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Biomedical subjects

T D Stephens

Publications and source records attributed to T D Stephens.

32 records · Page 2Linked to original sources

Peripheral nerves do not play a trophic role in limb skeletal morphogenesis.

Research was undertaken to test the hypothesis that thalidomide-induced limb defects resulted from damage to the neural crest or peripheral nerves and that normal limb development depends upon either the quality (level specific) or quantity of peripheral nerves. Barriers which were placed into early chick embryos to block brachial plexus-level neural crest cells from reaching the limb resulted in normal limb skeletons. These data agree with previous work in suggesting that skeletal morphology is independent of innervation.

Animals↗

A critical review of the McCredie-McBride hypothesis of neural crest influence on limb morphogenesis.

A number of hypotheses have been presented to explain the mechanism of action of thalidomide. The most widely published and apparently widely accepted hypothesis is that of embryonic neuropathy advanced by McCredie and McBride. This paper reviews the points of the hypothesis and analyzes it in light of known limb embryology supported with recent experimental evidence which directly tests the hypothesis. The hypothesis may be considered as being composed of two separate parts. The first part proposes that thalidomide-induced limb defects exhibit a segmental pattern. The second proposes that the segmental pattern of limb defects is a result of segmental peripheral neuropathy. We are in complete agreement with the first portion of the hypothesis, but find the second portion quite unlikely.

Animals↗

A review of limb defects in a large fetus collection.

Although a considerable number of papers have been published dealing with the frequency and variety of genetic and nongenetic limb defects in newborns and to a lesser extent among embryos, little has been published about the range of limb defects among spontaneously aborted middle and late-term fetuses. This study reports on 133 limb defects from the Central Laboratory for Human Embryology (CLHE), Seattle, Washington. These constitute 34.1% of the total defective specimens in the collection and 5.4% of the total collection population. It is proposed that 30% of the limb defects described indicate a definite recurrence risk, 27% do not indicate recurrence, and the recurrence risk for 43% is unknown. The most interesting findings from this study include the observation that reduction defects affect predominantly the preaxial side of the upper limb and that addition defects (polydactyly) affect predominantly the postaxial side of the lower limb. The observation in relation to reduction defects agrees with U.S. newborn studies. The observation in relation to polydactyly is exactly opposite the studies of Latin American newborns and Japanese embryos.

Anencephaly↗

Parasitic conjoined twins, two cases, and their relation to limb morphogenesis.

Reports of parasitic conjoined twins have appeared rarely in the scientific literature and only one study has included a detailed description of the parasitic extremities. We report here two specimens consisting for the most part of normal hosts with ectopic legs attached to the thorax (case 1, thoracoparasitus) or the abdomen (case 2, gastroparasitus). These two specimens are in agreement with several others reported in the literature in having no sign of vertebral columns. These specimens also exhibit a marked decrease in innervation (case 1) or complete absence of somatic nerves (case 2). This finding is in complete contradiction with the idea of the dependence of limb skeletal structure upon peripheral nerves. The hypothesis is presented that this type of parasitic twin may result from duplication of the Wolffian ridge.

Bone and Bones↗

Determinants in the morphogenesis of muscle tendon insertions.

The factors that normally determine the location and insertion of a muscle were explored in human experiments of nature with early problems in morphogenesis. Monozygotic conjoined twins for whom there could be no genetic determinants for muscle attachments at the sites of juncture served as one model; these attachments had to follow general principles of morphogenesis. A second type of problem involved absence of bone that presumably antedated muscle and tendon development (e.g., genetically determined radial aplasia). A third category included mechanical alteration of early limb position that may have occurred prior to the development of muscle attachments (e.g., early amnion rupture sequence). The dissection findings from all three types imply a general hierachy of muscle tendon attachments. Tendons appear to attach preferentially to bone. In the absence of the bone to which they would normally attach, they will attach to the next closest bone. If no such bone is available, tendons may attach to other tendons; and if no tendons is available, occasionally they will attach to the fascia of another muscle. If there is no connective tissue attachment site, there will be no muscle, implying a need for function in the development and preservation of muscle.

Abnormalities, Multiple↗

Evidence for a metameric pattern in the development of the chick humerus.

It has been proposed that the wing bud is induced by some axial influence at a specific confined location and that the ZPA is the residual influence of such induction. The purpose of the present investigation was to test this hypothesis. Tantalum foil barriers were placed lateral to the mesonephric duct and parallel to the long axis of the embryo in the wing field of stage-12 to -15 chick embryos. These barriers blocked the somatopleure's communication with more medial tissues at specific somitic levels. The results of these experiments demonstrate that (1) the limb is not induced at one specific point, (2) portions of the humerus appear to be induced segmentally along the entire limb field and (3) the ZPA is not induced by axial structures. We propose a model of wing development suggesting that the humerus is induced as several separate components which then fuse to form the definitive bone.

Animals↗

The association of spinal retroflexion with limb anomalies.

The spectrum of conditions in which retroflexion of the spine occurs includes anencephaly, iniencephaly, and Klippel-Feil syndrome. It was suggested by Gimour ('41) that a continuum may exist linking the latter two entities. The present paper attempts to reopen this question by reporting two specimens which have none of the above conditions, yet have spinal retroflexion and limb malformations. Combined with other isolated case reports, they show that spinal retroflexion can arise over a variable period of time.

Abnormalities, Multiple↗

The Down syndrome in the fetus.

A significant number of fetuses with the Down syndrome are spontaneously lost before birth; however, very few such fetuses have been described. In the present study, 13 fetuses of 127--180 mm in crown-rump length were examined following amniocentesis diagnosis of trisomy 21 and therapeutic abortion. Four features, i.e., simian crease, clinodactyly, septal heart defects, and decreased size, were found to be relatively common in trisomy 21 fetuses as compared to controls. Other features were found to be less useful in identification. We conclude that the presence of two of the four features noted above is suggestive of trisomy 21 in the fetus.

Dermatoglyphics↗

Extracellular matrix synthesis in the chick embryo lateral plate prior to and during limb outgrowth.

Little is known at the present time about the molecular basis and mechanisms of morphogenesis. The present study is an attempt to determine what influence the extracellular matrix has on the initial outgrowth of the limb bud. Stage -12 to -18 chick embryo lateral plates were examined in relation to proline and sulfate incorporation into collagen and proteoglycan. The flank and limbs incorporated the same amount of labeled proline and sulfate before stage 16. At stage 16 the flank began to incorporate more of both isotopes until at stage 18 there was twice as much incorporation into the flank as into the limbs. The flank and limbs contained the same type of collagen during the period examined. The limbs contained both large and small proteoglycans but the flank contained only small proteoglycans. These data suggest that the extracellular matrix in the flank and limb regions may play a role in limb outgrowth and that the limb buds at these stages may be more inclined toward cartilage development.

Age Factors↗