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Biomedical subjects

D E Mitchell

Publications and source records attributed to D E Mitchell.

At least 19 recordsLinked to original sources

The long-term effectiveness of different regimens of occlusion on recovery from early monocular deprivation in kittens.

Although the behavioural effects of an early period of monocular deprivation imposed on kittens can be very severe, resembling an extreme form of the human clinical condition deprivation amblyopia, they are not necessarily irreversible. Considerable behavioural as well as physiological recovery can occur if normal visual input is restored to the deprived eye sufficiently early, particularly if the other (initially non-deprived) eye is occluded at the same time (reverse occlusion). However, past work has shown that in many situations the improvement in the vision of the initially deprived eye that occurs during reverse occlusion is not retained following the subsequent introduction of binocular visual input. Furthermore, the vision of the other eye is often reduced as well, with the result that the eventual outcome is a condition of bilateral amblyopia. This study first examines the consequences of several periods of reverse occlusion whose onset and duration would be thought to maximize the opportunity for good and long-standing recovery of vision in the initially deprived eye. However, only in a very restricted set of exposure conditions did animals acquire good vision in one or both eyes; in most situations the final outcome was one of bilateral amblyopia. A second set of experiments examined the consequences of various regimens of part-time reverse occlusion, where the initially non-deprived eye was occluded for only part of each day to allow a period of binocular visual exposure, on kittens that had been monocularly deprived until 6, 8, 10 or 12 weeks of age. Whereas short or long daily periods of occlusion of the initially non-deprived eye resulted eventually in amblyopia in one, or usually both, eyes, certain intermediate occlusion times (3.5 or 5 h each day) resulted in recovery of normal acuities, contrast sensitivity and vernier acuity in both eyes, in animals that had been monocularly deprived until 6, 8 or 10 weeks of age, but not in animals deprived for longer periods. Experiments were done to establish some of the factors that contributed to the successful outcome associated with certain of the regimens of part-time reverse occlusion. It was established that recovery was just as good in animals in which the visual axes were vertically misaligned by means of prisms during the daily period of binocular visual exposure, thereby indicating that the visual input to the two eyes need not be concordant. However, animals that received equivalent visual exposure of the two eyes each day, but successively rather than simultaneously, all developed very severe bilateral amblyopia.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors

Grating acuity of cats measured with detection and discrimination tasks.

In order to help resolve the widely discrepant claims for the grating acuity of the cat, behavioral measurements were made of the acuities of two normal adult cats using two different tasks. In one, a conventional detection task, the cats were required to discriminate between high contrast vertical gratings and a uniform field of the same space-averaged luminance. The second, less commonly-used task, required the cats to discriminate between vertical and horizontal gratings of the same spatial frequency. Both cats obtained thresholds of between 8.5 and 9 cycles/degree, with no difference between tasks. These results suggest that detection of aliased patterns is not a likely factor contributing to the wide range of published acuities, and they provide support for one of two competing models of beta-ganglion cell sampling in the retina.

Animals

Vernier acuity of normal and visually deprived cats.

This study examines the relationship between grating and vernier acuity in cats that were either normally reared, unilaterally amblyopic as a result of a period of monocular deprivation, or bilaterally amblyopic resulting from a period of reverse occlusion followed by binocular visual experience. Vernier acuity was assessed on a jumping stand by use of a vernier-grating stimulus similar to that devised for use with human infants. The vernier thresholds for normal cats were 1.2-1.3 min arc, values that were approx. 6 times better than their grating acuity, and hence may represent a true hyperacuity. By contrast, the vernier acuity of the visually deprived cats were substantially below normal (19-83 min arc). The vernier thresholds for the deprived eye of the monocularly deprived cat and both eyes of the reverse occluded cats had fallen to the point where they were at best equal, and sometimes worse than the corresponding grating acuity. This pattern of results is similar to those observed in some types of human amblyopia, where vernier acuity also no longer represents a hyperacuity, and where in severe cases the thresholds may be worse than grating acuity.

Amblyopia

The enzymes in cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism in human corpora lutea: dependence on luteal phase, cellular and subcellular distribution.

Eicosanoids synthesized within corpus luteum are presumed to regulate luteal function in women. However, the potential cellular source(s) of the eicosanoids, whether small and large luteal cells differ in eicosanoid synthesis and whether eicosanoids other than prostaglandin (PG)E2, PGF2 alpha and 6-keto-PGI1 alpha can be synthesized, have not been investigated. The present immunocytochemical studies were undertaken to answer these questions using mono and polyclonal antibodies to several enzymes in arachidonic acid metabolism by cyclooxygenase and lipoxygenase pathways. Human corpora lutea from early (n = 5), mid (n = 6) and late (n = 3) luteal phases were specifically immunostained for all the enzymes. All the enzymes were present in small and large luteal cells as well as in non luteal cells. However, small luteal cells contained more immunoreactive 5-lipoxygenase, PGD2 and PGF2 alpha synthases; large luteal cells contained more TXA2 synthase and 12-lipoxygenase; small and large luteal cells contained similar amounts of cyclooxygenase and PGI2 synthase. In all the cells, immunoreactive PGD2, PGI2 and TXA2 synthases increased from early to mid luteal phase and then declined in late luteal phase. Cyclooxygenase, 5- and 12-lipoxygenases and PGF2 alpha synthase, on the other hand, increased from early to mid and mid to late luteal phases. Immunoreactive cyclooxygenase and 5- and 12-lipoxygenases were present primarily in rough endoplasmic reticulum (ER) and/or smooth ER and cytoplasm. Quite unexpectedly, all three enzymes were also found in nuclear membranes, condensed chromatin and especially at the perimeter of condensed chromatin. Dispersed chromatin contained very little or no immunoreactive enzyme. These results indicate that regulation of human luteal function by eicosanoids synthesized within the corpus luteum is complex involving perhaps a) small and large luteal as well as non luteal cells, b) eicosanoids which have not been previously considered to play a role in luteal function and c) coordinate regulation of more than one enzyme in the pathways of arachidonic acid metabolism.

Amino Acid Sequence

Vernier acuity with opposite-contrast stimuli.

Vernier acuity has usually been tested with stimuli of the same contrast polarity (SC). This traditional vernier acuity was compared to that obtained with stimuli of opposite-contrast (OC) in which one target was brighter than the background and the other was darker. For both bar and dot targets vernier acuity with OC stimuli was about half as good as with SC stimuli. There were large individual differences in the size of the disadvantage with OC stimuli, although thresholds remained within the hyperacuity range. There were also individually-differing biases to see a dark vernier stimulus on one or the other side of a bright stimulus. Differences between OC and SC vernier acuities persisted over a wide range of interstimulus spacings, widths, and contrasts. At extremes of these spatial manipulations acuities became similar, but only because SC acuities were degraded to the level of OC acuities. Subjects showed little improvement in OC vernier acuity, even after 50,000 trials. It is concluded that finest judgements of spatial position arise in a level of the visual system at which light and dark stimuli are treated independently.

Discrimination Learning

Fertility after ectopic pregnancy.

In the period July 1983 to March 1985, 264 women had surgery for ectopic pregnancy at Grady Memorial Hospital; 76 had postoperative hysterosalpingograms. Of these, 55 (76.4%) women were followed up for 3 to 41 months (mean, 23.8) to determine subsequent fertility. During the follow-up period, 30 pregnancies occurred among the 55 patients; 24 were intrauterine and 6 were repeat ectopic pregnancies. In the surgical group of 39 patients with salpingectomy, 60.8% of those desiring pregnancy achieved an intrauterine pregnancy. Of the 12 patients with salpingostomy, the three who desired pregnancy achieved it (100%). In the tubal abortion group, the two women desiring pregnancy conceived (100%). There were six repeat ectopic pregnancies (10.9%). Of the ectopic pregnancies, one occurred in the salpingectomy group (2.6%), four in the salpingostomy group (33.3%), and one in the tubal abortion group (25%). Five of the six ectopic gestations were found in the contralateral fallopian tube. Hysterosalpingographic evidence of contralateral tubal patency was a good prognostic indicator for subsequent intrauterine pregnancy. By contrast, one half of study patients with findings suggesting tubal occlusion still achieved an intrauterine pregnancy.

Adult

Normal and abnormal visual development in kittens: insights into the mechanisms that underlie visual perceptual development in humans.

For many years the mechanisms that underlie normal and abnormal development of visual perception in human infants have been explored in anatomical and physiological studies on two species of frontal-eyed mammals, namely, cats and, to a lesser extent, monkeys. The unstated assumption underlying the investigations on cats is that despite substantial differences in the organization of the visual pathways of cats and humans, as well as quantitative differences in their perceptual abilities, principles of development established in the former also apply to humans. This review examines the extent to which this assumption may be valid. Following a review of certain anatomical peculiarities of the cat visual system, several of the differences as well as the parallels between the perceptual abilities of cats and humans are summarized. The latter similarities, as well as the larger number of parallels between the two species that can be drawn during development, attest to the validity of the choice of the cat for study of the mechanisms that underlie human visual development.

Animals

Hysteroscopic removal of an interstitial ectopic gestation. A case report.

A 31-year-old woman with plauteauing quantitative serial beta-human chorionic gonadotropin levels, suspect pelvic sonography and the absence of products of conception on uterine curettage was suspected of having an interstitial ectopic pregnancy. Confirmation was by endoscopy. Cornual uterine wedge resection was avoided with laparoscopically guided hysteroscopic removal of the products of conception.

Adult

The extent of visual recovery from early monocular or binocular visual deprivation in kittens.

1. The rate and extent of recovery of vision was studied in the deprived eye of kittens that had been monocularly deprived from near birth for periods that lasted from 6 weeks to 18 months. Recovery was measured in the two situations, where either both eyes were open following the initial deprivation (binocular recovery), or else the non-deprived eye was occluded so as to force the animal to employ its deprived eye (reverse occlusion). 2. Measurements were made of the visual acuity of the deprived eye for gratings at frequent intervals during recovery by means of a simple behavioural technique. 3. The acuity that the deprived eye eventually attained declined with increasing length of deprivation in a manner that could be approximated by a simple exponential decay. Only minimal visual recovery was observed in animals deprived beyond 1 year of age; only two of six animals recovered sufficient vision to enable measurement of visual acuity. In general, animals that were reverse occluded recovered better vision than did those that had both eyes open during recovery. 4. The recovery of vision in the deprived eye of monocularly deprived kittens was compared to that observed following equivalent periods of two forms of binocular deprivation, namely dark-rearing and binocular eyelid suture. 5. The recovery from the two forms of binocular deprivation was quite different. Whereas the extent of recovery from dark-rearing was considerably greater than that observed after equivalent periods of monocular deprivation, the recovery of a limited sample of cats that were binocularly deprived by eyelid suture was worse. 6. These findings suggest that some plasticity remains in the visual pathways for a longer time than indicated by experiments that examine the physiological effects of monocular deprivation on various visual cortical structures.

Animals

Assessment of depth perception in cats.

A behavioural method is described for the assessment of depth perception of kittens. Measurement is made of the smallest separation in depth that can be discriminated between two adjacent stimuli under both monocular and binocular viewing conditions. Normal animals can discriminate much smaller separations in depth when using two eyes than with monocular viewing, implying the presence of a cue to depth that is uniquely available with binocular viewing. The test provides a quick and reliable way of screening animals for stereopsis.

Animals

The development of vision in cats after extended periods of dark-rearing.

The time course of development of visual acuity for square wave gratings was measured behaviourally in a number of cats that were reared in total darkness until they were either 4 (5 cats) or 6 (1 cat) months of age. Less extensive measurements were also made on animals reared in a similar manner until they were either 1 1/2 or 10 months old. Initially, all the animals appeared to be blind, but signs of vision became evident after periods of time in an illuminated environment that ranged from a few days, in the case of animals dark-reared for only 1 1/2 to 4 months, to 1 to 2 months for those animals that were deprived for 6 months or more. Thereafter, visual acuity as measured on a jumping stand progressively improved, reaching, in the case of animals deprived for 4 months, values that were comparable to those of normal animals (6.9 cycles/deg) after 4 months of exposure to light. The animal deprived for 6 months remained apparently blind for a month and eventually attained an acuity (5.7 cycles/deg) that was somewhat less than that of normal animals. The fact that such high acuities can be achieved after periods of binocular deprivation that extend throughout the classically defined "critical period" suggest that the effect of dark-rearing is somehow to impede the natural decline with age in the degree to which cortical neurones are susceptible to environmental modification.

Animals

The rate of recovery of vision after early monocular deprivation in kittens.

1. Fifteen kittens were monocularly deprived of vision by suturing the lids of the right eye together for various periods of time at different ages. A simple behavioural technique was used to assess the immediate effects of the period of monocular deprivation on the visual acuity of the deprived eye as well as the time course of any subsequent recovery.2. The extent of the recovery of vision was measured under conditions where the animal was either forced to use its deprived eye by performing a reverse suture or where the animal had both eyes open after the initial period of monocular occlusion.3. The initial effects of monocular deprivation were graded in severity according to the age at which the deprivation was imposed, ranging from apparent blindness in animals deprived at 6 weeks of age to only a small loss of acuity in kittens deprived at 12 weeks of age.4. The effects of deprivation imposed from birth were particularly severe, leading to a temporary blindness. Nevertheless after a period of time that became progressively longer with increasing deprivation, all animals showed some recovery of pattern vision over the course of the next 2 or 3 months. The extent of this recovery became progressively less as the period of deprivation was prolonged. There was even some recovery of vision (an acuity of 2.5 cycles/deg) in animals that were deprived throughout the duration of the ;critical period' to 4 months of age.5. Direct comparison of the rate of behavioural recovery between animals that were reverse sutured with that of litter-mates that received binocular input after monocular occlusion to either 45 or 60 days of age proved to be remarkably similar, although the acuity that was eventually attained by the reverse sutured animals was always slightly higher.6. The recoveries observed after reverse suturing were reasonably well correlated with changes observed in the ocular dominance of visual cortical cells under similar circumstances.7. Although the recovery in these animals can be accounted for by the simple notion of a competitive interaction between the two eyes, the recovery observed in animals that had both eyes open after the initial period of deprivation cannot be so readily explained. Evidently there must be an additional non-competitive mechanism of recovery.

Age Factors