Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “replication stress”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources
PubMed1992

Declination of supralaryngeal gestures in spoken Italian.

Two experiments investigate a weakening of supralaryngeal gestures in an utterance, analogous in some ways to declination of fundamental frequency and amplitude. In one experiment, acoustic measures revealed progressive centralization of stressed /i/, /a/ and /u/ left to right in trisyllabic utterances read by Tuscan subjects. A second experiment, using speakers of a different (Northern) variety of Standard Italian, found reduction in jaw opening for stressed /a/ left to right, but generally failed to replicate a centralization of /i/. This experiment further suggested that the progressive weakening of supralaryngeal gestures is largely a phrase level rather than a word level phenomenon. Both experiments found a different, V-shaped, pattern of opening to be generally characteristic of unstressed syllables.

Adult↗
PubMed2004

Cigarette smoke induces senescence in alveolar epithelial cells.

Cellular senescence is a state of irreversible growth arrest induced either by telomere shortening (replicative senescence) or by telomere-independent signals (stress-induced senescence). The alveolar epithelium is often injured by a variety of inhaled toxins, including cigarette smoke (CS). In the present study, we investigated whether exposure to CS induces senescence of alveolar epithelial cells. In vitro experiments showed that exposure of A549 cells or normal human alveolar epithelial cells to sublethal concentrations of aqueous CS extracts induced cellular senescence. The senescence was characterized by a dose- and time-dependent increase in senescence-associated beta-galactosidase activity, senescence-associated changes in cell morphology, an increase in cell size and lysosomal mass, accumulation of lipofuscin, overexpression of p21(CIP1/WAF1/Sdi1) protein, and irreversible growth arrest. In vivo experiments in Institute for Cancer Research mice showed that inhalation of CS for 2 wk induced increases in senescence-associated beta-galactosidase activity, lipofuscin accumulation, and p21(CIP1/WAF1/Sdi1) protein expression in alveolar epithelial cells. These results suggest that CS induces a phenotype that is indistinguishable from that of senescence in alveolar epithelial cells. The induction of cellular senescence by CS may contribute to impaired re-epithelialization, leading to CS-related chronic lung diseases.

Animals↗
PubMed1992

Age as a bona fide occupational qualification for firefighting. A review on the importance of measuring aerobic power.

Recent federal and judicial initiatives have led to controversy over the justification of mandatory retirement policies applied to public safety occupations. The Equal Employment Opportunity Commission has been mandated to study this issue, and a critical element of that study will be to determine the types of tests to be employed as substitutes for a mandatory retirement age. In this review, a rationale is presented for the measurement of aerobic power (VO2max) as a predictor of the physical performance capability of firefighters. We conclude that task simulations rarely replicate the environmental conditions present at structural fires that stress the cardiorespiratory capability of firefighters. VO2max is an important predictor of performance effectiveness of firefighters to be used in conjunction with task-specific testing.

Age Factors↗
PubMed1993

Endothelial nuclear factor-kappa B and the initiation of the atherosclerotic lesion.

The genes for several endothelial-leukocyte adhesion molecules implicated in the initiation of the atherosclerotic lesion contain functional NF-kappa B binding sites which are required for cytokine induction in endothelial cells. Activation of this pleiotropic family of transcription factors may explain in part the diversity of growth factor and cytokine gene expression associated with dysfunctional endothelium, as well as the increased endothelial cell replication observed at lesion prone anatomic sites. Endothelial oxidant stress and activation of the NF-kappa B family of transcription factors may link the otherwise seemingly diverse risk factors associated with the initiation of the atherosclerotic lesion into a final common pathway for induced endothelial gene activation.

Arteriosclerosis↗
PubMed1997

The DNA binding regulatory domain of p53: see the C.

The p53 tumor suppressor gene is a critical regulator of normal development involved in cell cycle control pathways, such as growth arrest, differentiation and apoptosis. The DNA binding activity of p53 is central to its function. In addition to the specific DNA binding activity that is confined to the "core" domain of the molecule, the C-terminus seems to play an important role in both controlling the specific as well as exhibiting a non-specific DNA binding activity, which is directly associated with sensing damaged DNA. The C-terminal DNA binding activity appears to be regulated by phosphorylation, glycosylation, splicing and binding of several factors. The C-terminus seems to recognize single and double stranded DNA breaks that occur during DNA replication and recombination, as well as following external DNA stress signals. Unless the cell manages to correct the DNA damage it has the tempting option to progress towards apoptosis. Imagine the C-terminus as a traffic light ensuring the safe "on going" through the cell cycle; in case damaged DNA could not be corrected, p53 dependent apoptosis or terminal differentiation "signs" are turned on!

Animals↗
PubMed1985

Psychophysiological response specificities: a replication over a 12-month period.

A sample of 58 students was subjected to four stress conditions (mental arithmetic, reaction time, free speech, cold-pressor test). Eight physiological variables (skin conductance, heart rate, pulse amplitude, Heather index, eye blinking, horizontal eye movements, respiration rate, blood pressure) and five psychological variables (self-rated anger, irritability, tenseness, motivation, indifference) were monitored. Proportions of variance in a three-factor ANOVA (subjects, situations, variables) accounted for by individual specific response patterns (ISR) amounted to 33-40% for physiological and 9-13% for psychological variables. Stimulus specific response patterns (SSR) accounted for 11-19% for physiological and 8-14% for psychological variables, and motivation specific response patterns (MSR) for 17% for physiological and 14-16% for psychological variables. About one-fourth of the subjects showed a rather stable ISR in physiological variables when tested again after two months, and about 14% when tested again after twelve months. Overall, the results replicated earlier findings from this laboratory.

Adaptation, Physiological↗
PubMed1998

Changes in stress and burden in families seeking therapy following traumatic brain injury: a follow-up study.

The current project is a preliminary investigation of changes in levels of distress and burden and family and marital adjustment in families following traumatic brain injury (TBI), replicating measures-used in the earlier Glasgow, TBI outcome research on relatives' stress and burden. Fifteen families (32 individuals) seeking family counselling in a publicly funded family therapy centre were monitored over a two year period: prior to commencing counselling; 12 months following the commencement of counselling; and 24 months following the commencement of counselling. The most significant and sustained changes in psychosocial outcome were a decrease in distress for both individuals with TBI and their carers as well as a reduction in relatives' burden and strain. Family conflict also reduced, just as family cohesion increased and adjustment within the family unit improved from pre-therapy to the time of follow-up 24 months later. However, reported levels of anger, despite significantly reducing during the first 12 months of the study, actually increased back to their original levels at the 24 month follow-up. Marital adjustment also worsened in the latter half of the study, with couples reporting a similar level of marital adjustment to that which they had experienced prior to counselling. These findings are discussed and recommendations made for more rigorous, controlled, longitudinal studies of the effectiveness of family therapy. It was also recommended that marital couples receive longer-term counselling to address their specific needs, and that the issue of anger be further investigated with a view to either reducing family members' anger, or bearing witness to the legitimacy of their anger in the longer-term, and assisting with anger-management programmes.

Adolescent↗
PubMed2003

MutY is down-regulated by oxidative stress in E. coli.

In Escherichia coli, MutM (8-oxoG DNA glycosylase/lyase or Fpg protein), MutY (adenine DNA glycosylase) and MutT (8-oxodGTPase) function cooperatively to prevent mutation due to 7, 8-dihydro-8-oxoguanine (8-oxoG), a highly mutagenic oxidative DNA adduct. MutM activity has been demonstrated to be induced by oxidative stress. Its regulation is under the negative control of the global regulatory genes, fur, fnr and arcA. However, interestingly the presence of MutY increases the mutation frequency in mutT- background because of MutY removes adenine (A) from 8-oxoG:A which arises from the misincorporation of 8-oxoG against A during DNA replication. Accordingly we hypothesized that the response of MutY to oxidative stress is opposite to that of MutM and compared the regulation of MutY activity with MutM under various oxidative stimuli. Unlike MutM, MutY activity was reduced by oxidative stress. Its activity was reduced to 30% of that of the control when E. coli was treated with paraquat (0.5mM) or H2O2 (0.1 mM) and induced under anaerobic conditions to more than twice that observed under aerobic conditions. The reduced mRNA level of MutY coincided with its reduced activity by paraquat treatment. Also, the increased activity of MutY in anaerobic conditions was reduced further in E. coli strains with mutations in fur, fnr and arcA and the maximum reduction in activity was when all mutations were present in combination, indicating that MutY is under the positive control of these regulatory genes. Therefore, the down-regulation of MutY suggests that there has been complementary mechanism for its mutagenic activity under special conditions. Moreover, the efficacy of anti-mutagenic action should be enhanced by the reciprocal co-regulation of MutM.

DNA↗
PubMed1995

In utero ethanol exposure elicits oxidative stress in the rat fetus.

Prior studies in our laboratory have shown that exposure of cultured fetal rat hepatocytes to ethanol (E) blocks epidermal growth factor-dependent replication and that this is paralleled by cell membrane damage, mitochondrial dysfunction, membrane lipid peroxidation (LP), and enhanced generation of reactive oxygen species. These measures of E-mediated oxidative stress (OS) were mitigated by treatment with antioxidants, and cell replication could be normalized by maintaining cell glutathione (GSH) pools. We have now extended these studies to an in vivo model. Rats were administered E (4 g/kg, po) at 12-hr intervals on days 17 and 18 of gestation and killed on day 19, 1 hr following a final dose of E (a total of 5 doses). Fetal and maternal brain and liver were assayed for signs of OS. The 2-day in utero E exposure increased membrane LP in fetal brain as evidenced by increased malondialdehyde (MDA) levels from 1.76 +/- 0.12 SE (nMol/mg protein) to 2.00 +/- 0.08 (p < 0.05) and conjugated dienes from 0.230 +/- 0.006 SE (OD223/mg lipid) to 0.282 +/- 0.006 (p < 0.05). In fetal liver, MDA levels increased from 2.39 +/- 0.08 SE (nMol/mg protein) to 2.87 +/- 0.08 (p < 0.05), whereas dienes differed significantly only between ad libitum controls and the E and pair-fed control groups (p < 0.05). E decreased GSH levels in fetal brain by 19%, from 19.88 +/- 0.72 to 16.13 +/- 1.06 (nMol/mg protein) (p < 0.05). A 10% decrease in GSH was seen in fetal liver (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Dephosphorylation of Rb (Thr-821) in response to cell stress.

The retinoblastoma tumor suppressor Rb is regulated by reversible phosphorylation that is dependent upon cyclin-dependent kinase (CDK) and protein phosphatase type 1 (PP1) activity in replicating cells. Hyperphosphorylated Rb allows cells to proliferate, whereas the hypophosphorylated isoform of Rb inhibits proliferation. Of the many phosphorylation sites of Rb, there is functional information available for a very few. In this report, we show that threonine-821 (Thr-821) of Rb is dephosphorylated earlier than other phosphorylation sites when cells are grown under hypoxic conditions which leads to Rb activation and G(1) arrest. This finding is interesting because Thr-821 of Rb remains phosphorylated throughout the cell division cycle in replicating cells. We hypothesized that the phosphorylation state of Thr-821 of Rb may depend on cellular stress. We report in this study that, when nontransformed CV1 epithelial cells and Hs578T breast cancer cells are treated with the chemotherapeutic agent cytosine arabinoside (Ara-C), Thr-821 of Rb is rapidly dephosphorylated concomitant with dissociation of the PP1 regulatory subunit PNUTS (phosphatase nuclear targeting subunit) from PP1 enzyme. These data are consistent with the concept that differential regulation of Rb-directed phosphatase activity exists when cells are progressing through the cell cycle compared to that observed when cells are under stress.

Antimetabolites, Antineoplastic↗
PubMed1995

Life events and hypertension--a negative finding.

Thirty black Xhosa-speaking unskilled workers, aged between 28 and 59 years, completed three questionnaire measures of stress: Bluen and Odesnik's Township Life Events Scale, Weiman's Occupational Stress Scale and Melamed's Emotional Reactivity Scale. Other variables measured were age, systolic and diastolic blood pressure and body mass index (BMI). Stress levels on all the measures were particularly high in comparison with other groups studied with the same instruments. The well-known relationship between body mass and blood pressure was replicated. However, there was no correlation between blood pressure and any of the stress measures, even when variance in respect of age and body mass was partialled out. It is concluded that the pathways linking stressors to high blood pressure are complex and that caution must be exercised in claiming that there is a link between high levels of urban stress and high incidence of hypertension.

Adult↗
PubMed2005

Sir2 blocks extreme life-span extension.

Sir2 is a conserved deacetylase that modulates life span in yeast, worms, and flies and stress response in mammals. In yeast, Sir2 is required for maintaining replicative life span, and increasing Sir2 dosage can delay replicative aging. We address the role of Sir2 in regulating chronological life span in yeast. Lack of Sir2 along with calorie restriction and/or mutations in the yeast AKT homolog, Sch9, or Ras pathways causes a dramatic chronological life-span extension. Inactivation of Sir2 causes uptake and catabolism of ethanol and upregulation of many stress-resistance and sporulation genes. These changes while sufficient to extend chronological life span in wild-type yeast require severe calorie restriction or additional mutations to extend life span of sir2Delta mutants. Our results demonstrate that effects of SIR2 on chronological life span are opposite to replicatve life span and suggest that the relevant activities of Sir2-like deacetylases may also be complex in higher eukaryotes.

Adenylyl Cyclases↗
PubMed2003

Epstein-Barr virus can inhibit genotoxin-induced G1 arrest downstream of p53 by preventing the inactivation of CDK2.

Epstein-Barr virus (EBV) is involved in the pathogenesis of several B cell lymphoproliferations, but the precise contribution it makes to the aetiology of each remains unclear. In vitro, the virus has potent growth transforming activity and efficiently induces the continuous proliferation of normal human B cells. A comparison of EBV-infected primary B cells with an isogenic population induced to proliferate by CD40-ligand (CD40L) and IL4 has revealed that EBV can override - by a novel mechanism - the p53/pRb-mediated G1 checkpoint activated in normal B cells by a genotoxic stress. In cells responding to cisplatin, although p53 is stabilized and activated, EBV latent gene expression appears to inhibit the accumulation of newly synthesized p21(WAF1/CIP1) and the downregulation of cyclin D2 that occur in the normal cells. Consequently, in the EBV-infected cells, CDK2 remains active, hyperphosphorylation of pRb is maintained and the replication of damaged DNA can occur. Under conditions of severe genomic stress, this absence of p21(WAF1/CIP1) function can result in apoptosis; however, when damage is less sustained, genomic instability may arise and this in turn could contribute to the development of a variety of EBV-associated B cell malignancies.

B-Lymphocytes↗
PubMed2000

Guanidine hydrochloride blocks a critical step in the propagation of the prion-like determinant [PSI(+)] of Saccharomyces cerevisiae.

The cytoplasmic heritable determinant [PSI(+)] of the yeast Saccharomyces cerevisiae reflects the prion-like properties of the chromosome-encoded protein Sup35p. This protein is known to be an essential eukaryote polypeptide release factor, namely eRF3. In a [PSI(+)] background, the prion conformer of Sup35p forms large oligomers, which results in the intracellular depletion of functional release factor and hence inefficient translation termination. We have investigated the process by which the [PSI(+)] determinant can be efficiently eliminated from strains, by growth in the presence of the protein denaturant guanidine hydrochloride (GuHCl). Strains are "cured" of [PSI(+)] by millimolar concentrations of GuHCl, well below that normally required for protein denaturation. Here we provide evidence indicating that the elimination of the [PSI(+)] determinant is not derived from the direct dissolution of self-replicating [PSI(+)] seeds by GuHCl. Although GuHCl does elicit a moderate stress response, the elimination of [PSI(+)] is not enhanced by stress, and furthermore, exhibits an absolute requirement for continued cell division. We propose that GuHCl inhibits a critical event in the propagation of the prion conformer and demonstrate that the kinetics of curing by GuHCl fit a random segregation model whereby the heritable [PSI(+)] element is diluted from a culture, after the total inhibition of prion replication by GuHCl.

Cell Division↗
PubMed2003

The role of social support in well-being and coping with self-reported stressful events in adolescents.

OBJECTIVE: This study investigated the role that social support plays in well-being and in coping after a stressful event in a group of non-clinical adolescents. Furthermore, this study aimed at replicating the finding that adolescents who reported sexual abuse reported more symptoms and less adequate coping strategies than adolescents who reported another type of stressful event or no stressful episode. METHOD: Eight hundred and twenty adolescents between 12 and 18 years of age filled out questionnaires assessing social support (Social Support Questionnaire, Sarason, Shearin, Pierce, & Sarason, 1987), trauma-related symptoms (Trauma Symptom Checklist for Children, Briere, 1996), behavior problems (Youth Self-Report, Achenbach, 1991), and coping (How I Cope Under Pressure Scale, Ayers, Sandler, West, & Roosa, 1996). RESULTS: 42% of the adolescents reported a stressful experience, and 4.4% reported sexual abuse. Sexually abused adolescents reported more stress-related symptoms and used more avoidance and fewer support-seeking coping strategies than the other adolescents. The main-effect hypothesis of social support was sustained, but social support did not moderate the relation between a stressful event and coping. Yet, a trend was found suggesting that high support from the family was associated with less avoidance coping and more support-seeking in adolescents who reported a non-sexually abusive, stressful event. CONCLUSIONS: Our findings show that a highly perceived availability of social support is directly associated with fewer trauma-related symptoms, especially in adolescents who are non-sexually abused. For adolescents who reported a sexual or another type of stressful event, social support did not play a different role in coping.

Adaptation, Psychological↗
PubMed2003

Caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein.

Prion diseases are characterized by accumulation of misfolded prion protein (PrP(Sc)), and neuronal death by apoptosis. Here we show that nanomolar concentrations of purified PrP(Sc) from mouse scrapie brain induce apoptosis of N2A neuroblastoma cells. PrP(Sc) toxicity was associated with an increase of intracellular calcium released from endoplasmic reticulum (ER) and up-regulation of several ER chaperones. Caspase-12 activation was detected in cells treated with PrP(Sc), and cellular death was inhibited by overexpression of a catalytic mutant of caspase-12 or an ER-targeted Bcl-2 chimeric protein. Scrapie-infected N2A cells were more susceptible to ER-stress and to PrP(Sc) toxicity than non-infected cells. In scrapie-infected mice a correlation between caspase-12 activation and neuronal loss was observed in histological and biochemical analyses of different brain areas. The extent of prion replication was closely correlated with the up-regulation of ER-stress chaperone proteins. Similar results were observed in humans affected with sporadic and variant Creutzfeldt-Jakob disease, implicating for the first time the caspase-12 dependent pathway in a neurodegenerative disease in vivo, and thus offering novel potential targets for the treatment of prion disorders.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Evaluation of dream content in combat-related PTSD.

Nightmares that replicate traumatic events are among the criteria that define posttraumatic stress disorder (PTSD); however, there has been limited systematic assessment of the content of dreams in PTSD. A PTSD dream rating instrument was developed to operationalize features attributed to dreams associated with combat-related PTSD that incorporated dimensions from the dream content analysis literature, and its reliability was assessed. Then the instrument was used to characterize dream reports in 18 Vietnam combat veterans diagnosed with PTSD. Approximately half of the group's target dreams contained features characteristic of combat, and all but 3 (17%) were moderately to highly threatening. Fifty-three percent were set at least partially in the present and 79% contained distorted elements. We therefore conclude that target dreams of combat veterans with PTSD vary with regard to replication of trauma and elements normally associated with dreaming, but typically are threatening.

Adult↗
PubMed1988

Evaluation of stem cell reserve using serial bone marrow transplantation and competitive repopulation in a murine model of chronic hemolytic anemia.

Serial transplantation and competitive repopulation were used to evaluate any loss of self-replicative capacity of bone marrow stem cells in a mouse model with increased and persistent hemopoietic demands. Congenic marrows from old control and from young and old mice with hereditary spherocytic anemia (sphha/sphha) were serially transplanted at 35-day intervals into normal irradiated recipients. Old anemic marrow failed or reverted to recipient karyotype at a mean of 3.5 transplants, and young anemic marrow reverted at a mean of 4.0 transplants, whereas controls did so at a mean of 5.0 transplants. In a competitive assay in which a mixture of anemic and control marrow was transplanted, the anemic marrow persisted to 10 months following transplantation; anemic marrow repopulation was greater if anemic marrow sex matched with the host. It is possible that lifelong stress of severe anemia decreases stem cell reserve in the anemic sphha/sphha mouse marrow. However, marginal differences in serial transplantation number and the maintenance of anemic marrow in a competition assay would suggest that marrow stem cells, under prolonged stress, are capable of exhibiting good repopulating and self-replicating abilities.

Aging↗