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 8, 1997

Volume 8, Issue 1
Volume 8, Issue 2
Volume 8, Issue 3
Volume 8, Issue 4

Volume 8, Issue 1

• Maas R, Bei M.
• Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Pages 4-39

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. Msxl-deficient 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, Lefl, and Activin beta A 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 Msxl is required for the transmission of Bmp4 expression from dental epithelium to mesenchyme and also for Lefl 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.

• Murakami S, Okada H.
• Department of Periodontology and Endodontology, Osaka University Faculty of Dentistry, Japan.
• Pages 40-50

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 IFN gamma-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-I), 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.

• Denny PC, Ball WD, Redman RS.
• Department of Basic Sciences, School of Dentistry, University of Southern California, Los Angeles 90089-0641, USA.
• Pages 51-75

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.

• Mathur A, Michalowicz BS.
• Department of Oral Science, School of Dentistry, University of Minnesota, Minneapolis, USA.
• Pages 76-89

The adaptive immune system consists of humoral and cell-mediated immunity. T-lymphocytes are the key components of cell-mediated immunity. CD4+ helper T-lymphocytes facilitate B-cells to differentiate and produce specific antibodies, whereas CD8+ cytotoxic T-lymphocytes kill virally infected cells. Periodontal diseases have been associated with a variety of imbalances in the regulation of immune responses. Changes in the ratios of peripheral blood CD4+ and CD8+ T-lymphocytes, depressed proliferative responses of peripheral blood lymphocytes, and increased frequency of CD45RO+ memory T-lymphocytes in diseased tissues have been reported in individuals with various forms of periodontal disease. While some studies have shown an increased frequency of gamma delta + T-cells in periodontal lesions, the role of gamma delta + T-cells in periodontal disease remains controversial. The ability of putative periodontopathic bacteria selectively to stimulate certain V beta-expressing T-cells is intriguing and could determine whether a CD4+ Th1 or a CD4+ Th2 cell response is elicited. The prominence of a particular subset of helper T-cells within the periodontal lesion could be a reflection of the stage and activity of the disease, or the types of bacteria present. Regardless, longitudinal studies of the involvement of T-cell subsets and cytokines in periodontal disease are clearly needed.

• Korioth TW, Versluis A.
• Department of Oral Science, Minnesota Dental Research Center for Biomaterials and Biomechanics (MDRCBB), School of Dentistry, University of Minnesota, Minneopolis, Minnesota 55455, USA.
• Pages 90-104

In this paper, we provide a review of mechanical finite element analyses applied to the maxillary and/or mandibular bone with their associated natural and restored structures. It includes a description of the principles and the relevant variables involved, and their critical application to published finite element models ranging from three-dimensional reconstructions of the jaws to detailed investigations on the behavior of natural and restored teeth, as well as basic materials science. The survey revealed that many outstanding FE approaches related to natural and restored dental structures had already been done 10-20 years ago. Several three-dimensional mandibular models are currently available, but a more realistic correlation with physiological chewing and biting tasks is needed. Many FE models lack experimentally derived material properties, sensitivity analyses, or validation attempts, and yield too much significance to their predictive, quantitative outcome. A combination of direct validation and, most importantly, the complete assessment of methodical changes in all relevant variables involved in the modeled system probably indicates a good FE modeling approach. A numerical method for addressing mechanical problems is a powerful contemporary research tool. FE analyses can provide precise insight into the complex mechanical behavior of natural and restored craniofacial structures affected by three-dimensional stress fields which are still very difficult to assess otherwise.

Volume 8, Issue 2

• Kremenak NW, Squier CA.
• Dows Institute for Dental Research, College of Dentistry, University of Iowa, Iowa City 52242, USA.
• Pages 108-28

Following the annexation of Austria by Hitler's Germany in 1938, officials at the eminent University of Vienna Medical School purged faculty ranks of Jews. Among those forced out were several distinguished physician dentists, several of whom emigrated to the United States. The assimilation of foreign-trained dentists raised questions at national meetings of the AADS and the National Association of Dental Examiners. Already existing ties between dental schools in Chicago and the University of Vienna, including the 1928 appointment of Rudolf Kronfeld to the faculty at Loyola, led to the relocation of Balint Orban, Harry Sicher, and Joseph Peter Weinmann in that city. Bernhard Gottlieb, who had been director of the Dental Institute in Vienna, transplanted less easily, but eventually found a niche at the Baylor College of Dentistry in Dallas. The careers of the Vienna dentist-scientists strengthened the scientific foundations of clinical dentistry in the United States, contributed to the development of a stronger research establishment, and enlarged the scope of oral biology.

• Bailit H.
• Center for Health Services and Primary Care Research, School of Medicine, University of Connecticut Health Center, Farmington 06030, USA.
• Pages 129-35

This paper examines the restructuring of the delivery system resulting from managed care. As HMOs consolidate to a few large companies in urban areas, they put great pressure on medical providers to reduce their costs and excess delivery capacity. In this environment, academic health centers face serious problems, because HMOs are reluctant to pay their higher charges, and public educational subsidies are declining. Managed care is unlikely to have the same impact on dentistry. Although managed dental care is growing, most Americans will not be enrolled, since they do not have dental insurance. Also, the supply of dentists is starting to decline, increasing the relative demand for dental services. Managed care will have only a limited direct impact on most dental schools, but a significant indirect effect. As academic health center budgets are reduced, all health professional schools can expect to contribute to solving the financial problems of University hospitals and medical schools. The response of dental academicians to these challenges will determine the future of dental education and research for the next decade. Bold new initiatives are needed to find new sources of revenue to support educational and research programs.

• Aoba T.
• Nippon Dental University, Department of Pathology, Tokyo, Japan.
• Pages 135-53

Fluoride participates in many aspects of calcium phosphate formation in vivo and has enormous effects on the process and on the nature and properties of formed mineral. The most well-documented effect of fluoride is that this ion substitutes for a column hydroxyl in the apatite structure, giving rise to a reduction of crystal volume and a concomitant increase in structural stability. In the process of enamel mineralization during amelogenesis (a unique model for the cell-mediated formation of well-crystallized carbonatoapatite), free fluoride ions in the fluid phase are supposed to accelerate the hydrolysis of acidic precursor(s) and increase the driving force for the growth of apatitic mineral. Once fluoride is incorporated into the enamel mineral, the ion likely affects the subsequent mineralization process by reducing the solubility of the mineral and thereby modulating the ionic composition in the fluid surrounding the mineral, and enhancing the matrix protein-mineral interaction. But excess fluoride leads to anomalous enamel formation by retarding tissue maturation. It is worth noting that enameloid/enamel minerals found in vertebrate teeth have a wide range of CO3 and fluoride substitutions. In the evolutionary process from elasmobranch through enameloid to mammalian enamel, the biosystems appear to develop regulatory functions for limiting the fluoridation of the formed mineral, but this development is accompanied by an increase of carbonate substitution or defects in the mineral. In research on the cariostatic effect of fluoride, considerable emphasis is placed on the roles of free fluoride ions (i.e., preventing the dissolution and accelerating the kinetics of remineralization) in the oral fluid bathing tooth mineral. Fluoride also has been used for the treatment of osteoporosis, but much still remains to be learned about maximizing the benefit and minimizing the risk of fluoride when used as a public health measure.

• Ripamonti U, Reddi AH.
• Bone Research Laboratory, MRC/University of the Witwatersrand, Medical School, Johannesburg, South Africa.
• Pages 154-63

Tissue engineering is the emerging field of science developing techniques for fabrication of new tissues for replacement based on principles of cell and developmental biology and biomaterials. Morphogenesis is the cascade of pattern formation and the attainment of form of the various organs and the organism as a whole. The periodontium consist of the periodontal ligament, cementum, and alveolar bone. Bone has considerable potential for regeneration and therefore is a prototypic model for tissue engineering. The three main ingredients for tissue engineering are regulatory signals, responding stem cells, and extracellular matrix. Recent advances in molecular biology of the bone morphogenetic proteins (BMPs) have set the stage for tissue engineering of bone and related tissues, including the periodontium. Bone-derived BMPs, with a collagenous matrix as carrier, induced cementum and alveolar bone regeneration in surgically created furcation defects in the primate. It is noteworthy that there was morphogenesis of periodontal ligament and a faithful insertion of Sharpey's fibers into cementum. In the same furcation model, recombinant human osteogenic protein-1 (rhOP-1, also known as BMP-7), in conjunction with the collagenous carrier, induced extensive cementogenesis with insertion of Sharpey's fibers into the newly formed cementum. The observation that BMPs induce cementogenesis and periodontal ligament formation indicates that these proteins may have multiple functions in vivo not limited to cartilage and bone induction. The rapid advances in the molecular biology of BMPs and their receptors bode well for novel strategies to engineer the regeneration of the periodontal tissues.

• Soskolne WA.
• Department of Periodontics, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem, Israel.
• Pages 164-74

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.

• Jenkinson HF, Lamont RJ.
• Department of Oral Biology and Oral Pathology, University of Otago, Dunedin, New Zealand.
• Pages 175-200

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.

• Woo SB, Lee SJ, Schubert MM.
• Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
• Pages 201-16

Bone marrow transplantation (BMT) is the treatment of choice for many leukemias, lymphomas, bone marrow failure syndromes, and immunodeficiency disorders, and is the primary and salvage therapy for many solid malignancies. With the establishment of national and international marrow banks, unrelated allogeneic BMT is being performed with increasing frequency. Graft-vs.-host disease (GVHD) remains a major complication of allogeneic BMT, occurring in 25% to 70% of patients despite GVHD prophylaxis, with the skin, gastro-intestinal tract, and liver as primary target organs. Oral findings are seen in both acute and chronic GVHD. In acute GVHD, the oral lesions are often painful, erythematous, ulcerative, and desquamative. In chronic GVHD, they are lichenoid with associated erythema and ulcerations; additionally, they may be associated with a sicca syndrome characterized by xerostomia and progressive salivary gland atrophy. General principles of BMT are discussed, as are systemic and local therapeutic options for oral GVHD.

• Havemose-Poulsen A, Holmstrup P.
• Department of Periodontology, School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Denmark.
• Pages 217-36

Fibroblasts have been studied extensively for their contribution to connective tissue destruction in diseases where the metabolism of extracellular matrix components plays an essential part in their pathogenesis. A considerable dissolution, especially of collagen fibrils, is a well-known characteristic of the periodontal ligament and the gingival connective tissue in microbial-induced periodontal disease. Fibroblasts, responsible for the assembly of the extracellular matrix, are capable of responding directly to oral microbial challenges or indirectly, following activation of the host immune response, and can alter the composition of connective tissue in several ways: synthesis of inflammatory mediators, their receptors and antagonists; fibroblast proliferation; collagen synthesis; phagocytosis of collagen fibrils; and synthesis of proteolytic enzymes, including matrix metalloproteinases and their corresponding inhibitors. The contributions of these cellular fibroblastic properties to the pathogenesis of periodontal disease are reviewed in the context of the cytokine, interleukin-1, as the inflammatory regulator.

Volume 8, Issue 3

• Ann DK, Lin HH, Kousvelari E.
• Department of Molecular Pharmacology and Toxicology, University of Southern California-HSC, Los Angeles 90033, USA.
• Pages 244-52

The results from in vivo transgenic and in vitro transfection studies designed to identify cis-element(s) and transfactor(s) governing the salivary proline-rich proteins (PRPs), amylase, and parotid secretory protein (PSP) gene expression are utilized as a paradigm to discuss the regulation of salivary-specific gene expression. Particular attention is given to the molecular mechanism(s) underlying the salivary PRP R15 gene regulation. In rodents, the PRPs are selectively expressed in the acinar cells of salivary glands, and are inducible by the beta-agonist isoproterenol and by dietary tannins. The results from a series of experiments using chimeric reporter constructs containing different lengths of the R15 distal enhancer region, their mutations, and various expressing constructs are analyzed and discussed. These data suggest that the inducible nuclear orphan receptor NGFI-B may participate in the regulation of salivary acinar-cell-specific and inducible expression of the rat R15 gene via three distinct distal NGFI-B sites. Taken together, a model for the induction of R15 gene expression by Ipr is proposed. However, the exact molecular basis of this NGFI-B-mediated transactivation of cAMP-regulated R15 expression remains to be established.

• Lekic PC, Pender N, McCulloch CA.
• Department of Clinical Sciences, Faculty of Dentistry, University of Manitoba, Winnipeg, Canada.
• Pages 253-68

There are wide variations of gene expression and strikingly different responses to extracellular signals among different fibroblast populations. This has prompted a large number of in vitro studies which suggest that fibroblasts are not homogeneous but instead comprise multiple subpopulations with extensive site-to-site and intra-site variations. Conceivably, either fibroblasts are not all created equal, or, alternatively, discrete subpopulations may emerge in development, inflammatory lesions, or wound healing. While the heterogeneous nature of cultured fibroblasts has been known for some time, are these variations relevant to our understanding of the biology of oral tissues, their involvement in disease, and their response to therapy? Since fibroblasts are the predominant cell type in soft connective tissue matrices, the regulation of their proliferative, synthetic, and degradative behavior is likely to be important in tissue physiology and pathology. In this review, we use the current literature to assess whether fibroblast subpopulations really make a difference in the health and disease of periodontal tissues. We address the following questions: (1) Is fibroblast heterogeneity a real in vivo phenomenon? (2) How can we advance our knowledge of phenotypic variations and the regulation of fibroblast differentiation? (3) Could a knowledge of fibroblast heterogeneity have an impact on the development of new approaches to pathogenesis and the treatment of periodontal tissues?

• Niederman R, Zhang J, Kashket S.
• Department of Periodontology, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA.
• Pages 269-90

This communication reviews the effects of short-chain carboxylic acids on human cells of importance to the periodontium. The central hypothesis is that these acids can alter both cell function and gene expression, and thus contribute to the initiation and prolongation of gingival inflammation. Short-chain carboxylic acids [CH3-(CH2)x-COOH, x < 3] are metabolic intermediates with a broad range of apparently paradoxical biological effects. For example, lactic acid (CH3-CHOH-COOH), a 3-carbon alpha-hydroxy-substituted acid, is widely recognized for its cariogenicity. Lactic acid, however, also occurs in tropical fruits, and is the active ingredient in a variety of anti-wrinkle creams developed by dermatologists. In marked contrast, the unsubstituted 3-carbon propionic acid (CH3-CH2-COOH) is used as a food preservative and is the active principle for one class of non-steroidal anti-inflammatory agents. Interestingly, the addition of one carbon to propionic acid dramatically changes the biological effects. The unsubstituted 4-carbon butyric acid (CH3-CH2-CH2-COOH) is used by hematologists as a de-differentiating agent for the treatment of sickle cell anemia, but by oncologists as a differentiating agent for cancer chemotherapy. Finally, acting either individually or in concert, these acids can increase vascular dilation. Clearly, these acids, while metabolically derived, have a number of very divergent activities which are cell-type-specific (Fig. 1). It may be telling that periodontal bacteria produce these acids in millimolar concentrations, and that these bacteria can be characterized by their acid production profiles. It is no less interesting that these acids occur in the gingival crevices of human subjects with severe periodontal disease at millimolar levels which are > 10-fold higher than those found in mildly diseased subjects, and are undetectable in healthy subjects. Further, when applied directly to healthy human gingiva, short-chain carboxylic acids stimulate a gingival inflammatory response and inflammatory cytokine release. At the cellular level, these acids inhibit proliferation of gingival epithelial and endothelial cells, and inhibit leukocyte apoptosis and function, but can stimulate leukocyte cytokine release. At the molecular level, these acids can stimulate neutrophil gene transcription, translation, and protein expression. Thus, the likelihood is high that these acids, in addition to their cariogenic activity, can promote and prolong gingival inflammation. Our challenge will be to identify the cell or cells of the periodontium which respond to short-chain carboxylic acids, to delineate their responses and the molecular mechanism(s) of these effects, and to categorize the aspects of the inflammatory components which damage and those which protect the host. With this information, it may be possible to begin to rationally identify and test pharmaceutical agents which diminish the harmful aspects, while enhancing the beneficial components, of the inflammatory response.

• LeResche L.
• Department of Oral Medicine, University of Washington, Seattle 98195-6370, USA.
• Pages 291-305

Epidemiology is the study of the distribution, determinants, and natural history of disease in populations. Epidemiology has several uses in addition to its traditional role of documenting the public health significance of a condition. Notably, epidemiologic methods and data can be used to identify and verify causes of disease. This article reviews the epidemiologic data on pain in the temporomandibular region, and on signs and symptoms associated with specific subtypes of temporomandibular disorders, with the aim of identifying possible etiologic factors for these conditions that deserve further study. Despite methodologic and population differences, several consistencies are apparent in the epidemiologic literature. Pain in the temporomandibular region appears to be relatively common, occurring in approximately 10% of the population over age 18; it is primarily a condition of young and middle-aged adults, rather than of children or the elderly, and is approximately twice as common in women as in men. This prevalence pattern suggests that etiologic investigations should be directed at biologic and psychosocial factors that are more common in women than in men, and diminish in older age groups. Most signs and symptoms associated with particular temporomandibular disorders (e.g., joint sounds, pain in the joint) also appear to be more prevalent in women than in men, although age patterns for these signs and symptoms are not as clear as for temporomandibular pain. The available data highlight the need for further research on etiologic factors associated with temporomandibular pain and with specific diagnostic subtypes of temporomandibular disorders.

• Eick JD, Gwinnett AJ, Pashley DH, Robinson SJ.
• Department of Oral Biology, School of Dentistry, University of Missouri at Kansas City 64108-2716, USA.
• Pages 306-35

This review examines fundamental concepts in bonding to dentin. Emphasis is placed on the structure and permeability characteristics of dentin and how they may influence its interaction with adhesive resin. Several new techniques to examine the interfaces between resin and dentin are reviewed along with some of their limitations. The advantages and disadvantages of acid etchants/conditioners vs. self-etching conditioners/primers are discussed. The problems of matching the surface tension of resin-bonding systems to the surface energy of the substrate are reviewed in terms of wetting the various components of dentin. The problems associated with matching the permeability of intertubular dentin to the diffusibility of bonding reagents are explored. Speculation is advanced on how to ensure polymerization and wetting of dentinal collagen. Theoretical problems associated with dentin bonding and with bond testing are reviewed to encourage future research in this rapidly developing area.

• Hefti AF.
• Periodontal Disease Research Center, University of Florida College of Dentistry, JHMHC, Gainesville 32610-0442, USA.
• Pages 336-56

For decades, probing clinical pocket depth and attachment level have been recognized as the dentist's most important tools in diagnosing periodontal health and disease. They are physical methods to measure the distance from the bottom of a pocket to a reference line, usually the gingival margin or the cemento-enamel junction. Probing accuracy and precision are affected by factors like the design of the probe, probing force, probe position, pocket depth, or tissue inflammation. Recently, several new electronic periodontal probes have been developed. They feature high instrument precision, allowing for measurements to the nearest tenth of a millimeter. They control for probing force and permit data to be collected and stored electronically. The purpose of this review paper is to summarize various aspects of periodontal probing. First, the history of periodontal probes will be briefly recollected, and interesting and significant inventions of the past and the present emphasized. Then, the importance of the periodontal tissues relative to probe tip penetration will be reviewed, and the probing performance will be discussed. The paper will conclude with notes on selected statistical issues.

Volume 8, Issue 4

• Veis A, Sfeir C, Wu CB.
• Department of Basic and Behavioral Sciences, Northwestern University Dental School, Chicago, Ilinois 60611, USA.
• Pages 360-79

The extracellular matrix of the connective tissue contains non-collagenous proteins (NCP) which are acidic in character. The NCP of mineralizing systems (bone, dentin) differ from those of the non-mineralizing systems (skin, tendon) in that the mineralized tissue NCP are frequently phosphorylated. The phosphorylated proteins have been implicated in various aspects of the mineralization process. Thus, it is of interest to consider the mechanism and regulation of phosphorylation of the major matrix NCP. The majority of the phosphorylation takes place at Ser or Thr residues embedded within acidic sequences, and therefore are targets for casein kinase I (CK1) or casein kinase II (CK2)-like kinases. CK1 and CK2 are distantly related members of the protein kinase family. They are ubiquitous, constitutively active, second-messenger-independent kinases. CK1 is found in a variety of isoforms, all homologous to the alpha-subunit of the protein kinase family. It acts as a monomer. The active form of CK2 is a tetrameric holoenzyme, with 2 alpha catalytic subunits and 2 beta regulatory subunits. The CK2 alpha has activity alone, but the holoenzyme is four- to five-fold that activity. CK2 can use either ATP or GTP as the phosphate donor, but CK1 can use only ATP. The CK2 activity which phosphorylates the mineralized tissue NCP appears to be localized to membrane-associated cell fractions, and is present in the endoplasmic reticulum and Golgi compartments in osteoblasts, where phosphorylation of the secreted proteins appears to take place as co- and post-translational processes. Data indicate that both alpha and beta subunits of the membrane-associated CK2 are isoforms of the cytosolic CK2 in the same cells. The CK1 has not been specifically localized. Studies of dephosphorylated NCP such as phosphophoryn (PP) have shown that CK1 will not phosphorylate dephosphorylated dPP unless prior phosphorylation with CK2 has been carried out. In turn, CK2 activity may be initiated only after an initial phosphorylation of one of the messenger-dependent kinases. Thus, the phosphorylation reactions in mineralized tissues may be a tightly regulated hierarchical or sequential cascade of intracellular phosphorylation events.

• Penberthy TW, Jiang Y, Graves DT.
• Department of Endodontics, Boston University School of Dental Medicine, Massachusetts 02118, USA.
• Pages 380-8

Recruitment of leukocytes is critical to many of the processes studied in oral biology. With the development of new tools such as monoclonal antibody production and transgenic mice, the specific adhesion molecules thought to be important in leukocyte recruitment have been identified and their function examined. These molecules can be divided into three major classes: selectins, members of the immunoglobulin superfamily, and integrins. They mediate interactions between leukocytes and endothelial cells, facilitating the initial process of leukocyte rolling, firm attachment to endothelium, transendothelial migration, diapedesis, and migration along connective tissue. The goal of this paper is to provide an understanding of which molecules are involved in the above processes by discussing their cellular distribution, counter-receptors, and physiologic function.

• Meyer DH, Mintz KP, Fives-Taylor PM.
• Department of Microbiology and Molecular Genetics, University of Vermont, Burlington 05405, USA.
• Pages 389-409

Bacterial invasion of epithelial cells is associated with the initiation of infection by many bacteria. To carry out this action, bacteria have developed remarkable processes and mechanisms that co-opt host cell function and stimulate their own uptake and adaptation to the environment of the host cell. Two general types of invasion processes have been observed. In one type, the pathogens (e.g., Salmonella and Yersinia spp.) remain in the vacuole in which they are internalized and replicate within the vacuole. In the other type, the organism (e.g., Actinobacillus actinomycetemcomitans, Shigella flexneri, and Listeria monocytogenes) is able to escape from the vacuole, replicate in the host cell cytoplasm, and spread to adjacent host cells. The much-studied enteropathogenic bacteria usurp primarily host cell microfilaments for entry. Those organisms which can escape from the vacuole do so by means of hemolytic factors and C type phospholipases. The cell-to-cell spread of these organisms is mediated by microfilaments. The investigation of invasion by periodontopathogens is in its infancy in comparison with that of the enteric pathogens. However, studies to date on two invasive periodontopathogens. A actinomycetemcomitans and Porphyromonas (Bacteroides) gingivalis, reveal that these bacteria have developed invasion strategies and mechanisms similar to those of the enteropathogens. Entry of A. actinomycetemcomitans is mediated by microfilaments, whereas entry of P. gingivalis is mediated by both microfilaments and microtubules. A. actinomycetemcomitans, like Shigella and Listeria, can escape from the vacuole and spread to adjacent cells. However, the spread of A. actinomycetemcomitans is linked to host cell microtubules, not microfilaments. The paradigms presented establish that bacteria which cause chronic infections, such as periodontitis, and bacteria which cause acute diseases, such as dysentery, have developed similar invasion strategies.

• Mackert JR Jr, Berglund A.
• Medical College of Georgia, Augusta 30912-1260, USA.
• Pages 410-36

This review examines the question of whether adverse health effects are attributable to amalgam-derived mercury. The issue of absorbed dose of mercury from amalgam is addressed first. The use of intra-oral Hg vapor measurements to estimate daily uptake must take into account the differences between the collection volume and flow rate of the measuring instrument and the inspiratory volume and flow rate of air through the mouth during inhalation of a single breath. Failure to account for these differences will result in substantial overestimation of the absorbed dose. Other factors that must be considered when making estimates of Hg uptake from amalgam include the accurate measurement of baseline (unstimulated) mercury release rates and the greater stimulation of Hg release afforded by chewing gum relative to ordinary food. The measured levels of amalgam-derived mercury in brain, blood, and urine are shown to be consistent with low absorbed doses (1-3 micrograms/day). Published relationships between the number of amalgam surfaces and urine levels are used to estimate the number of amalgam surfaces that would be required to produce the 30 micrograms/g creatinine urine mercury level stated by WHO to be associated with the most subtle, pre-clinical effects in the most sensitive individuals. From 450 to 530 amalgam surfaces would be required to produce the 30 micrograms/g creatinine urine mercury level for people without any excessive gum-chewing habits. The potential for adverse health effects and for improvement in health following amalgam removal is also addressed. Finally, the issue of whether any material can ever be completely exonerated of claims of producing adverse health effects is considered.

• Barbour SE, Nakashima K, Zhang JB, Tangada S, Hahn CL, Schenkein HA, Tew JG.
• Clinical Research Center for Periodontal Diseases, School of Dentistry, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0566, USA.
• Pages 437-60

This review summarizes the current data on the effects of smoking and tobacco on the immune system and its potential impact on periodontal health. Smokers are 2.5-6 times more likely to develop periodontal disease than non-smokers, and there is evidence for a direct correlation between the number of cigarettes smoked and the risk of developing disease. Tobacco users also tend to exhibit increased severity of periodontal disease. Direct correlations between tobacco use and increased attachment loss and pocket depth and reduced bone crest height have been reported. Although the correlation between tobacco use and periodontal disease is quite strong, the role of tobacco in the pathogenesis of periodontal disease is uncertain. Recent studies indicate that one potential mechanism is that tobacco use exacerbates periodontal disease because it alters the immune response to periodontal pathogens. Indeed, smokers exhibit increased numbers of peripheral blood mononuclear phagocytes which appear to be functionally compromised. Inadequate phagocyte activity could reduce the clearance of pathogens from the oral cavity and thereby facilitate the development of periodontal disease. Tobacco-exposed B- and T-lymphocytes exhibit reduced proliferative capacities which could limit the production of protective immunoglobulins against oral pathogens. The risk factors for periodontal disease can be broadly classified as genetic, environmental, host-response factors, and host-related factors such as age. Tobacco, an environmental factor, undermines the host response and may facilitate the development and progression of periodontal disease. This review highlights the inter-relatedness of two of the risk factors associated with periodontal disease.

• Valdimarsdottir HB, Stone AA.
• Department of Psychiatry, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
• Pages 461-74

This review focuses on studies that have examined the relation between psychosocial factors and secretory immunoglobulin A (s-IgA). Several studies have examined the relation between s-IgA and stressful circumstances ranging from major life events to minor daily events. The findings from these studies were often contradictory, since different experimenters reported different stress-related changes in s-IgA. The effects of stress reduction interventions, such as relaxation and imagery, on s-IgA levels have also been examined. Although these studies indicate that various interventions are associated with increases in s-IgA levels, methodological refinements are needed before more definitive conclusions can be made. The possibility that the relation between stress and s-IgA may be moderated by personality characteristics or mediated by psychological distress was supported in some studies. The review concludes with suggestions for future research.