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Biomedical subjects

M W Ferguson

Publications and source records attributed to M W Ferguson.

At least 127 records · Page 7Linked to original sources

Fracture repair of reptilian dermal bones: can reptiles form secondary cartilage?

The fracture repair of reptilian dermal bones has not previously been reported. Moreover, repair of fractured dermal bones in birds and mammals involves secondary chondrogenesis whereas that of amphibians does not. Therefore an investigation into the repair of fractured reptilian dermal bones could reveal the stage during vertebrate evolution at which the process of secondary chondrogenesis appeared. Experimental incisions were made in the parietal bones of seventeen lizards (3 species) and 2 snakes (1 species). These resulted in a fracture environment of limited vascularity and increased movement--two known stimuli of secondary chondrogenesis in birds and mammals. Re-epithelialisation was rapid and dead bony fragments quickly sequestered. The blood blot was quickly organised into connective tissue, the dural periostea proliferated, osteoblasts differentiated and bony union was effected after 18 days. The width of the fracture gap was the principal variable affecting the chronology of fracture repair. Secondary cartilage was not detected in any specimen, of any species, at any stage of the fracture repair. It therefore appears that the progenitor cells on reptilian dermal bones are not capable of forming secondary cartilage and that this tissue arose comparatively late in vertebrate evolution.

Animals↗

Experimental fusion of the naturally cleft, embryonic chick palate.

The palatal shelf medial edges of day 8 (Hamburger-Hamilton [HH] stages 32-33) and day 9 (HH stage 35) embryonic chicks were surgically disrupted in ovo and in vitro in an attempt to discover if the naturally cleft chick palate could be induced to fuse experimentally. At HH stages 32-33 (day 8) the chick palatal shelves were apart at the time of in ovo operation. Consequently, their medial edges did not fuse but rather underwent embryonic would healing with re-epithelialisation (which often formed needle track invaginations), but no signs of inflammation or scar or scab tissue formation. Conversely, at HH stage 35 (day 9) the palatal shelves are in contact at the time of in ovo operation and so underwent fusion. The extent of palatal fusion depended upon the extent of initial medial edge epithelial disruption. Fusion did not spread from the operated sites to adjacent unoperated areas, where the palatal shelves were in contact with each other. Occasional epithelial seams were formed, but these persisted and did not undergo cell death. There was no evidence of inflammation or scar or scab tissue at the operated sites. Abnormal bony and muscular blastemae appeared in the continuity zones of these experimentally intact chick palates. Mortality was high for embryos operated upon in ovo. Palatal shelves explanted from HH stages 32, 33, and 35 chick embryos and cultured in vitro with their medial edges in contact did not fuse unless their medial edge epithelia were surgically disrupted, in which cases fusion always occurred regardless of the stage of the explanted shelves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Differentiation of cultured palatal shelves from alligator, chick, and mouse embryos.

Palatal shelves from embryonic alligators, chicks, and mice were explanted at various stages of development and organ cultured in either chemically defined, serumless media or the same media supplemented with 10% fetal calf serum. Shelves from each vertebrate were either cultured singly or in contact, and heterologous combinations of palatal shelves from different animals were made: chick/mouse, chick/alligator, and mouse/alligator. Epithelial differentiation (particularly that of the medial shelf edge) was assayed by vital staining, histology, and scanning electron microscopy. In vitro medial edge epithelial differentiation, and consequently the mechanisms of palatal closure, were identical to those normally seen in vivo for each species, i.e., cobble-stoned migrating epithelia in the alligator, cell death and fusion in the mouse, and keratinisation and cleft palate in the chick. Differentiation was optimal in the chemically defined, serumless media and was independent of shelf contact in all three species. No heterologous combinations of palatal shelves closed with each other: Evidently, the modes of palatal closure in mice and alligators are sufficiently different to prevent them forming a chimeric palate, whilst neither is capable of inducing closure in a cocultured chick palatal shelf. These unified defined culture conditions make possible a large number of epithelial-mesenchymal recombination studies as well as specific inhibitor, teratogenic, and hormonal investigations.

Alligators and Crocodiles↗

The effects of mesencephalic neural crest cell extirpation on the development of chicken embryos.

The mesencephalic neural crest cells of Hamburger-Hamilton Stage 9-Stage 11 chick embryos were surgically extirpated unilaterally in 148 embryos and bilaterally in 8 embryos. Sham operations were performed unilaterally on 16 control embryos and bilaterally on one control embryo. Embryos were fixed at various time intervals after operation, studied macroscopically, and by light and scanning electron microscopy, and their development compared with that of 47 normal embryos. The extirpated mesencephalic region was repopulated by crest cells within 6-8 hours after operation. These 'new' crest cells migrated from adjacent neuraxial levels (principally the metencephalon and prosencephalon) along the basement membrane of the neural tube and the regenerating ectoderm. At prosencephalic and metencephalic levels, both intrinsic hyperplasia of migrating cells and prolonged migration of crest cells from the dorsomedian part of the neural tube contributed the additional cells required to repopulate the mesencephalic region. Morphogenesis and differentiation of all crest cell derivatives were normal and craniofacial malformations were absent. Thus the neural crest and neural tube can compensate for an extensive regional loss, premigratory crest cells are neither regionally patterned nor determined (as prosencephalic and metencephalic cells give rise to normal mesencephalic derivatives) and regional failure of crest cell formation is an unlikely facial pathogenetic mechanism. Previous workers who observed facial malformations following crest cell extirpations performed the latter by removing the lips of the neural tube which not only removed the crest cells but also the compensatory mechanism. Cervical scoliosis was observed in extirpated embryos but not in controls. The pathogenesis of this scoliosis may be related to the process of compensation, which could disturb the sequential differentiation of the neural tube and so disorganise the mechanisms of normal axial flexion. These observations may be relevant to the pathogenesis of some forms of congenital and infantile idiopathic scoliosis; such scoliosis in man is frequently present in neurofibromatosis--a neural crest lesion.

Animals↗

Developmental mechanisms in normal and abnormal palate formation with particular reference to the aetiology, pathogenesis and prevention of cleft palate.

Palatal development was studied macroscopically, microscopically and ultrastructurally in foetuses of inbred Wistar rats and Alligator mississippiensis. In the rat, elevation of the palatal shelves from a vertical position lateral to the tongue to a horizontal position above the tongue, occurs very rapidly. This reorientation is postulated to be caused by an intrinsic turgor shelf force generated by the hydration of mesenchymal mucopolysaccharides (predominantly hyaluronic acid). Cleft palate was induced in rat foetuses using 5-fluoro-2-desoxyuridine and was associated with greatly decreased mucopolysaccharide synthesis. The alligator is the only animal which develops in an external egg and which possesses a true mammal-like secondary palate: it is therefore a useful animal model system because longitudinal studies and direct surgical and pharmacological manipulations can be performed. The palatal shelves of alligators grow horizontally above the dorsum of the tongue from their first appearance. This de novo horizontal shelf growth is associated with an increase amount of space in the alligator oronasal cavity due to the small, fatty, alligator tongue. It is postulated that the evolution of the large muscular mammalian tongue constrains the palatal shelves to grow vertically until sufficient space can be created to form the common nasal passage simultaneous with shelf elevation.

Alligators and Crocodiles↗

Review: the value of the American alligator (Alligator mississippiensis) as a model for research in craniofacial development.

American alligators exhibit a number of morphological features which are more characteristic of mammals than reptiles. This unique combination makes an extremely useful animal for experimental investigations of craniofacial development. Thus, it is possible to make a longitudinal study of the development of the alligator's secondary palate by utilizing shell-less culture techniques. Incubation of eggs at 28 degrees C, as opposed to 3 degrees C, slows development sufficiently to enable both the recovery of critical intermediate stages, and also great precision in the timing of teratogen administration. Injection of either 0.01 mg of 5-fluoro-2-desoxyuridine or 0.05 mg of hydrocortisone into the yolks of Days 12, 14, and 17 embryos produces cleft lip, cleft lip and palate, and cleft palate, respectively. Application of the teratogen at critical developmental stages on Day 12 reliably induces unilateral cleft lip on either the right or left sides, while injection on Day 10 yields embryos with normal lips and palates but virtually no lower jaw. The spontaneous malformation rate is very low, but highest in eggs laid by young and old animals. Changes in eggshell banding provide a noninvasive method for monitoring embryonic development. Detailed comparisons of palatal development in birds and alligators permit an accurate phylogenetic study of physiological clefting in the aves. The alligator dentition is readily amenable to experimental studies.

Abnormalities, Drug-Induced↗

Turricephaly.

An unusual case of uncomplicated turricephaly is reported, in which all the cranial sutures were prematurely fused from birth. Nevertheless, the skull underwent growth by surface deposition and resorption leaving the patient remarkably free from any neurological signs or symptoms. A review of previous cases is given and the possible etiology and pathogenesis of the disorder are discussed. Attention is drawn to the need for more relevant experimental and clinical data on the etiology and pathogenesis of craniosynostosis.

Adolescent↗

The american alligator (Alligator mississipiensis): a new model for investigating developmental mechanisms in normal and abnormal palate formation.

Despite numerous investigations, there are still many unsolved problems concerning normal and abnormal palatal development. The American Alligator is here put forward as a new model for the investigation of a variety of developmental phenomena associated with palatogenesis. The structure of the palate of the adult Alligator is reported. This animal exhibits a unique combination of reptilian and mammalian features in its craniofacial anatomy and so its craniofacial development should be of considerable interest.

Alligators and Crocodiles↗

An unusual case of acquired unilateral condylar hypoplasia.

A case is described of acquired unilateral condylar hypoplasia, in which the right condyle seemed to have been fractured at an early age. There is evidence to suggest that the unresorbed condylar remnant persisted in the glenoid fossa and that a new condylar head had developed anterior to the articular emminence. This 'new head' showed a carrot-shaped radiolucent wedge suggestive of the condylar growth cartilage and, clinically, exhibited some growth potential. A complex composite odontome present in place of the mandibular right third molar may also have been caused by this early trauma.

Child↗

The teratogenic effects of 5-fluoro-2-desoxyuridine (F.U.D.R.) on the Wistar rat fetus with particular reference to cleft palate.

The teratogenic effects of 5-fluoro-2-desoxyuridine on Wistar rat fetuses were studied macroscopically, microscopically and ultrastructurally. In no case did palatal shelf elevation occur, and a palatal shelf elevating force could not be demonstrated in freshly-removed fetuses. The shelves, like the connective tissues generally, showed clear evidence of depressed mucopolysaccharide synthesis. The shelves eventually ossified in the vertical position, and in some cases their free edges fused with the lateral wall of the oral cavity (palato-oral fusion). The results were consistent with the mucopolysaccharide-turgor hypothesis advanced by the author in a previous paper to account for normal shelf elevation. Phocomelia, brain and limb bud haemorrhages, gross subcutaneous oedema, hyperextension of the cranial base, fused vertebrae, detached epithelia, bizarre brain abnormalities (including some remarkable attempts at neural reconstitution) and growth and ossification of the mandible in the virtual absence of Meckel's cartilages were also noted in these fetuses.

Abnormalities, Drug-Induced↗

Palatal shelf elevation in the Wistar rat fetus.

Palatogenesis in the Wistar rat fetus was studied macroscopically, microscopically, ultrastructurally and experimentally between days 13 and 19. The developmental ages of the fetuses were calculated from the smear age of the litter adjusted for individual variations in crown-rump lengths. Palatal shelf elevation occurs at day 16.4 +/- 0.1. Experimentally induced shelf elevation in freshly delivered fetuses was sluggish at day 14, but by day 16.3 it occurred in less than 1 second. Both shelf elevation and shelf fusion begin anteriorly where the shelves show a marked convexity of their margins, and proceed posteriorly. The extreme posterior part of each shelf (future soft palate) is horizontal from the beginning. The matrix of the shelf mesenchyme (especially in the region of the anterior convexities) shows an increasing accumulation of mucopolysaccharides from day 14 to day 16.3 and becomes increasingly oedematous. The shelf attachment to the main maxillary process is progressively undercut by epithelial invagination, producing a fulcrum for shelf elevation. The maxillary and palatine osteogenic blastemata are present at the base of the shelf prior to elevation and rapidly invade the shelves after the event. The elevated palatal shelves fuse with the nasal septum anteriorly, but posteriorly the palate is not attached to the septum. The posterior septum at first has a free lower edge, but then it develops lateral flanges which fuse with corresponding bulges on the lateral nasal walls. In this way two sphenoethmoidal recesses are formed above the fused flanges, while a common nasal passage is formed above the palate, roofed anteriorly by the septal flanges and posteriorly by the cranial base. The space needed to create (simultaneous with shelf elevation) the common nasal passage is made available by flattening of the tongue and protrusion of its tip out of the oral cavity--this protrusion being facilitated by the sloping bulge of the primary palate and nasal septum. Many existing theories of shelf elevation are inconsistent with these observations. It was concluded that shelf elevation occurs very rapidly at a rather precise developmental stage and that turgor (due to binding of water to mucopolysaccharides) is the intrinsic force which elevates the shelves, a force which at 16.4 days reaches a threshold level enabling the shelves to force their way up and over the intervening tongue.

Animals↗