Critical Reviews in Oral Biology & Medicine

The Official Publication of the American Association of Oral Biologists

A Publication of the International/American Associations for Dental Research
Table of Contents for Volume 7, 1996

Volume 7, Issue 1
Volume 7, Issue 2
Volume 7, Issue 3
Volume 7, Issue 4

Volume 7, Issue 1

• Thomas DD
• Department of Periodontics, University of Texas Health Science Center, San Antonio 78284, USA.
• Page 4-11

ral 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 Treponema denticola; however, where there is information regarding other oral spirochete species, it will be noted.

• Mitchell RJ, Okabe T.
• Department of Oral Health Science, University of Kentucky College of Dentistry, Lexington 40536-0084, USA.
• Pages 12-22

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 1 provides the background needed to understand the kinetics of the setting reactions, which is the topic of Part 2 of the review.

• Okabe T, Mitchell RJ.
• Department of Biomaterials Science, Baylor College of Dentistry, Dallas, Texas 75246, USA.
• Pages 23-35

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 1. 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 gamma 2 Sn-Hg phase are described. The nucleation and growth of eta' 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 beta 1 Ag-Hg phase in the surfaces of alloy particles, and the decomposition of initially formed gamma 2 Sn-Hg.

• Barrett AW, Cruchley AT, Williams DM.
• Department of Oral Pathology, Eastman Dental Institute for Oral Health Care Sciences, London, U.K.
• Pages 36-58

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.

• Hunt SW 3rd, Harris ES, Kellermann SA, Shimizu Y.
• Division of Immunopathology, Warner-Lambert/Parke-Davis Pharmaceutical Research Division, Ann Arbor, MI 48105, USA
• Pages 59-86

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 (5) the clinical relevance of adhesion molecules and the potential for targeting these molecules for the amelioration of immune-mediated diseases.

• Goldstein M, Brayer L, Schwartz Z.
• Department of Periodontics, Faculty of Dental Medicine, Hebrew University Hadassah School of Dental Medicine, Jerusalem, Israel.
• Pages 87-98

Gingival recession is the exposure of root surfaces due to apical migration of the gingival tissue margins. Although it seldom results in tooth loss, marginal tissue recession is associated with thermal and tactile sensitivity, esthetic complaints, and a tendency toward root caries. This article reviews the current surgical procedures for the coverage of exposed root surfaces, including their advantages and disadvantages. Today, the outcome of root coverage procedures is predictable, aesthetically acceptable, and, together with the use of guided tissue regeneration, at the forefront of regenerative procedures.

Volume 7, Issue 2

• Pashley DH.
• Department of Oral Biology, School of Dentistry, Medical College of Georgia, Augusta 30912-1129, USA.
• Pages 104-33

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.

• Deany IL.
• Ohio State University, College of Dentistry, Section of Restorative, Prosthodontics, and Endodontics, Columbus 43210-1241, USA.
• Pages 134-43

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.

• Fox PC, Speight PM.
• Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892-1190, USA.
• Pages 144-58

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.

• Olgart L.
• Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
• Pages 159-71

Blood flow of mammalian dental pulp is under both remote and local control. There is evidence for the existence of parasympathetic nerves in the pulp, but functionally the cholinergic influence is weak, and the physiological significance of this autonomic system seems to be low. The evidence for sympathetic vasoconstrictor nerves in the pulp is robust, and there is convincing support for the contention that these nerves play a physiological role, operating via release of noradrenaline and neuropeptide Y. However, there is no significant functional evidence in support of sympathetic beta-adrenoceptor-mediated vasodilation in the pulp. The local control of blood flow involves a subset of intradental sensory nerves. By virtue of their neuropeptide content, these afferent fibers cause vasodilation and inhibit sympathetic vasoconstriction in response to painful stimulation of the tooth. Such locally governed control may serve to meet immediate demands of the pulp tissue. A locally triggered reflex activation of sympathetic nerves in the pulp may modulate this control and limit its magnitude. Thus, there are competitive interactions between local and remote vascular controls which may be put out of balance in the injured and inflamed dental pulp.

• Hume WR, Gerzia TM.
• Department of Restorative Dentistry, University of California, San Francisco 94143-0758, USA.
• Pages 172-9

Chemical components of many materials used in dental practice can move into the local biophase, where they can have beneficial or adverse effects. The strongest indirect evidence that components of resin-based materials used in dentistry can move into the biophase are the many reports of allergic dermatitis in dental personnel. Direct measurement of component release has shown that triethylene glycol dimethacrylate (TEGDMA), hydroxyethyl methacrylate (HEMA), and, in the case of some orthodontic cements, bis-glycidyl methacrylate and benzoyl peroxide can move into an aqueous medium from a range of resin-based materials which are applied to teeth as part of oral care. In the case of resin composite restorations, HEMA and TEGDMA are available in microgram quantities via the salivary surface in the minutes and hours after clinical placement and via dentin and pulp in the hours and days after placement. Fortunately, moderate thickness of dentin protects pulp tissue against local toxicity. There are no data which suggest that systemic toxicity is a risk with any of these materials. There are some case reports of allergic responses to the monomers in patients, but the incidence of such responses appears at present to be much lower than that in dental personnel.

• Liljemark WF, Bloomquist C.
• Department of Diagnostic and Surgical Sciences, University of Minnesota School of Dentistry, Minneapolis 55455-0329, USA.
• Pages 180-98

In the human oral cavity, which is an open growth system, bacteria must first adhere to a surface in order to be able to colonize. Ability to colonize a non-shedding tooth surface is necessary prior to any odontopathic or periodontopathic process. Complex microbe-host relationships occur and must be studied before the commensal-to-pathogenic nature of the human indigenous oral flora can be understood. Medical pathogens, if present in the appropriate host, always produce specific disease. Caries and periodontal diseases are conditional diseases, requiring numbers of certain indigenous species at various sites, particularly the tooth surface. In the case of caries, the condition is related to sugar consumption. Periodontal disease/s may require certain host and environmental conditions, such as local environment or nutritional factors in gingival crevicular fluids. Nonetheless, critical numbers of certain indigenous species must be present in order for these diseases to occur. The aim of this review is to understand the acquisition of the indigenous oral flora and the development of human dental plaque. The role of the salivary pellicle and adherence of indigenous bacteria to it are critical first steps in plaque development. Bacterial interactions with saliva, nutritional factors, growth factors, and microbial physiologic processes are all involved in the overall process of microbial colonization.

Volume 7, Issue 3

• Garlick JA, Fenjves ES.
• Department of Oral Biology and Pathology, State University of New York at Stony Brook 11794-8702, USA.
• Pages 204-21

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.

• Herzberg MC.
• Department of Preventive Sciences, School of Dentistry, University of Minnesota, Minneopolis 55455, USA.
• Pages 222-36

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 alpha 2-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 alpha-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.

• Holland GR.
• Department of Cariology, Restorative Sciences and Endodontics, School of Dentistry, University of Michigan, Ann Arbor 48109-1078, USA.
• Pages 237-58

The successful reinnervation of peripheral targets after injury varies with the axonal population of the nerve that is injured and the extent of the dislocation of its central component from the peripheral endoneurial tube. Larger-diameter axons such as those supplying mechanoreceptors recover more readily than narrower axons such as those supplying taste. A complex, bi-directional interaction between lingual epithelium and sprouting nerve results in the redifferentiation of taste buds after denervation. Dentin and the dental pulp provide a strong attraction to sprouting nerves and will become reinnervated from collateral sources if recovery of the original innervation is blocked. The most effective repair technique for transected lingual nerves is one which brings the cut ends together rather than one that provides a temporary bridge. Injuries can result in cell death in the trigeminal ganglion but only if the injury is severe and recovery is prevented. Lesser damage results in chromatolysis and the increased expression of neuropeptides. All nerve injuries bring about changes in the trigeminal nucleus. These occur as changes in receptive field and the incidence of spontaneously active neurons, effects which are consistent with the unmasking of existing afferents. These functional changes are short-lived and reversible. Morphologically, nerve injury results in terminal degeneration in the nuclei and an increased expression of the c-Fos gene and some neuropeptides. Only a chronic constriction injury induces behavioral changes. The adult trigeminal system retains considerable plasticity that permits it to respond successfully to nerve injury. Much remains to be learned about this response, particularly of the trophic factors that control peripheral recovery and the central response to more severe injuries.

• Baehni PC, Guggenheim B.
• Department of Preventive Dentistry, School of Dental Medicine, Faculty of Medicine, University of Geneva, Switzerland.
• Pages 259-77

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.

• Meffert RM.
• Department of Periodontics, University of Texas Health Science Center, San Antonio 78284, USA.
• Pages 278-91

The microbial flora in the natural dentition sulcus/pocket and the implant crevice/pocket is very similar in both health and disease. In health, coccal forms predominate, and in disease, large numbers of Gram-negative pathogens are associated with both tooth and implant. It has also been demonstrated that the bacteria in the partially edentulous implant case may be more pathogenic (especially Gram-negative rods and spirochetes) than in the fully edentulous case, indicating a possible seeding mechanism from tooth pocket to implant crevice. Detoxification procedures involving the use of tetracycline and citric acid prior to regenerative procedures with the use of barrier membranes and grafting materials are necessary, and the same problems attendant to premature exposure of the barrier membrane(s) in the natural dentition situation apply to the implant case. It is apparent that periodontitis = peri-implantitis in etiology and therapy.

Volume 7, Issue 4

• Feliciani C, Gupta AK, Sauder DN.
• Department of Dermatology, University G. D'Annunzio, Chieti, Italy.
• Pages 300-18

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/cytokine-receptor 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.

• Wong DT, Todd R, Tsuji T, Donoff RB.
• Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA.
• Pages 319-28

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.

• Kieswetter K, Schwartz Z, Dean DD, Boyan BD.
• OsteoBiologics, Inc., San Antonio, Texas, USA.
• Pages 329-45

The surface of an implant determines its ultimate ability to integrate into the surrounding tissue. The composite effect of surface energy, composition, roughness, and topography plays a major role during the initial phases of the biological response to the implant, such as protein adsorption and cellular adherence, as well as during the later and more chronic phases of the response. For bone, the successful incorporation (and hence rigid fixation) of an alloplastic material within the surrounding bony bed is called osteointegration. The exact surface characteristics necessary for optimal osteointegration, however, remain to be elucidated. This review will focus on how surface characteristics, such as composition and roughness, affect cellular response to an implant material. Data from two different culture systems suggest that these characteristics play a significant role in the recruitment and maturation of cells along relevant differentiation pathways. In the case of osteointegration, if the implant surface is inappropriate or less than optimal, cells will be unable to produce the appropriate complement of autocrine and paracrine factors required for adequate stimulation of osteogenesis at the implant site. In contrast, if the surface is appropriate, cells at the implant surface will stimulate interactions between cells at the surface and those in distal tissues. This, in turn, will initiate a timely sequence of events which include cell proliferation, differentiation, matrix synthesis, and local factor production, thereby resulting in the successful incorporation of the implant into the surrounding bony tissue.

• Matteson SR, Deahl ST, Alder ME, Nummikoski PV.
• Department of Dental Diagnostic Science, University of Texas Health Science Center, San Antonio 78284-7919, USA.
• Pages 346-95

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.