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PubMed2002

Shielding, but not zeroing of the ambient magnetic field reduces stress-induced analgesia in mice.

Magnetic field exposure was consistently found to affect pain inhibition (i.e. analgesia). Recently, we showed that an extreme reduction of the ambient magnetic and electric environment, by mu-metal shielding, also affected stress-induced analgesia (SIA) in C57 mice. Using CD1 mice, we report here the same findings from replication studies performed independently in Pisa, Italy and London, ON, Canada. Also, neither selective vector nulling of the static component of the ambient magnetic field with Helmholtz coils, nor copper shielding of only the ambient electric field, affected SIA in mice. We further show that a pre-stress exposure to the mu-metal box is necessary for the anti-analgesic effects to occur. The differential effects of the two near-zero magnetic conditions may depend on the elimination (obtained only by mu-metal shielding) of the extremely weak time-varying component of the magnetic environment. This would provide the first direct and repeatable evidence for a behavioural and physiological effect of very weak time-varying magnetic fields, suggesting the existence of a very sensitive magnetic discrimination in the endogenous mechanisms that underlie SIA. This has important implications for other reported effects of exposures to very weak magnetic fields and for the theoretical work that considers the mechanisms underlying the biological detection of weak magnetic fields.

Analgesia↗

PubMed1991

Job stress in general practice: practitioner age, sex and attitudes as predictors.

South Australian general practitioners (n = 966) provided information in a questionnaire study about four indicators of job stress: the burnout components of emotional exhaustion, depersonalization, and personal accomplishment, and a three-item measure of job dissatisfaction. As job stress can arise from discrepancies between the nature of the work and the expectations of the worker, attitudes to general practice form and content were surveyed, using an existing Australian scale. This study largely replicated the factor structure originally reported for the scale. Up to one third of respondents reported significant levels of job stress, which varied according to age and sex as well as attitudes to general practice.

Adult↗

PubMed2005

Replicative senescence in patients with chronic kidney failure.

BACKGROUND: Chronic activation of immunocompetent cells may lead to stress-induced premature senescence (SIPS); these senescent cells are characterized by a decrease in telomere length. The present study evaluates SIPS in circulating immunocompetent cells from predialysis patients, patients on hemodialysis, and in renal transplant patients with normal renal function. METHODS: Determination of telomere length by flow-fluorescence in situ hybridization (FISH), expression of surface molecules, and evaluation of apoptosis was performed by flow cytometry. RESULTS: In uremic predialysis patients, we observed a subpopulation of lymphocytes with short telomeres. However, in this population of patients we did not observe SIPS mononuclear cells. In hemodialysis patients, we found a subpopulation of SIPS mononuclear cells that also showed phenotypic changes of proinflammatory activity. Finally, transplant patients with normal renal function also exhibited a subpopulation of SIPS lymphocytes, which can be attributed to chronic lymphocyte activation induced by the major histocompatibility complex. CONCLUSION: In chronic kidney disease patients, immunocompetent cells undergo SIPS, a process associated with chronic cell activation and induced by numerous stimuli including uremia, hemodialysis membranes, and bacterial products. Because SIPS immunocompetent cells are activated cells with proinflammatory features and live longer in peripheral blood, it is likely that SIPS cells contribute significantly to the chronic inflammatory state of patients with advanced renal failure.

Apoptosis↗

PubMed1996

Viral infection.

The relationship between viruses and the cellular stress response is a multifaceted and complex phenomenon which depends on the structural and genetic characteristics of the virus, on the type of infection, as well as on the environmental conditions. It is now well documented that infection of mammalian cells by several types of RNA and DNA viruses often results in alterations of the cellular stress response. Interactions between stress proteins and viral components have been described in a large variety of experimental models at different stages of the viral life cycle, depending on the type of virus and host cell. The presence of heat shock proteins in intact virions has also been described. On the other hand, induction of HSP expression by hyperthermia or other agents results in alterations of the virus replication cycle during acute or persistent infections of mammalian cells, and a possible role of heat shock proteins in the beneficial effect of fever and local hyperthermia during acute infection has been hypothesized. This chapter describes the different aspects of the interaction between viruses and the stress response, and discusses the possible role of stress proteins in the control of virus replication and morphogenesis.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Rapid evolution of viral RNA genomes.

Mutation rates during RNA virus replication are several orders of magnitude larger than those operating during replication of cellular DNA. This results in the continuous generation of mutant genomes and in their rating in competition with other variants present and arising in the population. The dynamic mutant distributions that constitute RNA virus populations are termed quasispecies. This concept has facilitated links between population genetics and virology and has a number of important implications for viral pathogenesis and the control of viral disease. One of them is that the mutant spectra in RNA viruses constitute large reservoirs of genetic and phenotypic variants with potentially altered biological properties. Individual mutants kept in a low proportion under a set of environmental conditions may become dominant following an environmental change. Relevant to this review are possible links between the alteration of quasispecies distributions and nutritional deficiencies and oxidative stress in cells. In addition to being a possible mechanism of viral pathogenesis, oxidative stress, and other environmental modifications resulting from nutritional imbalances, may promote population disequilibrium in replicating viruses. In particular, the increased mutagenesis mediated by oxidative DNA damage could also affect replicating RNA and integrated provirus, extending the mutant repertoire of viruses. Also, the impairment of humoral and cellular immune functions may delay or prevent viral clearance, leading to an expanded representation of viral mutants in the infected organism. Thus, nutritional deficiencies are a potential source of viral mutants with altered biological properties.

Biological Evolution↗

PubMed1994

Immune system-central nervous system interactions: effect and immunomodulatory consequences of immune system mediators on the brain.

A bidirectional circuit exists between the central nervous system and the immune system, since activation of the immune system results in the elaboration of cytokines and inflammatory mediators; these mediators induce hypothalamic CRF, which stimulates the release of the same immunosuppressive molecules that mediate the response to stress. The brain, therefore, is likely to be involved in immune system regulation. Hypofunctioning of the HPA axis with insufficient down regulation may be involved in autoimmune or other diseases with excessive immune system activation. Hyperfunctioning of the HPA axis, which is not appropriately suppressed, has been found in a large number of patients with major depression. Evidence that stress is an important factor in both lowering resistance to infectious agents and contributing to the reactivation of latent viruses is discussed. Also discussed is the evidence that stress induces proinflammatory cytokines which may contribute to both the pathogenesis of inflammatory diseases of unknown etiology and the progression of HIV infection to AIDS by activation of HIV replication.

Adjuvants, Immunologic↗

PubMed1981

The ecology of anxiety: situational stress and rate of self-stimulation in Turkey.

Twelve community behavior settings in Ankara, Turkey, were ranked with high agreement by 30 judges (average r = .80, p less than .001) according to the amount of situational stress, defined as evaluative apprehension and uncertainty, generated by each setting. The rate of hand-to- face or body (self-stimulation) behavior was observed systemically in stressful compared to relaxed settings. Analysis by a stepwise multiple regression procedure showed higher rates in stressful settings, F(1, 587) = 9.33, p less than .01. This finding was successfully replicated one year after the original study with new samples of settings, observers, and observed individuals, F(1, 351) = 7.38, p less than .01. Sex of the observed individuals had no relationship to rate of self-stimulation, and smoking appeared to act as a suppressor variable. These results suggest that other sources of variance from persons and Person X Situation interactions can be safely ignored if one's purpose in an investigation is to make ecological comparisons in anxiety rates.

Anxiety↗

PubMed1988

[Correlates of disordered sleep: a replication study].

90 good and 106 bad sleepers were compared in respect to sleep quality and quantity as well as to several other aspects of life. Several questionnaires were used to measure sleep and day time behavior. In addition, a newly developed sleep questionnaire, containing 60 items, was used and factor analysed. The three resulting factors were "helplessness", "distress" and "attitude about sleep". The comparisons between good and poor sleepers showed that stress and insufficient coping skills contribute to the maintenance of sleeping disorders. These results represent a successful replication of a previous study. The comparisons between the different subclasses of sleep disorders showed a few differences, but essentially the conclusions are true for all of the three kinds of sleep disorders. Consequences for the target areas addressed in the treatment of sleep disorders are discussed.

Adaptation, Psychological↗

PubMed2002

Explant-induced reactivation of herpes simplex virus occurs in neurons expressing nuclear cdk2 and cdk4.

Herpes simplex virus (HSV) establishes productive (lytic) infections in nonneuronal cells and nonproductive (latent) infections in neurons. It has been proposed that HSV establishes latency because quiescent neurons lack cellular factors required for productive infection. It has been further proposed that these putative factors are induced following neuronal stress, as a requirement for HSV reactivation. To date, the identity of these putative cellular factors remains unknown. We have demonstrated that cyclin-dependent kinase (cdk) 1, 2, or 7 is required for HSV replication in nonneuronal cells. Interestingly, cdks 1 and 2 are not expressed in quiescent neurons but can be induced in stressed neurons. Thus, cdks may be among the cellular proteins required for HSV reactivation whose neuronal expression is differentially regulated during stress. Herein, we determined that neuronal expression of nuclear cdk2, cdk4, and cyclins E and D2 (which activate cdks 2 and 4, respectively) was induced following explant cultivation, a stressful stimulus that induces HSV reactivation. In contrast, neuronal expression of cdk7 and cytoplasmic cdk4 decreased during explant cultivation, whereas cdk3 was detected in the same small percentage of neurons before and after explant cultivation and cdks 1, 5, and 6 were not detected in neuronal cell bodies. HSV-1 reactivated specifically in neurons expressing nuclear cdk2 and cdk4, and an inhibitor specific for cdk2 inhibited HSV-1 reactivation. We conclude that neuronal levels of cdk2 are among the factors that determine the outcome of HSV infections of neurons.

Animals↗

PubMed1989

Adrenergic urticaria: a first report from Thailand.

A 22-year-old, female patient came to see the allergists because of a 10-year history of chronic urticaria. Widespread pruritic, urticarial papules developed at times of stress and exercise, each papule being surrounded by a striking blanched vasoconstricted halo. The halo hives could be replicated with an intradermal injection of adrenaline. This is the first report of adrenergic urticaria from Thailand.

Adrenergic beta-Antagonists↗

PubMed1999

Heat stress activates production of herpes simplex virus type 1 from quiescently infected neurally differentiated PC12 cells.

We have previously described a novel in vitro model of a non-productive herpes simplex virus type 1 (HSV-1) infection in neurally differentiated (Nd)-PC12 cells that allows for inducible virus replication upon forskolin treatment. In this study, we further characterized the quiescent state of infection and examined the ability of heat stress (HS) to induce virus from this non-productive state. These studies demonstrated that (i) the quiescent state is characterized by the absence of cell-associated virus, capsids, and viral antigens; (ii) HS (43 degrees C, 3 h) efficiently activated virus from quiescently infected Nd-PC12 (QIF-PC12) cells; (iii) the rate of virus production was significantly greater following HS than forskolin treatment, and the rates of both were dependent on MOI; (iv) forskolin and HS appeared to affect pathways of viral activation from a quiescent state as they did not enhance viral growth in Nd-PC12 cells; (v) viral alpha4 gene and host HSP72 gene transcription were rapidly induced in QIF-PC12 as soon as 3 h post-HS initiation; (vi) induction of the viral alpha27 gene followed that of representative beta and gamma genes, U(L)30 and U(L)18, respectively, and (vii) HS induced asynchronous HSV-1 replication from QIF-PC12 cells with 1:400 to 1:22000 positive foci detected as rapid as 24 h post-induction when established at MOIs of 30 and 3, respectively. These findings provide evidence that alpha4 may be involved in the switch from quiescence to productive infection. Furthermore, this model has the potential to advance our understanding of how HS initiates the HSV-1 productive cycle from a cryptic viral genome.

Animals↗

PubMed1999

Mechanisms of cytokine-mediated inhibition of viral replication.

In this report, the role of nitric oxide synthase (NOS) and IL-12 administration in inhibition of vesicular stomatitis virus (VSV) from infected neuroblastoma cells was examined. We previously have shown that cytokine treatment of cells results in the induction of NOS-1, and this is associated with a 2 log inhibition of VSV production. We performed these studies to examine the mechanism by which viral replication is suppressed. Neuroblastoma cells (NB41A3) were treated with either IL-12 or medium and subsequently infected with VSV. Viral protein and mRNA were isolated from these cells, and their levels were measured by Western or Northern blots, respectively. mRNA levels were decreased modestly, but viral proteins were decreased substantially in cells pretreated with IL-12, suggesting that the inhibitory effect of NO is working at the translational level. Cytokine treatment of cells was not associated with oxidative stress. The viral proteins also were nitrosylated. These data suggest that the mechanism of NO inhibition of viral replication occurs through translational interference and posttranslational modifications of viral components.

Blotting, Northern↗

PubMed1999

TNFalpha, interferon, and stress response induction as a function of age-related susceptibility to fatal Sindbis virus infection of mice.

The age-related acquisition of resistance to fatal Sindbis virus infection was examined using a molecularly cloned laboratory strain of the AR339 isolate designated TRSB. TRSB caused 100% mortality in mice up to 5 days of age. Resistance to fatal infection developed abruptly between 5 and 9 days of age. Lethal Sindbis virus infection of mice inoculated at 4 days of age was characterized by high levels of virus replication, induction of high levels of interferon-alpha/beta and TNF-alpha and severe thymic involution indicative of a systemic stress response. These changes correlated with predominantly noninflammatory lesions. In contrast, TRSB infection of older mice was characterized by survival, more limited virus replication, reduced cytokine induction, and the development of inflammatory responses leading to encephalitis, myositis, and myocarditis. Previous studies utilized infections of neonatal mice with TRSB and an attenuated mutant of TRSB to compare fatal and nonfatal Sindbis infection (Trgovcich et al., 1996. Virology 224, 73-83). The experiments reported here utilize mouse age at the time of infection to create conditions for examination of fatal and nonfatal TRSB infections. Both experiments suggest that fatal infection is associated with a shock-like syndrome and little or no inflammatory pathology, while survival is correlated with greatly reduced cytokine levels and inflammatory lesions.

Aging↗

PubMed1998

Hypoxic stimulation of the stress-activated protein kinases in pulmonary artery fibroblasts.

Pulmonary hypertension in response to chronic hypoxia is invariably accompanied by remodeling of the pulmonary vessels but the mechanism by which hypoxia increases the replication of vascular cells is unknown. To investigate the hypothesis that hypoxia stimulates intracellular kinase cascades we measured the activity of "classic" mitogen-activated protein (MAP) kinase pathways and "stress- activated" MAP kinase pathways in bovine pulmonary artery fibroblasts subjected to hypoxia for up to 30 h. Hypoxia (1% O2) stimulated strongly the stress-activated protein kinases, c-Jun NH2-terminal kinase (JNK) and p38 MAP kinase. Two peaks of p38 MAP kinase activity at 6 and 24 h were associated with an increase in the activity of mitogen-activated protein kinase-activated protein (MAPKAP) kinase-2, the immediate downstream target of p38 MAP kinase. Furthermore, the second phase of p38 MAP kinase activity could be reversed if cells were reoxygenated after 12 h. These data suggest that hypoxic stimulation of pulmonary artery cells is mediated by activation of the stress-activated protein kinases.

Animals↗

PubMed2001

Polymerization contraction stress in light-cured packable composite resins.

OBJECTIVE: Determination of the polymerization contraction stress of packable composites (ALERT, Surefil, Solitaire, Solitaire 2) and a packable ORMOCER material (Definite) in comparison with a conventional hybrid composite (Tetric Ceram). METHODS: Contraction force generated by the test materials (10 replications each) was measured by polymerizing the composites filled in a plastic tray between two aluminum attachments mounted in a Stress-Strain-Analyzer testing machine (specimen size: 4x4x2 mm, C-factor=0.33). Contraction force was recorded for 300s under a standard exposure condition (40s, 800mW/cm(2)). Maximum contraction stress (MPa), force rate (N/s), relative force rate (%/s) of each material were statistically analyzed by ANOVA (alpha=0.05) and post-hoc Tukey's test. RESULTS: Maximum contraction stresses of the packable materials were 4.60 +/- 0.32MPa (ALERT), 4.16 +/- 0.18MPa (Definite), 3.36 +/- 0.08MPa (Solitaire 2), 3.33 +/- 0.23MPa (Solitaire) and 3.13 +/- 0.18MPa (Surefil), which were significantly higher than that of Tetric Ceram (2.51 +/- 0.14MPa). Tetric Ceram exhibited the significantly lowest force rate. Force/time curves were S-shaped. Solitaire especially showed a longer pre-gelation phase before contraction force was recorded. SIGNIFICANCE: High contraction stress and rapid contraction force development can lead to failure of bond to tooth structure. This study suggested that, packable composite resins are less capable of reducing the contraction stress during the early setting stage, thus not superior in maintaining the bond with cavity walls to conventional hybrid composite Tetric Ceram.

Analysis of Variance↗

PubMed2005

Bloom syndrome, genomic instability and cancer: the SOS-like hypothesis.

Bloom syndrome (BS) displays one of the strongest known correlations between chromosomal instability and an increased risk of malignancy at an early age. The prevention of genomic instability and cancer depends on a complex network of pathways induced in response to DNA damage and stalled replication forks, including cell-cycle checkpoints, DNA repair, and apoptosis. Several studies have demonstrated that BLM is involved in the cellular response to DNA damage and stalled replication forks. BLM interacts physically and functionally with several proteins involved in the maintenance of genome integrity and BLM is redistributed and/or phosphorylated in response to several genotoxic stresses. The data concerning the relationship between BLM and these cellular pathways are summarized and the role of BLM in the rescue of arrested replication forks is discussed. Moreover, I speculate that BLM deficiency is lethal, and that BLM-deficient cells escaping apoptotic death do so by constitutively inducing a bacterial SOS-like response including the induction of alternative replication pathway(s) dependent on recombination, contributing to the mutator and hyper-Rec phenotypes characteristic of BS cells. This mechanism may be dependent on the RAD51 gene family, and involved in carcinogenesis in the general population.

Adenosine Triphosphatases↗

PubMed2003

A preliminary investigation into light-modulated replication of nanobacteria and heart disease.

OBJECTIVE: The purpose of this preliminary study is to evaluate the effect of various wavelengths of light on nanobacteria (NB). BACKGROUND DATA: NB and mitochondria use light for biological processes. NB have been described as multifunctional primordial nanovesicles with the potential to utilize solar energy for replication. NB produce slime, a process common to living bacteria. Slime release is an evolutionary important stress-dependent phenomenon increasing the survival chance of individual bacteria in a colony. In the cardiovascular system, stress-induced bacterial colony formation may lead to a deposition of plaque. METHODS: Cultured NB were irradiated with NASA-LEDs at different wavelengths of light: 670, 728 and 880 nm. Light intensities were about 500k Wm(-2), and energy density was 1 x 10(4) J m(-2). RESULTS: Monochromatic light clearly affected replication of NB. Maximum replication was achieved at 670 nm. CONCLUSIONS: The results indicate that suitable wavelengths of light could be instrumental in elevating the vitality level of NB, preventing the production of NB-mediated slime, and simultaneously increasing the vitality level of mitochondria. The finding could stimulate the design of cooperative therapy concepts that could reduce death caused by myocardial infarcts.

Bacteria↗

PubMed2004

Effects of the C4'-oxidized abasic site on replication in Escherichia coli. An unusually large deletion is induced by a small lesion.

The C4'-oxidized abasic site (C4-AP) is produced in DNA as a result of oxidative stress by a variety of agents. For instance, the lesion accounts for approximately 40% of the DNA damage produced by the antitumor antibiotic bleomycin. The effect of C4-AP on DNA replication in Escherichia coli was determined using the restriction endonuclease and postlabeling (REAP) method. Three-nucleotide deletion products are the sole products observed following replication of plasmids containing C4-AP under SOS conditions in wild-type cells. Full-length products are formed in varying amounts depending upon the local sequence in wild-type cells under non-SOS-induced conditions. The "A-rule" is followed for the formation of substitution products. C4-AP is the first example of a DNA lesion that produces significant levels of three-nucleotide deletions in a variety of sequence contexts. Experiments carried out in cells lacking specific polymerases reveal that formation of three-nucleotide deletion products results from a coordinated effort involving pol II and pol IV. This is the first example in which these SOS inducible polymerases are shown to work in concert during lesion bypass. Three-nucleotide deletions are not observed during the replication of other abasic lesions, and are rarely produced by bulky adducts. The effect of C4-AP on DNA replication suggests a significant role for this lesion in the cytotoxicity of bleomycin. Formation of the C4-AP lesion may also be responsible for the formation of mutant proteins containing single-amino acid deletions that exhibit altered phenotypes.

Apurinic Acid↗