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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

High dose chemotherapy and autologous bone marrow transplantation in advanced Hodgkin's disease.

OBJECTIVE: To present the use of high dose chemotherapy with autologous bone marrow transplantation as salvage therapy for advanced Hodgkin's disease in Australia. DESIGN: A prospective open study for patients whose disease was resistant to conventional treatment. SETTING: The bone marrow transplantation units of four Australian tertiary hospitals. PATIENTS: Seventeen patients (median age 30 years) entered and completed the study. The stage of the disease at initial diagnosis was I or II (seven patients), III (seven patients) and IV (three patients). Histological types were lymphocyte predominant (one), nodular sclerosis (12), mixed cellularity (three) and unknown (one). Therapy before consideration for transplantation included radiotherapy (13), mustine, vincristine, procarbazine and prednisone (MOPP--17 patients) or doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD--13 patients) and other chemotherapy regimens (five). The median interval from diagnosis to transplantation was 29 months (range, 9-178 months). The patient's disease was classified as sensitive (nine) or resistant (eight) to treatment, depending on the response to the most recent course of chemotherapy. INTERVENTIONS: Morphologically normal autologous bone marrow was harvested and cryopreserved. The conditioning regimen given was cyclophosphamide, carmustine and etoposide (14) or busulphan and cyclophosphamide (three). The marrow was then infused. MAIN OUTCOME MEASURES: Remission (complete or partial), disease-free survival and overall survival. RESULTS: Over all, 10 of 17 patients (59%) entered or remained in complete remission and four of 17 (24%) achieved partial remission. The overall actuarial survival at 30 months was 70%. Eight of the nine patients with treatment-sensitive disease (89%) remain disease-free at a median of 22 months (range, 18-29 months) after transplantation. Two of the eight patients with resistant disease (25%) are disease-free at 20 and 28 months. There was one procedure-related death from haemorrhage and four disease-related deaths at six, seven, eight and 13 months after transplantation. CONCLUSION: Autologous bone marrow transplantation may provide an effective salvage therapy in advanced Hodgkin's disease, particularly for patients with treatment-sensitive disease and a low tumour burden.

Adult

Dichromats detect colour-camouflaged objects that are not detected by trichromats.

To explain the surprisingly high frequency of congenital red-green colour blindness, the suggestion has been made that dichromats might be at an advantage in breaking certain kinds of colour camouflage. We have compared the performance of dichromats and normal observers in a task in which texture is camouflaged by colour. The texture elements in a target area differed in either orientation or size from the background elements. In one condition, the texture elements were all of the same colour; in the camouflage condition they were randomly coloured red or green. For trichromats, it proved to be more difficult to detect the target region in the camouflage condition, even though colour was completely irrelevant to the task. Dichromats (n = 7) did not show this effect, and indeed performed better than trichromats in the camouflage condition. We conclude that colour can interfere with segregation based upon texture, and that dichromats are less susceptible to such interference.

Color Perception

Effects of pattern element density upon displacement limits for motion detection in random binary luminance patterns.

The upper motion displacement threshold (Dmax) was determined with two-frame motion sequences of random binary luminance patterns, over a range of pattern element sizes and densities. Dmax was little affected by density at small element sizes (less than 5 arcmin), in agreement with previous reports. However, at larger element sizes (greater than 9 arcmin) Dmax increased as element density was reduced in the range 50-5%. We explain our findings by a model which takes into account spatial-frequency filtering prior to motion detection, and the effects of pattern density upon the statistics of random binary patterns. We also implicate the dependence of Dmax upon the contrast energy of the elements in broadband patterns, and provide a direct demonstration that Dmax is contrast limited over a wide range of pattern contrasts (72-2.5%). Previous reports that Dmax is independent of density should be modified to take into account the complex effects of density upon the statistics of random patterns, and the existence of physiological filtering prior to motion detection.

Humans

Spatial filtering precedes motion detection.

When we perceive motion on a television or cinema screen, there must be some process that allows us to track moving objects over time: if not, the result would be a conflicting mass of motion signals in all directions. A possible mechanism, suggested by studies of motion displacement in spatially random patterns, is that low-level motion detectors have a limited spatial range, which ensures that they tend to be stimulated over time by the same object. This model predicts that the direction of displacement of random patterns cannot be detected reliably above a critical absolute displacement value (Dmax) that is independent of the size or density of elements in the display. It has been inferred that Dmax is a measure of the size of motion detectors in the visual pathway. Other studies, however, have shown that Dmax increases with element size, in which case the most likely interpretation is that Dmax depends on the probability of false matches between pattern elements following a displacement. These conflicting accounts are reconciled here by showing that Dmax is indeed determined by the spacing between the elements in the pattern, but only after fine detail has been removed by a physiological prefiltering stage: the filter required to explain the data has a similar size to the receptive field of neurons in the primate magnocellular pathway. The model explains why Dmax can be increased by removing high spatial frequencies from random patterns, and simplifies our view of early motion detection.

Humans

Acute tryptophan depletion blocks morphine analgesia in the cold-pressor test in humans.

The effects of depletion of the serotonin precursor, L-tryptophan, on the threshold and tolerance to cold pressor pain, and the analgesic effect of morphine (10 mg intramuscularly), were tested in a double blind trial on human volunteers. Effects on mood were also assessed using the Profile of Mood States and the Addiction Research Center Inventory (ARCI) Scales. To deplete tryptophan, subjects were fed a tryptophan-deficient amino acid mixture 4.5 h before morphine was administered. Controls received the mixture with tryptophan, which is equivalent to a nutritionally balanced protein. The tryptophan-deficient meal reduced plasma tryptophan more than 70% but had no effect on threshold or tolerance to cold pressor pain. After morphine, tolerance to cold pressor pain increased in controls. Tryptophan depletion abolished this analgesic effect. Pain threshold was not altered by morphine. In subjects with normal tryptophan, the analgesic effect of morphine was predicted by the level of plasma morphine-6-glucuronide, but not by the level of morphine. Morphine increased scores on the LSD scale of the ARCI, but had no effect on other measures of mood. Tryptophan depletion also failed to alter mood in these subjects, who had unusually low depression scores before tryptophan depletion.

Adolescent

Effects of colour substitutions upon motion detection in spatially random patterns.

To investigate the effects of colour upon motion detection, the short-range motion displacement limit (Dmax) was determined using two-frame kinematograms in which the two classes of square comprising the pattern differed both in luminance and in colour. In the second motion frame, the squares retained either the same luminance and colour as in the first frame, or they changed their colour while retaining their luminance. The experiment was repeated at three different viewing distances to investigate the effects of element angular size. Two of the four observers had normal trichromatic colour vision; the other two were dichromats (protanopes). For the trichromatic observers, the change of colour between frames made motion displacements harder to detect when the squares were large, but not when they were small. The result accords with an input of colour into motion detection at low but not at high spatial frequencies. For the dichromats, the colour change had little effect at any of the viewing distances, thus ruling out the possibility that the deleterious effects of colour substitution upon motion detection in trichromats was due to chromatic aberration or other artefacts.

Color Perception

Ambiguous motion in a two-frame sequence.

We measured the ability of ten different observers to identify the direction of motion displacement of a 1.77 c/deg grating in a two-frame sequence. One subject showed virtually errorless performance, in agreement with Derrington and Cox [(1992) Vision Research, 32, 2191-2193], but most subjects found the task difficult and made many errors. One subject saw motion in the reverse of the actual direction of displacement. We conclude that the two-frame sequence contains motion signals in both directions, and that selective attention to the forward direction is necessary for errorless performance.

Attention

Effects of contrast substitutions upon motion detection in spatially random patterns.

We report the effects of contrast changes between frames in a random-square kinematogram. When the contrasts of both frames are too low to permit directional discrimination, increasing the contrast of either the first or the second frame alone makes directional discrimination possible. However, at suprathreshold contrasts for motion detection, increasing the contrast of either the first or the second frame alone makes discrimination more difficult. We conclude that motion detection is a special case of contrast discrimination, in agreement with the Reichardt model of motion detection.

Contrast Sensitivity

On the scaling of size judgements by orientational cues.

Observers carried out multiple, concurrent size discriminations with a range of size standards. The task was to classify each stimulus as larger or smaller than the appropriate standard size for the set to which it belonged. The set to which each stimulus belonged was indicated by its orientation, or in different experiments, by its spatial location. Observers were able to maintain appropriate discrimination, both when there were four concurrent standards and when there were eight. Both angle and position functioned as effective cues. The size of the orientational cue appeared to make little difference to the efficiency of discrimination. However, when the relationship between standard size and orientation was random, rather than regular, performance got worse. The analogy between such discrimination and size constancy is pointed out, and the results are discussed in relation to Andrews, D. P.'s [(1964) Quarterly Journal of Experimental Psychology, 16, 104-115)] account of perceptual calibration.

Discrimination, Psychological

Possible roles for nitric oxide in AIDS and associated pathology.

The endogenous free radical, nitric oxide (NO), plays a neurotransmitter-like role in vascular endothelium, a second-messenger role in N-methyl-D-aspartate (NMDA)-responsive neurons in the central nervous system (CNS), a neurotoxic role after its release from these neurons, and a cytotoxic role after its release by macrophages. NO also derives from exogenous sources, such as the nitrite inhalants, amyl, butyl and isobutyl nitrite. There is evidence that abuse of nitrite inhalants can affect immunomodulation, and epidemiological studies suggest that such abuse may be a cofactor in the pathogenesis of acquired immunodeficiency syndrome (AIDS). Hitherto, however, the potential role of NO in such pathogenesis has not been examined. This paper presents some current evidence that implicates both endogenous and exogenous sources of NO in AIDS and associated pathology.

Acquired Immunodeficiency Syndrome

Glucose repression of the yeast ADH2 gene occurs through multiple mechanisms, including control of the protein synthesis of its transcriptional activator, ADR1.

The rate of ADH2 transcription increases dramatically when Saccharomyces cerevisiae cells are shifted from glucose to ethanol growth conditions. Since ADH2 expression under glucose growth conditions is strictly dependent on the dosage of the transcriptional activator ADR1, we investigated the possibility that regulation of the rate of ADR1 protein synthesis plays a role in controlling ADR1 activation of ADH2 transcription. We found that the rate of ADR1 protein synthesis increased 10- to 16-fold within 40 to 60 min after glucose depletion, coterminous with initiation of ADH2 transcription. Changes in ADR1 mRNA levels contributed only a twofold effect on ADR1 protein synthetic differences. The 510-nt untranslated ADR1 mRNA leader sequence was found to have no involvement in regulating the rate of ADR1 protein synthesis. In contrast, sequences internal to ADR1 coding region were determined to be necessary for controlling ADR1 translation. The ADR1c mutations which enhance ADR1 activity under glucose growth conditions did not affect ADR1 protein translation. ADR1 was also shown to be multiply phosphorylated in vivo under both ethanol and glucose growth conditions. Our results indicate that derepression of ADH2 occurs through multiple mechanisms involving the ADR1 regulatory protein.

Alcohol Dehydrogenase

The asymmetrical genetic determination of laterality: flatfish, frogs and human handedness.

The determination of the left-right body axis is unlike that of the two other axes because left-right positional information is not required to specify mirror-image structures on the two sides. When the left and right sides of the body are not mirror symmetrical such positional information is required, as is a mechanism for reading that information. There are several possible gradient schemes for left-right information, including symmetrical gradients from which the information is extracted by spatial differentiation. The genetic mechanisms for the control of handedness are not known. There is no evidence for 'left-handed' and 'right-handed' genes, only for mutations that can interfere with handedness in a non-specific manner. Such mutations never produce situs inversus with a frequency greater than 50%. The situs of individual organs shows a strong correlation, suggesting a global mechanism such as a gradient of left-right positional information. Many asymmetries in vertebrates follow a pattern in which growth on the left is favoured over growth on the right. This may be related to the 'dexiothetism' of chordate ancestors postulated by Jefferies.

Animals

Efficiency of locating centres of dot-clusters by human observers.

A spatial interval acuity task was used to determine the efficiency with which observers located the centroids of circular clusters of individually-small elements. A cluster was defined by its radius and by the number of elements within it. The observer's task was to compare the horizontal distance between the centres of two such clusters to a standard distance, and to decide whether it was greater or smaller. The standard distance was made explicit by two markers on the display screen. As expected on statistical grounds, thresholds increased with the radius of the clusters, and decreased as a function of the number of elements. There were considerable individual differences in efficiency between observers, but the best observers achieved efficiencies close to 100% in many of the conditions. One anomalous observer showed virtually no decrease in thresholds as the number of elements increased, and thus her efficiencies declined to as little as 10%. The ability to combine positional information over spatially-separated elements to obtain an estimate of their central tendency appears in general to be high, and may underlie the perceptual biases revealed in certain geometric illusions, such as the Müller-Lyer.

Adolescent

Dopamine receptor subtypes and formalin test analgesia.

The role played by dopamine D1 and D2 receptors in formalin test analgesia was explored by challenging D-amphetamine- and morphine-induced analgesia with mixed and selective D1 and D2 antagonists, and by examining the relative analgesic activity of mixed and selective D1 and D2 agonists. The mixed D1/D2 dopamine antagonist cis-flupenthixol (0.5 mg/kg), the D2 antagonist pimozide (0.5 mg/kg), and the D1 antagonist SCH 23390 (0.1 mg/kg) attenuated both D-amphetamine and morphine analgesia. The mixed D1/D2 agonist apomorphine and the selective D2 agonist quinpirole produced dose-dependent analgesia while the selective D1 agonist SKF 38393 was without effect. These data suggest that D1 receptors play an "enabling" role in D2 receptor-mediated analgesia in the formalin test.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben

Spatial filtering and spatial primitives in early vision: an explanation of the Zöllner-Judd class of geometrical illusion.

The apparent length and orientation of short lines is altered when they abut against oblique lines (the Zöllner and Judd illusions). Here we present evidence that the length and orientation biases are geometrically related and probably depend upon the same underlying mechanism. Measurements were done with an 'H' figure, in which the apparent length and orientation of the cross-bar was assessed by the method of adjustment while the orientation of the outer flanking lines was varied. When the flanking lines are oblique the apparent length of the central line is reduced and its orientation is shifted so that it appears more nearly at right-angles to the obliques than is in fact the case. Measurements of the orientation and length effects were made in three observers, over a range of flanking-line angles (90, 63, 45, 34 and 27 deg) and central line lengths (9, 17, 33 and 67 arc min). The biases increased with the tilt of the flanking-lines, and decreased with central line length. The extent of the length bias could be accurately predicted from the angular shift by simple trigonometry. We describe physiological and computational models to account for the relation between the orientation and length biases.

Humans

6-Hydroxydopamine lesions of the ventral tegmentum abolish D-amphetamine and morphine analgesia in the formalin test but not in the tail flick test.

The effect of bilateral 6-hydroxdopamine (with desipramine) lesions of the ventral tegmental area-substantia nigra region on analgesia produced by morphine and D-amphetamine was examined with the formalin and tail flick tests in rats. These lesions depleted dopamine, but not noradrenaline, in the ventral and anterior striatum. Morphine and D-amphetamine produced analgesia in the formalin test in sham lesioned rats but not in lesioned rats. In contrast, morphine produced the same degree of analgesia in the tail flick test in sham lesioned and lesioned rats while D-amphetamine did not produce analgesia in this test. These data suggest that morphine and D-amphetamine analgesia in the formalin test involves dopamine, whereas morphine analgesia in the tail flick test does not.

Analgesia

Biases and sensitivities in geometrical illusions.

Psychometric functions were collected to measure biases and sensitivities in certain classical illusory configurations, such as the Müller-Lyer. We found that sensitivities (thresholds or just noticeable differences) were generally not affected by the introduction of illusory biases, and the implications of this for theories of the illusions are discussed. Experiments on the Müller-Lyer figure showed that the effect depends upon mis-location of the ends of the figure, rather than upon a global expansion as demanded by the size-constancy theory. A new illusion is described in which the perceived position of a dot is displaced towards the centre of a surrounding cluster of dots, even though it is clearly discriminable from other members of the cluster by their colour. We argue that illusions illustrate powerful constraints upon visual processing: they arise when subjects are instructed to carry out a task to which the visual system is not adapted.

Distance Perception