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Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 163 records · Page 9Linked to original sources
PubMed1999

The safety and usefulness of routine bronchoscopy before stem cell transplantation and during neutropenia.

Fibreoptic bronchoscopy with bronchoalveolar lavage (BAL) is used for clinical investigation and research into pulmonary complications of stem cell transplantation. Adverse effects of BAL are common in neutropenic patients with lung disease; there are few data on its safety when used routinely in transplant recipients without lung impairment. We describe the complications and usefulness for infection surveillance of routine BAL pre-transplantation and during neutropenia. Thirty-three patients before autologous or allogeneic BMT or PBSCT (B1) and 24 during post-transplant neutropenia (B2) underwent BAL; patients with pulmonary disease were excluded. Subjects were monitored for adverse effects, and BAL fluid was examined for pathogens. Complications of B2 were compared with events seen in 35 neutropenic patients who did not undergo BAL (C). Eighteen percent B1 and 33% B2 subjects showed complications of BAL. Fever occurred in 12% B1 and 26% previously afebrile B2 subjects, compared to 11% of C (P = 0.3). Epistaxis occurred in one B2 subject and two C. Potentially pathogenic organisms were isolated from 18% B1 and 13% B2 BAL fluids; none caused later respiratory infection. Bronchoscopy and BAL pre- and post-transplant had acceptable safety for a research procedure, but were not clinically helpful for infection surveillance.

Adolescent↗
PubMed1999

Neuroprotection in acute ischaemic stroke. II: Clinical potential.

In the 4 years since our first article, there has been considerable progress in our understanding of the pathophysiology of acute ischaemic stroke, and the results of well-conducted trials have at last begun to change everyday clinical practice. The timing of the various processes of the ischaemic cascade and the potential time windows for different interventions are better understood. Furthermore, the importance of maintaining cerebral perfusion and optimizing systemic physiological and biochemical factors in order to prevent neurological deterioration ('progressing stroke') is increasingly being realized. Numerous antithrombotic and neuroprotective drugs have been evaluated in clinical trials, and while none has shown unequivocal benefits on its own, prospects for successful intervention are still good. This will probably involve different combinations of treatments targeted on different pathophysiological stroke types, so that the management of acute stroke will offer a considerable challenge to the stroke physicians of the future.

Animals↗
PubMed1999

Intern discussion group: a supportive educational experience for junior doctors.

The intern year is often a very demanding and stressful experience. To support the interns in a New Zealand hospital, a facilitated weekly discussion group was set up. The group's main goals were to provide training in the management of personal and professional stress while encouraging frank and open discussion. It proved to be a supportive and valuable learning experience for the interns. A similar format could be beneficial for senior hospital doctors.

Communication↗
PubMed1999

Accessible dental care for children.

The development of a school-based comprehensive and cost-efficient oral health care program requires careful planning centered on the needs expressed by the community. Gaining the support and the cooperation of school officials and parents creates an environment that has a significantly greater opportunity for success. Location, appropriate design of the facility and support from a local charitable organization further insure excellent access and expeditious care.

Child↗
PubMed1999

Cryosurgical effects on growing vessels.

Cryosurgical treatment of unresectable hepatic malignancies has proven beneficial in adults. Concerns regarding its use in children include the effect on growth and the risk of injury to adjacent structures. To test the effect of cryoablation on adjacent vascular structures in a growing animal, liquid nitrogen cryoablation was performed on a juvenile murine model. Sprague Dawley rats underwent double freeze-thaw cryoablation of the abdominal aorta with interposed liver tissue. Serial sacrifices were performed over 120 days. Comparisons were made with sham-operated controls. Overall, animal growth paralleled that of sham controls through all time points. Gross examination of aortic diameter also showed similar growth in vessel size between the groups. Histologic analysis demonstrated injury after cryoablation with smooth muscle cell vacuolization, followed by cell death. Aortic media layer collapse resulted from cellular loss, however, elastin fiber composition was maintained. Aortic patency was preserved despite evidence of cellular injury and aortic wall remodeling. An associated thermal sink effect on the opposing wall was identified. After cryoablation adjacent to the abdominal aorta in adolescent rats, vascular patency is maintained and animal growth and structural function is preserved, despite cellular injury and wall compression. These observations suggest that cryoablation may be a useful treatment adjunct in young subjects.

Animals↗
PubMed1998

Are different parts of the extended amygdala involved in fear versus anxiety?

Although there is a close correspondence between fear and anxiety, and the study of fear in animals has been extremely valuable for understanding brain systems that are important for anxiety, it is equally clear that a richer animal model of human anxiety disorders would include measures of both stimulus-specific fear and something less stimulus specific, more akin to anxiety. Studies in patients with posttraumatic stress syndrome indicate these individuals seem to show normal fear reactions but abnormal anxiety measured with the acoustic startle reflex. Studies in rats, also using the startle reflex, indicate that highly processed explicit cue information (lights, tones, touch) activates the central nucleus of the amygdala, which in turn activates hypothalamic and brain stem target areas involved in specific signs of fear. Somewhat less explicit information, such as that produced by exposure to a threating environment for several minutes or by intraventricular administration of the peptide corticotropin-releasing hormone may activate a brain area closely related to the amygdala, called the bed nucleus of the stria terminalis, which in turn activates hypothalamic and brain stem target areas involved in specific signs of fear or anxiety. Because the nature of this information may be less specific than that produced by an explicit cue, and of much longer duration, activation of the bed nucleus of the stria terminalis may be more akin to anxiety than to fear.

Amygdala↗
PubMed1998

Identification of the receptor component of the IkappaBalpha-ubiquitin ligase.

NF-kappaB, a ubiquitous, inducible transcription factor involved in immune, inflammatory, stress and developmental processes, is retained in a latent form in the cytoplasm of non-stimulated cells by inhibitory molecules, IkappaBs. Its activation is a paradigm for a signal-transduction cascade that integrates an inducible kinase and the ubiquitin-proteasome system to eliminate inhibitory regulators. Here we isolate the pIkappaBalpha-ubiquitin ligase (pIkappaBalpha-E3) that attaches ubiquitin, a small protein which marks other proteins for degradation by the proteasome system, to the phosphorylated NF-kappaB inhibitor pIkappaBalpha. Taking advantage of its high affinity to pIkappaBalpha, we isolate this ligase from HeLa cells by single-step immunoaffinity purification. Using nanoelectrospray mass spectrometry, we identify the specific component of the ligase that recognizes the pIkappaBalpha degradation motif as an F-box/WD-domain protein belonging to a recently distinguished family of beta-TrCP/Slimb proteins. This component, which we denote E3RSIkappaB (pIkappaBalpha-E3 receptor subunit), binds specifically to pIkappaBalpha and promotes its in vitro ubiquitination in the presence of two other ubiquitin-system enzymes, E1 and UBC5C, one of many known E2 enzymes. An F-box-deletion mutant of E3RS(IkappaB), which tightly binds pIkappaBalpha but does not support its ubiquitination, acts in vivo as a dominant-negative molecule, inhibiting the degradation of pIkappaBalpha and consequently NF-kappaB activation. E3RS(IkappaB) represents a family of receptor proteins that are core components of a class of ubiquitin ligases. When these receptor components recognize their specific ligand, which is a conserved, phosphorylation-based sequence motif, they target regulatory proteins containing this motif for proteasomal degradation.

Amino Acid Sequence↗
PubMed1998

Effects of experimental context and explicit threat cues on acoustic startle in Vietnam veterans with posttraumatic stress disorder.

BACKGROUND: The hypothesis that exaggerated startle in Vietnam veterans with posttraumatic stress disorder (PTSD) reflects an anxiogenic response to stressful contexts was tested. METHODS: Thirty-four nonmedicated Vietnam veterans with PTSD, and 17 combat and 14 civilian non-PTSD controls participated in two testing sessions over separate days. Acoustic startle stimuli were delivered alone or in a test of prepulse inhibition. In the first session, startle was assessed without experimental stress. In the second session, startle was investigated during a stressful "threat of shock" experiment, when subjects anticipated the administration of shocks during threat periods and during safe periods when no shocks were anticipated. RESULTS: The magnitude of startle did not differ significantly among the three groups in the first session, but was increased throughout the threat of shock experiment in the PTSD veterans in the second session. The actual increase in startle in the threat compared to the safe condition did not significantly differ among the three groups. Prepulse inhibition was reduced in the PTSD veterans, compared to the non-PTSD civilians, but not compared to the non-PTSD veterans. CONCLUSION: Exaggerated startle in Vietnam veterans with PTSD reflects an anxiogenic response to an environment that is experienced as stressful.

Acoustic Stimulation↗
PubMed1998

Probing the structure of complex macromolecular interactions by homolog specificity scanning: the P1 and P7 plasmid partition systems.

The P1 plasmid partition locus, P1 par, actively distributes plasmid copies to Escherichia coli daughter cells. It encodes two DNA sites and two proteins, ParA and ParB. Plasmid P7 uses a similar system, but the key macromolecular interactions are species specific. Homolog specificity scanning (HSS) exploits such specificities to map critical contact points between component macromolecules. The ParA protein contacts the par operon operator for operon autoregulation, and the ParB contacts the parS partition site during partition. Here, we refine the mapping of these contacts and extend the use of HSS to map protein-protein contacts. We found that ParB participates in autoregulation at the operator site by making a specific contact with ParA. Similarly, ParA acts in partition by making a specific contact with ParB bound at parS. Both these interactions involve contacts between a C-terminal region of ParA and the extreme N-terminus of ParB. As a single type of ParA-ParB complex appears to be involved in recognizing both DNA sites, the operator and the parS sites may both be occupied by a single protein complex during partition. The general HSS strategy may aid in solving the three-dimensional structures of large complexes of macromolecules.

Amino Acid Sequence↗
PubMed1998

Identification of a form of acyl-CoA:cholesterol acyltransferase specific to liver and intestine in nonhuman primates.

The present study demonstrates that two different forms of the intracellular cholesterol esterification enzyme acyl-CoA:cholesterol acyltransferase (ACAT) are present in the nonhuman primate hepatocyte; one is similar to that originally cloned from human genomic DNA, here termed ACAT1, while a second gene product, termed ACAT2, is reported here. The primate ACAT2 gene product was cloned from an African green monkey liver cDNA library. Sequence analysis of an isolated, full-length clone of ACAT2 cDNA identified an open reading frame encoding a 526-amino acid protein with essentially no sequence similarity to the ACAT1 cDNA over the N-terminal 101 amino acids but with 57% identity predicted over the remaining 425 amino acids. Transfection of the cloned ACAT2 cDNA into two different mammalian cell types resulted in the production of abundant ACAT activity which was sensitive to ACAT inhibitors. Northern blot analysis showed that the ACAT2 mRNA was expressed primarily in liver and intestine in monkeys. In contrast, ACAT1 mRNA was expressed in almost all tissues examined. Topologic predictions from the amino acid sequence of ACAT2 indicates that it has seven trans-membrane domains in a configuration that places the putative active site of the enzyme in the lumen of the endoplasmic reticulum. This orientation of ACAT2 in the endoplasmic reticulum membrane, in addition to its expression only in liver and intestine, suggests that this enzyme may have as a primary function, the secretion of cholesteryl esters into apoB-containing lipoproteins.

Amino Acid Sequence↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗