An articulate advocate for science as a way of knowing, as well as an advocate for health and well-being equity for all people of all ages. My scholarship spends 50 years of biomedical research and university-level education, coupled with several opportunities to lead complex organizations.
Progress in in vivo and in situ experimentation has led many researchers to speculate as to the r... more Progress in in vivo and in situ experimentation has led many researchers to speculate as to the relevance and importance of in vitro testing protocols in caries research. A Medline/Biosis search for the present review revealed well over 300 citations (since 1989) documenting in vitro tests associated with caries research on mineralization and fluoride reactivity. The present survey documents these recent applications of in vitro test methods in both mechanistic and 'profile'* caries research. In mechanistic studies, in vitro protocols over the past five years have made possible detailed studies of dynamics occurring in mineral loss and gain from dental tissues and the reaction dynamics associated with fluoride anticaries activity. Similarly, in profile applications, in vitro protocols make possible the inexpensive and rapid-yet sensitive-assessment of F anticaries efficacy within fluoride-active systems, and these tests represent a key component of product activity confirmat...
According to the World Health Report 2004, infectious diseases accounted for 26% of the 57 millio... more According to the World Health Report 2004, infectious diseases accounted for 26% of the 57 million deaths worldwide in 2002. Infectious diseases are the leading cause of death and healthy years lost to illness among people under the age of 50. Lower respiratory tract infections, HIV/AIDS, diarrhoeal disease, tuberculosis and malaria are the main infectious causes of death. In Western countries, including Belgium, infectious diseases are no longer in the top 5 ranking of causes of death (i.e. ischaemic heart disease, cancer, stroke, chronic obstructive pulmonary disease and accidents). On a global scale, the World Health Statistics Report 2007 foresees a similar shift in the distribution of death from communicable to non-communicable diseases between 2002 and 2030 with the exception of HIV/ AIDS. Public health offi cials and the scientifi c medical community, however, should not forget the lesson of the past when it was wrongly suggested that all major infections would disappear within some measurable time (1). Emerging and re-emerging infectious diseases will remain a threat to human health. Underlying factors for the emergence of infectious diseases are grouped in 4 categories: 1) genetic and biologic factors; 2) physical environmental factors; 3) ecologic factors; 4) social, political and economic factors. These domains can work individually or in combination to affect the interaction of humans and microbes. Most of the emerging diseases are zoonotic, arising from an animal reservoir. Diseases such as HIV, Ebola, SARS, avian infl uenza illustrate how man exposes himself to risks by disturbing the balance with microbial species in their natural environment. Microbes have another characteristic that allows them to escape control, namely, they replicate and mutate at a far greater rate than man can ever develop interventions with new antimicrobial agents, vaccines or public health measures (1). Furthermore, travel, migration and trade promote the rapid spread of new pathogens to other parts of the world. Finally, bioterrorism can intentionally introduce new diseases into the population. Anthrax, botulism, Ebola haemorrhagic fever, plague, smallpox and tularaemia are considered high-priority (CDC category A) diseases in this respect (2). Newly emerging diseases are clinical syndromes or pathogens that have never been recognized before. Lyme borreliosis, Bartonella henselae, Helicobacter pylori, hepatitis C, HIV, Nipah and Hendra virus, SARS and H5N1 avian infl uenza are well-known examples. Reemerging or resurging diseases are diseases that are or have been endemic in some parts of the world and come back in a different form or a different location, such as West-Nile virus in the United States of America, Dengue
The International journal of developmental biology, 1992
Occipital somites provide progenitor cells for craniofacial muscle development including the tong... more Occipital somites provide progenitor cells for craniofacial muscle development including the tongue musculature. Serum-derived factors are assumed to be pre-requisite for myogenesis in vitro. To test these assertions, we designed experiments to determine whether early mouse tongue development in general, and desmin localization in particular, were expressed during the development of embryonic mouse first branchial arch explants cultured in serumless, chemically-defined medium. Immunohistochemical techniques determined the chronology and positions of desmin expression during early craniofacial development. Occipital somites expressed desmin at E9 (9 days +/- 2 h post-fertilization, 18-20 somites). A discrete cell migration pathway initiating in the somites and terminating in the lateral lingual processes of the tongue primordium was defined based upon desmin expression patterns in E9-E11 embryos and computer-assisted three dimensional reconstructions. The in vitro model system was pe...
It has been suggested that an extracellular matrix - and cell surface - associated glycoprotein, ... more It has been suggested that an extracellular matrix - and cell surface - associated glycoprotein, fibronectin, plays a role in the positioning of cells in morphogenesis and in the maintenance of orderly tissue organization. In the present study the appearance and distribution of fibronectin during in ovo chick limb development has been investigated by indirect immunofluorescence techniques in H.H. stages 20–30. Fibronectin is not detectable until just prior to the transition from the morphogenetic to the cytodifferentiation phase of development. Beginning at H.H. stage 25, successive nonrandom patterns of fibronectin detection and distribution, which resemble the subsequent cartilaginous elements, precede overt chondrogenesis as detected by Alcian blue staining. This corresponds to the onset of the cytodifferentiation phase of limb development. As the accumulation of acidic proteoglycan increases in the cartilage matrix and the mesenchymal cells become more round in appearance, the p...
A major issue in developmental biology is to determine how time and position-restricted instructi... more A major issue in developmental biology is to determine how time and position-restricted instructions are signaled and received during morphogenesis of different phenotypes, of which tooth, Meckel's cartilage and tongue formation are classical examples. It is now evident that a hierarchy of growth factors and their downstream transcription factors regulate the timing, sequence and position of cells and tissues in forming different phenotypes during embryogenesis. Here we report the development of an early mandibular organ culture model. Explants of E8 and E9 first branchial arch were cultured and produced mandibular processes with cap stage tooth formation, Meckel's cartilage and tongue development. In tandem, vital dye (Dil) labeling studies confirmed that rhombomeres 1-4 give rise to craneal neural crest (CNC) cells which emigrate from the neural fold to the forming maxillary and mandibular arches. Furthermore, we have tested the feasibility of investigating the regulation ...
The International journal of developmental biology, 1996
Pattern formation is intrinsically hierarchical, increasing in complexity from the first early em... more Pattern formation is intrinsically hierarchical, increasing in complexity from the first early embryonic inductive tissue interactions to the eventual integration of multiple organ systems. Viewed as a problem in pattern formation, the vertebrate ear is an exceedingly complex organ system in which normal morphogenesis requires multiple inductive interactions between a variety of adjacent tissues. In order to model the process of higher level pattern formation, we have developed a method for organ culture of the embryonic murine ear. E10.5 mouse embryos (38 to 42 somite pairs) were microdissected into explants that consist of the first and second branchial arches, the otocyst, and the adjacent neural tube. The growth of these explants in a serumless, chemically-defined medium was compared to medium supplemented with 10% fetal calf serum. After 6 days in culture using serumless medium, we observed that this environment was permissive for the formation of pinnae, rudimentary semicircul...
Epidermal organogenesis (thyroid gland, salivary gland, feather, hair, skin, thymus gland, tooth,... more Epidermal organogenesis (thyroid gland, salivary gland, feather, hair, skin, thymus gland, tooth, etc.) generally follows a basic rule; epithelium exhibits well-documented interdependence with adjacent mesenchyme for a specific path of development (Grobstein, 1967, for review). Koch (1967) demonstrated in rodent embryos that isolates of incisor epithelial and mesenchymal tissue, separated by a millipore filter, continued to develop. When homotypic tissues were placed in juxtaposition to the filter, no evidence of continued differentiation was observed. Isolated cervical loop tissues of tooth germs from mammalian embryos have been shown to develop into an entire tooth in vitro (Slavkin & Bavetta, 1968 a; Kollar & Baird, 1969). Our laboratory recently reported that isolated tissue preparations (Slavkin & Bavetta, 1968 a) or cell suspensions (Slavkin, Beierle & Bavetta, 1968) of epithelial and mesenchymal cells from the embryonic cervical loop, in recombination on the chick chorioallan...
Publisher Summary This chapter indicates several issues of interest to developmental biologists. ... more Publisher Summary This chapter indicates several issues of interest to developmental biologists. It indicates a few problems that seem important for the understanding of craniofacial developmental biology. The developing secondary palate is an attractive system for morphogenetic studies. Being much less complex than the development of the whole embryo, palate morphogenesis provides examples of the fundamental problems found within developmental biology. During early stages of development, for example, epithelial–mesenchymal interactions between oral ectoderm and adjacent cranial, neural crest-derived ectomesenchyme result in the determination of bilateral palate morphogenetic fields. The determination of polarity in the secondary palate is observed along the anteroposterior axis. Interactions among cells, tissues, and the extracellular matrix milieu result in the induction, determination, and expression of a number of phenotypes including ectodermally derived nasal, oral, and medial edge palatal epithelia, and ectomesenchyme-derived chondrogenesis, osteogenesis, and fibrogenesis. Programmed cell death of medial edge epithelia during mammalian palate fusion is a fascinating developmental problem. Phylogenetic differences among Reptilia, Aves, and Mammalia offer significant developmental questions for the craniofacial developmental biologists.
Position- and time-restricted amelogenin gene transcription was analysed in developing tooth orga... more Position- and time-restricted amelogenin gene transcription was analysed in developing tooth organs using in situ hybridization with asymmetric complementary RNA probes produced from a cDNA specific to the mouse 26 × 10(3) Mr amelogenin. In situ analysis was performed on developmentally staged fetal and neonatal mouse mandibular first (M1) and maxillary first (M1) molar tooth organs using serial sections and three-dimensional reconstruction. Amelogenin mRNA was first detected in a cluster of ameloblasts along one cusp of the M1 molar at the newborn stage of development. In subsequent developmental stages, amelogenin transcripts were detected within foci of ameloblasts lining each of the five cusps comprising the molar crown form. The number of amelogenin transcripts appeared to be position-dependent, being more abundant on one cusp surface while reduced along the opposite surface. Amelogenin gene transcription was found to be bilaterally symmetric between the developing right and le...
During tooth development, enamel organ epithelial cells express a tissue-specific gene product (a... more During tooth development, enamel organ epithelial cells express a tissue-specific gene product (amelogenin) which presumably functions to control calcium hydroxyapatite crystal growth patterns during enamel biomineralization. The present studies were designed to test the hypothesis that amelogenin as a supramolecular aggregate regulates crystal growth during enamel biomineralization. Antisense oligodeoxynucleotide strategy was used in a simple organ culture system to inhibit amelogenin translation. Under these experimental conditions, antisense treatment prior to and during amelogenin expression resulted in inhibition of amelogenin translation products within immunoprecipitated [35S]methionine metabolically labeled proteins. To determine the efficiency of antisense treatment in this model system, digoxigenin-labeled oligodeoxynucleotides were observed to diffuse throughout the tooth explants including the target ameloblast cells within 24 hours. Ultrastructural analyses of amelogeni...
We are living in an extraordinary time in human history punctuated by the convergence of major sc... more We are living in an extraordinary time in human history punctuated by the convergence of major scientific and technological progress in the physical, chemical, and biological ways of knowing. Equally extraordinary are the sparkling intellectual developments at the interface between fields of study. One major example of an emerging influence on the future of oral health education is at the interface between the human genome, information technology, and biotechnology with miniaturizations (nanotechnology), suggesting new oral health professional competencies for a new century. A great deal has recently been learned from human and non-human genomics. Genome databases are being "mined" to prompt hypothesis-driven "postgenomic" or functional genomic science in microbial models such as Candida albicans related to oral candidiasis and in human genomics related to biological processes found in craniofacial, oral, and dental diseases and disorders. This growing body of knowledge is already providing the gene content of many oral microbial and human genomes and the knowledge of genetic variants or polymorphisms related to disease, disease progression, and disease response to therapeutics (pharmacogenomics). The knowledge base from human and non-human genomics, functional genomics, biotechnology, and associated information technologies is serving to revolutionize oral health promotion, risk assessment using biomarkers and disease prevention, diagnostics, treatments, and the full range of therapeutics for craniofacial, oral, and dental diseases and disorders. Education, training, and research opportunities are already transforming the curriculum and pedagogy for undergraduate science majors, predoctoral health professional programs, residency and specialty programs, and graduate programs within the health professions. In the words of Bob Dylan, "the times they are a-changing."
Progress in in vivo and in situ experimentation has led many researchers to speculate as to the r... more Progress in in vivo and in situ experimentation has led many researchers to speculate as to the relevance and importance of in vitro testing protocols in caries research. A Medline/Biosis search for the present review revealed well over 300 citations (since 1989) documenting in vitro tests associated with caries research on mineralization and fluoride reactivity. The present survey documents these recent applications of in vitro test methods in both mechanistic and 'profile'* caries research. In mechanistic studies, in vitro protocols over the past five years have made possible detailed studies of dynamics occurring in mineral loss and gain from dental tissues and the reaction dynamics associated with fluoride anticaries activity. Similarly, in profile applications, in vitro protocols make possible the inexpensive and rapid-yet sensitive-assessment of F anticaries efficacy within fluoride-active systems, and these tests represent a key component of product activity confirmat...
According to the World Health Report 2004, infectious diseases accounted for 26% of the 57 millio... more According to the World Health Report 2004, infectious diseases accounted for 26% of the 57 million deaths worldwide in 2002. Infectious diseases are the leading cause of death and healthy years lost to illness among people under the age of 50. Lower respiratory tract infections, HIV/AIDS, diarrhoeal disease, tuberculosis and malaria are the main infectious causes of death. In Western countries, including Belgium, infectious diseases are no longer in the top 5 ranking of causes of death (i.e. ischaemic heart disease, cancer, stroke, chronic obstructive pulmonary disease and accidents). On a global scale, the World Health Statistics Report 2007 foresees a similar shift in the distribution of death from communicable to non-communicable diseases between 2002 and 2030 with the exception of HIV/ AIDS. Public health offi cials and the scientifi c medical community, however, should not forget the lesson of the past when it was wrongly suggested that all major infections would disappear within some measurable time (1). Emerging and re-emerging infectious diseases will remain a threat to human health. Underlying factors for the emergence of infectious diseases are grouped in 4 categories: 1) genetic and biologic factors; 2) physical environmental factors; 3) ecologic factors; 4) social, political and economic factors. These domains can work individually or in combination to affect the interaction of humans and microbes. Most of the emerging diseases are zoonotic, arising from an animal reservoir. Diseases such as HIV, Ebola, SARS, avian infl uenza illustrate how man exposes himself to risks by disturbing the balance with microbial species in their natural environment. Microbes have another characteristic that allows them to escape control, namely, they replicate and mutate at a far greater rate than man can ever develop interventions with new antimicrobial agents, vaccines or public health measures (1). Furthermore, travel, migration and trade promote the rapid spread of new pathogens to other parts of the world. Finally, bioterrorism can intentionally introduce new diseases into the population. Anthrax, botulism, Ebola haemorrhagic fever, plague, smallpox and tularaemia are considered high-priority (CDC category A) diseases in this respect (2). Newly emerging diseases are clinical syndromes or pathogens that have never been recognized before. Lyme borreliosis, Bartonella henselae, Helicobacter pylori, hepatitis C, HIV, Nipah and Hendra virus, SARS and H5N1 avian infl uenza are well-known examples. Reemerging or resurging diseases are diseases that are or have been endemic in some parts of the world and come back in a different form or a different location, such as West-Nile virus in the United States of America, Dengue
The International journal of developmental biology, 1992
Occipital somites provide progenitor cells for craniofacial muscle development including the tong... more Occipital somites provide progenitor cells for craniofacial muscle development including the tongue musculature. Serum-derived factors are assumed to be pre-requisite for myogenesis in vitro. To test these assertions, we designed experiments to determine whether early mouse tongue development in general, and desmin localization in particular, were expressed during the development of embryonic mouse first branchial arch explants cultured in serumless, chemically-defined medium. Immunohistochemical techniques determined the chronology and positions of desmin expression during early craniofacial development. Occipital somites expressed desmin at E9 (9 days +/- 2 h post-fertilization, 18-20 somites). A discrete cell migration pathway initiating in the somites and terminating in the lateral lingual processes of the tongue primordium was defined based upon desmin expression patterns in E9-E11 embryos and computer-assisted three dimensional reconstructions. The in vitro model system was pe...
It has been suggested that an extracellular matrix - and cell surface - associated glycoprotein, ... more It has been suggested that an extracellular matrix - and cell surface - associated glycoprotein, fibronectin, plays a role in the positioning of cells in morphogenesis and in the maintenance of orderly tissue organization. In the present study the appearance and distribution of fibronectin during in ovo chick limb development has been investigated by indirect immunofluorescence techniques in H.H. stages 20–30. Fibronectin is not detectable until just prior to the transition from the morphogenetic to the cytodifferentiation phase of development. Beginning at H.H. stage 25, successive nonrandom patterns of fibronectin detection and distribution, which resemble the subsequent cartilaginous elements, precede overt chondrogenesis as detected by Alcian blue staining. This corresponds to the onset of the cytodifferentiation phase of limb development. As the accumulation of acidic proteoglycan increases in the cartilage matrix and the mesenchymal cells become more round in appearance, the p...
A major issue in developmental biology is to determine how time and position-restricted instructi... more A major issue in developmental biology is to determine how time and position-restricted instructions are signaled and received during morphogenesis of different phenotypes, of which tooth, Meckel's cartilage and tongue formation are classical examples. It is now evident that a hierarchy of growth factors and their downstream transcription factors regulate the timing, sequence and position of cells and tissues in forming different phenotypes during embryogenesis. Here we report the development of an early mandibular organ culture model. Explants of E8 and E9 first branchial arch were cultured and produced mandibular processes with cap stage tooth formation, Meckel's cartilage and tongue development. In tandem, vital dye (Dil) labeling studies confirmed that rhombomeres 1-4 give rise to craneal neural crest (CNC) cells which emigrate from the neural fold to the forming maxillary and mandibular arches. Furthermore, we have tested the feasibility of investigating the regulation ...
The International journal of developmental biology, 1996
Pattern formation is intrinsically hierarchical, increasing in complexity from the first early em... more Pattern formation is intrinsically hierarchical, increasing in complexity from the first early embryonic inductive tissue interactions to the eventual integration of multiple organ systems. Viewed as a problem in pattern formation, the vertebrate ear is an exceedingly complex organ system in which normal morphogenesis requires multiple inductive interactions between a variety of adjacent tissues. In order to model the process of higher level pattern formation, we have developed a method for organ culture of the embryonic murine ear. E10.5 mouse embryos (38 to 42 somite pairs) were microdissected into explants that consist of the first and second branchial arches, the otocyst, and the adjacent neural tube. The growth of these explants in a serumless, chemically-defined medium was compared to medium supplemented with 10% fetal calf serum. After 6 days in culture using serumless medium, we observed that this environment was permissive for the formation of pinnae, rudimentary semicircul...
Epidermal organogenesis (thyroid gland, salivary gland, feather, hair, skin, thymus gland, tooth,... more Epidermal organogenesis (thyroid gland, salivary gland, feather, hair, skin, thymus gland, tooth, etc.) generally follows a basic rule; epithelium exhibits well-documented interdependence with adjacent mesenchyme for a specific path of development (Grobstein, 1967, for review). Koch (1967) demonstrated in rodent embryos that isolates of incisor epithelial and mesenchymal tissue, separated by a millipore filter, continued to develop. When homotypic tissues were placed in juxtaposition to the filter, no evidence of continued differentiation was observed. Isolated cervical loop tissues of tooth germs from mammalian embryos have been shown to develop into an entire tooth in vitro (Slavkin & Bavetta, 1968 a; Kollar & Baird, 1969). Our laboratory recently reported that isolated tissue preparations (Slavkin & Bavetta, 1968 a) or cell suspensions (Slavkin, Beierle & Bavetta, 1968) of epithelial and mesenchymal cells from the embryonic cervical loop, in recombination on the chick chorioallan...
Publisher Summary This chapter indicates several issues of interest to developmental biologists. ... more Publisher Summary This chapter indicates several issues of interest to developmental biologists. It indicates a few problems that seem important for the understanding of craniofacial developmental biology. The developing secondary palate is an attractive system for morphogenetic studies. Being much less complex than the development of the whole embryo, palate morphogenesis provides examples of the fundamental problems found within developmental biology. During early stages of development, for example, epithelial–mesenchymal interactions between oral ectoderm and adjacent cranial, neural crest-derived ectomesenchyme result in the determination of bilateral palate morphogenetic fields. The determination of polarity in the secondary palate is observed along the anteroposterior axis. Interactions among cells, tissues, and the extracellular matrix milieu result in the induction, determination, and expression of a number of phenotypes including ectodermally derived nasal, oral, and medial edge palatal epithelia, and ectomesenchyme-derived chondrogenesis, osteogenesis, and fibrogenesis. Programmed cell death of medial edge epithelia during mammalian palate fusion is a fascinating developmental problem. Phylogenetic differences among Reptilia, Aves, and Mammalia offer significant developmental questions for the craniofacial developmental biologists.
Position- and time-restricted amelogenin gene transcription was analysed in developing tooth orga... more Position- and time-restricted amelogenin gene transcription was analysed in developing tooth organs using in situ hybridization with asymmetric complementary RNA probes produced from a cDNA specific to the mouse 26 × 10(3) Mr amelogenin. In situ analysis was performed on developmentally staged fetal and neonatal mouse mandibular first (M1) and maxillary first (M1) molar tooth organs using serial sections and three-dimensional reconstruction. Amelogenin mRNA was first detected in a cluster of ameloblasts along one cusp of the M1 molar at the newborn stage of development. In subsequent developmental stages, amelogenin transcripts were detected within foci of ameloblasts lining each of the five cusps comprising the molar crown form. The number of amelogenin transcripts appeared to be position-dependent, being more abundant on one cusp surface while reduced along the opposite surface. Amelogenin gene transcription was found to be bilaterally symmetric between the developing right and le...
During tooth development, enamel organ epithelial cells express a tissue-specific gene product (a... more During tooth development, enamel organ epithelial cells express a tissue-specific gene product (amelogenin) which presumably functions to control calcium hydroxyapatite crystal growth patterns during enamel biomineralization. The present studies were designed to test the hypothesis that amelogenin as a supramolecular aggregate regulates crystal growth during enamel biomineralization. Antisense oligodeoxynucleotide strategy was used in a simple organ culture system to inhibit amelogenin translation. Under these experimental conditions, antisense treatment prior to and during amelogenin expression resulted in inhibition of amelogenin translation products within immunoprecipitated [35S]methionine metabolically labeled proteins. To determine the efficiency of antisense treatment in this model system, digoxigenin-labeled oligodeoxynucleotides were observed to diffuse throughout the tooth explants including the target ameloblast cells within 24 hours. Ultrastructural analyses of amelogeni...
We are living in an extraordinary time in human history punctuated by the convergence of major sc... more We are living in an extraordinary time in human history punctuated by the convergence of major scientific and technological progress in the physical, chemical, and biological ways of knowing. Equally extraordinary are the sparkling intellectual developments at the interface between fields of study. One major example of an emerging influence on the future of oral health education is at the interface between the human genome, information technology, and biotechnology with miniaturizations (nanotechnology), suggesting new oral health professional competencies for a new century. A great deal has recently been learned from human and non-human genomics. Genome databases are being "mined" to prompt hypothesis-driven "postgenomic" or functional genomic science in microbial models such as Candida albicans related to oral candidiasis and in human genomics related to biological processes found in craniofacial, oral, and dental diseases and disorders. This growing body of knowledge is already providing the gene content of many oral microbial and human genomes and the knowledge of genetic variants or polymorphisms related to disease, disease progression, and disease response to therapeutics (pharmacogenomics). The knowledge base from human and non-human genomics, functional genomics, biotechnology, and associated information technologies is serving to revolutionize oral health promotion, risk assessment using biomarkers and disease prevention, diagnostics, treatments, and the full range of therapeutics for craniofacial, oral, and dental diseases and disorders. Education, training, and research opportunities are already transforming the curriculum and pedagogy for undergraduate science majors, predoctoral health professional programs, residency and specialty programs, and graduate programs within the health professions. In the words of Bob Dylan, "the times they are a-changing."
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Papers by Harold Slavkin