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H C Slavkin

Publications and source records attributed to H C Slavkin.

288 records · Page 16Linked to original sources
PubMedDate not supplied

Self-assembly of a recombinant amelogenin protein generates supramolecular structures.

Amelogenin proteins are the principal constituents of the extracellular organic matrix associated with the nucleation and growth of the carbonated calcium hydroxyapatite (HAP)-containing mineral phase of dental enamel. Amelogenins are believed to function in controlling the sizes and organization of the developing enamel crystals. Previous studies have shown that enamel proteins exhibit unusual reversible aggregation properties. The present studies were designed to test the hypothesis that self-assembly of recombinant amelogenin generates supramolecular structures that are indistinguishable from the electron-dense particles associated with HAP crystal growth in vivo. A recombinant amelogenin analog of the murine 180-residue protein was analyzed by high-resolution size exclusion chromatography, atomic force (AFM), and transmission electron (TEM) microscopy. It was found that the amelogenin formed supramolecular aggregates which were in a concentration-dependent equilibrium with protein monomers. Imaging of the amelogenin by both AFM and TEM techniques revealed spherical aggregate structures of about 18 nm diameter which were seen to be similar to electron-dense enamel structures observed in vivo. We interpret these results to suggest that, in vivo, the amelogenin protein self-assembles through functional motifs of the protein primary structure, generating specific supramolecular aggregates which we hypothesize function to control the ultrastructural organization of the developing enamel crystallites.

Amelogenin↗
PubMedDate not supplied

Evidence for amelogenin "nanospheres" as functional components of secretory-stage enamel matrix.

Amelogenins are the principal proteins of the extracellular matrix of developing dental enamel and are postulated to function in the processes of biomineralization of the developing tooth although the molecular mechanisms concerned are poorly understood. Recent imaging studies, employing dynamic light scattering, atomic force, and transmission electron microscopy (TEM) have shown that a recombinant amelogenin (M(r) approximately 20,000 Da) spontaneously forms supramolecular quasi-spherical aggregates ("nanospheres") of 15-20 nm in diameter. By comparison with in vitro experiments employing the recombinant amelogenin we show that the nanospheres appear as electron-lucent structures when treated with conventional electron microscopy contrast reagents (phosphotungstate or uranyl acetate) and we speculate that this property derives from the hydrophobic nature of the amelogenin protein. Employing TEM preparations of developing enamel from mouse, bovine, and hamster we demonstrate that the amelogenin nanospheres occur as beaded rows of electron-lucent structures aligned with, and separating, the enamel mineral crystallites. We postulate that the amelogenin monomers self-assemble to form nanospheres which function to space the initial crystallites, control crystal habit, inhibit intercrystalline fusions, and, through the apposition of their surfaces, create anionic channels which facilitate ion transport within the mineralizing matrix.

Amelogenesis↗
PubMedDate not supplied

The Surgeon General's Report and special-needs patients: a framework for action for children and their caregivers.

The Surgeon General's Report, Oral Health in America, is the first comprehensive assessment of oral, dental, and craniofacial health in the history of our nation. The intent of this first-ever Report is to alert Americans to the full meaning of oral health and its importance to general health and well-being across the lifespan. Moreover, the Report has been released at a time in human history of enormous changes as well as opportunities. The convergence of public health policies, "quality of life" expectations, global informatics, a new century of biotechnology, the completion of the Human Genome Project, changes in the management of health care, and the acknowledgment of enormous health disparities herald a call to action. These profound dynamics particularly affect children and their caregivers and the multitude of social, economic, and health issues associated with special patients and developmental disabilities. This paper will highlight the issues, provide recommendations, and suggest a call to action.

Adolescent↗
PubMedDate not supplied

Molecular determinants during dental morphogenesis and cytodifferentiation: a review.

Craniofacial development provides a number of opportunities to investigate the cellular and molecular biology of morphogenesis, cytodifferentiation, tissue-specific extracellular matrix (ECM) formations, and biomineralization. Regulatory processes associated with mandibular morphogenesis and specifically tooth formation are being investigated by the identification of when and where molecular determinants such as cell adhesion molecules (CAMs), substrate adhesion molecules (SAMs), and tissue-specific structural gene products are expressed during sequential developmental stages. Based upon in vitro organotypic culture studies in serumless, chemically defined medium, instructive and permissive signaling has been found to be required for both mandibular and dental morphogenesis and cytodifferentiation. For example, intrinsic developmental instructions (autocrine and paracrine factors), independent of long-range hormonal or exogenous growth factors, mediate morphogenesis from the initiation of the dental lamina through crown and initial root stages of tooth development. This review summarizes recent results using experimental embryology, organ culture, recombinant DNA technology, and immunocytology to elucidate mechanisms responsive to instructive epithelial-mesenchymal interactions associated with mandibular morphogenesis, tooth positional information, and subsequent tooth crown and initial root development.

Amelogenesis Imperfecta↗
PubMedDate not supplied

Inner enamel epithelia synthesize and secrete enamel proteins during mouse molar occlusal "enamel-free area" development.

Mesenchyme-derived instructions for odontogenic epithelial differentiation into ameloblasts and the production of enamel matrix has been well established. However, it is not known how position-specific differences within the enamel organ of rodent molar tooth organs regulate the enamel-forming vs. the enamel free areas in the developing cusp. Light microscopy, transmission electron microscopy, and immunocytochemistry using a rabbit anti-mouse amelogenin antibody, were used to map the position-specific patterns within the enamel organ. In the enamel-forming area, ameloblasts were associated with stratum intermedium. In the enamel-free area, another cell type was interposed between inner enamel epithelia (IEE) and stratum intermedium. IEE in the enamel-free area did not have Tomes' processes and secreted enamel matrix not only toward dentin but also between IEE cells. IEE became confluent with stellate reticulum; at this position stratum intermedium cells were no longer detected. The thickness and orientation of dentin matrix collagen fibers in the enamel-free area were different from the fibers in the enamel-forming area. These results suggest that the patterns of epithelial cell-cell and cell-matrix associations during position-specific enamel organ epithelial differentiation may regulate ameloblast matrix synthesis and/or the matrix secretion pathway.

Animals↗
PubMedDate not supplied

Recombinant DNA technology and clinical dentistry.

The introduction of recombinant DNA technology in the late 1970s led to rapid advancements in our knowledge of genes and genomic structure in the 1980s. Such technology, applied to the human genome, provides new information concerning the nature and possible treatment of inherited disorders throughout the human lifespan. Methods to clone structural genes of interest to clinical dentistry now provide strategies to produce genetically engineered biomaterials for prosthetic dentistry. This methodology is also being used to clone microbial DNAs for periodontal disease diagnosis, therapy, and prognostic applications.

DNA, Recombinant↗