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Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 145 records · Page 8Linked to original sources

Regulation of heregulin beta1-induced differentiation in a human breast carcinoma cell line by the extracellular-regulated kinase (ERK) pathway.

The AU565 breast carcinoma cell line was used to determine the role of the extracellular-regulated kinase (ERK) pathway in mediating Heregulinbeta1 (HRGbeta1)-induced mammary cell differentiation. ERK activation remained elevated for 2 h following high doses of HRG which induce differentiation. In contrast, a transient 5 min peak of ERK activation in response to doses of HRG which induce proliferation was observed. A MEK specific inhibitor, PD98059, which inhibited activation of ERK in response to HRG, completely blocked HRG-induced differentiation and reversed cell growth arrest. To further assess the importance of sustained ERK activity in cellular differentiation, we transiently transfected a mutant constitutively active MEK1 construct into AU565 cells. Differentiation was induced in the absence of HRG and treatment with HRG potentiated this response. These data indicate that sustained activation of the MEK/ERK pathway is both essential and sufficient for HRG-induced differentiation of AU565 cells.

Breast Neoplasms↗

Modulation of the acoustic startle reflex by infusion of corticotropin-releasing hormone into the nucleus reticularis pontis caudalis.

The amplitude of the acoustic startle reflex can be modulated by exposure to aversive stimuli or other conditions which evoke a state of fear. The neurotransmitters involved in this modulation are currently being investigated. Unilateral local infusion of corticotropin-releasing hormone (CRH; 0, 10, 20, 40 and 80 ng) into the nucleus reticularis pontis caudalis (PnC), an obligatory synapse in the acoustic startle reflex, significantly elevated startle amplitude in a dose-dependent manner. The facilitation of startle began immediately following infusion, reached asymptote approximately 20-25 min later, and persisted throughout the remaining 60 min test session. This CRH-enhanced startle effect was blocked by infusion of the CRH antagonist, alpha-helical CRH9-41, immediately prior to CRH infusion. These results support an involvement of CRH at the level of the PnC in modulating the acoustic startle reflex.

Acoustic Stimulation↗

Cosmic velocity fields and their interpretation.

We review the current status of our knowledge of cosmic velocity fields, on both small and large scales. A new statistic is described that characterizes the incoherent, thermal component of the velocity field on scales less than 2h-1 Mpc (h is H0/100 km.s-1.Mpc-1, where H0 is the Hubble constant and 1 Mpc = 3.09 x 10(22) m) and smaller. The derived velocity is found to be quite stable across different catalogs and is of remarkably low amplitude, consistent with an effective Omega approximately 0.15 on this scale. We advocate the use of this statistic as a standard diagnostic of the small-scale kinetic energy of the galaxy distribution. The analysis of large-scale flows probes the velocity field on scales of 10-60 h-1 Mpc and should be adequately described by linear perturbation theory. Recent work has focused on the comparison of gravity or density fields derived from whole-sky redshift surveys of galaxies [e.g., the Infrared Astronomical Satellite (IRAS)] with velocity fields derived from a variety of sources. All the algorithms that directly compare the gravity and velocity fields suggest low values of the density parameter, while the POTENT analysis, using the same data but comparing the derived IRAS galaxy density field with the Mark-III derived matter density field, leads to much higher estimates of the inferred density. Since the IRAS and Mark-III fields are not fully consistent with each other, the present discrepancies might result from the very different weighting applied to the data in the competing methods.

Journal Article↗

2-year tracking of children's fruit and vegetable intake.

OBJECTIVE: To evaluate the tracking of children's fruit and vegetable intake over 2 years. DESIGN: Children in the control group from the Gimme 5 nutrition education intervention trial completed three 7-day food diaries once a year in 1994, 1995, and 1996, beginning when they were in third grade. SUBJECTS: Five hundred sixty-one students from public elementary schools. STATISTICAL ANALYSES PERFORMED: Tracking was examined through correlation of fruit and vegetable servings over the 2 years as well as the percent of subjects remaining in the same or adjacent quintiles of fruit and vegetable intake, using the kappa statistic. RESULTS: Tracking of fruit and vegetable intake was fair to moderate over the 2 years. One-year correlations for total fruit and vegetable servings were .37 for boys and .46 for girls; 2-year correlations were .48 for boys and .40 for girls. kappa values for remaining in the same quintile generally exceeded chance rates only for the top and bottom quintiles. No values exceeded .50. APPLICATION/CONCLUSION: The drift in ranking may have been a result of true changes in fruit and vegetable intake or measurement error (i.e., inability to accurately assess actual intake). If this drift reflects true change, it may be difficult for nutrition education programs targeting this age group to demonstrate long-term behavioral effects on fruit and vegetable intake. If the drift is the result of measurement limitations, improved dietary assessment may yield stronger tracking.

Child↗

Lesions of the bed nucleus of the stria terminalis block sensitization of the acoustic startle reflex produced by repeated stress, but not fear-potentiated startle.

1. The effects of lesions of the bed nucleus of the stria terminalis (BST) on the acquisition of conditioned fear were examined. In Experiment 1, BST lesions did not block acquisition of fear-potentiated startle to an explicit visual conditioned stimulus (CS) over 20 days of training. However, BST lesions blocked a gradual elevation in baseline startle also seen over the course of training. 2. The gradual increase in baseline startle was replicated in Experiment 2 without the presence of an explicit CS, using unoperated subjects. Experiment 2 showed that the elevation was due to repetitive exposure to shock, because unshocked control subjects did not show any elevation over sessions. 3. In Experiment 3, lesions of the BST did not disrupt rapid sensitization of the startle reflex by footshock, showing that different neural substrates underlie sensitization of startle by acute and chronic exposure to footshock. 4. These data indicate that the BST, despite its anatomical continuity with the amygdala, is not critically involved in the acquisition of conditioned fear to an explicit CS. Nevertheless, the BST is involved in mediating a stress-induced elevation in the startle reflex. This suggests that the BST and the CeA, which constitute part of the "extended amygdala" have complementary roles in responses to stress.

Acoustic Stimulation↗

The dorsal cochlear nucleus contributes to a high intensity component of the acoustic startle reflex in rats.

The dorsal cochlear nucleus (DCN) has been shown to project to a region of the nucleus reticularis pontis caudalis (PnC) critical for the evocation of startle in rats, suggesting a possible modulatory influence of the DCN on startle. This study examined the involvement of the DCN in the acoustic startle reflex and various other forms of behavioral plasticity seen with this response. Animals received bilateral electrolytic lesions of the DCN and were tested for acoustic startle responses, background noise facilitation, short-term habituation, prepulse inhibition and facilitation, and fear conditioning. Compared to sham lesioned rats, DCN lesioned rats showed a significant reduction in startle amplitude at the two highest startle-eliciting intensities (110 and 115 dB SPL) and normal responses on all other measures. Hence, the DCN appears to contribute to a high intensity component of the acoustic startle response in rats.

Acoustic Stimulation↗

Results of a domestic violence training program offered to the staff of urban community health centers. Evaluation Committee of the Philadelphia Family Violence Working Group.

INTRODUCTION: Domestic violence (DV) against women often goes unrecognized by health care providers due to multiple barriers. In an effort to increase screening, identification, and referral for services, the RADAR Training Project was created for the health care staff of 12 federally qualified community health centers (CHCs). METHODS: A two-phase evaluation was conducted to assess the intervention. Phase one evaluated the health care providers' perceived knowledge and comfort pre-training, post-training, and at 3 months follow-up. The second phase included a medical chart review of 4 CHCs to assess the rates of screening, documentation of abuse, assessment of safety, and referrals for help at baseline (6 months pre-training) as compared to the intervention period (6 months post-training). RESULTS: The health care providers' perceived level of knowledge and comfort increased significantly post-training and then later decreased at 3 months follow-up. The rate of screening for DV (25% vs. 5%), suspicion of DV (6% vs. 2%), completion of safety assessments (17% vs. 5%), and referrals (4% vs. 0%) increased significantly between the intervention and baseline periods. However, the rates of documentation of abuse did not change. CONCLUSIONS: This intervention was successful in increasing provider perceived knowledge and comfort; however, comfort decreased at follow-up. Additionally, the rates of screening and referrals increased 6 months post-training. Health care provider training and support and integrated quality assurance mechanisms may be necessary to increase the overall rate of these activities, and to sustain this effort over time. Further study is needed to identify effective methods to increase provider comfort regarding DV screening.

Adolescent↗

Fifty year follow-up of a patient with central core disease shows slow but definite progression.

The follow-up of a patient with central core disease (CCD) over 50 years showed that although initially the condition was moderately non-progressive, progression of a significant degree did eventually occur. Histopathological and electron microscopic data were available from muscle biopsies carried out at the ages of 19 and 55 years, and show a marked predominance of type 1 fibres with central cores in most fibres at both ages. The four mutations within the RYR1 gene described in association with CCD and three of the more common malignant hyperthermia-associated mutations within RYR1 were not present.

DNA↗

How best to measure implementation of school health curricula: a comparison of three measures.

The impact of school health education programs is often attenuated by inadequate teacher implementation. Using data from a school-based nutrition education program delivered in a sample of fifth graders, this study examines the discriminant and predictive validity of three measures of curriculum implementation: class-room observation of fidelity, and two measures of completeness, teacher self-report questionnaire and post-implementation interview. A fourth measure, obtained during teacher observations, that assessed student and teacher interaction and student receptivity to the curriculum (labeled Rapport) was also obtained. Predictive validity was determined by examining the association of implementation measures with three study outcomes; health knowledge, asking behaviors related to fruit and vegetables, and fruit and vegetable intake, assessed by 7-day diary. Of the 37 teachers observed, 21 were observed for two sessions and 16 were observed once. Implementation measures were moderately correlated, an indication of discriminant validity. Predictive validity analyses indicated that the observed fidelity, Rapport and interview measures were significantly correlated with post-test student knowledge. The association between health knowledge and observed fidelity (based on dual observation only), Rapport and interview measures remained significant after adjustment for pre-test knowledge values. None of the implementation variables were significantly associated with student fruit and vegetable intake or asking behaviors controlling for pre-test values. These results indicate that the teacher self-report questionnaire was not a valid measure of implementation completeness in this study. Post-implementation completeness interviews and dual observations of fidelity and Rapport appear to be more valid, and largely independent methods of implementation assessment.

Child↗

Effect of darkness on acoustic startle in Vietnam veterans with PTSD.

OBJECTIVE: Exaggerated startle is a symptom of posttraumatic stress disorder (PTSD), but empirical studies have not consistently documented elevated baseline startle in PTSD. The authors proposed in a previous study that Vietnam veterans with PTSD exhibit exaggerated startle only under stressful conditions. They reported that darkness facilitated startle in humans, suggesting that the startle reflex is sensitive to the aversive nature of darkness. In the present study they tested the hypothesis that the magnitude of facilitation of startle by darkness would be greater in Vietnam veterans with PTSD than in comparison groups of subjects without PTSD. Prepulse inhibition was also investigated. METHOD: The magnitude of startle and prepulse inhibition were assessed in alternating periods of darkness and light in 19 nonmedicated Vietnam veterans with PTSD, 13 Vietnam veterans without PTSD, and 20 civilians without PTSD. RESULTS: The overall startle level was higher in the veterans with PTSD than in either of the two groups of subjects without PTSD. Startle was facilitated by darkness, and the magnitude of this facilitation was greater in the veterans with PTSD than in the civilians without PTSD, but it was not greater in the veterans without PTSD. Prepulse inhibition was not affected by darkness and did not significantly differ among groups. CONCLUSIONS: Contrary to the hypothesis, elevated sensitivity to darkness was specific to individuals with combat experience, not to individuals with PTSD, perhaps because veterans had become aversively conditioned to darkness during their combat experiences. The more general increase in startle reactivity in the veterans with PTSD is consistent with clinical observations and descriptions of symptoms in DSM-IV.

Acoustic Stimulation↗

Results of the TeachWell worksite wellness program.

OBJECTIVE: This study examined whether providing a school-based teacher wellness program enhances the impact of a health curriculum on student outcomes and improves cognitive, behavioral, and physiological outcomes among participating teachers. METHODS: Thirty-two elementary schools were randomly assigned to experimental or comparison conditions. Comparison group schools received the Gimme-5 program, a curriculum designed to increase fourth and fifty graders' consumption of fruits and vegetables. Experimental schools received Gimme-5 and the teacher wellness program, which included 54 workshops over 2 years, along with several schoolwide health activities. Physiological, behavioral, and cognitive outcomes were assessed in teachers and students. RESULTS: There was no evidence that the intervention favorably modified any student or teacher end points; nor did intervention teachers deliver the Gimme-5 program with greater fidelity than comparison teachers. CONCLUSION: Confidence in the null results is bolstered by the randomized design, baseline sample equivalence, appropriate mixed-model analyses, and lack of selective or differential attrition. Insufficient participation in the wellness program appears a likely explanation for the lack of teacher and student effects. Factors specific to the school setting and intervention may have diminished participation and, thus, intervention effects.

Adult↗

[Serum lipids and blood pressure levels in the +Mapuche population living in the Chilean region of Araucanía].

BACKGROUND: Chilean aboriginal populations (Mapuche) predominantly live in the region of Araucanía, in the southern part of the country. Their cardiovascular risk factors have not been systematically assessed. AIM: To study the prevalence of cardiovascular risk factors in the Mapuche population. SUBJECTS AND METHODS: Blood pressure, weight, height, dietary habits, fasting serum total cholesterol, HDL cholesterol and triglycerides were measured in 1.948 adults living in 28 Mapuche communities. RESULTS: Thirteen percent of males and 16% of females had high blood pressure. Body mass index was 25.5 kg/m2 in males and 28.1 kg/m2 in females. Forty five percent of women and 24% of men were classified as obese. Mean serum total cholesterol was 186.7 +/- 9.6 mg/dl, HDL cholesterol was 58.7 +/- 30.7 mg/dl, total cholesterol/HDL cholesterol was 3.4 +/- 2 and triglycerides were 155.2 +/- 91.2 mg/dl. Twenty eight percent of males and 9.6% of females smoked. CONCLUSIONS: Mapuche individuals have higher levels of HDL cholesterol a better total cholesterol/HDL cholesterol ratio and lower frequency of smoking than non aboriginal Chileans subjects.

Adult↗

Effects of simulated gastroesophageal reflux on the untraumatized rabbit larynx.

OBJECTIVE: Gastroesophageal reflux (GER) has been shown, clinically and experimentally, to cause inflammation of traumatized laryngeal mucosa. This study was performed to determine if GER causes inflammation of untraumatized laryngeal mucosa. METHOD: Sixteen adult New Zealand white rabbits underwent tube pharyngostomy under general anaesthesia without endotracheal intubation. After 7 days recovery, 1 mL/kg of normal saline or HCl (pH 1.5) with pepsin (0.3 mg/mL) was infused into the piriform sinus while the rabbit was under mild sedation: once, twice, or three times per day, for 14 consecutive days. RESULTS: Rabbits that received HCl and pepsin exhibited various degrees of apnea and coughing. Eventually, most developed biphasic stridor on exertion. Histologically, the degree of laryngeal inflammation was greatest when GER was simulated three times per day. Glottic inflammation was greatest in one rabbit, which responded to GER simulation with paroxysmal coughing. CONCLUSION: The mechanism of injury in GER laryngitis is postulated to be a combination of chemical trauma (due to HCl and pepsin) and mechanical trauma (due to an individually variable laryngeal chemoreflex). Further study of GER laryngitis in this new animal model is warranted.

Animals↗

Qualification of discordant responses in utility assessment.

In many studies of utility assessment, the discordant response rate is significantly high. Discordant responses suggest inconsistency and, in turn, suggest inaccurate measurement of personal values that can lead to erroneous medical recommendations. The most common method of dealing with these responses is to exclude them from the sample statistics as incoherent or confused respondents. This paper proposes another perspective on discordant responses. In a recent study eliciting utility values for states of health that follow stroke, we observed a high rate of discordant responses. Closer examination of these discordant responses reveals that discordant responses are not all alike. Simple qualitative and quantitative views of these differences suggest that there may be information outside the concordant population of responses, which is lost by their exclusion. In an effort to understand the elevated discordant response rate, the effect of relaxing the defining boundaries of a discordant response was explored.

Adult↗