bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Saliva in the Maintenance of Taste Sensitivity
Authors: Matsuo R.
Published: January 2009

Saliva is the principal fluid component of the external environment of the taste receptor cells and, as such, could play a role in taste sensitivity. Its main role includes transport of taste substances to and protection of the taste receptor. In the initial process of taste perception, saliva acts as a solvent for taste substances; salivary water dissolves taste substances, and the latter diffuse to the taste receptor sites. During this process, some salivary constituents chemically interact with taste substances. For example, salivary buffers (e.g., bicarbonate ions) decrease the concentration of free hydrogen ions (sour taste), and there are some salivary proteins which may bind with bitter taste substances. Another effect of saliva on taste transduction is that some salivary constituents can continuously stimulate the taste receptor, resulting in an alteration of taste sensitivity. For example, the taste detection threshold for NaCI is slightly above the salivary sodium concentrations with which the taste receptor is continuously stimulated. In contrast, saliva protects the taste receptor from damage brought about by dryness and bacterial infection, and from disuse atrophy via a decrease in transport of taste stimuli to the receptor sites. This is a long-term effect of saliva that may be related to taste disorders. These various effects of saliva on the taste perception differ depending on the anatomical relationship between the taste buds and oral openings of the ducts of the salivary glands. Many taste buds are localized in the trenches of the foliate and circumvallate papillae, where the lingual minor salivary glands (von Ebner's glands) secrete saliva. Taste buds situated at the surface of the anterior part of the tongue and soft palate are bathed with the mixed saliva secreted mainly by the three major salivary glands.
Genetic and Teratogenic Approaches To Craniofacial Development
Authors: Young D.L. , Schneider R.A. , Hu D. , Helms J.A.
Published: January 2009

Craniofacial malformations are the most common birth defects that occur in humans, with facial clefting representing the majority of these defects. Facial clefts can arise at any stage of development due to perturbations that alter the extracellular matrix as well as affect the patterning, migration, proliferation, and differentiation of cells. In this review, we focus on recent advances in the understanding of the developmental basis for facial clefting through the analysis of the effects of gene disruption experiments and treatments with teratogens in both chickens and mice. Specifically, we analyze the results of disruptions to genes such as S onic hedgehog (S hh), epidermal growth factor receptor ( EGFR), D istal-less (Dlx), and transforming growth factor beta 3 ( TGFβ3) . We also describe the effects that teratogens such as retinoic acid, jervine, and cyclopamine have on facial clefting and discuss mechanisms for their action. In addition to providing insight into the bases for abnormal craniofacial growth, genetic and teratogenic techniques are powerful tools for understanding the normal developmental processes that generate and pattern the face.
Calcium Transport Across the Dental Enamel Epithelium
Authors: Hubbard Michael J.
Published: January 2009

Dental enamel is the most highly calcified tissue in mammals, and its formation is an issue of fundamental biomedical importance. The enamel-forming cells must somehow supply calcium in bulk yet avoid the cytotoxic effects of excess calcium. Disrupted calcium transport could contribute to a variety of developmental defects in enamel, and the underlying cellular machinery is a potential target for drugs to improve enamel quality. The mechanisms used to transport calcium remain unclear despite much progress in our understanding of enamel formation. Here, current knowledge of how enamel cells handle calcium is reviewed in the context of findings from other epithelial calcium-transport systems. In the past, most attention has focused on approaches to boost the poor diffusion of calcium in cytosol. Recent biochemical findings led to an alternative proposal that calcium is routed through high-capacity stores associated with the endoplasmic reticulum. Research areas needing further attention and a working model are also discussed. Calcium-handling mechanisms in enamel cells are more generally relevant to the understanding of epithelial calcium transport, biomineralization, and calcium toxicity avoidance.
New Approaches To the Understanding of the Molecular Basis of Oral Cancer
Authors: Patel V. , Ieethanakul C. , Gutkind J.S.
Published: January 2009

Cancers of the oral cavity, salivary glands, larynx, and pharynx, collectively referred to as squamous cell carcinomas of the head and neck (HNSCC), are the sixth most common cancer among men in the developed world. The prognosis of HNSCC patients is still poor, which reflects the fact that although the risk factors for HNSCC are well-recognized, very little is known about the molecular mechanisms responsible for this malignancy. This review describes some of the current efforts and technological advances that have focused on the creation of a complete information infrastructure for genes expressed during squamous cell carcinogenesis. These include: the recently described HNSCC-specific chromosomal alterations (cCAP); the Head and Neck Cancer Genome Anatomy Project (HN-CGAP), whose goal is the systematic identification and cataloguing of known and novel genes expressed during tumor development; and the use of laser-capture microdissection (LCM), which is pivotal for the comprehensive molecular characterization of normal, pre-cancerous, and malignant cells by means of DNA-array technology. The latter provides the means for the analysis of expression patterns of thousands of genes simultaneously. The use of LCM for proteomics and DNA analysis is also included in this review. These revolutionary approaches are likely to have an unprecedented impact on cancer biology, and provide exciting opportunities to unravel the still-unknown mechanisms involved in squamous cell carcinogenesis. They are also expected to provide a molecular blueprint for HNSCC, thus helping to identify suitable markers for the early detection of pre-neoplastic lesions, as well as novel targets for pharmacological intervention in this disease.
Morphology and Physiology of Masticatory Muscle Motor Units
Authors: van Eijden T.M.G.J. , Turkawski S.J.J.
Published: January 2009

Motor unit territories in masticatory muscles appear to be smaller than territories in limb muscles, and this would suggest a more localized organization of motor control in masticatory muscles. Motor unit cross-sectional areas show a wide range of values, which explains the large variability of motor unit force output. The proportion of motor unit muscle fibers containing more than one myosin heavy-chain (MHC) isoform is considerably larger in masticatory muscles than in limb and trunk muscles. This explains the continuous range of contraction speeds found in masticatory muscle motor units. Hence, in masticatory muscles, a finer gradation of force and contraction speeds is possible than in limb and in trunk muscles. The proportion of slow-type motor units is relatively large in deep and anterior masticatory muscle regions, whereas more fast-type units are more common in the superficial and posterior muscle regions. Muscle portions with a high proportion of slow-type motor units are better equipped for a finer control of muscle force and a larger resistance to fatigue during chewing and biting than muscle portions with a high proportion of fast units. For the force modulation, masticatory muscles rely mostly on recruitment gradation at low force levels and on rate gradation at high force levels. Henneman's principle of an orderly recruitment of motor units has also been reported for various masticatory muscles. The presence of localized motor unit territories and task-specific motor unit activity facilitates differential control of separate muscle portions. This gives the masticatory muscles the capacity of producing a large diversity of mechanical actions. In this review, the properties of masticatory muscle motor units are discussed.
Beyond the Specific Plaque Hypothesis: Are Highly Leukotoxic Strains of Actinobacillus Actinomycetemcomitans a Paradigm for Periodontal Pathogenesis?
Authors: Guthmiller J.M. , Lolly E.T. , Korostoff J.
Published: January 2009

Actinobacillus actinomycetemcomitans is a facultative anaerobe implicated in a variety of periodontal diseases. Its presence is most closely associated with localized juvenile periodontitis (LJP), although the exact role of the organism in this and other periodontal diseases is not entirely clear. While A. actinomycetemcomitans produces several different putative virulence factors, the most widely studied is the leukotoxin. The leukotoxin selectively kills polymorphonuclear leukocytes and macrophages in vitro, constituting the host's first line of defense. Interestingly, even though all strains of A. actinomycetemcomitans have the genes encoding the leukotoxin, there is variability in leukotoxin expression. Differences in the structure of the promoter region of the leukotoxin gene operon were shown to correlate directly with levels of leukotoxin production. Highly leukotoxic forms appear to exhibit increased pathogenic potential, as evidenced by recent studies that have shown a significant association between the prevalence of such strains and the occurrence of LJP in several different populations. This represents the first demonstration of an association between a particular subset of a pathogenic species and a specific periodontal disease. Early identification of A. actinomycetemcomitans by microbial and genetic assays to evaluate leukotoxicity may enhance the efficacy of preventive and/or therapeutic techniques. Future investigations should continue to evaluate pathogenic variations of additional virulence factors expressed in vivo, not only of A. actinomycetemcomitans, but also of other periodontal bacteria and infectious disease pathogens.
Relation of Dental Composite Formulations To Their Degradation and the Release of Hydrolyzed Polymeric-Resin-Derived Products
Authors: Santerre J.P. , Shajii L. , Leung B.W.
Published: January 2009

This article reviews the principal modes of dental composite material degradation and relates them to the specific components of the composites themselves. Particular emphasis is placed on the selection of the monomer resins, the filler content, and the degree of monomer conversion after the clinical materials are cured. Loss of mechanical function and leaching of components from the composites are briefly described, while a more detailed description is provided of studies that have considered the chemical breakdown of materials by agents that are present in the oral cavity, or model the latter. Specific attention will be given to the hydrolysis process of monomer and composite components, i.e., the scission of condensation-type bonds (esters, ethers, amides, etc.) that make up the monomer resins, following reaction of the resins with water and salivary enzymes. A synopsis of enzyme types and their sources is outlined, along with a description of the work that supports their ability to attack and degrade specific types of monomer systems. The methods for the study of biodegradation effects are compared in terms of sensitivity and the information that they provide. The impact of biodegradation on the ultimate biocompatibility of current materials is discussed from the perspective of what is known to date and what remains to be studied. The findings of the past decade clearly indicate that there are many reasons to probe the issue of biochemical stability of composite resins in the oral cavity. The challenge will now be to have both industry and government agencies take a pro-active approach to fund research in this area, with the expectation that these studies will lead to a more concise definition of biocompatibility issues related to dental composites. In addition, the acquired information from such studies will generate the development of alternate polymeric chemistries and composite formulations that will require further investigation for use as the next generation of restorative materials with enhanced biostability.
Genetic Competence and Transformation in Oral Streptococci
Authors: Cvitkovitch D.G.
Published: January 2009

The oral streptococci are normally non-pathogenic residents of the human microflora. There is substantial evidence that these bacteria can, however, act as "genetic reservoirs" and transfer genetic information to transient bacteria as they make their way through the mouth, the principal entry point for a wide variety of bacteria. Examples that are of particular concern include the transfer of antibiotic resistance from oral streptococci to Streptococcus pneumoniae. The mechanisms that are used by oral streptococci to exchange genetic information are not well-understood, although several species are known to enter a physiological state of genetic competence. This state permits them to become capable of natural genetic transformation, facilitating the acquisition of foreign DNA from the external environment. The oral streptococci share many similarities with two closely related Gram-positive bacteria. S. pneumoniae and Bacillus subtilis. In these bacteria, the mechanisms of quorum-sensing, the development of competence, and DNA uptake and integration are well-charaterized. Using this knowledge and the data available in genome databases allowed us to identify putative genes involved in these processes in the oral organism Streptococcus mutans. Models of competence development and genetic transformation in the oral streptococci and strategies to confirm these models are discussed. Future studies of competence in oral biofilms, the natural environment of oral streptococci, will be discussed.
Pathogenetic Factors in Sjögren's Syndrome: Recent Developments
Authors: Esch T.R.
Published: January 2009

The study of pathogenetic factors in Sjogren's syndrome [SS] has been problematic, given the overall paucity of coherent data that integrate basic research with clinical findings. The presumed autoimmune nature of SS suggests T-cells, autoantibodies, and cytokines as possible immune factors in the initiation and progression of SS. Recent work on programmed cell death (apoptosis) in SS and its models suggests this as a fourth potential mechanism of disease. These four areas of SS research are reviewed with an emphasis on the most recent findings related to mechanisms of disease. New findings confirm the potential for antigen presentation to T-cells in the salivary glands, as well as involvement of other adhesion molecules with respect to T-cell functions. Restrictions on the receptor repertoires of infiltrating T-cells are discussed, as are new findings on antigenic specificities of these cells. New findings on the specificities of autoantibodies observed in SS are reviewed with an eye toward potential mechanisms for depression of exocrine secretory capacity. Stimulating new findings concerning cytokine production in salivary and lacrimal gland are noted. Particular points of interest with regard to apoptosis include the wide range of values obtained for apoptotic activity in SS and its models, and potential means of resolving discongruent results and the study of factors influencing apoptosis are discussed.
The Impact of Microgravity on Bone Metabolism in vitro and in vivo
Authors: Loomer Peter M.
Published: January 2009

Exposure to microgravity has been associated with several physiological changes in astronauts and cosmonauts, including an osteoporosis-like loss of bone mass. In-flight measures used to counteract this, including intensive daily exercise regimens, have been only partially successful in reducing the bone loss and in the process have consumed valuable work time. If this bone loss is to be minimized or, preferably, prevented, more effective treatment strategies are required. This, however, requires a greater understanding of the mechanisms through which bone metabolism is affected by microgravity. Various research strategies have been used to examine this problem, including in vitro studies using bone cells and in vivo studies on humans and rats. These have been conducted both in flight and on the ground, by strategies that produce weightlessness to mimic the effects of microgravity. Overall, the majority of the studies have found that marked decreases in gravitation loading result in the loss of bone mass. The processes of bone formation and bone resorption become uncoupled, with an initial transitory increase in resorption accompanied by a prolonged decrease in formation. Loss of bone mass is not uniform throughout the skeleton, but varies at different sites depending on the type of bone and on the mechanical load received. It appears that the skeletal response is a physiologic adaptation to the space environment which, after long space flights or repeated shorter ones, could eventually lead to significant reductions in the ability of the skeletal tissues to withstand the forces of gravity and increased susceptibility to fracture.
Genetics of Acid Adaptation in Oral Streptococci
Authors: Quivey Robert G. , Kuhnert Wendi L. , Hahn Kristina
Published: January 2009

A growing body of information has provided insights into the mechanisms by which the oral streptococci maintain their niches in the human mouth. In at least one case, Streptococcus mutans, the organism apparently uses a panel of proteins to survive in acidic conditions while it promotes the formation of dental caries. Oral streptococci, which are not as inherently resistant to acidification, use protective schemes to ameliorate acidic plaque pH values. Existing information clearly shows that while the streptococci are highly related, very different strategies have evolved for them to take advantage of their particular location in the oral cavity. The picture that emerges is that the acid-adaptive regulatory mechanisms of the oral streptococci differ markedly from those used by Gram-negative bacteria. What future research must determine is the extent and complexity of the acid-adaptive systems in these organisms and how they permit the organisms to maintain themselves in the face of a low-pH environment and the microbial competition present in their respective niches.
Therapeutic Uses of Non-Steroidal Anti-Inflammatory Drugs in Dentistry
Authors: Dionne Raymond A. , Berthold Charles W.
Published: January 2009

The non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used classes of drugs for the management of acute and chronic pain in dentistry. Their therapeutic efficacy and toxicity are well-documented and provide evidence that NSAIDs generally provide an acceptable therapeutic ratio of pain relief with fewer adverse effects than the opioid-mild analgesic combination drugs that they have largely replaced for most dental applications. The great many studies done with the oral surgery model of acute pain indicate that a single dose of an NSAID is more effective than combinations of aspirin or acetaminophen plus an opioid, with fewer side-effects, thus making it preferable for ambulatory patients. The combination of an NSAID with an opioid generally results in marginal analgesic activity but with an increased incidence of side-effects, which limits its use to patients in whom the NSAID alone results in inadequate analgesia. The selective COX-2 inhibitors hold promise for clinical efficacy with less toxicity from chronic administration and may prove advantageous for the relief of chronic orofacial pain. The use of repeated doses of NSAIDs for chronic orofacial pain should be re-evaluated in light of a lack of documented efficacy and the potential for serious gastrointestinal and renal toxicity with repeated dosing.
Is it Time to Change State and Regional Dental Licensure Board Exams in Response to Evidence from Caries Research?
Authors: Anusavice K.J. , Benn D.K.
Published: January 2009

State and regional board exams the final gateway to dental licensure. One would expect the requirements for licensure would reflect procedures that are to each patient's oral health and are consistent with the of most dental schools. We conducted an Internet survey to determine whether Class 2 tooth preparations based on caries lesions whose radiolucencies were confined to enamel were allowed for state and regional exams. Information obtained for 46 of the 50 states revealed that 33 of the states (72%) allowed teeth with either an E1 of E2 lesion to be restored. Seventeen of these states allowed teeth with an E1 to be restored. Only 12 of the 46 states (26%) covered by these boards did not allow teeth with E1 or E2 lesions to be surgically treated. In contrast, a recent report indicates that only 30% of dental schools permit teeth with enamel lesions to be restored to satisfy clinical requirements and competencies.
Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules
Authors: Steffensen Bjorn , Häkkinen Lari , Larjava Hannu
Published: January 2009

During wound-healing, cells are required to migrate rapidly into the wound site via a proteolytically generated pathway in the provisional matrix, to produce new extracellular matrix, and, subsequently, to remodel the newly formed tissue matrix during the maturation phase. Two classes of molecules cooperate closely to achieve this goal, namely, the matrix adhesion and signaling receptors, the integrins, and matrix-degrading and -processing enzymes, the matrix metalloproteinases (MMPs). There is now substantial experimental evidence that blocking key molecules of either group will prevent or seriously delay wound-healing. It has been known for some time now that cell adhesion by means of the integrins regulates the expression of MMPs. In addition, certain MMPs can bind to integrins or other receptors on the cell surface involved in enzyme activation, thereby providing a mechanism for localized matrix degradation. By proteolytically modifying the existing matrix molecules, the MMPs can then induce changes in cell behavior and function from a state of rest to migration. During wound repair, the expression of integrins and MMPs is simultaneously up-regulated. This review will focus on those aspects of the extensive knowledge of fibroblast and keratinocyte MMPs and integrins in biological processes that relate to wound-healing.
Role of Treponema Denticola in Periodontal Diseases
Authors: Sela Michael N.
Published: January 2009

Among periodontal anaerobic pathogens, the oral spirochetes, and especially Treponema denticola, have been associated with periodontal diseases such as early-onset periodontitis, necrotizing ulcerative gingivitis, and acute pericoronitis. Basic research as well as clinical evidence suggest that the prevalence of T. denticola, together with other proteolytic Gram-negative bacteria in high numbers in periodontal pockets, may play an important role in the progression of periodontal disease. The accumulation of these bacteria and their products in the pocket may render the surface lining periodontal cells highly susceptible to lysis and damage. T. denticola has been shown to adhere to fibroblasts and epithelial cells, as well as to extracellular matrix components present in periodontal tissues, and to produce several deleterious factors that may contribute to the virulence of the bacteria. These bacterial components include outer-sheath-associated peptidases, chymotrypsin-like and trypsin-like proteinases, hemolytic and hemagglutinating activities, adhesins that bind to matrix proteins and cells, and an outer-sheath protein with pore-forming properties. The effects of T. denticola whole cells and their products on a variety of host mucosal and immunological cells has been studied extensively (Fig. 1). The clinical data regarding the presence of T. denticola in periodontal health and disease, together with the basic research results involving the role of T. denticola factors and products in relation to periodontal diseases, are reviewed and discussed in this article.
Cell Adhesion Molecules and Oral Cancer
Authors: Thomas GJ , Speight P.M.
Published: January 2009

Cell adhesion molecules (CAMs) are found on the surfaces of all cells, where they bind to extracellular matrix molecules or to receptors on other cells. As well as having a structural role, CAMs function as signaling receptors, transducing signals initiated by cellular interactions which regulate many diverse processes, including cell division, migration, and differentiation. Cell adhesion molecules are essential for maintaining stable tissue structure. However, cell adhesion must be dynamic to facilitate the mobility and turnover of cells. In dynamic situations, cells alter their cell-cell and cell-matrix interactions by virtue of altered expression and function of CAMs. The expression of CAMs is normally tightly regulated, thereby controlling cell proliferation, mobility, differentiation, and survival. Many of these processes are misregulated in malignant tumors, and it has been shown that many of the characteristics of tumor cells are attributable to the aberrant expression or function of CAMs. Integrins and E-cadherin are the most important CAMs expressed by stratified squamous epithelium. Altered expression of these molecules has been found in oral carcinoma, where loss of CAM expression is often seen in poorly differentiated lesions. However, up-regulation of certain integrins, such as av(36, has consistently been found in oral cancer, suggesting that it may play an active role in disease progression.
Nerve Regeneration: Basic and Applied Aspects
Authors: Donoff R. Bruce
Published: January 2009

Increased knowledge is shedding new light on our understanding of central and peripheral nerve anatomy and molecular biology and function. New tools and methods provide important methods for the study of the behavior of cells, axons, and receptors. This review discusses the current state of that knowledge, with particular regard to the efficacy of the Seddon classification of nerve injury. The correlation of that new information to damage and repair of the peripheral sensory nerve, especially the inferior alveolar and lingual nerves, serves to highlight the progress and problems that exist.
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 TGFas, RARas, 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.
Bionutrition and Oral Cancer in Humans
Authors: Enwonwu C.O. , Meeks V.I.
Published: January 2009

Tobacco (smoking and smokeless) use and excessive consumption of alcohol are considered the main risk factors for oral cancer (ICD9 140-149). Conspicuous national and international variations in oral cancer incidence and mortality rates, as well as observations in migrant populations, raise the possibility that diet and nutritional status could be an important etiologic factor in oral carcinogenesis. As shown in this report, abuse of alcohol and tobacco has serious nutritional implications for the host, and generates increased production of reactive free radicals as well as eliciting immunosuppression. Maintenance of optimal competence of the immune system is critical for cancer surveillance. Active oxygen species and other reactive free radicals mediate phenotypic and genotypic alterations that lead from mutation to neoplasia. Consequently, the most widely used chemopreventive agents against oral cancer (e.g., vitamins A, E, C, and β-carotene) are anti-oxidants/free radical scavengers. These anti-oxidants, both natural and synthetic, neutralize metabolic products (including reactive oxygen species), interfere with activation of procarcinogens, prevent binding of carcinogens to DNA, inhibit chromosome aberrations, restrain replication of the transformed cell, suppress actions of cancer promoters, and may even induce regression of precancerous oral lesions such as leukoplakia and erythroplakia. Malnutrition is characterized by marked tissue depletion of anti-oxidant nutrients, including GSH (y-glutamyl-cysteinyl-glycine), a key cellular anti-oxidant as well as a modulator of T-cell activation. GSH or its precursor cysteine inhibits activation of the nuclear transcription factor kB (NFkB), and has been shown to be protective against chemically induced oral cancer and leukoplakia. Alcohol-, tobacco-, and/or malnutrition-induced immunosuppression promotes impaired salivary gland function and oral mucosal immunity, a prominent reduction in the number of helper CD4 cells with less marked changes in number of suppressor T-cells, and depressed NK cell activity, among others. These suggest a breakdown in the capacity of the malnourished to mount effective tumor surveillance. This review article underscores the compounding but important roles of nutritional/dietary factors in the long-established causal link between abuse of alcohol and tobacco (smoking and smokeless) and oral cancer.
The Role of Phosphotyrosine Signaling Pathway in Parotid Gland Proliferation and Function
Authors: Purushotham K.R. , Humphreys-Beher M.G.
Published: January 2009

Tyrosine phosphorylation and the intracellular signaling processes associated with it have been the focus of intense study due to its importance in the regulation of biological processes as diverse as cell proliferation and cell differentiation. While much of what we now understand has been derived from the study of cell lines and tumor cells, the salivary glands provide a model to examine the effects of tyrosine kinases and tyrosine phosphatases in a normal differentiated tissue. This review will focus, therefore, on the role tyrosine kinases and phosphatases play in inducing the transition from stasis to active proliferation and their potential role in mediating secretory function of the salivary glands.
Complement Biosynthesis in the Central Nervous System
Authors: Barnum S.R.
Published: January 2009

Complement is an important effector arm of the human immune response. Binding of proteolytic fragments derived from activation of complement by specific receptors leads to responses as diverse as inflammation, opsonization, and B-cell activation. The importance of characterizing the expression and regulation of complement in the CNS is highlighted by growing evidence that complement plays a significant role in the pathogenesis of a variety of neurological diseases, such as multiple sclerosis and Alzheimer's disease. In vitro studies have demonstrated that astrocytes, the predominant glial cell type in the brain, are capable of expressing or producing a majority of the components of the complement system. Expression of many complement proteins synthesized by astrocytes is regulated by both pro- and anti-inflammatory cytokines, many of which are also produced by several cell types in the CNS. In addition to astrocytes, ependymal cells, endothelial cells, microglia, and neurons have recently been shown to synthesize various complement proteins or express complement receptors on their cell surfaces. Together, these studies demonstrate that several cell types throughout the brain have the potential to express complement and, in many cases, increase expression in response to mediators of the acute phase response. These studies suggest that complement may play a greater role in CNS immune responses than previously thought, and pave the way for better understanding of the dynamics of complement expression and regulation in vivo. Such understanding may lead to therapeutic manipulation of complement host defense functions in a variety of inflammatory and degenerative diseases in the CNS.
Molecular Mechanisms of Dental Enamel Formation
Authors: Simmer J.P. , Fincham A.G.
Published: January 2009

Tooth enamel is a unique mineralized tissue in that it is acellular, is more highly mineralized, and is comprised of individual crystallites that are larger and more oriented than other mineralized tissues. Dental enamel forms by matrix- mediated biomineralization. Enamel crystallites precipitate from a supersaturated solution within a well-delineated biological compartment. Mature enamel crystallites are comprised of non-stoichiometric carbonated calcium hydroxyapatite. The earliest crystallites appear suddenly at the dentino-enamel junction (DEJ) as rapidly growing thin ribbons. The shape and growth patterns of these crystallites can be interpreted as evidence for a precursor phase of octacalcium phosphate (OCP). An OCP crystal displays on its (100) face a surface that may act as a template for hydroxyapatite (OHAp) precipitation. Octacalcium phosphate is less stable than hydroxyapatite and can hydrolyze to OHAp. During this process, one unit cell of octacalcium phosphate is converted into two unit cells of hydroxyapatite.

During the precipitation of the mineral phase, the degree of saturation of the enamel fluid is regulated. Proteins in the enamel matrix may buffer calcium and hydrogen ion concentrations as a strategy to preclude the precipitation of competing calcium phosphate solid phases. Tuftelin is an acidic enamel protein that concentrates at the DEJ and may participate in the nucleation of enamel crystals. Other enamel proteins may regulate crystal habit by binding to specific faces of the mineral and inhibiting growth. Structural analyses of recombinant amelogenin are consistent with a functional role in establishing and maintaining the spacing between enamel crystallites.
Genetically Engineered Mice: Tools To Understand Craniofacial Development
Authors: Ignelzi Michael A. , Liu Yi-Hsin , Maxson Robert E. , Snead Malcolm L.
Published: January 2009

In this review, we provide a survey of the experimental approaches used to generate genetically engineered mice. Two specific examples are presented that demonstrate the applicability of these approaches to craniofacial development. In the first, a promoter analysis of the Msx2 gene is presented which illustrates the cis regulatory interactions that define cell-specific gene expression. In the second, a mouse model of the human disease craniosynostosis, Boston type, has been created by misregulation of the Msx2 gene product. Finally, we present a formulary of spontaneously occurring and genetically engineered mice that exhibit defects in developmental processes affecting the craniofacial complex. The purpose of this review is to provide insight into the experimental approaches that are used to create genetically engineered mice and to impress upon the reader that genetically engineered mice are well-suited to address fundamental questions pertaining to the development, maintenance, and regeneration of tissues and organs.
Setting Reactions in Dental Amalgam Part 2. the Kinetics of Amalgamation
Authors: Okabe T. , Mitchell R.J.
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. Part 2 is a review of the kinetics of the reactions that convert the mixture of alloy powder and liquid mercury to hardened amalgam containing the phases and microstructures described in Part I . It is emphasized that amalgamation is a non-equilbrium process in which hardened microstructures are determined as much by kinetics as by chemistry. The setting reaction begins with dissolution of silver and tin into liquid mercury; most of the product phases precipitate in the liquid mercury. The processes that produce supersaturation in the liquid mercury and the subsequent nucleation and growth of solid phases are considered. Mass balance relationships that provide insight into the factors that control the volume fraction of the undesirable γ2 Sn-Hg phase are described. The nucleation and growth of η' Cu-Sn crystals are also discussed : it is found that these crystals nucleate on copper-rich phases and grow into the liquid mercury. Finally, aspects of the setting reaction that are controlled by intergranular and interphase diffusion in the solid are discussed. These aspects include the supersaturation of silver and tin within the liquid mercury, nucleation and growth of the β1 Ag-Hg phase in the surfaces of alloy particles, and the decomposition of initially formed γ2 Sn-Hg.
Oral Mucosal Langerhans' Cells
Authors: Barrett A.W. , Cruchley A.T. , Williams D.M.
Published: January 2009

Langerhans' cells (LC) are dendritic, antigen-presenting cells present within the epithelium of skin and mucosa, including that of the oral cavity. This article reviews the literature on the phenotypic and functional features of oral mucosal Langerhans' cells, and speculates on other aspects by extrapolating from data on their epidermal counterparts.
Aspects of Adherence of Oral Spirochetes
Authors: Denee Thomas D.
Published: January 2009

Oral spirochetes are present in the oral cavity in various numbers and forms and have been strongly implicated as playing a role in the etiology of periodontal disease. Because adherence to host tissues is a critical first step in establishing a bacterial infection, reports on the attachment of oral spirochetes to host tissues and matrix components were reviewed. The great bulk of the literature concerns T reponema denticola ; however, where there is information regarding other oral spirochete species, it will be noted.
Dynamics of the Pulpo-Dentin Complex
Authors: Pashley D.H.
Published: January 2009

Dentin has a relatively high water content due to its tubular structure. Once dentin is exposed, this intratubular water is free to move in response to thermal, osmotic, evaporative, or tactile stimuli. Fluid shifts across dentin are thought to cause sufficient shear forces on odontoblasts, nerve endings, nearby fibroblasts, and blood vessels to cause significant mechanical irritation, disruption, or damage, depending on the magnitude of the fluid shift. Even in the absence of fluid shifts, the water-filled tubules provide diffusion channels for noxious (i.e., bacterial products) substances which diffuse inward toward the pulp, where they can activate the immune system, provide chemotactic stimuli, cytokine production, and produce pain and pulpal inflammation. Viewed from this perspective, dentin is a poor barrier to external irritants.

However, pulpal tissues react to these challenges by increasing the activity of nerves, blood vessels, the immune system, and interstitial fluid turnover, to make the exposed dentin less permeable either physiologically, via increased outward fluid flow, or microscopically, by lining tubules with proteins, mineral deposits, or tertiary dentin, thereby enhancing the barrier properties of dentin, and providing additional protection to pulpal tissues. These reactions involve dentin and pulp, both in the initiation of the processes and in their resolution. These responses of the dental pulp to irritation of dentin demonstrate the dynamic nature of the pulpo-dentin complex.
Current Concepts of Autoimmune Exocrinopathy: Immunologic Mechanisms in the Salivary Pathology of Sjögren's Syndrome
Authors: Fox P.C. , Speight P.M.
Published: January 2009

Sjogren's syndrome is a systemic autoimmune disorder characterized by symptoms of oral and ocular dryness and a chronic, progressive loss of salivary and lacrimal function. The exocrine involvement is the result of a focal, peri-ductal mononuclear cell infiltrate and the subsequent loss of secretory epithelial cells. The mechanisms of this autoimmune exocrinopathy are not understood fully. Many recent investigations have described alterations in a number of immune mediators within the salivary glands. These studies provide new insights into the immune regulation of normal salivary gland functions and the mechanisms of gland damage in Sjogren's syndrome.
Platelet-Streptococcal Interactions in Endocarditis
Authors: Herzberg M.C.
Published: January 2009

Infective endocarditis is characterized by the formation of septic masses of platelets on the surfaces of heart valves and is most commonly caused by viridans streptococci. Streptococcal virulence in endocarditis involves factors that promote infectivity and pathogenicity. Adhesins and exopolysaccharide (glycocalyx) contribute to infectivity. Although many factors may contribute to pathogenicity, the platelet aggregation-associated protein (PAAP) of Streptococcus sanguis contributes directly to the development of experimental endocarditis. PAAP is synthesized as a rhamnose-rich glycoprotein of 115 kDa and contains a collagen-like platelet-interactive domain, pro-gly-glu-gln-gly-pro-lys. Expressed on the cell wall of platelet aggregation-inducing strains (Agg+) of S. sanguis, PAAP apparently interacts with a signal-transducing receptor complex on platelets, which includes a novel 175-kDa α2-integrin-associated protein and a 65-kDa collagen-binding component. From available data, the role of PAAP in the pathogenesis of experimental endocarditis may be explained by a proposed mechanistic model. On injured heart valves, PAAP first enhances platelet accumulation into a fibrin-enmeshed thrombus (vegetation), within which S. sanguis colonizes. Colonizing bacteria must resist platelet microbicidal protein (PMPR). The aggregation of platelets on the heart valve may be potentiated by an ectoATPase expressed on the surface of the S. sanguis and platelet a-adrenoreceptors that respond to endogenous catecholamines. The expression of PAAP may be modified during infection. Collagen is exposed on damaged heart valves; fever (heat shock) occurs during endocarditis. In response to heat shock or collagen in vitro, PAAP expression is altered. After colonization, streptococcal exotoxin(s) may cause fever. Proteases and other enzymes from streptococci and host sources may directly destroy the heart valves. When PAAP is unexpressed or neutralized with specific antibodies, experimental endocarditis runs a milder course and vegetations are smaller. The data suggest strongly, therefore, that the role of PAAP may overlap the colonization function of putative adhesins such as FimA or SsaB. Finally, PAAP also contributes to the development of the characteristic septic mural thrombus (vegetation) of infective endocarditis and the signs of valvular pathology.
Lymphocyte-Fibroblast Interactions
Authors: Murakami S. , Okada H.
Published: January 2009

Chronic inflammatory reactions are usually characterized by inflammatory cell accumulation in the extravascular connective tissue. In such sites, inappropriate activation of circulating or resident lymphocytes becomes self-perpetuating and can lead to chronic tissue destruction. In addition to that, the locally infiltrated lymphocytes should have an opportunity to interact directly with fibroblasts composing the connective tissue. The direct interactions of those different cell types seem to play important roles in lymphocyte lodging and retention in such sites. Thus, for clarification of the immunopathogenesis of the chronic inflammatory diseases, including periodontitis, it is important that the molecular mechanisms involved in the heterotypic cell-cell interactions be revealed. In fact, it has been demonstrated that lymphocytes interact with various non-hematopoietic cells, such as epithelial cells and endothelial cells. Regarding interactions with fibroblasts, it has been shown that IFNγ-stimulated fibroblasts can regulate the proliferative responses of T-lymphocytes both positively and negatively. Furthermore, activated lymphocytes have demonstrated strong binding ability to various fibroblast cell lines. Blocking experiments utilizing monoclonal antibodies specific to various cell adhesion molecules revealed that very late antigen (VLA) integrins, lymphocyte-function-associated antigen (LFA-1)/intercellular adhesion molecule-1 (ICAM-1), CD44/hyarulonate are, at least in part, involved in lymphocyte-fibroblast interactions. In addition, recent findings raised the possibility that the adhesive interactions between lymphocytes and fibroblasts influenced the various cellular functions of each cell type. In fact, it was recently demonstrated that the adhesive interactions stimulated fibroblasts to increase expression of inflammatory cytokine mRNA. These results strongly suggest that fibroblasts are not merely innocent bystanders but actively participate in local inflammatory reactions by directly interacting with locally infiltrated lymphocytes.