bluuebunny/crossref_metadata_2025 huggingface dataset:
A Possible Role for the Wnt~1 Pathway in Oral Carcinogenesis
Authors: Lo Muzio Lorenzo
Published: January 2009

Reductions in cell-cell adhesion and stromal and vascular invasion are essential steps in the progression from localized malignancy to metastatic disease for all cancers. Proteins involved in intercellular adhesion, such as E-cadherin and catenin, probably play an important role in metastatic processes and cellular differentiation. While E-cadherin and beta-catenin expression has been extensively studied in many forms of human cancers, less is known about the role of the Wingless-Type-1 (WNT-1 ) pathway in human tumors. A large body of genetic and biochemical evidence has identified beta-catenin as a key downstream component of the WNT signaling pathway, and recent studies of colorectal tumors have shown a functional link among beta-catenin, adenomatous polyposis coli gene product (APC), and other components of the WNT-1 pathway. WNT-1 pathway signaling is thought to be mediated via interactions between beta-catenin and members of the LEF-1/TCF family of transcription factors. The WNT signal stabilizes beta-catenin protein and promotes its accumulation in the cytoplasm and nucleus. In the nucleus, beta-catenin associates with TCF to form a functional transcription factor which mediates the transactivation of target genes involved in the promotion of tumor progression, invasion, and metastasis, such as C-Myc, cyclin DI, c-jun, fra-1, and u-PAR. There is a strong correlation between the ability of the WNT-1 gene to induce beta-catenin accumulation and its transforming potential in vivo, suggesting that the WNT-1 gene activates an intracellular signaling pathway that can induce the morphological transformation of cells. For these reasons, data obtained from the study of the WNT-1 pathway could be important in our understanding of the mechanisms of epithelial tumors, in general, and probably also of oral squamous cell carcinoma, in particular.
Immunodominant Antigens in Periodontal Disease: a Real or Illusive Concept?
Authors: Podmore M. , Ebersole J.L. , Kinane D.F.
Published: January 2009

The humoral arm of the immune system provides protection from many medically significant pathogens. The antigenic epitopes of the pathogens which induce these responses, and the subsequent characteristics of the host response, have been extensively documented in the medical literature, and in many cases have resulted in the development and implementation of effective vaccines or diagnostic tests. There is a substantial body of literature on the humoral immune response in periodontal disease, which is targeted at micro-organisms present within periodontal pockets. However, the significance and specificity of the immune response in periodontal disease have proved difficult to elucidate, due to the large number of potential pathogens in the plaque biofilm and the apparent commensal nature of many of these opportunistic pathogens. This review addresses our current knowledge of the approaches and strategies which have been used to elucidate and examine the concept of immunodominant antigens in medical infections and, more recently, periodontal disease. An identification/understanding of the immunodominant antigens would be informative with respect to: (i) the relative importance of the implicated pathogens, (ii) new approaches to immunological diagnosis, (iii) specific bacterial virulence determinants, (iv) natural protective responses, and (v) the selection of potential vaccine candidate antigens. We conclude that immunodominance of antigens in periodontal disease may be relevant to our understanding of periodontal disease pathogenesis, but due to the complexity and diversity of the 'pathogenic microbial ecology', it is currently an enigmatic topic requiring a multidisciplinary approach linking clinical, microbiological, and immunological investigations. We also conclude, after assessing the literature available on the topic of immunodominance, that it is a term that, if used, must be clearly defined and understood, since it is often used loosely, leading to a general misinterpretation by readers of oral and medical literature.
Cysteine Proteases of Porphyromonas Gingivalis
Authors: Curtis M.A. , Aduse-Opoku J. , Rangarajan M.
Published: January 2009

The cysteine proteases of Porphyromonas gingivalis are extracellular products of an important etiological agent in periodontal diseases. Many of the in vitro actions of these enzymes are consistent with the observed deregulated inflammatory and immune features of the disease. They are significant targets of the immune responses of affected individuals and are viewed by some as potential molecular targets for therapeutic approaches to these diseases. Furthermore, they appear to represent a complex group of genes and protein products whose transcriptional and translational control and maturation pathways may have a broader relevance to virulence determinants of other persistent bacterial pathogens of human mucosal surfaces. As a result, the genetics, chemistry, and virulence-related properties of the cysteine proteases of P. gingivalis have been the focus of much research effort over the last ten years. In this review, we describe some of the progress in their molecular characterization and how their putative biological roles, in relation to the in vivo growth and survival strategies of P. gingivalis, may also contribute to the periodontal disease process.
Changing Paradigms in Implant Dentistry
Authors: Salvi Giovanni E. , Lang Niklaus P.
Published: January 2009

This review focuses on five paradigms of implant dentistry which have undergone considerable modifications in recent years. An attempt was made to select and include all the relevant citations of the past 10 years. These five paradigms document the debate in the clinical and scientific community and include the aspects of (1) smooth vs. rough implant surfaces, (2) submerged vs. non-submerged implant installation techniques, (3) mixed tooth-implant vs. solely implant-supported reconstructions, (4) morse-taper abutment fixation vs. butt-joint interfaces, and (5) titanium abutments vs. esthetic abutments in clinical situations where esthetics is of primary concern.
Proteoglycans in Dentinogenesis
Authors: Embery Graham , Hall Rachel , Waddington Rachel , Septier Dominique , Goldberg Michel
Published: January 2009

The predominant proteoglycans present in predentin and dentin are the chondroitin-sulphate-rich decorin and biglycan and the keratan-sulphate-rich lumican and fibromodulin. These are small, interstitial, leucine-rich proteoglycans which have recently been shown to exist in gradients across the predentin. Antibodies recognizing chondroitin sulphate show a decreasing gradient from the pulpal aspect toward the mineralizing front, the converse being true for keratan sulphate. Anti-decorin shows an increase toward the mineralization front. Evidence from biochemical, autoradiographic, and immunohistochemical studies implies that such changes may be brought about by gradients of metalloproteinases. This offers the possibility that the proteoglycans organize the collagen network for receipt of phosphoproteins and phospholipids, the former being evident only at the onset of dentin formation. The suggestion is raised that glycosaminoglycan-depleted leucine-rich protein cores act as sequester points for receipt of phosphoproteins in particular. The rigid, spatially oriented glycosaminoglycan chains on decorin and biglycan are known to bind calcium and may feature directly in mineral initiation.
Fatigue of Restorative Materials
Authors: Baran G. , Boberick K. , McCool J.
Published: January 2009

Failure due to fatigue manifests itself in dental prostheses and restorations as wear, fractured margins, delaminated coatings, and bulk fracture. Mechanisms responsible for fatigue-induced failure depend on material ductility: Brittle materials are susceptible to catastrophic failure, while ductile materials utilize their plasticity to reduce stress concentrations at the crack tip. Because of the expense associated with the replacement of failed restorations, there is a strong desire on the part of basic scientists and clinicians to evaluate the resistance of materials to fatigue in laboratory tests. Test variables include fatigue-loading mode and test environment, such as soaking in water. The outcome variable is typically fracture strength, and these data typically fit the Weibull distribution. Analysis of fatigue data permits predictive inferences to be made concerning the survival of structures fabricated from restorative materials under specified loading conditions. Although many dental-restorative materials are routinely evaluated, only limited use has been made of fatigue data collected in vitro: Wear of materials and the survival of porcelain restorations has been modeled by both fracture mechanics and probabilistic approaches. A need still exists for a clinical failure database and for the development of valid test methods for the evaluation of composite materials.
Induction and Regulation of Crown Dentinogenesis: Embryonic Events as a Template for Dental Tissue Repair?
Authors: Smith A.J. , Lesot H.
Published: January 2009

Close regulation of odontoblast differentiation and subsequent secretory activity is critical for dentinogenesis during both embryogenesis and tissue repair. Some dental papilla cells achieve commitment and specific competence, allowing them to respond to epithelially derived inductive signals during the process of odontoblast differentiation. Temporo-spatial regulation of odontoblast differentiation is dependent on matrix-mediated interactions involving the basement membrane (BM). Experimental studies have highlighted the possible roles of growth factors in these processes. Regulation of functional activity of odontoblasts allows for both ordered secretion of the primary dentin matrix and maintenance of vitality and down-regulation of secretory activity throughout secondary dentinogenesis. After injury to the mature tooth, the fate of the odontoblast can vary according to the intensity of the injury. Milder injury can result in up-regulation of functional activity leading to focal secretion of a reactionary dentin matrix, while greater injury can lead to odontoblast cell death. Induction of differentiation of a new generation of odontoblast-like cells can then lead to reparative dentinogenesis. Many similarities exist between development and repair, including matrix-mediation of the cellular processes and the apparent involvement of growth factors as signaling molecules despite the absence of epithelium during repair. While some of the molecular mediators appear to be common to these processes, the close regulation of primary dentinogenesis may be less ordered during tertiary dentinogenic responses.
Sensory and Affective Components of Orofacial Pain: Is it all in your Brain?
Authors: Tenenbaum H.C. , Mock D. , Gordon A.S. , Goklberg M.B. , Grossi M.L. , Locker D. , Davis K.D.
Published: January 2009

In this paper, we shall review several chronic orofacial pain conditions with emphasis on those that are essentially refractory to treatment. We shall present a review of current and past literature that describes the various pain phenomena as well as their underlying central mechanisms. New data concerning refractory pain will be used to underscore the importance of central processing of pain, with particular emphasis on neuropsychological and cognitive function and capacity that may play important roles in pain processing and maintenance of the pain state. Further, neurophysiological data showing that the anterior cingulate cortex (ACC) and other structures in the brain may play key roles in modulation of chronic pain will also be discussed. Although peripheral triggering events surely play an important role in initiating pain, the development of chronic and, in particular, refractory pain may depend on changes or malfunctions in the central nervous system. These changes may be quite subtle and require sophisticated approaches, such as functional MRI, to study them, as is now being done. New findings obtained therefore may lead to more rational and reliable treatment for orofacial pain.
Adhesive Mechanisms Regulating Invasion and Metastasis in Oral Cancer
Authors: Ziober Barry L , Silverman Sol S. , Kramer Randall H.
Published: January 2009

It is the relentless invasion and growth into surrounding tissue that characterize oral squamous cell carcinoma. Metastasis is perhaps the most challenging and important aspect of cancer progression, in that it generally signifies limited survival and ineffective therapy. Inherent in metastasis is invasion, the process by which cells infiltrate into adjacent tissues, degrading basement membranes and extracellular matrix and disrupting tissue architecture and sometimes organ function. The factors that regulate these processes are complex and likely involve loss of the controls that are normally in place in physiologic tissue modeling. Adhesion receptors and their ligands are important in modulating not only invasion of oral squamous cell carcinoma cells but also their survival and proliferation. Normal oral mucosal epithelial cells use integrins to maintain their anchorage to the basement membrane, whereas the formation of stratifying cell layers depends on the formation of intercellular adhesions mediated by cadherins. The process of squamous cell carcinoma invasion and dissemination requires active cell migration through the extracellular matrix with the simultaneous remodeling of intercellular adhesions. Integrins are clearly important in the invasive process, whereas intercellular adhesion receptors restrain invasion and promote a more differentiated phenotype.
Oral Leukoplakia
Authors: Sdubba J.J.
Published: January 2009

Leukoplakia has evolved as a clinico-pathologic concept over many years, with the current clinical designation being accepted worldwide. Reflective of the biology of leukoplakia is the concept of cellular atypia and epithelial dysplasia. Adding to a better understanding of leukoplakia in general has been the definition of relevant clinical subsets which, in some cases, includes etiology (snuff), while in other cases a verrucous clinical appearance will suggest a more aggressive anticipated behavior pattern. Tobacco usage, in many of its forms, remains the prime etiologic factor; however, other considerations also apply. More recently, the potential etiologic role of Candida albicans has been stressed, as well as its possible role in carcinogenesis. So-called oral hairy leukoplakia has been defined in relation to a possible Epstein-Barr viral infection, usually in the immunosuppressed patient. Other viruses, human papilloma virus in particular, have been implicated in leukoplakia, while genetic alterations involving tumor suppressor elements (p53) have also been investigated. Finally, the management of this common condition remains a variable and includes local, topical, and systemic therapies such as anti-oxidants, carotenoids, and retinoids.
Biochemical Composition of Human Saliva in Relation To Other Mucosal Fluids
Authors: Schenkels Léon C.P.M. , Veerman Enno C.I. , Nieuw Amerongen Arie V.
Published: January 2009

This paper describes several salivary components and their distribution in other mucosal secretions. Histatins are polypeptides which possess exceptional anti-fungal and anti-bacterial activities, but are nevertheless present only in saliva. Proline-rich proteins (PRPs) are members of a closely related family, of which the acidic PRPs are found solely in saliva, whereas the basic PRPs are also found in other secretions. Mucins are a group of glycoproteins that contribute to the visco-elastic character of the mucosal secretions. Despite the similarities in their structure and behavior, mucins have distinct tissue distributions and amino acid sequences. Other salivary proteins are present in one or more mucosal secretions. Lysozyme is an example of a component belonging to an ancient self-defense system, whereas secretory immunoglobulin A (slgA) is the secreted part of a sophisticated adaptive immune system. Cystatins are closely related proteins which belong to a multigene family. a-Amylase is a component that is believed to play a specific role in digestion, but is nevertheless present in several body fluids. Kallikrein and albumin are components of blood plasma. But whereas albumin diffuses into the different mucosal secretions, kallikrein is secreted specifically by the mucosal glands.

The presence of these proteins specifically in saliva, or their distribution in other mucosal secretions as well, may provide important clues with respect to the physiology of those proteins in the oral cavity.
Programmed Cell Death and Cell Transformation in Craniofacial Development
Authors: Shuler Charles F.
Published: January 2009

Fusion of branchial arch derivatives is an essential component in the development of craniofacial structures. Bilaterally symmetric branchial arch processes fuse in the midline to form the mandible, lips, and palate. The mechanism for fusion requires several different morphologic and molecular events prior to the completion of the mesenchymal continuity between opposing tissue processes. The ectodermal covering of the branchial arches is one of the cell types that has an important role during craniofacial development. The surface epithelia provide the initial adherence between the processes; however, this population of cells is ultimately absent from the fusion zone. The medial edge epithelium of the secondary palatal shelves is one example of such an epithelium that must disappear from the fusion zone of the secondary palate during development in order to complete palatal fusion. The mechanisms for removal of the epithelial cells from the fusion zone could include either programmed cell death, epithelial-mesenchymal transformation, or migration to adjacent epithelia. All three of these fates have been hypothesized as a mechanism for the removal of the palatal medial edge epithelia. The processes of programmed cell death, epithelial-mesenchymal transformation, and epithelial migration are reviewed with respect to both palatal fusion and results reported in other model systems.
The Pathophysiology of Angiogenesis
Authors: Polverini P.J.
Published: January 2009

The formation of new capillary blood vessels, a process termed "angiogenesis", is one of the most pervasive and fundamentally essential biological processes encountered in mammalian organisms. Angiogenesis is an important event in a variety of physiological settings, such as embryonic development, chronic inflammation, and wound repair. It is a process that is tightly regulated in both time and space. Angiogenesis is driven by a cocktail of growth factors and pro-angiogenic cytokines and is tempered by an equally diverse group of inhibitors of neovascularization. Angiogenesis is also central to the etiology and pathogenesis of a number of pathological processes that include, among others, solid tumors, diseases of the eye, and chronic inflammatory disorders such as rheumatoid arthritis, psoriasis, and periodontitis. Based on recent work from several laboratories, it is now eminently clear that most if not all angiogenesis and vasoproliferative-dependent disease processes are not only a consequence of the unrestricted production of normal or aberrant forms of pro-angiogenic mediators but also the result of a relative deficiency in angiogenic-inhibitory molecules. In this review, I will describe how these multifunctional mediator systems function to coordinate and regulate the angiogenic response, and how disruption in the molecular controls that regulate the production of pro-angiogenic and angiostatic mediators leads to aberrant angiogenesis and disease. The implications of these findings in the development of novel therapeutic strategies for the treatment of diseases characterized by disregulated angiogenesis will also be discussed.
Pathogenesis of Degenerative Joint Disease in the Human Temporomandibular Joint
Authors: Haskin Christine L. , Milam Stephen B. , Cameron Ivan L.
Published: January 2009

The wide range of disease prevalences reported in epidemiological studies of temporomandibular degenerative joint disease reflects the fact that diagnoses are frequently guided by the presence or absence of non-specific signs and symptoms. Treatment is aimed at alleviating the disease symptoms rather than being guided by an understanding of the underlying disease processes. Much of our current understanding of disease processes in the temporomandibular joint is based on the study of other articular joints. Although it is likely that the molecular basis of pathogenesis is similar to that of other joints, additional study of the temporomandibular joint is required due to its unique structure and function. This review summarizes the unique structural and molecular features of the temporomandibular joint and the epidemiology of degenerative temporomandibular joint disease. As is discussed in this review, recent research has provided a better understanding of the molecular basis of degenerative joint disease processes, including insights into: the regulation of cytokine expression and activation, arachidonic acid metabolism, neural contributions to inflammation, mechanisms of extracellular matrix degradation, modulation of cell adhesion in inflammatory states, and the roles of free radicals and heat shock proteins in degenerative joint disease. Finally, the multiple cellular and molecular mechanisms involved in disease initiation and progression, along with factors that may modify the adaptive capacity of the joint, are presented as the basis for the rational design of new and more effective therapy.
Retinoid Receptors and Keratinocytes
Authors: Fisher Cynthia , Blumenberg Miroslav , Tomić-Canić Marjana
Published: January 2009

In 1987, a tremendous boost in our understanding of the action of dietary vitamin A occurred with the discovery and characterization of nuclear receptors for retinoic acid, the active form of the vitamin, in the laboratories of P. Chambon and R. Evans. They have shown that the nuclear receptors are ligand-activated transcription factors capable of specific gene regulation. Since that discovery, it has been determined that there are at least six retinoic acid receptors belonging to two families, RARs and RXRs, that they are differentially expressed in various mammalian tissues, and that they act as homo- and heterodimers interacting with other ligand-activated nuclear receptors. The domain structure of the receptors has been described, and their DNA-binding, ligand-binding, dimerization, and transcriptional activation regions characterized. Among the most important retinoid-regulated genes are the homeobox proteins, regulatory transcription factors which are responsible for body axis formation, patterning, limb formation, and other crucial processes during development. Retinoic acid and its receptors also regulate many differentiation markers which are particularly important in stratified epithelia, such as skin and oral epithelia. Our increased understanding led to improved therapy of a large number of skin disorders, ranging from acne to wrinkles and including epidermal and oral carcinomas.
Current Trends in Dental Composites
Authors: Ferracane J.L.
Published: January 2009

The clinical performance of dental composites has been significantly improved over the past decade through modifications in formulation that include: using more stable polymerization promoters for greater color stability; incorporating high concentrations of finely ground fillers to produce adequate strength and excellent wear resistance while retaining translucency ; adding radiopacifying agents for improved diagnostics; and utilizing dentin adhesives. However, there are problems which limit the use of composites, especially in posterior teeth. The materials remain very technique-sensitive, due to the extensive contraction which accompanies polymerization and negatively influences marginal sealing. In addition, the materials are generally considered to have inadequate mechanical properties and wear resistance in contact areas to serve as total replacements for amalgams. Current efforts are focusing on several areas, including the development of non- or minimally-shrinking dental composites containing spiro-orthocarbonates as additives to dimethacrylates or epoxy-base resins, and the production of alternative filler materials for ideal wear resistance and esthetics. This paper reviews the composition and characteristics of current dental composites, as well as recent areas of study.
Genetic Influences in Caries and Periodontal Diseases
Authors: Hassell Thomas M. , Harris Emily L
Published: January 2009

Deciphering the relative roles of heredity and environmental factors ("nature vs. nurture") in the pathogenesis of dental caries and diseases of the periodontium has occupied clinical and basic researchers for decades. Success in the endeavor has come more easily in the case of caries; the complex interactions that occur between host-response mechanisms and putative microbiologic pathogens in periodontal disease have made elucidation of genetic factors in disease susceptibility more difficult. In addition, during the 30-year period between 1958 and 1987, only meager resources were targeted toward the "nature" side of the nature/nurture dipole in periodontology. In this article, we present a brief history of the development of genetic epistemology, then describe the three main research mechanisms by which questions about the hereditary component of diseases in humans can be addressed. A critical discussion of the evidence for a hereditary component in caries susceptibility is next presented, also from a historical perspective. The evolution of knowledge concerning possible genetic ("endogenous", "idiotypic") factors in the pathogenesis of inflammatory periodontal disease is initiated with an analysis of some foreign-language (primarily German) literature that is likely to be unfamiliar to the reader. We identify a turning point at about 1960, when the periodontal research community turned away from genetics in favor of microbiology research. During the past five years, investigators have re-initiated the search for the hereditary component in susceptibility to common adult periodontal disease; this small but growing body of literature is reviewed. Recent applications of in vitro methods for genetic analyses in periodontal research are presented, with an eye toward a future in which persons who are at risk-genetically predisposed-to periodontal disease may be identified and targeted for interventive strategies. Critical is the realization that genes and environment do not act independently of each other; the appearance or magnitude of heritability may differ with various environments.
Prenatal Craniofacial Development: New Insights on Normal and Abnormal Mechanisms
Authors: Johnston M.C. , Bronsky P.T.
Published: January 2009

Technical advances are radically altering our concepts of normal prenatal craniofacial development. These include concepts of germ layer formation, the establishment of the initial head plan in the neural plate, and the manner in which head segmentation is controlled by regulatory (homeobox) gene activity in neuromeres and their derived neural crest cells. There is also a much better appreciation of ways in which new cell associations are established. For example, the associations are achieved by neural crest cells primarily through cell migration and subsequent cell interactions that regulate induction, growth, programmed cell death, etc. These interactions are mediated primarily by two groups of regulatory molecules: "growth factors" (e.g., FGF and TGFa) and the so-called steroid/thyroid/retinoic acid superfamily. Considerable advances have been made with respect to our understanding of the mechanisms involved in primary and secondary palate formation, such as growth, morphogenetic movements, and the fusion/merging phenomenon. Much progress has been made on the mechanisms involved in the final differentiation of skeletal tissues.

Molecular genetics and animal models for human malformations are providing many insights into abnormal development. A mouse model for the fetal alcohol syndrome (FAS), a mild form of holoprosencephaly, demonstrates a mid-line anterior neural plate deficiency which leads to olfactory placodes being positioned too close to the mid-line, and other secondary changes. Work on animal models for the retinoic acid syndrome (RAS) shows that there is major involvement of neural crest cells. There is also major crest cell involvement in similar syndromes, apparently including hemifacial microsomia. Later administration of retinoic acid prematurely and excessively kills ganglionic placodal cells and leads to a malformation complex virtually identical to the Treacher Collins syndrome. Most clefts of the lip and/or palate appear to have a multifactorial etiology. Genetic variations in TGFαs, RARαs. NADH dehydrogenase, an enzyme involved in oxidative metabolism, and cytochrome P-450, a detoxifying enzyme, have been implicated as contributing genetic factors. Cigarette smoking, with the attendant hypoxia, is a probable contributing environmental factor. It seems likely that few clefts involve single major genes. In most cases, the pathogenesis appears to involve inadequate contact and/or fusion of the facial prominences or palatal shelves. Specific mutations in genes for different FGF receptor molecules have been identified for achondroplasia and Crouzon's syndrome, and in a regulatory gene (Msx2) for one type of craniosynostosis. Poorly co-ordinated control of form and size of structures, or groups of structures (e.g., teeth and jaws), by regulatory genes should do much to explain the very frequent "mismatches" found in malocclusions and other dentofacial "deformities".

Future directions for research, including possibilities for prevention, are discussed.
Setting Reactions in Dental Amalgam Part 1. Phases and Microstructures Between One Hour and One Week
Authors: Mitchell R.J. , Okabe T.
Published: January 2009

The literature on the setting mechanisms of dental amalgams made from powders of silver-rich alloys of tin and/or copper has been critically reviewed. In Part 1 of the review, the microstructure and phase content of recently set amalgams are described. The composition, morphology, and location of product phases are emphasized, since these features are clues to the setting reaction. Thus, Part I provides the background needed to understand the kinetics of the setting reactions, which is the topic of Part 2 of the review.
T-Lymphocyte Interactions With Endothelium and Extracellular Matrix
Authors: Hunt Stephen W. , Harris Estelle S. , Kellermann Sirid-Aimée , Shimizu Yoji
Published: January 2009

T-lymphocyte movement out of the bloodstream and into tissue is critical to the success of these cells in their role in immunosurveillance. This process involves interactions of the T-cell with endothelium as well as with extracellular matrix. Central to these interactions are a number of T-cell adhesion molecules and their endothelial and extracellular matrix ligands. The identification and functional characterization of adhesion molecules have been the subject of intensive research in recent years. We highlight here the latest developments in this rapidly expanding field as they pertain to T-cell interactions with endothelial cells and extracellular matrix components, including: (1) identification of adhesion molecule families, including the selectins, mucins, integrins, immunoglobulin superfamily members, and cadherins; (2) elucidation of the multi-step adhesion cascade that mediates the rolling, arrest, and eventual diapedesis of T-cells through the vascular endothelium into the surrounding tissue; (3) the changes in adhesion molecule expression that accompany T-cell maturation and activation, and the impact of those changes on T-cell migration; (4) the functional relevance of the extracellular matrix for T-cell function; and (51 the clinical relevance of adhesion molecules and the potential for targeting these molecules for the amelioration of immune-mediated diseases.
Recent Advances in Ceramics for Dentistry
Authors: Denry Isabelle L.
Published: January 2009

For the last ten years, the application of high-technology processes to dental ceramics allowed for the development of new materials such as heat-pressed, injection-molded, and slip-cast ceramics and glass-ceramics. The purpose of the present paper is to review advances in new materials and processes available for making all-ceramic dental restorations. Concepts on the structure and strengthening mechanisms of dental ceramics are provided. Major developments in materials for all-ceramic restorations are addressed. These advances include improved processing techniques and greater mechanical properties. An overview of the processing techniques available for all-ceramic materials is given, including sintering, casting, machining, slip-casting, and heat-pressing. The most recent ceramic materials are reviewed with respect to their principal crystalline phases, including leucite, alumina, forsterite, zirconia, mica, hydroxyapatite, lithium disilicate, sanidine, and spinel. Finally, a summary of flexural strength data available for all-ceramic materials is included.
Keratinocyte Gene Transfer and Gene Therapy
Authors: Garlick J.A. , Fenjves E.S.
Published: January 2009

Gene therapy has moved beyond the pre-clinical stage to the treatment of a variety of inherited and acquired diseases. For such therapy to be successful, genes must be efficiently delivered to target cells and gene products must be expressed for prolonged periods of time without toxic effects to the host. This may be achieved by means of an in vivo strategy where genes are transferred directly into a host cell, or by means of an ex vivo approach through which cells are removed, cultured, targeted for gene delivery, and grafted back to the host. Several obstacles continue to delay safe and effective clinical application of gene therapy in a variety of target cells. The limited survival of transplanted cells, transient expression of transferred genes, and difficulties in targeting stem cells are technical issues requiring further investigation.

Epidermal and oral keratinocytes are potential vehicles for gene therapy. Several features of these tissues can be utilized to achieve delivery of therapeutic gene products for local or systemic delivery. These qualities include: (1) the presence of stem cells; (2) the cell-, strata-, and site-specific regulation of keratinocyte gene expression; (3) tissue accessibility; and (4) secretory capacity. Such features can be exploited by the use of gene therapy strategies to facilitate: (1) identification, enrichment, and targeting of stem cells to ensure the continued presence of the transferred gene; (2) high-level and persistent transgene expression using keratinocyte-specific promoters; (3) tissue access needed for culture and grafting for ex vivo therapy and direct in vivo gene transfer; (4) secretion of transgene product for local or systemic delivery; and (5) monitoring of genetically modified tissue and removal if treatment termination is required. Optimal gene therapy strategies are being tested in a variety of tissues to treat dominant and recessive genetic disorders as well as acquired diseases such as neoplasia and infectious disease. This experience provides a basis for the application of such clinical studies to a spectrum of diseases effecting epidermal and oral keratinocytes. Gene therapy is in an early stage yet holds great promise for its ultimate clinical application.
Potential of Diagnostic Microbiology for Treatment and Prognosis of Dental Caries and Periodontal Diseases
Authors: Baehni P.C. , Guggenheim B.
Published: January 2009

Most evidence suggests that only a finite number of bacteria are responsible for dental caries and periodontal diseases. This knowledge led to the development of microbial tests which can identify suspected pathogens. Current evaluation of the diagnostic power of microbial tests has shown that they have a low sensitivity and a low prognostic value. Despite these shortcomings, there are valid indications for microbiological-based diagnosis. Salivary microbial tests for the detection of mutans streptococci and lactobacilli may be useful, for example, in young children, oligosialic patients, and orthodontic patients. These tests can be used to monitor the success of chemopreventive measures or compliance with dietary recommendations. Microbial diagnosis may also be valuable in the treatment of early-onset periodontitis or in subjects who respond poorly to periodontal therapy. The use of microbial tests to monitor the efficacy of chemotherapy or mechanical treatment is of particular interest.
Keratinocytes and Cytokine/Growth Factors
Authors: Feliciani C. , Gupta A.K. , Saucier D.N.
Published: January 2009

Cytokines are polypeptide growth factors produced by most nucleated cells in the body, including epithelial cells, keratinocytes, and Langerhans cells in the skin. Cytokines can be classified into interleukins, tumor necrosis factors, chemokines, colony-stimulating factor, interferons, and growth factors. Like classic hormones, cytokines bind to specific receptors to transmit their messages to target cells. Cytokine receptors can be divided into three cytokine receptor superfamilies: the immunoglobulin superfamily, the hematopoietin family, and the tumor necrosis factor family. Following cytokine/cytokinereceptor binding (first messenger), a signal transduction pathway is initiated. Factors affecting homeostasis in the skin and oral mucosa include a delicate balance between cytokines/cytokine-receptors and their antagonists. An imbalance in these variables can influence the development of cutaneous and oral diseases—such as lichen planus, autoimmune disorders, and some neoplastic processes—and can affect wound healing. Potential uses of cytokines include cancer and antiviral therapy.
Molecular Biology of Human Oral Cancer
Authors: Wong D.T.W. , Todd R. , Tsuji T. , Donoff R.B.
Published: January 2009

The application of molecular biological tools to the study of cancer has significantly advanced the field of human cancer research. Such study has demonstrated the involvement of two classes of highly conserved cellular genes in the malignant transformation process: oncogenes and tumor suppressor genes. Despite these advances in the molecular biology of human cancers, our understanding of human oral cancer lags behind that of cancer of other body sites. This review attempts to assess the current status of the molecular biology of human oral cancer.
Advanced Imaging Methods
Authors: Matteson S.R. , Deahl S.T. , Alder M.E. , Nummikoski P.V.
Published: January 2009

Recent developments in imaging sciences have enabled dental researchers to visualize structural and biophysical changes effectively. New approaches for intra-oral radiography allow investigators to conduct densitometric assessments of dento-alveolar structures. Longitudinal changes in alveolar bone can be studied by computer-assisted image analysis programs. These techniques have been applied to dimensional analysis of the alveolar crest, detection of gain or loss of alveolar bone density, peri-implant bone healing, and caries detection.

Dental applications of computed tomography (CT) include the detailed radiologic anatomy of alveolar processes, orofacial soft tissues and air spaces, and developmental defects. Image analysis software permits bone mass mineralization to be quantified by means of CT data. CT has also been used to study salivary gland disease, injuries of the facial skeleton, and dental implant treatment planning.

Magnetic resonance imaging (MRI) has been used extensively in retrospective and prospective studies of internal derangements of the temporomandibular joint. Assessments based on MRI imaging of the salivary glands, paranasal sinuses, and cerebrovascular disease have also been reported. Magnetic resonance spectroscopy (MRS) has been applied to the study of skeletal muscle, tumors, and to monitor the healing of grafts.

Nuclear imaging provides a sensitive technique for early detection of physiological changes in soft tissue and bone. It has been used in studies of periodontitis, osteomyelitis, oral and maxillofacial tumors, stress fractures, bone healing, temporomandibular joint, and blood flow.

This article includes brief descriptions of the technical principles of each imaging modality, reviews their previous uses in oral biology research, and discusses potential future applications in research protocols.
The Genetic Control of Early Tooth Development
Authors: Maas R. , Bei M.
Published: January 2009

Most vertebrate organs begin their initial formation by a common, developmentally conserved pattern of inductive tissue interactions between two tissues. The developing tooth germ is a prototype for such inductive tissue interactions and provides a powerful experimental system for elucidation of the genetic pathways involved in organogenesis. Members of the Msx homeobox gene family are expressed at sites of epithelial-mesenchymal interaction during embryogenesis, including the tooth. The important role that Msx genes play in tooth development is exemplified by mice lacking Msx gene function. Msxldeficient mice exhibit an arrest in tooth development at the bud stage, while Msx2-deficient mice exhibit late defects in tooth development. The co-expression of Msx, Bmp, L ef1, and Activin βA genes and the coincidence of tooth phenotypes in the various knockout mice suggest that these genes reside within a common genetic pathway. Results summarized here indicate that Msx1 is required for the transmission of Bmp4 expression from dental epithelium to mesenchyme and also for L ef1 expression. In addition, we consider the role of other signaling molecules in the epithelial-mesenchymal interactions leading to tooth formation, the role that transcription factors such as Msx play in the propagation of inductive signals, and the role of extracellular matrix. Last, as a unifying mechanism to explain the disparate tooth phenotypes in Msxl- and Msx2-deficient mice, we propose that later steps in tooth morphogenesis molecularly resemble those in early tooth development.
Salivary Glands: A Paradigm for Diversity of Gland Development
Authors: Denny P.C. , Ball W.D. , Redman R.S.
Published: January 2009

The major salivary glands of mammals are represented by three pairs of organs that cooperate functionally to produce saliva for the oral cavity. While each type of gland produces a signature secretion that complements the secretions from the other glands, there is also redundancy as evidenced by secretion of functionally similar and, in some cases, identical products in the three glands. This, along with their common late initiation of development, in fetal terms, their similarities in developmental pattern, and their proximate sites of origin, suggests that a common regulatory cascade may have been shared until shortly before the onset of overt gland development. Furthermore, occasional ectopic differentiation of individual mature secretory cells in the "wrong" gland suggests that control mechanisms responsible for the distinctive cellular composition of each gland also share many common steps, with only minor differences providing the impetus for diversification. To begin to address this area, we examine here the origins of the salivary glands by reviewing the expression patterns of several genes with known morphogenetic potential that may be involved based on developmental timing and location. The possibility that factors leading to determination of the sites of mammalian salivary gland development might be homologous to the regulatory cascade leading to salivary gland formation in Drosophila is also evaluated. In a subsequent section, cellular phenotypes of neonatal and adult glands are compared and evaluated for insights into the mechanisms and lineages leading to cellular diversification. Finally, the phenomena of proliferation, repair, and regeneration in adult salivary glands are reviewed, with emphasis on the extent to which the cellular diversity is reversible and which cell type other than stem cells has the ability to redifferentiate into other cell types.
Subgingival Delivery of Therapeutic Agents in the Treatment of Periodontal Diseases
Authors: Soskolne W. Aubrey
Published: January 2009

This article reviews the current status of controlled local delivery of antibacterial agents in the treatment of periodontitis. The principle of local intrapocket delivery of antibacterial agents and their delivery are discussed. The dosage forms include fibers, film/slabs, and injectable systems, some of which are degradable, while others are not and need to be removed at the termination of the treatment. The antibacterial agents used cover a range of antibiotics as well as antiseptics, and the composition of the delivery systems, their reported use, and the clinical results are summarized. The use of these systems in clinical practice is relatively recent, and therefore their application and integration into the dental office are not yet clearly defined. Clinical applications that have been tested are critically reviewed, and clinical situations in which controlled delivery of antibacterial agents may prove to be clinically useful are suggested for scientific evaluation.
Streptococcal Adhesion and Colonization
Authors: Jenkinson H.F. , Lamont RJ
Published: January 2009

Streptococci express arrays of adhesins on their cell surfaces that facilitate adherence to substrates present in their natural environment within the mammalian host. A consequence of such promiscuous binding ability is that streptococcal cells may adhere simultaneously to a spectrum of substrates, including salivary glycoproteins, extracellular matrix and serum components, host cells, and other microbial cells. The multiplicity of streptococcal adherence interactions accounts, at least in part, for their success in colonizing the oral and epithelial surfaces of humans. Adhesion facilitates colonization and may be a precursor to tissue invasion and immune modulation, events that presage the development of disease. Many of the streptococcal adhesins and virulence-related factors are cell-wall-associated proteins containing repeated sequence blocks of amino acids. Linear sequences, both within the blocks and within non-repetitive regions of the proteins, have been implicated in substrate binding. Sequences and functions of these proteins among the streptococci have become assorted through gene duplication and horizontal transfer between bacterial populations. Several adhesins identified and characterized through in vitro binding assays have been analyzed for in vivo expression and function by means of animal models used for colonization and virulence. Information on the molecular structure of adhesins as related to their in vivo function will allow for the rational design of novel acellular vaccines, recombinant antibodies, and adhesion agonists for the future control or prevention of streptococcal colonization and streptococcal diseases.