Biomedical subjects

L D Beazley

Publications and source records attributed to L D Beazley.

At least 37 records · Page 2Linked to original sources

PubMed1999

Effect of corticosteroids on brain growth in fetal sheep.

OBJECTIVE: To compare the effects of single and repeated courses of corticosteroids on brain growth in fetal sheep. METHODS: Pregnant sheep were given intramuscular betamethasone (0.5 mg/kg) at 104 days' gestation followed at 111, 118, and 124 days by equivalent volumes of sterile normal saline (n = 12) or betamethasone (n = 12). Controls received equivalent volumes of sterile normal saline at all four intervals (n = 12). Lambs were delivered at 125 (preterm) or 145 (term) days. After perfusion, we measured weights (grams) for whole brain, cerebrum, cerebellum, and brain stem, volumes (milliliters) for whole brain and cerebrum, and maximum cerebral anterior-posterior length, width, and depth (centimeters). RESULTS: In the single-injection group at preterm, there were no significant differences (P = .070) in whole-brain weight between the corticosteroid-treated animals (38.0 +/- 1.81 g) and controls (42.5 +/- 1.65 g). Cerebral length and depth were significantly reduced in the corticosteroid group (P < .05); other measures were not significantly different. At term, whole-brain weight was significantly lower (47.5 +/- 1.70 g; P = .022) compared with controls (53.4 +/- 1.73 g). All other measures were significantly reduced (P < .05) except cerebral and brain-stem weights and cerebral length. In the group that received repeated injections at preterm, whole-brain weight was significantly reduced (35.5 +/- 1.65 g; P = .005) compared with controls (42.5 +/- 1.65 g). All other measures were significantly reduced (P < .05) except cerebellar and brain-stem weights. At term, whole-brain weight was also significantly reduced (42.4 +/- 1.52 g; P = .001) compared with controls (53.4 +/- 1.73 g) as were all other measures (P < .05). CONCLUSION: Administration of single and repeated courses of corticosteroids to pregnant sheep retarded fetal brain growth.

Animals↗

PubMed1999

Retinal structure and visual acuity in a polyprotodont marsupial, the fat-tailed dunnart (Sminthopsis crassicaudata).

The visual system of the fat-tailed dunnart (Sminthopsis crassicaudata), a small polyprotodont marsupial, has been examined both anatomically and behaviourally. The ganglion cell layer was examined in cresyl-violet stained wholemounts and found to contain a mean of 81,400 ganglion cells (SD +/- 3,360); the identification of ganglion cells was supported by a correspondence to optic axon counts. Ganglion cells were distributed as a mid-temporally situated area centralis, embedded in a pronounced visual streak. Localised implants of horseradish peroxidase into retinal wholemounts revealed both A-type and B-type horizontal cells. Sections of the outer retina showed it to be rod-dominated, with a rod-to-cone ratio of 40:1 at the area centralis; cones were found to contain oil droplets but double cones were not a prominent feature. The retinal pigment epithelium consisted of squamous cells. Visual acuity, estimated from counts of peak ganglion cell density (8,300/mm2, SD +/- 1,180) and measurements of posterior nodal distance (2.9 mm), was found to be 2.30 cycles per degree. The value was close to that of 2.36 cycles per degree estimated by behavioural tests using a Mitchell jumping stand; values were similar at low, intermediate and high light levels. Our findings are discussed in relation to the lifestyle of the dunnart.

Animals↗

PubMed1998

Anatomical comparison of the macaque and marsupial visual cortex: common features that may reflect retention of essential cortical elements.

This study identifies fundamental anatomical features of primary visual cortex, area V1 of macaque monkey cerebral cortex, i.e., features that are present in area V1 of phylogenetically distant mammals of quite different lifestyle and features that are common to other regions of cortex. We compared anatomical constituents of macaque V1 with V1 of members of the two principal marsupial lines, the dunnart and the quokka, that diverged from the eutherian mammalian line over 135 million years ago. Features of V1 common to both macaque and marsupials were then compared with anatomical features we have previously described for macaque prefrontal cortex. Despite large differences in overall area and thickness of V1 cortex between these animals, the absolute size of pyramidal neurons is remarkably similar, as are their specific dendritic branch patterns and patterns of distribution of intrinsic axons. Pyramidal neuron patchy connections exist in the supragranular V1 in both the marsupial quokka and macaque as well as in macaque prefrontal cortex. Several specific types of aspinous interneurons are common to area V1 in both marsupial and macaque and are also present in macaque prefrontal cortex. Spiny stellate cells are a common feature of the thalamic-recipient, mid-depth lamina 4 of V1 in all three species. Because these similarities exist despite the very different lifestyles and evolutionary histories of the animals compared, this finding argues for a highly conserved framework of cellular detail in macaque primary visual cortex rather than convergent evolution of these features.

Anatomy, Artistic↗

PubMed1998

An in vitro technique for electrophysiological mapping of reptilian retinotectal projections.

An in vitro procedure is described for electrophysiological mapping of the retinotectal projections using an eye-cup and brain stem preparation which remains viable for up to 30 h. The technique has been found to be successful in turtles and lizards and may be useful for other species in which metabolism is greatly depressed by low temperatures. There are several advantages over in vivo recording, including the longevity and stability of the preparation, an absence of confounding anaesthetic effects and the ability to record from the retina as well as from the brain. The technique offers opportunities to introduce pharmacological agents via the perfusate or to conduct anatomical tracing studies coincident with electrophysiological recording.

Animals↗

PubMed1998

Axon order in the visual pathway of the quokka wallaby.

Axon order throughout the visual pathway of the quokka wallaby (Setonix brachyurus) was determined after localised retinal applications of the tracers DiI and/or DiASP. Postnatal days (P) 22-90 were studied to encompass the development and refinement of retinal projections. Order was essentially similar at all stages. Axons entered the optic nerve head true to their sector of retinal origin. In the optic nerve, nasal and temporal axons continued to reflect their retinal origin, dominating, respectively, the medial and lateral halves. By contrast, dorsal and ventral axons exchanged locations between the retrobulbar level and one-third the distance along the nerve; thus, the inversion of the dorsoventral retinal axis, imposed by the lens, was corrected. Decussating axons maintained their relative locations through the chiasm. At the base of the optic tract, nasal and temporal axons underwent an axial rotation to lie on the medial and lateral sides, respectively; thus nasal overlapped with ventral axons and temporal with dorsal axons. Axons maintained their alignments throughout the tract, and as a result, nasal and ventral axons invaded the superior colliculus medially, whereas temporal and dorsal axons invaded laterally. Each retinal quadrant terminated preferentially in its retinotopically appropriate sector of the colliculus. The arrangement of axons in the quokka visual pathway displays several novel features. Axon order is distinct throughout, involving a well-demarcated exchange of dorsal and ventral axons in the nerve and an axial rotation of nasal and temporal axons at the base of the tract; these relocations suggest decision regions for growing axons. The organisation presumably underlies the less extensive searching within the developing superior colliculus to generate retinotopic maps in the quokka and also in tammar wallaby [Marotte, J. Comp Neurol. 293:524-539, 1990] than in the rat [Simon and O'Leary, J. Neurosci. 12:1212-1232, 1992].

Animals↗

PubMed1998

The primary visual system of adult lizards demonstrates that neurogenesis is not obligatorily linked to central nerve regeneration but may be a prerequisite for the restoration of maps in the brain.

Following optic nerve crush in the adult lizard Ctenophorus ornatus, most retinal ganglion cells regrow their axons into visual brain centres: however, the regenerated projections lack retinotopic order and the animals are blind via the experimental eye. Here we have used 3H-thymidine autoradiography to demonstrate that cell division is no longer taking place in the retina of normal adult lizards. We conclude that the optic nerve can regenerate in lizard even though cells are no longer being added to the retina. However, continued retinal neurogenesis may be linked to the ability to restore topographic maps.

Age Factors↗

PubMed1998

Fetal growth retardation, particularly within lymphoid organs, following repeated maternal injections of betamethasone in sheep.

OBJECTIVE: To examine the effect of single or repeated injections of maternally administered corticosteroids on fetal growth in sheep. METHODS: Forty-six date-mated singleton gestation ewes were allocated at random to one of 3 groups: a single, or repeated injections of betamethasone, or a control group which received saline. On days 125 (preterm) or 145 (term) caesarean section delivery was performed. After lambs were killed, measures of size and weight were recorded. Data were analysed using Fishers Exact test and the Student's t-test. RESULTS: Significant betamethasone dose dependent reductions in body and organ weights and biometry were found at preterm and term gestational ages (p < 0.05). There was little catch up growth in those in whom delivery was delayed until term. Thymus, spleen and liver were particularly targeted. CONCLUSION: Repeated injections of betamethasone to the pregnant ewe cause significant reductions in fetal growth with little evidence of catch up by term. The effect of repeated maternal injections of corticosteroids in human pregnancy will await the results of randomized controlled trails.

Animals↗

PubMed1998

Use of corticosteroids by Australian obstetricians--a survey of clinical practice.

All Fellows, Members and trainees of the Royal Australian College of Obstetricians and Gynaecologists resident in Australia (n= 1,281) received a questionnaire relating to their practice of prescribing antenatal corticosteroids. 833 (65%) responded. The key findings were that 97% of Australian obstetricians prescribe antenatal corticosteroids in the classical setting of uncomplicated early preterm labour and 85% prescribe repeated courses in those cases in which the risk of preterm birth persists or recurs; 50% of obstetricians prescribe this agent weekly in cases with persisting risk of preterm birth. Some of the prescribing practices were found to be related to the number of years since obtaining specialist qualification. In view of the widespread clinical use of repeated doses of corticosteroids revealed in this present survey, it is clear that further research is warranted to determine the possible benefits and hazards of repeated exposures of the developing fetus to this therapy.

Australia↗

PubMed1997

Development of primary visual projections occurs entirely postnatally in the fat-tailed dunnart, a marsupial mouse, Sminthopsis crassicaudata.

We have examined the development of retinal projections in a diminutive polyprotodont marsupial, the fat-tailed dunnart, Sminthopsis crassicaudata. Here, we document the most immature mammalian visual system at birth described to date. At postnatal day (P) 0, the retinal ganglion cell layer has yet to form, and axons have not entered the optic stalk. By P4, the retinal ganglion cell layer could be distinguished at the posterior pole, and the front of growing axons extended one-third the length of the optic stalk, a distance of approximately 150 microm; a few pioneer growth cones had grown beyond the main axon group but had still to reach the midline. Axons had decussated at the optic chiasm by P10 to penetrate the base of the contralateral optic tract and, by P15, had reached the dorsal lateral geniculate nucleus (dLGN), superior colliculus (SC), and accessory optic system (AOS); ipsilaterally projecting axons matured slightly later. From P20, axons had reached the caudal SC both contralaterally and ipsilaterally and terminated throughout the depth of the retinorecipient layers. After P30, the projections gradually refined. Within the rostral dLGN, segregation into four contralateral and four ipsilateral bands occurred by P50, approximately 5 days after eye opening. The projection to the ipsilateral SC underwent refinement by P50, becoming restricted to its rostral pole, and presented as discrete patches within the stratum opticum. At birth, the dunnart visual system is comparable to early to midembryonic stages [embryonic day (E) 12, E14, E19, E24, and E30, respectively] in the mouse, rat, ferret, cat, and monkey. The extreme immaturity of the neonatal dunnart together with the observation that the entire development of the primary optic pathway occurs postnatally over a protracted period make this marsupial especially valuable for investigating factors that control pathway formation in the early developing mammalian primary visual system.

Age Factors↗

PubMed1997

Optic nerve regenerates but does not restore topographic projections in the lizard Ctenophorus ornatus.

In adult fish and amphibians, the severed optic nerve regenerates and visual behaviour is restored. By contrast, optic axons do not regenerate in the more recently evolved birds and mammals. Here we have investigated optic nerve regeneration in a member of the class Reptilia, phylogenetically intermediate between the fish and amphibians and the birds and mammals. We assessed visual recovery anatomically and behaviourally one year after unilateral optic nerve crush in the adult ornate dragon lizard. Ctenophorus ornatus. Ganglion cell densities and numbers of axons in the optic nerve on either side of the crush site indicated that two-thirds of ganglion cells survived axotomy and regrew their axons. However, myelination fell from a mean of 21% in normals to 5.5% and 3%, proximal and distal to the crush, respectively. Anterograde labelling of the entire optic nerve showed that axons regenerated along essentially normal pathways and that the major projection, as in normals, was to the superficial one-third of the contralateral optic tectum. However, localised retinal injections indicated that regenerated projections lacked retinotopic order. Any one retinal region projected to the entire tectum. This feature presumably explains why the experimental lizards consistently appeared blind to stimuli via the regenerated nerve. Our findings indicate that although axons regenerate along essentially normal pathways in adult lizards, conditions within the visual centres do not allow regenerating optic axons to select appropriate central connections. In a wider context, the result suggests that the ability for regenerating central axons to form topographic maps may also have been lost in the more recently evolved vertebrate classes.

Animals↗

PubMed1997

Toluidine blue-O is a Nissl bright-field counterstain for lipophilic fluorescent tracers Di-ASP, DiI and DiO.

The stain toluidine blue-O (tol blue), applied to sections of neural tissue, is shown to be compatible with the vivid fluorescent lipophilic neural tracers 4-(4-dihexadecylaminostyryl)-N-methylpyridinium iodide (Di-ASP), 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO) and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). As with other Nissl stains, toluidine blue-O fluoresces in the red end of the spectrum but such fluorescence quenches upon binding with tissue. Moreover, progressive staining occurs at concentrations low enough to minimise any background fluorescence attributable to non-specific residence of the stain. The bright yellow Di-ASP and vivid green DiO signals are spectrally removed from the red fluorescence of toluidine blue-O. With toluidine blue-O counterstaining, Di-ASP generally offers contrast superior to that with DiI, however, the latter is improved by viewing in a polarised green bright field. Visible Di-ASP emission, although broad, peaks at a more film-sensitive region of the spectrum than that for DiI, thus reducing the photographic exposure required.

Animals↗

PubMed1997

Impaired vision for binocular tasks after unilateral optic nerve regeneration in the frog Litoria moorei.

Behavioural responses to objects in the binocular field were examined in frogs with one regenerate and one intact optic nerve. Data were compared to those for normal controls and for frogs with vision via one intact optic nerve. During prey acquisition, frogs with regenerated optic nerves underestimated the distance to the prey on their first strike; as a consequence, the regenerate series made several attempts to achieve a successful prey capture. By contrast, normal frogs and those using only one eye struck accurately at the prey and usually captured it on the first attempt. However, frogs using only one eye struck from a closer distance than either the regenerate or normal series. Frogs with regenerated optic nerves also made more errors than either of the other series when leaping through a set of closely spaced horizontally aligned rods. Our results show that prey capture and the negotiation of horizontally aligned rods is impaired in animals using one regenerated and one intact optic nerve as compared to both normal frogs and those using only one eye. We suggest that the poor visual performance for frogs with one regenerated and one intact optic nerve for tasks presented in the binocular field is related to the integration of a degraded and a normal image within the visual centres.

Animals↗

PubMed1997

Changing patterns of vasculature in the developing amphibian retina.

Patterns of vascularisation were examined in whole-mounted retinae from tadpole stages to adulthood in the tree frog Litoria moorei using perfusion with Indian ink. Changing cell densities in the underlying ganglion cell layer were studied in a parallel Cresyl-stained series. Throughout development, the vasculature was pan-retinal and the hyaloid vessel was prominent. In early tadpole stages, capillaries were arranged as a honeycomb, and their number increased at a rate sufficient to maintain high densities in the face of increasing retinal area; major arteries and veins condensed within the capillary network. By early post-metamorphic life, the retinal vasculature was remodelled by the loss of four-fifths of the capillaries; the reduction in their density was far greater than could be accounted for by continuing retinal growth. This loss resulted in a change from the honeycomb appearance to one with largely parallel vessels linked by fewer connecting ones, an arrangement that became increasingly pronounced. In post-metamorphic life, the number of branch points increased such that their density decreased only slightly in the face of considerable increases in retinal area. The density of branch points varied across the retina and changed with age. Initially, the vasculature was most dense centrally, but by mid-larval life densities were highest in two patches located in the mid-temporal and mid-nasal retina. Thereafter, the vasculature increasingly assumed gradients resembling an area centralis and visual streak, a profile that survived the vascular remodelling. The development of density gradients in the vasculature preceded that of cells in the ganglion cell layer, the latter appearing only following metamorphosis. However, in post-metamorphic life, the topographies of the retinal vasculature and cells in the ganglion cell layer were closely related.

Animals↗

PubMed1996

Genesis of the frog retinal pigment epithelium.

To examine cell generation in the frog retinal pigment epithelium (RPE), representative developmental stages from tail-bud to adulthood received a single injection of [3H]thymidine. Animals were killed either 24 h or several weeks later; eyes were sectioned and processed by standard autoradiographic procedures and viewed by epi-polarised illumination. The distribution of [3H]thymidine-labelled cells indicated that the RPE is formed throughout life, including in adulthood, by cell addition at the ciliary margin, matching the pattern for the neural retina. In addition, a very small number of peripapillary RPE cells underwent division but only in the adult.

Animals↗

PubMed1996

Retinal pigment epithelium and photoreceptor maturation in a wallaby, the quokka.

Cell generation and the early stages of maturation of the retinal pigment epithelium (RPE) and photoreceptors were examined in a marsupial, the quokka, Setonix brachyurus. Results are presented for animals aged up to postnatal day (P)250. RPE cell generation was studied by analysis of cell number from wholemounted retinae and by tritiated thymidine (3HThy) autoradiography in sectioned material. For 3HThy autoradiography, quokkas aged P1-P200 were injected with 3HThy and killed either 6-20 hours later (pulse-kill) or at P100 or P250 (pulse-leave). The extent of pigmentation of the RPE sheet was examined from sections of embryonic and early postnatal stages. Retinae from animals aged P5 to P160 were also examined at the electron microscope. By P100, RPE cell number is within the range found in adults. New RPE cells are generated in a peripheral band which moves outwards as cells leave the cell cycle in more central locations. RPE cells thus complete their last cell division in a centre-to-periphery wave centred about the optic nerve head. At any given retinal location, RPE cells complete their last cell division earlier than the overlying layers of the neural retina. Cells of the RPE rapidly develop a mature morphology. For example, melanin granules are observed at P5 and Verhoeff's membrane (the terminal bar complex) is evident by P25. By contrast, photoreceptor development in this species is protracted; cone inner segments are observed by P40, whilst the first rod inner segments are observed at P60. Despite being generated earlier, morphological maturation of the cones appears retarded and prolonged compared with that of the rods. The last stages of RPE cell maturation occur late in development, in synchrony with the generation of rods.

Animals↗

PubMed1996

Retinal pigment epithelium topography in the mature quokka, Setonix brachyurus.

In this paper we describe cell topography of the retinal pigment epithelium (RPE) for the mature marsupial wallaby, the quokka, Setonix brachyurus. RPE topography was analysed in bleached and stained whole mounted retinae, sampling from the entire surface area. The mature adult quokka RPE has a distinct topography in terms of both cell density and the distribution of multinucleate cells. Peripheral RPE demonstrates the lowest cell density and the greatest proportion of multinucleate cells. In an annulus surrounding central retina, corresponding to equatorial retina, RPE cell density is relatively high and multinucleate cells are at the lowest frequency. Cell density is highest in central temporal retina, in the regions adjacent to some of the highest densities in the neural retina. Other regions of central retina exhibit moderate cell densities. A small proportion of central cells are multinucleate. The RPE topography may result from, or account for, regional differences in susceptibility of this tissue to environmental influences and stressors. Understanding of this topography may throw light on the marked localization of certain human retinal diseases inherent to this tissue.

Animals↗

PubMed1996

Development and ageing of the RPE in a marsupial, the quokka.

We have previously shown that the mature adult quokka, aged between 8 and 15 years, has a distinct cell topography in the retinal pigment epithelium (RPE). We reported that the adult cell densities were high in central temporal retina and low in a peripheral band, adjacent to the ora serrata, a region with a concentration of multinucleate cells. In the present paper, we have studied the development of these features in order to understand how they mature, as well as to gain insight into regional specializations of the RPE. Retinal area, cell density and the extent of multinucleation were analysed using whole-mounted retinae from animals aged post-natal day (P) 2 to 15. The retina continues to grow in area throughout life, however, RPE cell number does not change. The features of the mature adult RPE develop at different times over the entire lifespan of the animal. In peripheral retina, cell density decreases throughout life and the band of low cell density becomes progressively wider and more distinct with age with an increasing proportion of multinucleate cells. By contrast, RPE cell density in equatorial retina remains, throughout life, at the level observed in 1-year-old animals. A specialization of high cell density in temporal central RPE was discernible in animals older than 2 years, with the cell density of this region increasing steadily beyond this age. Central regions of other quadrants demonstrate a constant and relatively uniform density with age. The RPE in the marsupial quokka is a dynamic tissue, demonstrating topographic changes throughout life.

Aging↗

PubMed1996

Segregation of optic input in a three-eyed mammal.

Using a marsupial mouse, we have transplanted additional eye primordia to the midbrain at stages before host visual centers are normally innervated; transplant or host projections were later traced. In contrast to the normally continuous crossed retinocollicular input, both transplant and host projections were arranged as rostrocaudally aligned stripes or as discrete patches. We propose that competitive interactions between transplant and host axons have induced the discontinuous input.

Afferent Pathways↗