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Biomedical subjects

A Hayes

Publications and source records attributed to A Hayes.

At least 91 records · Page 5Linked to original sources

On the role of second-order signals in the perceived direction of motion of type II plaid patterns.

Second-order Type I and Type II plaids were constructed by combining two random-dot gratings. Each component consisted of a dynamic random-dot field, the contrast of which was modulated by a drifting sinusoidal grating. Orienting the two components suitably and interleaving at 120 Hz allowed us to produce a two-dimensional plaid pattern made from one-dimensional second-order components. The perceived direction of motion of both Type I and Type II plaids was measured as a function of stimulus duration. Type I plaids had a perceived direction close to the intersection of constraints/vector sum solution (which only coincide for these patterns) at all durations. Type II plaids had a perceived direction that moved away from the vector sum and toward the intersection of constraints solution as the duration of presentation increased. These results are similar in form to those found for plaids made from first-order (luminance-defined) components [Yo & Wilson (1992), Vision Research, 32, 135-147]. This suggests that a delay which operates specifically on second-order signals cannot be the sole cause for the change in perceived direction of Type II plaids made from first-order components [Wilson, Ferrera & Yo (1992), Visual Neuroscience, 9, 79-97].

Humans↗

Long-term clenbuterol administration alters the isometric contractile properties of skeletal muscle from normal and dystrophin-deficient mdx mice.

1. This study was designed to establish whether long-term treatment with the powerful anabolic agent clenbuterol has beneficial effects on dystrophin-deficient skeletal muscle function. 2. Normal (C57BL/10) and dystrophic (mdx) mice were administered clenbuterol (2 mg/kg per day) for 15 weeks. At 20 weeks of age, the extensor digitorum longus (EDL) and soleus muscles were removed, and their contractile and histochemical properties analysed. 3. Absolute and relative muscle masses were larger (P < 0.001) in mdx compared to C57BL/10 mice. These larger muscles produced larger absolute forces (P < 0.01) in the soleus of mdx mice compared to normal mice. Relative tetanic force was also larger (P < 0.05) in the soleus of mdx mice. In contrast, the absolute tetanic tension of the EDL was reduced (P < 0.01) in mdx mice compared to C57BL/10 mice, and both relative twitch and tetanic tensions were also lower (P < 0.001) in mdx mice. 4. Clenbuterol increased the lean muscle mass in both normal (10%, P < 0.05 and 20%, P < 0.01 for the EDL and soleus, respectively) and dystrophic (7%, P < 0.05 and 11%, P < 0.01) groups. Twitch contraction times were significantly faster in both the EDL (P < 0.001) and soleus (P < 0.01) muscles following clenbuterol administration, supported by fibre-type transitions towards fast-twitch fibres. Relative force levels of the soleus muscle of both C57BL/10 (40%, P < 0.01) and mdx (20%, P < 0.01) mice were increased significantly following clenbuterol treatment. No changes in the absolute or relative forces of the EDL muscles were observed in response to clenbuterol administration. 5. Clenbuterol was thus able to increase the force output of a slow-twitch, mixed (hence human-like) muscle but not fast-twitch muscle from mdx mice. The results lend tentative support to the potential role of clenbuterol as an anabolic agent in the treatment of muscle wasting diseases.

Animals↗

Rhodopsin accumulation at abnormal sites in retinas of mice with a human P23H rhodopsin transgene.

PURPOSE: To investigate the mechanism by which photoreceptors degenerate in transgenic mice carrying a mutant human rhodopsin gene (P23H). METHODS: The temporal and spatial pattern of the retinal degeneration caused by P23H rhodopsin was mapped using immunocytochemistry with rhodopsin-specific antibodies. The subcellular localizations of rhodopsin, transducin, and rod cGMP phosphodiesterase (PDE) were also determined, and rhodopsin localization was compared among P23H transgenic mice, rd mice, and Royal College of Surgeons (RCS) rats. RESULTS: In transgenic mice that express P23H rhodopsin, photoreceptors are lost centrally by postnatal day 10. As the retina degenerates, rhodopsin accumulates in the outer nuclear layer and within the photoreceptor synaptic terminals. The P23H transgenic retinas also show an accumulation of transducin and PDE within the outer plexiform layer. In contrast, other types of hereditary retinal degenerations studied show a similar pattern of rhodopsin accumulation in the outer nuclear layer but not in the outer plexiform layer of the retina. CONCLUSIONS: The pattern of degeneration in the P23H transgenic retina is consistent with a model in which the centrally located, first-born photoreceptors are the first to die. In contrast to other animal models for hereditary retinal degeneration (rd, RCS), a novel feature of the P23H degeneration is an accumulation of rhodopsin, transducin, and PDE within the outer plexiform layer of the retina. One hypothesis to explain this observation is that P23H rhodopsin is routed intracellularly through a pathway not used by normal rhodopsin. Nonmutant forms of the peripheral transducing proteins normally associated with disk membrane, such as transducin and PDE, may accompany the aberrantly routed rhodopsin.

3',5'-Cyclic-GMP Phosphodiesterases↗

The effects of endurance exercise on dystrophic mdx mice. I. Contractile and histochemical properties of intact muscles.

Genetically normal (C57BL/10) and dystrophic (mdx) mice underwent a 15 week endurance swimming programme (2 hours per day, 5 days per week) where animals were weighted (5% body weight) during most sessions. No significant changes were seen in the contractile properties or morphology of muscles from control mice following the exercise protocol. In contrast, the soleus muscles of exercised mdx mice displayed higher normalized tensions, and the extensor digitorum longus (EDL) exhibited longer half-relaxation times compared with sedentary mdx mice. Both the EDL and soleus muscles of mdx mice exhibited increased resistance to fatigue after endurance exercise. Sedentary mdx mice exhibited increased proportions of type I (slow oxidative) fibres in the soleus and type IIA (fast, oxidative glycolytic) fibres in the EDL compared with animals of the normal strain. In both the EDL and soleus muscles of mdx mice an even greater proportion of type I fibres was apparent following the training programme. The endurance exercise was beneficial to the mdx mice, enhancing the regeneration of function of their muscles by increasing the proportion of oxidative fibres and reducing muscle fatiguability.

Animals↗

The effects of endurance exercise on dystrophic mdx mice. II. Contractile properties of skinned muscle fibres.

Dystrophic (mdx) mice were subjected to a 15 week exercise programme consisting of endurance swimming. Single fibres from the extensor digitorum longus (EDL, fast-twitch) and soleus (SOL, mixed fast- and slow-twitch) muscles were attached to a sensitive force-recording apparatus, and activated in Ca(2+)- and Sr(2+)-buffered solutions. In addition to the normal well-defined fibre types in these muscles, a small number of fibres were also sampled from the soleus of both experimental groups, which were 'Intermediate' to the other two SOL fibre types. Type IIB fibres from the EDL and type IIA fibres from the soleus of the Swim group were significantly less sensitive to Ca2+ and Sr2+ compared with those fibres sampled from the sedentary (Sedent) group, suggesting that endurance exercise was able to modify Ca(2+)- and Sr(2+)-activated contractile characteristics. The swim-trained (Swim) group's increased incidence of SOL fibres with characteristics intermediate to those of the fast- and slow-twitch fibre types suggests a possible exercise-induced fibre type transformation as an adaptation to the functional demand.

Animals↗

Neural recruitment explains "Weber's law" of spatial position.

We ask whether the well known Weber's law between spatial localization and element separation for high contrast, spectrally broad-band stimuli is a consequence of the organization of the early visual filters, or a fundamental constraint on the computation of spatial position by more central mechanisms. We address this question by identifying the individual contributions of mechanisms tuned to different ranges of spatial frequencies and contrast. We measure spatial-alignment and bisection error as a function of element separation at each of a number of spatial scales, using spectrally narrow-band stimuli of fixed supra-threshold contrast. We show that stimuli which minimize the extent of neural recruitment across different spatial channels before the site of extraction of the local contrast energy (and to a lesser extent across different contrast channels) do not exhibit Weber's law for either alignment or bisection. We present evidence that Weber's law for localization with increasing separation, found for stimuli of high contrast and broad-band spatial frequency content, is a consequence of the successive disengagement of unitary neural mechanisms, each of which has different spatial and contrast properties, and none of which individually exhibits Weber's law for spatial position.

Contrast Sensitivity↗

Contour integration by the human visual system: evidence for a local "association field".

The Gestalt law of "good continuation" has been used to describe a variety of phenomena demonstrating the importance of continuity in human perception. In this study, we consider how continuity may be represented by a visual system that filters spatial data using arrays of cells selective for orientation and spatial frequency. Many structures (e.g. fractal contours) show a form of redundancy which is well represented by the continuity of features as they vary across space and frequency. We suggest that it is possible to take advantage of the redundancy in continuous, but non-aligned features by associating the outputs of filters with similar tuning. Five experiments were performed, to determine the rules that govern the perception of continuity. Observers were presented with arrays of oriented, band-pass elements (Gabor patches) in which a subset of the elements was aligned along a "jagged" path. Using a forced-choice procedure, observers were found to be capable of identifying the path within a field of randomly-oriented elements even when the spacing between the elements was considerably larger than the size of any of the individual elements. Furthermore, when the elements were oriented at angles up to +/- 60 deg relative to one another, the path was reliably identified. Alignment of the elements along the path was found to play a large role in the ability to detect the path. Small variations in the alignment or aligning the elements orthogonally (i.e. "side-to-side" as opposed to "end-to-end") significantly reduced the observer's ability to detect the presence of a path. The results are discussed in terms of an "association field" which integrates information across neighboring filters tuned to similar orientations. We suggest that some of the processes involved in texture segregation may have a similar explanation.

Form Perception↗

Down syndrome.

Down syndrome remains one of the most common causes of mental retardation. Although knowledge of pathogenesis remains incomplete, recent molecular biologic techniques have identified regions of the 21st chromosome critical for expression of the Down syndrome phenotype, and animal models have helped elucidate the origins of the neurochemical and neuropathologic abnormalities. There also has been an improved understanding of the spectrum of medical complications of this disorder and the need for anticipatory management, including the search for atlantoaxial subluxation and hypothyroidism. With its increased risk of Alzheimer disease, Down syndrome is proving to be a useful model for studying aging. Accompanying greater knowledge has been improved functional outcome. Better medical care has made individuals with Down syndrome healthier; remaining at home through childhood has increased their cognitive function; and availability of increased numbers of group homes and supported employment opportunities has permitted the young adult with Down syndrome to live a more independent and full life. In this climate, the role of the pediatrician in early intervention and anticipatory guidance cannot be overemphasized.

Child↗

Load concentrations around crystal aggregates in articular cartilage under short-term loading.

The deposition of crystals in joints is a feature of a number of joint diseases. Crystals are frequently observed on the surface of articular cartilage and in the mid-zone. The purpose of this investigation was to model the stress concentrations in the mid-zone of the cartilage layer arising from the presence of large crystal aggregates. Scanning electron microscopy was used to determine the geometry and distribution of crystal aggregates within the cartilage layer. Finite element and photoelastic approaches were then used to predict the stress distribution around spherical aggregates 50 and 100 microns in diameter. The implication of the results is that very densely packed and tightly bound spherical aggregates will themselves carry a certain amount of load. However, less tightly packed aggregates, perhaps interspersed with fibrous tissue, are potentially much more damaging.

Cartilage, Articular↗

Wear of articular cartilage: the effect of crystals.

An investigation of the effect of crystals in a lubricant on the wear of articular cartilage in vitro was carried out in order to examine the hypothesis that crystals present in synovial fluid could cause abrasive damage of the articular surface. Plugs of cartilage were worn against a stainless steel counterface in a pin-on-disc wear rig. The concentration of cartilage debris present in the lubricant was assessed by measuring the bound sulphate originating from the glycosaminoglycans by ion chromatography. Results indicated that the presence of crystals in the lubricant significantly increased the concentration of wear debris and that the crystal size and morphology influenced the type of damage sustained by the cartilage. Other experimental evidence suggested that cartilage scratched in vivo was no more susceptible to further in vitro damage in this experimental model than normal cartilage. These results implied that crystals present in the synovial fluid of arthritic joints have the potential to cause excessive wear of the articular surface, but that if such crystals are removed the scratched cartilage may not be susceptible to any further damage by abrasive wear.

Animals↗

Analysis of soluble human and mouse interferon-gamma receptors expressed in eukaryotic cells.

The extracellular domains of the human and mouse interferon-gamma receptors were produced in insect Spodoptera frugiperda cells infected with recombinant baculoviruses and in mammalian Chinese-hamster-ovary cells. The receptors expressed in both systems are secreted into the culture medium. Their signal peptides are cleaved off and the proteins show heterogeneity in glycosylation which, however, does not affect the capacity to bind interferon gamma or specific antibodies. The soluble mouse receptors exhibit binding capacities similar to those of cell-surface-anchored receptors, whereas the human receptors exhibit a lower binding capacity. All soluble receptors inhibit the binding of interferon gamma to cellular receptors and neutralize the antiviral activity exerted by interferon gamma. These receptors could therefore be useful for structure/function analyses and in vivo studies.

Animals↗

Determinants of hemodynamic results of balloon dilation of aortic recoarctation.

Between October 1982 and May 1990, balloon dilation of aortic recoarctation was attempted in 27 patients. In 1 case dilation was not performed owing to suspected aortic perforation. The remaining 26 patients had 30 procedures. The age at the first dilation ranged between 2.6 months and 18.3 years. After dilation, systolic gradient decreased from 49 +/- 17 mm Hg to 20 +/- 17 mm Hg (p less than 0.001). A reduction of gradient to less than or equal to 20 mm Hg occurred after the first dilation in 17 of 26 (65%) patients. Residual gradients between 25 and 80 mm Hg were present in the remaining 9 patients. During follow-up of 2 months to 6.7 years, 5 of 17 patients with a good initial result developed further recoarctation (2 had successful redilation, 2 had reoperation, and 1 is awaiting repeat dilation). Of 9 patients with gradients greater than 20 mm Hg after the first dilation, 1 had successful redilation and 3 had reoperation. The remaining 5 patients are being managed conservatively. 2 patients developed aneurysms after dilation (1 immediately and the other at 2 months). In all, 15 patients (58%) had a good, and 11 (42%) a poor late hemodynamic result. Aortic diameters at different levels of the aortic arch and at the reconstructed isthmus (normalized to the aorta at the level of the diaphragm) were significantly higher in the group with a good late result than in that with a poor one. Balloon/aortic diameter ratio at diaphragm level also had a significant influence on the late results.

Adolescent↗

Transgenic mice with a rhodopsin mutation (Pro23His): a mouse model of autosomal dominant retinitis pigmentosa.

We inserted into the germline of mice either a mutant or wild-type allele from a patient with retinitis pigmentosa and a missense mutation (P23H) in the rhodopsin gene. All three lines of transgenic mice with the mutant allele developed photoreceptor degeneration; the one with the least severe retinal photoreceptor degeneration had the lowest transgene expression, which was one-sixth the level of endogenous murine rod opsin. Of two lines of mice with the wild-type allele, one expressed approximately equal amounts of transgenic and murine opsin and maintained normal retinal function and structure. The other expressed approximately 5 times more transgenic than murine opsin and developed a retinal degeneration similar to that found in mice carrying a mutant allele, presumably due to the overexpression of this protein. Our findings help to establish the pathogenicity of mutant human P23H rod opsin and suggest that overexpression of wild-type human rod opsin leads to a remarkably similar photoreceptor degeneration.

Animals↗

Morphological evidence for biological control of urate crystal formation in vivo and in vitro.

Urate crystal formation, and subsequent gout, occurs in only a minority of hyperuricaemic subjects indicating that factors other than hyperuricaemia are involved. Biological substances (especially proteins) alter crystal growth in vitro independently of uric acid concentration. Physiological crystal formation, known to be under biological control, is characterised morphologically by uniformity of size and constraint of crystal shape. To determine whether pathological urate crystal formation is influenced by the surrounding biological milieu we examined, using scanning electron microscopy, the morphology of urate crystals formed either in vivo or in vitro. We found morphological evidence of biological control of in vivo urate crystal formation and demonstrated that those characteristics could be induced in vitro by the addition of serum, synovial fluid and certain serum proteins to the growth medium during crystal formation. Urate crystal formation is dependent, not only on the degree of hyperuricaemia, but also on the surrounding biological milieu.

Blood Proteins↗

Automaticity and preattentive processing.

The characteristics of automatized performance resemble those of preattentive processing in some respects. In the context of visual search tasks, these include spatially parallel processing, involuntary calling of attention, learning without awareness, and time-sharing with other tasks. However, this article reports some evidence suggesting that extended practice produces its effects through different mechanisms from those that underlie preattentive processing. The dramatic changes in search rate seem to depend not on the formation of new preattentive detectors for the task-relevant stimuli, nor on learned abstracted procedures for responding quickly and efficiently, but rather on changes that are very specific both to the particular stimuli and to the particular task used in practice. We suggest that the improved performance may depend on the accumulation of separate memory traces for each individual experience of a display (see Logan, 1988), and we show that the traces differ for conjunction search in which stimuli must be individuated and for feature search where a global response to the display is sufficient.

Attention↗

Cytoskeletal specializations at the rod photoreceptor distal tip.

We have examined microtubules and microtubule-like elements within the toad rod photoreceptor outer segment in order to define regional specializations of the photoreceptor cytoskeleton. "Ciliary" microtubules were localized within the rod outer segment (ROS) by using thin section electron microscopy, immunofluorescence, and rapid-freeze deep-etch microscopy. All three methods showed that ciliary microtubules stop short of the extreme ROS distal tip, although abundant microtubule-like structures distinct from the ciliary microtubules were found within the distal 10-15 microns of the ROS tip. These heretofore undescribed "distal ROS tubules" are clustered at the clefts or incisures of the disk membrane stack and resemble microtubules in overall size and shape, although they are not closely related antigenically to tubulin. The distal ROS tubules are more abundant in green rods than red rods and vary in number during the daily light/dark cycle. Quantitation of these tubules at two time points during the light/dark cycle suggests that there are three- to fourfold more tubules in the ROS tip one hour after light onset than one hour before light onset. Retinas prevented from normal disk membrane shedding by separation of the retina from the adjacent pigment epithelium, failed to develop increased numbers of tubules after light onset. This suggests that the newly described distal ROS tubules may modulate or be modulated by light-induced interactions between the photoreceptors and pigment epithelium, such as those that occur during the disk shedding phase of membrane turnover.

Animals↗

Double-outlet right ventricle: morphologic demonstration using nuclear magnetic resonance imaging.

Sixteen patients with double-outlet right ventricle, aged 1 week to 29 years (median 5 months), were studied with a 1.5 tesla nuclear magnetic resonance (NMR) imaging scanner. Two-dimensional echocardiography was performed in all patients. Thirteen patients underwent angiography, including nine who underwent subsequent surgical correction. Three patients underwent postmortem examination. Small children and infants were scanned inside a 32 cm diameter proton head coil. Multiple 5 mm thick sections separated by 0.5 mm and gated to the patient's electrocardiogram were acquired with a spin-echo sequence and an echo time of 30 ms. A combination of standard and oblique imaging planes was used. Imaging times were less than 90 min. The NMR images were technically unsuitable in one patient because of excessive motion artifact. In the remaining patients, the diagnosis of double outlet right ventricle was confirmed and correlated with surgical and postmortem findings. The NMR images were particularly valuable in demonstrating the interrelations between the great arteries and the anatomy of the outlet septum and the spatial relations between the ventricular septal defect and the great arteries. Although the atrioventricular (AV) valves were not consistently demonstrated, NMR imaging in two patients identified abnormalities of the mitral valve that were not seen with two-dimensional echocardiography. In one patient who had a superoinferior arrangement of the ventricles, NMR imaging was the most useful imaging technique for demonstrating the anatomy. In patients with double-outlet right ventricle, NMR imaging can provide clinically relevant and accurate morphologic information that may contribute to future improvement in patient management.

Angiography↗