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Biomedical subjects

M A Wilson

Publications and source records attributed to M A Wilson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Sex differences in relation to conditioned fear-induced enhancement of morphine analgesia.

A number of studies have reported that both the immediate and proactive effects of exposure to a shock stressor are less pronounced in female than in male rats. A separate area of research has demonstrated that female rats are less sensitive to the analgesic effects of morphine than males. Experiments from our laboratory, as well as others, have found that exposure to a context associated with shock (i.e., conditioned fear context) at the time of morphine administration, enhances the analgesic effects of morphine. Since previous studies have exclusively employed male rats, the purpose of Experiment 1 was to determine if a sex difference exists to this context conditioned fear-induced enhancement of morphine-induced analgesia. The findings of Experiment 1 showed that females do not appear to exhibit conditioned fear-induced enhancement of morphine analgesia as compared to males. Experiment 2 demonstrated that females exhibited higher levels of conditioned fear-induced enhancement of morphine analgesia during diestrus I than estrous. Experiment 3 demonstrated that females exhibited lower levels of conditioned analgesia compared to males, while both groups exhibited similar freezing levels. The findings of the present experiments suggest that the sex difference observed in Experiment 1 may be due to differences in conditioned analgesia.

Analgesics, Opioid↗
PubMed2001

Age-dependent effects of trihexyphenidyl in extrapyramidal cerebral palsy.

Trihexyphenidyl (Artane) is a centrally active muscarinic antagonist commonly used to treat patients with generalized dystonia. In a retrospective survey of 22 consecutive children with extrapyramidal cerebral palsy, we evaluated trihexyphenidyl on upper extremity and lower extremity function, expressive language, and drooling. Functional changes were assessed using a parental questionnaire (rating scale 1-5: from 1 = little or no change to 5 = tremendous change, with scores in either a positive or negative direction). Improvements of +4 or +5 were reported in eight children for upper extremity function, in eight children for verbal expressive language, in five for drooling, and in none for lower extremity function. Using bivariate linear regression modeling to investigate variables associated with treatment effects, there was a significant inverse relationship between age at initiation of medication and therapeutic response. Furthermore, beneficial responses were specific to upper-extremity function and expressive language. These results suggest that younger children are more likely to respond to trihexyphenidyl and that primary functional benefits include improved fine motor abilities and expressive language. A prospective masked study with a standardized clinical instrument is needed to confirm these findings.

Age Factors↗
PubMed2001

Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep.

Human dreaming occurs during rapid eye movement (REM) sleep. To investigate the structure of neural activity during REM sleep, we simultaneously recorded the activity of multiple neurons in the rat hippocampus during both sleep and awake behavior. We show that temporally sequenced ensemble firing rate patterns reflecting tens of seconds to minutes of behavioral experience are reproduced during REM episodes at an equivalent timescale. Furthermore, within such REM episodes behavior-dependent modulation of the subcortically driven theta rhythm is also reproduced. These results demonstrate that long temporal sequences of patterned multineuronal activity suggestive of episodic memory traces are reactivated during REM sleep. Such reactivation may be important for memory processing and provides a basis for the electrophysiological examination of the content of dream states.

Action Potentials↗
PubMed2001

Hypercoagulability in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to cardiovascular complications such as stroke and myocardial infarction. Previous studies demonstrate that OSA patients show elevated fibrinogen levels and increased platelet aggregation that are reversed with 1 night of nasal continuous positive airway pressure treatment (NCPAP). Questioning overall coagulability in OSA, we examined whole blood coagulability in 11 chronically NCPAP treated OSA subjects, 22 previously untreated OSA subjects, and in 16 of these after 1 night of NCPAP treatment. PATIENTS AND METHODS: During full polysomnography, subjects from each group had blood drawn prior to bedtime (21:00 h) and upon waking in the morning (07:00 h). RESULTS: Untreated OSA patients had faster P.M. clotting times than chronically treated OSA patients (3.33+/-0.31 versus 6.12+/- 0.66 min, P<0.05 by ANOVA). A.M. values showed similar results (4.31+/- 0.34 min versus 7.08+/-0.52 min, P<0.05 by ANOVA) for the respective groups. One overnight treatment with nasal CPAP did not produce a significant change in A.M. whole blood coagulability (4.35 +/-0.43 to 5.31+/-0.53 min; n=16; P=0.1) in 16 treated subjects. CONCLUSIONS: These data indicate a relationship between obstructive sleep apnea and blood hypercoagulability status that appears to be reversed by chronic NCPAP treatment. These data suggest that NCPAP might protect against the development of cardiovascular complications in OSA patients.

Journal Article↗
PubMed2001

Neurotrophin-3 modulates noradrenergic neuron function and opiate withdrawal.

Somatic symptoms and aversion of opiate withdrawal, regulated by noradrenergic signaling, were attenuated in mice with a CNS-wide conditional ablation of neurotrophin-3. This occurred in conjunction with altered cAMP-mediated excitation and reduced upregulation of tyrosine hydroxylase in A6 (locus coeruleus) without loss of neurons. Transgene-derived NT-3 expressed by noradrenergic neurons of conditional mutants restored opiate withdrawal symptoms. Endogenous NT-3 expression, strikingly absent in noradrenergic neurons of postnatal and adult brain, is present in afferent sources of the dorsal medulla and is upregulated after chronic morphine exposure in noradrenergic projection areas of the ventral forebrain. NT-3 expressed by non-catecholaminergic neurons may modulate opiate withdrawal and noradrenergic signalling.

Aging↗
PubMed2001

Comparison of methylene blue-directed biopsies and conventional biopsies in the detection of intestinal metaplasia and dysplasia in Barrett's esophagus: a preliminary study.

BACKGROUND: The diagnostic advantage of methylene blue (MB) chromoendoscopy in Barrett's esophagus is unclear. METHODS: Patients with columnar-lined esophagus (CLE) were enrolled into a prospective, randomized crossover trial of MB-directed biopsy versus conventional biopsy. RESULTS: Forty-seven patients (19 long-segment CLE; 28 short-segment CLE) were enrolled and underwent MB-directed biopsy. Sensitivity and specificity of MB for specialized intestinal metaplasia were 53% and 51%, respectively. Sensitivity and specificity of MB for dysplasia were 51% and 48%, respectively. Thirty-five patients (15 long-segment CLE; 20 short-segment CLE) completed the crossover trial. Relative frequencies for specialized intestinal metaplasia were 73% and 71% from MB-directed and conventional biopsy specimens, respectively (p = 0.73). Relative frequencies for dysplasia were 20% and 18% from MB-directed and conventional biopsy specimens, respectively (p = 0.65). In patients with long-segment CLE, dysplasia was diagnosed in 10 patients with MB and 7 patients with conventional biopsy methods (p = 0.25). The number of biopsy specimens per EGD was greater with MB, which may have influenced the diagnosis. Histologically, the grade of dysplasia was indefinite/low in nearly all of the dysplastic specimens. CONCLUSIONS: Results of MB-directed biopsy were similar to conventional biopsy in detecting specialized intestinal metaplasia and indefinite/low-grade dysplasia. MB was not useful in short-segment Barrett's esophagus.

Barrett Esophagus↗
PubMed2001

PAF increases vascular permeability without increasing pulmonary arterial pressure in the rat.

In vivo pulmonary arterial catheterization was used to determine the mechanism by which platelet-activating factor (PAF) produces pulmonary edema in rats. PAF induces pulmonary edema by increasing pulmonary microvascular permeability (PMP) without changing the pulmonary pressure gradient. Rats were cannulated for measurement of pulmonary arterial pressure (Ppa) and mean arterial pressure. PMP was determined by using either in vivo fluorescent videomicroscopy or the ex vivo Evans blue dye technique. WEB 2086 was administered intravenously (IV) to antagonize specific PAF effects. Three experiments were performed: 1) IV PAF, 2) topical PAF, and 3) Escherichia coli bacteremia. IV PAF induced systemic hypotension with a decrease in Ppa. PMP increased after IV PAF in a dose-related manner. Topical PAF increased PMP but decreased Ppa only at high doses. Both PMP (88 +/- 5%) and Ppa (50 +/- 3%) increased during E. coli bacteremia. PAF-receptor blockade prevents changes in Ppa and PMP after both topical PAF and E. coli bacteremia. PAF, which has been shown to mediate pulmonary edema in prior studies, appears to act in the lung by primarily increasing microvascular permeability. The presence of PAF might be prerequisite for pulmonary vascular constriction during gram-negative bacteremia.

Animals↗
PubMed2001

A comparison of the firing properties of putative excitatory and inhibitory neurons from CA1 and the entorhinal cortex.

The superficial layers of the entorhinal cortex (EC) provide the majority of the neocortical input to the hippocampus, and the deep layers of the EC receive the majority of neocortically bound hippocampal outputs. To characterize information transmission through the hippocampal and EC circuitry, we recorded simultaneously from neurons in the superficial EC, the CA1 region of hippocampus, and the deep EC while rodents ran for food reward in two environments. Spike waveform analysis allowed us to classify units as fast-spiking (FS) putative inhibitory cells or putative excitatory (PE) cells. PE and FS units' firing were often strongly correlated at short time scales, suggesting the presence a monosynaptic connection from the PE to FS units. EC PE units, unlike those found in CA1, showed little or no tendency to fire in bursts. We also found that the firing of FS and PE units from all regions was modulated by the approximately 8 Hz theta rhythm, although the firing of deep EC FS units tended to be less strongly modulated than that of the other types of units. When we examined the spatial specificity of FS units, we determined that FS units in all three regions showed low specificity. At the same time, retrospective coding, in which firing rates were related to past position, was present in FS units from all three regions and deep EC FS units often fired in a "path equivalent" manner in that they were active in physically different, but behaviorally related positions both within and across environments. Our results suggest that while the firing of FS units from CA1 and the EC show similarly low levels of position specificity, FS units from each region differ from one another in that they mirrored the associated PE units in terms of their tendency to show more complex positional firing properties like retrospective coding and path equivalence.

Action Potentials↗
PubMed2001

Recent advances in the preparation and utilization of carbon nanotubes for hydrogen storage.

Recent progress in the production, purification, and experimental and theoretical investigations of carbon nanotubes for hydrogen storage are reviewed. From the industrial point of view, the chemical vapor deposition process has shown advantages over laser ablation and electric-arc-discharge methods. The ultimate goal in nanotube synthesis should be to gain control over geometrical aspects of nanotubes, such as location and orientation, and the atomic structure of nanotubes, including helicity and diameter. There is currently no effective and simple purification procedure that fulfills all requirements for processing carbon nanotubes. Purification is still the bottleneck for technical applications, especially where large amounts of material are required. Although the alkalimetal-doped carbon nanotubes showed high H2 weight uptake, further investigations indicated that some of this uptake was due to water rather than hydrogen. This discovery indicates a potential source of error in evaluation of the storage capacity of doped carbon nanotubes. Nevertheless, currently available single-wall nanotubes yield a hydrogen uptake value near 4 wt% under moderate pressure and room temperature. A further 50% increase is needed to meet U.S. Department of Energy targets for commercial exploitation. Meeting this target will require combining experimental and theoretical efforts to achieve a full understanding of the adsorption process, so that the uptake can be rationally optimized to commercially attractive levels. Large-scale production and purification of carbon nanotubes and remarkable improvement of H2 storage capacity in carbon nanotubes represent significant technological and theoretical challenges in the years to come.

Adenosine↗
PubMed2001

A methodology based on NMR spectroscopy for the forensic analysis of condoms.

Both solution and solid state Nuclear Magnetic Resonance (NMR) spectroscopic techniques have been used to determine differences in commercially available condoms. Whilst solid state NMR is useful for determining the polymer backbone, it is not useful for forensic analysis due to the commonality of the latex condom. However solution NMR spectra obtained following a simple extraction procedure using hexane, provides a fingerprint of the additives in the lubricants. Following the development of a flow chart, basing decisions on the presence of particular peaks present in the solution spectra, 33 of 38 condoms could be individualized. Samples were also analyzed after having the lubricant manually removed and soaking the condom in water for 3 to 24 h. These experiments were performed to simulate a case of the sample having been used and disposed of by flushing down the toilet, as may be experienced in a case of a sexual assault. The results indicated that the only significant water soluble component was polyethylene glycol. The overall results suggest that the method developed may be a quick and useful technique in characterizing condoms. The information obtained can be used to provide associative evidence between suspect and crime, and so be useful in sexual assault cases.

Condoms↗
PubMed2001

Wastage of a silicone impression material in a general practice setting: a comparison between hand and automixing methods.

A practice-based, randomised, controlled trial has been undertaken to investigate the wastage of impression material when recording full arch one-stage, polyvinyl siloxane impressions using four techniques: putty and automix light viscosity material, putty and automix regular viscosity material, putty and tubed light viscosity material, and putty and tubed regular viscosity material. A total of 100 maxillary impressions, comprising 25 recorded using each of the four techniques, were obtained according to a predetermined scheme for randomisation. All material wasted in dispensing, mixing and applying each impression was determined by repeated weighing. Statistical comparisons of the mean weights of material wasted for each type of impression revealed that significantly (P < 0.01) less wastage occurred with the automix techniques. It is concluded that automix impression techniques may, in more extensive studies, be found to be more cost effective than tubed impression material techniques when recording impressions of the type investigated.

Cost-Benefit Analysis↗
PubMed2000

Apoptosis has a prolonged role in the neurodegeneration after hypoxic ischemia in the newborn rat.

Birth asphyxia can cause moderate to severe brain injury. It is unclear to what degree apoptotic or necrotic mechanisms of cell death account for damage after neonatal hypoxia-ischemia (HI). In a 7-d-old rat HI model, we determined the contributions of apoptosis and necrosis to neuronal injury in adjacent Nissl-stained, hematoxylin and eosin-stained, and terminal deoxynucleotidyl transferase-mediated UTP nick end-labeled sections. We found an apoptotic-necrotic continuum in the morphology of injured neurons in all regions examined. Eosinophilic necrotic neurons, typical in adult models, were rarely observed in neonatal HI. Electron microscopic analysis showed "classic" apoptotic and necrotic neurons and "hybrid" cells with intermediate characteristics. The time course of apoptotic injury varied regionally. In CA3, dentate gyrus, medial habenula, and laterodorsal thalamus, the density of apoptotic cells was highest at 24-72 hr after HI and then declined. In contrast, densities remained elevated from 12 hr to 7 d after HI in most cortical areas and in the basal ganglia. Temporal and regional patterns of neuronal death were compared with expression of caspase-3, a cysteine protease involved in the execution phase of apoptosis. Immunocytochemical and Western blot analyses showed increased caspase-3 expression in damaged hemispheres 24 hr to 7 d after HI. A p17 peptide fragment, which results from the proteolytic activation of the caspase-3 precursor, was detected in hippocampus, thalamus, and striatum but not in cerebral cortex. The continued expression of activated caspase-3 and the persistence of cells with an apoptotic morphology for days after HI suggests a prolonged role for apoptosis in neonatal hypoxic ischemic brain injury.

Animals↗
PubMed2000

The 1.0 A crystal structure of Ca(2+)-bound calmodulin: an analysis of disorder and implications for functionally relevant plasticity.

Calmodulin (CaM) is a highly conserved 17 kDa eukaryotic protein that can bind specifically to over 100 protein targets in response to a Ca(2+) signal. Ca(2+)-CaM requires a considerable degree of structural plasticity to accomplish this physiological role; however, the nature and extent of this plasticity remain poorly characterized. Here, we present the 1.0 A crystal structure of Paramecium tetraurelia Ca(2+)-CaM, including 36 discretely disordered residues and a fifth Ca(2+) that mediates a crystal contact. The 36 discretely disordered residues are located primarily in the central helix and the two hydrophobic binding pockets, and reveal correlated side-chain disorder that may assist target-specific deformation of the binding pockets. Evidence of domain displacements and discrete backbone disorder is provided by translation-libration-screw (TLS) analysis and multiconformer models of protein disorder, respectively. In total, the evidence for disorder at every accessible length-scale in Ca(2+)-CaM suggests that the protein occupies a large number of hierarchically arranged conformational substates in the crystalline environment and may sample a quasi-continuous spectrum of conformations in solution. Therefore, we propose that the functionally distinct forms of CaM are less structurally distinct than previously believed, and that the different activities of CaM in response to Ca(2+) may result primarily from Ca(2+)-mediated alterations in the dynamics of the protein.

Adenosine Diphosphate↗
PubMed2000

The treatment of adult patients with a mental disability. Part 2: Assessment of competence.

Over recent years practitioners are increasingly being asked to attend to, or to provide treatment for, adult patients with some degree of mental illness, either in their homes or in the dental surgery. Because the issue of competence and the assessment of the patient is crucial to this aspect of dental practice this second paper is devoted to an overview of that assessment process; outlining the legal tests and standards to be employed.

Adult↗
PubMed2000

The treatment of adult patients with mental disability. Part 1: Consent and duty.

Over recent years practitioners are increasingly being asked to attend to, or to provide treatment for, adult patients with some degree of mental illness, either in their homes or in the dental surgery. Demographic changes, an ageing population with increasing incidence of dementia, and the philosophy of 'care in the community' for those with long-term mental health problems will ensure that such requests will continue. Such requests present the practitioner with a number of ethical and legal problems. This series of papers looks at the legal issues that arise by reference to case scenarios in this area of 'special needs' dentistry. This first paper deals with the issue of consent, and the legal duty of care that arises on the part of the dentist when attending a patient who is unable to consent to treatment.

Adult↗
PubMed2000

Neonatal lead exposure impairs development of rodent barrel field cortex.

Childhood exposure to low-level lead can permanently reduce intelligence, but the neurobiologic mechanism for this effect is unknown. We examined the impact of lead exposure on the development of cortical columns, using the rodent barrel field as a model. In all areas of mammalian neocortex, cortical columns constitute a fundamental structural unit subserving information processing. Barrel field cortex contains columnar processing units with distinct clusters of layer IV neurons that receive sensory input from individual whiskers. In this study, rat pups were exposed to 0, 0.2, 1, 1.5, or 2 g/liter lead acetate in their dam's drinking water from birth through postnatal day 10. This treatment, which coincides with the development of segregated columns in the barrel field, produced blood lead concentrations from 1 to 31 microg/dl. On postnatal day 10, the area of the barrel field and of individual barrels was measured. A dose-related reduction in barrel field area was observed (Pearson correlation = -0.740; P < 0.001); mean barrel field area in the highest exposure group was decreased 12% versus controls. Individual barrels in the physiologically more active caudoventral group were affected preferentially. Total cortical area measured in the same sections was not altered significantly by lead exposure. These data support the hypothesis that lead exposure may impair the development of columnar processing units in immature neocortex. We demonstrate that low levels of blood lead, in the range seen in many impoverished inner-city children, cause structural alterations in a neocortical somatosensory map.

Administration, Oral↗