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Biomedical subjects

D M Parker

Publications and source records attributed to D M Parker.

At least 37 records · Page 2Linked to original sources

TNF-alpha induces peroxynitrite-mediated depletion of lung endothelial glutathione via protein kinase C.

We tested the hypothesis that tumor necrosis factor-alpha (TNF) induces a peroxynitrite (ONOO-)-mediated depletion of glutathione via a protein kinase C (PKC)-dependent mechanism in pulmonary artery endothelial monolayers (PAEM). PAEM were incubated with TNF (1,000 U/ml) for 6 and 18 h. The PAEM were assayed for ONOO(-)-dependent changes in the concentration of luminol, free glutathione [Gfree; i.e., reduced glutathione and oxidized glutathione (GSSG)] and GSSG. TNF treatment decreased luminol and Gfree, and increased GSSG and GSSG/Gfree, compared with treatment with control media. The TNF-induced effects were prevented by co-incubation with the nitric oxide synthase inhibitors NG-monomethyl-L-arginine (1 mM), NG-nitro-L-arginine methyl ester (1 mM), or NG-nitro-L-arginine (1 mM). In addition, the TNF-induced effects were prevented by superoxide dismutase (10 U/ml), which removes O2-, and by urate (0.5 mM) and L-cysteine (3 mM), putative scavengers of ONOO-. The treatment of PAEM with the PKC activator phorbol 12-myristate 13-acetate (PMA, 1 microM) induced similar alterations in luminol and glutathione as TNF. TNF and PMA induced a protein of similar molecular weight (approximately 90 kDa) in the focal contact-rich fraction of PAEM lysate. TNF- and PMA-induced effects were prevented with the specific PKC inhibitor calphostin C (1 microM). The data indicate that TNF-induced PKC activation mediates ONOO- generation, which results in the oxidation and depletion of glutathione in PAEM.

Animals↗

The perception of spatial structure with oblique viewing: an explanation for Byzantine perspective?

Earlier work has confirmed that (i) observers can judge divergent receding lines, placed directly in front of them, to be parallel, and (ii) converging lines which are displaced laterally, so that they are viewed obliquely, can also be judged to be parallel. The former observation is in accord with traditional views of perspective while the latter, which is in accord with the depictions of objects found in Byzantine painting, is not in accord with perspective but is predicted by the relative magnitude of the visual angles subtended by the near and far ends of the pair of lines. To investigate whether these effects occurred when the stimulus was clearly three-dimensional, experiments were conducted with a novel apparatus, consisting of a framework of computer-controlled motor-driven luminous rods. This could be remotely adjusted so that all visible sides appeared to be parallel, ie to resemble a cube. Results showed that observers set the sides of this trapezohedron framework as diverging when it was viewed immediately in front of them, a result which is concordant with linear perspective, ie they see the normal projection of a cube as having converging edges. When the framework was displaced from the median plane so that it was viewed obliquely, the sides were set as converging and the magnitude of this effect was significantly related to angle of view, ie observers see the normal projection of a cube as having diverging sides.(ABSTRACT TRUNCATED AT 250 WORDS)

Art↗

Spatial content and spatial quantisation effects in face recognition.

It has recently become apparent that if face images are degraded by spatial quantisation, or block averaging, there is a nonlinear acceleration of the decline in accuracy of recognition as block size increases. This suggests recognition requires a critical minimum range of object spatial frequencies. Two experiments were performed to clarify the phenomenon. In experiment 1, the speed and accuracy of recognition for six frontoparallel photographs of faces were measured. After familiarisation training sessions, the images were shown for 100 ms with 11, 21, and 42 pixels per face, horizontally measured. Transformations calculated to remove the same range of spatial frequencies were performed by means of quantisation, a Fourier low-pass filter, and Gaussian blurring. Although accuracy declined and speed increased in a significant, nonlinear manner in all cases as the image quality was reduced, it did so at a faster rate for the quantised images. In experiment 2, faces rated as being typical were shown at 9, 12, 23, and 45 pixels per face and with appropriate Fourier low-pass versions. The nonlinear decline was confirmed and it was shown that it could not be attributed to a ceiling effect. A further condition allowed quantised and Fourier low-pass conditions to be compared with an unstructured-noise condition of equal strength to that of the quantised images. These gave comparable, but slightly less impaired, recognition than the quantised images. It can be inferred from these results that the removal of a critical range of at least 8-16 cycles per face of information explains the step decline in recognition seen with quantised images. However, the decline found with quantised images is reinforced by internal masking from pixelisation.

Adult↗

Tumor necrosis factor-alpha activates pulmonary artery endothelial protein kinase C.

We investigated the hypothesis that tumor necrosis factor-alpha (TNF) activates pulmonary endothelial protein kinase C (PKC). Confluent bovine pulmonary artery endothelial monolayers were exposed to recombinant human TNF, and the translocation of PKC, an indicator of enzyme activation, was studied using both slot immunoblotting and immunofluorescence. For slot immunoblot analysis, membrane and cytosol lysate fractions were prepared, and PKC antigen was assessed using MC5 monoclonal anti-PKC antibody. TNF (1,000 U/ml for 15 min) induced translocation of PKC into the membrane. Immunofluorescence analysis with the MC5 antibody was also used. Monolayers treated with culture medium showed diffuse cytoplasmic fluorescence. In contrast, treatment with either TNF (1,000 U/ml for 15 min) or 1,2-dioctanoylglycerol (4 x 10(-5) M for 5 min), a diacylglycerol that activates PKC, resulted in translocation of fluorescence to the cell periphery; fine, punctate PKC-associated fluorescence was localized to the margins of cells. The TNF-induced translocation of PKC was inhibited using either IP-300 polyclonal anti-TNF antibody (indicating that the TNF effect was not due to the vehicle or contaminating endotoxin) or calphostin C (10(-6) M for 15 min), which inhibits PKC activation by interacting with the regulatory diacylglycerol-binding domain. TNF treatment had no effect on either the content of PKC, or of total protein, in the membrane + cytosol, and cycloheximide (40 microM for 5 min) did not alter the translocation of PKC induced by TNF; these results indicate that the effect of TNF on PKC translocation was related to neither de novo membrane synthesis of PKC (as opposed to translocation per se) nor nonspecific augmentation of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Temporal integration of spatially filtered visual images.

Factors which govern the temporal integration of spatial information were examined in a group of five experiments. A series of high-pass and low-pass spatially filtered versions of a visual scene were generated. Observers' ratings of these filtered versions of the scene for perceived image quality indicated that quality was determined both by the bandwidth of spatial information and the presence of high-spatial-frequency edge information. When sequences of three different versions of the scene were presented over an interval of 120 ms the perceived quality of the resulting composite image was determined both from the ratings of the individual components of that sequence and from the order in which these components were presented. When the order of spatial information in a sequence moved from coarse to fine detail the perceived quality of the composite image was significantly better than when the order moved from fine to coarse. This evidence of a coarse-to-fine bias in pattern integration was further investigated with a detection paradigm. The pattern of errors once again indicated that temporal integration of spatial information was superior when a coarse-to-fine mode of information delivery was employed. Taken together the data indicate that the pattern-integration mechanism has an inherent order bias and does not accumulate spatial information so efficiently when the 'natural' coarse-to-fine order is violated.

Attention↗

Convergent and divergent perspective.

Use of divergent (or inverse) perspective in pictures is often regarded as arbitrary or even as erroneous in spite of the fact that entire schools of art exist in which this kind of perspective is regularly used. An experiment is reported which shows that a significant trend towards divergent perspective is experienced by subjects viewing laterally displaced three-dimensional arrays. Centrally viewed arrays show the expected perceptual convergence. It is therefore argued that divergent perspective, under appropriate conditions, is as perceptually legitimate an experience as convergent perspective.

Adult↗

Apparent duration and spatial structure.

In three experiments, we investigated the relative perceived duration of a full bandwidth image and a set of high- and lowpass filtered images of a scene, briefly presented on a visual display unit. In Experiment 1, the various images were compared with each other, using a paired comparison method. All images were presented for 40 msec, and observers were asked to judge which of each pair of images had the longest duration. The results showed that images containing a wide spatial frequency bandwidth were judged to be of longer duration than were images of a narrower bandwidth, regardless of whether the latter were high- or lowpass filtered. In Experiment 2, a 40-msec presentation of each of the images was compared with a presentation of a probe that was 20, 40, 60, or 80 msec in duration. Observers again judged which of each pair of images had the longest duration. The results were very similar to those of Experiment 1, with wide bandwidth images being judged to be of longer duration than were narrow bandwidth images. In Experiment 3, instead of comparing the various filtered versions of the image with each other, we attempted to obtain a direct measure of perceived duration by comparing a flashing LED to a 40-msec flash of a subset of the images used in the previous experiments. The observers' task was to adjust the duration of the LED flash to match the perceived duration of each image.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Three-space inference from two-space stimulation.

Oblique contours sloping at 30 degrees with respect to the horizontal were presented alone, in combination to form chevrons, or with a vertical line to form arrowhead or Y patterns; they were projected onto a screen in the frontal parallel plane and viewed from positions that gave viewing angles of 90 degrees (normal to the screen's surface), 53 degrees, or 34 degrees. The perceived orientation of the contours, as assessed by a movable arm that the subjects set to be parallel to the obliques, changed monotonically as a function of viewing angle. The change was as great for single obliques as for combinations of obliques within the chevron, arrowhead, and Y patterns. The results of Experiment 1 were extended in Experiment 2, in which obliques at 30 degrees and 50 degrees with respect to the horizontal were presented singly or in combination as chevron patterns. It is argued that the results of both experiments indicate that single two-space oblique lines are immediately interpreted as lying in three-space and that the changes in perceived orientation are a consequence of this perceptual inference.

Adult↗

Functional studies of a glutamate dehydrogenase with known three-dimensional structure: steady-state kinetics of the forward and reverse reactions catalysed by the NAD(+)-dependent glutamate dehydrogenase of Clostridium symbiosum.

Steady-state kinetic properties of glutamate dehydrogenase from Clostridium symbiosum are reported. Rates with NADP(H) are over three hundred times lower than with NAD(H) under identical conditions. The 3-acetyl pyridine and 6-deamino adenine analogues of NAD+, on the other hand, are used almost as well as NAD+ itself. Amino acid specificity is very tight at both pH 7 and pH 9. The best alternative substrate of those tested, L-alpha-amino-gamma-nitraminobutyrate, gave only 0.5% of the rate seen with glutamate. With 400 microM NAD+ a 160-fold variation of the glutamate concentration gave a linear Eadie plot apart from slight inhibition at the highest concentrations. With 40 mM L-glutamate and varied [NAD+], the Eadie plot appeared linear between 1.6 microM and 60 microM and again between 60 microM and 2000 microM, but the slopes of the two lines differed by a factor of 8.4. This striking pattern is not attributable to impurities in the coenzyme or to changes in the state of aggregation of the enzyme. For the high concentration range (greater than 60 microM NAD+), the presence of all four linear terms in the reciprocal form of the initial rate equation indicates a sequential mechanism. Similar measurements made for APAD+ and dnNAD+ show no sign of non-linearity in the Eadie plot over the wide concentration ranges explored. In the reductive amination direction, with NADH as coenzyme, linear reciprocal plots were obtained for all three substrates. Systematic variation of concentrations led via primary, secondary and tertiary plots to all eight possible initial-rate parameters in a linear reciprocal initial-rate equation. Compulsory-order and enzyme-substitution mechanisms appear to be excluded, and a random route to the central complex seems the only possibility compatible with the results.

Amines↗

The Short NART: cross-validation, relationship to IQ and some practical considerations.

Beardsall & Brayne (1990) have presented a method whereby the full-length National Adult Reading Test (NART) scores of subjects who are of below average reading ability can be predicted from performance on the first half of the test (termed the Short NART). The accuracy with which the Short NART predicted full-length NART scores was examined in a large cross-validation sample (N = 674). A subgroup of this sample (N = 142) was administered the WAIS. The results indicated that the Short NART was only moderately successful in predicting full-length NART scores. However, comparison of the accuracy with which the full-length NART and Short NART predicted WAIS IQs, revealed that the superiority of the former was very minimal. It is concluded that, despite some reservations regarding the Short NART's practical utility, it can be used with reasonable confidence in clinical practice to estimate premorbid IQ.

Adolescent↗

A synthesis of acylphosphonic acids and of 1-aminoalkylphosphonic acids: the action of pyruvate dehydrogenase and lactate dehydrogenase on acetylphosphonic acid.

Acylphosphonic acids, R-CO-PO(OH)2, have been synthesized by the steps [formula: see text] of which the last is new and provides a mild method for de-esterifying acylphosphonic acids. Their reductive amination gives a simple way of making 1-aminoalkylphosphonic acids. Acetylphosphonic acid inhibited NAD+ reduction by pyruvate with the pyruvate dehydrogenases from Escherichia coli and Bacillus stearothermophilus. The inhibition was competitive with pyruvate, with Ki of 6 microM for the E. coli enzyme (pyruvate Km 0.5 mM) and one of 0.4 mM of the B. stearothermophilus enzyme (pyruvate Km 0.1 mM). Acetylphosphonate and its monomethyl ester are substates for pig heart lactate dehydrogenase, with Km values of 15 mM and 10 mM respectively (pyruvate Km 0.05 mM) and specificity constants one thousandth that for pyruvate.

Acetaldehyde↗

Intermittent alexia.

A case of intermittent alexia, sometimes accompanied by severe dysgraphia and sometimes by mild dysgraphia, which had a probable migrainous origin, is described. On some occasions the patient could write to dictation, although with many errors, while unable to read words or letters. On other occasions the patient's writing to dictation was seriously disordered in terms of content and the letters were produced clumsily. Reading of numbers, colour vision and colour naming were normal although impairments on right-left orientation and visual short term memory were present and a mild finger agnosia was apparent. Blood flow scans (SPECT) taken under normal and alexic conditions support the view that the disturbance had a vascular origin.

Adolescent↗

Reaction time measures of feature saliency in schematic faces.

Two separate paradigms utilizing measurements of reaction time were employed to study facial feature saliency in schematic line drawn faces. In the first paradigm the speed of response to the omission of different facial components was measured, and in the second, the speed of response to feature substitution was measured. In both paradigms the facial features were presented in a random temporal sequence in order to minimise preferential scanning strategies. The two separate paradigms reflected the feature hierarchy most commonly found in the literature, ie the outline and eyes are more salient than the nose and mouth in terms of both speed of processing and error rate. In a third study the feature substitution paradigm was used to investigate the effects of feature saliency on the perception of emotional faces. The results suggest a change in the eyes/mouth hierarchy so that the mouth becomes the most salient feature in the surprised, happy, and sad target faces. This reverse in hierarchy, however, was not evident with the angry target face. These results are discussed in terms of changes in the focus of 'attention' and/or changes in 'processing efficiency'.

Adult↗

Assessing the validity of NART-estimated premorbid IQs in the individual case.

The National Adult Reading Test (NART: Nelson, 1982) has become the standard means of estimating premorbid intelligence. The danger in using the NART for this purpose is that it yields an invalid estimate if a client's performance on the test has suffered impairment. In the present study a sample of 659 healthy subjects was used to build a regression equation for the prediction of NART scores from demographic variables (i.e. years of education, social class, age and sex). The multiple correlation between these demographic variables and the NART was .70 (p less than .0001). Comparing a client's obtained and predicted NART score will permit the clinician to assess objectively whether NART performance is impaired, and thus whether or not the NART will provide a valid estimate of premorbid intelligence.

Adolescent↗

Multimodal imaging in Alzheimer's disease. The relationship between MRI, SPECT, cognitive and pathological changes.

Patients with a clinical diagnosis of Alzheimer's disease were studied using MRI, SPECT, and psychometric tests. Significant correlations between focal perfusion deficits and focal cognitive deficits were found. Significant correlations between regional relaxation time of white matter and psychometric tests of diffuse and focal categories were also found. Pathological examination confirmed Alzheimer's disease as the only diagnosis.

Aged↗