Biomedical subjects

M J Morgan

Publications and source records attributed to M J Morgan.

At least 37 records · Page 2Linked to original sources

PubMed2000

Smoking-related cues elicit craving in tobacco "chippers": a replication and validation of the two-factor structure of the Questionnaire of Smoking Urges.

RATIONALE: The reliability and validity of the Questionnaire of Smoking Urges (QSU), a multi-factorial measure of cravings to smoke cigarettes has recently been called into question. OBJECTIVE: In the first phase of the present study, the reliability of the two-factor structure of QSU was examined. The new and original factor structures were then used to investigate the effects of 2 h of abstinence from smoking, and exposure to smoking-related cues, in a subset of the same sample of regular smokers. The present study also investigated the effects of smoking-related cues on QSU measures in tobacco "chippers" (occasional non-dependent smokers). METHODS: The factor structure of the QSU was investigated with a factor analysis of responses to the 32 QSU items produced by a sample of 271 regular smokers. A subset of these data was used to assess the influence of abstinence and cues on QSU factor scores. The final study used a sample of 32 tobacco chippers to assess the effect of smoking-related cues on their QSU factor scores. RESULTS: The results revealed a two-factor structure almost identical to that published by Tiffany and Drobes. In the second experiment, a brief period of abstinence significantly elevated factor 1 scores, but not factor 2 scores, compared to the non-abstinent condition. Exposure to smoking-related cues significantly elevated factor 2 scores and also tended to elevate factor 1 scores. In experiment 3, exposure to smoking-related cues significantly elevated factor 1 scores, but not factor 2 scores, in tobacco chippers. CONCLUSION: The QSU is a psychometrically sound instrument for the assessment of urges to smoke, which shows good construct validity. The two factors of the QSU show differential discriminative properties.

Adolescent↗

PubMed2000

Ecstasy (MDMA): a review of its possible persistent psychological effects.

RATIONALE: Recreational use of "ecstasy" (3,4-methylenedioxymethamphetamine; MDMA) has become increasingly widespread. Until recently, however, little was known about the possible persistent psychological effects of extensive use of this drug. OBJECTIVE: The aim of the present review is to evaluate recent empirical evidence concerning the persistent psychological sequelae of recreational ecstasy use. METHODS: The methodologies of open trial studies of recreational ecstasy users are evaluated and reports of the presence or absence of persistent psychological problems are related to the extent of past exposure to ecstasy. RESULTS: There is growing evidence that chronic, heavy, recreational use of ecstasy is associated with sleep disorders, depressed mood, persistent elevation of anxiety, impulsiveness and hostility, and selective impairment of episodic memory, working memory and attention. There is tentative evidence that these cognitive deficits persist for at least 6 months after abstinence, whereas anxiety and hostility remit after a year of abstinence. The possibility that some of these psychological problems are caused by ecstasy-induced neurotoxicity is supported by preclinical evidence of MDMA-induced neurotoxicity and behavioural deficits, evidence of depleted serotonin in heavy ecstasy users, and by dose-response relationships between the extent of exposure to ecstasy and the severity of cognitive impairments. CONCLUSIONS: An increasing number of young, heavy ecstasy users are at significant risk of persistent cognitive impairments and disturbances of affect and personality. Some of these problems may remit after abstinence, but residual neurotoxicity and decline of serotonergic function with age may result in recurrent psychopathology and premature cognitive decline.

Affect↗

PubMed2000

Are there separate first-order and second-order mechanisms for orientation discrimination?

In a series of experiments we compared orientation discrimination performance for Gabor stimuli in which the stimulus profile was either matched to the receptive field profile of single V1 simple cells ('simple'), or in which the carrier and envelope orientations were different ('tigertails'). In the first Experiment, using small, high spatial frequency, peripheral stimuli to minimise the number of detectors involved, we found that simple stimuli were more detectable than tigertails of the same contrast energy, and that orientation discrimination thresholds for simple stimuli were lower than for tigertails of equal detectability. In later experiments with larger stimuli we measured thresholds for detecting tilts of the envelope with the carrier fixed in orientation. Envelope thresholds were similar for different carrier orientations, but carrier orientation had a strong biasing effect upon perceived envelope orientation. When the orientation difference between envelope and carrier was small, the carrier orientation was attracted to that of the envelope; when the difference was large (>10 degrees ) repulsion was found. The biases were reduced by half-wave rectifying the stimuli, putatively making the envelope visible to a first-order filter (Experiment 2). Discrimination thresholds for envelope orientation were higher than those for carrier orientation, and this difference was greater for briefly-presented parafoveal stimuli than for long duration foveal stimuli (Experiments 3 and 4). We conclude from these results that there are separate mechanisms for envelope and carrier orientation discriminations for large stimuli, but that first- and second-order mechanisms are not independent in the discrimination of orientation.

Analysis of Variance↗

PubMed2000

Motion-stereo mechanisms sensitive to inter-ocular phase.

We measured depth from interocular delay (The Pulfrich effect) using a dynamic random-dot pattern, consisting of a spatially-random noise field, the individual elements of which were sinusoidally-modulated in luminance over time. When an interocular phase difference in the flicker was introduced the display appeared to rotate in depth around a vertical axis like a transparent textured cylinder. The threshold phase lag was in the region of 5-10 degrees in different observers, which translated into a non-constant, decreasing interocular delay (ms) as the flicker frequency was increased. We conclude that phase, not delay, is the critical parameter in determining the detection of depth. Threshold signal/noise ratios were measured at different delays to determine the optimum phase difference, which was found to be in the region 60-90 degrees. However, delays centred around 180 degrees were less detectable than those around zero, ruling out a quadrature input to the stereo-motion mechanisms. We show that depth-from-phase is a natural consequence of paired monocularly motion-direction sensitive neurones. Complex energy-detecting neurones are not required to explain the findings.

Fourier Analysis↗

PubMed2000

The use of an implicit standard for measuring discrimination thresholds.

We measured thresholds for comparing the separation between lines, using either the method of constant stimuli (MCS) or the method of single stimuli (MSS). In the MCS an explicit standard is presented on each trial, whereas in the MSS the standard is the mean of the set. The thresholds for the MSS procedure were nearly identical to those with the MCS procedure, whether or not feedback was used. A statistical model is presented showing how the threshold error estimated by MSS varies according to the number of past stimuli used by the observer to calculate the mean of the set. If the model is an accurate representation of human processing, our observers were averaging over the last 10-20 trials to estimate the implicit standard. Our results show that the explicit standard in the MCS procedure is generally superfluous. Provided that the test range is small, and that the observer is given some practice trials, thresholds measured with MSS procedure are just as precise as those measured with the traditional MCS procedure.

Differential Threshold↗

PubMed2000

Facilitation from collinear flanks is cancelled by non-collinear flanks.

Detection of a central Gabor pattern is facilitated by the presence of collinear flanking patterns. We find that this facilitation is greatly reduced when the collinear flanks are combined with non-collinear flanks to form a coherent surround. These results are unlikely to be explained by mechanisms that merely transduce local contrast in a nonlinear fashion. A model wherein the outputs of such mechanisms are combined anisotropically provides a better account for these results.

Adaptation, Psychological↗

PubMed2000

Gelatinase-B (matrix metalloproteinase-9; MMP-9) secretion is involved in the migratory phase of human and murine muscle cell cultures.

The remodelling of connective tissue components is a fundamental requirement for a number of pivotal processes in cell biology. These may include myoblast migration and fusion during development and regeneration. In other systems, similar biological processes are facilitated by secretion of the matrix metalloproteinases (MMPs), especially the gelatinases. This study investigated the activity of the gelatinases MMP-2 and 9 by zymography on cell conditioned media in cultures of cells derived from explants of the human masseter muscle and in the murine myoblast cell-line C2C12. Expression of MMP-9 by western blotting and TIMP-1, the major inhibitor of MMPs, by northern blotting, during all phases of myoblast proliferation, migration, alignment and fusion, was also measured. Irrespective of the origin of the cultures, MMP-9 activity was secreted only by single cell and pre-fusion cultures whilst MMP-2 activity was secreted at all stages as well as by myotubes. The loss of MMP-9 activity was due to the loss of MMP-9 protein expression. TIMP-1 mRNA was not detectable at the single cell stage but its expression increased as cells progressed through the pre-fusion and post-fusion stages to reach a maximal in myotube containing cultures. Migration of cells derived from human masseter muscle was inhibited, using a specific anti-MMP-9 blocking monoclonal antibody (6-6B). These data are consistent with the concept that regulation of matrix turnover via MMP-9 may be involved in the events leading to myotube formation, including migration. Loss of expression of this enzyme and expression of TIMP-1 mRNA is associated with myotube containing cultures. Consequently, the ratio between MMPs and TIMPs maybe important in determining myoblast migration and differentiation.

Animals↗

PubMed2000

Slow troponin T mRNA in striated muscles is expressed in both cell type and developmental stage specific manner.

We have cloned cDNA sequences of both rat and mouse slow troponin T gene. These sequences share a high level of homology with each other and with the human slow troponin T gene although we were unable to detect an alternatively spliced exon present at 3' end of human slow troponin T cDNA in either mouse or rat cDNAs. Northern blot analysis detected a high level expression of slow troponin T in adult mouse Soleus with a lower level expression in mixed postnatal skeletal muscles. Unlike late fetal and postnatal skeletal muscles in which slow troponin T expression is restricted to slow muscle fibre rich regions only, in situ hybridisation analysis detected this isoform to be highly expressed in somitic myotome and all muscle masses at 10-14 days of gestation after which its expression was rapidly downregulated. The unexpected expression of slow troponin T mRNA in fetal heart was apparent by both northern blotting and in situ hybridisation analyses. Slow troponin T mRNA in fetal heart was first detected at 10 day in utero reaching maximum levels of expression at 12-15 days gestation. The slow troponin T in the heart was mainly expressed in the ventral ventricles until day 15 after which low level expression was also observed in both atria. Slow troponin T mRNA in both atrium and ventricle was mainly expressed in outer wall of the myocardium although it was also expressed in interventricular septum. This study therefore shows that in addition to being a cell type specific marker during later fetal and postnatal skeletal muscle development, slow troponin T represented one of the major developmental isoforms expressed in embryonic and fetal skeletal muscle as well as in the cardiac muscle.

Age Factors↗

PubMed2000

Metalloproteinase expression in normal and malignant oral keratinocytes: stimulation of MMP-2 and -9 by scatter factor.

Matrix metalloproteinases (MMPs) are Zn2+ dependent proteases produced by a variety of cell types. They have a fundamental role in tissue remodelling, tumour invasion and metastasis. Scatter factor (SF), secreted by fibroblasts, has a paracrine action on epithelial cells and binds the trans-membrane c-met receptor inducing loss of adhesion, cell motility and invasiveness in vitro. The purpose of this study was to test if SF can regulate the production of MMPs by epithelial cells. Supernatants from oral squamous cell carcinoma-derived cells (H375 and H376), a human keratinocyte line (UP), and primary cultures of oral mucosal keratinocytes, grown in the presence or absence of SF, were analysed using 0.1% gelatin zymography. MMPs were characterised by comparison with human recombinant enzymes and by the use of specific inhibitors. Oral mucosal keratinocytes, UP, and H357 cells expressed MMP-2 and MMP-9, whilst H376 cells only expressed MMP-2. SF increased the expression of MMP-9 in UP and MMP-2 in H376 supernatants. Both MMP-2 and MMP-9 activity were increased in H357 and normal keratinocyte supernatants. This could be blocked using a human recombinant anti-SF antibody. In all epithelial lines tested, c-Met, the cell surface receptor for SF, could be detected. The results indicate that SF stimulates MMP expression in UP, H376, H357, and normal oral mucosal cells and points to a role for SF in the regulation of oral keratinocyte behaviour in wound healing and neoplasia.

Analysis of Variance↗

PubMed2000

The spatio-chromatic sensitivity of the human visual system.

The response of the human visual system depends on a multitude of image features, such as the wavelength (colour) of the visual stimulus and its spatial frequency content. Hence we need to take into account the spatial and chromatic sensitivity as well as spatio-chromatic interactions to properly characterize visual sensitivity. In this paper we report two experiments that further characterize the spatio-chromatic sensitivity of the human visual system for stationary stimuli, namely the detection of small visual orientation differences and the detection of blur. In both cases we find that the visual system is equally sensitive to red-green and to black-white modulations for a wide range of spatial parameters. Furthermore, the contrast dependence for red green and black white modulations is identical, suggesting that the same mechanism mediates both types of stimulus. Our results are in accordance with the hypothesis that both tasks are mediated by the parvocellular as opposed to the magnocellular pathway.

Color Perception↗

PubMed1999

Saccadic suppression precedes visual motion analysis.

There is now good evidence that perception of motion is strongly suppressed during saccades (rapid shifts of gaze), presumably to blunt the disturbing sense of motion that saccades would otherwise elicit. Other aspects of vision, such as contrast detection of high-frequency or equiluminant gratings, are virtually unaffected by saccades [1] [2] [3] [4] [5]. This has led to the suggestion that saccades may suppress selectively the magnocellular pathway (which is strongly implicated in motion perception), leaving the parvocellular pathway unaffected [5] [6]. Here, we investigate the neural level at which perception of motion is suppressed. We used a simple technique in which an impression of motion is generated from only two frames, allowing precise control over the stimulus [7] [8]. One frame has a certain fixed contrast, whereas the contrast of the other (the test frame) is varied to determine the threshold for motion discrimination (that is, the lowest test-frame contrast level at which the direction of motion can be correctly guessed). Contrast thresholds of the test depended strongly and non-monotonically on the contrast of the fixed-contrast frame, with a minimum at medium contrast. To study the effect of saccadic suppression, we triggered the two-frame sequence by a voluntary saccade. Thresholds during saccades increased in a way that suggested that saccadic suppression precedes motion analysis: when the test frame was first in the motion sequence there was a general depression of sensitivity, whereas when it was second, the contrast response curve was shifted to a higher contrast range, sometimes even resulting in higher sensitivity than without a saccade. The dependence on presentation order suggests that saccadic suppression occurs at an early stage of visual processing, on the single frames themselves rather than on the combined motion signal. As motion detection itself is thought to occur at an early stage, saccadic suppression must take place at a very early phenomenon.

Humans↗

PubMed1999

The LIM proteins FHL1 and FHL3 are expressed differently in skeletal muscle.

We have determined the complete mRNA sequence of FHL3 (formerly SLIM2). We have confirmed that it is a member of the family of LIM proteins that share a similar secondary protein structure, renamed as Four-and-a-Half-LIM domain (or FHL) proteins in accordance with this structure. The "half-LIM" domain is a single zinc finger domain that may represent a subfamily of LIM domains and defines this particular family of LIM proteins. The distribution of FHL mRNA expression within a variety of murine tissues is complex. Both FHL1 and FHL3 were expressed in a number of skeletal muscles while FHL2 was expressed at high levels in cardiac muscle. Localisation of FHL3 to human chromosome 1 placed this gene in the proximity of, but not overlapping with, alleles associated with muscle diseases. FHL1 and FHL3 mRNAs were reciprocally expressed in the murine C2C12 skeletal muscle cell line and this suggested that the pattern of expression was linked to key events in myogenesis.

Amino Acid Sequence↗

PubMed1999

The fourth member of the FHL family of LIM proteins is expressed exclusively in the testis.

We have determined the sequence of a novel LIM protein, termed FHL4. It was found to contain the defining secondary structural arrangement of the FHL (formerly SLIM) family of LIM proteins. This sequence was assembled using EST sequences deposited on the dbEST database and from sequencing of PCR fragments, all of which were derived from murine testis cDNA. Northern analysis of a wide range of murine tissues demonstrated that the expression of FHL4 mRNA was restricted to the testis. Using in situ hybridisation, FHL4 mRNA was found to be associated with the seminiferous epithelium and not with the interstitial tissue surrounding the seminiferous tubules. It is suggested that mFHL4 is associated with the process of spermatogenesis.

Amino Acid Sequence↗

PubMed1999

Memory deficits associated with recreational use of "ecstasy" (MDMA).

Evidence from both animal, and human, studies suggests that repeated administration of 3,4-methylenedioxymethamphetamine (MDMA: "ecstasy") produces lasting decreases in serotonergic activity. Serotonin is believed to play a modulatory role in a variety of psychological processes, including learning and memory. There are recent reports that polydrug users, who have used ecstasy recreationally, exhibit selective impairments in memory. However, these studies did not compare ecstasy users with polydrug users who had not taken ecstasy, leaving open the possibility that the memory deficits may be associated with a history of use of other illicit drugs. The present study used the Rivermead Behavioural Memory test to investigate immediate and delayed recall in: 25 polydrug-users who had taken more than 20 tablets of ecstasy (MDMA group), 22 participants (polydrug controls) who had never taken ecstasy, but, otherwise has personal characteristics (e.g. age, gender, education, height, weight), and illicit drug use histories, that were generally not significantly different from those of the MDMA group, and 19 participants who had not used illicit drugs but who also had similar personal characteristics (non-drug controls). Participants in the MDMA group recalled significantly fewer ideas (approximately 75% of the number of ideas recalled by participants in either of the other two groups), in both immediate and delayed recall conditions. The two illicit drug-using groups did differ in their estimated IQ scores and their duration of use of LSD, but only the latter proved to be a statistically significant covariate, and the difference in recall performance between the MDMA and polydrug controls groups remained statistically significant when this variable was treated as a covariate. The present findings provide the first evidence that deficits in memory performance in recreational ecstasy users are primarily associated with past exposure to ecstasy, rather than with the other legal and illicit drugs consumed by these individuals, and are consistent with reduced serotonergic modulation of mnemonic function as a result of long-term neurotoxic effects of MDMA in humans.

Adult↗

PubMed1999

Passive stretch modulates denervation induced alterations in skeletal muscle myosin heavy chain mRNA levels.

The effect of denervation and denervation combined with immobilisation in either the shortened or lengthened position (passive stretch) upon myosin heavy chain (MyHC) mRNA levels was examined in three rat hind-limb muscles with differing phenotypes. Denervation alone caused a reduction in type I and type IIa MyHC transcripts in all three muscles. In contrast denervation caused a 72% increase in type IIb in the slow postural soleus muscle only which was prevented by immobilisation in the lengthened position. In the same muscle passive stretch also significantly retarded the effects of denervation upon the type I transcript (from 38% below control levels to 24% below) and type IIa transcript (from 59% to 32% below control levels). The levels of both type I and IIa transcripts, in the fast phasic plantaris muscle, were both unaffected by stretch combined with denervation when compared to denervation alone. In the mixed gastrocnemius muscle stretch affected the level of the type I but not the type IIa transcript. These data suggest that passive stretch can modulate MyHC gene expression independently of innervation but that it does so in a muscle-specific manner.

Animals↗

PubMed1999

Transducer model produces facilitation from opposite-sign flanks.

Small spots, lines and Gabor patterns can be easier to detect when they are superimposed upon similar spots, lines and Gabor patterns. Traditionally, such facilitation has been understood to be a consequence of nonlinear contrast transduction. Facilitation has also been reported to arise from non-overlapping patterns with opposite sign. We point out that this result does not preclude the traditional explanation for superimposed targets. Moreover, we find that facilitation from opposite-sign flanks is weaker than facilitation from same-sign flanks. Simulations with a transducer model produce opposite-sign facilitation.

Contrast Sensitivity↗

PubMed1999

The Poggendorff illusion: a bias in the estimation of the orientation of virtual lines by second-stage filters.

The veridical perception of collinearity between two separated lines is distorted by two parallel lines in the space between them (the Poggendorff illusion). This paper tests the conjecture that the perception of collinearity of separated lines is based on a two-stage mechanism. The first stage encodes the orientation of the virtual line between the proximal terminators of the target lines. The second stage compares this virtual orientation with the orientation of the target lines themselves. Errors can and do arise from either process. Two parallel lines, abutting against the target lines, cause the classical Poggendorff misalignment bias. The magnitude of the bias is increased by Gaussian blur, as is a version of the Poggendorff figure containing only acute angles. In the obtuse-angle figure, on the other hand, blur decreases the misalignment bias. We argue that the acute- and obtuse-angle biases depend upon different mechanisms, and that the obtuse-angle effect is more related to the obtuse-angle version of the Muller-Lyer illusion, which is also decreased by blur. If observers attempt to match the orientation of the virtual line between the two line intersections in the Poggendorff figure they make an error in the same direction as the Poggendorff bias. The orientation of the target lines in the figure, however, is veridically matched to a Gabor-patch probe, unless the target lines are very short, in which case the error is in the same direction as the Poggendorff bias. A small bend in the target lines where they abut the parallels increases the Poggendorff bias if it makes the line more orthogonal to the parallel, but has little effect in the opposite direction. The Poggendorff bias is unlikely to depend upon biases in first-stage linear filters because (a) it still exists in figures composed of short, luminance-balanced lines which are defined by contrast only; and (b) it also exists if the parallels are replaced by grating patches with the same mean luminance as the background. The orientation of the grating in the latter case affects the magnitude of the bias, but even an orientation which should reverse the Poggendorff bias by the mechanism of cross-orientation inhibition fails to do so. The Poggendorff bias is a complex effect arising from several sources. Blurring in second-stage filters with large receptive fields can explain many aspects of the phenomenon.

Contrast Sensitivity↗

PubMed1999

Dichoptically cancelled motion.

We sought to determine whether or not motion-from-texture mechanisms have access to monocular input. Adopting a strategy used by Kolb and Braun (1995. Nature, 377, 336-338), we created drifting textures that were invisible to purely binocular processes. Monocular signals readily conveyed motions defined by local orientation and flicker. However, when left- and right-eye signals were displayed simultaneously, only flicker motion was visible. We conclude that motion-from-texture mechanisms do not have access to monocular input. Further evidence suggests that motion from texture involves attentional tracking.

Discrimination, Psychological↗