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Biomedical subjects

M A Edwards

Publications and source records attributed to M A Edwards.

At least 37 records · Page 2Linked to original sources
PubMed1986

Development of cell and fiber lamination in the mouse superior colliculus.

The emergence of laminar organization in the superior colliculus was investigated in the mouse with several anatomical methods, including tritiated-thymidine autoradiography, Golgi impregnation, and general stains for cell bodies and for fibers. The sequence of neurogenesis, cell migration, and early morphological differentiation of neurons was shown to exhibit a discontinuity between the lower and upper divisions (i.e., between the deep and intermediate "gray" and "white" layers and the superficial "gray" and "white" layers). These events proceed in an inside-out order within the lower division, but the same events within the upper division commence in advance of the completion of this progression. Thus, peak generation times for layers of the lower division proceed from (embryonic day) E11 to E13 and for the upper division from E12 to E13. Cell migration, as monitored with tritiated-thymidine labelling, reflects closely the pattern of cytogenesis. This is most clearly evident on E15 when a population of E11-labelled cells is divided into superficial and deep layers (the strata superficiale and profundum--SS and SP) by the interposition of E13-labelled cells at an intermediate level (stratum intermedium--SI). A contingent of the latter cells continue their migration and join their predecessors within the SS on E17, a time point when cell migrations are largely complete. Paralleling this sequence of arrival of neurons and the formation of three primary layers, both the time course of accumulation of fiber fascicles and the early morphological differentiation of neurons in the interval from E13 to E17 tends to proceed from SP to SS and from SS to SI. Thus, the transverse fiber system and large multipolar neurons of SP develop in advance of the longitudinal fiber system and vertically oriented neurons of SS, which in turn develop precociously with respect to the longitudinal fibers and medium-sized multipolar neurons of SI. In contrast, later events of differentiation that underly a major radial growth and an architectonic sublamination of the primary strata proceed in a simpler inside-out sequence from E17 to (postnatal day) P6. The major morphogenetic events underlying the establishment of statification in the colliculus appear to involve the operation of relatively independent programs of assembly for the two basic subdivisions. It is probable that selective cell-cell interactions contribute to the delivery of concurrently generated neurons to different laminae as well as to the deployment of axons in a manner that respects laminar boundaries.

Animals↗
PubMed1986

Development of the crossed retinocollicular projection in the mouse.

Changes in the distribution of axons of the crossed retinal projection within the superior colliculus of the developing mouse were studied by means of normal fiber and Golgi impregnations and by anterograde horseradish peroxidase labelling. Retinal axons advance along the optic tract from gestational days E12 to E14 and first invade the superior colliculus on E15. Over the subsequent days until birth (E19), the retinal axons extend within rostrocaudally oriented fascicles that distribute through the full thickness of the uppermost collicular layer, the stratum superficiale (SS). A dramatic transformation of this fiber stratification pattern into the mature pattern occurs over the first postnatal week. The fiber bundles are progressively cleared from the upper half of SS, identified as the future stratum griseum superficiale (SGS). Concurrently, the fiber bundles in the deep SS, identified as the stratum opticum (SO), give rise to individual, nonfasciculated fibers, which arborize within SGS. The contralateral retinal origin of the transient population of axons in SGS as well as the majority of axons that persist in SO is evident from the observation that they degenerate following neonatal enucleation. The number of fiber bundles lost is estimated to be 40-50% of the total population present in the superficial layers at birth. The combined set of observations indicates that axon elimination plays a major role in shaping the laminar pattern of retinal innervation of the colliculus. Retinal ganglion cell death, and not axon pruning, is proposed as the most probable mechanism by which axon fascicles are eliminated from SGS.

Animals↗
PubMed1986

Retinotectal projection in reeler mutant mice: relationships among axon trajectories, arborization patterns and cytoarchitecture.

The distribution of axons in the midbrain and thalamus of homozygous reeler mutant mice is anomalous. The cytoarchitecture of these regions is normal. In the normal mouse SC there is a distinct SO in which fascicles of retinotectal axons pass caudally before terminating in the overlying SGS. In reeler, by contrast, fascicles of retinotectal axons are distributed through the entire thickness of SGS as well as through SO. There are also abnormalities of fiber pattern in the thalamus, most notably in the region of the dorsal nucleus of the LGd. Retinotectal axon trajectory and patterns of terminal arborization in reeler and normal animals were compared by single-fiber HRP axonography. In normal mice, two distinct morphological classes of retinotectal axons form focal terminal arborizations at different radial levels in the superficial layers of the SC. Class U axons are of relatively small diameter and terminate in upper portions of SGS. Class L1 axons are of larger diameter and form terminal arbors which are confined to SO and deeper regions of SGS. Axons of both classes ascend to their terminal zones from parent axons which course through SO. Similarly, in reeler mice axons of both large and small diameter can be distinguished. However, many axons of both classes pass caudally in anomalous fascicles distributed through the full thickness of SGS and descend to terminate. Other axons pass in normal fashion in SO and ascend to terminate in SGS. Regardless of their trajectories, the small axons terminate superficially in SGS while the thick axons terminate deeper in SGS and/or SO, as in normal mice. These findings suggest that the ingrowth of afferents and the formation of terminal arbors are regulated by different mechanisms and that fiber architecture and cytoarchitecture are regulated by different mechanisms. It is not known if the anomalous fiber pattern in reeler adults arises in development through a defect in initial patterns of axon fasciculation or from a failure of axon elimination.

Animals↗
PubMed1986

Diurnal change in refraction, corneal curvature, visual acuity, and intraocular pressure after radial keratotomy in the PERK Study.

Selected patients who complained of fluctuating visual acuity in the Prospective Evaluation of Radial Keratotomy (PERK) Study were examined before 8:00 a.m. and after 7:00 p.m. on the same day to determine diurnal change in uncorrected visual acuity, best corrected visual acuity, manifest refractive error, average central keratometric power, and intraocular pressure. Sixty-three operated eyes were examined at three months, while 46 operated and 40 unoperated contralateral eyes were examined at one year after radial keratotomy. One year after surgery, 42% of the operated eyes had an increase in minus power of the manifest refraction of 0.50 to 1.25 diopters, 26% of the eyes changed their uncorrected visual acuity by 2 to 4 Snellen lines, and 35% of the operated eyes showed central steepening of the cornea by 0.50 to 1.25 diopters. These changes in the operated eyes at one year were similar to the changes at three months. Minimal diurnal changes occurred in the unoperated eyes at one year. Only 11% of the unoperated eyes changed their manifest refraction by 0.50 to 1.00 diopters, none changed their uncorrected visual acuity by 2 to 4 Snellen lines, and only one of the unoperated eyes changed its central keratometric power by 0.50 diopters. This study documents that many patients who experience diurnal fluctuation of vision have steepening of the cornea and an increase in the minus power of their refraction during the day.

Biomechanical Phenomena↗
PubMed1985

Selective retinal reinnervation of a surgically created tectal island in goldfish. I. Light microscopic analysis.

Through anatomical and physiological studies of the regenerating retinotectal projection of goldfish, we sought to determine whether the establishment of a topographic projection is attained through a refinement of an initially less precise pattern of innervation. A 1-mm-wide mediolateral strip of caudal tectum was removed so that a small island of tectal tissue was spared at the caudal pole, and the contralateral nerve was either crushed (TIX) or left intact (TI). The presence of regenerated axons in the ablated zone and the reinnervation of the caudal island were assessed with anterograde and retrograde labeling methods in the following postoperative intervals: early, 20-50 days; middle, 50-110 days; and late, more than 170 days. The anterograde radioautographic method revealed that the appropriate layers of the tectal island became reinnervated by optic axons during the early period. During the middle and late periods, one to several large, discrete bundles bridging the lesion zone along the surface of exposed subtectal structures were readily identified both by radioautography and by anterograde or retrograde labeling following application of horseradish peroxidase to the transected optic nerve or tectal island, respectively. In contrast, the anterograde horseradish peroxidase method did not reveal axon bundles extending caudal to the half-tectum in the absence of a tectal island. Among TIX cases, retrograde horseradish peroxidase labeling of the contralateral nasal retina was more widespread in the middle period than in the late period, a result we interpret as reflecting an improvement in topographical precision with time. The area of retinal labeling among TIX cases in the late period was similar to that following caudal tectal injection in cases with simple nerve crush, although it was still elevated above normal control values. Physiological maps indicated a focal representation of the nasal retina in the tectal island in both periods and did not reveal a transient extreme convergence of retinal input. These findings are discussed in relation to Sperry's chemoaffinity theory.

Animals↗
PubMed1985

Selective retinal reinnervation of a surgically created tectal island in goldfish. II. Electron microscopic analysis.

In the preceding study (Edwards et al., '85), we showed that regenerating optic axons reestablish a topographically restricted projection to a caudal tectal island created by surgical removal of a 1-mm-wide strip of caudal tectum in goldfish. In the present ultrastructural study, we evaluated the dependence of this axonal outgrowth on the presence of tectal target tissue caudal to the gap. Axon counts in the lesion zone were compared between cases with complete caudal tectal ablation and cases with ablation sparing a caudal tectal island (with and without optic nerve crush). During the postoperative interval of 20-50 days (early period), up to about 1,000 unmyelinated axons with features characteristic of optic axons were present in numerous small subpial bundles in both preparations. In the subsequent interval of 50-110 days (middle period), less than 200 axons were counted caudal to simple half-tecta, whereas 4,000-14,000 myelinated and unmyelinated axons were present in a few large bundles which crossed the lesion zone of tectal island cases. In this period, optic terminals could be demonstrated in the tectal island using the anterograde horseradish peroxidase method. At 170-300 days after surgery (late period), bridging bundles contained between 2,000 and 6,000 largely myelinated axons. We conclude that caudal tectal tissue is not necessary for the initial outgrowth of a small number of axons beyond a rostral half-tectum. The target is essential, however, for the maintenance of these axon fascicles and for the subsequent massive outgrowth of axons to the island. The contributions of glial guidance, diffuse exploratory outgrowth, and target-produced trophic factors to the formation of an initially exuberant projection to the island are discussed. A process of selective axon collateral withdrawal is proposed to account for the decrease in axon numbers within bridging bundles in the late period and for the late restriction in the retinal origin of the island projection indicated by results in the preceding study (Edwards et al., '85).

Animals↗
PubMed1985

Glutaric aciduria type I misdiagnosed as Leigh's encephalopathy and cerebral palsy.

Two cases are reported of boys who suffer epileptic seizures only after playing video games. It is suggested that the amount of time the patient spends in front of the screen before the seizure is important, and also that video games trigger electrocortical activity far more efficiently than either television or intermittent photic stimulation.

Amino Acid Metabolism, Inborn Errors↗
PubMed1984

Effects of permeability of midtectal barriers in goldfish on compression of the visuotectal projection rostrally and regenerative escape caudally.

Physiological mapping and anatomical methods were used to evaluate changes in the retinotectal projection of goldfish 16-200 days after insertion of permeable or impermeable barriers that bisected the tectum into rostral and caudal halves. The projection to rostral tectum was left intact. Barriers composed of Gelfilm or impermeable Nucleopore material induced within 2-3 months an orderly compression of the visual field representation in rostral tectum only slightly less complete than that observed in animals with caudal half-tectal ablation. In contrast, Nucleopore filter barriers with 0.1-micron or 8-micron holes did not cause significant compression. According to both mapping and autoradiographic tracing, reinnervation of tectum behind the barriers occurred among all groups within 1-2 months. Physiologically, the projection caudal to permeable barriers was typically complete and appropriate, whereas the caudal projection in fish with impermeable barriers eventually consisted of a greatly expanded representation of the extreme temporal visual field. Autoradiography, normal fiber impregnations, and the orthograde horseradish peroxidase method revealed that regeneration past the barriers involved the formation of large bundles passing vertically along the cut tectal margin and through the underlying valvula cerebelli or lateral tegmentum. The simultaneous rostral compression and caudal expansion in the visual representation formed when more impermeable barriers were used provides evidence that, in addition to the influence of position-dependent properties, axonal competition for target territory contributes to the control of the distribution of optic arbors. Further research is required to determine why reinnervation of tectum caudal to the more permeable barriers was more complete with respect to visual representation.

Animals↗
PubMed1983

Complications of therapeutic apheresis, including a fatal case with pulmonary vascular occlusion.

A high incidence of anaphylactic reactions has been observed in patients undergoing therapeutic plasma exchange. In three of 22 patients who underwent multiple exchanges, urticaria, bronchospasm, and hypotension developed during a course of plasma exchange that responded to treatment with steroids, antihistamines, and epinephrine. Fatal pulmonary microvascular occlusion with platelets and granulocytes developed in an additional patient eight hours following an apheresis procedure involving albumin replacement. The mechanism for the latter complication is not known but did not appear to invoke complement activation. This unexpectedly high risk of potentially fatal complications must be considered when a course of therapeutic apheresis, particularly involving treatment of a chronic disease, is planned.

Adult↗
PubMed1982

A quantitative study of the reinnervation of the goldfish optic tectum following optic nerve crush.

Stereological and quantitative morphometric methods were used to study changes in the stratum fibrosum et griseum superficialis (SFGS), the major retinal target, in optic tectum of goldfish, during regeneration of the optic nerve. Orthograde transport of HRP by optic axons was used to characterize the retinal projection in SFGS. Profiles of HRP-labeled optic terminals contained rounded vesicles, contacted small dendrites, and were distributed uniformly throughout the area of SFGS sampled; labeling density estimates indicate that at least 37% of the total terminal population in SFGS is retinal in origin. Partial denervation of the tectum by optic nerve crush is accompanied by a loss of 40% of the total terminal population in SFGS and by a marked decrease of SFGS thickness. Entry of massive numbers of regenerating optic axons into SFGS begins about 3 weeks postoperatively, about the time that some visual function recovers and produces a marked increase in SFGS thickness which persists for several months postoperatively. The area occupied by regenerating axons and the number of terminals in the tectum only approach preoperative levels 3 months postoperatively. The recovery of normal synaptic number is therefore delayed several months beyond the time of entry of regenerative axonal sprouts. The results indicate that return of synaptic number to normal is temporally associated with the reduction of the excess number of regenerating optic axons and that both these processes are prolonged.

Animals↗
PubMed1982

Target regulation of synaptic number in the compressed retinotectal projection of goldfish.

In order to determine the morphological consequences of the formation of a compressed retinotectal projection, the optic neuropil lamina (stratum fibrosum et griseum superficialis, SFGS) was examined in large goldfish 3 months to 4 years after ablation of the caudal half of the tectum both with crush of the optic nerve (HTX) without (HT). In semithin sections, the SFGS, as delineated with orthograde HRP labeling, shows a persistent hypertrophy of about 25% in HTX and HT groups. Comparison of ultrastructural stereological data with similar data on control and regenerated projections to intact tecta (Murray and Edwards, '82) indicated that this hypertrophy can be attributed largely to an increased number of axons and not to increases in terminal or dendritic compartments. A normal number of synaptic terminals per column through SFGS is conserved in HTX and HT groups. Planimetric analysis and observations using orthograde HRP labeling reveal no group differences in size and shape of terminal profiles. The same number of retinal ganglion cells project to a half-tectum as to an intact tectum, as indicated by estimates of ganglion cell number and of the minimum percentage of them which project to the tectum using retrograde HRP labeling. The results suggest that the regenerating and sprouting optic axons participating in the formation of a compressed retinotopic projection compete for a limited accommodation inthe SFGS and that this capacity to accept synaptic input becomes saturated at the control innervation density. The results are consistent with the formation of a smaller than normal number of terminals per optic axon, numerical estimates for which are given. If the percentage of terminals which are optic does not change, then the number of terminals per axon is reduced by about 40%.

Animals↗
PubMed1978

Cobalt staining of Actinia equina nematocysts.

Nematocysts of Actinia equina are stained black by incubation in 2% CoCl2 followed by an aqueous wash and H2S treatment. They are also stained positively by morin. Nematocysts isolated from the acrorhage were found to have a high concentration of calcium of which only 30% was "free." It is suggested that the high concentration of calcium in the nematocysts accounts for their staining by cobalt and morin. Cobalt staining offers a simple and effective technique for investigation of nemotocysts.

Animals↗