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Biomedical subjects

R L Searls

Publications and source records attributed to R L Searls.

18 recordsLinked to original sources
PubMed1991

The mechanism of cervical flexure formation in the chick.

Chick embryos, during stages 14 to 25, undergo an arching of the hindbrain and cervical neural tube that is termed cervical flexure. We have found that if the truncus arteriosus is severed during stage 12-13, the embryos survive for more than 24 h and do not show cervical flexure. The embryos have a beating heart, the expected number of somites, and often have discernible wing and leg buds. Light and electron micrographs reveal no histological abnormalities. The percentage of cells that become labeled with tritiated thymidine is close to normal, indicating that most of the cells are healthy. These results suggest that cervical flexure is related to normal morphogenesis of the heart. At stage 10, the heart is almost straight, with the prospective ventricle cranial to the prospective sinus venosus. The heart tube loops between stage 10 and stage 23, first to the right and then caudad, so that the ventricle becomes caudal to the sinus venosus. The heart undergoes these morphogenetic movements autonomously. The truncus arteriosus does not increase in length during caudal movement of the ventricle, so the cervical region is pulled into an arch. Bending of the cervical region into an arch can be prevented in intact embryos by injecting agar into the foregut, so that the foregut cannot bend. However, after about 24 h of further growth, if the axis cannot bend, the truncus begins to leak blood and the embryo dies. We conclude that cervical flexure is a response of the embryonic axis to the morphogenesis of the heart.

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PubMed1991

Developmental changes in tracheal structure.

Mechanical properties of the proximal airways are known to change with development; the highly compliant airways of the immature animal become stiffer and less collapsible with increasing age. Although the relationship between tracheobronchial architecture and function has been described for adult physiology, little is known regarding this relationship during early development. This study was, therefore, designed to test the hypothesis that alterations in tracheal morphometry parallel developmental differences in tracheal functional properties. Tracheal segments obtained from 29 lambs ranging in age from 70% of gestation to full-term newborn lambs up to 6 d old were examined using anatomic, morphometric, and histochemical techniques. The results showed 1) progressive increases in the dimensions of the trachea and the tracheal wall components, 2) alterations in the geometric arrangement of the tracheal ring, and 3) changes in the compositional characteristics of the tracheal cartilage with maturation. These findings demonstrate alterations in tracheal architecture, each of which contribute to the greater stiffness of the trachea, in older animals. When considered together, these factors help explain the differences in tracheal functional characteristics with development.

Aging↗
PubMed1990

Altered patterns of proteoglycan deposition during maturation of the fetal mouse lung.

Previous studies have shown that beta-xyloside inhibits maturation of the fetal mouse lung (Smith et al., Dev. Biol. 138, 42-52, 1990). Insofar as this drug inhibits proteoglycan deposition, the present studies were undertaken to examine the chemical composition and tissue distribution of proteoglycans in order to determine, more precisely, their role during lung morphogenesis. Autoradiography of labeled 16- and 19-day embryonic lungs demonstrated greater incorporation over the mesenchyme. Treatment with beta-xyloside did not alter the autoradiographic appearance; however, beta-xyloside treatment followed by nitrous acid digestion, eliminated most silver grains. Isolation of proteoglycans from extracellular, membrane and intracellular pools over the 16- to 19-day interval demonstrated redistribution of heparan sulfate proteoglycan from an intracellular to a membrane location, while chondroitin sulfate proteoglycan redistributed from intracellular to extracellular. Only the synthesis of chondroitin sulfate proteoglycan was inhibited by beta-xyloside. On the basis of these results we suggest that a chondroitin sulfate proteoglycan is required for lung maturation and that inhibition of its synthesis results in inhibition of septa formation and subsequent failure of morphogenesis and differentiation.

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PubMed1990

Development of the embryonic chick wing bud from stage 24 to stage 32.

If a graft is placed in an early chick wing bud, the location of the graft after several days of further development cannot be predicted solely from the rate of proximal-distal outgrowth. The movement of the graft depends on the rate of outgrowth of the wing but also on morphogenetic tissue movements intrinsic to the wing and on accommodation to the growth and morphogenetic movements of the body of the embryo. Numerous experiments have been reported in which tissue grafted into ectopic sites in the wing causes abnormal wing development. These experiments have been discussed in terms of pattern formation or positional information. However, until the movement of wing tissue during normal development is understood, it cannot be known in what way the development of grafts placed in ectopic sites is abnormal. Previous experiments have demonstrated that carbon particles placed in the wing move in the same manner as grafts of wing mesenchyme, but the carbon particles do not affect normal wing development. Carbon particles were placed in the wing, dorsal to the base of the wing, and cranial and caudal to the wing, to plot the expected movement of a graft and to discover how this movement can be predicted from the tissue movements at the base of the wing. It is concluded that three tissue movements are responsible for the movement of a graft. These are outgrowth at a rate determined by the rate of cell division, formation of the shoulder through caudal movement of the tissues cranial to the wing, and ventral movement of prospective flank ventral to somite 19. These three tissue movements and their influence on normal wing development are discussed.

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PubMed1990

Use of a touch sensitive screen and computer assisted image analysis for quantitation of developmental changes in pulmonary structure.

The extensive changes in pulmonary function occurring during early development may reflect variations in the anatomic structure of the respiratory apparatus during this period. Accurate definition of these alterations could yield important information concerning the structure-function correlations of the respiratory system. To facilitate the acquisition of morphometric data from histologic sections of pulmonary tissues, we propose the use of a computer assisted image analysis system with a touch sensitive screen as an interactive peripheral. This allows planimetric measurements and computation of the dimensions of areas of selected light intensities within an image. We present the description, design, and applications of such an image analysis system and report representative results regarding developmental changes in pulmonary structure. In addition, we correlate these results with previously published information regarding pulmonary mechanics during early development to help clarify the maturational changes in pulmonary structure-function relationships.

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PubMed1990

Effects of beta-D-xyloside on differentiation of the respiratory epithelium in the fetal mouse lung.

Differentiation of respiratory endings in the fetal lung appears to be controlled by its surrounding mesodermal capsule. The capsule may exert its influence by controlling the composition of the epithelial basal lamina or of the extended extracellular matrix that is deposited during the period when alveolar sacs are formed. As a first step in testing this hypothesis, the effects of the drug, rho-nitrophenyl-beta-D- xylopyranoside (beta-xyloside), an inhibitor of proteoglycan synthesis, and its inactive alpha anomer (alpha-xyloside) were examined. Lung primordia from mice at 16 days of gestation were tested for inhibition of morphological and functional differentiation as a result of drug treatment. Pseudoglandular lung epithelium did not form respiratory endings, contained fewer specialized cells, and accumulated little additional surfactant when treated with beta-xyloside but developed normally when treated with alpha-xyloside or grown in control medium. The results are interpreted to suggest that deposition of an extracellular matrix rich in proteoglycan is required to support maturation of the respiratory epithelium.

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PubMed1987

Accumulation and distribution of sulfated materials in the maturing mouse lens capsule.

Lenses of late gestational and postnatal normal-eyed mice were tested for accumulated sulfated materials by using Spicer's high-iron-diamine staining method and also for newly incorporated sulfate autoradiographically following administration of 35SO4 either in vivo or in isolated and organ-cultured lenses. Accumulated and newly incorporated sulfate was observed in all lenses for each age group tested. Discrete regional differences were seen in histochemical staining patterns for sulfate on the lens capsule in specimens of all ages, and distinct laminar zonations were seen in the various regions of the capsule in older specimens. Typically, the anterior and equatorial regions of the capsule demonstrated three histochemically distinct laminar zones while the posterior capsule usually demonstrated two laminar zones. Autoradiographic results indicated that sulfate was indeed being incorporated into these regions, and in the same general pattern as seen with histochemistry. The materials were largely insensitive to testicular hyaluronidase but were preferentially sensitive to nitrous acid digestion, indicating the presence of capsular heparan sulfates. Autoradiographic results from organ-cultured lenses indicated that this tissue itself is a primary source of these materials.

Aging↗
PubMed1986

A description of caudal migration during growth leading to the formation of the pericardial and pleural coeloms, to caudal movement of the aortic arches, and to development of the shoulder.

Formation of the shoulder in the chick embryo results from movement of cells into the base of the wing from more cranial regions. Between stage 23 and stage 27, the lateral body wall overlying the pleural coelom is caused to move into the base of the wing because the cranial margin of the pleural coelom moves from the level of the tenth somite to the level of the 16th somite. Thus, formation of the shoulder is related to the formation of the pleural coelom. Textbook descriptions of the formation of the pleural coelom did not permit this relationship to be delineated. Therefore, investigation of the relationship between the formation of the shoulder and the formation of the pleural coelom seemed warranted. At stage 12 the coelom is lateral to the gut from the level of the second somite to the level of the 16th somite and is continuous with the extraembryonic coelom. During stage 13 the coelom obtains a ventral margin at the level of the third and fourth somites as the heart fuses with the lateral body wall to form the lateral mesocardium. Between stage 16 and stage 23, the second (cervical) flexure develops, causing the lateral mesocardium to form a ventral margin of the coelom from the level of the first to the 17th somites. Between stage 16 and stage 23, the coelom becomes ventral to the pharynx and lung to the level of the ninth somite. From stage 23 to stage 27, the lateral body wall from the cranial margin of the lung to the caudal margin of the hyoid arch moves in a caudal direction. During stage 27, the lateral body wall fuses with the lateral mesocardium to form the pleuro-pericardial membrane. The wing remains ventral to the 16th to 19th somites, causing a pileup of cells at the cranial base of the wing, the shoulder.

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PubMed1978

Patterns of cellular proliferation during thyroid organogenesis.

The changes in rate and location of cellular proliferation were analyzed to determine if localized areas of cell division were influencing shape changes in the chick thyroid. Pulse labeling with tritiated thymidine indicates that the gland's labeling index declines throughout its development. Initially, the thyroid placode has a lower labeling index than the neighboring pharyngeal epithelium. An evaluation of the positions of pulse-labeled cells reveals that the evaginating thyroid grows by annexing cells from the pharyngeal epithelium. The older evaginated regions of the gland exhibit the lowest labeling indices. The newly acquired regions still maintain higher labeling indices.

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PubMed1976

Effect of dorsal and ventral limb ectoderm on the development of the limb of the embryonic chick.

Limb ectoderm plus a small amount of subjacent mesoderm obtained from the dorsal or the ventral surface of each of the four limbs of the chick embryo were grafted to the dorsal surface of the right wing in either reversed or normal orientation. The host wings developed in abnormal humerus in all cases except when the graft was obtained from the dorsal surface of the right wing and was in normal orientation. However, the nature of the abnormalities varied with the source of the graft and with the orientation of the graft. It is unlikely that the abnormalities were related solely to the small amount of mesoderm grafted since previous experiments have demonstrated that the mesoderm would regulate. Flank ectoderm plus a small amount of flank mesoderm did not cause limb abnormalities when grafted in the same manner.

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PubMedDate not supplied

Effects of hormones on functional differentiation of mouse respiratory epithelium.

The effects of corticosteroids and thyroxine on morphogenesis and differentiation of fetal respiratory epithelium were tested in serum-free culture. Strips from the margins of 16-day fetal mouse lungs, containing future respiratory branches, were cultured in medium containing growth factors plus different concentrations of dexamethasone and/or thyroxine. After 5 days, some of the cultures were processed for electron microscopy and the rest were used to quantitate unsaturated and saturated phosphatidylcholine. In the absence of thyroxine and dexamethasone, the lung tissue developed the equivalent of one more day in utero during the 5 days of culture, perhaps because of residual hormone in the tissue. Thyroxine and dexamethasone in concentrations compatible with normal physiological conditions permitted normal development from the pseudoglandular stage to the saccular stage, differentiation of respiratory cell types, and normal surfactant accumulation. Thyroxine alone gave essentially the same lack of morphological maturation and accumulation of disaturated phosphatidylcholine as culture in the absence of all hormone, but columnar epithelial cells held increased numbers of lamellar bodies. Dexamethasone alone at 10(-6) M gave essentially normal development. Dexamethasone at 10(-9) M was sufficient to permit almost normal development when combined with 10(-7) M thyroxine. We conclude that dexamethasone is required for normal maturation of the fetal lung and that thyroxine acts synergistically to lower the dexamethasone requirement. The presence of apparently authentic lamellar bodies under some conditions of low disaturated phosphatidylcholine accumulation make this morphological criterion suspect as a test for differentiation of type II cells.

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