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Biomedical subjects

M J Morgan

Publications and source records attributed to M J Morgan.

At least 19 recordsLinked to original sources

Attentional capacity limit for visual search causes spatial neglect in normal observers.

When observers simultaneously monitor several positions in the visual field, distracting stimuli have a devastating effect on the ability to discriminate between similar shapes. For example, the minimum tilt necessary for an observer to discriminate between a clockwise and anticlockwise tilt has been shown to increase with the square root of the number of untilted distractors. Here we show that these rapid visual searches remain inefficient even with extended practice. Moreover, each of our observers performed particularly poorly when uncued targets appeared in certain idiosyncratic positions, as though he or she neglected to process part of the visual field. This type of neglect is not commensurate with the popular 'max rule' strategy, in which observers simply report the direction of the largest apparent tilt. Nor is it consistent with tilt averaging. It is, however, consistent with an attentional effect in which both the signal and the noise from neglected positions are decreased, leaving the local signal/noise ratio constant. We show that our data can be well fit by models in which discriminations are based on a combination of these locally weighted, noisy signals.

Attention↗

Dynamic imaging of the lungs using x-ray phase contrast.

High quality real-time imaging of lungs in vivo presents considerable challenges. We demonstrate here that phase contrast x-ray imaging is capable of dynamically imaging the lungs. It retains many of the advantages of simple x-ray imaging, whilst also being able to map weakly absorbing soft tissues based on refractive index differences. Preliminary results reported herein show that this novel imaging technique can identify and locate airway liquid and allows lung aeration in newborn rabbit pups to be dynamically visualized.

Animals↗

The visual computation of 2-D area by human observers.

Normal human observers compared either the width, height or area of two simultaneously-presented shapes (the standard and the test), with a cue to indicate which decision had to be made. On 'area' trials, test width was a random variable, ensuring that neither shape (aspect ratio), width nor height by themselves was a reliable signal. Weber fractions for width and height of both ellipses and rectangles were in the range 5-10%, but for area they were higher (10-20%) than predicted from the combination of noisy width and height decisions. With ellipses, observers were more likely to overestimate width or height when the other dimension differed from the standard in the same direction (e.g. both greater). We conclude that observers have no access to high-precision codes for 2-D area, and that they base their decisions on a variety of heuristics derived from 1-D codes. A second experiment measured acuity for changes in aspect ratio. For ellipses, accuracy for aspect ratio was higher than predicted by the combination of noisy width and height signals; for rectangles it was worse, suggesting that 2-D curvature is a potent cue to shape.

Cues↗

The adaptor protein TRADD activates distinct mechanisms of apoptosis from the nucleus and the cytoplasm.

TNFR1 associated death domain protein (TRADD) contains an N-terminal TRAF binding domain and a C-terminal death domain along with nuclear import and export sequences that cause shuttling between the cytoplasm and nucleus. The death domain of TRADD contains the nuclear import sequence and expression of the core death domain (nuclear TRADD) results in exclusive nuclear localization and activation of a distinct apoptotic pathway. Cytoplasmic TRADD activates apoptosis through Fas-associated death domain protein (FADD) and caspase-8 activation that was blocked by caspase inhibitors or dominant-negative FADD. These inhibitors did not inhibit death induced by nuclear TRADD, which could only be inhibited by combining caspase inhibitors and a serine protease inhibitor. The pathway activated by nuclear TRADD requires caspase-9 catalytic activity. However, apoptosis activating factor deficiency confers only partial protection from death. This pathway represents an alternate means by which TRADD can regulate cell death independently of FADD and caspase-8 that occurs from the nucleus rather than the cytoplasm.

Adaptor Proteins, Signal Transducing↗

Collection of reciprocal space maps using imaging plates at the Australian National Beamline Facility at the Photon Factory.

Weissenberg screens and a translating cassette have been employed to allow an imaging plate to collect 30 scans per readout. In this configuration the imaging plate functions as a curved one-dimensional position-sensitive detector and, by changing the sample angle for each of the scans, two-dimensional images were produced in reciprocal space. This method of data collection leads to a reduction in scan time compared with methods based on a scintillation detector, particularly for asymmetric reflections. The data-collection method was tested using InGaN/GaN/AlN multilayers on sapphire substrates, since these exhibit broad features in reciprocal space. The geometry of the scans in reciprocal space required the data to be interpolated onto a Cartesian grid. Several interpolation schemes were investigated, with the results compared with the reciprocal space maps collected using a triple-axis scheme with a point detector. The quality of the interpolated reciprocal space maps depends upon the size and shape of the feature in reciprocal space, the interpolation method used, and the step size of the sample rotation. The method can be extended to three dimensions without an increase in data-collection time.

Journal Article↗

Influence of nicotine gum on acute cravings for cigarettes.

Reviews of nicotine gum trials generally confirm the efficacy of this substitute in smoking cessation. However, little research has considered the efficacy of nicotine gum as a method for alleviating acute cravings in situations where smokers are not permitted to smoke. The aim of the present study was to evaluate the efficacy of nicotine gum in alleviating acute cravings for cigarettes using the subjective multi-dimensional Questionnaire of Smoking Urges (QSU) and the objective progressive ratio (PR) measures of craving. Forty-five regular smokers participated in a double-blind placebo-controlled trial. All participants were required to abstain from cigarettes for a period of 4 h. Fifteen of the participants were required to chew nicotine gum, 15 were required to chew placebo gum and 15 received no intervention during this abstinence period. All participants then completed the QSU, PR and mood and anxiety questionnaires. The results revealed that participants who had been in either of the gum conditions reported significantly lower QSU factor 1 and factor 2 craving scores after 4 h abstinence than those who had received no intervention. Although a significant partial correlation between QSU factor 1 and 2 scores and the number of reinforcers earned under the PR procedure was observed, the results revealed no significant difference between groups on measures of PR performance or mood and anxiety. Both nicotine and placebo gum are equally effective at reducing acute cravings for cigarettes.

Affect↗

Extracting material parameters from x-ray attenuation: a CT feasibility study using kilovoltage synchrotron x-rays incident upon low atomic number absorbers.

The work reported here is a feasibility study of the extraction of material parameters from measurements of the linear x-ray attenuation coefficient of low atomic number absorbers. Computed tomography (CT) scans of small samples containing several liquids and solids were carried out with synchrotron radiation at the Australian National Beamline Facility (BL 20B) in Japan. Average values of the x-ray linear attenuation coefficient were extracted for each material for x-ray energies ranging from 11 keV to 20.5 keV. The electron density was estimated by applying results derived from a parametrization of the x-ray linear attenuation coefficient first developed by Jackson and Hawkes and extended for this work. Average estimates for the electron density of triethanolamine and acetic acid were made to within +5.3% of the actual value. Other materials examined included furfuraldehyde, perspex and teflon, for which average estimates of the electron density were less than 10% in excess of the calculated value.

Acetic Acid↗

Functional magnetic resonance imaging of synesthesia: activation of V4/V8 by spoken words.

In 'colored-hearing' synesthesia, individuals report color experiences when they hear spoken words. If the synesthetic color experience resembles that of normal color perception, one would predict activation of parts of the visual system specialized for such perception, namely the human 'color center', referred to as either V4 or V8. Using functional magnetic resonance imaging (fMRI), we here locate the region activated by speech in synesthetes to area V4/V8 in the left hemisphere, and demonstrate overlap with V4/V8 activation in normal controls in response to color. No activity was detected in areas V1 or V2, suggesting that activity in primary visual cortex is not necessary for such experience. Control subjects showed no activity in V4/V8 when imagining colors in response to spoken words, despite overtraining on word-color associations similar to those spontaneously reported by synesthetes.

Adult↗

Ecstasy (MDMA): are the psychological problems associated with its use reversed by prolonged abstinence?

RATIONALE: Chronic, regular recreational use of ecstasy (MDMA) is associated with psychopathology, elevated behavioural impulsivity and persistent impairment of memory performance. OBJECTIVE: The aim of the present study was to investigate which of these sequelae persist after at least 6 months of abstinence from ecstasy. METHODS: Four groups of participants were compared: 18 current regular recreational ecstasy users, 15 ex-regular ecstasy users who had abstained from using the drug for an average of 2 years, 16 polydrug users who had never taken ecstasy and 15 drug-naive controls. RESULTS: There were no significant group differences in age, education level, or pre-morbid intelligence and, generally, the use of illicit drugs other than ecstasy was not significantly different among the three drug-using groups. Both current and ex-ecstasy users exhibited elevated psychopathology and behavioural impulsivity compared with polydrug users and drug-naive controls, but current ecstasy users exhibited a broader range of psychopathology than ex-users. Both groups of ecstasy users also exhibited impaired working memory and verbal recall performance compared with drug-naive controls, but only ex-users exhibited impaired verbal recall relative to polydrug users. Regression analysis indicated that psychopathology was primarily predicted by the extent of previous consumption of cannabis rather than ecstasy, whereas the majority of the cognitive deficits were only predicted by the extent of previous ecstasy use. CONCLUSIONS: Selective impairments of neuropsychological performance associated with regular ecstasy use are not reversed by prolonged abstinence. This is consistent with evidence that ecstasy has potent and selective neurotoxic effects on brain serotonergic systems in humans.

Adult↗

Linear mechanisms can produce motion sharpening.

Human observers are not normally conscious of blur from moving objects [Nature 284 (1980) 164]. Several recent reports have even shown that blurred images appear sharper when drifting than when stationary and have suggested different non-linear mechanisms to explain this phenomenon [Vision Res. 36 (1996) 2729; Vision Res. 38 (1998) 2099]. We demonstrate here that even though distortions of drifting narrow-band sine-wave gratings cannot be explained by linear mechanisms, these mechanisms may have an important role in sharpening of moving edges. We show first that the effective spatial filter for a moving object that is formed by a simple difference-of-Gaussians spatial filter and the typical biphasic temporal impulse response function can be approximated by a combination of Gaussian filters only. When this filter is applied to moving, Gaussian-blurred edges, regions of blurring and sharpening are found over the same ranges of blur widths and velocities where recent experimental findings have shown them to exist. In general, that means that the output of the filter shows blurring in response to small blur widths and sharpening in response to larger blur widths.

Discrimination, Psychological↗

Cephalosporins can be given to penicillin-allergic patients who do not exhibit an anaphylactic response.

STUDY OBJECTIVES: To assess the risk of intraoperative allergic reactions to cephalosporins in patients who claim to be allergic to penicillin. DESIGN: Retrospective chart review. SETTING: University-affiliated hospital. MEASUREMENTS: 2,933 intraoperative anesthesia records of all adult orthopedic patients treated at our institution during a 14-month period (7/96-8/97) were reviewed for antibiotic use and allergic reactions. MAIN RESULTS: Most of the 2,933 orthopedic patients, including 413 patients who were allergic to penicillin, received a cephalosporin (usually cefazolin) during their procedure. Only one of the penicillin-allergic patients may have had an allergic reaction to the cephalosporin, because diphenhydramine and hydrocortisone were given at the beginning of the case. However, no mention was made on the chart about itching or a rash or hives. One of the non-penicillin-allergic patients did develop a rash while the cephalosporin was infusing, requiring discontinuation of the antibiotic. CONCLUSIONS: Given the low incidence of allergic reactions, it appears to be safe to administer cephalosporins to patients who claim to be allergic to penicillin. However, no conclusion can be made concerning patients who report severe or anaphylactic reactions to penicillin, because these patients probably were excluded from the study.

Anaphylaxis↗

Measurement of caspase activity in individual cells reveals differences in the kinetics of caspase activation between cells.

Most forms of apoptosis involve activation of caspases and it is likely that differences between cells in their ability to activate caspases contributes to the responsiveness of any given cell within a population to apoptotic stimuli. To study the molecular mechanisms that underlie such differences, it is necessary to measure caspase activity in individual cells. Here, we describe a method that allows the continuous monitoring of caspase activity in individual, living mammalian cells. This approach allows studies of the kinetics of caspase activation to be performed in individual cells within a population. We demonstrate that in a group of cells where some cells die and some cells survive in response to the same stimulus, the cells that die can be differentiated from those that survive based on the amount of caspase activity in each cell several hours before death occurs.

Apoptosis↗

An apoptosis signaling pathway induced by the death domain of FADD selectively kills normal but not cancerous prostate epithelial cells.

The adaptor protein FADD directly, or indirectly via another adaptor called TRADD, recruits caspase 8 to death receptors of the tumor necrosis factor receptor family. Consequentially, a dominant-negative mutant (FADD-DN, which consists only of the FADD death domain) that binds to receptors but cannot recruit caspase 8 has been widely used to inhibit apoptosis by various stimuli that work via death receptors. Here, we show that FADD-DN also has another cell type- and cancer-dependent activity because it induces apoptosis of normal human prostate epithelial cells but not normal prostate stromal cells or prostate cancer cells. This activity is independent of FADD-DN's ability to bind to three known interacting proteins, Fas, TRADD or RIP suggesting that it is distinct from FADD's functions at activated death receptors. FADD-DN induces caspase activation in normal epithelial cells as demonstrated using a Fluorescence Resonance Energy Transfer assay that measures caspase activity in individual living cells. However, caspase-independent pathways are also implicated in FADD-DN-induced apoptosis because caspase inhibitors were inefficient at preventing prostate cell death. Therefore, the death domain of FADD has a previously unrecognized role in cell survival that is epithelial-specific and defective in cancer cells. This FADD-dependent signaling pathway may be important in prostate carcinogenesis.

Adaptor Proteins, Signal Transducing↗

Odd-men-out are poorly localized in brief exposures.

Signal detection theory (SDT) asserts that sensory analysis is limited only by noise, and not by the number of stimuli analysed. To test this claim, we measured the accuracy of visual search for a single tilted element (the target) among 7 horizontal elements (distractors) using several different exposure durations, each terminated by a random noise mask. In the uncued condition, each element was a potential target. In the cued condition only 2 were. SDT predicts that location errors should be evenly distributed among all distractors. For long exposures (eg, 5.0 seconds), this prediction was confirmed, and SDT could simultaneously fit uncued and cued accuracies. For short exposures (eg, 0.1 seconds), errors were concentrated among distractors adjacent to the target, and, unless modified to account for this, SDT underestimated the difference between uncued and cued accuracies. Therefore, when the time available for search is brief, odd-men-out (ie, featural discontinuities) can be seen, but their positions can be only roughly estimated.

Attention↗

Increased binocular enhancement of contrast sensitivity and reduced stereoacuity in Duane syndrome.

PURPOSE: To compare the binocular enhancement of contrast sensitivity and stereoacuity in patients with Duane syndrome and normal subjects. METHODS: Monocular and binocular contrast sensitivity functions were determined using a two-alternative, forced-choice method in 14 patients with Duane syndrome and 14 normal subjects. Monocular and binocular log minimum angle of resolution (logMAR) acuities were measured, and stereoacuity was determined using the Titmus and TNO stereotests. RESULTS: In the patients with Duane syndrome, the binocular enhancement of contrast sensitivity was increased across all spatial frequencies, although stereoacuity was reduced compared to that of the normal subjects. The increased enhancement was caused by a reduction in monocular contrast sensitivity rather than an increase in binocular contrast sensitivity. The patients with Duane syndrome also showed a generalized reduction of contrast sensitivity at high spatial frequencies. CONCLUSIONS: It is suggested that the combination of reduced stereoacuity and increased binocular enhancement of contrast sensitivity seen in Duane syndrome can be explained by a partial loss of binocular cortical cells, caused by intermittent misalignment of the eyes during early visual development.

Adolescent↗

The structure of the human LIM protein ACT gene and its expression in tumor cell lines.

We describe the human ACT genomic and cDNA sequence which like its murine counterpart contains the defining secondary structure of the FHL (Four-and-a-Half LIM-domain) LIM-protein family. The coding region of the human ACT gene spans five exons. This distribution is very similar to the FHL1 gene and includes the arrangement of split codons across exon boundaries suggesting that these genes share a common ancestor. The human ACT gene was not detected by Northern analysis in the adult testis although this is the only known site of expression found with its murine counterpart. However, the human ACT gene was found to be expressed in a panel of human tumor cell lines derived from squamous cell carcinomas, melanomas, and leukemias. Interestingly, FHL1, FHL2, and FHL3 were also found to be expressed in some of these cell lines and the results suggest an important role for FHLs in tumor biology.

Adult↗

VIP activates G(s) and G(i3) in rat alveolar macrophages and G(s) in HEK293 cells transfected with the human VPAC(1) receptor.

We have characterized vasoactive intestinal peptide (VIP) receptor/G-protein coupling in rat alveolar macrophage (AM) membranes and find that pertussis toxin treatment and antisera against G(alphai3) and G(alphas) reduce high-affinity (125)I-VIP binding, indicating that both G(alphas) and G(alphai3) couple to the VIP-receptor. The predominant VIP-receptor subtype in AM is VPAC(1) and we examined the G-protein interactions of the human VPAC(1) that had been transfected into HEK293 cells. VPAC(1) has a molecular mass of 56 kDa; GTP analogs reduced (125)I-VIP binding to this protein demonstrating that high-affinity binding of VIP to the receptor requires coupling to G-protein. Functional VIP/VPAC(1)/G-protein complexes were captured by covalent cross-linking and analyzed by Western blotting. The transfected human VPAC(1) receptor in HEK293 was found to be coupled to G(alphas) but not G(alphai) or G(alphaq). Furthermore, pertussis toxin treatment had no effect on VPAC(1)/G-protein coupling in these cells. These observations suggest that the G-proteins activated by VPAC(1) may be dependent upon species and cell type.

Animals↗