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Biomedical subjects

S R Hilfer

Publications and source records attributed to S R Hilfer.

At least 19 recordsLinked to original sources
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.

Animals↗
PubMed1990

Patterns of cell movement in early organ primordia of the chick embryo.

Purse-string constriction of the cytoskeleton at cell poles is generally accepted as the causal mechanism for invagination during early stages of organ formation. However, it is known that other cell movements, including intercalation, play a role in the organotypic shape changes that occur during gastrulation and neurulation. Such cell movements have not been investigated in pouching and branching epithelial primordia. There is reason to suspect that cells within these organ primordia might exchange their neighbors for others, that is, intercalate or translocate, at sites of sharp folding such as borders with the surrounding epithelial sheet or where a bend occurs within the primordium. The greatest difficulty in identifying these movements has been the need to use intact embryos so that the processes are not distorted. This study explores the possibility of using time-lapse video recording to identify cell movement at these locations. Three organ primordia were tested: otic and thyroid placodes, which had not been tested previously, and neural plate as a control, where movements of this sort have been documented. Embryos or parts containing the primordia were immobilized and cell apices visualized with Hoffman modulation contrast optics. Recordings to an optical memory disc recorder were transferred to a microcomputer for image analysis. The viewing procedure allows reasonably clear visualization of cell apices, and image analysis permits tracking of a number of adjacent cell apices over an extended time period. Several types of movement were found to occur within cell sheets, and the relative abundance of each type depends on the specific primordium. In the neural plate, some cells move many cell diameters from their neighbors. In the other two primordia, most cells show limited shifts in position relative to their neighbors except at regions where folds are formed. In other regions, adjacent cells move as a unit. Knowledge of the movements which occur in any particular primordium is essential to an understanding of the mechanisms controlling its formation.

Animals↗
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.

Animals↗
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.

Animals↗
PubMed1989

Invagination of the otic placode: normal development and experimental manipulation.

The inner ear forms from paired ectodermal primordia that lie to either side of the developing hindbrain. Initially each primordium forms a shallow depression in the ectodermal surface. Invagination to form an otic pit coincides with the formation of several deep folds in the epithelial surface. An initial fold appears parallel to the embryonic axis and at the junction of the rhombencephalon with somitomeric mesoderm. This is followed by formation of cranial and caudal folds perpendicular to the axis and minor folds that are within the pit formed by earlier folding. The central region of the otic primordium remains in close apposition to the lateral surface of the neural tube during the process of fold formation, until the otic pit becomes quite deep. At that time, mesenchymal cells penetrate between the two layers. Experimental analysis of invagination supports the conclusion that otic invagination is controlled differently from that of similar organ primordia, such as the eye and thyroid. Whereas these other primordia can be stimulated to undergo normal morphogenetic shape changes precociously by treatments that presumably activate motile processes in the cytoskeleton, the same conditions have little effect on the otic placode. Similarly, neither inhibitors of calcium transport nor inactivators of calmodulin activity prevent otic pit formation, while these drugs block invagination of other primordia. These results suggest that otic invagination may be caused by changes in the surrounding tissues rather than by an activation of motility within the primordium.

Animals↗
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

The effect of culture conditions on cytodifferentiation of fetal mouse lung respiratory passageways.

Differentiation of the respiratory region of fetal mouse lungs was investigated in serum-free medium supplemented with growth factors and hormones. Terminal buds from the margins of a lobe were removed from 16-day fetuses and organ cultures prepared either in submersion culture or at the air-medium interface. It was found that glycyl-L-histidyl-L-lysine, transferrin, and somatostatin were sufficient to promote branching in the absence of serum. However, type II pneumocytes containing lamellar bodies formed only in the presence of thyroxine or dexamethasone. At concentrations of these hormones slightly above the physiological range most of the cells became cuboidal and contained lamellar bodies; at lower concentrations regions of flattened cells appeared. In submersion culture a large, central cavity surrounded by saccules was formed rather than a branched tree. Thus, the pattern of differentiation is significantly influenced by culture conditions.

Animals↗
PubMed1985

Mesenchymal control of branching pattern in the fetal mouse lung.

The effect of mesenchyme on specialization of respiratory epithelium in the fetal mouse was tested in organ cultures. Heterologous combinations were made between respiratory and non-respiratory lung epithelia and the corresponding mesenchymes. Isolated terminal respiratory buds of fetal mouse lungs were recombined with mesenchyme from chick lung parabronchi, mouse trachea or from the avascular, non-respiratory air sacs of chick lungs. Isolated non-branching chick air sacs were combined with mouse terminal bud mesenchyme or mesenchyme from the respiratory branches of chick lungs. Air sac epithelia branched in a pattern characteristic of the chick lung when combined with chick respiratory mesenchyme and in a pattern characteristic of mouse lung when combined with mouse terminal bud mesenchyme. Mouse terminal bud epithelia did not branch with either mouse tracheal mesenchyme or chick air sac mesenchyme but branched in a chick pattern with chick parabronchial mesenchyme. Electron microscopic examination of the cultures showed that all chick air sac epithelial cultures failed to produce surfactant (lamellar bodies) even when they branched. Control cultures of mouse terminal buds contained large numbers of lamellar bodies; mesenchyme which suppressed branching reduced the number of lamellar bodies to only a few in a small proportion of the cells. Culture medium supplemented with growth factors and hormones increased the number of lamellar bodies in heterologous mouse combinations but did not bring the number to control levels. Supplemented medium had no effect on lamellar body production by chick air sac epithelium. The results indicate that branching pattern is determined by the mesenchyme surrounding the epithelial primordium. However, the capacity to synthesize surfactant is determined by the source of the epithelium; mesenchyme may control the degree of expression but not the absolute presence or absence of the differentiated condition.

Age Factors↗
PubMed1985

Cell proliferation in condensing scleral ectomesenchyme associated with the conjunctival papillae in the chick embryo.

The role of cell proliferation in the formation of scleral ectomesenchymal condensations underlying the conjunctival papillae was examined with in vivo tritiated thymidine labelling in chick embryos ranging in age from 8 days 0 h to 10 days 12 h. Percentages of labelled nuclei were determined in both ectomesenchyme and the deeper fibrous sclera for short-term and continuous tritiated thymidine incubations. During formation of the ectomesenchymal condensations the percentages of labelled nuclei were consistently higher within the condensations than in corresponding non-condensing ectomesenchyme between papillae. The consistent differences of labelling percentages observed within the condensing versus non-condensing ectomesenchyme were not found in the fibrous sclera at any stage. All areas of both the ectomesenchyme and fibrous sclera showed decreases in the percentages of labelled nuclei from 8 days 0 h to 10 days 12 h, although the decline in the ectomesenchymal condensations beneath papillae occurred more slowly than in areas between papillae. The data suggest that the conjunctival papillae directly influence the proliferation in the subjacent condensing ectomesenchyme but have no effect on the ectomesenchyme between papillae or any region of the deeper fibrous sclera. The observations of this investigation are discussed in relation to other studies of the development of the pre-ossicular mesenchyme.

Animals↗
PubMed1979

Follicle formation in the embryonic chick thyroid. III. Initiation of follicle formation.

It has been proposed that the follicular spaces in the thyroid form by either the coalescence of intracellular droplets or by separation of cell apices by secretion into the extracellular space. On the basis of examination of thyroid primordia in early chick embryos this study provides evidence that in the chick, at least, follicle formation conforms to the second model. The first indications of change in the chick thyroid is the appearance of interdigitations of the cell apices. These interdigitations form microvilli as the two surfaces become separated and the follicular space is established. Vesicles with two types of contents can be identified in proximity with the cell surface during follicle formation, but it is not clear if either the dense particulate or the more electron-lucid materials that they contain actually enter the follicular space. Neither removal of the pituitary gland by decapitation nor inhibition of collagen synthesis and a concomitant failure of the invasion of capsular mesenchyme prevents the initiation of normal follicle formation.

Animals↗
PubMed1978

Embryologic origin of the various epithelial cell types in the second kind of thyroid follicle in the C3H mouse.

The thyroid gland of the C3H mouse is composed largely of the usual follicle but it also contains a second kind of follicle. To ascertain the embryologic origin of the cell types in each of these follicles, ventral pharyngeal outpocketings and ultimobranchial outpocketings were isolated (before they fused to form the thyroid gland) from the 12-day-old fetus of the C3H mouse. The outpocketings were implanted into different kidney capsules of adult C3H mice and were allowed to grow for several months. Transplants were then excised and examined by electron microscopy. The ventral contribution formed large aggregates of follicles and was recognized as a distinct bump on the surface of the kidney. It formed only typical thyroid ultimobranchial contribution usually formed only a small number of follicles, generally of small size. It was readily located because the follicles occurred next to a white plaque of bone or cartilage at the site of implantation. The ultimobranchial contribution formed follicles containing four cell types: a ciliated cell, a cell with abundant agranular reticulum, a cell with many free ribosomes and fiber and occasional hemidesmosomes, and the C cell which was the most frequent cell type. No typical thyroid epithelium was observed in the ultimobranchial transplant. These observations suggest that the C cell in the usual follicle is derived from the ultimobranchial contribution, and that the second kind of follicle is largely an ultimobranchial contribution but the typical thyroid epithelium in it is largely or entirely a ventral contribution.

Animals↗
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.

Animals↗
PubMed1977

Embryologic origin of various epithelial cell types in the thyroid gland of the rat.

Ventral pharyngeal outpocketings and ultimobranchial outpocketings from the 14-day-old fetus of the Fischer rat were isolated before they fused to form thyroid glands. The outpocketings were implanted into different kidney capsules of adult male Fischer rats, and were allowed to grow for several months. Transplants were then excised and examined by electron microscopy. The ultimobranchial outpocketing gave rise to two types of follicles. One contained ciliated cells, cells with an abundant agranular reticulum, U cells with basal hemidesmosomes, and two types of cells with secretory vesicles. The other contained C cells separated from the follicular lumen by a single flat fiber-containing cell. The ventral outpocketing formed typical thyroid epithelium making up the usual thyroid follicles differing from follicles in the thyroid in situ by the absence of C cells. These follicles were functional as determined by autoradiographic studies with 125I but differed from thyroid follicles in situ with respect to size distribution. The results suggest that (1) in the adult thyroid gland the C cell in the usual follicle is an ultimobranchial contribution and (2) the so-called ultimobranchial follicle is ultimobranchial in origin but that the typical thyroid epithelium in mixed follicles of U cells and typical thyroid epithelium is a ventral contribution. The reason for the absence in the thyroid gland in situ of the variety of other cell types observed in ultimobranchial transplants is unknown.

Animals↗
PubMed1977

Interference with thyroid histogenesis by inhibitors of collagen synthesis.

Histogenesis of thyroid follicles in the chick embryo begins with a penetration by cells of the mesenchymal capsule into a solid epithelial primordium. Before penetration occurs, slits containing fibrillar material form between the epithelial cells. The fibrillar material is an epithelial cell product as shown by its formation within channels that form in cultures of isolated epithelial primordia. The drugs L-azetidine-2-carboxylic acid (LACA) and alpha, alpha'-dipyridyl, which interfere with collagen synthesis, prevent the formation of fibrils in cultured epithelial primordia and in cultures of whole thyroids. Furthermore, mesenchymal cells do not invade when whole thyroid primordia are cultured in the presence of either drug. The effects of alpha, alpha'-dipyridyl are reversed by washing out the drug; the effects of LACA are reversed by incubation with equimolar or greater amounts of L-proline added to the medium along with the drug. The results are interpreted to mean that the fibrillar material is collagen of epithelial origin, that the collagen in some way plays a role in mesenchymal penetration of the epithelial primordium, and that the epithelium is responsible for the pattern of lobulation within the developing gland.

2,2'-Dipyridyl↗