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Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 127 records · Page 7Linked to original sources
PubMed1999

Absence of EWS/FLI1 fusion in olfactory neuroblastomas indicates these tumors do not belong to the Ewing's sarcoma family.

The balanced reciprocal translocation t(11;22)(q24;q12) is a specific molecular marker for the Ewing's sarcoma family of tumors (ESFT). Based on the detection of this translocation in some olfactory neuroblastomas (ONBs), it has been proposed that ONBs also belong to the ESFT. Others have challenged this hypothesis; however, the rarity of ONBs, as well as the lack of molecular techniques that work reliably on formalin fixed tissue, have precluded the molecular analysis of a significant number of cases. We evaluated the immunophenotypic and molecular features of 17 paranasal small round neuroectodermal tumors using routinely fixed tissue. Probes localizing to 22q12 (EWS) and 11q24 (FLI-1) were used in a standard 2-color fluorescence in situ hybridization (FISH) assay to evaluate EWS/FLI1 fusion on the der(22). Sixteen tumors were mic-2 negative, whereas 1 tumor was mic-2 positive, compatible with ONB and ESFT, respectively. Thirteen of 15 ONBs could be evaluated by FISH, and all 13 were negative for the EWS/FLI1 fusion. Distinct fusion signals were identified in the single paranasal ESFT. Our findings indicate that ONBs lack the EWS/FLI1 fusion and are unrelated to the ESFT; however, true ESFTs may rarely occur as primary sinonasal tumors.

Adolescent↗
PubMed1999

Systemic and pulmonary oxidative stress in idiopathic pulmonary fibrosis.

An oxidant/antioxidant imbalance has been proposed in patients with idiopathic pulmonary fibrosis (IPF). We tested this hypothesis by measuring various parameters of the oxidant/antioxidant balance in the plasma of 12 patients with IPF (7 nonsmokers and 5 smokers); in the bronchoalveolar lavage fluid (BALF) of 24 patients with IPF (17 nonsmokers and 7 smokers) and 31 healthy subjects (23 nonsmokers and 8 smokers). The trolox equivalent antioxidant capacity (TEAC) in plasma and BALF was lower in nonsmoking patients with IPF (plasma 0.55+/-0.1 mM, p<.001; BALF 4.8+/-1.2 microM, mean +/-SEM, p<.01), compared with healthy nonsmokers (plasma 1.33+/-0.03 mM; BALF 10+/-2 microM). Similar trends in plasma and BALF TEAC were observed in smoking patients with IPF in comparison with healthy smokers. The decrease in BALF TEAC was concomitant with a decrease in BALF protein thiol levels, but the decrease TEAC levels in plasma in IPF patients was not accompanied by a decrease in protein thiol levels. Reduced glutathione (GSH) was lower in BALF in nonsmoking patients with IPF (1.0+/-0.1 microM) compared with healthy nonsmokers (2.3+/-0.2 microM, p<.001). In contrast, GSH levels were higher in smoking patients with IPF (5.2+/-1.1 microM, p<.001) than in nonsmoking patients. GSSG levels were not different in any of the groups. The levels of products of lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) in plasma and BALF were significantly increased in both smoking (plasma 2.2+/-0.5 microM, p<.01; BALF 0.18+/-0.04 microM, p<.001), and nonsmoking (plasma 2.1+/-0.3 microM, p<.01; BALF 0.22+/-0.05 microM, p<.001) IPF patients, compared with healthy nonsmokers (plasma 1.4+/-0.3 microM; BALF 0.05+/-0.004 microM). These data show evidence of oxidant/antioxidant imbalance in the lungs of patients with IPF, which is also reflected as systemic oxidant stress.

Bronchoalveolar Lavage Fluid↗
PubMed1999

Muscimol in the deep layers of the superior colliculus/mesencephalic reticular formation blocks expression but not acquisition of fear-potentiated startle in rats.

Deposits of the retrograde tracer Fluoro-Gold into the ventrolateral nucleus reticularis pontis caudalis labeled neurons in the deep layers of the superior colliculus/mesencephalic reticular formation (deep SC/Me). To test the involvement of this area in the fear-potentiated startle effect, rats were implanted with cannulas into the deep SC/Me and trained for fear-potentiated startle after infusion of the GABA(A) agonist muscimol (0.1 microg/0.5 microl). Two days later, they were tested for fear-potentiated startle. Rats then received a 2nd training session without any infusions, and 2 days later they were reinfused with muscimol (0.1 microg/0.5 microl) and tested for fear-potentiated startle. Local infusion of muscimol into the deep SC/Me completely blocked the expression but not the acquisition of fear-potentiated startle. These results indicate that a synapse in the midbrain is critical for the expression of fear-potentiated startle.

Animals↗
PubMed1999

A radiation hybrid map of the rat genome containing 5,255 markers.

A whole-genome radiation hybrid (RH) panel was used to construct a high-resolution map of the rat genome based on microsatellite and gene markers. These include 3,019 new microsatellite markers described here for the first time and 1,714 microsatellite markers with known genetic locations, allowing comparison and integration of maps from different sources. A robust RH framework map containing 1,030 positions ordered with odds of at least 1,000:1 has been defined as a tool for mapping these markers, and for future RH mapping in the rat. More than 500 genes which have been mapped in mouse and/or human were localized with respect to the rat RH framework, allowing the construction of detailed rat-mouse and rat-human comparative maps and illustrating the power of the RH approach for comparative mapping.

Animals↗
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↗