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J C Horton

Publications and source records attributed to J C Horton.

At least 19 recordsLinked to original sources

Metabolic mapping of suppression scotomas in striate cortex of macaques with experimental strabismus.

Misalignment of the ocular axes induces double vision and rivalry. To prevent these unpleasant sensations, most subjects fixate preferentially with one eye and suppress entirely the deviating eye or else suppress portions of the visual field of either eye. To explore the mechanism of visual suppression, a divergent strabismus (exotropia) was induced in six normal, adult Macaca fascicularis by disinserting the medial rectus muscles. After 4-8 weeks, each animal was chaired to measure its exotropia and to determine its ocular fixation preference. Five of the monkeys developed a clearly dominant eye. It was injected with [(3)H]proline. Alternate sections from flat-mounts of striate cortex were then processed either for autoradiography to label the ocular dominance columns or for cytochrome oxidase (CO) to assess local metabolic activity. Two CO patterns were seen, often in the same cortex. The first consisted of thin dark columns alternating with wide pale columns. This pattern arose from reduced CO activity in the suppressed eye's monocular core zones and both eyes' binocular border strips. The second pattern consisted of thin pale bands from reduced metabolic activity in both eyes' border strips. The thin dark-wide pale CO pattern was more widespread in the three animals with a strong fixation preference. The dark CO columns usually fit in register with the ocular dominance columns of the fixating eye, suggesting that perception was suppressed in the deviating eye. In most animals, however, the correlation switched in peripheral cortex contralateral to the deviating eye, implying local suppression of the fixating eye's temporal retina (beyond 10 degrees), as reported in humans with divergent strabismus. In the two animals with a weak fixation preference, pale border strips were found within the central visual field representation in both hemispheres. This CO pattern was consistent with alternating visual suppression. These experiments provide the first anatomical evidence for changes in cortical metabolism that can be correlated with suppression scotomas in subjects with strabismus.

Animals↗

Akinetopsia from nefazodone toxicity.

PURPOSE: To investigate two cases of selective impairment of motion perception (akinetopsia) induced by toxicity from the antidepressant nefazodone, a new drug that blocks serotonin reuptake and antagonizes 5-HT2 receptors. METHODS: Case reports. RESULTS: A 47-year-old man receiving nefazodone (Serzone; Bristol-Meyers Squibb, New York, N.Y.) (100 mg twice daily), reported a bizarre derangement of motion perception. Moving objects were followed by a trail of multiple "freeze-frame" images, which dissipated promptly when motion ceased. A 48-year-old woman receiving nefazodone (400 mg daily at bedtime) reported a similar phenomenon, with visual trails following moving objects. In both patients, vision returned to normal after the dosage of nefazodone was reduced or eliminated. CONCLUSIONS: Nefazodone toxicity can result in akinetopsia, characterized by the inability to perceive motion in a normal, smooth fashion; persistence of multiple, strobelike images; and visual trails behind moving objects. In this rare syndrome, stationary elements are perceived normally, indicating that nefazodone causes selective impairment of pathways involved in motion processing in the visual system.

Antidepressive Agents, Second-Generation↗

COVOL: an interactive program for evaluating second virial coefficients from the triaxial shape or dimensions of rigid macromolecules.

An interactive program is described for calculating the second virial coefficient contribution to the thermodynamic nonideality of solutions of rigid macromolecules based on their triaxial dimensions. The FORTRAN-77 program, available in precompiled form for the PC, is based on theory for the covolume of triaxial ellipsoid particles [Rallison, J. M., and S.E Harding. (1985). J. Colloid Interface Sci. 103:284-289]. This covolume has the potential to provide a magnitude for the second virial coefficient of macromolecules bearing no net charge. Allowance for a charge-charge contribution is made via an expression based on Debye-Hückel theory and uniform distribution of the net charge over the surface of a sphere with dimensions governed by the Stokes radius of the macromolecule. Ovalbumin, ribonuclease A, and hemoglobin are used as model systems to illustrate application of the COVOL routine.

Animals↗

Monocular core zones and binocular border strips in primate striate cortex revealed by the contrasting effects of enucleation, eyelid suture, and retinal laser lesions on cytochrome oxidase activity.

In primate striate cortex, geniculocortical afferents in layer IVc terminate in parallel stripes called ocular dominance columns. We propose that this segregation of ocular inputs generates a related but distinct columnar system of monocular core zones alternating with binocular border strips. Evidence for this functional parcellation was obtained by comparing the effects of enucleation, eyelid suture, and retinal laser lesions on cytochrome oxidase (CO) activity in eight macaques. Enucleation produced a high-contrast pattern of dark and light columns in layer IVc, corresponding precisely to the ocular dominance columns, whereas eyelid suture produced a low-contrast pattern of thin dark columns alternating with wide pale columns. [3H]Proline eye injection showed that the thin dark columns corresponded to the core zones of the open eye's ocular dominance columns. The wide pale columns resulted from loss of CO activity in the sutured eye's core zones and within both eyes' border strips. Loss of CO activity within both eyes' border strips suggested that these regions are binocular. To confirm our findings, we compared different CO patterns in the same cortex by making retinal laser lesions in four animals. They produced a CO pattern tantamount to "focal" enucleation, although contrast was low when laser damage was confined to the outer retina. CO levels in cortical scotomas remained severely depressed for months after retinal lesions, even when the other eye was enucleated. This observation provided little anatomical support for the notion of topographic plasticity after visual deafferentation. In a single human subject with macular degeneration, CO revealed a low-contrast pattern of ocular dominance columns, resembling the pattern in monkeys with laser-induced photoreceptor damage.

Aged↗

Intraocular coccidioidomycosis diagnosed by skin biopsy.

OBJECTIVE: To describe ocular findings in 2 patients with disseminated coccidioidomycosis diagnosed by skin biopsy. METHODS: The clinical and histopathologic findings of the 2 patients were reviewed retrospectively. RESULTS: One patient had a unilateral, granulomatous iridocyclitis with multiple iris nodules and a large vascularized anterior chamber mass, in the setting of pulmonary, cutaneous, and skeletal infection by Coccidioides immitis. The second patient developed papilledema and multifocal chorioretinitis accompanied by pulmonary, cutaneous, and meningeal C immitis infection. In each case, examination of the skin biopsy specimen revealed C immitis spherules. Treatments included local and systemic amphotericin B and oral fluconazole. CONCLUSIONS: Although rare, intraocular involvement can occur in the setting of disseminated coccidioidomycosis. A thorough systemic evaluation and biopsy of suspicious skin lesions can aid in the diagnosis.

Adult↗

Timing of the critical period for plasticity of ocular dominance columns in macaque striate cortex.

Visual deprivation induced by monocular eyelid suture, a laboratory model for congenital cataract, results in shrinkage of ocular dominance columns serving the closed eye. We performed monocular suture in macaques at ages 1, 3, 5, 7, and 12 weeks to define the critical period for plasticity of ocular dominance columns. After a minimum survival of 8 months, complete montages of [3H]proline-labeled columns were reconstructed from flat-mounts of striate cortex in both hemispheres. In any given monkey, visual deprivation induced the columns throughout striate cortex (V1) to retract the same distance from their original borders in layer IVcbeta. After deprivation, the widest columns remained in the foveal representation and along the V1/V2 border, where columns are widest in control animals. The narrowest deprived columns belonged to the ipsilateral eye, especially along the horizontal meridian and in the periphery, where columns are narrowest in control animals. At the earliest age that we tested (1 week), visual deprivation reduced the columns to fragments. These fragments always coincided with a cytochrome oxidase patch, or a short string of patches, in the upper layers. More severe column shrinkage occurred in layer IVcbeta (parvo) than layer IVcalpha (magno). The geniculate input to the patches in layer III (konio) appeared normal after deprivation, despite loss of CO activity. Surprisingly, the blind spot representation of the open eye was shrunken by monocular deprivation, although binocular competition is absent in this region. Our principal finding was that eyelid suture at age 1 week caused the most severe column shrinkage. With suture at later ages, the degree of column shrinkage showed a progressive decline. Deprivation commencing at age 12 weeks caused no column shrinkage. These results imply that primate visual cortex is most vulnerable to deprivation during the first weeks of life. Our experiments should provide further impetus for the treatment of children with congenital cataract at the earliest possible age.

Age Factors↗

Transneuronal retinal input to the primate Edinger-Westphal nucleus.

The Edinger-Westphal nucleus of the oculomotor nuclear complex provides preganglionic parasympathetic innervation to the pupil. We labelled its retinal input by transneuronal autoradiography after an eye injection of [3H]proline in the macaque monkey. The primary retinal projection to the pretectum terminated in the ipsilateral and contralateral olivary nuclei. These nuclei were intensely labelled and sharply delimited, with a mean diameter of 590 microm and a rostrocaudal length of 2.52 mm. The caudal half of the olivary nucleus on each side broke into multiple clumps of label. Fragments of label also surrounded each olivary nucleus. The exact pattern of pretectal labelling varied considerably among animals and even from side to side in the same animal. In 5 of 6 monkeys, label from the olivary nucleus reached the Edinger-Westphal nucleus transneuronally. In transverse sections, the Edinger-Westphal label appeared as a circular patch located on either side of the midbrain ventral to the cerebral aqueduct in the central gray matter. It averaged 230 microm in diameter and 610 microm in length. In Nissl-stained sections, the autoradiographic label corresponded to a distinct nucleus comprised of neurons that were smaller than neurons in nearby somatic subdivisions of the oculomotor complex. The mean area of Edinger-Westphal neurons was 295 microm2. Transneuronal retinal input to the Edinger-Westphal nucleus mediating pupillary constriction terminates in a single, well-defined cell group in the midbrain.

Animals↗

The ELLIPS suite of macromolecular conformation algorithms.

This paper describes a series of four programmes for the PC based on ellipsoidal representations of macromolecular shape in solution using Universal shape functions, ELLIPS1 is based on simple ellipsoid of revolution models (where two of the three axes of the ellipsoid are fixed equal to each other). If the user types in a value for a shape function from sedimentation or other types of hydrodynamic measurement, it will return a value for the axial ratio of the ellipsoid. ELLIPS2 is based on the more general triaxial ellipsoid with the removal of the restriction of two equal axes. The user enters the three semi-axial dimensions of the molecule or the equivalent two axial ratios and ELLIPS2 returns the value of all the hydrodynamic shape functions. It also works of course for ellipsoids of revolution. ELLIPS3 and ELLIPS4 do the reverse of ELLIPS2, that is they both provide a method for the unique evaluation of the triaxial dimensions or axial ratios of a macromolecule (and without having to guess a value for the so-called "hydration") after entering at least three pieces of hydrodynamic information: ELLIPS3 requires EITHER the intrinsic viscosity with the second virial coefficient (from sedimentation equilibrium, light scattering of osmometry) and the radius of gyration (from light or x-ray scattering) OR the intrinsic viscosity with the concentration dependence term for the sedimentation coefficient and the (harmonic mean) rotational relaxation time from fluorescence depolarisation measurements. ELLIPS4 evaluates the tri-axial shape of a macromolecule from electro-optic decay based Universal shape functions using another Universal shape function as a constraint in the extraction of the decay constants.

Algorithms↗

Myelin patterns in V1 and V2 of normal and monocularly enucleated monkeys.

A pattern of alternating light and dark columns was observed in wet, unstained sections of macaque striate cortex after monocular enucleation. The columns were clearest in layer IV, but could be detected through the full thickness of the cortex. Subsequent processing for cytochrome oxidase (CO) showed that the light columns in wet sections viewed under darkfield illumination matched the ocular dominance columns serving the enucleated eye. These columns labeled preferentially with an antibody to myelin basic protein, suggesting that greater myelin content accounted for their brighter appearance. However, when sections were counterstained with luxol fast blue, Gallyas and Woelcke myelin techniques, the enucleated eye's columns appeared pale. It is unclear why classical myelin stains and myelin basic protein immunohistochemistry yielded opposite results. Discrepant patterns of myelin distribution were also found in normal animals using different myelin stains. Luxol fast blue showed homogeneous staining in layer IVc of macaque striate cortex, but the Gallyas stain revealed a pattern of thin pale bands alternating with wide dark bands, matching the pattern seen with the Liesegang stain. The CO patches in layers II and III fit in register with the wide dark myelin bands. In layers II and III of striate cortex, the Gallyas and luxol fast blue methods both labeled the CO patches. However, in squirrel monkey V2 the Gallyas stain labeled the pale CO stripes, whereas luxol fast blue labeled the dark CO stripes. These results indicate that pattern of myelin staining in visual cortex can vary according to the choice of technique, and may not reflect the true distribution of myelin. Studies of myeloarchitecture should employ a variety of myelin techniques, including examination of unstained sections, to obtain the most accurate picture of cortical myelin content.

Animals↗

Wilbrand's knee of the primate optic chiasm is an artefact of monocular enucleation.

PURPOSE: The anterior chiasmal syndrome consists of a temporal hemianopia or complete visual field loss in one eye, plus a superior temporal hemianopia in the other eye. The superior temporal hemianopia in the other eye is thought to result from injury to Wilbrand's Knee of the optic chiasm. Wilbrand's Knee is a loop of decussating fibers which detours into the contralateral optic nerve before entering the optic tract. I studied the organization of fibers in the optic chiasm of monkeys and humans to verify the existence of Wilbrand's Knee and to elucidate further the pattern of visual field loss seen from lesions of the sellar region. METHODS: The primary optic pathway was labelled in monkeys by injection of [3H] proline into one eye, followed by autoradiography. There were 8 intact Rhesus monkeys and 3 intact squirrel monkeys. In addition, the optic pathway was studied in the Rhesus monkey 6 months and 4 years after monocular enucleation. The optic chiasm was also examined using myelin stains in specimens obtained post-mortem from 3 patients. The patients had lost 1 eye 5 months, 2 years, and 28 years prior to their deaths. Finally, clinical observations were recorded in 3 patients with the anterior chiasmal syndrome. RESULTS: In normal Rhesus and squirrel monkeys, optic nerve fibers crossed the optic chiasm without entering the contralateral optic nerve. After short-term monocular enucleation, fibers from the normal optic nerve were drawn closer to the entry zone of the degenerating optic nerve, but Wilbrand's Knee was still absent. After long-term enucleation, a typical Wilbrand's Knee was induced to form. In the human, Wilbrand's Knee was absent 5 months after monocular enucleation, but emerged in the two cases involving long-term enucleation, in a fashion analogous to the monkey. The case reports describe 3 patients with variants of the anterior chiasmal syndrome from parasellar tumors. CONCLUSIONS: Wilbrand's Knee does not exist in the normal primate optic chiasm. It forms gradually over a period of years following monocular enucleation, presumably from shrinkage of the optic chiasm caused by atrophy of fibers from the enucleated eye. Therefore, the superior temporal hemianopia in the "other eye" seen in the anterior chiasmal syndrome cannot be due to compression of Wilbrand's Knee. I propose that it occurs from combined compression of the optic chiasm and one (or both) optic nerves.

Aged↗

Intrinsic variability of ocular dominance column periodicity in normal macaque monkeys.

Little is known about intrinsic variation from animal to animal in the periodicity of columnar systems within various regions of the mammalian cerebral cortex. To address this issue, complete mosaics of the ocular dominance columns were reconstructed from flat-mounts of the left and right striate cortex (V1) in six normal adult macaques (Macaca fascicularis). To identify the columns, we enucleated the right eye and subsequently processed striate cortex for cytochrome oxidase (CO) activity. Average column areas for the intact eye and the missing eye were nearly equal, confirming that monocular enucleation in adult macaques produces negligible column shrinkage. The contralateral eye's columns occupied more territory than the ipsilateral eye's columns, even in the central visual field representation (0 degree to 8 degrees), where they predominated by 52 to 48%. The column mosaics showed remarkable variation in periodicity. The number of column pairs along the V1/V2 border ranged from 101 sets in one monkey to 154 sets in another. Average column width along the V1/V2 border ranged between 670 and 395 microns, a nearly twofold difference. The widest columns were found in the foveal representation. This high degree of innate variability should be taken into account when considering the effects of various sensory manipulations (e.g., strabismus, anisometropia), which have been reported to alter the periodicity of ocular dominance columns. We found pronounced intrinsic variation in the width and number of ocular dominance columns in a sample of six M. fascicularis, indicating that the number of hypercolumns within a given cortical area can range widely among normal members of the same species.

Age Factors↗

Anatomical demonstration of ocular dominance columns in striate cortex of the squirrel monkey.

The squirrel monkey is the only primate reported to lack ocular dominance columns. Nothing anomalous about the visual capacity of squirrel monkeys has been found to explain their missing columns, leading to the suggestion that ocular dominance columns might be "an epiphenomenon, not serving any purpose" (Livingstone et al., 1995). Puzzled by the apparent lack of ocular dominance columns in squirrel monkeys, we made eye injections with transneuronal tracers in four normal squirrel monkeys. An irregular mosaic of columns, averaging 225 microns in width, was found throughout striate cortex. They were double-labeled by placing wheat germ agglutinin-horseradish peroxidase into the left eye and [3H]proline into the right eye. The tracers labeled opposite sets of interdigitating columns, proving they represent ocular dominance columns. The columns were much clearer in layer IVc alpha (magno-receiving) than IVc beta (parvo-receiving). In the lateral geniculate body, the parvo laminae showed extensive mixing of ocular inputs, suggesting that increased label spillover contributes to the blurred columns in layer IVc beta. The cytochrome oxidase (CO) patches were organized into distinct rows, but they bore no consistent relationship to the ocular dominance columns. These experiments indicate that ocular dominance columns are less well segregated in squirrel monkeys than macaques, but they are present. This fact is pertinent to a recent study reporting that ocular dominance columns are absent in normal squirrel monkeys, but induced to form by strabismus (Livingstone, 1996).

Animals↗

An adult-like pattern of ocular dominance columns in striate cortex of newborn monkeys prior to visual experience.

In macaque monkeys, the geniculocortical afferents serving each eye segregate in layer IVc of striate cortex during early life into a pattern of alternating inputs called ocular dominance columns. It has been disputed whether visual experience is necessary for the formation of ocular dominance columns. To settle this issue, fetal monkeys were delivered prematurely by Caesarean section at embryonic day 157 (E157), 8 d before the end of normal gestation. To avoid light exposure, the Caesarean section and all subsequent feedings and procedures were done in absolute darkness, using infrared night-vision goggles. Tritiated proline was injected into the right eye 1 d after delivery (E158). One week later at postnatal age 0 (P0), the equivalent of a full-term pregnancy (E165/P0), alternate sections of unfolded and flattened visual cortex were prepared for autoradiography or cytochrome oxidase (CO). All three newborns studied at E165/P0 had well segregated ocular dominance columns organized into the characteristic mosaic present in adults. In the upper layers, a mature pattern of CO patches (also known as blobs or puffs) was visible, aligned with the ocular dominance columns in layer IVc. Every other row of patches in layers II, III was labeled by [3H]proline. In V2, a distinct system of alternating thick-pale-thin-pale CO stripes was present. These findings indicate that stimulation of the retina by light is not necessary for the development of columnar systems in the visual cortex. Ocular dominance columns, patches, and V2 stripes all are well formed before visual experience. Even the thalamic input to the patches in the upper layers of striate cortex is segregated by eye in newborns.

Aging↗

Central retinal artery occlusion after manipulation of the neck by a chiropractor.

PURPOSE: To document a case of central retinal artery occlusion after chiropractic treatment. METHODS: An 87-year-old man suffered a central retinal artery occlusion immediately after chiropractic neck manipulation. RESULTS: A magnetic resonance angiogram showed an atherosclerotic plaque in the ipsilateral carotid artery, which probably shed emboli during cervical joint mobilization. CONCLUSION: The carotid arteries should be approached carefully in patients with known or suspected atherosclerotic disease of the carotid arteries.

Aged↗