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H C Slavkin

Publications and source records attributed to H C Slavkin.

At least 91 records · Page 5Linked to original sources
PubMed1997

Timing of the expression of enamel gene products during mouse tooth development.

In order to understand the mechanisms involved in tooth development it is important to define the timing for tissue-specific gene expression. A consequence of ameloblast cell differentiation is the sequential expression of tissue-specific genes whose products form the enamel extracellular matrix. The ameloblast phenotype has been characterized as consisting of two major classes of proteins: amelogenins and non-amelogenin proteins such as anionic enamel proteins (enamelins, tuft proteins, tuftelin, sulfated proteins) and enamel proteases. The postulated functions for the anionic enamel proteins are as nucleators for hydroxyapatite crystal formation while amelogenins control the crystal size, growth and orientation. While the amelogenins have been well characterized, detailed knowledge for anionic enamel proteins has been sparse. In the present study, we designed experiments to characterize one of the anionic enamel proteins from mouse molars, tuftelin, and to determine the timing of expression of this protein during molar tooth development. Our results showed the initial detection of tuftelin transcripts within proliferating inner enamel epithelial cells at very early stages of tooth development (13 days of embryonic development equivalent to the bud stage of tooth development). These data provide direct evidence that invalidates previous dogmas that enamel proteins were synthesized by polarized, non-dividing, fully differentiated ameloblast cells. In addition, tuftelin was found to be synthesized also by dental papilla mesenchyme cells suggesting that this protein is not enamel-specific. These data taken together open the possibility that the tuftelin present in the dentino-enamel junction could be secreted by both, preodontoblast cells and preameloblast cells. It might also suggest a possible different role for tuftelin than nucleator of hydroxyapatite crystals.

Amelogenin↗
PubMed1997

Clinical dentistry in the 21st century.

What will oral health care be like in the 21st century? During the 20th century, American dental education evolved from freestanding and often proprietary schools to become an integral part of research-intensive university professional education. This evolution provided a formidable scientific basis for diagnosis, therapeutics, disease prevention, and health promotion. The development of clinical skills coupled with advanced dental materials and therapeutics has truly been remarkable. And now we approach the 21st century as a nation of changing demographics. By 2010, nearly 40 million Americans will be 65 years old or older. Expectations for "quality of life" now punctuate American values. In 1900, the human life span was 45 years, but today it approaches 80 years. Although in 1900, the primary causes of mortality and morbidity were acute infectious diseases, today our challenges include complex viral-infectious as well as neoplastic and chronic disabling diseases (e.g., chronic facial pain, musculoskeletal degeneration, osteoporosis, osteoarthritis, and cerebrovascular and coronary diseases and disorders). In fact, one American dies every hour from oral cancer. Changes in the practice of clinical dentistry in the 21st century will: (1) integrate dental practice into comprehensive health care; (2) become increasingly proactive for health promotion; (3) represent an increased knowledge-base and computer-assisted technology approach for diagnostics and therapeutics; and (4) use novel strategies for oral health care ranging from gene-mediated therapeutics to community-based health promotion.

Delivery of Health Care, Integrated↗
PubMed1996

Abrogation of transforming growth factor-beta type II receptor stimulates embryonic mouse lung branching morphogenesis in culture.

TGF-beta1 is a known inhibitor of branching morphogenesis when added exogenously to mouse embryonic lungs in culture. However, the issue of whether endogenous TGF-beta signaling has a function in the process of lung organogenesis is not completely resolved. We utilized immunoperturbation and antisense oligodeoxynucleotide inhibitory strategies to abrogate TGF-beta type II receptor function in embryonic mouse lungs undergoing branching morphogenesis in serumless explant culture. Antisera directed against a TGF-beta type II receptor N-terminal peptide that perturbs TGF-beta ligand-receptor binding increased branching by 70%. Similarly, antisense TGF-beta type II receptor oligodeoxynucleotides (40 microM) resulted in a 58% increase in branching, compared to scrambled and mismatched sequence controls, while TGF-beta, type II receptor mRNA and its protein expression levels were suppressed by 95 and 84%, respectively. Addition of exogenous TGF-beta1 did not overcome the stimulatory effects either of TGF-beta type II receptor immunoperturbation or of antisense oligodeoxynucleotide treatment on lung branching morphogenesis. Using in situ hybridization and immunohistochemistry, both TGF-beta type II receptor mRNA and protein were localized to the epithelium lining the developing airways, and to the surrounding mesenchyme, indicating that TGF-beta type II receptor is an important regulator of epithelial-mesenchymal interaction. Exogenous TGF-beta1 decreased cyclin A mRNA levels in control embryonic lung explants, while TGF-beta type II receptor antisense oligodeoxynucleotides prevented the downregulation of cyclin A mRNA expression by exogenous TGF-beta1. In addition, PCNA immunostaining of the primitive bronchial epithelium was increased in the presence of TGF-beta type II receptor antisense oligodeoxynucleotides either alone or together with exogenous TGF-beta1, whereas TGF-beta1 alone decreased PCNA staining. Thus, abrogation of TGF-beta type II receptor expression prevented TGF-beta1-induced epithelial cell G1 arrest. These results demonstrate, for the first time, that abrogation of the TGF-beta type II receptor stimulates embryonic lung organogenesis in culture and reverses the negative influence of endogenous TGF-beta signaling upon epithelial cell cycle progression.

Animals↗
PubMed1996

And the next 50 years? The future of recombinant DNA technology in oral medicine.

As we celebrate this spectacular 50th anniversary, fluoridation continues to be the most effective public health strategy to reduce the disease burden of dental caries. Curiously, while H. Trendley Dean and his colleagues at the National Institutes of Health were investigating the effects of fluoride on tooth enamel in the mid-1930s, two young boys, one in London and the other in Chicago, were growing up to become the catalysts for another "biological revolution." These two very talented individuals, James Watson and Francis Crick, would later meet by accident at Cambridge and produce their seminal discovery published in April 1953 as a letter in Nature, a one-page article provoking an international scientific adventure to understand living organisms in terms of the structure and function of deoxyribonucleic acid (DNA), a universal genetic code and a rationale for the applications of recombinant DNA technology (rDNA) in fields as diverse as agriculture, energy, industry, and health. As we now reflect upon the triumphs from fluoridation and ponder the next 50 years and the complexities of craniofacial, oral, and dental diseases, it becomes increasingly evident that recombinant DNA technology coupled with health promotion, disease prevention, and public education offers the promise for remarkable advances in prevention, diagnosis, and therapeutics in oral medicine.

Animals↗
PubMed1996

Embryonic mouse lung epithelial progenitor cells co-express immunohistochemical markers of diverse mature cell lineages.

Developmental expression of marker genes representative of different mature cell types can be used to study differentiation of cell lineages. We used immunohistochemistry to study expression in developing mouse lung of calcitonin gene-related peptide (CGRP), Clara cell 10-KD protein (CC10), and surfactant protein-A (SP-A), markers that are differentially expressed in neuroendocrine cells, Clara cells, and Type II alveolar cells. Two distinct developmental phases were revealed. The earlier phase (embryonic days 13-15; E13-E15) was characterized by CGRP, CC10, and SP-A immunostaining in all epithelial cells of the distal airways, with the three patterns being virtually identical in adjacent sections. The later phase (E16-E18) was characterized by emergence of staining of the differentiated cell types. These expression patterns were recapitulated in serumless organ culture, demonstrating that information necessary to generate both phases of gene expression is present within the lung analage by E11. We conclude that CGRP, CC10, and SP-A are co-expressed in most or all cells of the distal lung epithelium at E13-E15 and later become restricted to different cell lineages. This transient expression in progenitor cells of gene products characteristic of diverse differentiated cell types may reflect an underlying mechanism of gene regulation.

Animals↗
PubMed1996

'The flu zone'.

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Antigenic Variation↗