Biomedical subjects

C F Shuler

Publications and source records attributed to C F Shuler.

At least 19 recordsLinked to original sources

PubMed2007

Evaluation of student and faculty perceptions of the PBL curriculum at two dental schools from a student perspective: a cross-sectional survey.

Problem-based learning (PBL) research has primarily highlighted issues related to medical education and less evaluation has been reported from the field of dental education. Furthermore, literature reports tend to focus mainly on PBL from a pedagogic and curriculum constructional view and up to this date, studies from a student perspective are lacking. The aim of this study was to approach the evaluation of student and staff perceptions of PBL curricula from a student perspective at two separate schools: the Faculty of Odontology at the University of Malmö, Sweden and the dental school of the University of Southern California, School of Dentistry (USCSD), Los Angeles, CA, USA. The study was initiated and conducted by two of the authors, at the time senior students at the Faculty of Odontology in Malmö, Sweden. The study was comprised of a literature search, a 2 week field trip to USCSD, USA, survey distribution to students and faculty in both schools, analysis of the data and a written report for oral defence. The results from the survey were intended to provide feedback on student and faculty perceptions regarding the PBL curriculum. The results indicate a general student and faculty satisfaction with the PBL curriculum. Perhaps, surprisingly their perceptions did not differ significantly despite differences in geography, culture and implementation of PBL pedagogy.

Attitude of Health Personnel↗

PubMed2004

Effects of diet consistency on the expression of insulin-like growth factors (IGFs), IGF receptors and IGF binding proteins during the development of rat masseter muscle soon after weaning.

A soft diet facilitates the development of faster-type fibres in rat masseter muscle in the 9 days after weaning compared with a hard diet. To determine whether insulin-like growth factors (IGFs), IGF receptors (IGFRs) and IGF binding proteins (IGFBPs) are involved in this fibre-type alteration, the expression of myosin heavy chain (MHC), IGF, IGFR and IGFBP mRNAs in the masseter muscle of rats fed a hard or soft diet for 9 days after weaning was analysed using competitive, reverse transcriptase-polymerase chain reaction. A soft diet decreased the expression of MHC IIa (slower type) by 70%, but increased the expression of MHC IIx (intermediate type) and IIb (faster type) by 80 and 582%, respectively, compared with a hard diet. These findings verified that a soft diet facilitates the development of faster-type fibres in rat masseter muscle compared with a hard diet. A soft diet induced reductions of 25-76% (P < 0.05-0.01) in the expression of IGF-I, IGF-II, IGFR2, IGFBP4 and IGFBP6 compared with a hard diet, but induced a 25% (P < 0.05) increase only in expression of IGFBP3. These findings suggest that the changes in expression of IGF-I, IGF-II, IGFR2, IGFBP3, IGFBP4 and IGFBP6 are associated with the fibre-type alteration of rat masseter muscle in response to diet consistency soon after weaning.

Animals↗

PubMed2001

Antagonistic effects of Smad2 versus Smad7 are sensitive to their expression level during tooth development.

Members of the transforming growth factor-beta (TGF-beta) superfamily regulate cell proliferation, differentiation, and apoptosis, controlling the development and maintenance of most tissues. TGF-beta signal is transmitted through the phosphorylation of Smad proteins by TGF-beta receptor serine/threonine kinase. During early tooth development, TGF-beta inhibits proliferation of enamel organ epithelial cells but the underlying molecular mechanisms are largely unknown. Here we tested the hypothesis that antagonistic effects between Smad2 and Smad7 regulate TGF-beta signaling during tooth development. Attenuation of Smad2 gene expression resulted in significant advancement of embryonic tooth development with increased proliferation of enamel organ epithelial cells, while attenuation of Smad7 resulted in significant inhibition of embryonic tooth development with increased apoptotic activity within enamel organ epithelium. These findings suggest that different Smads may have differential activities in regulating TGF-beta-mediated cell proliferation and death. Furthermore, functional haploinsufficiency of Smad2, but not Smad3, altered TGF-beta-mediated tooth development. The results indicate that Smads are critical factors in orchestrating TGF-beta-mediated gene regulation during embryonic tooth development. The effectiveness of TGF-beta signaling is highly sensitive to the level of Smad gene expression.

Animals↗

PubMed2001

The Krox-20 null mutation differentially affects the development of masticatory muscles.

The Krox-20 null mutation results in a loss of rhombomeres 3 and 5, which give rise to neurons that are essential to oral motor behaviors. Thus, the Krox-20 null mutant is an excellent model to investigate the development of oral motor circuitry. Our morphological examination of embryonic and neonatal Krox-20 null mutants revealed that a significant reduction of anterior digastric and mylohyoid muscles, the primary jaw openers, occurs between embryonic days 15 and 19. There are no gross morphological alterations in other masticatory muscles. These findings demonstrate that Krox-20 expression is critical for the normal development of the primary jaw opener musculature and they help explain previous studies documenting a reduction in jaw opening in Krox-20 null mutants. Since jaw opening is the power stroke of suckling behavior, our data help explain the reduction of colostrum/milk ingestion in Krox-20 null mutant neonates.

Animals↗

PubMed2001

Molecular regulation of tongue and craniofacial muscle differentiation.

The molecular regulation of muscle development is tightly controlled at three distinct stages of the process: determination, differentiation, and maturation. Developmentally, specific populations of myoblasts exhibit distinct molecular phenotypes that begin to limit the ultimate characteristics of the muscle fibers. The expression of the myogenic regulatory factor family of the transcription process plays a key role in muscle development and, ultimately, in the subset of contractile genes expressed in a specific muscle. Craniofacial muscles have distinct functional requirements and associated molecular phenotypes that distinguish them from other skeletal muscles. The general principles of muscle molecular differentiation with specific reference to craniofacial muscles, such as the tongue, are discussed in this review.

Animals↗

PubMed2001

The changing face of dental education: the impact of PBL.

The past decade has seen increasing demands for reform of dental education that would produce a graduate better equipped to work in the rapidly changing world of the twenty-first century. Among the most notable curriculum changes implemented in dental schools is a move toward Problem-Based Learning (PBL). PBL, in some form, has been a feature of medical education for several decades, but has only recently been introduced into dental schools. This paper discusses the rationale for the introduction of a PBL pedagogy into dental education, the modalities of PBL being introduced, and the implications of the introduction of PBL into dental schools. Matters related to implementation, faculty development, admissions, and assessment are addressed. Observations derived from a parallel-track dental PBL curriculum at the University of Southern California (USC) are presented and discussed. This program conforms to the Barrows (1998) concept of "authentic PBL" in that the program has no scheduled lectures and maintains a PBL pedagogy for all four years of the curriculum. The USC dental students working in the PBL curriculum have attained a high level of achievement on U.S. National Dental Boards (Part I) examinations, significantly superior to their peers working in a traditional lecture-based curriculum.

Achievement↗

PubMed2001

Inherited risks for susceptibility to dental caries.

Dental caries incidence is affected by host factors that may be related to the structure of dental enamel, immunologic response to cariogenic bacteria, or the composition of saliva. Genetic variation of the host factors may contribute to increased risks for dental caries. This systematic review examined the literature to address the question, "Is the risk for dental decay related to patterns of genetic inheritance?" Numerous reports have described a potential genetic contribution to the risk for dental caries. Studies on twins have provided strong evidence for the role of inheritance. Establishing a basis for a genetic contribution to dental caries will provide a foundation for future studies utilizing the human genome sequence to improve understanding of the disease process. Inherited disorders of tooth development with altered enamel structure increase the incidence of dental caries. Specific genetic linkage has not been determined for all of the syndromes of altered tooth development. Consequently, genetic screens of large populations for genes or mutations associated with increased caries susceptibility have not been done. Altered immune response to the cariogenic bacteria may also increase the incidence of caries. Association between specific patterns of HLA genetic inheritance and dental caries risk is weak and does not provide a predictable basis for predicting future decay rates. The evidence supporting an inherited susceptibility to dental caries is limited. Genetic linkage approaches on well-characterized populations with clearly defined dental caries incidence will be required to further analyze the relationship between inheritance and dental caries.

Dental Caries↗

PubMed2001

Keeping the curriculum current with research and problem-based learning.

Active learning is more effective than passive learning and the critical activities are discovery, mastery, and application. Only 10% of a typical dentist's career is spent in dental school, so the educational experience must provide the tools used for lifelong learning. Problem-Based Learning is a model used in several dental schools that is grounded in these assumptions. PBL makes use of small groups, patient cases serving as the vehicle for learning, with student directed outcomes.

Curriculum↗

PubMed2000

True enamel covering in teeth of the Australian lungfish Neoceratodus forsteri.

Lungfish are a unique order of sarcopterygian fish cleidographically positioned between tetrapods and fish. An uninterrupted 400-million-year-old fossil record has documented lungfish skeletal elements to remain virtually unchanged since the Early Devonian. In the current study we investigated the enamel layer of lungfish teeth in order to determine whether there was evidence for higher vertebrate "true" enamel in the Australian lungfish. Juvenile lungfish from the Brisbane River were processed for light and electron microscopy and analyzed for parameters indicative of true enamel formation. Using anti-amelogenin primary antibodies for immunodetection and Western blots, enamel protein epitopes were detected in developing lungfish teeth. Using transmission electron microscopy and electron diffraction analysis, long and parallel-oriented hydroxyapatite crystals were observed in lungfish outer tooth coverings. Our findings indicate that Australian lungfish teeth are covered by a layer of true enamel. Based on the lungfish fossil record we conclude that features of true enamel formation may be as old as 400 million years. Based on taxonomic classification we confirm that true enamel is found not only in tetrapods but also in the sarcopterygian clade of the Gnathostomata.

Aging↗

PubMed2000

Embryonic, fetal, and neonatal tongue myoblasts exhibit molecular heterogeneity in vitro.

Variable gene expression patterns have been shown to exist between embryonic, fetal, and neonatal lineages of limb skeletal myoblasts in vitro and in vivo. In this study, we examined the molecular phenotype of embryonic, fetal, and neonatal tongue myoblasts in primary culture for comparison with in vivo developmental tongue myoblasts. Myogenic regulatory factor (MRF) and myosin heavy chain (MHC) gene expression were determined in culture during both growth and differentiation conditions by PCR, immunoblotting, and immunohistochemistry. Unlike their in vivo tongue myoblast equivalents, developmental tongue myoblast cultures featured the expression of MyoD when kept in growth conditions. Differentiation conditions in vitro induced myogenic tongue lineages to maintain characteristics of their in vivo morphologic and contractile gene phenotype. Both in vivo and in vitro, embryonic tongue lineages predominantly expressed MHC-embryonic isoforms, while fetal and neonatal tongue lineages predominantly expressed fast and perinatal isoforms of contractile genes. A notable difference from the in vivo condition that was observed in differentiated tongue myotubes in vitro was the presence of the MHC-slow protein. It was previously demonstrated that MHC-slow protein was undetectable during the in vivo development of the tongue musculature despite the abundance of slow isoform transcripts. The present characterization of primary tongue myogenic cultures indicates that murine myoblast heterogeneity exists primarily between developmental lineages at the level of contractile gene expression. Outside their native surroundings, developmental myogenic tongue populations are unable to recapitulate the determination and differentiation molecular profiles that occur in vivo.

Animals↗

PubMed2000

Characterization of desmosomal component expression during palatogenesis.

Adhesion of the opposing palatal shelves is a critical first step in the mechanism for palatal fusion. Formation of desmosomal junctions between the two medial edge epithelia provides a mechanism for palatal shelf adhesion. RT-PCR and immunohistochemistry were used to determine the pattern of expression of desmosomal components during palatogenesis. Desmosomal expression was specifically upregulated in the medial edge epithelia (MEE) at the early stages of palatal fusion as detected by both immunohistochemistry and electron microscopy. RT-PCR characterization of the desmosomal components detected all known elements, except desmocollin 1 (DSC1). Desmocollin 2 (DSC2) was expressed as both the DSC2a and DSC2b variants. The two variants are expressed at the same level. Western analysis of desmoglein expression paralleled the RT-PCR result. The temporal and spatial upregulation of desmosomal gene expression is evidence that the MEE induce new gene expression required to accomplish palatal shelf adhesion and initiate the first stage of palatal fusion.

Animals↗

PubMed2000

The TGF-beta type III receptor is localized to the medial edge epithelium during palatal fusion.

During palatal fusion, the medial edge epithelial cells (MEE) but not the oral/nasal palatal epithelium, selectively undergo epithelial-mesenchymal transformation. It is known that this process is regulated, at least in part, by endogenous TGF-beta3. One conceivable mechanism is that restricted expression of TGF-beta receptors (TbetaRs) in a subpopulation of cells may localize TGF-beta responsiveness (Brown et al., 1999). However, TGF-beta type II receptor (TbetaR-II) is expressed by all palatal epithelial cells during palatal fusion (Cui et al., 1998) and therefore cannot localize TGF-beta3 responsiveness. To investigate the role of TGF-beta type III receptor (TbetaR-III) in MEE transformation, we examined the expression pattern of TbetaR-III in the developing palate from E12 to E15 mice in vivo and in vitro by immunohistochemistry and compared the expression pattern to that of type I receptor (TbetaR-I). The expression of TbetaR-III was temporo-spatially restricted to the MEE during palatal fusion, while the expression of TbetaR-I was primarily localized in all palatal epithelia, consistent with the expression patterns of TbetaR-II and TGF-beta3 (Cui et al., 1998). These results support our hypothesis that TbetaR-III localizes and mediates the developmental role of TGF-beta3 on MEE transformation by specific expression in the MEE. TbetaR-III may modulate TGF-beta3 binding to TbetaR-II in the MEE cells to locally enhance TGF-beta3 autocrine signaling through the TbetaR-I/TbetaR-II receptor complex, which contributes to MEE selective epithelial-mesenchymal transformation.

Activin Receptors, Type I↗

PubMed1999

Epidermal growth factor receptor function is necessary for normal craniofacial development and palate closure.

Craniofacial malformations are among the most frequent congenital birth defects in humans; cleft palate, that is inadequate fusion of the palatal shelves, occurs with an annual incidence of 1 in 700 to 1 in 1,000 live births among individuals of European descent. The secondary palate arises as bilateral outgrowths from the maxillary processes, and its formation depends on the coordinated development of craniofacial structures including the Meckel's cartilage and the mandible. Cleft lip and palate syndromes in humans are associated with polymorphisms in the gene (TGFA) encoding transforming growth factor-alpha (TGF-alpha), an epidermal growth factor receptor (EGFR) ligand made by most epithelia. Here we have characterized craniofacial development in Egfr-deficient (Egfr-/-) mice. Newborn Egfr-/- mice have facial mediolateral defects including narrow, elongated snouts, underdeveloped lower jaw and a high incidence of cleft palate. Palatal shelf explants from Egfr-/- mice fused, but frequently had residual epithelium in the midline. In addition, morphogenesis of Meckel's cartilage was deficient in cultured mandibular processes from Egfr-/- embryos. The secretion of matrix metalloproteinases (MMPs) was diminished in Egfr-/- explants, consistent with the ability of EGF to increase MMP secretion and with the decreased MMP expression caused by inhibition of Egfr signalling in wild-type explants. Accordingly, inactivation of MMPs in wild-type explants phenocopied the defective morphology of Meckel's cartilage seen in Egfr-/- explants. Our results indicate that EGFR signalling is necessary for normal craniofacial development and that its role is mediated in part by its downstream targets, the MMPs, and may explain the genetic correlation of human cleft palate with polymorphisms in TGFA.

Animals↗

PubMed1999

Keratin 19 downregulation by oral squamous cell carcinoma lines increases invasive potential.

Squamous cell carcinoma (SCC) of the head and neck is the sixth most frequent cancer worldwide. The survival rate is among the lowest of the major cancers and has not improved significantly in the past two decades. Extensive local invasion and regional lymph node metastasis are, in large part, responsible for the poor clinical outcome of these tumors. Keratin intermediate filaments are the most abundant cytoskeletal proteins in SCCs and regulate the migration of normal and transformed epithelial cells. Previous studies have shown that expression of the 40-kDa keratin K19 is dysregulated in SCCs arising from oral epithelium. Immunohistochemical experiments demonstrated that, while normal epithelium and dysplastic lesions expressed abundant K19 protein, invasive SCCs exhibited a patchy or negative staining pattern. We subsequently determined that K19 expression was consistently downregulated in seven SCC lines compared with normal epithelium. We therefore wanted to determine if K19 downregulation affected the invasive phenotype of these cells. We found that SCC lines which do not express K19 are significantly more invasive in vitro than those which retain expression of this gene. Stable expression of the K19 cDNA in K19 negative cell lines altered cell morphology and intercellular adhesiveness, and significantly decreased the number of cells able to migrate through a reconstituted basement membrane. Reduced invasiveness was not due to decreased metalloproteinase activity in the K19-expressing clones. We conclude that K19 overexpression in oral SCCs decreases their invasive potential by diminishing migratory capability.

Basement Membrane↗

PubMed1999

Regulation of tumor cell invasion by extracellular matrix.

The ability of malignant tumor cells to invade normal surrounding tissue contributes in large part to the significant morbidity and mortality of these cancers. The process of invasion involves adherence of the tumor cells to the extracellular matrix (ECM), degradation of matrix components, and movement of the cell body. Attachment-to ECM molecules is mediated by the integrin family of extracellular matrix receptors. Integrins are a large family of heterodimeric proteins which transduce a variety of signals from the ECM. Ligand occupancy is critical for activation of integrin signaling. This signaling may occur via several different pathways. One of the best characterized of these pathways is the mitogen activated protein kinase (MAPK) cascade. This serial phosphorylation of substrate proteins terminates in activation of transcription factors which regulate expression of target genes. Many of these genes are critical for extracellular matrix degradation or cell migration. Among these are the matrix metalloproteinases (MMPs), a large family of ECM-degrading enzymes. Regulatory elements in the promoters of MMPs have been characterized, providing insight into how MMP expression is controlled. This review focuses on mechanisms by which the ECM regulates tumor cell invasion through integrin signaling via the MAPK pathway using MMP expression as the model.

Animals↗

PubMed1999

Murine tongue muscle displays a distinct developmental profile of MRF and contractile gene expression.

Few studies have addressed the molecular differences that exist between muscles of the body and those of the craniofacial apparatus. In this study, we characterize the molecular events associated with determination and differentiation of the tongue musculature. We assess the expression of myogenic regulatory factors as well as the developmentally regulated myosin heavy chain, (MHC), genes which serve as markers of differentiation. These results suggest that tongue and limb muscle form by distinct molecular pathways. The myoblasts that contribute to the formation of the tongue preferentially express Myf-5 during myoblast determination rather than MyoD. Subsequently, isolated regions of myogenin expression mark the differentiation of first, the small primary myofibers and later, the larger secondary myofibers. Analysis of differentiation markers demonstrates that the tongue muscle also assumes a unique profile of MHC expression as compared to that of the muscles of the body. Unlike the myoblasts of the developing limb, which express embryonic and neonatal forms of MHC and later express MHC-slow, the tongue myoblasts co-express MHC-embryonic, MHC-slow and MHC-fast isoforms from gestational age E12. Proteins for MHC embryonic and MHC fast isoforms are detected almost simultaneously. Interestingly, MHC-slow transcripts do not appear to be translated into a detectable MHC slow protein at any developmental stage assayed. These results provide further evidence to suggest that skeletal tongue muscle represents a myoblast lineage that develops differently than the limb.

Age Factors↗

PubMed1998

PDGF-A and PDGFR-alpha regulate tooth formation via autocrine mechanism during mandibular morphogenesis in vitro.

Platelet-derived growth factor A (PDGF-A) binding to the PDGF receptor alpha (PDGFR-alpha) mediates signal transduction processes related to DNA synthesis, cell migrations, cytodifferentiation, and wound healing. Recent studies indicate that PDGFR-alpha functions during cranial neural crest cell migrations and first branchial arch morphogenesis (Stephenson et al. [1991] Proc. Natl. Acad. Sci. USA 88:6-10; Morrison-Graham et al. [1992] Development 115:133-142; Hu et al. [1995] Int. J. Dev. Biol. 39:939-945; Soriano [1997] Development 124:2691-2700). The present studies were designed to test the hypothesis that PDGF-A, interacts with its cognate receptor PDGFR-alpha via an autocrine mechanism that regulates the timing, rates, and size of embryonic mouse tooth morphogenesis. Both PDGF-A and PDGFR-alpha transcripts were coordinately expressed in mandibular prominences prior to and during tooth formation using reverse transcriptase-polymerase chain reaction (RT-PCR). During the dental lamina stage, ligand and receptor were present in both enamel organ epithelium and adjacent mesenchymal cells. During the bud stage, ligand and receptor were localized mainly to the enamel organ epithelium. Exogenous PDGF-A at 20 ng/ml enhanced tooth development to reach the cap stage with increased tooth size (P < 0.05) using embryonic day (E)10 mandibular explants cultured in serumless, chemically defined medium. A significant increase in DNA synthesis was observed within enamel organ epithelium at E10+4 when the mandibular explants were treated with PDGF-A at 20 ng/ml. These data suggest that PDGF-A and its cognate receptor (PDGFR-alpha) regulate the size and stage of tooth development via an autocrine mechanism during odontogenesis in vitro.

Animals↗

PubMed1998

Tumor suppressor function of a dominant negative retinoic acid receptor mutant.

Mutations in receptors for the vitamin A metabolite retinoic acid (RAR) that repress retinoic acid (RA)-responsive gene expression have been identified and characterized. We previously reported an absence of target gene response to RA in all but one of a series of transformed human epithelial cell lines. To elucidate the mechanisms of this unresponsiveness, we created stable transfectants that expressed an RARalpha mutant (RARalpha403) previously shown to have dominant negative activity due to a C-terminal truncation. All clones exhibited repressed RA-responsive gene expression. These cells grew slowly and demonstrated greater growth inhibition by RA. Pretreatment of both control and experimental groups with RA enhanced epidermal growth factor-induced proliferation despite RA-dependent downregulation of epidermal growth factor receptor expression. In addition, clones expressing the mutant RARalpha were 60% less invasive in an in vitro assay. This reduced invasiveness correlated with decreased gelatinase activity in these cells. We showed for the first time that a dominant negative mutation in RARalpha can function as a tumor suppressor in transformed epithelial cells.

Carcinoma, Squamous Cell↗