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Biomedical subjects

H C Slavkin

Publications and source records attributed to H C Slavkin.

At least 199 records · Page 11Linked to original sources
PubMed1984

De novo gene expression detected by amelogenin gene transcript analysis.

Reciprocal epithelial-mesenchymal interactions are responsible for mouse molar tooth organogenesis. Only dental ectomesenchymal cells are capable of instructing adjacent epithelial cells to become determined to synthesize and secrete enamel-specific proteins termed the amelogenins. To identify when inner enamel epithelial cells first express enamel specific gene products, cytoplasmic RNA has been analyzed from developing teeth by hybridization to a cloned cDNA probe to one of the amelogenins. It is reported that the de novo expression of amelogenin-encoding RNA as well as immunoprecipitated amelogenin polypeptides are first detected at Theiler stage 27. These data indicate that ectomesenchymal-mediated induction of inner enamel organ epithelia results in both the nascent transcription of amelogenin RNA and subsequent translation of amelogenin polypeptides, which are first detected at birth.

Amelogenin↗
PubMed1984

Localization of pulmonary surfactant protein during mouse lung development.

During lung development type II alveolar epithelial cells produce extracellular pulmonary surfactant. Polyclonal antibodies were produced against nonserum proteins associated with human surfactant. The present studies were designed (i) to determine if mouse surfactant proteins were antigenically cross-reactive with polyclonal antibodies directed against human surfactant proteins; and (ii) to determine surfactant protein localization during fetal, neonatal, and adult mouse lung development. Two-dimensional gel electrophoresis studies in conjunction with immunologic techniques provided evidence that mouse and human surfactant proteins shared antigenic determinants. The major monomeric form of mouse surfactant protein in a glycoprotein of approximately Mr 35,000 under reducing conditions. A less abundant form was identified as a Mr 45,000 polypeptide. Immunohistochemical localization showed that type II cells contain surfactant protein at Theiler stage 26. A gradient of immunostaining was localized within alveolar surfaces. The antigen was not detected in heart, blood vessels, or pulmonary interstitial cells. Surfactant protein was detected lining alveolar surfaces in mature adult lung. The distribution of this protein during fetal and neonatal lung morphogenesis suggests that this extracellular constituent of pulmonary surfactant may be extremely useful as a phenotypic marker with which to evaluate normal and abnormal lung development.

Animals↗
PubMed1984

Congenital craniofacial malformations: issues and perspectives.

Congenital craniofacial malformations represent an extremely fascinating and complex set of biomedical problems. The complexity includes early detection, diagnosis, treatment, habilitation, and prevention. Genetic and environmental issues that appear to interact and result in congenital craniofacial malformations are becoming better understood. Advances in mouse and human immunogenetics now suggest several possible explanations for why some individuals acquire certain birth defects and others do not. Recent discoveries concerning the MHC and its association with a number of human birth defects have stimulated interesting speculations concerning genetic and environmental factors that might be responsible for predispositions to congenital malformations. Of particular interest is the possible function of the MHC of the mother during early stages of embryogenesis (the first trimester) and how this assembly of genes may infer susceptibility to environmentally induced birth defects in mouse and human reproduction. A number of environmental chemicals have been implicated in causing birth defects. A large amount of exciting information regarding the genetic regulation of certain drug-metabolizing enzymes (for example, the cytochrome P-450 system) has developed. Basic research and biotechnology continue to advance our appreciation for and knowledge of craniofacial development biology.

Abnormalities, Drug-Induced↗
PubMed1984

Ultrastructural and immunofluorescence studies of basal-lamina alterations during mouse-lung morphogenesis.

Epithelial differentiation during lung development appears to be influenced by mesenchyme-derived instructions coupled with hormonal regulations. The basal lamina which is associated with progenitor and differentiating epithelia during mouse embryogenesis (Theiler-stages 16-28) was examined by transmission electron microscopy and indirect-immunofluorescence microscopy. During the embryonic phase of lung development, progenitor epithelia for the pulmonary acinus projected microvilli or cytoplasmic "feet" through the basal lamina, which resulted in discontinuities and a close approximation of the adjacent mesenchymal-cell processes. These changes were also associated with the transitory polarization of mesenchymal cells perpendicular to the plane of the basal lamina, which resulted in a sheet of cuboidal mesenchymal cells adjacent to the developing acinar-tubule epithelium. During the embryonic phase of lung development, these specific interstitial or mesenchymal cells stained for heparan-sulfate proteoglycans; no other cell types were immunostained. By Theiler-stage 25, the acinar-tubule epithelia had differentiated into type-II pneumonocytes which contained lamellar bodies and significant amounts of glycogen. Fibronectin, laminin, and heparan-sulfate proteoglycan were localized in the basement membranes during the embryonic, canalicular, and terminal sac phases of lung morphogenesis. A diffuse localization of fibronectin of the interstitial cell surfaces was observed. These observations indicate that major changes in the structure and composition of basal lamina occur during the embryonic and fetal phases of pulmonary-acinus epithelial-cell differentiation and the production of pulmonary surfactant. The major changes in the basal lamina may be partly mediated by mesenchyme-derived instructions for type-II epithelial-cell differentiation.

Animals↗
PubMed1984

Developmental and immunogenetic features of biologic aging.

As the direct result of improved health measures and medical/dental care during the 20th century, the longevity of individuals within the United States has significantly lengthened from 45 years in 1900 to 75 years in the 1980s. It is now projected that during the remaining 2 decades of the 20th century, approximately 18% of the total American population will be 65 years and older by the year 2000. Paradoxically, success in reducing acute diseases and postponing death has resulted in costly long-term disabilities and complexities of chronic disease. This review focuses, therefore, on the major issues of prevention of chronic diseases to demonstrate that biologic aging is a normal sequela of developmental biology and not a disease; diseases are separated from aging. Emphasis is placed on advances in genetics, molecular biology, immunology, and neurology toward understanding the ultimate prevention of chronic disease. An emphasis on prevention during the development of the individual, from conception through senescence, is necessary.

Adolescent↗
PubMed1984

Influence of the major histocompatibility complex (H-2) on glucocorticoid-stimulated pulmonary surfactant synthesis in two congenic mouse strains.

Mice with different histocompatibility alleles in otherwise identical backgrounds (congenic inbred strains of H-2a and H-2b haplotypes), were used to study the possible influence of the major histocompatibility complex (MHC) upon glucocorticoid-stimulated pulmonary surfactant synthesis during embryonic and fetal stages of mouse lung development. Pregnant C57BL/10SnJ (H-2b) and congenic B10.A/SnSgJ (H-2a) mice were administered single or consecutive intraperitoneal injections of betamethasone during the period of 14 through 17 days gestation. Assays for incorporation of [3H]choline into total lipid and saturated phosphatidylcholine (an index for pulmonary surfactant synthesis) were conducted, 24 hr following the last treatment, on Days 17 or 18 of gestation. Control mice received injections of phosphate-buffered saline. The H-2 genotype appears to influence the relative responsiveness of glucocorticoid-stimulated surfactant synthesis during fetal lung development. The B10.A strain (H-2a haplotype) was more responsive to glucocorticoid-stimulated pulmonary surfactant synthesis than the H-2b haplotype. Whereas both strains were responsive to glucocorticoid-stimulated [3H]choline incorporation into lung surfactant, the differences in responsiveness at specific fetal stages suggest that genes within or closely linked to the H-2 complex might have a role in pulmonary surfactant biosynthesis during mouse lung development. The results also suggest the possibility that relative susceptibility to congenital pulmonary disorders may be influenced by the H-2 complex.

Alleles↗
PubMed1984

Identification of inner and outer cell proliferation centers during fetal tooth morphogenesis.

Patterns of cell division have been examined in the proliferative cervical loop tissues of fetal rabbit incisor tooth organs. Evaluation of the distribution patterns of silver grains, resulting from the incorporation of [3H]-thymidine into newly synthesized DNA within tooth organs in vitro, resulted in identification of two proliferation centers: (1) an inner center consisting of inner enamel epithelial cells (i.e., preameloblasts) and predontoblasts ; and (2) an outer center consisting of outer enamel epithelium and adjacent mesenchyme. In contrast to the classically held description of epithelial cell differentiation during tooth morphogenesis, our data suggest that outer enamel epithelial cells do not migrate around the cervical loop and do not provide progenitor cells for subsequent ameloblast cytodifferentiation. During tooth development, epithelial and mesenchymal cells, which arise from either an inner or outer proliferative center, migrate in distal directions relative to the proliferative sites. Therefore, the progenitor cells for ameloblasts and odontoblasts were found to be localized in the inner proliferation zone. The implications of these findings regarding the development of continuously erupting rabbit and rodent incisor tooth organs are discussed in the context of a model.

Animals↗
PubMed1983

Biosynthesis and secretion of enamel proteins during hamster tooth development.

Experiments were designed to detect and determine the biosynthetic behavior of enamel proteins in Syrian Golden hamsters. Enamel matrix proteins were extracted from 3-day-old postnatal first molar tooth organs. Labeling pulse/chase experiments with [35S]-methionine followed by light microscopic autoradiography, or polyacrylamide slab gel electrophoresis and fluorography, showed the synthesis of epithelial-specific gene products. Synthesis and secretion of enamel proteins required approximately 30 min under these in vitro organ culture conditions; both enamelin and amelogenin proteins were synthesized and secreted into the forming extracellular matrix. Amelogenin proteins were secreted initially and rapidly degraded into increasingly smaller polypeptides. In contrast, enamelin proteins were secreted at a slower rate and remained more or less stable over the duration of the experiment. The specific activities of both classes of proteins increased over a 6-hour synthesis period, indicating the accumulation of both proteins into the forming extracellular matrix. Comparisons of the kinetics of formation and posttranslational processing of enamelin and amelogenin are consistent with the presence of possibly two different gene products in hamster secretory ameloblasts.

Amelogenesis↗
PubMed1983

Construction and identification of mouse amelogenin cDNA clones.

The determination of the biochemical phenotype of tooth epithelium requires specification by the dental mesenchyme. This is a general feature of epithelial-mesenchymal interaction in a number of different epidermal organ systems (e.g., salivary gland, mammary gland, feather, skin, and hair morphogenesis). To investigate these developmental processes, we have identified a cDNA clone representing the major group of gene products associated with enamel extracellular matrix formation. The mRNAs for mouse amelogenins, representing approximately equal to 90% of the total enamel proteins, have been isolated and partially characterized by specific immunoprecipitation. The poly(A)-containing RNAs were used for the synthesis and cloning of the mouse amelogenin cDNA. Recombinant plasmids containing amelogenin cDNA sequences were identified by differential hybridization, hybrid-selected translation, and blot hybridization analyses. A cloned sequence was used to identify the expression of amelogenins during tooth development. The mouse cDNA sequence hybridized to genomic mouse and human DNAs. This amelogenin cDNA probe now enables molecular investigations of a number of classical problems in developmental biology.

Amelogenin↗
PubMed1983

The epithelial genotype controls the pattern of extracellular enamel prism formation.

Enamel formation in the developing tooth organ is the product of epithelial-mesenchymal interactions which result in the differentiation of ameloblasts, the secretion of enamel proteins, and the production of a highly organized extracellular matrix. The three-dimensional organization of enamel prisms is species-specific: irregular polygon-shaped in rabbit and rectangular-shaped in mouse. We designed experiments to test the hypothesis that three-dimensional organization of enamel prism formation is genetically determined by epithelium; the prediction being that species-specific enamel prism pattern formation is expressed independent of mesenchymal instructions. Our strategy employs scanning electron microscopy to examine enamel prism patterns formed during rabbit and mouse tooth morphogenesis in situ and in vitro, and to then determine the specific tissue type required for regulating these patterns using heterotypic tissue recombinations. Morphometric analyses demonstrated that cap stage tooth organs cultured on the chick chorioallantoic membrane (CAM) formed enamel prisms equivalent to prism patterns observed for in situ controls. Heterotypic tissue recombinations, using cap stage molar organs, formed rabbit-like prisms with rabbit epithelium/mouse mesenchyme, and mouse-like prisms with mouse epithelium/rabbit mesenchyme. These results indicate that dental papilla mesenchyme has no apparent influence on enamel prism pattern formation. Enamel prism pattern appears to be genetically regulated by the inner enamel epithelium.

Animals↗
PubMed1983

Enamelin gene expression during fetal and neonatal rabbit tooth organogenesis.

Epithelial differentiation is a complex process which requires an integrated synthesis of DNA along with synthesis of a full complement of unique mRNAs and their respective proteins characteristic for each cell type. The time of initial transcription of enamel protein mRNAs and subsequent translation of proteins characteristic for secretory ameloblasts is not known. In order to determine when enamel protein mRNAs appear during New Zealand White rabbit molar tooth organogenesis, and when nascent enamel proteins are first translated, we analyzed early cap stages through late crown stages of molar tooth formation (i.e., 21-days gestation through 2-days postnatal). The biochemical phenotype which characterized rabbit ameloblasts were the acidic glycoproteins termed enamelins. Polyclonal antibodies were produced against the major fetal rabbit enamelin of approximately 70,000 daltons. Immunoprecipitation of enamelins from mRNA-directed translation products in a reticulocyte cell-free system, was used to characterize enamelin mRNAs. Enamelin mRNAs were first detected during bell stages (circa 23-days gestation), and persisted till crown stage (circa 28-days gestation). Indirect immunofluorescent localization of enamelin antigen showed staining over the extracellular enamel organ matrix by 23-days gestation. Neither enamelin mRNAs or polypeptides were detected during early or late cap stages of odontogenesis. Transcription of enamelin mRNAs coding for two enamelins of 65 an 58 kd (kilodaltons) appeared to be closely coupled with the translation of these enamel proteins. We assume that close-range ectomesenchyme- derived instructions mediate the biochemical differentiation of ameloblasts between 21-days and 23-days gestation during fetal rabbit development.

Ameloblasts↗
PubMed1983

Murine tooth organ transplantation after in vitro culture.

Molar tooth organs were transplanted from fetal and neonatal mouse donors as well as from cap-stage molar tooth organs following ten days of in vitro culture. Tooth organs from neonatal donors appeared to develop better than those from fetal donors in syngeneic recipients. Cultured allogeneic molar tooth organs appeared to survive longer than uncultured controls.

Animals↗
PubMed1983

Selachian tooth development: II. Immunolocalization of amelogenin polypeptides in epithelium during secretory amelogenesis in Squalus acanthias.

We have determined the distribution of amelogenin polypeptides in an order of elasmobranchs using indirect immunofluorescence with rabbit polyclonal antibodies prepared to purified murine amelogenins. We find that amelogenins are definitely present within the inner enamel epithelium prior to the production of the extracellular matrix component termed "enameloid" (row II developing tooth organs). During subsequent stages of selachian tooth development (row III tooth organs), immunofluorescence staining data indicated localization of amelogenin antigens within epithelium as well as the enameloid extracellular matrix. The results from these immunohistochemical studies suggest that the 16-20 kdalton amelogenins, which are characteristic of murine inner enamel epithelial cells undergoing terminal biochemical differentiation into secretory ameloblasts, may also be regarded as molecular markers for amelogenesis in developing teeth in the spiny dogfish, Squalus acanthias.

Amelogenesis↗
PubMed1983

Research on craniofacial genetics and developmental biology: implications for the future of academic dentistry.

The literature of biology abounds in awe-inspiring acts of iridescent genius. Although a law of nature is phrased in abstract language and is itself devoid of passion and sensibility, the history of its discovery may be an epic worthy of Homer, every page of which bears the stamp of the personality of people. Clearly, scientific truth can be defended by dispassionate logic, but its discovery cannot be promoted this way. The human factor in the creative equation is an important aspect. The discovery of the principles that now form the foundation of developmental craniofacial biology is a story of irony and paradox. Although much progress has been made in many scientific endeavors, many questions regarding craniofacial growth and development remain unanswered. One of the main problems encountered in studies of mammalian growth and development, specifically those dealing with developmental craniofacial biology, has been the apparent lack of application of advances in parallel fields of scientific endeavor. The time seems appropriate for commingling clinical problems with the recently acquired principles of cellular, molecular, and developmental biology.

Animals↗
PubMed1983

Criteria for distinction of different epithelial phenotypes covering murine palatal shelves at the stage of fusion.

Of the major three positional regions associated with secondary palate morphogenesis, the medial edge epithelium facilitates palate fusion during mouse embryogenesis. The epithelial phenotype appears to be acquired vis-a-vis reciprocal and interdependent epithelial-mesenchymal interactions. The objective of the present study is to describe the histological features of the oral, nasal, and medial edge epithelia as well as adjacent ectomesenchyme in vivo and in vitro, during the 14th day of gestation and through 16 hr incubation. Swiss strain mouse embryos were used to investigate epithelial differentiation in vivo as well as in vitro. Histologic criteria used to distinguish different epithelial phenotypes included: (i) orientation of the nucleus, (ii) staining properties of the nuclei, (iii) pattern of intercellular spaces, and (iv) cell degeneration. These criteria were also effective in identifying different populations of ectomesenchymal cells adjacent to the oral, nasal, and medial edge palatal epithelia.

Animals↗