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PubMed2000

Texture response patterns associated with sexual trauma of childhood and adult onset: developmental and recovered memory implications.

OBJECTIVE: Reduce texture sensitivity on the Rorschach is proposed as a sequela of early sexual abuse that is unlikely to be contaminated by situational variables. If this conceptualization has merit, texture attributes offer a roadmap for studying vying claims in the recovered memory debate. To explore this possibility, we examined the extent to which intense preoccupation with sexual trauma of childhood and of adult onset was related to reduced texture productivity. METHOD: Texture productivity was measured in 4 groups comprised of 108 patients using the Rorschach. Twenty-seven patients with recovered memory were compared with 27 patients with continuous memory of childhood sexual trauma, 27 post trauma stress patients with sexual trauma of adult onset, and 27 non-abused patients. RESULTS: The study replicated previous findings of reduced texture productivity among patients who always remembered sexual trauma of childhood-onset. The same texture deficiency pattern was observed among patients who recovered memory of childhood sexual abuse. This pattern was not observed in Post Traumatic Stress Disorder (PTSD) patients intensely preoccupied with sexual trauma of adult onset despite the fact that they mimicked the recovered memory group in respect to enduring preoccupation with distressing thoughts of sexual abuse. CONCLUSION: The findings indicate that intrusive memories of sexual trauma do not shape patients' response to textural cues on the Rorschach. Variations in texture productivity are primarily moderated by age of trauma onset. Dismissal of claims of recovered memories on the basis of intense sexual preoccupation is not warranted.

Adult↗
PubMed1980

Selection of layers for rapid recovery from stress.

A one-generation experiment was conducted to evaluate response to selection of layers for rapid recovery from stress and to estimate genetic parameters associated with the selected trait. Stress was induced at 55 weeks of age and maintained for 8 days on 1450 laying hens of a randombred White Leghorn population. Egg production persisted an average of 3.5 days after onset of stress and had ceased in all birds by 8 days. Average recovery time, from cessation of lay to first poststress egg, was 27.1 days, and heritability estimated from the sire component of variance was .30 for the selected trait. Hens with higher rates of lay resumed production sooner after stress and tended to continue production longer duration stress. Selection of 11% of layers in generation 0 with shortest recovery time in each of 11 replicates resulted in a significant (P < .05) reduction of 4.1 days in recovery time in generation 1.

Animals↗
PubMed2001

Integrating stress-response and cell-cycle checkpoint pathways.

The DNA integrity checkpoint and stress kinase (SAPK/JNK and p38) pathways function to modulate cell-cycle, apoptotic and transcriptional responses to stress. Although initially considered to function independently, recent advances indicate a number of links between the stress-response and checkpoint pathways. Here, we consider the relationship between the stress-response and checkpoint pathways and how they interact to modulate cell-cycle control.

Animals↗
PubMed2003

The possible mechanism of action of ciclopirox olamine in the yeast Saccharomyces cerevisiae.

Ciclopirox olamine is a synthetic antifungal agent with a high affinity for trivalent metal cations. Ciclopirox olamine can be used to synchronize mammalian cells, but its mechanism of action is not understood well. In this study, we investigated the effect of ciclopirox olamine in yeast cells and used a genetic approach to identify potential ciclopirox olamine targets in yeast. Wild type strains of the yeast Saccharomyces cerevisiae were weakly sensitive to ciclopirox olamine, but high concentrations of the drug arrested their growth at many different stages. MMS-mutagenized yeast clones were screened for increased sensitivity to ciclopirox olamine. Fourteen mutants, cos101-cos114, were identified and characterized. The targets of ciclopirox olamine in S. cerevisiae appear to include multiple proteins that participate in various components of cellular metabolism, including DNA replication, DNA repair, and cellular transport. Three genes were cloned: a Fe/Cu reductase (FRE1/COS107), an oxidative stress response gene (YAP1/COS110), and a gene involved in signal transduction (YBR203W/COS111). These results suggest that CPO inhibits multiple aspects of cell growth and metabolism, possibly via multiple targets.

Antifungal Agents↗
PubMed1996

Coordinating DNA replication to produce one copy of the genome requires genes that act in ubiquitin metabolism.

We have developed a genetic screen of the yeast Saccharomyces cerevisiae to identify genes that act to coordinate DNA replication so that each part of the genome is copied exactly once per cell cycle. A mutant was recovered in this screen that accumulates aberrantly high DNA contents but does not complete a second round of synthesis. The mutation principally responsible for this phenotype is in the DOA4 gene, which encodes a ubiquitin hydrolase, one of several yeast genes that encode enzymes that can remove the signalling polypeptide ubiquitin hydrolase, one of several yeast genes that encode enzymes that can remove the signaling polypeptide ubiquitin from its covalently linked conjugated forms. DOA4 is nonessential, and deleting this gene causes uncoordinated replication. Overreplication does not occur in cells with limiting amounts of Cdc7 protein kinase, suggesting that entry into S phase is required for this phenotype. The DNA formed in doa4 mutants is not highly unusual in the sense that mitotic recombination rates are normal, implying that a high level of repair is not induced. The temperature sensitivity of doa4 mutations is partially suppressed by extra copies of the polyubiquitin gene UB14, but overreplication still occurs in the presence of this suppressor. Mutations in DOA4 cause loss of the free ubiquitin pool in cells under heat stress conditions, and extra copies of UB14 restore this pool without restoring coordination of replication. We conclude that a ubiquitin-mediated signaling event directly involving the ubiquitin hydrolase encoded by DOA4 is needed in S. cerevisiae to prevent uncoordinated DNA replication.

DNA Polymerase II↗
PubMed2006

Cell cycle checkpoints: the role and evaluation for early diagnosis of senescence, cardiovascular, cancer, and neurodegenerative diseases.

Maintenance of genomic integrity is critical for prevention of a wide variety of adverse cellular effects including apoptosis, cellular senescence, and malignant cell transformation. Under stress conditions and even during an unperturbed cell cycle, checkpoint proteins play the key role in genome maintenance by and mediating cellular response to DNA damage, and represent an essential part of the "cellular stress response proteome". Intact checkpoint signal transduction cascades check the presence of genome damage, trigger cell cycle arrest, and forward the information to the protein core of cell cycle machinery, replication apparatus, repair, and/or apoptotic protein cores. Genetic checkpoint defects lead to syndromes that demonstrate chromosomal instability, increased sensitivity to genotoxic stress, tissue degeneration, developmental retardation, premature aging, and cancer predisposition that is most extensively studied for the ATM-checkpoint mutated in Ataxia telangiectasia. Tissue specific epigenetic control over the function of cell cycle checkpoints can be, further, misregulated by aberrant DNA methylation status. The consequent checkpoint dysregulation may result in tissue specific degenerative processes such as degeneration and calcification of heart aortic valves, diabetic cardiomyopathy, hyperhomocysteinemic cerebrovascular, peripheral vascular and coronary heart diseases, neurodegenerative disorders (Alzheimer and Parkinson diseases, amyotrophic lateral sclerosis, glaucoma), and accelerated aging frequently accompanied with cancer. This review focuses on the checkpoints shown to be crucial for unperturbed cell cycle regulation, dysregulation of which might be considered as a potential molecular marker for early diagnosis of and therapy efficiency in neurodegenerative, cardiovascular and cancer diseases. An application of the most potent detection technologies such as "Disease Proteomics and Transcriptomics" also considered here, allows a most specific selection of diagnostic markers.

Animals↗
PubMed2006

Hepatocyte nuclear factor (HNF) 1 and HNF4 mediate hepatic multidrug resistance protein 2 up-regulation during hepatitis C virus gene expression.

Hepatitis C virus (HCV) is known to induce hepatic oxidative stress that is implicated in the up-regulation of multidrug resistance proteins (MRPs). The relationship between increased prooxidant production, MRPs, and HCV has not been investigated. Here, we report that a homeodomain-containing transcription factor, hepatocyte nuclear factor (HNF) 1, plays a central role in liver gene regulation during HCV gene expression and/or subgenome replication. MRP2 protein and mRNA expression were increased and MRP2 promoter activity was increased 7-fold. Mutations within the putative HNF1 binding site of the human MRP2 promoter abrogated HCV-induced activation, implicating HNF1 in the induction of MRP2 by HCV. The mechanism by which HNF1-mediated activation occurs seems to be transcriptional, because the regulated expression of HNF4, which is known to control HNF1 expression, was also increased. Consistent with this finding, HNF1 mRNA was increased 10-fold. A promoter-luciferase construct of the human HNF1 gene was activated in an HNF4-dependent manner, and a mutant construct lacking the HNF4 binding site was not activated in HCV-positive cells. Consistent with this hypothesis, HNF4 protein and mRNA levels as well as HNF4 promoter activity and DNA binding activity were increased. The expression of HNF1 seems to play a critical role in the induction of hepatic MRP2 secondary to HCV subgenomic replication. The ability of HCV to induce HNF1 and HNF4 is attributed to 1) increased oxidative stress and 2) direct protein-protein interactions between HCV nonstructural component (NS) 5A and HNF1, leading to enhanced HNF1 DNA binding. In conclusion, we describe a novel mechanism by which HCV gene expression may induce adaptive responses involving MRP2 via HNF1 activation. This may constitute, in part, the cellular detoxification task force during HCV infection.

Cell Line↗
PubMed2006

The effect of dietary probiotic supplementation on tibial bone characteristics and strength in broilers.

A 6-wk study with 50 birds was conducted to investigate the effects of a dietary supplemental probiotic on morphometric parameters and yield stress of the tibia. Twenty-five 1-d-old broiler chicks were assigned to a control or an experimental diet containing Bacillus licheniformis and Bacillus subtilis (BioPlus 2B, CHR Hansen BioSystems, Denmark, Ugur Ecza Deposu, Turkiye Distributoru, Adapazari 41400, Turkey; each containing 2.3 x 10(8) cfu/g of spores) supplemented to the starter and finisher diets at 500 g/1000 kg of feed. Each diet was replicated 5 times with 5 birds in each replicate. Tibiotarsi weight, length, and weight/length index, robusticity index, diaphysis diameter, modulus of elasticity, yield stress parameters, and percentage Ca content were not affected by the dietary supplementation of probiotic, whereas thickness of the medial and lateral wall of the tibia, tibiotarsal index, percentage ash, and P content were significantly improved by the probiotic. Medullary canal diameter of the tibia of the birds fed the control diet was significantly greater than that of birds fed the probiotic diet. There was no treatment impact on live performance of the birds throughout the 6-wk feeding trial.

Animal Feed↗
PubMed2001

Does long term potentiation in periacqueductal gray (PAG) mediate lasting changes in rodent anxiety-like behavior (ALB) produced by predator stress?--Effects of low frequency stimulation (LFS) of PAG on place preference and changes in ALB produced by predator stress.

The effects on rodent behavior of low frequency bilateral stimulation (LFS, 900 pulses at 1 Hz) of periacqueducatal gray (PAG) was investigated. The first experiment examined aversive qualities of LFS in a place preference paradigm. There was no evidence of a place preference after 1 or 7 applications of LFS. After the first LFS, rats showed longer latencies to leave the conditioned chamber, suggesting a positively reinforcing effect of LFS. Latency differences were not accounted for by freezing or immobility prior to leaving. Rats with electrodes outside the PAG did not show these effects. After repeated LFS, stimulated rats did not differ from controls in place preference or in anxiety-like behavior (ALB). Experiment 2 studied the effects of predator stress in unimplanted rats on an extended battery of measures of ALB in hole board, plus maze and light/dark box tests of rodent anxiety. Effects of electrode damage in the PAG on ALB was also examined. In addition, the effect of 7 applications of bilateral LFS of PAG on ALB following a 5 min unprotected exposure of rats to a cat (predator stress) was examined. Predator stress lastingly changed a wide variety of behaviors in the plus maze, [Rodgers, Behav. Pharmacol. 8 (1997) 477] replicating and extending previous reports. A new finding is an increase in light avoidance in the light/dark box test. Moreover, factor analysis revealed open arm avoidance, risk assessment, light avoidance and cautious exploration loaded on independent factors, replicating and extending previous findings. Bilateral, but not unilateral, damage specific to PAG was also found to be anxiolytic in plus maze measures of ALB. Bilateral implants in the PAG seemed to prevent many of the effects of predator stress on ALB measured 8 days later. Nevertheless, predator stress did decrease head dips in the open arm and LFS reversed this effect. Light avoidance also increased following predator stress and LFS reversed this increase. These findings suggest the PAG occupies an important position in the final common path of substrate changes mediating effects of predator stress on a range of behaviors in the rodent. The fact that LFS in the PAG can reverse stress induced changes in behavior supports the idea that LTP in PAG mediates stress induced increases in anxiety in rodents, as it does in the cat [Adamec, Neurosci. Biobevav. Rev. 21(6) (1997) 755; Adamec, J. Psychopharmacol. 2000 (in press); Adamec, J. Psychopharmacol. 2000 (in press); Adamec, J. Psychopharmacol. 12(2) (1998) 129; Adamec, J. Psychopharmacol. 12(13) (1998) 227].

Animals↗
PubMed1993

Physical and chemical methods for enhancing rapid detection of viruses and other agents.

Viral replication events can be enhanced by physical, chemical, or heat treatment of cells. The centrifugation of cells can stimulate them to proliferate, reduce their generation times, and activate gene expression. Human endothelial cells can be activated to release cyclo-oxygenase metabolites after rocking for 5 min, and mechanical stress can stimulate endothelial cells to proliferate. Centrifugation of virus-infected cultures can increase cytopathic effects (CPE), enhance the number of infected cells, increase viral yields, and reduce viral detection times and may increase viral isolation rates. The rolling of virus-infected cells also has an effect similar to that of centrifugation. The continuous rolling of virus-infected cultures at < or = 2.0 rpm can enhance enterovirus, rhinovirus, reovirus, rotavirus, paramyxovirus, herpesvirus, and vaccinia virus CPE or yields or both. For some viruses, the continuous rolling of infected cell cultures at 96 rpm (1.9 x g) is superior to rolling at 2.0 rpm for viral replication or CPE production. In addition to centrifugation and rolling, the treatment of cells with chemicals or heat can also enhance viral yields or CPE. For example, the treatment of virus-infected cells with dimethyl sulfoxide can enhance viral transformation, increase plaque numbers and plaque size, increase the number of cells producing antigens, and increase viral yields. The infectivity of fowl plague virus is increased by 80-fold when 4% dimethyl sulfoxide is added to culture medium immediately after infection. The heat shocking of virus-infected cells also has been shown to have a stimulatory effect on the replication events of cytomegalovirus, Epstein-Barr virus, and human immunodeficiency virus. The effects of motion, chemicals, or heat treatments on viral replication are not well understood. These treatments apparently activate cells to make them more permissive to viral infection and viral replication. Perhaps heat shock proteins or stress proteins are a common factor for this enhancement phenomenon. The utility of these treatments alone or in combination with other methods for enhancing viral isolation and replication in a diagnostic setting needs further investigation.

Animals↗
PubMed1987

Critical care nursing.

The research pertaining to the delivery of nursing care in the ICU was reviewed to describe: the impact of the unit structure and organization, including policies and procedures, on patients, nurses, and families; the process of critical care nursing; the outcomes of critical care nursing; some of the ethical issues germane to the care of the critically ill patient. Although these areas of inquiry are quite diverse, a number of similarities can be identified. The most obvious of the similarities was that, with few exceptions, the studies pertaining to delivery of nursing care were performed by researchers from a variety of disciplines other than nursing, including medicine, psychology, public health, and economics. In many instances, such as the studies of patients' stress experiences in ICUs, these efforts enhanced our knowledge of the phenomena and complemented or replicated the efforts of nurse researchers. Unfortunately, in some areas nurse researchers were quite absent, with the result that the studies lacked a nursing perspective. For example, the large body of knowledge related to the effects of critical care on patient outcome reflected medicine's orientation toward cure. While it is important to measure the effect of nursing care in the ICU on patient survival, the effect of nursing efforts on short- and long-term quality of life, functional status, and health maintenance is also critical and remains unknown. Nurse researchers need to build on the data base already acquired about critical care. Even more important, they need to fashion programs of research focused on the concepts central to the discipline of nursing. A second similarity relates to the increasing quality of the reported research over the past decade. In general, early descriptive studies were conducted in a single critical care unit with a small and often biased sample. These gave way to more carefully designed, multicenter studies, although lack of randomization procedures continued to be a significant problem. Increasing attention was paid to the psychometric properties of instruments, and the validity and reliability of these instruments were appropriately discussed by the researchers using them. However, the area of family stress is a remarkable exception to this positive trend. Investigators also began to address the problem of sample homogeneity in some of the areas of inquiry by replicating their work outside the often favored CCU. The third and final similarity lies with the preponderance of descriptive studies in all areas reviewed.(ABSTRACT TRUNCATED AT 400 WORDS)

Critical Care↗
PubMed2006

An empirical delineation of the heterogeneity of chronic unexplained fatigue in women.

OBJECTIVES: To test the hypothesis that medically unexplained chronic fatigue and chronic fatigue syndrome (CFS) are heterogeneous conditions, and to define the different conditions using both symptom and laboratory data. METHODS: We studied 159 women from KS, USA. A total of 51 of these suffered from fatigue consistent with established criteria for CFS, 55 had chronic fatigue of insufficient symptoms/severity for a CFS diagnosis and 53 were healthy controls matched by age and body mass index (BMI) against those with CFS. We used principal components analyses to define factors that best described the variable space and to reduce the number of variables. The 38 most explanatory variables were then used in latent class analyses to define discrete subject groups. RESULTS: Principal components analyses defined six discrete factors that explained 40% of the variance. Latent class analyses provided several interpretable solutions with four, five and six classes. The four-class solution was statistically most convincing, but the six-class solution was more interpretable. Class 1 defined 41 (26%) subjects with obesity and relative sleep hypnoea. Class 2 were 38 (24%) healthy subjects. Class 3 captured 24 (15%) obese relatively hypnoeic subjects, but with low heart rate variability and cortisol. Class 4 were 23 (14%) sleep-disturbed and myalgic subjects without obesity or significant depression. The two remaining classes with 22 (14%) and 11 (7%) subjects consisted of the most symptomatic and depressed, but without obesity or hypnoea. Class 5 had normal sleep indices. Class 6 was characterized by disturbed sleep, with low sleep heart rate variability, cortisol, and sex hormones. CONCLUSION: Chronic medically unexplained fatigue is heterogeneous. The putative syndromes were differentiated by obesity, sleep hypnoea, depression, physiological stress response, sleep disturbance, interoception and menopausal status. If these syndromes are externally validated and replicated, they may prove useful in determining the causes, pathophysiology and treatments of CFS.

Adult↗
PubMed2000

Accumulation of single-strand breaks is the major cause of telomere shortening in human fibroblasts.

Telomere shortening triggers replicative senescence in human fibroblasts. The inability of DNA polymerases to replicate a linear DNA molecule completely (the end replication problem) is one cause of telomere shortening. Other possible causes are the formation of single-stranded overhangs at the end of telomeres and the preferential vulnerability of telomeres to oxidative stress. To elucidate the relative importance of these possibilities, amount and distribution of telomeric single-strand breaks, length of the G-rich overhang, and telomere shortening rate in human MRC-5 fibroblasts were measured. Treatment of nonproliferating cells with hydrogen peroxide increases the sensitivity to S1 nuclease in telomeres preferentially and accelerates their shortening by a corresponding amount as soon as the cells proliferate. A reduction of the activity of intracellular peroxides using the spin trap alpha-phenyl-t-butyl-nitrone reduces the telomere shortening rate and increases the replicative life span. The length of the telomeric single-stranded overhang is independent of DNA damaging stresses, but single-strand breaks accumulate randomly all along the telomere after alkylation. The telomere shortening rate and the rate of replicative aging can be either accelerated or decelerated by a modification of the amount of oxidative stress. Quantitatively, stress-mediated telomere damage contributes most to telomere shortening under standard conditions.

Alkylation↗
PubMed2004

Genotype-specific responses of fluctuating asymmetry and of preadult survival to the effects of lead and temperature stress in Drosophila melanogaster.

Although fluctuating asymmetry (FA) increases with exposure to certain types of environmental stressors such as temperature extremes, relatively little is known about the effects of interaction (e.g., synergism) between known sources of environmental stress on FA. Knowledge of such interaction effects, and of the magnitude of genotype-by-environment interaction, are of fundamental importance toward predicting the usefulness of FA as a bioindicator of environmental pollution. We tested for synergistic effects on FA between elevated temperature and exposure to lead, and examined FA responses simultaneously in four genetic strains of Drosophila melanogaster known to differ in their degree of developmental instability, and presumably in their buffering capacity. In the absence of heavy metal, bristle FA increased with temperature, but in the presence of lead, FA at high temperature (30 (degrees)C) was reduced to levels similar, or below, that at lower temperature (25 (degrees)C). This temperature by lead interaction was statistically significant, but paradoxical in that the disruptive effects of temperature appeared to be attenuated in the presence of the heavy metal. In no case was there a significant effect of lead on bristle FAs, despite documented assimilation of heavy metal by flies, and in no case was the genotype by environment interaction significant. Whereas lead treatment did not influence survival, survival was reduced at the high temperature, but significantly so only in one genetic strain (Oregon-R). There was no relationship between survival and FA across stress treatments within lines. Thus, any disproportionate stress-induced mortality in developmentally unstable classes (developmental selection) was unlikely to bias the FA results. Our results underscore the need for independent replication of significant findings before FA-based biomonitoring can be responsibly and effectively implemented. The results call for caution in using FA as a biomarker of stress, because stress factors may interact in complex and unpredictable ways, which could result in erroneous conclusions about real levels of stress present in field populations, under the unduly simplistic assumption that stress factors will act additively to increase FA.

Animals↗
PubMed1996

Knowledge and conscious control of motor actions under stress.

A recent study by Masters (1992) investigated the effect of stress upon the performance of a well-learned motor skill, golf putting, acquired under implicit and explicit learning conditions. Masters found that stress had a detrimental effect on performance for the explicit learning group but not for the implicit learning group. However, the implicit learning group was required to perform articulatory suppression during the learning trials but not during the stress trials. As such, it is possible that the subjects in the implicit learning group continued to improve during the stress session simply because they were performing an easier task. This paper reports an experiment which re-examines Masters' (1992) conclusions by replicating and extending his method. An additional implicit learning group was included which was required to carry out articulatory suppression during both the learning trials and the stress trials. It was hypothesized that this 'new' implicit learning group would suffer the same disruption to performance as the explicit learning group, providing evidence which would contradict Masters' explanation. Thirty-two subjects were allocated to one of four groups. Performance measures were analysed using two-factor analysis of variance (4 x 5: groups x sessions) with repeated measures on the sessions factor. The main dependent variable was the number of putts successfully completed. The analysis revealed that both the implicit learning groups continued to improve their performance under stress whilst the explicit learning group did not. Despite limitations to both Masters' (1992) and the present study, these results add support to Masters' explicit knowledge hypothesis.

Adult↗
PubMed1982

Production and level of genetic stability of an influenza A virus temperature-sensitive mutant containing two genes with ts mutations.

Temperature-sensitive (ts) reassortant vaccine strains derived from the A/Udorn/72 ts-1A2 donor virus were not sufficiently stable genetically in humans. We therefore sought to produce a new, more stable donor virus. We had previously identified a stable ts virus with a ts P3 gene and in the current study identified another relatively stable single-lesion ts virus with a ts mutation in the NP gene. A new ts reassortant virus was constructed by mating these two single mutants and by isolating three reassortant progeny, clones 20, 53, and 55, that contained both a ts P3 and a ts NP gene. These reassortant progeny possessed a 37 to 38 degrees C shutoff temperature and were as restricted in their replication in hamster lungs as the A/Udorn/72 ts-1A2 virus. All isolates from the lungs and nasal turbinates of hamsters were temperature sensitive. An in vitro stress test was used to determine whether the new ts P3 ts NP reassortant virus would undergo loss of its ts phenotype after replication at semipermissive temperature. Clone 20 and 55 reassortants underwent progressive loss of their ts phenotype in vitro, although at a rate slightly less than that of the A/Udorn/72 ts-1A2 virus. The level of genetic stability after replication in vivo was assessed in cyclophosphamide-treated hamsters in which virus replication continued for up to 15 days. Again, both the A/Udorn/72 ts-1A2 and the new ts P3 ts NP reassortant clone 55 manifested a progressive loss of temperature sensitivity after 7 days of replication. Clone 55 virus lost temperature sensitivity significantly less rapidly than the A/Udorn/72 ts-1A2 virus. These results indicated that, although the new ts P3 ts NP reassortant virus was more stable than the A/Udorn/72 ts-1A2 virus, it nevertheless underwent progressive loss of temperature sensitivity after replication in vitro and in vivo. Therefore, it does not appear to be a satisfactory donor virus. This experience plus that gained earlier with other ts mutants of influenza A virus suggest that influenza A virus mutants that rely solely upon their ts phenotype for attenuation are unlikely to exhibit the phenotypic stability required of a vaccine virus. Other genetic techniques are needed to produce more stable influenza A virus strains.

Animals↗
PubMed1983

Individual differences in cortisol secretory patterns in the wild baboon: role of negative feedback sensitivity.

It was previously shown that rank-related differences in adrenocortical function existed among the males of a troop of olive baboons living in their natural habitat in East Africa. High-ranking males, by the criterion of reproductive activity, had significantly lower cortisol titers than those of subordinates, when measured immediately after immobilization with anesthetic. However, high-ranking males elevated titers rapidly during the early period of immobilization stress, attaining titers equal to those of subordinates at 60 min. The present study replicates these rank differences and provides possible endocrine mechanisms underlying them. Males with low basal titers (predominantly high-ranking males) had the fastest and most extreme suppressions of circulating cortisol titers after dexamethasone administration. However, they had cortisol clearance rates similar to those of individuals with high initial cortisol titers. These data suggest that the rank-related variance in basal cortisol levels is attributable to differential sensitivity to negative feedback regulation. Males who elevated cortisol titer most rapidly during the early poststress period (again, predominantly high-ranking males) had adrenals no more responsive to an ACTH challenge than those of remaining subjects. This suggests that a rapid adrenocortical secretory response during stress is not attributable to enhanced adrenal sensitivity to ACTH, but rather to an accelerated secretion of ACTH by the pituitary gland.

Adrenocorticotropic Hormone↗
PubMed1994

Social stress and state-to-state differences in smoking and smoking related mortality in the United States.

This paper reports on the relationship between the stressfulness of the social environment, smoking and mortality rates for malignant neoplasms of the respiratory system and chronic obstructive pulmonary disease (COPD). A macro-social approach was employed with the 50 states of the United States serving as the units of analysis. A 'State Stress Index' was computed using stressful events in 15 categories (divorce rate, business failures, natural disasters, etc.). Smoking behavior was measured by percentage smokers and the average cigarette sales per capita. Mortality rates for lung cancer and COPD were standardized by age. The percent population living in metropolitan areas, black, below poverty line, and with less than high school education were included as controls in the multiple regression analysis. The results show that populations that experience higher levels of stressful events smoke more heavily and eventually experience higher mortality from lung cancer and COPD. These relationships are robust: they are replicated for different time periods, for different measures of the independent and dependent variables, and with different analytic methods. The pattern of findings is consistent with a 'health behavior' model of stress in which populations under stress engage in behavior which is extremely inimical to health.

Aged↗