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At least 595 records · Page 33Linked to original sources
PubMed2006

DNA recombination-initiation plays a role in the extremely biased inheritance of yeast [rho-] mitochondrial DNA that contains the replication origin ori5.

Hypersuppressiveness, as observed in Saccharomyces cerevisiae, is an extremely biased inheritance of a small mitochondrial DNA (mtDNA) fragment that contains a replication origin (HS [rho(-)] mtDNA). Our previous studies showed that concatemers (linear head-to-tail multimers) are obligatory intermediates for mtDNA partitioning and are primarily formed by rolling-circle replication mediated by Mhr1, a protein required for homologous mtDNA recombination. In this study, we found that Mhr1 is required for the hypersuppressiveness of HS [ori5] [rho(-)] mtDNA harboring ori5, one of the replication origins of normal ([rho(+)]) mtDNA. In addition, we detected an Ntg1-stimulated double-strand break at the ori5 locus. Purified Ntg1, a base excision repair enzyme, introduced a double-stranded break by itself into HS [ori5] [rho(-)] mtDNA at ori5 isolated from yeast cells. Both hypersuppressiveness and concatemer formation of HS [ori5] [rho(-)] mtDNA are simultaneously suppressed by the ntg1 null mutation. These results support a model in which, like homologous recombination, rolling-circle HS [ori5] [rho(-)] mtDNA replication is initiated by double-stranded breakage in ori5, followed by Mhr1-mediated homologous pairing of the processed nascent DNA ends with circular mtDNA. The hypersuppressiveness of HS [ori5] [rho(-)] mtDNA depends on a replication advantage furnished by the higher density of ori5 sequences and on a segregation advantage furnished by the higher genome copy number on transmitted concatemers.

Alloxan↗
PubMed2003

Stress and coping in accident and emergency senior house officers.

OBJECTIVES: To identify levels of psychological distress in accident and emergency (A&E) senior house officers (SHOs). METHODS: Questionnaire survey given to SHOs at training sessions. MEASURES: General Health Questionnaire (GHQ) and the Brief COPE. RESULTS: Over half of the 37 respondents (51%; 95% CI: 36% to 67%) scored over the threshold for psychological distress on the GHQ. This is considerably higher than for other groups of doctors and for other professional groups. Correlational analysis revealed that the coping style Venting was significantly related to greater anxiety (r=0.34; p<0.05) and depression (r=0.33; p<0.05), while the coping style Active was significantly related to lower anxiety (r=-0.38; p<0.05), somatic complaints (r=-0.46; p<0.001) and years since qualification (r=0.40; p<0.05). CONCLUSIONS: Replicating findings from a study of stress in A&E consultants, this study shows higher levels of overt psychological distress among A&E SHOs than among other groups of doctors. An intervention to improve coping strategies may be useful for this group of doctors.

Adaptation, Psychological↗
PubMed1997

Oxidative stress in human immunodeficiency virus infection.

Infection by the human immunodeficiency virus (HIV-1) causes chronic ongoing inflammation in HIV-1 seropositive individuals as shown by high plasma levels of inflammatory cytokines and production of reactive oxygen intermediates (ROIs). One source of ROIs is provided from the very early stages of HIV infection by activated polymorphonuclear neutrophils. Tat, the viral protein, is also specifically responsible for an endogenous cellular increase of ROI. In this review we also evaluate the effects of this oxidative stress on various biological parameters such as immune response and survival of T lymphocytes, virus transcription and replication. It was clearly demonstrated in ex vivo experiments that the oxidative stress due to infection itself participates in CD4+ T lymphocyte depletion by increasing their rate of apoptosis and particularly of Fas-induced apoptosis. This oxidative stress also facilitates NF-kappa B-dependent activation of HIV transcription. In vitro studies suggest that the early steps of HIV activation from its quiescent state might be subsequently facilitated by this oxidative environment. Whereas already active replication is not influenced. The data presented here lead to a better understanding of the consequences of oxidative stress on the pathophysiology of HIV infection and also enable us to evaluate the potential use of antioxidant molecules as therapeutic agents against AIDS.

Antioxidants↗
PubMedDate not supplied

Beta-adrenergic receptor changes in learned helplessness may depend on stress and test parameters.

Behavioral deficits following inescapable stress (learned helplessness) may serve as an animal model of depression. Previous studies using foot-shock stress to induce learned helplessness and a bar-press test for the stress-induced behavioral deficit have found increased beta-adrenergic receptor density in the hippocampus of learned helpless rats. We replicated these experiments using a tail-shock stress and the shuttle-box test. In our experiments, rats that developed learned helplessness after inescapable stress did not demonstrate any significant differences in beta-adrenergic receptor density or affinity in the frontal cortex, cerebellum, or hippocampus compared to the nonhelpless rats, nor to the tested control rats. These results suggest that beta-adrenergic receptor changes in learned helplessness may depend on the specific stress and test procedures used.

Animals↗
PubMed2003

Increased expression of p21(waf) cyclin-dependent kinase inhibitor in asthmatic bronchial epithelium.

Because the asthmatic bronchial epithelium is characterized by widespread damage, we postulated that this is associated with expression of cell cycle inhibitors that control proliferation. Using bronchial biopsies, the epithelium was the major site of expression of the cyclin-dependent kinase inhibitor, p21(waf). Immunostaining usually occurred in the cytoplasm of columnar cells; however, in severe asthma, nuclear staining was also evident in the proliferative, basal cell compartment. p21(waf) expression was significantly higher in asthmatic versus nonasthmatic epithelium and was unaffected by corticosteroid treatment; proliferating cell nuclear antigen was not significantly different in any group. p21(waf), but not p27(kip1), mRNA and protein were induced by treatment of bronchial epithelial cells in vitro with transforming growth factor (TGF)-beta or H2O2, but not by dexamethasone, which induced p57(kip2). TGF-beta and dexamethasone inhibited epidermal growth factor (EGF)-induced DNA synthesis, whereas low concentrations of H2O2 synergized with EGF; at higher doses, growth inhibition and induction of apoptosis occurred. TGF-beta caused p21(waf) to become nuclear, suggesting interaction with the replicative machinery; however, in oxidant-stressed cells, p21(waf) was predominantly cytoplasmic, where it has been linked to cell survival. We conclude that p21(waf) overexpression in asthma influences cell proliferation and survival. This may cause abnormal repair responses that contribute to airway inflammation and remodeling.

Asthma↗
PubMed1999

A comparative study of stress between pre- and post-Project 2000 students.

This paper reports upon a comparative study in an English health authority of stress experiences between 146 current Diploma in Nursing (Project 2000) Adult Branch students and a prior study of a sample of 146 students who undertook a certificate course leading to Registered General Nurse (RGN) in 1988. Both groups were administered the same questionnaire. The number of stressors common to both groups were two in education and nine in the clinical environment. Three prominent feelings of stress were expressed by both groups along with two methods of coping with stress. A constellation of 11 personality type characteristics labelled 'determination', which enabled students to sustain themselves, was identified. Three characteristics of 'determination', plus a feeling of uselessness and inability to contribute to the nursing team effort, and the intense amount of academic work were statistically significantly higher for Diploma students. Six prominent clinical stressors were experienced more intensely by third-year diploma students than first- or second-year students. Stress was found to increase with the level of training. This finding replicated the picture found among 324 students in 1988. Differences in stress experiences for different age groups were not statistically significant with the exception of physical hard work. A number of stressors experienced by students in 1988 were also experienced by students in 1997.

Adaptation, Psychological↗
PubMed2006

The nitrosative stress response of Staphylococcus aureus is required for resistance to innate immunity.

Staphylococcus aureus is a highly virulent human pathogen with an extensive array of strategies to subvert the innate immune response. An important aspect of innate immunity is the production of the nitrogen monoxide radical (Nitric Oxide, NO.). Here we describe an adaptive response to nitrosative stress that allows S. aureus to replicate at high concentrations of NO.. Microarray analysis revealed 84 staphylococcal genes with significantly altered expression following NO. exposure. Of these, 30 are involved with iron-homeostasis, potentially under the control of the Fur regulator. Another seven induced genes are involved in hypoxic/fermentative metabolism, including the flavohaemoprotein, Hmp. The SrrAB two-component system has been shown to regulate the expression of many of the NO.-induced metabolic genes. Indeed, inactivation of hmp, srrAB and fur resulted in heightened NO. sensitivity. Hmp was responsible for c. 90% of measurable staphylococcal NO. consumption and therefore critical for efficient NO. detoxification. While SrrAB was required for maximal hmp expression, srrAB mutants still exhibited significant NO. scavenging and NO.-dependent induction of hmp. Yet S. aureus lacking SrrAB were more sensitive to nitrosative stress than hmp mutants, indicating that the contribution of SrrAB to NO. resistance extends beyond the regulation of hmp expression. Both Hmp and SrrAB were required for full virulence in a murine sepsis model, however, only the attenuation of the hmp mutant was restored by the abrogation of host NO. production. Thus, the S. aureus Hmp protein has evolved to serve as an iNOS-dependent virulence determinant.

Animals↗
PubMed1995

[Can HIV infection be treated with antioxidants?].

Several recent reports have indicated high levels of reactive oxygen species, causing oxidative stress, in the pathogenesis of HIV infection. Oxidative stress may lead to enhanced HIV replication in infected cells and may also aggravate the immunodeficiency by reduction of cellular immunity and possibly by increased programmed cell death of lymphocytes. Moreover, reduced levels of antioxidants have been found in patients with HIV infection. This raises the question of whether antioxidant therapy might be beneficial in patients with HIV infection. Until now, only a few preliminary, clinical studies have been completed. Further clinical trials are needed to assess the possible role of antioxidants in the treatment of HIV infection.

Antioxidants↗
PubMed1993

Cell and tissue responses to oxidative damage.

A broad array of oxidative stresses modulates gene expression in a variety of mammalian cells. One goal of this review was to characterize cellular responses to oxidative injury, how these processes are regulated, and the outcome for a particular cell or tissue. Many genes induced in response to specific oxidant stresses have been identified and include transcription factors, replication proteins, proteases, protease inhibitors, proteins affecting cell proliferation and various antioxidants, i.e. heme oxygenase, MT, and MnSOD. The latter enzyme is induced after a number of cytokines and oxidant stresses including hyperoxia and mineral dusts causing inflammation. Moreover, increases in mRNA levels of TNF and IL-1, cytokines inducing MnSOD, are observed after exposure to UV and ionizing radiation. Since increased electron flow could lead to generation of more AOS within mitochondria, increased levels of MnSOD might be necessary to maintain normal functioning of the mitochondria after oxidative stress. Alterations in cell growth are intrinsically related to the pathogenesis of many diseases. Paradoxically, some of the responses of cells to oxidative stress reflect cytotoxicity and cytostasis, whereas others result in increased cell proliferation. For example, induction of gadd genes observed after oxidative stress is related to growth arrest of cells, a response which might enable the cell to repair oxidative damage prior to replication. This phenomenon might prevent fixation of mutations associated with oxidative DNA damage. On the other hand, increased mRNA expression and activity of ODC, observed after exposure of cells to UV or asbestos is associated with increased cell proliferation. In addition, increased mRNA expression of cellular proto-oncogenes observed after exposure to oxidants could also be related to increased DNA synthesis or proliferation. Figure 5 provides a general scheme of cell responses to oxidative stress and possible ramifications. AOS can react with a number of target molecules including proteins, lipids, and DNA. These interactions elicit a number of signals including activation of gene regulatory factors (transcription factors) which in turn activate oxidative stress-responsive genes or regulons. Consequently, a number of proteins are produced with distinctive functions including DNA repair enzymes, antioxidants, proteases inhibitors, cytokines and proteins affecting cell proliferation. These cellular responses to AOS can lead to restoration of normal cellular function and adaptation to oxidative stress, cell death or aberrant proliferation. It is the latter two responses which can lead to a variety of disease states including cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2003

Cell cycle- and age-dependent activation of Sod1p drives the formation of stress resistant cell subpopulations within clonal yeast cultures.

Phenotypic heterogeneity describes non-genetic variation that exists between individual cells within isogenic populations. The basis for such heterogeneity is not well understood, but it is evident in a wide range of cellular functions and phenotypes and may be fundamental to the fitness of microorganisms. Here we use a suite of novel assays applied to yeast, to provide an explanation for the classic example of heterogeneous resistance to stress (copper). Cell cycle stage and replicative cell age, but not mitochondrial content, were found to be principal parameters underpinning differential Cu resistance: cell cycle-synchronized cells had relatively uniform Cu resistances, and replicative cell-age profiles differed markedly in sorted Cu-resistant and Cu-sensitive subpopulations. From a range of potential Cu-sensitive mutants, cup1Delta cells lacking Cu-metallothionein, and particularly sod1Delta cells lacking Cu, Zn-superoxide dismutase, exhibited diminished heterogeneity. Furthermore, age-dependent Cu resistance was largely abolished in cup1Delta and sod1Delta cells, whereas cell cycle-dependent Cu resistance was suppressed in sod1Delta cells. Sod1p activity oscillated approximately fivefold during the cell cycle, with peak activity coinciding with peak Cu-resistance. Thus, phenotypic heterogeneity in copper resistance is not stochastic but is driven by the progression of individual cells through the cell cycle and ageing, and is primarily dependent on only Sod1p, out of several gene products that can influence the averaged phenotype. We propose that such heterogeneity provides an important insurance mechanism for organisms; creating subpopulations that are pre-equipped for varied activities as needs may arise (e.g. when faced with stress), but without the permanent metabolic costs of constitutive expression.

Carrier Proteins↗
PubMed1991

In vitro roles of Escherichia coli DnaJ and DnaK heat shock proteins in the replication of oriC plasmids.

Heat shock proteins have been shown to be involved in many cellular processes in procaryotic and eucaryotic cells. Using an in vitro DNA replication assay, we show that DNA synthesis initiated at the chromosomal origin of replication of Escherichia coli (oriC) is considerably reduced in enzyme extracts isolated from cells bearing mutations in the dnaK and dnaJ genes, which code for heat shock proteins. Furthermore, unlike DNA synthesis in wild-type extracts, residual DNA synthesis in dnaK and dnaJ extracts is thermosensitive. Although thermosensitivity can be complemented by the addition of DnaK and DnaJ proteins, restoration of near wild-type replication levels requires supplementary quantities of purified DnaA protein. This key DNA synthesis initiator protein is shown to be adsorbed to DnaK affinity columns. These results suggest that at least one of the heat shock proteins. DnaK, exerts an effect on the initiation of DNA synthesis at the level of DnaA protein activity. However, our observation of normal oriC plasmid transformation ratios and concentrations in heat shock mutants at permissive temperatures would suggest that heat shock proteins play a role in DNA replication mainly at high temperatures or under other stressful growth conditions.

Bacterial Proteins↗
PubMed1995

Tumour necrosis factor-alpha induces preferential expression of stress proteins in virulent promastigotes of Leishmania donovani.

Intracellular replication of Leishmania donovani inside macrophages is essential for production of disease and development of the parasite. Tumour necrosis factor-alpha (TNF) plays an integral role in host response to Leishmania. The effect of TNF on expression of heat-shock proteins (Hsp) was examined in promastigotes of L. donovani. TNF treatment led to an increased expression of Hsp83, Hsp70 and Hsp65 in virulent, but not avirulent, parasites. In response to stress by H2O2 or sodium arsenite, an increased expression of Hsp60 was observed in the virulent, but not avirulent, parasites. The virulent promastigotes were found to be more resistant to the toxic effects of TNF and other stresses. The data indicated that Hsp expressed in response to stress encountered in macrophages may confer protection to parasites and play a crucial role in their survival in the mammalian host.

Animals↗
PubMed1990

Failure to detect fabricated posttraumatic stress disorder with the use of the MMPI in a clinical population.

The authors attempted to replicate previous studies that used the Frequency (F) scale and the posttraumatic stress disorder (PTSD) subscale of the MMPI to discriminate Vietnam veterans with PTSD from well-adjusted veterans and mental health professionals who feigned symptoms of PTSD. Profiles of veterans with PTSD were compared to those of veterans with non-PTSD psychiatric disorders and veterans with fabricated PTSD symptoms who sought treatment. Discriminant analysis of F scale and PTSD subscale scores correctly identified only 43.59% of the subjects, thus failing to support use of the MMPI in detecting fabricated symptoms of PTSD in a clinical population.

Adult↗
PubMed2006

[Experimental study of protective effects of Xuebijing injection on stress-induced organ damage in rabbit].

OBJECTIVE: To investigate the protective effects of the integrated traditional Chinese and western medicine Xuebijing injection on stress-induced organ damage in rabbits. METHODS: Forty rabbits were randomly divided into four groups: the control group, the model group, the western medicine group, and the Xuebijing group. The stress-induced organ damage model was replicated by soak the rabbits in water, the animals in the western medicine group and Xuebijing group received injection of lytic cocktail and Xuebijing, respectively. The changes in cortisol (Cor), thromboxane A(2) (TXA(2)), endothelin (ET), nitric oxide synthase (NOS) were determined at different time points in all the groups. The pathologic changes of the gastric mucosa, the adrenal gland and the cardiac muscle cell were observed. RESULTS: The content of Cor increased significantly in model group (P<0.01). The content of Cor decreased in the western medicine group and Xuebijing group, the changes showed no significant difference between two groups (P>0.05). The contents of ET, TXA(2) decreased and NOS increased in Xuebijing group compared with the western medicine group, the differences were significant (all P<0.05). The pathological changes of the gastric mucosa, the adrenal gland and the cardiac myocyte were less marked in Xuebijing group, compared with the western medicine group, the difference was significant (P<0.05). CONCLUSION: Xuebijing has better protective effects on stress-induced organ damage.

Adrenal Glands↗
PubMed2003

The effect of clamping a tensioned wire: implications for the Ilizarov external fixation system.

This study demonstrates that clamping a tensioned wire can cause a reduction in wire tension. Tension (about 1275 N) was applied to a wire that was subsequently clamped, using cannulated bolts, to the steel half-ring of an Ilizarov external fixator. The tension in the wire was monitored before, during and after clamping. The apparatus was disassembled and the deformations in the wire caused by the clamps were measured. This experiment was repeated 15 times. When the wire was clamped to the frame, the wire tension was reduced by 22 +/- 7 per cent (mean +/- standard deviation, SD). The drop in wire tension was linearly correlated (r = 0.96; p < 0.001) with the deformation caused by the bolts. A finite element (FE) model of the wire was also constructed. The model was pre-stressed (tensioned), and the clamping effect replicated. This analysis showed that clamping the wire could be considered to squeeze the wire outwards (like toothpaste from a tube) and so reduce its tension during fixator assembly. To assess the magnitude of this effect in the clinical situation, the FE model analysis was repeated to replicate clamping a 1.8-mm-diameter wire to a 180-mm-diameter steel Ilizarov ring component. The analysis showed that for these conditions the tension reduced by 8-29 per cent. The results of this study highlight a general engineering problem: how can a tensioned wire be secured to a structure without an appreciable loss of tension? If the performance of the structure depends on the wire tension, this performance will change when the wire is secured.

Bone Wires↗
PubMed1997

Quantitative aspects of evaluating the consequences of pollution for parasite populations and communities.

The utility of parasites as indicators of environmental health depends upon scientists' ability to understand how environmental stress may cause changes in parasite populations and communities. Predicting the changes due to pollution calls for dynamic models and experimentally determined knowledge of the consequences of pollution on the parameters of the model. Through an interplay of modeling, laboratory experiments, and field comparisons scientists can develop a theory of pollution and parasites and perhaps use it to assess the impact of pollution. To develop a theoretical framework for the effects of pollution on host-parasite relationships will require an identification of the appropriate scale and a determination of whether the host and parasite populations should be treated as open and recruitment-driven or closed and reproduction-driven. A theory can then be developed using epidemiology models. Those models are divided into prevalence models that track the prevalence of infection and abundance models that track the number of parasites per host. Whether a deterministic model or a stochastic counterpart should be used depends upon the scale but generally a stochastic model will give a more realistic picture. Mimicking the variability inherent in natural systems is the goal of stochastic models. The models emphasize that field tests of their predictions can only be made by studies designed with extensive replication of samples from reference and stressed sites.

Animals↗
PubMed1995

Stimulation of DNA synthesis by mouse DNA helicase B in a DNA replication system containing eukaryotic replication origins.

A number of DNA helicases have been isolated from mammalian cells, but their abilities to stimulate DNA replication accompanied with DNA unwinding have not been addressed so far. We constructed a model DNA replication system using the yeast autonomously replicating sequence (ARS) as the replication origin. In this system, SV40 T antigen as a DNA helicase assembles to the replication origin where the DNA duplex is unwound by torsional stress due to the negative supercoiling of template DNA, which leads to bidirectional DNA replication from the origin. We report here that DNA helicase B isolated from mouse FM3A cells can greatly stimulate DNA synthesis in this replication system in place of SV40 T antigen. DNA synthesis was dependent on the presence of single-stranded DNA binding protein (RP-A), DNA polymerase alpha/primase from mouse cells, and Escherichia coli DNA gyrase. DNA gyrase was required not only at elongation as a DNA swivelase but also at initiation to increase negative superhelical density of template DNA with the assistance of RP-A. A mammalian DNA fragment containing a replication initiation zone upstream of the c-myc gene as well as the yeast ARS fragment acted as a cis-element in this system using DNA helicase B. Both DNA helicase B and SV40 T antigen have the ability to extensively unwind the template DNA in the presence of RP-A and DNA gyrase, which may be crucial for stimulation of DNA synthesis in this system.

Adenosine Triphosphatases↗