes (1985) Ways of Coping Questionnaire and a demographic questionnaire. Findings revealed that all students were significantly distressed, exceeding a conventional cut-off score of 5 on the 30-item General Health Questionnaire. Students were found to have limited coping skills. Preparing to become a nurse in this setting was found to be significantly emotionally stressful and a possible risk to the well-being of students. This study provides a baseline from which to address the problem of stress among diplomate psychiatric nursing students.

Adaptation, Psychological↗

Differential mRNA translation contributes to gene regulation under non-stress and dehydration stress conditions in Arabidopsis thaliana.

Translational regulation was evaluated for over 2000 genes by measurement of the proportion of individual mRNA species in polysomal (PS) complexes in leaves of non-stressed and moderately dehydration-stressed Arabidopsis. The amount of each mRNA in polysomes ranged from 23 to 97% in non-stressed leaves and was significantly reduced for a large portion of the genes (71%) in response to dehydration. The effect of dehydration on translational status varied extensively between mRNA species. Sixty per cent of the dehydration-inducible mRNAs with twofold or greater increase in abundance maintained PS levels in response to water-deficit stress, while 40% showed impaired ribosome loading (RL). PS association declined significantly for 92% of the mRNAs that displayed a strong decrease in abundance, indicating a relationship between translation and decreased gene transcription and/or mRNA stability. Interestingly, many mRNAs that encode proteins of similar biological function displayed coordinate translational regulation. Thus, the abundance of PS mRNA may provide a more accurate estimate of gene expression than total cellular mRNA because of extensive differential translational regulation.

Arabidopsis↗

A novel high-throughput genetic screen for stress-responsive mutants of Arabidopsis thaliana reveals new loci involving stress responses.

Activation sequence-1 (as-1) cognate promoter elements are widespread in the promoters of plant defense-related genes as well as in plant pathogen promoters, and may play important roles in the activation of defense-related genes. The as-1-type elements are highly responsive to multiple stress stimuli such as jasmonic acid (JA), salicylic acid (SA), H(2)O(2), xenobiotics and heavy metals, and therefore provide a unique opportunity for identifying additional signaling components and cross-talk points in the various signaling networks. A single as-1-type cis-element-driven GUS reporter Arabidopsis line responsive to JA, SA, H(2)O(2), xenobiotics and heavy metals was constructed for mutagenesis. A large-scale T-DNA mutagenesis has been conducted in the reporter background, and an efficient high-throughput mutant screen was established for isolating mutants with altered responses to the stress chemicals. A number of mutants with altered stress responses were obtained, some of which appear to identify new components in the as-1-based signal transduction pathways. We characterized a mutant (Delta8L4) with a T-DNA insertion in the coding sequence of the gene At4g24275. The as-1-regulated gene expression and GUS reporter gene expression were altered in the Delta8L4 mutant, but there was no change in the expression of genes lacking as-1 elements in their promoters. The phenotype observed with the Delta8L4 mutant was further verified using RNAi plants for At4g24275 (8L4-RNAi), suggesting the feasibility of use of this high-throughput mutant screening in isolating stress-signaling mutants.

Arabidopsis↗

Single injection thallium-201 stress and redistribution myocardial perfusion imaging: comparison with stress electrocardiography and coronary arteriography.

The efficacy of single injection thallium-201 exercise stress and rest redistribution imaging in the evaluation of myocardiacl ischemia was compared with stress electrocardiography and coronary arteriography. Thallium-201 imaging was interpreted at two levels of sensitivity in order to define the circumstances under which it best serves as a screening modality for coronary arteriography. With the prevalence of coronary disease usually found in patients referred for coronary arteriography (75%), unprocessed thallium-201 imaging is as good as stress electrocardiography in identifying patients apt to show coronary artery abnormalities, but not much better than stress electrocardiography in delineating those patients unlikely to show coronary artery disease. In contrast, processed lesion enhanced images showing normal results virtually eliminate the possibility of significant arteriographic findings. With this screening technique, many patients may be spared unnecessary coronary arteriography.

Adult↗

Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocardiography.

BACKGROUND: The analysis of wall motion abnormalities with dobutamine stress echocardiography (DSE) is an established method for the detection of myocardial ischemia. With ultrafast magnetic resonance tomography, identical stress protocols as used for echocardiography can be applied. METHODS AND RESULTS: In 208 consecutive patients (147 men, 61 women) with suspected coronary artery disease, DSE with harmonic imaging and dobutamine stress magnetic resonance (DSMR) (1.5 T) were performed before cardiac catheterization. DSMR images were acquired during short breath-holds in 3 short-axis views and a 4- and a 2-chamber view (gradient echo technique). Patients were examined at rest and during a standard dobutamine-atropine scheme until submaximal heart rate was reached. Regional wall motion was assessed in a 16-segment model. Significant coronary heart disease was defined as >/=50% diameter stenosis. Eighteen patients could not be examined by DSMR (claustrophobia 11 and adipositas 6) and 18 patients by DSE (poor image quality). Four patients did not reach target heart rate. In 107 patients, coronary artery disease was found. With DSMR, sensitivity was increased from 74.3% to 86.2% and specificity from 69.8% to 85.7% (both P<0.05) compared with DSE. Analysis for women yielded similar results. CONCLUSIONS: High-dose dobutamine magnetic resonance tomography can be performed with a standard dobutamine/atropine stress protocol. Detection of wall motion abnormalities by DSMR yields a significantly higher diagnostic accuracy in comparison to DSE.

Aged↗

Induction of a ribotoxic stress response that stimulates stress-activated protein kinases by 13-deoxytedanolide, an antitumor marine macrolide.

13-Deoxytedanolide is a structurally unique macrolide with strong antitumor activity isolated from a marine sponge. Recently, we showed that 13-deoxytedanolide bound to the large subunit of the yeast ribosome and inhibited polypeptide elongation in vitro, but the mechanism by which it exerts antitumor activity is still unknown. Here we show that 13-deoxytedanolide strongly induces plasminogen activator inhibitor 1 (PAI-1) promoter-derived gene expression. 13-Deoxytedanolide, unlike TGF-beta, did not cause apparent nuclear translocation of Smad2/3, but it relocalized the temperature-sensitive mutant of mouse p53 (p53Val153) from the cytoplasm to the nucleus at a nonpermissive temperature, suggesting that 13-deoxytedanolide inhibits protein synthesis. Indeed, the drug inhibited in vivo protein synthesis at low nanomolar concentrations and strongly activated stress-activated protein kinases such as p38 mitogen-activated protein kinase and Jun NH2-terminal protein kinase (JNK). Anisomycin, a well-known inducer of ribotoxic stress that activates both p38 and JNK, also activated PAI-1 gene expression, while other protein synthesis inhibitors that do not activate the kinases failed to do so. PAI-1 gene expression by 13-deoxytedanolide and anisomycin was blocked by SB202190, a specific inhibitor of p38, and SP600125, an inhibitor of both p38 and JNK. 13-Deoxytedanolide and anisomycin caused activation of apoptosis signal-regulating kinase 1, MKK3/MKK6, and SEK1/MKK4, the regulatory kinases upstream of p38 and JNK. These results suggest that 13-deoxytedanolide, like anisomycin, triggers a ribotoxic stress response that activates stress-activated protein kinase cascades, thereby inducing PAI-1 gene expression and apoptosis.

Animals↗

Simple approach to determining the minimum measurable stress length and stress measurement accuracy in distributed Brillouin sensing.

A simple approach is proposed for quantifying the errors in measuring the Brillouin frequency shifts associated with stresses whose lengths are shorter than the pulse length. The smallest detectable Brillouin frequency shift is thus determined with respect to the size of the stressed sections and the frequency resolution. The lowest detectable frequency shift is found to be approximately 42% of the Brillouin gain natural linewidth. A worst-case iso-error curve that associates the minimum frequency shift to the length of the stressed region is derived. A minimum resolvable frequency shift and minimum detectable stress length are defined with an approach based on a Rayleigh equivalent criterion.

Journal Article↗

Stress induction of Bm1 RNA in silkworm larvae: SINEs, an unusual class of stress genes.

This study surveys the induction of RNA polymerase III (Pol III)-directed expression of short interspersed element (SINE) transcripts by various stresses in an animal model, silkworm larvae. Sublethal heat shock and exposure to several toxic compounds increase the level of Bm1 RNA, the silkworm SINE transcript, while also transiently increasing expression of a well-characterized stress-induced transcript, Hsp70 messenger RNA (mRNA). In certain cases, the Bm1 RNA response coincides with that of Hsp70 mRNA, but more often Bm1 RNA responds later in recovery. Baculovirus infection and exposure to certain toxic compounds increase Bm1 RNA but not Hsp70 mRNA, showing that SINE induction is not necessarily coupled to transcription of this particular heat shock gene. SINEs behave as an additional class of stress-inducible genes in living animals but are unusual as stress genes because of their high copy number, genomic dispersion, and Pol III-directed transcription.

Animals↗