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No evidence of genetic heterogeneity in dominant optic atrophy.

Autosomal dominant optic atrophy (OPA, MIM 165500) is an eye disease causing a variable reduction of visual acuity with an insidious onset in the first six years of life. It is associated with a central scotoma and an acquired blue-yellow dyschromatopsia. A gene for dominant optic atrophy (OPA1) has recently been mapped to chromosome 3q in three large Danish pedigrees. Here, we confirm the mapping of OPA1 to chromosome 3q28-qter by showing close linkage of the disease locus to three recently reported microsatellite DNA markers in the interval defined by loci D3S1314 and D3S1265 in four French families (Zmax = 5.13 at theta = 0 for probe AFM 308yf1 at locus D3S1601). Multipoint analysis supports the mapping of the disease gene to the genetic interval defined by loci D3S1314 and D3S1265. The present study provides three new markers closely linked to the disease gene for future genetic studies in OPA.

Chromosome Mapping↗

Visual recovery after perinatal stroke evidenced by functional and diffusion MRI: case report.

BACKGROUND: After perinatal brain injury, clinico-anatomic correlations of functional deficits and brain plasticity remain difficult to evaluate clinically in the young infant. Thus, new non-invasive methods capable of early functional diagnosis are needed in young infants. CASE PRESENTATION: The visual system recovery in an infant with perinatal stroke is assessed by combining diffusion tensor imaging (DTI) and event-related functional MRI (ER-fMRI). All experiments were done at 1.5T. A first DTI experiment was performed at 12 months of age. At 20 months of age, a second DTI experiment was performed and combined with an ER-fMRI experiment with visual stimuli (2 Hz visual flash). At 20 months of age, ER-fMRI showed significant negative activation in the visual cortex of the injured left hemisphere that was not previously observed in the same infant. DTI maps suggest recovery of the optic radiation in the vicinity of the lesion. Optic radiations in the injured hemisphere are more prominent in DTI at 20 months of age than in DTI at 12 months of age. CONCLUSION: Our data indicate that functional cortical recovery is supported by structural modifications that concern major pathways of the visual system. These neuroimaging findings might contribute to elaborate a pertinent strategy in terms of diagnosis and rehabilitation.

Asphyxia Neonatorum↗

Meiotic breakpoint mapping of a proposed X linked visual loss susceptibility locus in Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited degenerative disorder characterised by an acute or subacute optic nerve degeneration resulting in visual failure. Mitochondrial DNA mutations have been reported and a nuclear modifier gene(s) on the X chromosome is thought to play an important role in the onset of this disorder. We analysed a LHON family with a novel and more accurate approach using 27 X chromosomal microsatellite markers. Meiotic breakpoint mapping and two point lod score did not point to any particular area on the X chromosome which might contain the X susceptibility locus.

Adult↗

Sculpting the visual map: the distribution and function of serotonin-1A and serotonin-1B receptors in the optic tectum of the frog.

Agonists of serotonin (5-HT)-1 receptors modulate the synaptic strength of the connection between retinal ganglion cells and neurons of the frog optic tectum in brain slices (Brain Res. 1998;781:167-181). We have now used autoradiographic receptor binding techniques to determine the location of 5-HT1A and 5-HT1B binding sites in the laminated optic tectum. 5-HT1A binding sites, as labeled with [3H]8-hydroxy-dipropylaminotetralin (8-OH-DPAT), were highest in the superficial, retinorecipient layers of the tectum, intermediate in layers 6 and 7 and low in the remaining layers. Binding densities in all of these layers were unaffected by optic nerve lesion. 5-HT1B binding sites were visualized using [125I]iodocyanopindolol (ICYP). Binding densities were highest in the plexiform layers 5 and 7 and intermediate in layers 6 and 8. Binding sites were present at low levels in layer 9; however, optic nerve lesion resulted in a strong upregulation of these sites in this layer. Pharmacological manipulation of receptor activation resulted in changes in the activity-dependent visual map that is created at the tectum by retinal ganglion cell terminals. Chronic treatment of the tectum with SB-224289, a selective antagonist of 5-HT1B receptors, disrupted the topographic map. In contrast, exposure to WAY-100635, a selective antagonist of 5-HT1A receptors, refined it. We conclude that both 5-HT1A and 5-HT1B receptors are present in the adult frog tectum and that changes in their activation levels can produce changes in retinotectal transmission levels that drive visual plasticity in opposite directions.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Transient up-regulation of the rostrocaudal gradient of ephrin A2 in the tectum coincides with reestablishment of orderly projections during optic nerve regeneration in goldfish.

During development, a graded expression of ephrin A2 has been implicated in retinotectal map formation. Here we have examined ephrin A2 expression during optic nerve regeneration in the mature goldfish. In the tecta of normal animals, a gradient of ephrin A2 expression is detected in cell bodies within the stratum fibrosum et griseum superficiale with more immunopositive cells caudally than rostrally. The gradient in the mature animal presumably reflects the plasticity associated with continued retinal and tectal neurogenesis. During optic nerve regeneration, expression throughout the tectum is increased by 1 month as a strong rostrocaudal gradient. The gradient declines to normal by 3 months. The up-regulation of ephrin A2 during optic nerve regeneration is likely to be instrumental in reestablishing the retinotectal map.

Animals↗

Topographic representation of odorant molecular features in the rat olfactory bulb.

Individual glomeruli in the mammalian olfactory bulb (OB) most probably represent a single odorant receptor (OR). The assembly of glomeruli thus forms the maps of ORs. How is the approximately 1,000 ORs represented spatially in the glomerular map? Using the method of optical imaging of intrinsic signals and systematic panels of stimulus odorants, we recorded odorant-induced glomerular activity from the dorsal and dorsolateral areas of the rat OB, and examined the molecular receptive range (MRR) of individual glomeruli. We then deduced the characteristic molecular features that were shared by odorants effective in activating individual glomeruli. Analysis of the spatial representation of the MRR showed that glomeruli with similar MRRs gathered in close proximity and formed molecular feature clusters and subclusters. Although the shape of the clusters varied among different OBs, the clusters were arranged at stereotypical positions in relation to the zonal organization of the OB. Examination of the spatial representation of the characteristic molecular features of odorants using structurally semirigid aromatic compounds suggest a systematic and gradual change in the characteristic molecular features according to the position of subclusters in the map. The topographic map of the characteristic molecular features may reflect a systematic spatial representation of the ORs and may participate in the neural bases for the odorant structure-odor quality relationship.

Animals↗

Nondestructive, three-dimensional internal fit mapping of fixed prostheses.

Crown fit may be three-dimensionally mapped by using a nondestructive optical technique. Reflected light transmission through thicknesses of a colored impression material was shown to follow the Beer-Lambert relationship over a range of approximately 10 to 300 microns, a useful range of interest for study of cement layer thickness. Control thicknesses of impression material were first formed between the measuring platens of a micrometer, and light transmission values (relative reflections) were measured through these control thicknesses of impression material held against air-abraded, noncast gold alloy. Relative reflection values were similarly measured from impression material formed inside cast gold crowns seated on their respective dies and these values were plotted against direct thickness measurements by using the Beer-Lambert relationship. It was established that the micrometer-produced control specimens yielded a valid standard curve for use with the cast gold crowns. Precementation space measurements determined photometrically were found to correlate significantly (r = 0.72, p less than 0.001) with zinc phosphate cement thickness measured on subsequently cemented and cross-sectioned crowns. A three-dimensional representation of the precementation space inside one crown was developed after mapping of 45 points in less than 5 minutes.

Cementation↗

Ground-based imaging differential optical absorption spectroscopy of atmospheric gases.

We describe a compact remote-sensing instrument that permits spatially resolved mapping of atmospheric trace gases by passive differential optical absorption spectroscopy (DOAS) and present our first applications of imaging of the nitrogen dioxide contents of the exhaust plumes of two industrial emitters. DOAS permits the identification and quantification of various gases, e.g., NO2, SO2, and CH2O, from their specific narrowband (differential) absorption structures with high selectivity and sensitivity. With scattered sunlight as the light source, DOAS is used with an imaging spectrometer that is simultaneously acquiring spectral information on the incident light in one spatial dimension (column). The second spatial dimension is scanned by a moving mirror.

Journal Article↗

Long-term optical imaging and spectroscopy reveal mechanisms underlying the intrinsic signal and stability of cortical maps in V1 of behaving monkeys.

Explorations of learning and memory, other long-term plastic changes, and additional cognitive functions in the behaving primate brain would greatly benefit from the ability to image the functional architecture within the same patch of cortex, at the columnar level, for a long period of time. We developed methods for long-term optical imaging based on intrinsic signals and repeatedly visualized the same functional domains in behaving macaque cortex for a period extending over 1 year. Using optical imaging and imaging spectroscopy, we first explored the relationship between electrical activity and hemodynamic events in the awake behaving primate and compared it with anesthetized preparations. We found that, whereas the amplitude of the intrinsic signal was much larger in the awake animal, its temporal pattern was similar to that observed in the anesthetized animals. In both groups, deoxyhemoglobin concentration reached a peak 2-3 sec after stimulus onset. Furthermore, the early activity-dependent increase in deoxyhemoglobin concentration (the "initial dip") was far more tightly colocalized with electrical activity than the delayed increase in oxyhemoglobin concentration, known to be associated with an increase in blood flow. The implications of these results for improvement of the spatial resolution of blood oxygenation level-dependent functional magnetic resonance imaging are discussed. After the characterization of the intrinsic signal in the behaving primate, we used this new imaging method to explore the stability of cortical maps in the macaque primary visual cortex. Functional maps of orientation and ocular dominance columns were found to be stable for a period longer than 1 year.

Anesthesia↗

Quantitative X-ray mapping of biological cryosections.

The potential for applying X-ray mapping to the elemental microanalysis of biological cryosections is discussed. Methods are described for acquiring and processing data, including use of the top-hat digital filter to remove the average effects of the background contribution. Practical considerations for X-ray mapping are discussed in terms of typical counts per pixel and minimum detectability which depends on the number of pixels chosen to integrate the signal. These aspects are illustrated with elemental maps (Na, P, K, Ca and Fe) from freeze-dried cryosections of mouse cerebellar cortex. A calcium sensitivity in the range 0.5 to 2.5 mmol/kg wet weight of tissue is demonstrated. The correction for overlap of potassium K beta and calcium K alpha is demonstrated with X-ray maps from cryosectioned synaptosomes of squid optic lobe. Quantitative results obtained using internal standards to determine wet weight concentrations are in reasonable agreement with expected values. Alternate schemes applicable to X-ray maps for determining the dry mass concentration, such as the peak/continuum (Hall method), are also discussed.

Electron Probe Microanalysis↗

A systematic map of direction preference in primary visual cortex.

Neurons in the primary visual cortex respond selectively to the orientation of edges and their direction of motion. Orientation preference is mapped in a systematic fashion across the cortical surface, such that neurons in adjacent columns have similar but slightly shifted preferred orientations. Microelectrode studies have suggested that direction preference is also arranged in a systematic fashion, but exactly how this response property is mapped remains unclear. Here we show by optical imaging of intrinsic signals in ferret cortical area 17 that there is a mosaic-like map of direction preference. This map consists of numerous regions within which direction preference changes in a slow, continuous fashion. These regions are separated by winding boundaries (fractures) across which direction preference shifts abruptly, often by 180 degrees. Comparison of direction and orientation preference maps shows that these fractures subdivide iso-orientation domains into regions selective for opposite directions of motion.

Animals↗

A spatial property of the retino-cortical mapping.

Striate cortex topography derives from a stretching of retinal space along the optic axis. At the retina, relative distances are preserved in a mapping of retinal space onto a spherical surface in the environment. At the cortex, relative distances along visual meridia in the cortical map are preserved in a mapping of striate cortex onto an environmental conic surface whose base is in the plane of the eye. This eco-cortical relationship can be considered a reference frame through which spatial relationships at the cortex might provide information about the environment. The present analysis provides an explanation of changes in cortical magnification with visual eccentricity in the primate and a detailed three-dimensional model of striate topography for the macaque monkey. In man, a conic environmental surface is shown to be uniformly resolvable along meridia in the visual field. Finally, the implications of this analysis of the structural properties of the retino-striate pathway and visual resolution are considered in relation to depth and distance perception.

Brain Mapping↗

Fast orientation mapping from HARDI.

This paper introduces a new, accurate and fast method for fiber orientation mapping using high angular resolution diffusion imaging (HARDI) data. The approach utilizes the Fourier relationship between the water displacement probabilities and diffusion attenuated magnetic resonance (MR) signal expressed in spherical coordinates. The Laplace series coefficients of the water displacement probabilities are evaluated at a fixed distance away from the origin. The computations take under one minute for most three-dimensional datasets. We present orientation maps computed from excised rat optic chiasm, brain and spinal cord images. The developed method will improve the reliability of tractography schemes and make it possible to correctly identify the neural connections between functionally connected regions of the nervous system.

Algorithms↗

Nanometer-scale optical imaging of epitaxially grown GaN and InN islands using apertureless near-field microscopy.

Nanometer-scale chemical imaging of epitaxially grown gallium nitride (GaN) and indium nitride (InN) islands is performed using scattering-type apertureless near-field scanning optical microscopy (ANSOM). The scattering of 633 nm laser radiation is modulated by an oscillating metallic probe, and the scattered radiation is detected by homodyne amplification, followed by high-harmonic demodulation, yielding optical near-field scattering maps with a spatial resolution better than 30 nm. The image contrast between InN and GaN, and the tip-sample distance dependence, can be qualitatively explained by a simple dipole-coupling model. The ANSOM images of InN and GaN also show structures that are absent in the topographic counterpart, and these substructures are explained by the variations of the local dielectric environment of InN and GaN.

Journal Article↗

Vasodilator effects of desflurane and isoflurane in the feline small intestine.

The influence of desflurane (DES) and isoflurane (ISO) on the intestinal vasculature was investigated in normoventilated cats (n = 10) during basal chloralose anesthesia (control). We measured heart rate, mean arterial pressure (MAP), and intestinal blood flow (optical drop flowmetry). Intestinal vascular resistance (IVR) was derived. To avoid changes in local vascular tone related to alterations in transmural pressure gradients, intestinal arterial pressure was controlled and kept constant by a variable aortic clamp. Measurements were performed during control and during the administration of DES (3.5% and 7.0% end-tidal) or ISO (0.8% and 1.6% end-tidal). Each animal was exposed to both agents, prior to and after intestinal postganglionic denervation. In the innervated intestine, both DES and ISO dose-dependently decreased IVR. At the high dose, DES (50 +/- 10% decrease in IVR) was a significantly more powerful vasodilator than ISO (37 +/- 12% decrease in IVR). In the denervated intestine, less pronounced vasodilations were produced by both DES and ISO, as compared to the innervated state, and there were, in this situation, no significant differences between agents concerning the magnitude of the vasodilation. As indicated by comparisons between the innervated versus the denervated state, both neurogenic and non-neurogenic mechanisms contributed to the vasodilator responses. The vascular relaxation at the high dose was for ISO associated with a significantly more powerful non-neurogenic vasodilation, and for DES associated with a significantly more powerful neurogenic vasodilation. This suggests that withdrawal of sympathetic neurogenic vasoconstrictor tone is more important for the vasodilation produced by DES than it is for ISO.

Anesthetics, Inhalation↗

Scar resurfacing with high-energy, short-pulsed and flashscanning carbon dioxide lasers.

BACKGROUND: Scars have a significant effect on a person's physical and social being. Many treatment modalities for scar improvement such as surgical scar revision, electrosurgical planing, chemical peeling, filler substance implantation, and dermabrasion have been developed. Recently, the resurfacing carbon dioxide (CO2) laser systems have proven to be a useful and safe treatment in the treatment of facial rhytides and acne scarring. OBJECTIVE: The purpose of this study was to evaluate the resurfacing CO2 lasers in the treatment of various surgical, traumatic, acne, and varicella scars. METHODS: Thirty subjects, aging between 14 and 84 years, with surgical, traumatic, acne, or varicella scars were evaluated. Two types of resurfacing laser systems were utilized in this study, a high-energy, short-pulsed CO2 laser and a continuous wave CO2 laser with an optico-mechanical computer flash-scanner. Post-surgical scars were treated with laser resurfacing between 4 and 6 weeks after scar formation. Traumatic, acne, and varicella scars were treated after scar maturation (range, 1-10 years). Scar improvement was evaluated by photographic analysis of before and after images by four independent health care workers using a quartile scale of improvement (< 25%, 25-49%, 50-74%, > 75%) as well as optical profilometry using silicone surface impressions in 12 scars. RESULTS: Twenty of 24 surgical scars had greater than 75% improvement, and 24 of 24 had greater than 50% improvement by photographic analysis. All six traumatic, acne and varicella scars had greater than 50% improvement. Optical profilometry and surface topography maps reveal a significant flattening of related and depressed scars. CONCLUSION: The high-energy, short-pulsed CO2 laser and the continuous wave CO2 laser with flash-scanning attachment are safe and effective as a treatment modality for scar revision. In general, elevated scars improve more dramatically than depressed scars.

Adolescent↗