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Biomedical subjects

J G May

Publications and source records attributed to J G May.

At least 19 recordsLinked to original sources

Change in the mode of inhibition of acetylcholinesterase by (4-nitrophenyl)sulfonoxyl derivatives of conformationally constrained choline analogues.

A chiral, five-step synthesis of 2-(hydroxymethyl)-2,4-dimethylmorpholine (12) from (R)- and (S)-2-methylglycidols gives an overall yield of 63%. Morpholines (R)- and (S)-12 are converted into 2-(azidomethyl)-2,4-dimethylmorpholine (15) via 2,4-dimethyl-2-[[(4-nitrophenyl)sulfonoxy]methyl]morpholine (14). The tertiary morpholines 12, 14, and 15 are quaternarized to afford 2-(hydroxymethyl)-2,4,4-trimethylmorpholinum iodide (2), 2,4,4-trimethyl-2-[[(4-nitrophenyl)sulfonoxy]methyl]morpholinium iodide (3), and 2-(azidomethyl)-2,4,4-trimethylmorpholinium iodide (4), respectively, which all inhibit acetylcholinesterase (AChE). These morpholinium inhibitors are compared with conformationally constrained aryl hemicholinium AChE inhibitors. Enantiomers of 2 and 4 are reversible competitive inhibitors of AChE, with values of Ki = 360 +/- 30 microM for (S)-2, 650 +/- 90 microM for (R)-2, 450 +/- 70 microM for (S)-4, and 560 +/- 30 microM for (R)-4, respectively. Enantiomers of 3 are noncompetitive inhibitors of AChE with values of Ki = 19.0 +/- 0.9 microM for (S)-3 and 50 +/- 2 microM for (R)-3, respectively. AChE shows a 2-fold chiral discrimination in the case of inhibition by 2 and 3. Inhibition also changes from competitive to noncompetitive when (3-hydroxyphenyl)-N,N,N-trimethylammonium iodide (18) [Ki = 0.21 +/- 0.06 microM; Lee, B. H., Stelly, T. C., Colucci, W. J., Garcia, J. G., Gandour, R. D., and Quinn, D. M. (1992) Chem. Res. Toxicol. 5, 411-418] is converted into [3-[(4-nitrophenyl)sulfonoxy]phenyl]-N,N,N-trimethylammonium iodide (5), Ki = 6.0 +/- 0.5 microM. These results indicate that the 4-nitrobenzenesulfonyl group controls the mode of inhibition.

Acetylcholinesterase

On a failure to replicate: methodologically close, but not close enough. A response to hogben et al.

Williams, Brannan and Lartigue (1987) (Clinical Vision Science, 1, 367-371) reported that poor readers took significantly longer to search letter arrays for a target than did good readers. In addition, they reported that blurring the letter arrays leads to faster search times for poor readers and a loss of the significant differences between the groups seen with unblurred displays. In a recent attempt to replicate these findings, Hogben et al. (1996) (Vision Research, 36, 1503-1507) found no differences in search rates between good and poor readers using unblurred arrays, and no differences in search rate between the groups when blurred arrays were used. In the present article, we have compared these two research efforts, and a third paper on the same topic, with regard to methodological factors in an attempt to understand how these two different results could occur. It is our belief that the letter spacing employed in the two studies may account for the difference and should be the focus of future studies of the original effect.

Child

The effects of spatial filtering and contrast reduction on visual search times in good and poor readers.

Recent experiments with reading disabled children have shown that image blurring (produced with frosted acetate overlays) results in an immediate benefit in search performance, eye movement pattern and reading comprehension. This suggests that the contrast and spatial frequency content of visual stimuli are important factors for these children. In the present experiment, spatial frequency filtering and contrast reduction were employed to determine whether either of these factors contributes to the beneficial effects observed. Letter arrays were spatially filtered to produce low pass (< 3.5 c/deg) and high pass (> 7.0 c/deg) images. In addition, a low contrast control image was generated to match the low contrast of the high pass image. Children classified as good reader controls (CON), specific reading disabled (SRD), attention deficit disordered (ADD) or comorbid SRD/ADD (COM) were asked to perform a visual search task with each type of image. With high contrast, unfiltered arrays, the search times for the CON and ADD groups were much shorter than those of the SRD and COM groups. While both high pass and low pass filter conditions improved the search speed for the COM group, improvement for the SRD group was only obtained with low contrast stimuli. These results support the notion that the beneficial results of image blurring with SRDs derives from the contrast reduction produced by such manipulations.

Child

The effectiveness of a motion sickness counselling programme.

Unselected volunteers were offered a course of instruction in using the cognitive-behavioural approach to helping individuals tolerate the deleterious effects of different motion environments. In order to evaluate that programme, 11 of the participants volunteered to counsel independently individuals who were prone to motion sickness, using cognitive-behavioural training which included reinforcement by visually induced apparent motion. The subjects were pre- and post-tested by an independent observer using tolerance and motion response as the dependent variables. These test scores were compared to previous data obtained with subjects who had received counselling from an experienced counsellor, or had received no such counselling. The results indicated that the newly trained counsellors' subjects showed significant pre- to post-test tolerance to the motion stimulus, although they did not benefit as much as subjects trained by the experienced counsellor. However, in terms of post-test symptomatology and magnitude estimates of motion sickness, the trainees' subjects exhibited as much benefit as did those of the experienced counsellor. These data are taken as strong support for the feasibility of training counsellors to employ this method of alleviating motion sickness.

Adolescent

The time-course of global precedence and consistency effects.

The global precedence effect refers to the finding that global aspects of a scene are processed more rapidly than local detail in the scene. In experiments with large Hs and Ss (global stimuli) made up of small Hs and Ss (local stimuli), choice reaction time (RT) to the global letters is shorter than RT to the local letters (global precedence effect). In addition, RT for local letters is shorter when the local letters are the same as the global letter (consistency effect). We sought to determine the time course of the global precedence and consistency effects by delaying the global information relative to the local information. In Experiment I, the middle cross-bar of the global letter (S or H) was presented followed by the rest of the global letter at delays of 0, 48, 80, 160, 320 and 640 ms. The results indicated that the global precedence effect was obtained at delays < 48 ms and local precedence effects are obtained at delays > 80 ms. Consistency effects were found in the absence of global precedence effects, but only at delays of 48 and 80 ms. Experiment II was a replication with delays of 16, 32, 48, 64, 80, and 96 ms. The results of this experiment were in agreement with those of Experiment I. These findings offer support for the notion that the consistency effect is mediated by a higher level process than is the global precedence effect.

Adult

Reading-related wavelength and spatial frequency effects in visual spatial location.

Specific deficits in the processing of transient visual stimuli have been identified in reading-disabled children, and it has been shown that the filtering out of some medium to high spatial frequencies and some visible wavelengths impacts on their performance in a number of visual tasks. To assess further how these light diffusing and colour filtering manipulations might mediate visual processing, this study compared the letter-naming accuracy and visual spatial location judgements of eighteen poor readers with those made by eighteen good readers of the same age. Naming and spatial discrepancy measures were recorded for briefly displayed target letters at varying eccentricities, for each child, under a normal (NI) condition and wearing blue (Be), yellow (Yw), diffusion (Dn), blue with diffusion (BeDn), and yellow with diffusion (YwDn) optical framed lenses. A preliminary analysis of the data detected larger spatial discrepancies for the poor readers, and this finding was consistent with the presence of a deficit in transient (or magnocellular) activity in these children. Both the naming accuracy data and the spatial location data showed filter-dependent differences in reading ability. The letter-naming data showed that the addition of the blue filter to the diffusion lens significantly depressed performance only for the good readers, and that the addition of the yellow filter to the diffusion lens significantly improved performance only for the poor readers. Comparison of the spatial discrepancies showed that the rate at which location accuracy declined with increasing target eccentricity was smaller for the blue and yellow lenses than for normal viewing in the case of the good readers but not in the case of the poor readers.(ABSTRACT TRUNCATED AT 250 WORDS)

Child

Stimulus manipulations that reduce the square-wave illusion.

When observers view a triangle-wave luminance profile, they often report a square-wave illusion with a depth component. Alternate bars appear to be in different depth planes and the surface appears corrugated; illuminated from either the right or the left. These perspectives alternate with continuous viewing. One explanation for this illusion stems from a local energy model of feature detection proposed by Morrone and Burr (Proc. Roy. Soc. Lond. B235, 221-245, 1988). This model assumes two phase-sensitive mechanisms that process lines and edges in the visual image. It is suggested that the square-wave illusion derives from rivalry between these two mechanisms. In experiment 1, the aim was to determine whether phase alternation of the triangle wave would lead to differences in the duration and number of perceptual reversals of the illusion. The results indicate a decline in illusion duration and frequency of reversal rate with increased alternation rate. With the addition of some assumptions about the temporal resolution of the line and edge detectors, the results support the proposed explanation. In Experiment 2, the effects of high spatial-frequency contrast increments and decrements were explored. Increments did not lead to significant increases in the duration of the square-wave illusion or reversal rate, but decrements resulted in a substantial reduction in the illusion duration and reversal rate. The results indicate that manipulations which alter the phase relationships of the triangle wave decrease the illusion, but manipulations which maintain them do not.

Contrast Sensitivity

Cognitive-behavioral management of motion sickness.

This monograph is intended to provide health professionals with information on a cognitive-behavioral technique which was developed to teach individuals who are prone to motion sickness to better cope with motion environments. It includes an overview of motion sickness, describing the signs and symptoms, etiology and incidence of this malady. Prevention and treatment are then reviewed, including both pharmacological and non-pharmacological therapies. The historical background on the cognitive-behavioral technique is then discussed. This is followed by a review of supporting experimental work, and an account of how such counselling should be carried out. Finally, a number of current military desensitization programs are compared and contrasted with cognitive-behavioral therapy.

Biofeedback, Psychology

Effects of spatial filtering and lack of effects of visual imagery on pattern-contingent color aftereffects.

Checkerboards contain fundamental two-dimensional Fourier components oriented 45 degrees from the edges of individual checks. Previous studies have shown that contingent color aftereffects following adaptation to chromatic checkerboard stimuli were associated with the fundamental components rather than the edges. In the present experiments, we measured contingent color aftereffects, using the method of constant stimuli, after subjects adapted to unfiltered checkerboards and checkerboards with the fundamental Fourier components removed. The adaptation stimuli were magenta (or green) squares and green (or magenta) diamonds; the test stimuli were vertical or oblique sine-wave gratings with different saturations. After adaptation to unfiltered checkerboards, aftereffects contingent on the fundamental components were obtained. In contrast, after adaptation to filtered stimuli, aftereffects of smaller magnitude were found to be aligned with the edges. The data support the previous findings of spatial-frequency-contingent color aftereffects with checkerboard adaptation stimuli and indicate that the aftereffects can be associated with edges if the fundamental components of adaptation stimuli are removed by spatial filtering. We reexamined the possibility of color aftereffects induced by imagery of checkerboards. Contrary to the previous reports, no significant aftereffects were obtained.

Adult

Immunohistochemical organization of the ventral lateral geniculate nucleus in the ground squirrel.

The ventral lateral geniculate nucleus (vLGN) of the thirteen-lined ground squirrel (Citellus tridecemlineatus) is a highly differentiated nucleus that is divisible into five major subdivisions on the basis of retinal projections and cytoarchitecture. To pursue the likelihood that these subdivisions (the dorsal cap, intergeniculate leaflet, external magnocellular lamina, internal magnocellular lamina, and parvicellular segment) correlate with the functional diversity of this complex, the present study examined the neurochemical composition of the vLGN with regard to substances that have previously proved useful in distinguishing functionally distinct subregions within nuclei (i.e., neuropeptide Y (NPY), substance P (SP), leucine and methionine enkephalins, gamma-aminobutyric acid (GABA), cytochrome oxidase (CO), acetylcholinesterase (AChE), and NADPH-diaphorase). The results showed a clear differential neurochemical distribution within the nucleus. Neuropeptide Y immunoreactive perikarya were found predominantly in the intergeniculate leaflet and external magnocellular lamina, with only a few present in the internal magnocellular lamina and dorsal cap, and none observed in the parvicellular segment. NPY+ fibers, however, were present in all divisions except the parvicellular segment. The highest concentration of SP immunoreactive cells was observed in the internal magnocellular lamina, and substantial numbers also were scattered in the external magnocellular lamina and parvicellular segment. SP+ fibers were seen predominantly in the intergeniculate leaflet and the magnocellular laminae. The heaviest concentration of enkephalinergic fibers occurred in the internal magnocellular lamina and dorsal cap, but fibers were also observed in the external magnocellular lamina and intergeniculate leaflet. GABA reactivity was widespread throughout the vLGN, with the dorsal cap and external magnocellular lamina most heavily labeled, followed by the intergeniculate leaflet and the internal magnocellular lamina. Cytochrome oxidase, AChE, and NADPH-diaphorase histochemistry revealed rich reactivity within the dorsal cap, and external and internal magnocellular laminae and paler reactivity in the intergeniculate leaflet and parvicellular segment. The external magnocellular lamina was more reactive for CO and NADPH-diaphorase than AChE, while the internal magnocellular lamina showed the opposite pattern of reactivity. In addition, NADPH-diaphorase reactive cells were present in caudal intergeniculate leaflet and lateral external magnocellular lamina. These local differences in the neurochemical character of the vLGN support its parcellation into multiple subdivisions. Taken in conjunction with the differences in cytoarchitecture and retinal projections, these results suggest substantial functional diversity within the ventral lateral geniculate complex.

Acetylcholinesterase

Immunohistochemical organization of the ventral lateral geniculate nucleus in the tree shrew.

The ventral lateral geniculate nucleus (vLGN) of the tree shrew (Tupaia belangeri) was differentiated into multiple subdivisions (dorsal cap, intergeniculate leaflet, parvicellular segment, and internal and external magnocellular laminae, the latter being further divisible into a lateral and medial division) on the basis of retinal projections, immunochemistry, and histochemistry. Retinal projections traced with intravitreal injections of wheat germ agglutinin conjugated horseradish peroxidase revealed direct bilateral input to all subregions of the vLGN, except for the internal magnocellular lamina (which received only contralateral input) and the parvicellular segment (which was not retinorecipient). Furthermore, retinal inputs clearly distinguished the relatively heavily retinorecipient intergeniculate leaflet from the less prominently labeled dorsal cap. Immunohistochemical localization of Neuropeptide Y (NPY) perikarya revealed their prominence in the intergeniculate leaflet and the external magnocellular laminae with a concentration along the optic tract. NPY immunoreactive fibers were seen in all but the parvicellular subregion. Gamma amino butyric acid immunoreactivity was seen throughout the vLGN, but was most concentrated in the dorsal cap and the magnocellular laminae, followed by the intergeniculate leaflet. Histochemical studies of cytochrome oxidase and nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase localization revealed similar patterns of dense reactivity within the external magnocellular lamina, intergeniculate leaflet and dorsal cap, and somewhat less dense, but substantial reactivity in the internal magnocellular lamina. Within the external magnocellular lamina, cells reactive for cytochrome oxidase were noted in the lateral portion bordering the optic tract, whereas those specific for NADPH-diaphorase were dispersed throughout the lamina. Poor reactivity for both histochemical markers was evident in the parvicellular segment. Overall, the markedly different patterns of retinal input and neurochemical organization between the subdivisions of the tree shrew vLGN suggest their involvement in diverse functions. Furthermore, the basic similarity of the organization of the tree shrew vLGN to that of the taxonomically unrelated ground squirrel may indicate a common mammalian scheme.

Animals

A posteriori digital filtering to reduce signal-averaging of steady-state evoked potentials.

This paper describes a signal extraction technique that involves taking the time series representation of signals, transforming them into the frequency domain, determining the chance occurrence of power at each frequency, and filtering accordingly. An inverse Fourier transform is then used to recreate the new time domain representation, which has been appropriately filtered for extraneous noise. Thus, this technique involves a posteriori digital filtering based on a statistical criterion for component inclusion. Computer simulation indicated that, at poor signal-to-noise ratios and with fewer samples, this technique is 5 to 10 times better at signal extraction than conventional signal averaging. Examples of pattern-elicited electroretinograms (PERG's) are used to illustrate the efficacy of this method.

Computer Simulation

Phase shifts and the square-wave illusion.

When observers view a vertical triangle-wave luminance profile, they often report a square-wave illusion with a depth component, resembling a corrugated surface. Alternate bars seem to be in front of or behind adjacent bars and the surface appears to be illuminated from the right or left. These perspectives alternate with continuous viewing. One explanation for this illusion stems from the notion of instability among phase-selective mechanisms. Two experiments (1 and 3) were designed to determine whether systematic phase shifts introduced between the fundamental and the odd harmonics of the waveform would lead to a systematic bias of the illusion. The results indicated that a significant bias occurred when a phase shift as small as 9 deg was introduced, and that the bias from the phase shifts was more powerful than previous reports of drift-induced bias. There was a highly significant effect of direction of phase shift and the corresponding perceived direction of illumination. Another experiment (2) was designed to determine if illusional cues within the phase-shifted profiles aided phase discrimination. The results indicated that experienced subjects, presumably using cues within the profiles, discriminated between the stimuli significantly better than did naive subjects. These data support the role of phase in the square-wave illusion, but they also raise questions about the role of contrast changes in local regions of the stimulus.

Adaptation, Ocular

Visual search for simple volumetric shapes.

Five experiments measured reaction time (RT) to detect the presence or absence of a simple volumetric shape (target) dependent on the number of display items (distractors) and their depicted three-dimensional (3-D) orientation. Experiments 1-4 examined every pairwise combination of two different simple volumetric shapes in two 3-D orientations. Conditions exhibiting "pop-out" could be predicted by differences in their two-dimensional (2-D) features. Conditions in which search was slower support previously found search asymmetries for particular 2-D features. When the distractors were a mixture of the other shapes in the same 3-D orientation, search was serial, except when the target had a curved principal axis (Experiment 5). The results suggest that these simple volumetric shapes are not processed preattentively.

Adult

The effects of spatial phase on reaction time to spatially filtered images.

Many studies of visual perception have used periodic stimuli such as sine-wave gratings and checkerboard patterns. It is well known that reaction time (RT) to such stimuli increases with increasing spatial frequency and decreasing contrast. While this is the case with periodic stimuli it is not clear that these relationships obtain for aperiodic stimuli such as natural scenes. A digitized image of an object (a vase) was submitted to two-dimensional Fourier analysis. Four pairs of spatial frequency band-limited images were created for each image. Each pair consisted of a normal-phase (NP) and a scrambled-phase (SP) version, with the magnitude spectrum and space-averaged luminance the same within each pair. Filter band-widths were 1 octave wide. Manual RT was measured for onset and offset of each spatially filtered image. Mean RT for SP images increased significantly with increasing spatial frequency, while no other significant differences were found with the NP images. This suggests that the temporal processing of complex, aperiodic images is influenced by the spatial frequency and contrast of local regions within the image, rather than by the space-averaged contrast of the entire image, and cannot be predicted by global estimates of contrast and spatial frequency.

Adult

Eye movement indices of mental workload.

Four investigations were carried out to assess the feasibility of using eye movement measures as indices of mental workload. In the first experiment, saccadic extent was measured during free viewing while subjects performed low, moderate and high complexity, auditory tone counting as the workload tasks. The range of saccadic extent decreased significantly as tone counting complexity (workload) was increased. In the second experiment the range of spontaneous saccades was measured under three levels of counting complexity with a visual task that did not require fixation or tracking. The results indicated that the extent of saccadic eye movements was significantly restricted as counting complexity increased. In the third experiment, the effects of practice were examined and decreased saccadic range under high tone counting complexity was observed even when significant increases in performance occurred with practice. Finally, in experiment 4, the first experiment was repeated with additional optokinetic stimulation and the saccadic range was again observed to decrease with tone counting complexity. The results indicated that the extent of spontaneous and elicited eye movements was significantly restricted as counting complexity increased. We conclude that this measure may provide a valuable index of mental workload.

Adult

Emotional processing and fear measurement synchrony as indicators of treatment outcome in fear of flying.

Minimal-therapist-involvement stress inoculation training was used to treat flying phobics. Relative to no-treatment controls, treatment subjects reported more fear reduction, were more likely to participate in an exposure session, and flew more during a two-month follow-up period. Subjects who exhibited synchronous changes in heart rate and report of anxiety during exposure had greater fear reduction than subjects showing less synchrony. Subjects who voluntarily took plane flights in the two months following treatment showed greater indications of emotional processing during in vivo exposure. Relative to flight avoiders, fliers had higher mean heart rate in the plane, a greater reduction in heart rate from the beginning to the end of the flight, and greater reported fear reduction from pre- to post-flight.

Adult

Relaxation pretraining, pulse wave velocity and thermal biofeedback in the treatment of essential hypertension.

Twelve white male subjects with a physician's diagnosis of essential hypertension participated in the study over a 3- to 4-month period (23-38 sessions). Subjects were assigned to one of four sequences of training in which the order of presentation of pulse wave velocity (PWV) or thermal feedback, and presence or absence of relaxation pretraining were varied. The overall effectiveness of the treatment program was demonstrated by average blood pressure decreases of 8.8 mm Hg/4.1 mm Hg from initial session measures to follow-up one month after completion of the program. Systolic pressures were significantly lower at follow-up but not diastolic. In addition, 3 subjects had ceased taking any blood pressure medication by follow-up, and maintained normal pressure. The effectiveness of relaxation pretraining was demonstrated by the fact that relaxation pretrained subjects attained significantly greater blood pressure decreases from baseline to the last 3 sessions of training, and by the fact that relaxation pretraining appeared critical in the acquisition of PWV feedback training.

Adult