Effect of pullet body weight and hen dietary amino acid treatments on their progeny fed high and low amino acid diets.

Four studies were conducted on Cobb 700 broilers to evaluate the dietary protein and any maternal effects on live production and processing parameters. Day-old Cobb 700 broiler breeder pullets were reared to conform to 2 different BW curves (control BW and increased BW) with 8 replicate pens per treatment. Birds were fed common diets from 1 d of age until first egg (24 wk). At 24 wk, 12 pens of each pullet treatment were given different amino acid (AA) diets (low = 14% CP, high = 15% CP). The performance of female and male progeny from 32 and 45 wk hens were evaluated on low AA and high AA density diets. The 4 progeny trial designs were identical factorial 2 × 2 × 2 designs, with 2 pullet BW curves (control BW and increased BW), 2 dam CP diet levels (low and high), and 2 progeny CP diets (low and high), with 6 replicates each containing 18 birds, for a total of 108 broiler progeny per treatment. Broiler chickens on the higher AA density feed exhibited consistent improvement in mid-growth BW and FCR and white meat yield percentage. Some maternal effects were noted, including increased carcass yield in female broilers from 32 wk old hens. There were 3-way interactions of pullet BW × hen dietary AA × progeny dietary AA treatments for female progeny carcass yield (from 32-week-old hens) and male tender yield (from 45-week-old hens). There were 2-way interactions of pullet BW x hen dietary AA treatments effect on female and male progeny drumstick yield from 32-week-old hens, pullet BW × progeny dietary AA treatments effect on male 27 d BW from 32-week-old hens, and hen dietary AA × progeny dietary AA treatments effect on male thigh yield from 45-week-old hen. The epigenetic effects of maternal pullet BW and dietary AA treatments were seen in processing yields suggesting, the need of dietary CP changes of the progeny.

Self-efficacy, coping, and difficulties interacting with health care professionals among women living with breast cancer in rural communities.

This study examined self-efficacy, coping, and social support in relation to difficulties interacting with physicians and nurses among women living with breast cancer. One hundred women living in rural, mountainous communities of northeastern California were recruited, with 89 providing complete data for this study. All women completed a battery of questionnaires that included the CARES--Medical Interaction Subscale and measures of self-efficacy, coping, satisfaction with social support, and demographic and medical characteristics. In a multiple regression analysis, difficulties interacting with medical professionals were found to be greater among women who were not married, who used more behavioral disengagement or less self-distraction to cope with breast cancer, and who reported less self-efficacy for affect regulation and for seeking and understanding medical information. Emotional venting and satisfaction with social support for dealing with cancer-related stress were not, however, significantly related to difficulties in interacting with the medical team. This model accounted for an adjusted value of 42% of the variance. Further research is needed to identify possible causal relationships related to these findings and to determine what interventions might be warranted to improve medical interactions for women with breast cancer living in rural areas.

Revictimization and information processing in women survivors of childhood sexual abuse.

This study examined the effect of sexual revictimization on information processing of trauma-related stimuli in a sample of child sexual abuse (CSA) survivors diagnosed with posttraumatic stress disorder (PTSD). Fifty-one treatment-seeking women participated in this study. Participants completed the Sexual Experiences Survey regarding sexual revictimization in the last 6 months and performed a modified emotional Stroop task in which they named the colors of neutral words (e.g., apple), general threat words (e.g., malignant and death), and sexual/victimization words (e.g., penis and abuser). As predicted, the revictimized participants (n = 16) took significantly longer to color-name sexual/victimization words than did the nonrevictimized participants. These results suggest that revictimization serves to prime preexisting "trauma" memory networks, thereby amplifying the impact of childhood sexual trauma on selective attention toward trauma-related stimuli.

Supportive-expressive group therapy and distress in patients with metastatic breast cancer: a randomized clinical intervention trial.

BACKGROUND: Metastatic breast cancer carries with it considerable psychosocial morbidity. Studies have shown that some patients with metastatic breast cancer experience clinically significant anxiety and depression and traumatic stress symptoms. Supportive-expressive group psychotherapy was developed to help patients with cancer face and adjust to their existential concerns, express and manage disease-related emotions, increase social support, enhance relationships with family and physicians, and improve symptom control. METHODS: Of 125 women with metastatic breast cancer recruited into the study, 64 were randomized to the intervention and 61 to the control condition. Intervention women were offered 1 year of weekly supportive-expressive group therapy and educational materials. Control women received educational materials only. Participants were assessed at baseline and every 4 months during the first year. Data at baseline and from at least 1 assessment were collected from 102 participants during this 12-month period, and these participants compose the study population. RESULTS: Primary analyses based on all available data indicated that participants in the treatment condition showed a significantly greater decline in traumatic stress symptoms on the Impact of Event Scale (effect size, 0.25) compared with the control condition, but there was no difference in Profile of Mood States total mood disturbance. However, when the final assessment occurring within a year of death was removed, a secondary analysis showed a significantly greater decline in total mood disturbance (effect size, 0.25) and traumatic stress symptoms (effect size, 0.33) for the treatment condition compared with the control condition. CONCLUSION: Supportive-expressive therapy, with its emphasis on providing support and helping patients face and deal with their disease-related stress, can help reduce distress in patients with metastatic breast cancer.

Relationships of perceived stress to coping, attachment and social support among HIV-positive persons.

The purpose of this study was to examine the relationships of coping, attachment style and perceived social support to perceived stress within a sample of HIV-positive persons. Participants were 147 HIV-positive persons (80 men and 67 women). Multiple regression analysis was used to examine the relationships of the demographic variables, AIDS status, three coping styles, three attachment styles and perceived quality of general social support with total score on the Perceived Stress Scale (PSS). PSS score was significantly associated with less income, greater use of behavioural and emotional disengagement in coping with HIV/AIDS, and less secure and more anxious attachment styles. These results indicate that HIV-positive persons who experience the greatest stress in their daily lives are those with lower incomes, those who disengage behaviourally/emotionally in coping with their illness, and those who approach their interpersonal relationships in a less secure or more anxious style.

Traumatic stress, life events, and emotional support in women with metastatic breast cancer: cancer-related traumatic stress symptoms associated with past and current stressors.

This study examined levels of intrusion and avoidance symptoms and their relationships to past life stress, current emotional support, disease-related variables, and age in 125 women with metastatic breast cancer. The results indicate that a sizable proportion of these women experienced clinically significant levels of intrusion and avoidance symptoms related to their cancer, particularly those with both more stressful past life events and higher current levels of aversive emotional support. Additionally, both types of symptoms were associated with shorter time since recurrence, and avoidance symptoms were associated with smaller emotional support networks. These results indicate that metastatic breast cancer is an emotionally traumatic event for a significant proportion of women, particularly those with past life stressors and unsupportive social environments.

Cell-free synthesis of anticoagulant heparan sulfate reveals a limiting converting activity that modifies an excess precursor pool.

LTA cells synthesize a minor population of heparan sulfate proteoglycans (HSPGact) bearing anticoagulant heparan sulfate (HSact) with a specific monosaccharide sequence that accelerates the action of antithrombin (AT). LTA cells also synthesize a major population of heparan sulfate proteoglycans endowed with nonanticoagulant heparan sulfate (HSinact) lacking the AT-binding site. To investigate the pathway-specific features of HSPGact generation, we established a novel detergent-containing cell-free system with unlabeled and labeled microsomes from wild-type and variant LTA cells, respectively. The unlabeled microsomes provide "HSact conversion activity" that requires 3'-phosphoadenosine 5'-phosphosulfate to convert [35S]HSPGinact into [35S] HSPGact, presumably by sulfation. The reaction kinetics demonstrate that the rate of HSact synthesis is constant over the first 4 h of incubation. During this time, the rate of HSact production is linearly dependent on the amount of unlabeled LTA microsomal protein over a range of 10 to 50 microg as well as on the level of [35S]HS substrate over a range of 0.4 to 4.0 microg, microsomal protein. Compared with labeled microsomes, equivalent or slightly greater levels of HSact were generated from 35S-labeled HSPG, microsomal HS, or cell surface HS, which demonstrates that HSinact is the minimal substrate and that large amounts of HSact precursor exit the Golgi apparatus. Indeed, extensive modification of wild-type LTA cell surface [35S]HS elevated HSact content from 9 to 35%. The hypothesis that microsomal HSact conversion activity predicts the cellular rate of HSact generation was tested with wild-type or variant LTA cells in which production of HSact has been significantly altered by mutagenesis or overexpression of core protein or growth conditions. The data demonstrate that microsomal HSact conversion activity accurately reflects the cellular rate of HSact synthesis over a very wide range of conditions. The possibility that the reduced HSact generation is due to an inhibitor was excluded by mixing experiments. The possibility that reduced HSact generation is caused by decreased levels of HSact precursor was excluded as equivalent levels of HSact were formed from wild-type and variant [35S]HS. Based upon the above data, the LTA cell microsomal HSact conversion activity contains one or more limiting components that kinetically regulate the rate of cellular HSact generation and the levels of HSact precursor in HS greatly exceed HSact production.

Hypnotizability and traumatic experience: a diathesis-stress model of dissociative symptomatology.

OBJECTIVE: The authors propose a diathesis-stress model to describe how pathological dissociation may arise from an interaction between innate hypnotizability and traumatic experience. METHOD: To support the proposition that pathological dissociation may reflect autohypnotic process, the authors highlight clinical and research data indicating parallels between controlled hypnotic dissociative states and uncontrolled pathological dissociative symptoms and summarize evidence of hypnotizability in persons with psychiatric disorders that manifest these symptoms. The authors present this evidence by examining dissociative symptomatology in four psychological domains: perception, behavior and will, affect, and memory and identity. In addition, modern cognitive and neuropsychological models of dissociation are briefly reviewed. RESULTS: Several lines of evidence converge in support of the role of autohypnosis in pathological dissociation. There is considerable evidence that controlled formal hypnosis can produce a variety of dissociations of awareness and control that resemble many of the symptoms in uncontrolled pathological dissociative conditions; and it is possible to discern in dissociative pathology the features of absorption, dissociation, and suggestibility/automaticity that characterize formal hypnotic states. There is also accumulating evidence of high levels of hypnotic capacity in all groups with dissociative symptomatology that have been systematically assessed. In addition, the widespread and successful therapeutic use of hypnosis in the treatment of many dissociative symptoms and conditions (and the potential for hypnosis to induce dissociative symptomatology) also supports the assumption that hypnosis and pathological dissociation share an underlying process. CONCLUSIONS: High hypnotizability may be a diathesis for pathological dissociative states, particularly under conditions of acute traumatic stress.

Psychophysiological consequences of unexplained arousal: a posthypnotic suggestion paradigm.

This experiment compared the emotional, cognitive, and physiological responses of Ss experiencing induced physiological arousal with and without awareness of the source of their arousal. Nine highly hypnotizable Ss and 9 nonhypnotizable controls were used in a within-subjects design. Each S received posthypnotic suggestions for arousal (increases in heart and respiration rate) with and without amnesia for its source in a two-phase procedure. Only the hypnotizable Ss were expected to differ between conditions. As predicted, for the hypnotizable Ss, unexplained arousal produced significant and dramatic effects when compared with explained arousal, including misattributions. These results are considered within a conceptual framework of the role of discontinuous experiences in the development of psychopathological symptoms in normal persons.

Contagion in schizophrenia: a critique of Crow and Done (1986).

This article discusses the literature on the possible role of viruses in the development of schizophrenia and outlines the evidence that compelled Crow and Done (1986) to reject a horizontal contagion hypothesis (e.g., sibling to sibling transmission). We posit a genetically determined age after which one becomes vulnerable to the illness, rather than a strict age of onset. We also propose an environmentally determined range of resistance to this susceptibility as an alternative conceptualization of the role of inheritance and of viral exposure in the etiology of the disease. The predictions derived from our new model fit the findings of Crow and Done and are consistent with the older literature of possible viral factors, thus reaffirming the horizontal contagion hypothesis.

Endotoxin tolerance: independent regulation of interleukin-1 and tumor necrosis factor expression.

The injection of lethal or sublethal doses of bacterial lipopolysaccharide (LPS) into mice results in transient increases in both serum tumor necrosis factor (TNF) and interleukin-1 (IL-1). The peak in serum TNF was detected prior to maximal elevation in endogenous corticosterone and was no longer apparent 3 to 4 h post-LPS injection, a point at which corticosterone and IL-1 levels had significantly increased. The initial increase in serum IL-1 may, in part, be modulated by the preceding TNF peak, as pretreating animals with a monoclonal antibody against murine TNF resulted in a significant decrease in IL-1 levels 3 h post-LPS injection. A second injection of LPS at 20 h failed to result in a secondary TNF peak, suggesting an endotoxin-tolerant state. However, in contrast to TNF, significant increases in serum IL-1 were detected in the endotoxin-tolerant animals following a repeated LPS stimulus. This secondary increase in IL-1 occurred despite the elevation in serum corticosterone. While peritoneal macrophages from endotoxin-tolerant mice demonstrated only a modest 10 to 15% increase in TNF and IL-1 mRNA relative to the levels after the primary 1-h LPS stimulus, a secondary increase in IL-1 but not TNF mRNA in the spleen was apparent following a second LPS injection. The spleen, however, was not essential for the increase in serum IL-1, as endotoxin-tolerant splenectomized mice had comparable increases in IL-1 following a repeated LPS stimulus. These results demonstrate the differential regulation of IL-1 and TNF in vivo during endotoxin tolerance.

Quantitation of cytokine mRNA levels utilizing the reverse transcriptase-polymerase chain reaction following primary antigen-specific sensitization in vivo--I. Verification of linearity, reproducibility and specificity.

The role of cytokines in vivo has been difficult to assess. This difficulty is due, in part, to the limited number of producer cells and the strict regulation of cytokine production. In order to address this situation, we have developed assays which allow us to quantitate both protein production and steady state mRNA levels from specific in vivo sites. In this report, we present data utilizing these assays on cells obtained from draining LN following specific sensitization with antigen in vivo. In order to determine the relative quantities of cytokine mRNA, we modified the reverse transcriptase-polymerase chain reaction which had been previously described. The modified assay is (1) linear over a large concn range of input template (2) demonstrates a high degree of reproducibility (SE approximately 13%) and (3) is very sensitive. Utilizing this assay, we have measured a constitutive mRNA (DHFR), quantitated both the presence of lymphokine mRNA (IL-2) and the induction of cytokine mRNA (TNF alpha). In this report we have examined the kinetics of TNF alpha mRNA expression and have demonstrated that following epicutaneous sensitization with picryl chloride, there is rapid induction (within 24 hr) of TNF alpha mRNA in the draining LN and that the levels of mRNA remain detectable through d7. In addition, we determined the time course of production of TNF protein by the draining LN cells and found that it was similar to that of the mRNA levels. A potential pathologic role for immune response generated TNF alpha is also discussed. We believe these experiments demonstrate that cytokine production following antigen-specific sensitization in vivo can be analyzed at both the cellular and molecular level. The data suggests that this approach can be used to study cytokine regulation in vivo.

Dissociation of immunosuppression by chlorpromazine and trifluoperazine from pharmacologic activities as dopamine antagonists.

Neuroleptic compounds may affect the immune system through a variety of mechanisms. Most possess a complex pharmacology, which makes specific, causal relationships difficult to discern. In this study, a series of experiments was performed to examine the effects of dopamine antagonists on a battery of immunologic parameters. Mitogen-induced lymphocyte proliferation in vitro was inhibited by haloperidol, chlorpromazine, and trifluoperazine at 10, 1 and 1 microM concentrations, respectively. Sulpiride and metoclopramide had no direct effect in vitro. In vivo lymphocyte proliferation was significantly reduced by chlorpromazine at the highest tested doses (12.5 and 15 mg/kg) and by trifluoperazine at the highest tested dose (30 mg/kg). All other dopamine antagonists had no significant effect on in vivo lymphocyte proliferation. A murine graft vs host (GVH) response was unaffected by haloperidol, sulpiride, and metoclopramide. Chlorpromazine and trifluoperazine exhibited significant inhibition of the GVH response at the highest doses only (15 and 30 mg/kg, respectively). In a picryl chloride induced delayed type hypersensitivity (DTH) assay, haloperidol, metoclopramide, and sulpiride had no effect. However, both chlorpromazine and trifluoperazine significantly reduced DTH-induced paw swelling at the higher doses (7.5 mg/kg, and 10 and 30 micrograms/kg, respectively). These studies indicate that the more specific dopamine antagonists (e.g. sulpiride, metoclopramide, and haloperidol) do not share the immunologic profiles of chlorpromazine and trifluoperazine, suggesting that these effects of chlorpromazine and trifluoperazine are not related to their dopamine antagonist properties.

Differential production of IL-2 and IL-4 mRNA in vivo after primary sensitization.

The study of lymphokines has been almost entirely conducted by utilizing in vitro assay systems, long term cell lines, and clones. Thus, little information is available concerning the production of lymphokines/cytokines in vivo after specific antigenic stimulation. In order to address this limitation, we have modified the mRNA phenotyping system to allow for the quantitation of lymphokine mRNA after antigenic stimulation in vivo. We report here the production of both IL-2 and IL-4 mRNA in vivo after primary sensitization with picryl chloride. However, the time course of IL-2 and IL-4 mRNA production is discordant. The majority of IL-2 mRNA expression occurs from 1 to 3 days after antigenic exposure, whereas IL-4 mRNA expression occurs mainly from day 3 through day 5. Thus, the production in vivo of these two lymphokine mRNA after sensitization with picryl chloride appears to occur as a "cascade." These results 1) demonstrate that IL-4 mRNA is induced during a primary immune response in vivo and 2) raise the possibility that the generation of an immune response in vivo may involve a specific sequential production of certain lymphokines.

Interleukin 1-induced pathophysiology: induction of cytokines, development of histopathologic changes, and immunopharmacologic intervention.

In this report, we describe a murine system in which treatment with recombinant human interleukin 1 (IL-1) induced an acute lethal state with pathologic changes similar to septic shock at high doses and development of arthritic and other tissue changes following more prolonged treatment with lower doses. We have demonstrated that both recombinant human interleukin 1 alpha and recombinant human interleukin 1 beta could be administered to an endotoxin hyporesponsive strain, C3H/HeJ, and produce these pathologic changes. Induction of tumor necrosis factor (TNF) and colony-stimulating factor activity was noted. The ability to induce these changes was dose and time dependent. Histopathologic changes included lesions in the lung, heart, liver, adrenal glands, intestines, and joints. Neutrophil infiltration was a prominent feature in many organs. Drugs, immunotherapy, or other treatments which have been effective in delaying or preventing a lethal syndrome induced following high dose interleukin 2 therapy were not effective in preventing the interleukin 1-induced lethal syndrome. Interestingly, pretreatment with low nonlethal doses of IL-1 (but not lipopolysaccharides or TNF) could prevent deaths from an LD100 challenge dose of IL-1.

Differential expression of interleukin-1 and tumor necrosis factor in murine septic shock models.

Murine shock models have employed bolus endotoxin as well as cecal ligation and puncture (CLP) in an attempt to understand the pathophysiologic changes associated with human septic shock. Injection of endotoxin results in a rapid but transient rise in tumor necrosis factor (TNF), with maximal levels between 1 and 2 hr followed by an increase in serum interleukin-1 (IL-1) by 3 hr which remains elevated at 24 hr. CLP animals in contrast do not demonstrate an elevation in serum TNF, and the increase in IL-1 is less significant relative to the endotoxin model. Whereas both models demonstrate comparable increases in serum amyloid A protein and result in host death between 24 and 48 hr, these models respond differently to therapeutic modalities. Steroids and an anti-TNF monoclonal antibody administered prophylactically are effective at preventing death in the endotoxin model and yet had no beneficial effect in antibiotic-treated CLP animals. Experiments with adrenalectomized mice suggest that the absence of serum TNF in the CLP model is in part due to the modulatory effects of endogenous corticosteroids.

Neuroendocrine regulation of in vivo cytokine production and effects: I. In vivo regulatory networks involving the neuroendocrine system, interleukin-1 and tumor necrosis factor-alpha.

We have investigated the in vivo regulatory network involving the neuroendocrine system, interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF). Adrenalectomy or hypophysectomy shifted the sensitivity curve to lipopolysaccharide (LPS)-induced lethal shock as well as TNF- and IL-1-induced deaths. Serum levels of IL-1 or TNF were altered in adrenalectomized or hypophysectomized mice following in vivo stimulation with LPS when compared to appropriate sham-operated control mice. Exogenous administration of either IL-1 or TNF could induce increases in serum corticosterone in sham-operated mice. Finally, treatment of adrenalectomized mice with corticosterone or dexamethasone could inhibit the induction of serum IL-1 and TNF and modified the pattern of these cytokine-induced deaths. Dexamethasone was more effective in these conditions than the natural glucocorticoid, corticosterone. Taken together, these data provide in vivo evidence for a feedback system involving the neuroendocrine axis (hypothalamus, pituitary and adrenal glands) leading to corticosterone production and subsequent regulation and/or modulation of IL-1 or TNF levels or activity.