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Biomedical subjects

M W Quick

Publications and source records attributed to M W Quick.

44 records · Page 3Linked to original sources

Regions of beta 4.beta 2 subunit chimeras that contribute to the agonist selectivity of neuronal nicotinic receptors.

Fifteen chimeric nicotinic receptor beta subunits were constructed consisting of N-terminal neuronal beta 4 sequences and C-terminal beta 2 sequences. Responses to cytisine, nicotine, or tetramethylammonium were compared to acetylcholine responses for these subunits expressed in Xenopus oocytes with alpha 3 subunits. The results show that (i) two residues in the extracellular domain of chimeric beta 4.beta 2 subunits (108 beta 2F/beta 4V, 110 beta 2S/beta 4T) account for much of the relative cytisine sensitivity; and (ii) four extracellular residues of chimeric beta 4.beta 2 subunits (112 beta 2A/beta 4V, 113 beta 2V/beta 4I and 115 beta 2S/beta 4R, 116 beta 2Y/beta 4S) account for most of the relative tetramethylammonium sensitivity. The data did not permit localization of nicotine sensitivity to any particular region.

Acetylcholine↗

Natural strabismus in monkeys. Convergence errors assessed by cover test and photographic methods.

A standard set of clinical prism and cover tests and a recently developed photographic method were used to assess binocular alignment in ten monkeys that previously were determined to have a naturally occurring infantile strabismus. Extensive measurements of the alignment state were made for fixation attempts throughout the field of gaze. Patterns of alignment errors were examined in an attempt to compared the strabismus found in individual monkeys with common syndromes of human infantile strabismus. Two monkeys showed patterns consistent with the syndrome of essential infantile esotropia. Five monkeys had patterns consistent with accommodative esotropia. One monkey that had bilateral anterior chamber hemorrhage at birth had a constant-angle esotropia. One monkey that previously had been shown to have a large-angle esotropia during development exhibited only exophoria, and in a final monkey in which large-angle esotropia was found during development, the strabismus had resolved. These results demonstrate that naturally occurring strabismus in monkeys might be related to syndromes seen in children. In addition, they provide extensive information about other characteristics of strabismus that have not been examined previously. These include a characterization of the magnitude of the misalignment in terms of error surface plots of bias and a detailed analysis of scatter in the measurements that show coupling relationships between the two eyes.

Animals↗

A photographic technique for measuring horizontal and vertical eye alignment throughout the field of gaze.

We present a photographic method based upon corneal light reflections for the measurement of binocular misalignment. Our procedures allow for the measurement of eye alignment errors to fixation targets presented at any distance throughout the subject's field of gaze, and allow for the measurement of errors in the horizontal and vertical directions. Furthermore, estimates of the alignment state can be made simultaneously from both eyes while fixation targets are presented monocularly or binocularly. This photographic method represents an enhancement of typical clinical prism and cover methods because: (1) it can provide extensive information efficiently about patterns of misalignment across a large number of fixation locations; (2) it also can provide information about the scatter in addition to the magnitude of convergence error; and (3) it can be easily applied to noncooperative subjects such as animals and young children. Furthermore, the procedure requires relatively inexpensive equipment and technical expertise that are readily available in most clinical or animal research laboratory settings. The method is validated by comparing the results obtained photographically to standard prism and cover assessments of macaque monkeys with strabismus. This comparison demonstrates that results obtained by the two methods are in good agreement and that the degree of accuracy is similar for the two methods. An estimate of the angle of deviation based on 10 photographs has a 95% confidence interval of about two degrees.

Animals↗

Accessory lateral rectus orbital geometry in normal and naturally strabismic monkeys.

We conducted anatomic dissections of macaque monkey orbits and made a quantitative assessment of the orbital geometry of the accessory lateral rectus muscle. Our results show that the expected effect of this muscle on rotations of the globe is to produce elevation and abduction. The abducting component could counteract nasal drifts, and thus our findings provide support for the hypothesis that this muscle could render monkeys resistant to the development of esodeviations. Dissections of the orbits from two naturally esotropic monkeys also are consistent with this hypothesis. The accessory lateral rectus muscle was absent in one of them and abnormally small in the other. Humans do not have an accessory lateral rectus muscle, and we speculate that the high prevalence of esodeviations in humans may be related to an evolutionary loss of this muscle system.

Animals↗

Early abnormal visual experience induces strabismus in infant monkeys.

We measured ocular alignment in the horizontal direction for 17 monkeys reared under deprivation paradigms that involved monocular defocus, monocular occlusion and optically corrected aphakia coupled with continuous or partial occlusion of the fellow eye. Alignment was measured at 3 and 7 months with a photographic corneal light reflex method. Results showed that a majority of the monkeys in each paradigm developed strabismus following deprivation rearing, the common factor being early abnormal visual experience. Results also indicated a trend in which many of the deviations seen at 3 months of age were exotropic while all of the animals with deviations at 7 months of age were esotropic. These results on deprivation-induced strabismus, which are the first reported in monkeys, are consistent with previous findings in cats and humans, providing further evidence that deprivation affects not only sensory, but motor systems as well. These findings provide evidence that infant monkeys are a good model for studies of the possible relationships between amblyopia and strabismus that are often noted in children with early visual deprivation. Furthermore, it raises the prospect that some of the findings in previous animal studies that have been attributed to the direct effects of deprivation may actually be secondary to the induced misalignment.

Animals↗

Measurement of binocular alignment in normal monkeys and in monkeys with strabismus.

Accurate assessment of ocular alignment in monkeys is difficult because typical clinical methods require extensive cooperation by the subject or provide only a rough estimate of the misalignment. Recently, Brodie derived a geometrical model for determining the Hirschberg ratio in humans, and validated it photographically. In this study, we have applied these procedures in order to determine corresponding values for monkeys. We have found the average Hirschberg ratio for macaques to be approximately 14 degrees of rotation per millimeter corneal light reflex displacement. We extended the model to binocular viewing conditions, which allows for a description of the visual axes in Cartesian coordinates in relation to the head. Fixation errors, computed in terms of lateral and axial error vectors from intended fixation targets, were then determined for one normal monkey and for three monkeys that have a naturally occurring strabismus. Assessment of the fixation errors was made at several different distances and angles in the horizontal plane. The standard deviation for our measurements averaged 2.1 degrees. Our data indicate that measurements must be made at multiple locations throughout the visual field in order to accurately specify the pattern of misalignment. Finally, a procedure is demonstrated which specifies the misalignment in terms of a cyclopian eye, which is independent of the interocular separation.

Animals↗

Syntaxin 1A up-regulates GABA transporter expression by subcellular redistribution.

Neurotransmitter transporters are regulated through a variety of signal transduction mechanisms which appear to operate in order to maintain appropriate levels of transmitter in the synaptic cleft. One such mechanism is the trafficking of the transporter in association with synaptic vesicle release machinery. This report examines the specifics of trafficking regulation of the rat brain GABA transporter GAT1 by syntaxin 1A, a plasma membrane component of the SNARE complex which is involved in vesicle membrane fusion. In hippocampal neurons, botulinum neurotoxin 1C, which specifically cleaves syntaxin 1A, down-regulates plasma membrane GAT1 levels as assessed by surface biotinylation, suggesting that syntaxin 1A is a positive regulator of GAT1 surface expression. The up-regulation correlates with a decrease in intracellular GAT1 levels and is complete within several minutes. These data suggest that syntaxin 1A mediates the redistribution of GAT1 on a time scale important for the rapid regulation of extracellular GABA levels. Expression of different syntaxin 1A constructs in Xenopus oocytes suggests that several portions of the syntaxin 1A molecule are required for the trafficking of GAT1. These data suggest that the trafficking of GAT1 will be subject to regulatory control by the many molecules known to interact with various domains of syntaxin 1A.

Animals↗